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AT EVEN WE DO ONLY VIDEOCONSULTATIONS THROUGH G MEET WHICH ARE RECORDED FOR POSTERITY THESE VIDEOCONSULTATIONS HAVE TO BE DONE ON A DESK TOP OR A LAP TOP AND NOT ON MOBILE PHONES

1. **Identity:** Telemedicine consultation should not be anonymous: both the patient and the Registered Medical Practitioner (RMP) need to know each other’s identity. 1. The patient’s and the RMP’s camera should be on for the videoconsultation 2. An RMP should verify and confirm the patient’s identity by comparing the photo in Pulse and patient in videoconsultation 2. **Consent and doctor-patient confidentiality:** 1. Patient initiates the Telemedicine consultation and thereby consent is implied 2. Where the patient is a minor (\<16 years of age), after confirming the age, teleconsultation would be allowed only if the minor is consulting along with an adult whose identity needs to be ascertained. For minors, caregivers are authorized to seek care even in the absence of the minor 3. For non-minor patients, caregivers should be given advice for the patient without the patient’s consent only if the patient is incapacitated, for example, in medical conditions like dementia or physical disability, etc. or the caregiver has a formal authorization or a verified document establishing his/her relationship with the patient and/or has been verified by the patient in a previous in-person consult (explicit consult). 4. If the patient is present with the caregiver during the consultation, consent should be confirmed.

3. **Emergency consult for immediate assistance or first aid etc.** In case alternative care is not present, teleconsultation might be the only way to provide timely care. In such situations, RMPs may provide consultation to their best judgment. In all cases of emergency, the patient must be advised for in-person interaction with a doctor at the earliest.

Even recommends the following equipment to conduct consultation in a professional manner: * Ring Light \- Digitek * Lapel mic or Headphone with mic (Same as CX) * Webcam \- Logitech or Lenovo * Internet \- speed 100mbps or more 2\. **Create a professional space.** Whether working from home or the office, healthcare professionals need to ensure that the space is clean and quiet before any virtual visit. Please be seated comfortably, the angle of the camera should be such that your face and the upper part of the body up to the chest are visible. While speaking, try to look at the camera as much as possible. Start the call with an introduction and pleasantries and end the call with specific actionable points and follow-up. 3\. **Check that records are available and abreast yourself with the patient's medical history/reports etc. before joining.** 4\. **Present yourself professionally** Healthcare professionals should dress in clean and neat attire, avoid oiling hair, and wear gym clothes, and T-shirts without a collar. 5\. **Be punctual** 6\. **Try to keep the patient feel connected** Try to maintain eye contact with the patients by looking straight into the webcam instead of their onscreen faces. 7\. **Properly define the post-appointment instructions.** Make sure that the patient knows the next steps

* How they will get their e-prescription * How membership status will be conveyed * How tests/visits will be facilitated * When and how to follow up 8\. **Make time to answer any final questions and clarify instructions before saying good-bye.** All doctors have to follow the telemedicine guidelines as published by the ministry of health and family

Our protocols for screening for prediabetes/diabetes are the following: * All nonpregnant adults should undergo HBA1c. If the results are normal the test needs to be repeated once in 1-2 years * For newly diagnosing DM, HbA1c should not be the sole criteria \- a FBS as well as repeat HbA1c should be done * Repeat every year if prediabetic * If WNL, repeat test in 1-3 years * Prediabetes: HbA1c is 5.7% or more but is less than 6.5% (Prediabetes), the patient is not a known case of Diabetes. * DM: HBA1c is 6.5% or more HbA1c and anaemia In general, conditions associated with decreased erythropoiesis (e.g., IDA) can falsely increase HbA1c because of the longer half-life of red blood cells. On the contrary, increased erythropoiesis resulting in rapid turnover of red blood cells can falsely lower HbA1c. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336595/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336595/) In cases of mild anemia, there is a minimal effect in HbA1c and can be used as a diagnostic and management tool for diabetes Anaemia classification Mild: Male: 11-13 mg/dl. Female: 11-12 mg/dl. Moderate: 8-11 mg/dl. Severe: \<8 mg/dl Furthermore, anemia should be corrected before setting the treatment goal of optimal HbA1c control, especially in moderate or severe anaemia

* Fasting plasma glucose \- Greater than 125 mg/dL * Random plasma glucose \- Greater than 200 mg/dL with symptoms * Postprandial glucose at 2 hours \- Greater than 200 mg/dL * Fasting plasma glucose \- 100-125 mg/dL * Random plasma glucose \- 140-199 mg/dL * Postprandial glucose at 2 hours \- 140-199 mg/dL ADA 2023 Standard of care recommendation: Metformin therapy for the prevention of type 2 diabetes should be considered in adults at high risk of type 2 diabetes, as typified by the DPP, especially those aged 25–59 years with BMI ≥35 kg/m2, higher fasting plasma glucose (FPG) (e.g., ≥110 mg/dL), and higher A1C (e.g., ≥6.0%), and in individuals with prior GDM Types of DM \- when to suspect and work up

| | Characteristics | Treatment | Workup | | :---- | :---- | :---- | :---- | | Type 2 DM | BMI \- high, concurrent lipid abnormality, fatty liver, age \>35 are typical but can present even in children Family history may be present Acanthosis nigricans | OHAs But since there is gradual loss of beta cell function Insulin may be required later | Antibodies: Positive in Type 1, , but in early disease later can become negative, Negative in type 2 **We at even do only GAD65, in adults** Five of the most common diabetes-related autoantibody tests include: Islet Cell Cytoplasmic Autoantibodies (ICA) Glutamic Acid Decarboxylase Autoantibodies (GAD) Insulinoma-Associated-2 Autoantibodies (IA-2A) Insulin Autoantibodies (IAA) Zinc Transporter-8 Autoantibodies (ZnT8A) **GAD 65 most reliable, but 2 out of 3 commonly done (GAD65 antibodies (GADA), IA2A, Anti Insulin antibodies IAA) is diagnostic** C peptide A plasma C-peptide cutoff of ≤0.20 mmol/L is indicative of T1D and of ≥0.30 mmol/L in the fasting or random state is indicative of T2D. However, in early Type 1 , the C peptide levels may be in range, hence after 2 years of diagnosis the predictibility is higher No need to do Insulin along with C Peptide for differentiating between type 1 and 2 | | Type 1 DM/ LADA | No family history younger age at diagnosis (\<35 years) with lower BMI (\<25 kg/m2), unintentional weight loss, ketoac

idosis, and glucose \>360 mg/dL (20 mmol/L) at presentation Adult \- newly diagnosed DM in age\<35, thin patient, no family history- important to consider and test An adult onset and slow progressing DM type 1 , common in whites is called LADA | Insulin In adult onset for some time beta cell reserve may still persist, but later can present with DKA or symptoms, hence test | | | | | | | | MODY | (1) mild hyperglycemia or overt diabetes in at least three consecutive generations; (2) onset usually before the age of 25 years; (3) absence of islet autoantibodies and lack of characteristics of type 2 diabetes (i.e., insulin resistance, obesity). | Sulphonylureas are effective in managing patients with HNF1A- and HNF4A–MODY, while additional treatment with other oral hypoglycemic agents may improve blood glucose control. | Strong history is highly suggestive. Genetic testing: consider as some forms of MODY may not need treatment | | Diseases of the exocrine pancreas (such as cystic fibrosis and pancreatitis), | Chronic calcific pancreatitis: if the patient is lean, there is H/O malabsorption, alcohol consumption, Family or patient H/O recurrent pancreatitis. Cystic fibrosis \- lung, pancreas related symptoms | Multiteam involvement Insulin | USG abdomen/CT abdomen C peptide | | Drug- or chemical-induced diabetes (such as with glucocorticoid use, in the treatment of HIV/AI

DS, or after organ transplantation) | | Careful drug titration/substitution under specialist care \+/- OHA and/or Insulin | |

| When | What to do | | :---- | :---- | | 1st consult | Workup: (Even complete blood profile if not done in the past year, Even 3 months DM follow up or annual DM follow up packages) includes HbA1c, Lipid profile, CBC, TSH, Blood pressure, Urine R/M, ECG Annual DM package \- urine microalbumin, LFT, KFT, TFT, CBC, Urine R/M, Lipid profile, Fundoscopy History for peripheral neuropathy, erectile dysfunction etc. Assess CVD risk [As per CVD risk assessment protocol](https://docs.google.com/presentation/u/0/d/14YZyqa_dFRUqlv8x0Kpd2xSrhQCsOZS8azVnuGDmysY/edit) Treatment optimisation Check the requirement of and optimize medicines for For DM For cholesterol For BP Lifestyle assessment and advice Goal setting: ABCDEMS management to be communicated A for HbA1c B for Blood Pressure C for cholesterol D for diet/weight- dietician consult Exercise M for monitoring S for smoking and alcohol | | DM program | [Template Progress notes EMR Chronic disease](https://docs.google.com/document/d/1AaDtUTiRYBsBKh6iau6lEvjlbQJiGOoZ6BOHqrX2tY4/edit?tab=t.0#heading=h.w1tpkw90x2yp) CONSIDER PUTTING IN PROGRAM NEWELY DIAGNOSED NOT WELL CONTROLLED BMI \>27 | Decision algorithm for drug therapy for DM Type 2

| HBA1c LEVEL | | | | :---- | :---- | :---- | | \<8 % | 8 to 10% | \>10 % | | FOR GLP1 CANDIDATES CARE TO BE HANDLED BY INTERNAL MEDICINE SPECIALIST- REST GPs should try and manage | BEST THAT CARE BE HANDLED BY INTERNAL MEDICINE SPECIALIST | CARE TO BE HANDLED BY INTERNAL MEDICINE SPECIALIST | | Can start with Monotherapy and escalate if control not achieved Not a known ℅ CVD, CKD or heart failure or high risk for CVD Metformin: start with 500 mg SR switch to 1000 mg SR within two weeks if FBS and PP targets not reached (FBS\<130, PP\<180) on blood test or glucometer Check control again in a month, if FBS and PP still not achieved Switch to combination of Gliptins (DPP4 inhibitors) and Metformin for example : Galvus met 50/500 (Vildagliptin \+ Metformin) BD (preferred by both UpToDate and ADA) OR Change Metformin dose to 1000 mg BD or 850 mg TDS OR Add Sulphonylureas (Glimepiride, Gliclazide preferred) to Metformin if BMI\<25 or cost is a concern for example: Tablet Amaryl (Glimepiride): start with 1-2 mg with the first big meal (breakfast or lunch), gradually increase over 2-4 weeks in 1 mg increments, up to 4 mg. Educate patient about r/o hypoglycemia If a known case of CVD or at high risk Metformin As per ADA, Metformin usually is given to everybody PLUS Jardiance (empagliflozin ) or other SGLT2 inhibitors start with 10 mg daily can be increased to 25 mg after 1-3

months OR if BMI\>27.5 **GLP1 analogues:** HAVE A DISCUSSION: approach [here](https://docs.google.com/document/d/1LvUlacVb3OqZZgDQmRZ2cTXkQNMVHk0tKIRRP-Ql59g/edit?tab=t.0) \+Metformin | Start with combination therapy (Metformin nearly always given) if BMI\>27 and patient can afford) GLP1 analogs: HAVE A DISCUSSION: approach [here](https://docs.google.com/document/d/1LvUlacVb3OqZZgDQmRZ2cTXkQNMVHk0tKIRRP-Ql59g/edit?tab=t.0) \+Metformin BMI patient can not afford GLP1 \- If a known case of CVD, CKD or heart failure or high risk for CVD: Metformin \+ Jardiance Metformin 1000 mg BD AND Jardiance (empagliflozin ) start with 10 mg daily can be increased till 25 mg after 1-3 months \- If not a known case of CVD, CKD or heart failure or high risk for CVD: Metformin \+ Gliptins E.g. Galvus Met 50/1000 BD OR Metformin+Sulfonylurea if cost is an issue If BMI\<25 Metformin \+ Gliptins E.g. Galvus Met 50/1000 BD OR Metformin+Sulfonylurea if cost is an issue Metformin 1000 mg BD and Amaryl (Glimepiride): start with 1-2 mg with the first big meal (breakfast or lunch), gradually increase over 2-4 weeks in 1 mg increments, up to 4 mg. Educate patients about risk and symptoms of hypoglycemia. Avoid starting with elderly or high CVD-risk people | Optimise OHAs or start insulin NEW CASE Urine ketone negative- OHA trial. TRIPLE OHA (Oral Hypoglycemic Agents) Urine ketone positive-

Start insulin OLD CASE Urine ketone negative- OHA optimization, BUT, If on maximum tolerated dose of 3 OHAs START Insulin or GLP1 depending on weight and cost considerations AND continue OHAs except secretagogues TRIPLE THERAPY (Maximum tolerated dose of \-Metformin 2.5 gm/day \+ Gliptins \-Vildagliptin 50 mg BD, \-Sitagliptin 50 mg BD OR \-Sulfonylureas Glimepiride 4 mg/day OR \-Jardiance 25 mg or equivalent OR \-Pioglitazone 30 mg/day Urine ketone positive- Start insulin Start night-time NPH at dose 10 units or 0.1-0.2 units/kg weight. Blood sugar target: Fasting and pre-meals: 70-110 Hypoglycemia risk and glucometer charting to be explained to the patient Increase dose every 3 days, by only 2 units at a time, till FBS target is reached. If hypoglycemia episodes happen, reduce dose by 15-20% If basal/night time NPH starts approaching 0.5 unit/kg body weight or hypoglycemia episodes happen or PP control is poor Consider splitting NPH dose in two: Reduce total dose by 20% Divide the new dose in ⅔ for the morning (before breakfast) and ⅓ for the night (after breakfast) Insulin glargine or detemir cause less hypoglycemia, but are costly, should be considered if hypoglycemia is bothersome and cost is not a constraint | | GLUCOMETER TESTING: Educate about options and encourage readiness to use | GLUCOMETER TESTING: Encourage Glucometer testing at least once

a week, fasting and pre meals | GLUCOMETER TESTING: If on insulin Monitor everyday blood sugar level \- fasting, pre meals, before and after exercise and whenever hypoglycemia is suspected until insulin requirements are stabilised, then 2 \-3 days/week If on OHA Encourage Glucometer testing at least 2-3 days a week, fasting, pre meals, and whenever hypoglycemia is suspected Once pre meals are controlled and there is no hypoglycemia, control PP levels, consider Rapid acting is PPs out of range | | DM with CKD management Optimize glucose and BP control and reduce BP variability to reduce the risk or slow the progression of CKD. Screening: At least annually, urinary albumin (e.g., spot UACR) and eGFR should be assessed in people with type 1 diabetes with duration of ≥5 years and in all people with type 2 diabetes regardless of treatment. In people with established DKD, urinary albumin (e.g., spot UACR) and eGFR should be monitored 1–4 times per year depending on the stage of the disease Diagnosis Two of three specimens of UACR collected within a 3- to 6-month period should be abnormal before considering a patient to have albuminuria. eGFR should be calculated from serum creatinine using a validated formula. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is generally preferred. Microalbuminuria management In people with CKD who have ≥300 mg/g urinary a

lbumin, a reduction of 30% or greater in mg/g urinary albumin is recommended to slow CKD progression In nonpregnant people with diabetes and hypertension, either an ACE inhibitor or an ARB is recommended for those with moderately increased albuminuria (UACR 30–299 mg/g creatinine) and is strongly recommended for those with severely increased albuminuria (UACR ≥300 mg/g creatinine) and/or eGFR \<60 mL/min/1.73 m2 An ACE inhibitor or an ARB is not recommended for the primary prevention of CKD in people with diabetes who have normal BP, normal UACR (\<30 mg/g creatinine), and normal eGFR. Deranged eGFR with/without microalbuminuria For people with type 2 diabetes and DKD, use of an SGLT2 inhibitor is recommended to reduce CKD progression and CV events in patients with an eGFR ≥20 mL/min/1.73 m2 and urinary albumin ≥20 mg/g creatinine. In people with CKD and albuminuria who are at increased risk for CV events or CKD progression, a nonsteroidal MRA (mineralocorticoid) FINERENONE shown to be effective in clinical trials is recommended to reduce CKD progression and CV events. Protein intake For people with non–dialysis-dependent stage 3 or higher CKD, dietary protein intake should be aimed to a target level of 0.8 g/kg body weight per day Nephrology referral Promptly refer to a nephrologist for uncertainty about the etiology of kidney disease, difficult management issues, and rapi

dly progressing kidney disease. Patients should be referred for evaluation by a nephrologist if they have continuously increasing (checked every 3 months) urinary albumin levels and/or continuously decreasing eGFR and if the eGFR is \<30 mL/min/1.73 m2 Metformin- when to stop can be used in patients with eGFR ≥30 mL/min/1.73 m2. Reassess benefits and risks of continuing treatment when eGFR falls to \<45 mL/min/1.73 m2, and do not initiate metformin in patients with an eGFR already at this level. Temporarily discontinue at the time of or before iodinated contrast imaging procedures in patients with eGFR 30–60 mL/min/1.73 m2. | | |

| TARGETS | | | | :---- | ----- | ----- | | Continuous Glucose Monitoring in Type 2 as well as 1 )- exapmle Abbott’s Frees style Libre | | | * Level 1 hypoglycemia (\<70 but ≥54 mg/dL) — patients with drug-treated diabetes should take action. Options include repeating the measurement within 15 to 60 minutes (depending on the setting), avoiding critical tasks such as driving, ingesting carbohydrates, and adjusting the treatment regimen . * Level 2 hypoglycemia (\<54 mg/dL) — Patients should ingest 15 to 20 grams of fast-acting carbohydrate ([table](https://www.uptodate.com/contents/image?imageKey=PI%2F71872&topicKey=ENDO%2F1805&search=hypoglycemia%20diabetes&rank=1%7E150&source=see_link) below), which is usually sufficient to raise the blood glucose into a safe range without inducing hyperglycemia. Patients should be instructed to retest after 15 minutes. If the glucose remains \<70 mg/dL (3.9 mmol/L), repeat treatment may be necessary. Acute treatment can be followed by long-acting carbohydrate (a meal or a snack) to prevent recurrent symptoms.

In patients using insulin or an insulin secretagogue in combination with an alpha-glucosidase inhibitor ([acarbose](https://www.uptodate.com/contents/acarbose-drug-information?search=hypoglycemia%20diabetes&topicRef=1805&source=see_link), [miglitol](https://www.uptodate.com/contents/miglitol-drug-information?search=hypoglycemia%20diabetes&topicRef=1805&source=see_link), voglibose), only pure glucose (eg, glucose tablets) should be used to treat symptomatic hypoglycemia. Other forms of carbohydrates, such as table sugar (sucrose), will be less effective in raising blood sugar as alpha-glucosidase inhibitors slow digestion of disaccharides. * Level 3 hypoglycemia (requiring assistance) — Severe hypoglycemia requires the assistance of another person to actively administer carbohydrate, [glucagon](https://www.uptodate.com/contents/glucagon-drug-information?search=hypoglycemia%20diabetes&topicRef=1805&source=see_link), or other resuscitative actions. Glucagon should be prescribed for all individuals at increased risk of level 2 or 3 hypoglycemia, so that it is available should it be needed Table : Quick sources of sugar to treat low blood sugar

| 3 or 4 glucose tablets | | :---- | | ½ cup of juice or regular soda (not sugar-free) | | 2 tablespoons of raisins | | 4 or 5 saltine crackers | | 1 tablespoon of sugar | | 1 tablespoon of honey or corn syrup | | 6 to 8 hard candies | | | \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

All nonpregnant adults should have their BP checked at age 20 or at the earliest BP measurement in the clinic Must be performed correctly. (a) Timing: Take BP after the patient is rested for at least 5 minutes, no tea/coffee or tobacco in the past half an hour (b) Patient: seated in a chair, feet flat on the floor, arm supported, remove clothing covering the location of cuff placement (c)The technique (eg, calibrated device, proper-sized cuff), Calibration, cuff, and bladder size should be appropriate (d) Number of readings: Takes 3 readings at least 5 minutes apart, if initial is high (\>140/90). Record the lower of the last 2 measurements as the clinic blood pressure. (e) Urgent/same day referrals * suspected pheochromocytoma (for example, labile or postural hypotension, headache, palpitations, pallor, abdominal pain or diaphoresis) * Hypertensive crisis/emergency: If BP is \>180/120 in clinic (for Even reported on TC \- more than two reading 5 minute apart) and there are * life-threatening symptoms such as new onset confusion, chest pain, signs of heart failure, or acute kidney injury * signs of retinal haemorrhage or papilloedema (accelerated hypertension) (f) Postural hypotension: In people with symptoms of postural hypotension, including falls or postural dizziness:

* measure blood pressure with the person lying on their back (or consider a seated position, if it is inconvenient to measure blood pressure with the person lying down) * measure blood pressure again after the person has been standing for at least 1 minute. * If the person's systolic blood pressure falls by 20 mmHg or more, or their diastolic blood pressure falls by 10 mmHg or more, after the person has been standing for at least 1 minute: * consider likely causes, including reviewing their current medication * manage appropriately (for example, for advice on preventing falls in older people,) * measure subsequent blood pressures with the person standing * consider referral to specialist care if symptoms of postural hypotension persist despite addressing likely causes * If the blood pressure drop is less than the thresholds in recommendation despite suggestive symptoms and the baseline measurement was previously taken from a seated position, repeat the measurements this time starting with the person lying on their back. * Consider referring the person for further specialist assessment if blood pressure measurements do not confirm postural hypotension despite suggestive symptoms. If clinic blood pressure is between 140/90 mmHg and 180/120 mmHg, offer home blood pressure monitoring (HBPM) to confirm the diagnosis of hypertension.

* Blood pressure is recorded twice daily, ideally in the morning and evening * Blood pressure recording continues for at least 4 days, ideally for 7 days. * Discard the measurements taken on the first day and use the average value of these measurements for management. | | NICE guidelines | | US definitions | Indian definitions | | :---- | :---- | :---- | :---- | :---- | | | Clinic BP | Home BP | | | | Normal | | | Normal \<120-80, Elevated 120-129, 80-89 | Optimal: \<120 & \<80 Normal: \<130 & \<85 High normal: 130–139 or 85–89 | | Stage 1 HT | 140-159/90-99 | 135-149/85-94 | \<140/90 | 140–159 or 90–99 | | Stage 2 | 160-179/100-119 | 150/95 or more | 140-179/90-119 | 160–179 or 100–109 | | Stage 3 | 180/120 or more | \-- | \>180/120 | ≥180 or ≥110 | | White-coat effect | A discrepancy of more than 20/10 mmHg between clinic and average daytime ABPM or average HBPM blood pressure measurements at the time of diagnosis. | | | |

| Looking for secondary hypertension | | | :---- | :---- | | When to suspect and what to check for | What to do | | In patients aged \< 40 years with evidence of target organ damage: cardiovascular disease, renal disease , retinopathy BP remains uncontrolled with optimal or maximum tolerated doses of multiple antihypertensive drugs ( 3 medicines) If hypokalaemia is present S/O PHAEOCHROMOCYTOMA Patient age \<30 years with no family history, Triad of headache (usually pounding), palpitations, and sweating S/O CUSHING’S Weakness, easy bruising, OLIGOMENORRHOEA Cushingoid facies, central obesity, proximal muscle weakness, and ecchymoses Lab tests S/O RENAL CAUSES Elevated serum creatinine concentration in young patients OR WORSENING OF CREAT/EGFR ON STARTING ACEI/ARB \- s/o renal artery setonis of more than 30% Unexplained hypokalemia (with urinary potassium wasting): Primary hyperaldosteronism (e.g. Conn’s syndrome): If there is unexplained hypokalaemia or hypokalaemia is triggered by a low-dose of diuretic, consider the possibility of hyperaldosteronism. Approximately 2-5% of patients with hypotension are thought to have a diagnosis of Conn’s syndrome. The plasma aldosterone/renin ratio (ARR) should be checked, and the patient referred to an endocrinologist if it is high Abnormal urinalysis (RBC, hematuria, protein) Elevated serum calcium S/O ACROMEGALY Brow protrusion Prognathism Macroglossia Hyperpigmentation Carpal tunnel syndrome | SEND TO IHS FOR EVALUATION | | Loud snoring or witnessed apneic episodes Daytime somnolence BMI \>30 | Sleep apnoea evaluation \- SEND TO PULMONOLOGIST | | Drug-induced hypertension: Glucocorticoids Oral contraceptives Anabolic steroids NSAIDs Chemotherapeutic agents (eg, tyrosine kinase inhibitors/VEGF blockade) Stimulants (eg, cocaine, methylphenidate) Calcineurin inhibitors (eg, cyclosporine) Antidepressants (eg, venlafaxine) | Consider stopping or replacing the medicine if possible |

| When | What to do | | :---- | :---- | | 1st consult | Workup: Even Basic HCU (HbA1c, Lipid profile, CBC, TSH, Blood pressure, Urine R/M, KFT including S. Potassium and S. calcium) ECG, ECHO,+/- fundoscopy Check requirements of and optimize medicines for ABC (HbA1c, BP, cholesterol) Assess CVD risk Q risk or WHO colour chart Lifestyle assessment and advice | | Follow up | Weight, BP, Lipids and sugar (if required), others if required as per control Smoking Alcohol intake Diet \- salt intake | | BP control targets | | | | :---- | :---- | :---- | | US guidelines | | NICE | | | Home blood pressure | Clinic based | | Higher-risk population | | | | Known CVD Heart failure Diabetes mellitus Chronic kidney disease Age ≥65 years WHO CVD Risk- Orange or more | 130/80 in clinic (lesser by 5 mm HG for home) | \<130/80 type 1 diabetes plus albumin to creatinine ratio of 70 mg/mmol or more or chronic kidney disease plus albumin to creatinine ratio of 70 mg/mmol or more | | Lower-risk | Less than 140-90 in clinic (lesser by 5 mm HG for home) | \<140/90 hypertension (with or without type 2 diabetes) or type 1 diabetes plus albumin to creatinine ratio less than 70 mg/mmol or chronic kidney disease plus albumin to creatinine ratio less than 70 mg/mmol |

Decision algorithm for drug therapy for primary/essential HT, not a k/c/o DM, CVD or heart failure or arrhythmias or proteinuric CKD [https://www.ncbi.nlm.nih.gov/books/NBK9626/table/A66/](https://www.ncbi.nlm.nih.gov/books/NBK9626/table/A66/) [https://www.ihci.in/resources/protocols](https://www.ihci.in/resources/protocols)

| Blood Pressure average | | | | :---- | :---- | :---- | | 140-159/90-99 in clinic 135/85 in home monitoring | \>160/100 150/95 in home monitoring | \>180/110 | | Monotherapy | Combination therapy | Refer for urgent management | | ACEI (Angiotensin Converting Enzyme Inhibitors) or ARBs (Angiotensin Receptor Blockers): For young patients For those with diabetes For those with microalbuminuria LVH on ECHO/ECG but no overt heart failure Baseline and Periodic (Within 1 to 2 weeks after initiation and 3 monthly) serum potassium, KFT and LFT are required after initiation of an ARB/ACEI ACEIs have side effects of dry cough, whereas ARBs don't, but cost of treatment is higher with ARBs Starting dose ACEI Ramipril 2.5 mg orally daily Enalapril 5 mg orally daily Perindopril 4 mg orally daily ARB Telmisartan 40 mg orally once daily Candesartan 4 mg orally once daily Valsartan 20 mg orally twice daily OR Long-acting CCBs (Calcium Channel Blockers) For patients with high potassium, For those with LFT or KFT derangement When follow up is difficult For people with age\>55 years Starting Dose Amlodipine 5 mg orally daily Felodipine 5 mg orally daily Monitoring: Ask the patient to do BP charting, Assess treatment after every 2 weeks, until under control. Dose escalation- If BP is not in the target range after 2-4 weeks of

initiation of treatment: Double the dose once If control is achieved, continue If the target still not achieved, switch CCB to ACEI/ARB or vice versa or start combination therapy (ACEI/ARB \+ CCB) Consider drug treatment if aged ≥80 years old with clinic BP ≥ 150/90 | 2 Drug: (ACEI/ARB \+ CCB) Preferably COMBINATION PILL OF THESE Telmisartan (40mg) \+ Amlodipine (5mg) OR Olmesartan (20mg) \+ Amlodipine (5mg) Monitoring: Ask the patient to do BP charting, Assess treatment after every 2 weeks, until under control. Dose escalation- If BP is not in target range after 2-4 weeks of initiation of treatment: Double the dose of one of the drugs once, If control achieved, continue If target still not achieved, Add 3 rd drug: Diuretics or Alpha-blockers IF Control not achieved on two drugs at optimum/maximum tolerated dosage, consider sending to IHS, they will consider 3 drug therapy (ACEI/ARB \+ CCB+thiazide like diuretics) and if required 4 drug therapy OR refer to endocrinology/cardiology for evaluation thiazide like diuretics and chlorthalidone or indapamide, assess for postural hypotension if required spironolactone (low dose 25 mg daily) if potassium \<4.5 with caution for eGFR and alpha blocker if it is \>4.5 or increase dose of thiazide diuretic OR Refer to super specialist | Hypertensive urgency Or Malignant hypertension/hypertensive emergency Malignant hypertension (als

o referred to as ‘accelerated hypertension’ or ‘hypertensive emergency’) is a syndrome characterised by severe a systolic BP \> 180 mmHg and/or diastolic BP \> 110 mmHg accompanied by end-organ damage (e.g. encephalopathy, chest pain , ,pulmonary oedema, nephropathy, eclampsia, papilloedema or retinal haemorrhage,and/or angiopathic haemolytic anaema or Suspected pheochromocytoma Urgent referral if any of the s/s/o malignant HT to emergency |

| Drug therapy for HT in patients with complications/comorbidity | | | | :---- | :---- | :---- | | Complication | Management | When to refer | | DM | Drug treatment Step 1: Offer an ACE inhibitor or an angiotensin-2 receptor blocker (ARB) to adults starting step 1 antihypertensive treatment who have type 2 diabetes. Step 2: If hypertension remains uncontrolled with an ACE inhibitor or ARB, offer the choice of a calcium-channel blocker (CCB) or a thiazide-like diuretic. Step 3: If hypertension is still not controlled, offer a combination of an ACE inhibitor or ARB, a CCB and a thiazide-like diuretic. Step 4: If hypertension is not controlled in adults taking the optimal tolerated doses of an ACE inhibitor or an ARB plus a CCB and a thiazide-like diuretic Confirm elevated clinic blood pressure using ambulatory or home blood pressure recordings. Assess for postural hypotension. For people with confirmed resistant hypertension, consider adding a fourth antihypertensive drug or seeking specialist advice. Consider further diuretic therapy with low-dose spironolactone if blood potassium level is 4.5 mmol/L or less. Consider an alpha-blocker or beta-blocker if blood potassium level is more than 4.5 mmol/L. Step 5: If blood pressure remains uncontrolled in people with resistant hypertension taking the optimal tolerated doses of four drugs, seek specialist advice. | Consider If unc

ontrolled on 3 drugs , refer if uncontrolled on 4 drugs or if e ondary HT suspected | | Heart failure with reduced ejection fraction | Patients with established heart failure should already be taking a cardioselective beta-blocker (bisoprolol, carvedilol and nebivolol), and an ACEi or an ARB. If BP remains poorly controlled, a thiazide-like diuretic should be added. If BP control remains poor despite the addition of a thiazide-like diuretic specialist advice should be sought and the addition of spironolactone or eplerenone considered. If patient not on treatment Step 1 Start with a low oral dose of an ACE inhibitor (eg, lisinopril 2.5 to 5 mg/day) or candesartan 4 to 8 mg/day or valsartan 40 mg bid Candesartan : start regimen as 4mg BD for 7 days then 4mg-8mg for 7 days and finally to 8mg BD Routine \- CBC and RFT after one month of starting the tablet CI in :severe liver disease and biliary obstruction. Step 2 Increase ACEI/ARB to a moderate dose as tolerated in approximately two weeks Step 3 If not on beta blockers Begin an initial dose of a beta-blocker (eg, carvedilol 3.125 mg twice daily or metoprolol succinate 12.5 mg), Gradually up titrate the beta blocker toward the highest tolerated dose up to the target maximal dose of beta-blocker. Step 4 After the beta blocker titration is completed, the ACE inhibitor, or single agent ARB titration is completed ALTERNATIVE TO ARB/

ACEI Change to ARNI (if the patient can afford) Sacubitril-valsartan 24 to 26 mg twice daily or IVABRADIN FOR CARDIOLOGIST | If decompensated heart failure (NYHA score 3 and above) | | Postmyocardial infarction | ACE inhibitor or ARB, beta blocker, aldosterone antagonist (spironolactone) | | | CKD \- non proteinuric | In patients with an ACR \<30 and no history of diabetes the standard treatment algorithm above should be followed | | | Proteinuric chronic kidney disease Or diabetes mellitus | ACE inhibitor or ARB | Persistent microalbuminuria ( 2 tests at least one month apart, with ACEI/ARB treatment) \>30 or one reading\>300. Also if eGFR \<60 CKD stage I and creat\>2, if suspicious and biopsy | | Angina pectoris | Beta blocker, calcium channel blocker (Non dihydropyridine-Diltiazem 90 mg-180 mg) | If the diagnosis is not confirmed, CT Angiography or interventional cardiology referral as per [protocol](https://docs.google.com/document/d/1b6OiQKFaX45DRPQZyBTldhbT-CO2LbjBxN5d5DwuzZQ/edit#bookmark=id.eur4oq1f0d8n) | | Atrial fibrillation rate control | Beta blocker, nondihydropyridine calcium channel blocker (Diltiazem 90 mg-180 mg), If a patient is already taking amlodipine, consider switching to a rate-controlling CCB. | Refer or treat inhouse depending on control | | Atrial flutter rate control | Beta blocker, nondihydropyridine calcium channel blocker (Diltiazem 90 mg

-180 mg) | Refer or treat inhouse depending on control | | Migraine | Beta Blocker \-Propranolol: starting dose is 40 mg and can go up to 320 mg daily.Other beta-blockers that can be used are timolol, atenolol, and metoprolol. Contraindications include severe asthma, peripheral vascular disease, severe bradycardia, and heart block | |

All nonpregnant adults should have their lipid profile test (Total, LDL, and HDL cholesterol and fasting Triglycerides) done at age 20 or at the earliest 1. For Cholesterol 1. Severe hypercholesterolemia: LDL cholesterol \>190 mg/dL 2. Significant Hypercholesterolemia 1. Total cholesterol \>240 mg/dL 2. LDL cholesterol \>160 mg/dl 3. Mild hypercholesterolemia 1. Total cholesterol \>200 mg/dL 2. LDL cholesterol \>130 mg/dl 4. Suboptimal cholesterol levels 1. LDL cholesterol \>100 mg/dl in adults with no CVD, 2. in established CVD now targets have been mostly revised to 77 for LDL Control possible common secondary causes of dyslipidaemia (such as excess alcohol intake, uncontrolled diabetes, hypothyroidism, liver disease and nephrotic syndrome) 1. Likey familial hypercholesterolemia: total blood cholesterol \>348mg /dL or a non-HDL cholesterol level \>OR 290 mg/dL even in the absence of a first-degree family history of premature coronary heart disease, 2. Suspect familial hypercholesterolaemia (FH) as a possible diagnosis in adults with: * a total cholesterol level \>290 mg/dL * a personal or family history (first degree relative) of premature coronary heart disease (an event before 60 years, Confirmed FH in the family Classification of LDL Cholesterol and Non-HDL Cholesterol

| Classification | LDL Goal,mg/dL | Non-HDL Goal,mg/dL | | :---- | :---- | :---- | | CHD and CHD risk equivalent 10-year risk for CHD \>20% | \< 100 (in recent years this has come to 70 ) NICE : For secondary prevention of CVD, aim for LDL \<77 OR non-HDL \< 100 mg/dL ADA: For people with diabetes and ASCVD, treatment with high-intensity statin therapy is recommended to target an LDL cholesterol reduction of ≥50% from baseline and an LDL cholesterol goal of \<55 mg/dL. Addition of ezetimibe or a PCSK9 inhibitor with proven benefit in this population is recommended if this goal is not achieved on maximum tolerated statin therapy | \< 130 (in recent years this has come to 100\) | | 10-year risk \< 20% or two or more CVD risk factors | \<100) | \< 160 (recent \<130) | | 10 year risk less than 7.5%, only risk factor is dyslipidemia | \<130) | \< 190 (recent \<100) | The primary target of drug treatment is LDL cholesterol, the secondary target is TG and for HDL derangement, lifestyle management is the only management strategy. However if TG is alone elevated \>500 \- it is a primary target from both pancreatitis and CVD risk view perspective If the secondary conditions that raise triglyceride levels cannot be managed successfully and if triglycerides are 200-499 mg/dL, the non–HDL cholesterol can be used as the initial target of using LDL-lowering medication.

| LDL management | Statin therapy for LDL lowering | | :---- | :---- | | Where Statins are indicated regardless of the LDL/non HDL levels | type 1 diabetes \- statin therapy for adults with type 1 diabetes who are over the age of 40, who have had diabetes for more than 10 years, or those with nephropathy or other CVD risk factors. Consider statin treatment even for people aged 18 to 40 with type 1 diabetes, including those who have had diabetes for 10 years or less. CKD: an estimated glomerular filtration rate less than 60 ml per minute per 1.73 m2 and/or albuminuria Familial hypercholesterolemia | | [CVD risk](https://docs.google.com/document/d/1b6OiQKFaX45DRPQZyBTldhbT-CO2LbjBxN5d5DwuzZQ/edit#bookmark=id.eur4oq1f0d8n)/Q Risk more than 10% | Offer atorvastatin 20 mg for the primary prevention of CVD to people who have a 10‑year QRISK3 score of 10% or more regardless of LDL level (atorva 20 mg or equivalent) | | LDL\>190 mg/dL | Start with high-intensity therapy: Atorvastatin 20-80 mg, Rosuvas 10-40 mg OD Start intensive lifestyle modification as well Side effects to watch out for New onset muscle pains New onset jaundice or itching or severe nausea/loss of appetite Do not start if LFT, KFT deranged, refer to IHS Repeat test in 3 months Target reduction in 3 months 40-50%, if not achieved, highest tolerated intensity: Atorva 40-80, Rosuvas 20 mg | | CVD risk \<10% bu

t LDL: \>160 | RECOMMEND STATIN Start at medium intensity: (atorvastatin: 10 mg/fluvastatin: 80 mg/rosuvastatin: 5 mg/simvastatin: 20 mg to 40 mg) or low intensity (fluvastatin: 20 mg to 40 mg/ pravastatin: 5 mg to 40 mg/ simvastatin: 10 mg) | | CVD risk \<10%, LDL: \<160 but \>100 or additional risk factors | Additional risk factors Lipids/biomarkers associated with increased ASCVD risk ( Lp(a) ≥50 mg/dL or ≥125 nmol/L, hsCRP \>2, Elevated apoB (≥130 mg/dL): A relative indication for its measurement would be triglyceride ≥200 mg/dL. A level ≥130 mg/dL corresponds to an LDL cholesterol \>160 mg/dL and constitutes a risk-enhancing factor) \- we do not offer these tests actively though TG\>175 fasting or metabolic syndrome Family history of premature ASCVD (males, age \<55 years; females, age \<65 years) Chronic inflammatory conditions, such as psoriasis, RA, lupus, or HIV/AIDS ABI (\<0.9) \- Peripheral Vascular Disease No additional risk factors: Discuss with patient [CG181 Patient decision aid on should I take a statin?](https://www.nice.org.uk/guidance/ng238/resources/patient-decision-aid-on-should-i-take-a-statin-pdf-243780159) | | Escalation of medical therapy | For secondary prevention in established CVD: REFER TO SPECIALIST to consider ezetimibe in addition to the maximum tolerated intensity and dose of statin to reduce CVD risk further, even if the lipid target

for secondary prevention of CVD is met If the lipid target for secondary prevention of CVD is not met : REFER TO SPECIALIST to consider additional lipid-lowering treatments (see [NICE's technology appraisal guidance on alirocumab](https://www.nice.org.uk/guidance/ta393), [evolocumab](https://www.nice.org.uk/guidance/ta394), and [inclisiran](https://www.nice.org.uk/guidance/ta733)). In patients with no established CVD: If LDL target of \<100 is not met , consider ezetimibe |

LFT deranged: Do not routinely exclude from statin treatment people who have liver transaminase levels that are raised but are less than 3 times the upper limit of normal Muscle pains \- Ifl 10,000 people took a statin, on average an extra 3 people would get severe muscle damage * Ask for history of severe muscle ache, if it is there , test for CPK * CPK\>5 times elevated, repeat after 7 days, still raised do not start * If muscle pain comes after starting major CPK \> 5 times, stop treatment and refer to IHS, if not try reducing dose once restarted after symptoms subside or switching to another statin Pregnancy Contraindicated in preganancy and breastfeeding , should be stopped 3 months before attempting to conceive

[Hypertriglyceridemia Management According to the 2018 AHA/ACC Guideline \- American College of Cardiology](https://www.acc.org/latest-in-cardiology/articles/2019/01/11/07/39/hypertriglyceridemia-management-according-to-the-2018-aha-acc-guideline) | | | | | :---- | :---- | :---- | | Very severe | \>20 mmol/dL \= 1776 mg/dL | Endocrinology referral, risk of pancreatitis | | Severe | \> 10 [mmol.dL](http://mmol.dL) \= 888 mg/dL | repeat the triglyceride measurement with a fasting test (after an interval of 5 days, but within 2 weeks) and review for potential secondary causes of hyperlipidaemia and seek specialist advice if the triglyceride level remains at more than 10 mmol per litre | | Significant | \>4.5 mmol/dL \= 399 mg/dL | seek specialist advice if non-HDL cholesterol level is more than 7.5 mmol per litre/ 290 mg/dL Statin \+/- Fibrate | | Mild | \>1.69mmol/dL=150 mg/dL | Lifestyle factors, statin if mixed lipid disorder | What the Even Team has chosen as definitions Very Severe hypertriglyceridemia: Fasting TG \> 880 mg/dL (risk of pancreatitis high) Severe hypertriglyceridemia: Fasting TG 500-999 mg/dL Moderate hypertriglyceridemia: Fasting TG 300- 499 mg/dL Mild hypertriglyceridemia: Fasting TG 150- 299 mg/dL

| TG level | Management along with LDL lowering therapy | | :---- | :---- | | \>500 | If \>888, refer to IHS Check for pancreatitis history- pain upper abdomen \+/- radiation to back, heavy alcohol consumption, LFT derangement, if positive refer to specialist If LDL raised, start statin If there is no history suggestive of high risk of pancreatitis, start Fenofibrate (along with statin as per LDL levels) starting dose 160 mg OD If CVD risk is high (\>30%) add fish oil capsules or other omega 3, such as Capsule Mega-3 soft or any such, dose up to 2 gm/day (one capsule has 300 mg, so 2 capsules twice daily) If there is fatty liver also consider Saroglitazar (? with/in lieu of Fenofibrate) | | 300-499 | If LDL raised, start statin Repeat test in 3 months Target TG \<150 not acheived, add fenofibrate or saroglitazar (DM or fatty liver) ?omega 3 | | 150-299, CVD risk 10% or more | If LDL raised, start statin, or can give lifestyle trial of 3 months No need for adding Fenofibrate or Omega 3 | | 150-299, CVD risk low | If LDL raised, start statin, or can give lifestyle trial of 3 months No need for adding Fenofibrate or Omega 3 |

[https://www.who.int/docs/default-source/cardiovascular-diseases/south-asia.pdf?sfvrsn=c5b0d9a32](https://www.who.int/docs/default-source/cardiovascular-diseases/south-asia.pdf?sfvrsn=c5b0d9a32)

Acute gouty arthritis typically manifests as an acute monoarthritis, most commonly in the great toe and less frequently in the tarsal joint, knee, and other joints. In acute gouty arthritis, the affected joint is typically warm, erythematous, swollen, and exquisitely painful Assess the possibility of septic arthritis, calcium pyrophosphate crystal deposition and inflammatory arthritis in people presenting with a painful, red, swollen joint. Risk factors for increasing hyperuricemia and/or raising the likelihood of incident gout include: * Alcohol intake * High levels of meat and seafood ingestion * HT medications: diuretic, beta blocker,ACEI, and non-losartan ARBs * Obesity Gout is managed in the following 3 stages: * Treating the acute attack * Providing prophylaxis to prevent acute flares * Lowering excess stores of urate

Acute gouty arthritis Indomethacin and other NSAIDs: are the drugs of choice. NSAIDs are prescribed for approximately a 7- to 10-day course or until 3-4 days after all signs of inflammation have resolved. Use NSAIDs with caution or avoid them in patients in edematous states, such as heart failure, and in patients with peptic ulcer disease or kidney insufficiency. Colchicine: administered as a 0.6-mg dose every hour until improvement occurs, adverse gastrointestinal effects occur, or a total of 10 doses is reached and no relief is noted. The adverse gastrointestinal effects include abdominal pain, diarrhea, and nausea, which occur in most patients started on colchicine. Intra-articular glucocorticoids: in patients with contraindications to NSAID or colchicine use or in those refractory to NSAIDs or colchicine. The guidelines strongly recommend initiation of urate-lowering therapy (ULT) for patients the following indications : * 1 or more subcutaneous tophi * Evidence of radiographic damage attributable to gout * Frequent gout flares (\>2/year) ULT is conditionally recommended for patients with following indications : * History of \>1 flare and infrequent flares (\< 2/year) * First flare and CKD stage \>3, Serum uric acid \>9 mg/dl, or urolithiasis

One important point to consider is that abrupt lowering of urate levels can precipitate an attack of acute gout during the intercritical period. Thus, these patients should receive prophylactic colchicine coverage. The choice of urate-lowering medications is uricosuric drugs (which promote uric acid excretion: allopurinol, Febuxtat) or xanthine oxidase inhibitors (which inhibit uric acid production, probenacid). * Allopurinol and febuxostat should be initiated at a low dose with subsequent titration to target * Concomitant antiinflammatory prophylaxis therapy (e.g., colchicine, NSAIDs, prednisone/prednisolone) for 3–6 months with ongoing evaluation and continued prophylaxis as needed if the patient continues to experience flares. * Allopurinol is the preferred first-line urate-lowering therapy (ULT) for all patients Allopurinol is the most widely used antihyperuricemic agent. The ideal candidates for allopurinol treatment are as follows: * Uric acid overproducers (24-h urinary uric acid excretion \>800 mg on general diet or \>600 mg on a purine-restricted diet) * Patients with kidney insufficiency, nephrolithiasis, or tophaceous gout * Patients at risk for developing uric acid nephropathy

The usual maintenance dose for adults is 200-300 mg/d. The long half-life of oxypurinol makes once-daily dosing possible. Very importantly, adjust the dose in persons with chronic kidney disease because a higher incidence of adverse effects is observed if the dose is not adjusted. Allopurinol is well tolerated by most patients, but hypersensitivity reactions may develop, which can be severe or fatal. Because a skin rash may progress to a severe hypersensitivity reaction, patients who develop a skin rash should discontinue allopurinol. Hepatotoxicity, bone marrow depression, and interstitial nephritis are rare but serious adverse effects of allopurinol. * Febuxostat for the long-term treatment of hyperuricemia in patients with gout dose, 40/80 mg/day However, previous studies have identified cardiovascular events with febuxostat, and large ongoing trials are comparing the cardiovascular safety of febuxostat versus allopurinol.

* Probenecid, which is a uricosuric drug, inhibits the tubular reabsorption of filtered and secreted urate, thereby increasing urate excretion. The ideal candidates for probenecid therapy are those with a 24-hour urine uric acid excretion of less than 800 mg, no history of nephrolithiasis, and good kidney function (creatinine clearance \>80 mL/min). The starting dose for probenecid is 250 mg twice a day, which can be increased gradually to a maximum daily dose of 3 g/d. Some degree of gastrointestinal irritation is experienced by approximately 2% of patients.

* Lesinurad (Zurampic) is the first selective uric acid reabsorption inhibitor (SURI) approved by the FDA. Lesinurad must be coadministered with a xanthine oxidase inhibitor and is indicated for hyperuricemia associated with gout in patients who have not achieved target serum uric acid levels with a xanthine oxidase inhibitor alone. It is not approved for asymptomatic hyperuricemia . Kidney function should be assessed before initiating therapy and periodically thereafter. More frequent monitoring is required for an estimated creatinine clearance (CrCl) below 60 mL/min. Do not initiate therapy if the CrCl is below 45 mL/min and discontinue if CrCl decreases persistently to below 45 mL/min. * Pegloticase (Krystexxa) is a recombinant, pegylated, uric acid–specific enzyme that catalyzes the oxidation of uric acid to allantoin. It is approved for use in adults with chronic gout that is refractory to conventional therapy. It is administered by intravenous infusion. * SGLT2 inhibitors: In patients with diabetes mellitus or heart failure—conditions that promote uric acid hyperproduction and reduced renal clearance—treatment with SGLT2 inhibitors can lower serum uric acid levels by approximately 0.6-1.5 mg/dL. This effect develops within the first week of starting SGLT2 inhibitor therapy and continues for the duration of treatment.

Allopurinol is the mainstay of drug therapy The incidence of urolithiasis approaches 50 percent in patients in whom daily urinary uric acid excretion exceeds 1100 mg (6.5 micromol) . However, this degree of uric acid overexcretion is uncommon. Urate kidney stones: The primary therapeutic modality in hyperuricemic but non-gouty individuals who experience a uric acid urinary tract stone is hydration (fluid intake \>2 liters daily) and urinary alkalinization with potassium citrate or potassium bicarbonate

Uptodate recommends the use of a persistent urate level of \>8 mg/dL as the threshold Disorders that appear to be largely unrelated to crystal deposition * Chronic kidney disease (CKD) : Chronic urate nephropathy: chances are higher if if uric acid levels exceed at least 13 mg/dL in men and 10 mg/dL in women * It is a form of chronic kidney disease induced by the deposition of sodium urate crystals in the medullary interstitium. The clinical features of this disorder are nonspecific: kidney function impairment, bland urinary sediment, mild proteinuria, and serum urate concentrations often higher than expected for the degree of impaired kidney function. * Greater than 9 mg/dL if the serum creatinine concentration is ≤1.5 mg/dL * Greater than 10 mg/dL in creatinine between 1.5 and 2 mg/dL * Greater than 12 mg/dL with more advanced renal failure

Thus, chronic urate nephropathy is difficult to separate from the multiple other causes of kidney function impairment in people with gout, such as hypertension and diabetes mellitus. It is thought to be uncommon and some feel that the diagnosis cannot be made on clinical grounds in the absence of kidney biopsy, chances are higher if if uric acid levels exceed at least 13 mg/dL in men and 10 mg/dL in women * Patients with a strong family history of CKD and gout should be evaluated for autosomal dominant tubulointerstitial kidney disease (ADTKD- "Autosomal dominant tubulointerstitial kidney disease") ##### Even protocol for Management of asymptomatic dyslipidemia Sustained marked asymptomatic hyperuricemia: Selected patients with sustained marked asymptomatic hyperuricemia (\>13 mg/dL ) benefit or potentially benefit from the use of pharmacologic urate-lowering therapy Aim of urate-lowering therapy \< 6mg/dL if associated manifestations and \< 8 if isolated hyperuricemia Pharmacological intervention for other diseases Substitution: acceptable alternatives for the management of diseases accompanying hyperuricemia * Fenofibrate for hyperlipidemia * Losartan or calcium channel blockers for hypertension

* Patients with gout * Serum uric acid value greater than 11 mg/dL in asymptomatic hyperuricemia or * Repeat test after lifestyle interventions after 6 months in asymptomatic hyperuricemia, if still more than 8 mg/dL, especially in young males, females who are premenopausal 1) fractional urinary excretion of uric acid (FEur): measurement of the urate and creatinine concentration in a mid-morning spot urine collection and the serum urate and creatinine Fractional excretion of urate \= \[(urine uric acid)×(serum creatinine)×(100%)\]÷\[(serum uric acid)×(urine creatinine)\]

* Overproducers: urate overproduction with hyperuricosuria (FEur is usually \>10 percent) Further workup: A 24-hour urine collection should be carried out after the patient has been on an isocaloric, reduced purine diet for three to five days containing 1 gram/kg protein daily from dairy sources and excluding alcohol, meat, seafood, and medications known to affect urate metabolism; If uric acid excretion greater than 600 mg/day on such a diet, further tests for inherited causes of overproduction have to be looked for, otherwise lifestyle management * Underexcretors: reduced urinary uric acid clearance (FEur is usually \<6 percent): Most patients with underexcretion of uric acid and with a normal GFR have no other demonstrable abnormality in renal function, so if eGFR OK, nothing to do other than lifestyle management * Mixed: However, the vast majority of hyperuricemic individuals (80 to 90 percent) demonstrate mixed factors excess dietary purine or purine precursor consumption, uric acid underexcretion, or both. The remainder exhibit overproduction of urate from endogenous sources.

* Avoiding foods that are high in purines: Meats, Poultry, Fish, Seafood, Organ meats, Beans,Peas ; dairy products are good for gout/hyperuricemia * Avoidance of alcohol and sugar-sweetened beverages * Reduction to ideal body weight * Regular exercise * Adequate magnestium and zinc intake * Use of probiotics (eg, Bifidobacteria,Lactobacilli) Best Foods for a Gout Diet: low-purine options like: * Low-fat dairy products, such as yogurt and skim milk * Fresh [fruits and vegetables](https://www.webmd.com/food-recipes/ss/slideshow-exotic-fruits) * Nuts, peanut butter, and grains * Fat and oil * Potatoes, rice, [bread](https://www.webmd.com/food-recipes/cm/rm-quiz-bread-facts), and pasta * [Eggs](https://www.webmd.com/food-recipes/ss/slideshow-eggs-6-ways) (in moderation) * Meats like [fish](https://www.webmd.com/food-recipes/guide/vitamins-and-minerals-good-food-sources), chicken, and red meat are fine in moderation (around 4 to 6 ounces per day). * Vegetables: You may see veggies like spinach and asparagus on the high-purine list, but studies show they don’t raise your risk of gout or gout attacks. Causes of hyperuricemia due to decreased uric acid clearance

| Clinical disorders | | :---- | | Chronic kidney disease of any form | | Lead nephropathy (saturnine gout) | | Effective volume depletion (eg, fluid losses, heart failure) | | Diabetic or starvation ketoacidosis | | Lactic acidosis | | Preeclampsia | | Obesity and high circulating insulin | | Drug- or diet-induced decreased uric acid clearance | | Diuretics (thiazides and loop diuretics) | | Cyclosporine and tacrolimus | | Low-dose salicylates | | :---- | | Ethambutol | | Pyrazinamide | | Ethanol | | Levodopa | | Laxative abuse (alkalosis) | | Salt restriction | | Nicotinic acid | | Rare monogenic disorders causing decreased uric acid clearance | | Autosomal dominant tubulointerstitial kidney disease caused by UMOD pathogenic variants | | Glomerulocystic kidney disease |

| | Indian standards BMI | Waist circumference Indian | International BMI | Waist circumference International | CV risk associated with obesity | | :---- | :---- | :---- | :---- | :---- | :---- | | Severely underweight | \<16.5 | | \<16.5 | | | | Underweight | 16.5-18.4 | | 16.5-18.4 | | | | Normal | 18.5-22.9 | | 18.5-24.9 | | No risk | | Overweight | 23-24.9 | | 25-29.9 | | Low risk | | Obese | | \>35.4 (90 cms) inches in male \>31.5 in (80 cms) females | | \>40 inches in male \>35 in female | | | Grade 1 | | | 30-34.9 | | Moderate risk | | Grade 2 | | | 35-39.9 | | Moderate risk Or High risk Grade 2 Obesity \+ (DM/HTN/Dyslipidemia) | | Grade 3 | | | 40 or more | | High Risk | It is necessary to rule out medical causes of obesity when there are features suggesting the same either on Blood investigation or physical examination. These may include: 1\) Endocrine causes : Hypothyroidism, Cushing’s syndrome, Hypothalamic dysfunction. 2\) Drugs: Antipsychotics, Antidepressants, Anticonvulsants, Oral hypoglycemic agents. 3\) Others : Eating disorders, syndromes, smoking cessation.

1\) Insulin resistance and hyperinsulinemia progressing to Type 2 diabetes mellitus. 2\) Deranged lipids contributing to HTN 3\) LV remodelling due to HTN \- Increased LV filling pressure lead to LVH 4\) Sleep disorder \- OSA, Atrial fibrillation , Coronary artery disease, Stroke and PAH. 5\) Increase Systemic inflammation 6\) Increased activation of the sympathetic nervous system. 7\) Endothelial dysfunction In addition to CV risk, obesity is associated with increased incidence of Endometrial carcinoma, Gout, NASH, GERD, Renal calculi, severe lung infections etc. Obesity in pregnancy can lead to adverse outcomes such as Early pregnancy loss ( due to unfavourable hormonal levels), GDM, Type 2 DM, HTN, preterm delivery, Multiple pregnancy, OSA, increased detection of congenital anomaly, Increased rates of Operative deliveries, Macrosomia, Post partum Haemorrhage, Venous thromboembolism and post partum depression. All weight loss drugs available are contraindicated in pregnancy. Initial Lab evaluation in patient with obesity: * Even complete blood profile (FBS, PPBS, HbA1c, Lipid profile, LFT, RFT, urine routine, TSH, Uric acid) * ECG, * Cortisol axis assessment ( ONLY when CUSHING’S suspected): * USG abdomen, * Sleep apnoea assessment * Body composition analysis. 1\) Diet 2\) Exercise 3\) Drugs 4\) Devices 5\) Surgery

Indicated in all patients with obesity. A weight loss of 5 to 7% in 6 months is a practical target but at this level there is no significant reduction in CV events. Atleast 10% weight loss is the minimum required for CV benefit. A calorie restricted diet includes consumption of 75% or less of daily calorie requirement or a calorie deficit of 500 K . It can achieve a weight loss of roughly 0.5 Kg/Week. 150 mins / Week moderate intensity of physical activity \+ 2-4 fullbody work out sessions per week are recommended. Use of a weight or resistance level heavy enough to tire one's muscles after about 12 to 15 repetitions is recommended. A calorie restricted diet alone can lead to loss of lean muscle mass and hence it's recommended to combine both aerobic and strength training in order to retain lean muscle mass. On GLP1 agonists the muscle mass can be even more marked, so resistance training is very important However longer durations are required to promote calorie deficit and promote more weight loss.

| | Ozempic, injectable | Wegovy, s/c Injectable | Mounjaro, s/c Injectable | | :---- | :---- | :---- | :---- | | **Weight loss** | 14 lbs (6.4 kgs) over 40 weeks using the 2 mg weekly \~6.4 kg | 13.7% of body weight, over 68 weeks \~ 15 kg | 22.8 kg/20.2% at the highest dose (15mg), 19.5% at 10 mg dose and 15.4 kg at the lowest dose (5mg) over 72 weeks | | **Approved indications** | Weight loss, BMI\>30 or BMI\> 27 with Diabetes, high BP or dyslipidemia | | Diabetes Weight loss (BMI\>30 or 27 with comorbidities | | **Dose escalation** | | weeks 1 to 4: 0.25 mg weeks 5 to 8: 0.5 mg weeks 9 to 12 : 1 mg weeks 13 to 16:1.7 mg Week 17 onwards(if needed): 2.4 mg TO BE GIVEN FOR A YEAR IF RESPONDER | weeks 1 to 4: 2.5 mg weeks 5 to 8: 5 mg weeks 9 to 12 : 7.5 mg weeks 13 to 16:10 mg Week 17 onwards(if needed): 12.5 then 15 mg TO BE GIVEN FOR A YEAR IF RESPONDER | | **Usual maintenance dose** | 1 mg/2 mg weekly | 1.7-2.4 mg/weekly | 10 mg/weekly | | **Cost** | 5000-12000/month for .25 mg to 1.7 mg Other manufacturers: Semawin 1.7 mg Injection: 3251/month Obeda 1mg injection: \~ 5000/month | | \~12000-18000/month for 2.5 mg-10 mg dose | | **Availability/Patent protection** | Patent expired | Patent expired | Patent expiring in 2036/39 | **Contraindication checklist (when not be given)**

1. Type 1 diabetes 2. Previous history of pancreatitis 3. Previous history of thyroid cancer in patient or close family or MEN 2 4. Pregnant or considering pregnancy 5. Breast feeding 6. Diabetic retinopathy 7. Kidney problems 8. Gastroparesis 9. Planned surgery 10. Depression, suicidal thoughts, mental health issues **The suggested Even protocol for weight loss:** 1. Members with BMI \> 30, or BMI \>27 WITH high BP, dyslipidemia or type 2 DM, LDL\>140 or TG\> 300 joining the weight loss program will be offered 1. Baseline tests 1. **Blood tests:** Even complete blood profile (HbA1c, FBS, Lipid profile, TFT, LFT, KFT, Urine R/M, CBC 2. **Scans**: USG abdomen, USG Thyroid, Dexa scan OPTIONAL (measure bone density, lean muscle mass, and fat mass in different parts of the body) 2. Diet and exercise modifications 3. Discussion on prescription of **Wegovy** with maintenance dose of 1.7 mg or 2.4 mg for non responders for a minimum duration of 1 year , 4. Serious side effects: [The science of safety: adverse effects of GLP-1 receptor agonists as glucose-lowering and obesity medications](https://www.jci.org/articles/view/194740) [Exploring the Side Effects of GLP-1 Receptor Agonist: To Ensure Its Optimal Positioning](https://e-dmj.org/journal/view.php?doi=10.4093/dmj.2025.0242)

5. Common side effects : 1. GI symptoms: nausea, abdominal pain or discomfort, vomiting, stypsis, or diarrhea or constipation, dehydration leading to AKI, hypoglycemia \- to minimise the ​​Adequate hydration and fiber consumption, cessation of alcoholic beverage consumption, and eating lighter and smaller meals can be useful advice 2. Muscle mass loss: up to 40% of weight lost is muscle massif no resistance training, but with proper training 6. Weight gain on stopping the treatment : ⅔ of the weight is gained back within 1 year nearly all the weight is gained back within 3 years on average 7. Comparison with bariatric surgery * BMI\>35 or \>32.5 with comorbidities or \>27.5 with HbA1c\>7.5 despite appropriate medical management * **Endocrinologist Support:**Consultant endocrinologists will be available to support the IMS team, especially in cases where side effects are persistent or worrisome, and adjustments or discontinuation may be required. * **IMS Consultation Schedule:**Days 3, 7, and 14 after starting Wegovy, At every dose escalation checkpoint, Once every 4 weeks after reaching the maintenance dose * **Dietician Consultation Schedule:** Day 1 after each IMS consultation, Once every two weeks thereafter

* **Exercise/Physiotherapy Support:** Online consultations to define each patient’s personalized physical activity plan, Based on initial physical fitness evaluation * **Psychology Support**: Provided as needed, based on recommendations by the IMS or doctor **Patient Monitoring & Logging Requirements** * Body weight: Logged weekly * Food intake: Photographic food logs at least 2 days per week * Vitals: BP and glucometer readings as advised by the IMS * Exercise: Activity logging through app or via care team **Care Coordination & Progress Tracking** * Weekly coordination between the IMS and dietician to track progress * Escalation to consultant endocrinologists when clinically required * Care coordinators (with medical backgrounds): * First follow-up call after initial doctor and dietician consults * Ongoing support via WhatsApp and phone for coordination and issue resolution **Optional Add-ons: Glucometer, CGM, BP machine** At the end of the 12-month program, patients will receive guidance and options for: * Continuing if clinically appropriate * Discontinuing and transitioning to a lifestyle-based care plan with continued monitoring and follow-up by the clinical team as advised by the IMS

##### **TFT interpretation, for those not on treatment** The above table is showing TFT results which include \- TSH, total T4 and total T3 1. TSH normal T4 decreased \- do free T4 2. TSH high \- T4 normal (SUBCLINICAL HYPOTHYROIDISM) 1. First time TSH elevation : repeat TSH and add free T4 and anti TPO, in 6-8 weeks \-TREATMENT NOT TO BE STARTED UNLESS TSH \>10 (confirm TSH\>10 with repeat before starting treatment) 2. Repeat test : TSH still high \- FOLLOW THE ALGORITHYM BELOW \- target TSH and not dose is the guiding factor, Several approaches to initiating levothyroxine therapy are acceptable. * One approach, preferred when TSH is markedly high is to base the starting dose on the serum TSH level, with full replacement doses (1.6 μg/kg body weight) * Another is to start at and lower doses (e.g., 25–50 μg) and up titrate being required in milder degrees of hypothyroidism 3. TSH high, T4 decreased \- PRIMARY HYPOTHYROIDISM **When to refer to endocrinologist- never, refer to IHS** ##### **TFT interpretation, for those on treatment**

Until TSH 0.4-4 is achieved : every 6-8 weeksdo TSH and free T4 with dose adjustment Once TSH target is achieved: once a year if anti TPO is low If anti TPO is high \- control might fluctuate \- so counsel the patient on s/s/o hyperthyroid state \- anxiety, insomnia, tremor, palpitation, diaarhoea, oligomennohrhoea and ask to come back for consult with SOS tests should those symptoms come (fT4 and TSH) TFT Patterns in patients on Rx for hypothyroidism Low TSH, normal FT4: If TSH is less than 0.1, then reduce dose, otherwise OK unless symptoms of hyperthyroidism- palpitation, anxiety or age \>65 Low TSH, high FT4: Reduce dose, otherwise OK unless symptoms of hyperthyroidism- palpitation, anxiety or age \>65 High TSH and normal FT4 OR High TSH and low FT4: Check compliance and drug interactions, if compliance is OK increase dose as per algorithm above Because co-administration of food and levothyroxine is likely to impair levothyroxine absorption, we recommend that, if possible, levothyroxine be consistently taken either 60 minutes before breakfast or at bedtime (3 or more hours after the evening meal) for optimal, consistent absorption. levothyroxine should be separated from other potentially interfering medications and supplements . A 4-hour separation is traditional, but untested.

* Iron * Calcium * Antacid but not PPI * Oral estrogen therapy * Antiepileptics : phenytoin, carbamazepine * Rifampicin * Imatinib Approximately 85 μg of T4 is secreted by the thyroid gland daily. Of the total daily T3 production of about 33 μg in normal man, approximately 80% (about 26 μg) arises from peripheral conversion from T4, and only about 20% (approximately 6.5 μg) derives from direct thyroidal secretion. It is now well established that while T4 is the major secretory product of the thyroid gland, thyroid hormone action in peripheral tissues is due to the effects of T3 binding to its nuclear receptor, defining T4 as a pro-hormone for T3. Gastrointestinal absorption of the tablet formulation of LT4 is in the 70%–80% range in healthy fasting adults . The long (approximately 7 day) half-life allows once-a-day dosing, and stable serum levels of both T4 and T3 . With such therapy, there will be a transient peak in serum T4 and free (F)T4 levels of about 15% magnitude about 4 hours after LT4 administration The signs and symptoms associated with hypothyroidism are well known and include, but are not limited to, dry skin, cold intolerance, constipation, slowed thinking, weight gain, coarse skin, puffiness, slowed heart rate, and delayed relaxation of ankle reflexes.

What are the potential deleterious effects of high TSH? Inadequate therapy would be expected to be associated with the same comorbidities as untreated disease, especially * dyslipidemia * atherosclerotic cardiovascular disease * and congestive heart failure , although likely to a less severe degree. * Severe hypothyroidism is also a cause of reversible cardiomyopathy Although no RCTs are currently available, a recent meta-analysis showed that significantly increased risk of cardiovascular mortality and morbidity was primarily observed in individuals with TSH levels \>10 mIU/L, with potential effects of TSH values \>7 mIU/L. In an additional retrospective study, fewer ischemic heart disease events were associated with treatment of SCH in those under age 70 years What are the potential deleterious effects of excessive levothyroxine? The deleterious health effects of iatrogenic thyrotoxicosis include atrial fibrillation and osteoporosis. GOOD SOURCE: [https://www.liebertpub.com/doi/full/10.1089/thy.2014.0028](https://www.liebertpub.com/doi/full/10.1089/thy.2014.0028)

Fatty liver is mostly incidentally diagnosed on ultrasound of the abdomen and reported as Grade 1,2, 3 USG Grading of fatty liver * grade I: diffusely increased hepatic echogenicity but periportal and diaphragmatic echogenicity is still appreciable * grade II: diffusely increased hepatic echogenicity obscuring periportal echogenicity but diaphragmatic echogenicity is still appreciable * grade III: diffusely increased hepatic echogenicity obscuring periportal as well as diaphragmatic echogenicity **MAFLD** A recent systematic review and meta-analysis of MAFLD prevalence from an Asian context and comprising \> 13,044,518 individuals suggested that the prevalence of MAFLD in this region is 29.62% In rural India, a region characterized by traditional lifestyles and diets, the prevalence of MAFLD is remarkably low (\~ 9%), while it mimics other Asian country prevalence rates in urban populations (16–32%) **Establishing diagnosis of NAFLD is done by ruling out other etiologies**

In incidentally found Fatty liver on Imaging, it is important to rule out other etiologies before diagnosing it as NAFLD, this includes assessing the alcohol intake, ruling out viral hepatitis and the common autoimmune and metabolic causes **Ruling out ALD** For the assessment of alcohol intake, the concept of a “Standard Drink” is important which is defined by the WHO as 10 gms of alcohol and corresponds to \~ 30 ml of 80 Proof (40% alcohol) drinks such as whiskey, vodka, gin, etc, 150 ml of wine and \~ 1 pint (330 ml) of beer. For men 2 or fewer such drinks a day and/or less than 14 such drinks in a week and for women one such drink/day and less than 7 drinks/week is defined as low-risk drinking, if the consumption is above that then ALD can not be ruled out, and abstinence should be strongly advocated * Anti-hepatitis C virus antibody, Hepatitis B surface antigen **Ruling out autoimmune and metabolic causes** * only if liver enzymes are elevated more than 3 times the normal upper limit \- do autoimmune hepatitis panel: OR REFER TO internal medicine specialist * Ceruloplasmin in lean individuals/ those not fulfilling MAFLD criteria * Plasma iron, ferritin, and total iron binding capacity in lean individuals/ those not fulfilling MAFLD criteria

| | Overall prevalence | Progression | Prevalence in Normal weight | Prevalence in Overweight | Prevalence in obese | | :---- | :---- | :---- | :---- | :---- | :---- | | NAFLD | 28-40% | | 5-34% | 70.0% | 75.3% | | NASH (as % of total NAFLD cases) | 44% | within 7 year, | 39% | 33.5% (40%) | 33.7% (40%) | | Fibrosis (≥F2) as % of total NAFLD cases | 25% | The rate of progression corresponds to 1 fibrosis stage every 14 years in NAFL and every 7 years in NASH, and is doubled by arterial hypertension | 29% | 20.3% | 21.6% | | advanced fibrosis (≥F3) as % of total NAFLD cases | 3-9% | | | 6.7% | 6.9% | **Diagnosis of Nonalcoholic Steatohepatitis (NASH )** Once NAFLD is diagnosed, it is important to assess the probability of NASH, of which advanced liver fibrosis is the more advanced stage \- which can further result in cirrhosis. the gold standard for diagnosing this of course liver biopsy, but it can its own risks, therefore it has to be judiciously used Liver biopsy is DIRECTLY recommended if the patient has:

* peripheral stigmata of chronic liver disease (suggestive of cirrhosis) * splenomegaly (suggestive of cirrhosis) * cytopenias (suggestive of cirrhosis) * has serum ferritin \>1.5 times the upper limit of normal (suggestive of NASH and advanced fibrosis) * Uncertain diagnosis and evaluation for dual etiologies. * Non-invasive tests showing indeterminate or non-concordant results. 1) Use the clinical risk calculator : [FIB-4 Score](https://www.mdcalc.com/calc/2200/fibrosis-4-fib-4-index-liver-fibrosis#evidence) These scores have good negative predictive values to exclude advanced fibrosis and is the primary clinical utility of these scores FIB-4 Score \= (Age\* x AST) / (Platelets x √(ALT)) \*Use with caution in patients \<35 or \>65 years old, as the score has been shown to be less reliable in these patients. 2) Further Investigation based on Score: Fibroscan FibroScan® is a non-invasive device that assesses the ‘hardness’ (or stiffness) of the liver via the technique of transient elastography. . Liver stiffness measurement (LSM) by VCTE is widely used in the Asia–Pacific region, in part because of patient preference against biopsy. LSM \< 10 kPa in the absence of other known clinical signs rules out, whereas a LSM of 10–15 kPa is suggestive, and \> 15 kPa is highly suggestive of compensated advanced chronic liver diseas

Transient elastography does not directly measure fibrosis and hence, false elevations (ie. over-estimation of liver fibrosis) may be observed for several reasons. Therefore, liver stiffness readings need to be interpreted carefully, and with consideration to these potential confounding factors. * Inflammation Falsely Spikes Scores: High liver enzymes (ALT/AST) from recent acute hepatitis, inflammation, or even a recent flare-up can make a healthy liver appear stiff, leading to overestimates of fibrosis. * Heart Failure & Congestion: Liver stiffness is highly sensitive to blood flow. Conditions like congestive heart failure (right-sided) can cause blood to back up into the liver, swelling it and causing artificially high stiffness readings. * Alcohol Consumption: Recent heavy alcohol intake can cause acute liver swelling and falsely increase stiffness scores. * Fasting for at least 3-4 hours prior to the scan is also required, as eating can elevate blood flow to the liver and distort readings. * Obesity & Body Habitus: Standard probes often struggle to get accurate readings in patients with a high Body Mass Index (BMI \> 30\) because the ultrasound waves cannot penetrate deep enough. **This is typically resolved using an XL probe**, but false readings or test failures are still more common. * Ascites & Mass Lesions:

The following measures apply to all patients with NAFLD: * Abstain from alcohol * Modify risk factors for cardiovascular disease Management of metabolic syndrome components \- hypertension, diabetes, dyslipidemia * Weight loss Weight loss is the primary therapy for most patients with NAFLD. We should recommend weight loss for all patients with NAFLD who are overweight/obese (body mass index \[BMI\] \>25 kg/m2 ) A recent study (n = 293) showed an improvement in liver histology (steatohepatitis) in 58% of those achieving \> 5% and in 90% of those achieving weight loss of \> 10%, respectively; only the latter demonstrated an improvement in fibrosis stage (in 45%) * Drug therapy **Saroglitazar:** Saroglitazar received approval from Drugs Controller General of India for treatment of patients with Diabetic Dyslipidemia in 2013; in NOV 2023, SAROGLITAZAR was approved for NASH/NAFLD in INDIA by DGCI, backed by multiple International and Indian studies ([EVIDENCES IV](https://www.natap.org/2019/AASLD/AASLD_82.htm), [current status of trials](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10452531/) for NAFLD,only [Dyslipidemia with DM](https://journals.viamedica.pl/cli))

The drug has been found to be non inferior in studies to [fenofibrate](https://www.jlr.org/article/S0022-2275\(22\)00066-9/fulltext) for lipid profile improvement, to [pioglitazone](https://cardiab.biomedcentral.com/articles/10.1186/s12933-020-01073-w\)) for HbA1c reduction and lipid profile impact is better especially on HDL increase and non HDL cholesterol reduction. In addition drug has shown remarkable improvements in ALT , ALT and TG reduction in fatty liver **Pioglitazone**: The use of pioglitazone for the treatment of NAFLD in diabetics and prediabetics is endorsed both by the NICE and AASLD guidelines, with significant limitations. In the first case, pioglitazone should be prescribed only in second and third-level centers, after a careful evaluation. The main side effects of glitazones are weight gain, and bone fractures in women **Vitamin E:** Similarly to pioglitazone, vitamin E is recommended by the NICE and AASLD guidelines (at a dose of 800 IU/d of α-tocopherol for 96 weeks). EASL and AISF guidelines call for more evidence before any recommendation, while Asia-Pacific guidelines advise against the use of vitamin E which is described as not beneficial by the current evidence and there are concerns about long-term safety , especially prostate cancer

[https://link.springer.com/article/10.1007/s12072-020-10094-2](https://link.springer.com/article/10.1007/s12072-020-10094-2) * Immunizations \- Vaccination of hepatitis B virus should be given to patients who have not received a full schedule or 10 years have passed since the last dose

Abnormal LFT results should only be interpreted after a review of the previous results, past medical history, drug intake, and current medical condition including * Evidence of chronic liver disease (for example, cirrhosis, portal hypertension, liver failure) * Evidence of significant alcohol consumption more than 30 gram /day for men and more than 20 gm/day for women * Conditions which are associated with a high risk of developing liver disease, such as: * pre-existing autoimmune disease or presence of non-specific symptoms (for example, fatigue, nausea, or anorexia in autoimmune hepatitis) * patients with inflammatory bowel disease (including ulcerative colitis and Crohn’s disease) * Use of hepatotoxic drugs (for example, carbamazepine, methyldopa, minocycline, macrolide antibiotics) * Family history of liver diseases (for example, hemochromatosis, Wilson’s disease) * Viral hepatitis (hepatitis B, Hepatitis C) * Risk factors for NAFLD (for example, obesity, type 2 diabetes).

| LFT | Raise in | | | | | Action | | :---- | :---- | :---- | :---- | :---- | :---- | :---- | | | AST/ALT or both raised | ALP Raised | R Ratio | GGT Raised | Bilirubin Raised | Calculate R Ratio \= (ALT value/upper limit)/(ALP value/upper limit) Calculate if both ALT and ALP are raised | | Hepatotoxic | \+ | \+/- | \>5 | \+/- | \+/- | If elevation \> 5 times: refer to GE/IM specialist Needs evaluation for acute hepatitis \- workup for acute viral or toxic hepatitis as per history PT+INR, acute viral profile, assessment for acute liver failure, toxin history etc No symptoms If \< 5 order viral markers (HBsAg, Anti HCV rapid test, Do USG abdomen, if it shows fatty liver \- follow as per fatty liver Guideline Elevation \> 3 times the UL, in presence of non-specific symptoms (fatigue, nausea, or anorexia ) refer to a gastroenterologist to r/o autoimmune hepatitis In all cases: Ask to stop all supplements/alcohol and check if on any regular medication, or not. If on statin or NSAIDs- ask to stop. If any other medical specialist consults to decide whether to stop If work up is normal, repeat LFT after 3 months twice, if still abnormal \- refer to a gastroenterologist | | Cholestatic | \+/- | \+ | \<2 | \+/- | \+/- | Order USG abdomen and viral markers : If USG shows bile duct dilation \- surgical If not medical gastroenterology/internal medicine Refer as per finding

s to surgical or medical specialty as required If only ALP is raised If rise\<1.5 times UL, ignore IF existing bone conditions such as healing fracture, adolescent/young adult, hyperthyroidism, abnormal calcium level If \>1.5 times: workup If work up is normal, repeat LFT after 3 months | | Mixed | \+ | \+ | 2-5 | \+/- | \+/- | Same work up as hepatotoxic | | Isolated bilirubin rise | \- | \- | \- | \- | \+ | If elevation \> 5 times: refer to GE specialist If \< 5 If direct \<15%: unconjugated hyperbilirubinemia R/o drug intake: rifampin, probenecid, flavaspadic acid, and bunamiodyl. No anaemia : do Viral markers: HbsAg and anti-HCV rapid If anaemia present: do viral markers \+ peripheral smear \+ retic count+LDH If hemolytic anaemia and drug ntake ruled out diagnoses as Gilbert syndrome Isolated direct hyperbilirubinemia : rare syndromes, GPs refer to IHS IHS \- consider referral to GE specialist | | Isolated GGT rise | | | | \+ | | If elevation \> 5 times : GPs refer to IHS IHS \- consider referral to GE specialist Question about alcohol intake diligently Ask patient to absolutely abstain from alcohol and repeat after 1 month, if still elevated\> 3 times or rising refer to GI/hepatobiliary specialist |

Broad dyspepsia definition: recurrent epigastric pain, heartburn, or acid regurgitation ± bloating, nausea, vomiting. \- Review drugs contributing to symptoms (NSAIDs, corticosteroids, bisphosphonates, nitrates, calcium antagonists, theophyllines). \- Consider cardiac or biliary disease in the differential for upper GI symptoms Dyspepsia is defined as upper abdominal discomfort or pain, the symptoms include recurrent epigastric pain, heartburn or acid regurgitation, with or without bloating, nausea or vomiting, belching and gas, distension of abdomen/growling stomach 1. Epigastric pain syndrome 2. Postprandial distress syndrome 3. Mixed

* No evidence of systemic, organic, or metabolic disease, * At least 1 of the following symptoms is present: **epigastric burning, epigastric pain** (Pain that does not meet biliary pain criteria, it may be provoked or relieved by ingesting meals and can also occur while fasting), or both * Severe enough to impact usual activities, * Occurring at least once per week for 3 or more months, with onset at least 6 months before diagnosis * Supportive criteria include: Postprandial epigastric bloating, nausea, and belching 1. Cholelithiasis/chronic cholecystitis/biliary colic 2. Age\> 55/60 3. Unexplained weight loss 4. Anorexia 5. Persistent Vomiting 6. Abdominal lump 7. Dysphagia 8. Odynophagia 9. Family history of upper gastrointestinal cancer 10. Malena (can confirm with stool for occult blood (FOBT \- 2 samples) before referring endoscopy) 11. Haemaemesis Rule out systemic/organic causes by a set of investigations for everyone with no red flag

| Test | Why | In which type | | :---- | :---- | :---- | | Even complete blood profile | for baseline focus on anaemia, vit B12, D deficiencies, LFT , Thyroid and rest baseline | If not done in the last year | | Even stool for dyspepsia (before starting PPI or after stopping them for two weeks) | stool occult blood, R/M, H. pylori | If symptoms are not acute (duration more than two weeks) | | USG abdomen | To r/o biliary/GB causes , chronic pancreatitis | | | Upper GI Endoscopy indications | AGA/ACG/ASGE recommend endoscopy as initial evaluation when dysphagia with weight loss or GI bleeding are present, or multiple Barrett risk factors, which include: long duration of symptoms, increased frequency of symptoms, previous oesophagitis, previous hiatus hernia, oesophageal stricture or oesophageal ulcers, or male gender | | | Repeat Upper GI Indications | **Repeat Endoscopy 1\. New or evolving alarm features after a previous EGD** \- Development of **dysphagia, weight loss, anemia, vomiting, GI bleeding, or a mass** **2\. Surveillance and follow‑up in Barrett esophagus and dysplasia** \- EGD is the **procedure of choice** for diagnosing Barrett esophagus and is repeated for **surveillance** of Barrett segments, with intervals based on length and dysplasia (e.g., every 3–5 years for nondysplastic BE). \- After endoscopic eradication therapy for dysplastic BE or early adenocar

cinoma, ESGE recommends **structured follow‑up EGDs** (e.g., at 1, 2, 3, 4, 5, 7, 10 years after treatment for baseline HGD/EAC). \- In erosive esophagitis, repeat EGD **after mucosal healing** is recommended to ensure no underlying Barrett mucosa was obscured initially. **3\. Persistent or refractory GERD / hiatal hernia symptoms** \- For typical GERD symptoms (heartburn/regurgitation) that **persist despite optimized PPI**, guidelines recommend EGD to evaluate for erosive disease, strictures, Barrett, or alternative pathology and to guide further testing (pH‑impedance, manometry). \- Patients with chronic reflux and new extra‑esophageal symptoms (e.g., cough, laryngitis) plus incomplete response to PPI often undergo EGD before advanced reflux testing. | |

| Epigastric pain syndrome (EPS) | | | :---- | :---- | | Treatment groups | Details | | Those with red flags who need upper GI endoscopy | With red flags mentioned above H/o unintentional weight loss OR Stool occult blood \+ OR Age\> 50 years at onset **\- refer to specialist for Upper GI Endoscopy** | | Those who have no red flags and have EPS BUT have never had an endoscopy | **Otherwise:** \- Leave a 2‑week PPI washout before H. pylori urea breath test or stool antigen.1 \- Offer **H. pylori “test‑and‑treat”** in dyspepsia H. pylori positive H. pylori eradication therapy Followed by a full dose PPI for 4 weeks Periodic monitoring Do not routinely offer re-testing after eradication If symptoms recur after initial treatment, offer a PPI at the lowest dose possible to control symptoms as SOS or short periods H. Pylori negative Offer a full dose PPI for 4 weeks, can extend up to 8 weeks If symptoms recur after initial treatment, offer a PPI at the lowest dose possible to control symptoms as SOS or short periods Do not routinely offer endoscopy to diagnose Barrett’s oesophagus, but consider individually and decide basis: patient’s individual risk factors () and preferences **PPIs as maintenance (if patient is responding and there are no red flags on follow ups as well)** In patients showing improvement with PPIs,maintenance dose can be given, but therapy should be discont

inued every 6 to 12 months to mitigate long-term risks **Prokinetic Agents** A 4- to 8-week course of a prokinetic agent is recommended when the aforementioned therapies fail or when symptoms recur. However, in some patients, adverse effects may lead to discontinuation of therapy. **domperidone** 10 mg 3 times daily but in India combinations of 30 mg \+PPI single dose is quite common Domperidone is linked to a slight increase in the risk of serious ventricular arrhythmias or sudden cardiac death, particularly in patients aged 60 or older, those taking daily doses over 30 mg, or those with factors predisposing them to QT prolongation. Notably, it is contraindicated in patients with cardiac conduction prolongation, significant electrolyte disturbances, heart disease, moderate or severe liver impairment, and those taking QT-prolonging drugs and potent CYP3A4 inhibitors **Antidepressants** Patients whose symptoms remain refractory after the initial 8 weeks of PPI therapy should discontinue PPIs, with consideration for initiating a TCA For those who respond partially to PPIs, TCAs may be administered in combination with PPI therapy. The recommended approaches are mentioned below. The treatment can be initiated with either of the following low-dose TCAs at night: Amitriptyline: 10 mg, Mirtazapine has shown effectiveness in improving early satiation, nutrient tolerance, and gastroi

ntestinal-specific anxiety, and in addressing unintentional weight loss. Initial therapy typically begins with 7.5 mg, administered 1 hour before bedtime. Similar to other TCAs, starting with a low dose initially is advisable, which can be gradually increased up to 45 mg daily. TCAs are initially administered for 8 to 12 weeks and then continued for 6 months if the patient responds appropriately. They may be resumed if symptoms recur | | Drug induced dyspepsia | Those on bisphosphonates, corticosteroids, NSAIDs, calcium antagonists, nitrates, and theophyllines May require stopping the medicines or dose adjustments | | Those with red flags who need imaging tests such as USG abdomen, CECT abdoment | Significant pain in abdomen- first line test is USG abdomen, if USG normal, they need UGI- some of them may have liver/biliary disease Lump/mass felt in the abdomen | | Those who have had endoscopy in the past 1 year and have documented GERD with severe oesophagitis (no ulcer) | H. pylori positive H. pylori eradication therapy Followed by a high-dose PPI for 8 weeks Periodic monitoring Do not routinely offer re-testing after eradication If symptoms recur after initial treatment, offer a PPI at the lowest dose possible to control symptoms. H. Pylori negative Offer a full-dose PPI for **8 weeks** to heal severe oesophagitis. A full dose of orally administered proton pump inhib

itors include: Lansoprazole 30 mg daily, omeprazole 20 mg daily, pantoprazole 40 mg daily, rabeprazole 20 mg daily, esomeprazole 20 mg daily, or dexlansoprazole 30 mg daily. If initial treatment fails, consider a high/double dose of the initial PPI, switching to high-potency proton pump inhibitors \- esomeprazole or rabeprazole Offer a full-dose PPI long-term as maintenance treatment for people with severe oesophagitis. Consider laparoscopic fundoplication of hiatus hernia for people who have: a confirmed diagnosis of acid reflux and adequate symptom control with acid suppression therapy, but who do not wish to continue with this therapy long term Persistent symptoms despital medical therapy In patients showing improvement with PPIs,maintenance dose can be given, but therapy should be discontinued every 6 to 12 months to mitigate long-term risks. **Repeat Endoscopy 1\. New or evolving alarm features after a previous EGD** \- Development of **dysphagia, weight loss, anemia, vomiting, GI bleeding, or a mass** **2\. Surveillance and follow‑up in Barrett esophagus and dysplasia** \- EGD is the **procedure of choice** for diagnosing Barrett esophagus and is repeated for **surveillance** of Barrett segments, with intervals based on length and dysplasia (e.g., every 3–5 years for nondysplastic BE). \- After endoscopic eradication therapy for dysplastic BE or early adenocarcinoma,

ESGE recommends **structured follow‑up EGDs** (e.g., at 1, 2, 3, 4, 5, 7, 10 years after treatment for baseline HGD/EAC). \- In erosive esophagitis, repeat EGD **after mucosal healing** is recommended to ensure no underlying Barrett mucosa was obscured initially. **3\. Persistent or refractory GERD / hiatal hernia symptoms** \- For typical GERD symptoms (heartburn/regurgitation) that **persist despite optimized PPI**, guidelines recommend EGD to evaluate for erosive disease, strictures, Barrett, or alternative pathology and to guide further testing (pH‑impedance, manometry). \- Patients with chronic reflux and new extra‑esophageal symptoms (e.g., cough, laryngitis) plus incomplete response to PPI often undergo EGD before advanced reflux testing. | | Those who have had endoscopy in the past 1 year and have documented Peptic ulcer | H. Pylori Positive: Offer H pylori eradication therapy Followed by a high-dose PPI for 8 weeks Offer repeat endoscopy if a gastric ulcer was detected, 8 weeks after beginning treatment, make sure biopsy report is reviewed If initial treatment fails, consider a high dose of the initial PPI, switching to another full-dose PPI. High-dose proton pump inhibitors are double the standard dose. High-potency proton pump inhibitors include esomeprazole or rabeprazole Offer H pylori retesting 8 weeks after beginning treatment H. Pylori negative Offer full-

dose PPI for 8 weeks Offer additional H2 RA therapy if there is an inadequate response to a PPI People using NSAIDs with diagnosed peptic ulcer Stop the use of NSAIDs where possible. Offer full-dose PPI for 8 weeks if H pylori is present, subsequently offer eradication therapy Review the need for NSAID use regularly (at least every 6 months) and offer a trial of use on a limited, ‘as-needed’ basis. Consider reducing the dose, substituting an NSAID with paracetamol, or using an alternative analgesic or low-dose ibuprofen (1.2 g daily) consider a COX-2 selective NSAID instead of a standard NSAID. In either case, prescribe with a PPI Nonhealing ulcer In people with an unhealed ulcer, GASTROENTEROLOGIST to exclude non-adherence, malignancy, failure to detect H pylori, inadvertent NSAID use, other ulcer-inducing medication and rare causes such as Zollinger–Ellison syndrome or Crohn’s disease |

Traditionally: Clarithromycin based triple-drug therapy for 14 days has been the first line combination used for H. Pylori eradication. It includes PPI+Clarithromycin \+ Amoxicillin/ Metronidazole/Tinidazole If no Penicillin allergy and no recent exposure to clarithromycin or metronidazole 1) Amoxicillin 1000 mg twice daily \+ Clarithromycin 500 mg twice daily \+ PPI Full dose ( Lansoprazole 30 mg, omeprazole 20 mg, pantoprazole 40 mg, rabeprazole 20 mg, esomeprazole 20 mg, or dexlansoprazole 30 mg) twice daily 2) Amoxicillin 1000 mg twice daily \+ Tinidazole 500 mg twice daily \+ PPI Full dose twice daily MOST COMMONLY USED \+ BISMUTH HAS BECOME A COMMON PRACTICE (Bismuth subsalicylate 300 or 524 mg 4 TIMES A DAY) If patient has penicillin allergy but no recent exposure to clarithromycin 1) Clarithromycin 500 mg twice daily \+ Tinidazole 500 mg twice daily \+PPI in Full dose twice daily There are kits available, most commonly used are * Pylokit AC (Amoxicillin 750mg \+ Clarithromycin 500mg \+ Esomeprazole 40mg) * Ulcikit ( Amoxicillin 750mg \+ Tinidazole 500m \+ Omeprazole 20mg ) * Pylokit (Tinidazole 500mg \+ Clarithromycin 250mg \+ Lansoprazole 30mg), * HP kit (Omeprazole (20mg) \+ Tinidazole (500mg) \+ Amoxycillin (750mg))

But, it may be best to prescribe the drugs separately because the kits do not have the required dose of Amoxicillin and/or Clarithromycin If patient has used Clarithromycin and metronidazole in the past few months 1) Amoxicillin 1000 mg BD \+ Doxycycline 100 mg BD \+ PPI full dose BD 2) Amoxicillin 750 mg BD \+ Levofloxacin 500 mg once daily \+ PPI full dose BD If If patient has used Clarithromycin and metronidazole in the past few months and has penicillin allergy 1) Levofloxacin quadruple therapy – levofloxacin, omeprazole, nitazoxanide, and doxycycline (LOAD) but may be better to REFER TO GASTROENTEROLOGIST

* No evidence of systemic, organic, or metabolic disease, * At least 1 of the following symptoms is present: postprandial fullness (that impacts the quality of life) or early satiety that prevents finishing a regular-size meal. * severe enough to impact usual activities * occurring at least 3 days per week for 3 or more months, with onset at least 6 months before diagnosis * Supportive symptoms include the following: Loss of appetite, Nausea, Retching, Vomiting (persistent vomiting suggests another condition), epigastric bloating,

| Red flag | Concern | | :---- | :---- | | Age of onset after age 50 years | Malignancy | | Unexplained weight loss | Malignancy, IBD, malnutrition, tropical sprue | | Unexplained non minimal rectal bleeding or melena | Malignancy | | Unexplained anal mass or unexplained anal ulceration | Malignancy | | Changes in their bowel habit after age \>40 , increasing constipation | Malignancy | | Progressive abdominal pain : it is unusual except in individuals where the underlying diseases are the ones that cause malabsorption | IBD (Crohn's disease/ulcerative colitis) Chronic pancreatitis Intestinal pseudo-obstruction Intestinal lymphoma | | Chronic diarrhoea | IBD, food intolerance- milk, gluten (watery diarrhea, excess flatus, and bloating) infective \- amoebic, giardiasis (small-volume frequent diarrhea ) [Table](https://docs.google.com/document/d/1b6OiQKFaX45DRPQZyBTldhbT-CO2LbjBxN5d5DwuzZQ/edit#heading=h.iugwsenrrjju): [list of causes of watery or fatty or inflammatory diarrhea](https://docs.google.com/document/d/1b6OiQKFaX45DRPQZyBTldhbT-CO2LbjBxN5d5DwuzZQ/edit#heading=h.iugwsenrrjju) | | Nocturnal pain or diarrhoea | IBD | | Mucus AND blood in stool in chronic diarrhea (not acute infective) The occurrence of diarrhea during fasting | IBD | | New onset Iron deficiency anemia or anemia in men or low serum protein , (vitamin B12 and D deficiencies are quite common anyway) | Malabsorption | | Drug history | [Drugs causing diarrhea](https://docs.google.com/document/d/1b6OiQKFaX45DRPQZyBTldhbT-CO2LbjBxN5d5DwuzZQ/edit#heading=h.92lvmw792je5) |

| Test | Why | When to do | | :---- | :---- | :---- | | Even complete blood profile | Focus on anaemia, S. protein/albumin, vit B12, D deficiencies, LFT , Thyroid and rest baseline \+/- Iron studies+ferritin | IF not done in the past six months | | Even stool for dyspepsia | stool occult blood, R/M, H. pylori | If symptoms are not acute (duration more than two weeks) | | USG abdomen | To r/o biliary/GB causes , chronic pancreatitis | If pain abdomen or severe symptoms | | Stool for reducing substances | with reporting lactose/milk intolerance or prolonged distress after infective diarrhoea | per history | | Stool calprotectin | chronic diarrhoea, to r/o IBD , if two nutritional deficiencies, blood in stool history | per history | | Stool fat, RBC folate | if prolonged history of diarrhoea, weight loss , nutritional deficiencies present , to r/o tropical sprue or pancreatitis | per history | | Anti tTG | to r/o celiac sprue h/s/o gluten sensitivity, chronic, nutritional deficiencies present, weight suboptimata | per history | | Clostridium difficile | For patients who are currently taking antibiotics, who have taken antibiotics within the past three months, or who have been hospitalized within the past three months prior to presentation with diarrhea | |

if no red flags, investigations above \- not s/o other causes Definition 1 of IBS (Rome IV criteria for IBS) Recurrent abdominal pain, on average, at least one day per week in the last three months, * Associated with two or more of the following criteria * Related to defecation * Associated with a change in stool frequency * Associated with a change in stool form (appearance) A diagnosis of IBS should be considered only if for the last 6 months the person has had * abdominal discomfort that is either relieved by defecation or associated with altered bowel frequency or stool form AND * at least two of the following four symptoms: * altered stool passage (straining, urgency, incomplete evacuation) * abdominal bloating (more common in women than men), distension, tension or hardness * symptoms made worse by eating * passage of mucus * Other features such as lethargy, nausea, backache, and bladder symptoms are common in people with IBS and may be used to support the diagnosis

IBS with predominant constipation – Patient reports that abnormal bowel movements are usually constipation (type 1 and 2 in the BSFS) IBS with predominant diarrhea – Patient reports that abnormal bowel movements are usually diarrhea (type 6 and 7 in the BSFS) IBS with mixed bowel habits – Patient reports that abnormal bowel movements are usually both constipation and diarrhea (more than one-fourth of all the abnormal bowel movements were constipation and more than one-fourth were diarrhea) IBS unclassified – Patients who meet diagnostic criteria for IBS but cannot be accurately categorized into one of the other three subtypes. * Age-appropriate colorectal cancer screening in all patients. * In IBS patients with constipation, an abdominal radiograph to assess for stool accumulation and determine the severity. * Physiologic testing to be done by specialists/gastroenterologists (anorectal manometry and balloon expulsion testing) to rule out dyssynergic defecation in patients with severe constipation that is refractory to management with dietary changes and osmotic laxative therapy 1. Infective causes : amoebic colitis and giardiasis \- Ciplox TZ 2. SIBO \- Rifaximin for 14 days \+ or f/b probiotics thrice daily for 14 days (probiotics can be given for 4 weeks)

* Loperamide for diarrhoea: 2 mg 45 minutes before a meal on regularly scheduled doses. (maximum daily dose 16 mg/day). * Bile acid sequestrants: In patients with persistent diarrhea despite antidiarrheals, use bile acid sequestrants (eg, cholestyramine, colestipol, colesevelam). However, their use is controversial and is limited by associated gastrointestinal side effects including bloating, flatulence, abdominal discomfort, and constipation Antispasmodic agents for pain: Antispasmodics should be administered on an as-needed basis and/or in anticipation of stressors with known exacerbating effects Typical doses include: * Dicyclomine 20 mg orally four times daily as needed * Hyoscyamine 0.125 to 0.25 mg orally or sublingually three to four times daily as needed * Sustained release hyoscyamine 0.375 mg orally every 8 to 12 hours or 0.75 mg orally every 12 hours * [Drugs causing constipation](https://docs.google.com/document/d/1b6OiQKFaX45DRPQZyBTldhbT-CO2LbjBxN5d5DwuzZQ/edit#heading=h.ns3g0ibdg5iz) People with IBS should be advised how to adjust their doses of laxatives or antimotility agents according to the clinical response. The dose should be titrated according to stool consistency, with the aim of achieving a soft, well-formed stool (corresponding to Bristol Stool Form Scale type 4).

Isabgol husk: 1-2 tablespoons in a glass of water at night, try for 2 weeks PEG or lactulose: In patients with IBS with constipation (IBS-C) who have failed a trial of soluble fiber (eg, psyllium/ispaghula), we suggest polyethylene glycol (PEG). milk of magnesia, or lactulose.

Lubiprostone: Use lubiprostone in patients with IBS with persistent constipation despite medicines above. The approved dose for IBS-C is 8 micrograms twice daily in women. Discontinue lubiprostone in patients who fail to respond to a 12-week trial Linaclotide: Reserve for patients with persistent constipation despite osmotic laxative use. Oral: 290 mcg once daily; dose may be reduced to 145 mcg once daily if the patient develops diarrhea (typically occurs within 2 weeks). Symptoms of abdominal pain and bowel function generally improve by day 7, allow up to an 8-week trial before considering alternative therapy Tenapanor: use tenapanor in patients who fail other therapies for constipation. Improvement may be seen within seven days; discontinue tenapanor in patients who fail to respond to a four-week trial Consider tricyclic antidepressants (TCAs) as second-line treatment for people with IBS if laxatives, loperamide, or antispasmodics have not helped. Start with (5–10 mg equivalent of amitriptyline), take once at night, and review regularly. Increase the dose if needed, but not usually beyond 30 mg.

Referral for psychological interventions (cognitive behavioral therapy \[CBT\], hypnotherapy, and/or psychological therapy) should be considered for people with IBS who do not respond to pharmacological treatments after 12 months and who develop a continuing symptom profile (described as refractory IBS). Diet 1st level diet advice to be given by medical practitioners

* Have regular meals and take time to eat. * Drink at least 8 cups of fluid per day, especially water or other non-caffeinated drinks, for example, herbal teas. * Restrict tea and coffee to 3 cups per day. * Reduce intake of alcohol and fizzy drinks. * Reduce intake of 'resistant starch' (starch that resists digestion in the small intestine and reaches the colon intact), which is often found in processed or re-cooked foods. * Limit fresh fruit to 3 portions per day (a portion should be approximately 80 g). * It may be helpful to limit the intake of high-fiber food (such as wholemeal or high-fiber flour and breads, cereals high in bran, and whole grains such as brown rice, foods that increase flatulence (eg, beans, onions, celery, carrots, raisins, bananas, apricots, prunes, Brussels sprouts, wheat germ, pretzels, and bagels), alcohol, and caffeine) * People with diarrhea should avoid sorbitol, an artificial sweetener found in sugar-free sweets (including chewing gum) and drinks, and in some diabetic and slimming products. * People with wind and bloating may find it helpful to eat oats (such as oat-based breakfast cereal or porridge) and linseeds (up to 1 tablespoon per day) or ispaghula powder ( up to one tablespoon per day) * Empiric trial of a lactose-free diet should be given in patients who complain of persistent abdominal bloating despite the exclusion of gas-producing foods * Gluten avoidance — Nonceliac gluten sensitivity (NCGS) has been hypothesized as an underlying mechanism for symptom generation in patients with IBS but evidence to support gluten avoidance in patients with IBS has been conflicting

If these measures do not result in improvements in 6 weeks * A more structured single food avoidance and exclusion diets (for example, a low FODMAP \[fermentable oligosaccharides, disaccharides, monosaccharides, and polyols\] diet) have to be tried. These should be given by a healthcare professional with expertise in dietary management. IBS patients experience better management of the condition if they regularly take part in physical activity, sports or an exercise program - As stated by WHO & ACSM, 150 minutes of physical activity per week is beneficial for all individuals. It is especially beneficial for those affected with IBS as contraction of the abdominal muscles in turn helps smoother movement of the bowel. - A study in 2018 showed that low to moderate intensity aerobic activities have shown to relieve symptoms of IBS. - According to two other studies from 2011 & 2015, it was shown that in fact individuals who were not physically active had more severity of symptoms and an experiment with one hour of yoga sessions, three times a week increased the relief in symptoms of IBS. - The efficacy of techniques such as abdominal massage, pelvic floor exercises and breath training are all being considered in clinical trials.

The world gastroenterology organization mentions in its global guidelines that educating the patients about IBS has a positive effect on the treatment outcome. It is important that the physician takes time to explain the medical condition. This contains the name of the disease, development, pathophysiology, prognosis, and various treatment options The cognitive behavioral model for treating IBS focuses primarily on the following components: (1) psychoeducation about the stress response and its relationship to Gut related symptoms; (2) Building insight into cognitive and behavioral responses to IBS symptoms and/or fear of symptoms; and (3) Modifying those responses to decrease distress related to IBS and decrease physical reactivity to stress. Mindfulness-based therapy (MBT) is a form of treatment that uses meditation and relaxation to foster awareness and acceptance of the present moment The goal of these exercises is to notice and to accept discomfort (physical and/or mental) without making any judgments or attempts to change the present moment.

In clinical practice and guidelines, Diarrhea is primarily defined by increased stool looseness and frequency, usually operationalized as ≥3 loose or watery stools per day. **Duration qualifiers (acute vs chronic**) \- **Acute diarrhea**: abrupt onset of ≥3 loose stools per day, lasting **≤14 days**.12 \- **Chronic/persistent diarrhea**: episode **\>14 days**; this WHO‑supported distinction is used in classification and management

Acute Diarrhea is usually self‑limited; the approach centers on early triage for dehydration/sepsis, sparing tests in mild cases, and targeted stool work‑up plus antibiotics in severe or high‑risk presentations. red flags: high fever, bloody/mucoid stools, severe abdominal pain, ≥6 stools/24 h, immunocompromise, age \<3 months or frail elderly, recent antibiotics or hospitalization, IBD, pregnancy. No routine labs/stool tests in **mild, afebrile, nonbloody diarrhea** in immunocompetent adults/older children; treat supportively

When Tests should be done Fever, **bloody or mucoid stools**, severe cramping/tenderness, or signs of sepsis. Which tests? \- Stool Culture for **Salmonella, Shigella, Campylobacter,** \- **If STEC (Shiga Toxin producing E. coli)** suspected (bloody diarrhea, ground beef, outbreaks): order **Shiga toxin assay ± O157 culture**, and avoid empiric fluoroquinolones/β‑lactams until ruled out. \- **For Clostridioides difficile**: For symptomatic patients (≥3 unformed stools/24 h), recent antibiotics or hospitalization \- **GDH EIA** (antigen) \+ **toxin A/B EIA**, often arbitrated by **NAAT (PCR**); or NAAT \+ toxin \- Blood cultures in: infants \<3 months, toxic‑appearing patients, suspected enteric fever or bacteremia, or significant immunosuppression. \- **For Yersinia** **enterocolitica: UNCOMMON IN INDIA , BUT POINTER IS a pseudoappendiculitis in school children** **BUT IT IS ACCEPTABLE TO GO FOR EMPIRICAL ANTIBIOTIC THERAPY IN DIARRHOEA WITH FEVER+/- BLOOD IN STOOL**

\- **Oral rehydration therapy (ORT**) with reduced‑osmolarity ORS is first‑line for mild–moderate dehydration in adults and children.34 \- Mild–moderate dehydration: 50–100 mL/kg over 3–4 h \+ ongoing replacement (60–120 mL \<10 kg; 120–140 mL \>10 kg per stool/emesis).3 \- **Severe dehydration, shock, or altered mental status** → isotonic IV fluids (NS or LR; 20 mL/kg boluses) until perfusion and mentation normalize, then transition to ORS.34 \- **Diet**: early refeeding with age‑appropriate usual diet; avoid “BRAT” as sole regimen. Breastfeeding should continue.39 \- **Antimotility agents**: \- **Adults**: loperamide acceptable in acute watery diarrhea without fever or blood; avoid in suspected/confirmed inflammatory diarrhea, *C. difficile*, or toxic megacolon risk.43 \- **Children \<18 y**: avoid loperamide in acute infectious diarrhea.4 Most bacterial gastroenteritis is self‑limited; antibiotics are reserved for specific scenarios.103

\- **Empiric** (while awaiting tests) in adults with severe illness (high fever, dysentery, sepsis, traveler with severe diarrhea), or high‑risk hosts (elderly, immunocompromised, significant comorbidity): **ciprofloxacin or azithromycin**, chosen by local resistance and travel history.4 \- **Pathogen‑specific examples** (per Medscape pediatric/IDSA summaries; extrapolate to adults with dosing adjustments):3 \- *Shigella*: TMP‑SMX first‑line where susceptible; or ceftriaxone/cefotaxime. \- Invasive *Salmonella*: ceftriaxone/cefotaxime; treat infants \<3 mo, immunocompromised, or systemic disease. \- *Campylobacter*: macrolide (erythromycin/azithromycin) shortens course. \- *C. difficile*: stop inciting antibiotics; treat with oral metronidazole or vancomycin depending on severity and age.35 \- *Giardia*: metronidazole or nitazoxanide; *Entamoeba histolytica*: metronidazole followed by luminal agent (iodoquinol/paromomycin).3 Avoid antibiotics in suspected STEC O157 or other Shiga toxin–producing *E. coli* due to HUS risk.47

\- **Hospitalize** if: severe dehydration, inability to maintain ORT, sepsis, intractable vomiting, significant comorbidities, very young/elderly without reliable caregivers. \- **Specialist referral** if: persistent diarrhea ≥14 days, recurrent episodes, complicated infection (e.g., fulminant *C. difficile*), or suspicion of IBD or other chronic pathologies once infectious evaluation is negative.

**Common infectious causes of chronic (≥4 wk) diarrhea** **Protozoa (most important group**) \- *Giardia lamblia* and *Cryptosporidium* spp are among the most common parasitic causes of persistent diarrhea; both can present with \>7–14 days of watery diarrhea and malabsorption, especially in children and immunocompromised hosts. \- *Cyclospora cayetanensis* causes subacute–chronic watery diarrhea with fatigue, weight loss, and often requires targeted testing; outbreaks are foodborne. **Common in HIV/AIDS** \- *Entamoeba histolytica* may cause chronic dysenteric diarrhea and colitis. **Helminths** \- Soil‑transmitted helminths and others (e.g., *Strongyloides*, *Schistosoma* where endemic) may produce chronic diarrhea, often with eosinophilia or malabsorption. **Bacteria and C. difficile** \- Enteric bacteria (*Campylobacter, Salmonella, Shigella, Yersinia*, diarrheagenic *E. coli*) can have protracted courses, especially in immunocompromised patients or with ongoing exposure. \- *Clostridioides difficile* can cause subacute–chronic colitis and should be considered with antibiotic or healthcare exposure, IBD, or immunosuppression. **Non infectious chronic diarrhoea** Work up **Stool‑based evaluation to distinguish infectious from noninfectious causes** **1\. First‑line stool tests (all chronic diarrhea where infection possible**)

- Stool R/M for leukocytes \- s/o inflammatory causes \- **Stool culture** for *Salmonella, Shigella, Campylobacter, Yersinia* when there is fever, blood, or inflammatory features \- **C. difficile testing** (GDH/toxin/NAAT algorithm) on diarrheal stool in patients with recent antibiotics, hospitalization, IBD, surgery, or immunosuppression. \- **Ova and parasite (O\&P) examination**, ideally on three specimens 2–3 days apart, to detect protozoa and helminths. **2\. Targeted protozoal testing (high yield for chronic diarrhea**) (Stool for Ova \&Parasite ×3 days OR antigen/PCR for *Giardia* and *Cryptosporidium* and Entamoeba histolytica , modified acid‑fast stain or PCR for *Cyclospora/Cystoisospora* **3\. Interpreting results and pivoting to noninfectious work‑up** \- If repeated stool cultures, *C. difficile* assays, and parasite tests are negative, and diarrhea persists ≥4 weeks, noninfectious causes (IBS‑D, bile acid diarrhea, celiac disease, IBD, pancreatic insufficiency, microscopic colitis) become more likely and should be evaluated per chronic diarrhea algorithms (serology for celiac, fecal calprotectin, colonoscopy with biopsies, fecal elastase, bile acid tests).

**Treatment of chronic infective diarrhoea** Because chronic protozoal diarrhea is etiologically heterogeneous (Giardia, luminal *Entamoeba*, *Cryptosporidium*, *Cyclospora*, *Cystoisospora*), and each responds best to different agents, the referenced sources emphasize **organism‑specific therapy** rather than a single empiric drug. \- Prioritize **diagnostic stool work‑up** \- Then select **metronidazole, TMP‑SMX, nitazoxanide, or paromomycin** according to the most likely or identified pathogen and immune status, rather than giving one empiric antiprotozoal to all patients. \- **Giardia / luminal amebiasis / mixed nonbloody chronic diarrhea** \- **Metronidazole/Tinidazole** treats *Giardia lamblia* and *Entamoeba histolytica*, as well as *Balantidium coli* and *Blastocystis hominis*. \- In invasive Amebiasis, metronidazole must be followed by a luminal agent such as **paromomycin** or **iodoquinol** to eradicate intraluminal cysts; they are also used for asymptomatic luminal infection. \- **Cyclospora / Cystoisospora (Isospora**) \- **Trimethoprim–sulfamethoxazole (TMP‑SMX**) is considered the **drug of choice** for isosporiasis and cyclosporiasis and is used as targeted therapy where these are suspected.

\- **Cryptosporidium** \- In immunocompetent adults and children \>12 months, **nitazoxanide** is the only FDA‑approved therapy for cryptosporidiosis; it significantly shortens diarrhea and is given as a 3‑day course. \- **Paromomycin** is partially active and sometimes combined with azithromycin in immunocompromised patients. **Uncomplicated intestinal strongyloidiasis (including diarrhea**) \- **Indication**: All patients with documented *Strongyloides* should be treated, even if asymptomatic, because of hyperinfection risk. \- **First-line drug –Ivermectin for 2 days** * Metro (adult Giardia): 500 mg PO q12h × 5–7 d or 400 mg tds x 5 d * Tinidazole: 2 gm OD for 3 days * Metro (peds Giardia): 15 mg/kg/d PO divided q8h × 5 d * Nitazoxanide (adult): 500 mg PO q12h × 3 d * Nitazoxanide (peds): 100–200 mg PO q12h × 3 d (age-based) * Paromomycin (Giardia/pregnancy): 10 mg/kg PO TID × 5–10 d for strongyloides * 25–35 mg/kg/day PO ÷ q6h for 5–10 days as luminal amebicide in amoebic colitis * **Ivermectin**: 200 µg/kg PO once daily for **2 days** \- A 2‑day course has reported cure rates \~97%. Relative contraindications: pregnancy, breastfeeding, weight \<15 kg, and concomitant *Loa loa* infection. **Classify as small bowel vs large bowel diarrhoea**

* Small-bowel: * Large-volume, weight loss, steatorrhea, malabsorption, can have blood and mucus in IBD * Pain pattern: more periumbilical/upper abdominal; less urgency/tenesmus., * Mostly osmotic diarrhoea: stool output linked to offending nutrient, improves with fasting * stool osmotic gap \>100 mOsm/kg using 290 – 2×(Na+K) * Small-bowel etiologies: celiac, SIBO; colon: bile acid diarrhea, microscopic colitis, IBD * Colonic: * Frequent, low-volume, tenesmus, urgency/mucus, sometimes blood, secretory diarrhoea * Large bowel etiologies: Bile acid diarrhea, Microscopic colitis * Approach to differentiate: * history \+ * basic labs * fecal calprotectin * celiac tests → colonoscopy vs small-bowel evaluat (Upper GI endoscopy \+ biopsy) **Practical diagnostic approach implied** 1\. **History/PE** \- Classify as **large-volume ± weight loss/steatorrhea** (favor small bowel) vs **frequent, small-volume with urgency/mucus/blood** (favor colon).1 \- Screen for alarm signs (blood, nocturnal diarrhea, weight loss, anemia, age ≥45). 2\. **First-line tests** \- **Serology for celiac disease**: tTG‑IgA \+ total IgA to detect small-bowel celiac enteropathy.1 \- **Fecal calprotectin** to screen for colonic IBD.

3\. **Direction of endoscopy** \- **Colonic pattern or elevated fecal calprotectin** → **colonoscopy with random biopsies** to evaluate for IBD and microscopic colitis (microscopic colitis affects \~13% of chronic diarrhea).1 \- **Small-bowel pattern or positive celiac serology** → **upper endoscopy with duodenal biopsies** for celiac; consider small-bowel imaging or SIBO testing as indicated.1 4\. **Stool osmotic gap** (select cases) \- Use when osmotic vs secretory distinction will change the differential (e.g., carbohydrate malabsorption vs secretory colitis).

\- **Evaluation of colitis / IBD**: Define extent, differentiate UC vs Crohn colitis, intubate terminal ileum, assess strictures; multiple biopsies recommended , when fecal calprotectin is high in chronic diarrhoea **\- Rectal bleeding / lower GI bleeding**: Localization and potential endoscopic hemostasis (epinephrine, thermal, clips, banding) for diverticula, AVMs, post‑polypectomy bleeding, etc BUT in s/s/so Outlet bleeding: bright red, on paper/bowl, coats stool, end of defecation: first order is DRE+flexible sigmoidoscopy \- **Iron‑deficiency anemia, change in bowel habits, abdominal pain**: In adults where a colonic source is suspected; these are listed as common indications in rectal/colon cancer workups2 3. \- **Evaluation of suspected or known CRC / polyps**: Radiographic or sigmoidoscopic detection of a polyp or mass, especially ≥1 cm or proximal disease1 \- **Preoperative mapping for planned colon cancer resection** \- **Abnormal imaging**: Focal colonic wall lesions or strictures on barium enema, CT, or other imaging → colonoscopy for characterization and biopsy1 **\- Large-bowel obstruction / pseudo‑obstruction / volvulus**: For diagnosis and, in selected cases, therapeutic decompression (e.g., sigmoid volvulus, Ogilvie syndrome) or stent placement4 1.

\- **Average-risk CRC screening**: Begin at age **45**; colonoscopy every **10 years** is a primary option, typically continued through \~75 y if life expectancy ≥10 y \- **Positive noninvasive tests**: Abnormal FOBT/FIT, stool DNA, or blood-based CRC screening requires diagnostic colonoscopy to localize and treat lesions \- **Family history**: First-degree relative with CRC or advanced adenoma → colonoscopy starting at 40 y or 10 y younger than index case; usually every 5 y when higher risk \- **Hereditary syndromes (e.g., HNPCC, FAP)**: Intensified surveillance (e.g., q1–2 y starting 20–25 y in HNPCC; annual endoscopy from 10–12 y in FAP) and consideration of prophylactic colectomy in FAP \- **Polypectomy / EMR/ESD for early CRC**: Endoscopic resection is first‑line for most adenomas and many early cancers4 1. \- **Endoscopic treatment of bleeding**: Injection, coagulation, APC, clipping, banding for lower GI bleeding lesions1. \- **Balloon dilation of benign strictures, stent placement for malignant obstruction**, and **decompression of sigmoid volvulus or acute colonic pseudo‑obstruction** in selected patients4 1.

\- **Post‑adenoma polypectomy**: Interval based on number, size, histology (e.g., 3 y for advanced adenoma or ≥3 adenomas; 5–10 y for 1–2 small low‑grade tubular adenomas) \- **After CRC resection**: Colonoscopy at 6–12 months, then annually ×2; if negative, often every 3–5 y thereafter \- **Chronic IBD colitis (UC, Crohn colitis)**: Start 8–10 y after symptom onset; repeat every 1–2 (up to 3\) years depending on extent, inflammatory burden, PSC, and prior dysplasia1 Table: Differential diagnosis of chronic diarrhea by stool characteristics

| Watery diarrhea | | :---- | | Osmotic diarrhea | | Carbohydrate malabsorption | | Osmotic laxatives (eg, Mg++, PO4–3, SO4–2) | | Secretory diarrhea | | Bacterial toxins | | Bile acid malabsorption | | IBD (some cases) | | Medications and toxins | | Disordered motility | | Diabetic autonomic neuropathy | | IBS | | Postsympathectomy diarrhea | | Postvagotomy diarrhea | | Endocrinopathies | | Addison's disease | | Neuroendocrine tumors | | Hyperthyroidism | | Mastocytosis | | Medullary carcinoma of the thyroid | | Idiopathic secretory diarrhea (epidemic and sporadic) | | Stimulant laxative abuse | | Neoplasia | | Colon carcinoma | | Lymphoma | | Villous adenoma | | Vasculitis | | Inflammatory diarrhea | | Diverticulitis | | Infectious diseases | | Invasive bacterial infections (eg, tuberculosis, yersinosis) | | Invasive parasitic infections (eg, amebiasis, strongyloidiasis) | | Pseudomembranous colitis | | Ulcerating viral infections (eg, cytomegalovirus, herpes simplex virus) | | IBD (most cases) | | Ischemic colitis | | Neoplasia | | Colon cancer | | Lymphoma | | Radiation colitis | | Fatty diarrhea | | Malabsorption syndromes | | Mesenteric ischemia | | Mucosal diseases (eg, Crohn disease, Whipple's disease) | | SBS | | SIBO | | Maldigestion | | Inadequate luminal bile acid concentration | | Pancreatic exocrine insufficiency |

Mg++: magnesium; PO4-3: phosphate; SO4-2: sulfate; IBD: inflammatory bowel disease; IBS: irritable bowel syndrome; SBS: short bowel syndrome; SIBO small intestinal bacterial overgrowth. * Infective chronic diarrhoea: *Giardia, Cryptosporidium, Cyclospora, Cystoisospora, Entamoeba histolytica* * SIBO (Small intestinal bacterial overgrowth) * IBS ( Irritable Bowel Syndrome) * IBD (Inflammatory bowel disease) * Chronic pancreatitis * Food intolerance (especially carbs- lactose, FODMAP foods) * Automic dysfunction \- diabetic diarrhoea | System targeted by drug | Type of agent | Examples | | :---- | :---- | :---- | | Cardiovascular | Antiarrhythmics | Digoxin Procainamide Quinidine | | | Antihypertensives | ACE inhibitors Angiotensin II receptor blockers\* Beta blockers Hydralazine Methyldopa | | | Cholesterol-lowering agents | Clofibrate Gemfibrozil Statins | | | Diuretics | Acetazolamide Ethacrynic acid Furosemide | | Central nervous system | Antianxiety drugs | Alprazolam Meprobamate | | | Antiparkinsonian drugs | Levodopa | | | Other agents | Anticholinergic agents Fluoxetine Lithium Tacrine | | Endocrine | Oral hypoglycemic agents | Metformin | | | Thyroid replacement therapy | Synthroid |

| Gastrointestinal | Antiulcer/antacid drugs | H2RAs Magnesium-containing antacids Misoprostol Proton pump inhibitors | | :---- | :---- | :---- | | | Bile acids | Chenodeoxycholic acid Ursodeoxycholic acid | | | Laxatives | Cathartics Lactulose Sorbitol | | | Treatments for inflammatory bowel disease | 5-aminosalicylates (particularly olsalazine) | | Musculoskeletal | Gold salts | Auranofin | | | Nonsteroidal anti-inflammatory drugs | Ibuprofen Mefenamic acid Naproxen Phenylbutazone | | | Treatments for periodic fever syndrome or gout | Colchicine | | Other | Antibiotics¶ | Amoxicillin Ampicillin Cephalosporins Clindamycin Neomycin Tetracycline | | | Antineoplastic agents | Many | | | Dietary | Alcohol Sugar substitutes (eg, sorbitol) | | | Vitamins | Magnesium Vitamin C | ACE: angiotensin-converting enzyme; H2RA: histamine-2 receptor antagonist. \* Olmesartan has been associated with sprue-like enteropathy. ¶ Most antibiotics have been associated with diarrhea. | Analgesics | | :---- | | Anticholinergics | | Antihistamines | | Antispasmodics | | Antidepressants | | Antipsychotics | | Cation-containing agents | | Iron supplements | | Aluminum (antacids, sucralfate) | | Barium | | Neurally active agents | | Opiates | | Antihypertensives | | Ganglionic blockers | | Vinca alkaloids | | Calcium channel blockers | | 5HT3 antagonists |

Food intolerance — Food intolerance refers to difficulty digesting or metabolizing a particular food. Food intolerance disorders are reported by 15 to 20 percent of the population. Food intolerances are even more common among patients with irritable bowel syndrome and other functional gastrointestinal disorders, with 50 to 80 percent reporting consistent problems with certain foods A simple way to explain the difference is that food intolerance generally involves the digestive system, the amount of food ingested is directly related to the severity of symptoms, and the food causes similar symptoms with each exposure Excessive intestinal gas, bloating, abdominal pain, and diarrhea are common symptoms. As an example, a patient who can eat one or two strawberries without symptoms but develops erythema and irritation around the mouth with an entire bowl of strawberries likely has an intolerance to strawberries, rather than an IgE-mediated allergy. However, gastrointestinal symptoms are rarely the sole manifestations of a food-allergic reaction. More commonly, gastrointestinal symptoms occur in conjunction with involvement of other target organs **Nonimmunologic adverse food reactions**

| Gastrointestinal disorders | | :---- | | Nonceliac gluten sensitivity | | Gastroesophageal reflux | | Carbohydrate malabsorption | | Lactase deficiency | | Sucrose-isomaltase deficiency | | Irritable bowel syndrome | | Intolerance of short-chain fermentable carbohydrates (FODMAPs) | | Yeast overgrowth syndrome | | Pancreatic insufficiency (cystic fibrosis) | | Peptic ulcer disease | | Gallbladder disease | | Intolerances | | :---- | | Pharmacologic agents | | Caffeine | | Theobromine (tea, chocolate) | | Histamine and histamine-like compounds (berries, wine, fish, sauerkraut) | | Tryptamine (tomato, plum) | | Tyramine (aged cheeses, pickled fish) | | Serotonin (banana, tomato) | | Phenylethylamine (chocolate) | | Glycosidal alkaloid solanine (potatoes) | | Alcohol | | Flavorings and preservatives | | Sodium metabisulfite | | Monosodium glutamate | | Toxic reactions | | :---- | | Seafood | | Scombroid poisoning (fresh tuna and mackerel) | | Ciguatera poisoning (grouper, snapper) | | Saxitoxin (shellfish) | | Other food poisoning | | Fungal toxins | | Alcohol | | :---- | | Chocolate | | Aged cheeses | | Monosodium glutamate (MSG) | | Aspartame (NutraSweet) | | Caffeine | | Nuts | | Nitrites, nitrates |

Celiac disease – Celiac disease, also known as gluten-sensitive enteropathy, is an immune-mediated inflammatory disease. It classically presents in infants and young children with chronic diarrhea, anorexia, abdominal distension and pain, failure to thrive or weight loss, and sometimes also vomiting. The gastrointestinal manifestations are similar in older children and adults but usually milder and include steatorrhea, weight loss, and other signs of nutrient or vitamin deficiency due to malabsorption. Flatulence and steatorrhea are suggestive of celiac disease rather than other forms of food-protein-induced enteropathy or FPIES. Celiac disease is not classically considered a food allergy, but it is caused by a non-IgE-mediated immune reaction to a food protein (gluten). SKIN MANIFESTATION \- Dermatitis herpetiformis is characterized by an itchy papular vesicular eruption usually located symmetrically on the extensor surfaces of the elbows, knees, buttocks, sacrum, face, neck, trunk, and occasionally within the mouth. The predominant symptoms are itching and burning that are rapidly relieved with rupture of the blisters. MIXED IgE- AND NON-IgE-MEDIATED REACTIONS

The mixed disorders primarily include: ●Atopic dermatitis : Food allergies may exacerbate atopic dermatitis, especially in young children with more severe eczema. ●Eosinophilic esophagitis : should be suspected in patients of any age presenting with esophageal symptoms. Infants and young children may present with feeding disorders and failure to thrive, whereas older children and adults typically present with dysphagia, vomiting, and abdominal pain ●Eosinophilic gastroenteritis: In adolescents and adults, it can mimic irritable bowel syndrome. Approximately one-half of patients have allergic disease, such as defined food sensitivities, asthma, eczema, or rhinitis. However, food allergy testing has not been shown to effectively identify specific culprit foods. An empiric elimination diet or elemental diet may improve symptoms and histologic findings in up to half of patients

PCOS is one of the most common endocrinopathies in women of reproductive age, affecting between 6.5 and 10 percent of women overall The diagnosis of PCOS should be withheld or made very cautiously for girls in the first two years after menarche Proposed diagnostic criteria for polycystic ovary syndrome

| NIH consensus criteria 1990 (all required) | Rotterdam criteria 2003\* (two out of three required) | AES definition 2008 (all required) | | :---- | :---- | :---- | | Oligo- or anovulation oligo- or amenorrhea, classically have a peripubertal onset OR women may apparently have regular cycles at first and subsequently develop menstrual irregularity in association with weight gain OR Breakthrough bleeding and AUB (abnormal uterine bleeding ): Frequent or unusually heavy menstrual bleeding due to deficient progesterone secretion and chronic exposure to estrogen | | | | Clinical and/or biochemical signs of hyperandrogenism Hyperandrogenism may include clinical signs: Hirsutism acne, male-pattern hair loss (PCOS) is the underlying disorder in approximately 75 to 80 percent of women who present with hirsutism | | | | Polycystic ovaries (by ultrasound (transvaginal) 12 (revised to 20\) or more follicles in either ovary measuring 2 to 9 mm in diameter (The key ovarian findings in PCOS include multiple, small, preantral and antral follicles in a peripheral location) increased ovarian volume (\>10 mL) | | | | Exclusion of other disorders: NCCAH, androgen-secreting tumors thyroid disease, nonclassic congenital adrenal hyperplasia \[NCCAH\], hyperprolactinemia, and androgen-secreting tumors | | | | :---- | ----- | ----- |

NIH: National Institutes of Health; AES: Androgen Excess Society; NCCAH: nonclassic congenital adrenal hyperplasia; PCOS: polycystic ovary syndrome. As a sole finding, sonographically detected polycystic ovaries are not sufficient to make the diagnosis of PCOS, although they may represent a mild form of ovarian hyperandrogenism and insulin resistance. **However, from 8% to 25% of normal women, and even 14% of women using oral contraceptives, also meet the ultrasonographic criteria for polycystic ovarie**s. Normal cyclic menses result from normal ovulatory function. The normal inter-menstrual interval ranges between **24 and 35 days** and menses that occur less or more often are an indication of ovulatory dysfunction Cyclic menses occurring at normal intervals strongly suggest, but cannot be regarded as proof of ovulation. The majority of women with PCOS, approximately 60–85%, exhibit gross menstrual dysfunction. The most common abnormalities are oligomenorrhea and amenorrhea. Polymenorrhea (regular cycles occurring at intervals less than 25 days) is very uncommon, observed in less than 2% of untreated women with PCOS The prevalence of eumenorrhea among women with PCOS is significantly increased if the Rotterdam diagnostic criteria are applied, because hirsute eumenorrheic women with polycystic ovaries are included

The overall prevalence of insulin resistance among women with PCOS is between 50% and 75%, and greater in obese than in lean women with PCOS. A baseline 2-hour OGTT or HbA1c is recommended for all women with PCOS, as up to 35% exhibit impaired glucose tolerance and up to 10% have diabetes mellitus Screening for glucose intolerance also is recommended for girls with premature adrenarche or menstrual irregularity that persists for more than 2 years after menarche because hyperinsulinemia often is the cause and they are at high risk for developing diabetes and severe hyperandrogenism 1. Last sexual intercourse more than 15 days ago \- UPT stat and 7 days later 2. Last sexual intercourse more than 7 days ago- Serum beta HCG 3. \<7 days: wait to test for beta HCG 2. h/o irregular periods, \+/- USG s/o PCOS, no hirsutism 1. TSH, prolactin, FSH (LH/FSH ratio) \+/- 17 OHP \- this is not necessary if as per Rotterdam PCOS diagnosis is confirmed

In the past, many clinicians measured LH and FSH and used an elevated LH: FSH ratio ≥2 as evidence for the diagnosis of PCOS. However, the LH: FSH ratio was never a criterion for the diagnosis, and its use can be misleading (eg, if there has been recent ovulation, LH will be suppressed and the ratio will be ≤2:1). Hence order in early follicular phase after the next period (day2/3 of the menstrual cycle) Serum 17-hydroxyprogesterone – Uptodate suggests measuring a morning serum of 17-hydroxyprogesterone in the early follicular phase in all women with possible PCOS to rule out nonclassic congenital adrenal hyperplasia (NCCAH) due to 21-hydroxylase deficiency. For women who have some spontaneous menstrual cycles, this should be done in the early follicular phase, while for those without cycles, it can be drawn on a random day. Females with the non-classic type of 21-hydroxylase deficiency have normal female genitalia. As affected females age, they may experience hirsutism, male pattern baldness, irregular menstruation, and decreased fertility * Androgen measurements should also not be obtained when women are on OCPs, metformin, or spironolactone, as the interpretation of the result is confounded by the effects of these medications on androgen levels. * In general, we ask women to stop their medications at least four to six weeks before measuring serum androgens.

Use- Hirsutsm scoring \- as above in the table * If Score \< 7: * S. total Testosterone to be done. If T. Testosterone\>150, then DHEAS * If Score 7 or more: * S. Total Testosterone, DHEAS to be done * and if fast progressing symptoms or other symptoms of virilization, careful evaluation for more serious causes of hirsutism * Symptoms include: * [Acne](https://www.webmd.com/skin-problems-and-treatments/acne/default.htm) * Oily skin * Male pattern baldness * Changes in body fat and muscle distribution * Smaller breasts * Enlarged clitoris * Deeper voice

| Etiology | Clinical features | | :---- | :---- | | Common | | | PCOS | Peripubertal onset of symptoms, oligomenorrhea, obesity, polycystic ovaries on ultrasound. | | Nonclassic 21-hydroxylase deficiency | Similar presentation to PCOS, high serum 17-hydroxyprogesterone concentration, more common in certain ethnic groups. Change in voice(deepening), decrease in breast size. | | Uncommon | | | Classic 21-hydroxylase deficiency | Diagnosed during infancy, ambiguous genitalia. | | Androgen-secreting ovarian tumors (Sertoli-Leydig cell, granulosa-theca cell, hilus cell) | Onset in the third decade or later (usually postmenopausal), rapidly progressive hirsutism, virilization. | | Androgen-secreting adrenal tumors | Some women with adrenocortical cancer present with just virilization, but a mixed Cushing's and virilization syndrome is more common. | | Ovarian hyperthecosis | Onset in the third decade or later (usually postmenopausal), rapidly progressive hirsutism, virilization. | | Severe insulin-resistance syndromes | Virilization, amenorrhea, infertility, and the ovary show histologic changes of hyperthecosis. | | Cushing's disease | Corticotroph adenoma secreting ACTH results in excess cortisol and adrenal androgens. | | Drugs | Use of exogenous androgens (testosterone or DHEA) can cause hirsutism and acne. | | Acromegaly | Enlarged jaw (macrognathia) and enlarged, swollen hands and feet, which result in increasing shoe, glove, and ring sizes. Patients with large pituitary tumors may have headaches, visual field defects, and cranial nerve palsies. |

PCOS: polycystic ovary syndrome; ACTH: corticotropin; DHEA: dehydroepiandrosterone. Goals — The overall goals of therapy of women with PCOS include: * Amelioration of hyperandrogenic features (hirsutism, acne, scalp hair loss) * Management of underlying metabolic abnormalities and reduction of risk factors for type 2 diabetes and cardiovascular disease * Prevention of endometrial hyperplasia and carcinoma, which may occur as a result of chronic anovulation * Contraception for those not pursuing pregnancy, as women with oligomenorrhea ovulate intermittently and unwanted pregnancy may occur * Ovulation induction for those pursuing pregnancy

Approach to the use of COCs in women with PCOS is the same as in women without PCOS except that here less androgenic progesterones are preferred Risk factors for VTE including obesity, patient age, and family history of VTE should be assessed before prescribing. We currently suggest using caution if COCs are prescribed to obese women (body mass index \[BMI\] ≥30 kg/m2) over age 40 years because these women are at exceptionally high risk for VTE | Level of activity | Generic name(s) | Risk of VTE | | :---- | :---- | :---- | | High | Norgestrel | Standard risk | | | Levonorgestrel | Standard risk | | Middle | Norethindrone | Standard risk | | | Norethindrone acetate | Standard risk | | Low | Ethynodiol | Higher risk | | | Norgestimate | Standard risk | | | Desogestrel | Higher risk | | | Drospirenone | Higher risk | | | Dienogest | Higher risk | Recommendation: typically start with a Combined OC containing 20 mcg of ethinyl estradiol combined with a progestin such as norethindrone or norethindrone acetate, progestins that have lower androgenicity, but similar VTE risk compared with levonorgestrel-containing COCs Higher doses of ethinyl estradiol (30 to 35 mcg) are needed in some women for optimal suppression of ovarian androgens and management of hyperandrogenic features.

| OCP (Strip of 21 mostly- stop and restart on day 1-3 of the next periods) | Composition | Antiandrogenic property good for hirsutism Rx (antiandrogenic property) | Venous Thromboemembolism risk | Overall | | :---- | :---- | :---- | :---- | :---- | | Yasmin: [Link to drug leaflet](https://docs.google.com/document/d/1gBnFM7BRci70SYoJ1nGqmLEgrRzQppla-Jp1moHM8kM/edit) | Ethinyl Estradiol (0.03mg) \+ Drospirenone (3mg) | High | Higher | Preferred if the risk of VTE low | | Novelon | Ethinyl Estradiol (0.02mg) \+ Desogestrel (0.15mg) | High | Higher | Good starter drug if hirsutism bothersome- but risk of spotting/ intermenstrual bleed | | Loette | Ethinyl Estradiol (0.02mg) \+ Levonorgestrel (0.10mg) | Low | Lower | Good starter drug if hirsutism low- but there is risk of spotting/ intermenstrual bleed | | Femilon | Ethinyl Estradiol (0.03mg) \+ Desogestrel (0.15mg) | High | Higher | If, spotting is still a problem- after 3 months of OCP | | Yamini LS | Ethinyl Estradiol (0.02mg) \+ Drospirenone (3mg) | High | Higher | Good starter drug if hirsutism bothersome- but risk of spotting/ intermenstrual bleed | | Yamini | Ethinyl Estradiol (0.03mg) \+ Drospirenone (3mg) | High | | If, spotting is still a problem- after 3 months of OCP | | Diane 35/Crimson 35 | Cyproterone (2mg) \+ Ethinyl Estradiol (0.035mg) | High | Higher | If, spotting is still a problem- after 3 months of OCP |

* For women who have not had a period for more than 35 days and have h/o irregular periods or are /kc/c/o PCOD, this therapy is given to induce withdrawal bleeding. * For women with PCOS who choose not to or cannot take COCs, If cycles are longer than 35 days, alternative treatments for endometrial protection are intermittent or continuous progestin therapy, or a progestin-releasing intrauterine device (IUD) \[[5](https://www.uptodate.com/contents/treatment-of-polycystic-ovary-syndrome-in-adults/abstract/5)\]. In this setting, we recommend [medroxyprogesterone acetate](https://www.rxlist.com/provera-drug.htm) (5 to 10 mg) for 10 to 14 days every one to two months. Metformin It is a potential alternative to restore menstrual cyclicity as it restores ovulatory menses in approximately 30 to 50 percent of women with PCOS \[[6,7](https://www.uptodate.com/contents/treatment-of-polycystic-ovary-syndrome-in-adults/abstract/6,7)\]. Its ability to provide endometrial protection is less well established, When metformin is used, we suggest monitoring to confirm that ovulatory cycles have been established. This can be done with luteal phase serum progesterone measurements or transvaginal ultrasound. Antiandrogens An antiandrogen is then added after six months if the cosmetic response is suboptimal

For women with hirsutism and contraindications to COCs, we sometimes use spironolactone 50 to 100 mg twice daily. alone, but an alternative form of contraception is essential because, if pregnancy occurs, an antiandrogen such as spironolactone could prevent the development of normal external genitalia in a male fetus. Spironolactone alone does not regularize menstrual cycles; it is sometimes associated with menstrual irregularities.

Women with intermenstrual intervals \>35 days are oligo-ovulatory and may require weight loss and/or ovulation induction agents to conceive. Serum progesterone can be measured to assess whether ovulation has occurred. In normally cycling women, this is done on day 21 of a cycle; documenting ovulation in women with long intermenstrual intervals is more challenging, but the goal is to draw the sample 7 to 10 days before the next menses is expected. Ultrasound can also be used to document ovulation Fertility evaluation can be postponed until the patient is ready to pursue pregnancy. Lower BMI is associated with an improved likelihood of ovulation and conception. In obese women, weight loss is also associated with improved pregnancy outcomes. Endometrial cancer risk: A meta-analysis of five studies including 138 women with PCOS and 5593 controls without PCOS reported an excess risk of endometrial cancer among women with PCOS (odds ratio \[OR\] 2.79 Although there is no consensus on monitoring for endometrial hyperplasia in these patients, one study suggested that in oligo-ovulatory women with PCOS, an endometrial thickness \<7 mm on transvaginal ultrasound was not associated with histologic evidence of endometrial hyperplasia

Clinical examination should include grading of hirsutism with FG scale, site of acne and type of lesions, darkening and thickening of the skin on the neck, axilla, and groin, seborrhoea, and presence of alopecia. Examination of the genital region to look for the signs of virilization such as clitoromegaly should be done The cutaneous manifestations include hirsutism, acne, alopecia, and acanthosis nigricans Cosmetic/local therapy: Options available are medical therapy or physical method of removing hairs by threading, waxing, plucking, bleaching, or shaving Medical therapy: Topical Gels: Eflornithine hydrochloride 13.9%: it is an approved drug by the Food and Drug Administration for the treatment of unwanted facial hair growth. It helps in slowing and miniaturizing the hair follicle rendering them less coarse. The drug takes 8 weeks to show clinical improvement. Permanent methods of hair removal: Techniques for accomplishing permanent destruction of hair follicles are electro-epilation and laser photothermolysis. Laser therapy requires multiple sittings at regular intervals and it has been observed that 65–75% hair reduction is possible at 3 months after one to two sittings whereas \>75% hair reduction in 91% of cases at 8 months after four sittings with diode laser in women with hirsutism

Acne is one of the cutaneous manifestations of PCOS, but it is important to differentiate it from acne vulgaris which affects almost 80% of adolescents and the majority of them remit before the third decade of life. it has been seen that there is increased receptor sensitivity to circulating androgen in women with acne as compared to normal counterparts OCPs have been found effective for acne in PCOD as well and especially in cases of deep-seated nodules and relapsing acne on isotretinoin Routine first-line treatment: Offer people with acne a 12-week course of 1 of the following first-line treatment options, taking account of the severity of their acne and the person's preferences, and after a discussion of the advantages and disadvantages of each option.

* a fixed combination of topical adapalene with topical benzoyl peroxide for any acne severity * a fixed combination of topical adapalene with topical benzoyl peroxide, together with either oral lymecycline or oral doxycycline for moderate to severe acne * topical azelaic acid with either oral lymecycline or oral doxycycline for moderate to severe acne * a fixed combination of topical tretinoin with topical clindamycin for any acne severity * a fixed combination of topical benzoyl peroxide with topical clindamycin for mild to moderate acne * Consider oral isotretinoin for people older than 12 years \- REFER TO THE DERMATOLOGIST

* OCPs and antiandrogens are usually recommended for alopecia, but there are very limited data available to know the exact efficacy of all these drugs. * Topical minoxidil is considered as first-line treatment * The only evidence-based support for hormonal therapy appears to be the use of cyproterone acetate in female patients with clinical and biochemical evidence of hyperandrogenism. Cyproterone acetate (25-50 mg per day, days 1-10) is usually prescribed together with an oral contraceptive like estradiol. * Two drugs inhibiting the 5-alpha-reductase used in AGA are finasteride which is a type II 5-alpha-reductase-inhibitor, and dutasteride, which inhibits both types I and II 5-alpha-reductase. * Oral finasteride 1 mg a day is recommended to improve or to prevent the progression of AGA in male patients above 18 years with mild to moderate AGA. The response to treatment should be assessed at 6 months. *

It is characterized by brown velvety moist, verrucous hyperpigmentation of the skin, usually seen on the back of the neck and intertriginous areas like armpits and groins, underneath the breast, inside thighs. In PCOS, it has been reported in only 5% of women. * Topical retinoids: considered one of the first-line treatment options for AN. Combination therapy along with urea 12% creams and 12% ammonium lactace cream may also be used to successfully treat AN. * Topical Vitamin D analogs: Calcipotriene, a vitamin D analog, is another topical treatment option for AN * Chemical Peels: Although considered cosmetic in nature, superficial chemical peels are a relatively safe and effective treatment option for AN. Trichloroacetic acid (TCA) is a chemical exfoliating agent that causes destruction of the epidermis with subsequent repair and rejuvenation * Oral retinoids such as isotretinoin and acitretin can also be effective treatment options for AN. Should be used with contraceptive, and to avoid pregnancy for 6 months after stopping the drug. * Metformin and rosiglitazone: Metformin increases peripheral insulin responsiveness, resulting in a reduction of glucose production, hyperinsulinemia, body weight, and fat mass, as well as an increase in insulin sensitivity in patients with insulin resistance and AN

Excellent parent document: [Stepwise Guide for Diagnosis and Management of Acute Fever in Primary Care](https://www.ima-india.org/ima/pdfdata/Treatment-Algorithm-Booklet-03122021.pdf) [Management Guidelines for Short Febrile Illness including ILI](https://dhs.kerala.gov.in/wp-content/uploads/2020/06/iec6.pdf) AM temperature of more than 37.2 C (98.96 F) and PM temperature of \> 37.7 C (99.86) as measured in the oral cavity is considered fever. Note: rectal temperatures are slightly higher which correspond to core temperatures, and axillary temperatures are lower when compared to oral temperature. Note: subjective sensation of warmth \- is not fever. 1) Acute undifferentiated fever. 2) AFI with system specific signs or symptoms 3) PUO

Examination : **AVPU Conscious/oriented/alert** : mentally obtunded \- meningitis/encephalitis **Rash:**measles, dengue, rubella, IMN Iinfectitous mononucleosis) **Conjunctival injection, muscle tenderness:** leptospirosis **Eschar: scrub typhus** **** **Jaundice:** **Pulse**: for every degree raise in body temperature, basal heart rate goes up by 10 beats , suspect myocarditis if tachycardia is out of proportion with fever **RR**: any RR\> 30 s/o pneumonia , normal 18-24 BPM, In children: RR \> 60 upto 2 months, \> 50 \-2mo to 1 yr , \> 40 \- 1yr to 5 yr, and \> 30 in older children Elderly, DM : check skin turgor, tongue for hydration status. **BP** : **Hydration status:** oral intake, urine output, dirrhoea, vomiting, tongue, skin turgor Medications for comorbidities : check medication list \- rule out drug interactions with your present prescription. Also anticipate possible complications that can arise out of present illness and if any drug modifications necessary ( Example: Acute GE in a diabetic patient \- anticipate AKI \- If on ACE/ARB \- pay attention to S.Creat and potassium levels. ACE/ARB is commonly used with aldactone in heart failure so check potassium) Pallor : anaemia is an important risk factor for precipitating heart failure in compensated patients.

1. Age \>65 or those with significant comorbidities on multiple medicines 2. SOB without fever or k/h/o asthma/COPD with raised RR or laboured breathing 3. Dehydration likely \- AGE with compromised oral intake, decreased urine output \- none in the last 12 hours 4. Post-operative- first week 5. Pregnant 6. Postpartum- 42 days 7. Immunocompromised 8. Neutropenic 9. Red hot painful joint 10. UTI with flank pain or high grade fever \- especially if it persists after 24 hours of antibiotic | Even-FEVER profile (Day 1-4) No need to order the whole profile for localizing fevers \- can order specific Ix such as Urine R/M and C/S Ideally should be ordered only on day 3-4 | CBC, CRP, Urine R/M, LFT Mini(SGOT, SGPT, S. Bil), Dengue NS Antigen , Malarial Falciparum and Vivax Antigen (Parasite V & F) | | :---- | :---- | | | KFT/RFT : in the elderly or people with comorbidities | | | Chest X Ray and Sputum R/E and culture if pneumonia suspected \- especially in the elderly | | | USG abdomen \- if abdominal pain, jaundice |

| Even \-FEVER Profile (Day 5 or more) | CBC, CRP, Urine R/M, LFT Mini(SGOT, SGPT, S. Bil), Typhidot (IgM), Dengue Profile (NS-1 antigen, IgM and IgG antibodies), Malarial Falciparum and Vivax Antigen (Parasite V & F) | | :---- | :---- | | | Blood culture- if above investigations are negative or suspicion of typhoid | | | Targeted evaluation : Leptospira, Typhus, JE as per history | | | Tire 2 investigations: LDH, Total CPK, ANA screening , Skin test for TB, RA factor, Brucella antibody,, 2D ECHO, | * Increased TLC, neutrophil predominant \- Bacterial , stress (Acute MI, DKA) * Decreased/ low normal TLC \+/- Borderline platelet \+/- increased relative lymphocyte count \- consider viral. * Normal TLC with increased relative lymphocyte count \- consider viral or atypical bacterial \- **rickettsial.** * Eosinophilia \- Compare old reports if this was pre existing \- If new onset \- consider parasitic infections. * Low platelet : not specific for dengue can happen with any viral , atypical bacterial or in sepsis.

* Pus cells positive \+ leukocyte esterase positive \- Infection * \+ve nitrite : infection by enterobacteriaceae group. * Protein can be 1 to 2 \+ sometimes both in UTI and certain infections like hematuria. * RBC \+ and Blood \+ indicates hematuria * **RBC is absent but blood \+ i**ndicates haemoglobinuria/ myoglobinuria \- consider hemolysis \- malaria, myositis, rhabdomyolysis. CRP : monitor the trend. Not specific for infections. * enzymes * in 1000s and above \- consider possible autoimmune, ischemic hepatitis, severe infections. * In 100s \- 900s \- consider viral/ atypical bacteria. * Bilirubin * predominant indirect (\<15% direct with normal enzymes AST and ALT) \- possible hemolysis \- malaria \- we can see a mixed pattern with raised enzymes. * Both direct and indirect \- possibly due to hepatitis. RFT: AKI is common in infections, malaria, leptospira, typhus ( Scrub Typhus ) Chest x ray : Consolidation \- air bronchogram- pneumonia Peribronchial haziness, prominent bronchovascular markings \- viral/ atypical Effusion \- capillary leak \- serositis \- non specific. IgM/special tests for leptospirosis, scrub typhus (Weil Felix) , japanese encephalitis \- are lacking in sensitivity/specificity \- so empirical treatment is often prefeerd

USG abdomen: UTI \- Subjective. Splenomegaly : malaria, typhoid, certain viral infections \- CMV, EBV, lymphoma. Hepatomegaly : non specific. Pancreatitis Cholecystitis \- Acalculous \- can happen concurrently with other infections. Cholangitis \- DM, GB/CBD calculus. Liver abscess, splenic abscess. Peritoneal effusion Ileocolitis \- acute, typhoid, TB. dengue ( can show diffuse intestinal wall edema and peritoneal fluid) PID \- pelvic collection. Appendicitis. Sensitivity Vs specificity Antigen detection Vs PCR Vs serology (antibody detection) Vs culture PCR and antigen detection test \- positive much early in course of disease \- COST. Serology \- takes time to become positive, rising titres are more important than single test. (IgM vs IgG ) : IgM response takes at least 5 to 7 days. IgG we know that it is due to past infection. IgM levels can persist to be elevated for a few weeks to months. That is the reason why rising IgM titres are more important. Qualitative test : they say If IgM is present or absent : Ex: dengue rapid test. Semi quantitative : they say if the values are below a particular level or above it : Ex: LDH. Quantitative test: GIve us exact numbers/titres.

Culture \- Gold standard but false negatives are high. Most cultures are aerobic cultures. Anaerobic culture is not routinely done because of the complexity of the procedure and is treated empirically in our resource limited setting.

Clinical manifestations The clinical syndromes may be classified as: A. Uncomplicated acute malaria B. Severe complicated malaria (including cerebral malaria) C. Chronic complications of malaria 1\. Uncomplicated acute malaria This is the commonest presentation of malaria The patient initially has malaise, fatigue , abdominal discomfort, nausea, vomiting and headache followed by typical paroxysms of fever . The paroxysm of fever consists of a cold phase and hot phase. This is common with infections with P.Vivax and ovale. The cold phase lasts for 20-60 minutes when the patient experiences an abrupt onset of chills and covers himself with many layers of blankets. This is associated with uncontrollable rigors. The hot phase follows and temperature may reach 40o \- 41.7o C associated with headache, flushing and tachycardia. After 3-4 hours fever remits with profuse sweating, leaving the patient drenched in sweat – “the wet phase”. * Cerebral Malaria * Hematological abnormalities: Hematocrit of less than 15 mg/dl or Hb of less than 5 mg/dl. * Renal impairment * Non cardiogenic pulmonary edema * Hypoglycemia

It is seen in older children and adults in hyper endemic areas. Associated with exaggerated immune response to repeated malarial infections It is characterized by anemia, massive splenomegaly, elevated IgM levels, scanty or absent malarial parasites in blood smears and it responds to prolonged treatment with prophylactic anti-malarial drugs * Quartan Malarial Nephropathy: Chronic or repeated infections with P.malariae * Post Malarial Neurological syndrome: More commonly seen in children than in the adults, these can occur within two months of malaria. Hallucinations and delusions can occur ; hemiplegia , cerebral palsy cortical blindness impaired cognition have been reported. **G6PD deficiency test should be done before giving Primaqunie and it is contraindicated in pregnancy** **Treat all falciparum as resistant to chloroquine** **Chemoprophylaxis:** **Doxycycline is the preferred drug for up to 6 weeks , to be started 2 days before and continued till 4 weeks after ravel** 1\. All visitors from a non-malarious area to a malarious area. 2\. All pregnant women in a malarious area. 3\. Patients with major organ failure and other risks for severe malaria.

Chloroquine and Proguanil are the preferred chemoprophylactic drugs against malaria in the first 3 months of pregnancy. However, in case of unplanned pregnancy, malaria chemoprophylaxis is not considered an indication for termination of pregnancy.

* Generally defined as a rectal tempreture of 38 Celsius(100.4 F) or higher. * It is equvalent to an oral tempreture of 37.5 C(99.5 F) And axillary tempreture of 37.2 c(98.9 F) * HYPERPYREXIA-Tempreture above 41.5 C(107 F) * MEASUREMENT OF TEMPRETURE- * \-\<4 WEEKS-AXILLARY WITH DIGITAL THERMOMETER * \-\>4 WEEKS-AXILLARY WITH DIGITAL/INFRARED THERMOMETER(THERMOMETER) * Most common presenting complaints in pediatric practice * Most commom cause is viral infection-URI, gastroenteritis, ear infection, croup, bronchiolitis; Resolve in a week. * Other common causes-Bacterial URI, UTI, Malaria, Sepsis, Abscesses. * Symptoms that can help direct the evaluation toward noninfectious causes in pediatric patients include: (i) heart palpitations; (ii) recurrent/cyclic symptoms (rheumatoid, inflammatory, or hereditary disorder); and (iii) sweating/heat intolerance * Characteristics of fever(Onset, Intensity, Duration, Frequency and Pattern of fever-Continous, Remittent or intermittent) * If tempreture recorded * Localizing symptom of fever * Recent exposure-Vaccination, Animal/Insect bites or receipt of blood transfusion * Exposure to family Member * Past history-TB, UTI, CHD, Surgical procedure * History of travel in recent past * History of an underlying Chronic disease, medication history * Recurrent episodes-cyclic causes

| Localizing symptoms | | | :---- | :---- | | Cough and coryza | Viral fever | | Rash | Viral exanthematous fever(Measles,chicken pox,dengue, COVID, rubella ); MENINGOCOCEMIA, HSP, Kawasaki Disease, Leukemia | | Ear Pain | ASOM | | SKIN BOIL | Abscess, Pustules, Cellulitis, Impetigo | | Altered sensorium, Seizures, Neurological Deficit | Meningoencephalitis, Cerebral malaria, Enteric encephalopathy, Brain Abscess | | Throat pain, Difficulty in swallowing, Cervical nodes | Pharyngotonsillitis COVID | | Stridor, Dysphonia | ALTB, croup, Epiglotitis, Diptheria | | Fast breathing,cough,wheezing,chest indrawing, Chest pain | Pneumonia, Bronchiolitis, Pleural effusion, TB | | Joint Swelling, Pain, Limited movement | Septic arthritis, Rheumatic Fever, TB arthritis, Connective Tissue disease | | Vomiting | Gastritis, Gastroenteritis, Viral Hepatitis, Meningitis, Enteric Fever, UTI | | Diarrhea | Gastroenteritis, Enteric Fever, Dysentery | | Jaundice | Hepatitis, Malaria | | Pallor, Rash, Bleeding, Lymphadenopathy | Leukemia, IMN | | Urinary Frequency, Burning Micturition, Crying during Micturition, Hematuria | UTI,Cystitis | | Abdominal pain | GE, Appendicitis, Hepatitis, Liver abscess, pyelonephritis, Cholecystitis, Cholangitis | | Fever without focus/localizing symptoms | Diagnostic challenge in \<36 months of age Approach is divided Neonates upto 1 month of age Infants,1-3 months of age Infants, 3-36 months of age Certain high risk group require more aggressive approach-Hyperpyrexia; Fever with petechiae, Immunocompromised patient with asplenia, PID, CHD, AIDS | | | |

Prolonged fever-\>2 weeks- Different approach; Infection still remains the most important cause.Common causes are- 1. Infection-TB, HIV,UTI,Fungal 2. Inflammatory-JIA, SLE, KD, MIS-C,Wegeners granulomatosis 3. Malignancies 4. Endocrine-thyrotoxicosis 5. Neurological-familial dysautonomia, ectodermal dysplasia 6. Miscellaneous-Drug Fever, Periodic Fever, Factitious Fever * Every child in this group should be hospitalised * Tempreture Measurement- Rectal(gold std), Axillary using digital thermometer * IP- Adequate Hydration-🡪 Still febrile-🡪sepsis screening(CBC with band forms, Urine microscopy, Blood culture, Urine culture, Chest X ray,); LP in children with lethargy or refusal to breast feed Empirical Antibiotic-AMPICILLIN/GENTAMICIN OR Monotherapy with CEFTRIAXONE (100MG/KG/DAY)-🡪Modified later as per reports

* Self limited seasonal viral infections are most common cause * Possibility of serious Bacterial infection should always be ruled out in this age group and following condition should be ruled out (AOM, Pneumonia, Skin and soft tissue infection, UTI) * Risk stratification- * High Risk- Any child in this age group must be evaluated for sepsis and Risk stratification should be done * Diminished spontaneous activity, Lethargy, * Respiratory compromise(tachypnea, Chest retraction, Grunting) * Diminished muscle tone * Mottled cool extremity * Irritability * Weak sucking * TESTS: CBC, Blood Culture, Urinalysis, Urine Culture, Chest X ray(if any respiratory symptom is present), stool Routine if Diarrehea is present * High risk- * IP admission and care * Empirical Antibiotic-Ampicillin Gentamicin/Ceftriaxone Monotherapy * Vancomycin to be added if possibility of meningitis with MRSA is suspected * Antibiotic to be modified as per the culture

| PITTSBURGH GUIDELINES for low risk identification | | | :---- | :---- | | GENERAL APPEARANCE | WELL TERM INFANT | | PHYSICAL EXAMINATION | NORMAL, NO LOCALISING SIGNS | | TLC NEUTROPHILS/ ANC | \>5000, BUT \<15000, ABSOLUTE BAND COUNT \<1500 \<4000 | | Urine examination | NORMAL | | CSF (IF OBTAINED) | \<5 wbc/ML; No bacteria on gram stain WBC:RBC ≤ 1:500 | | Chest Radiograph | No infiltrates | | Stool | 5 wbc/HPF with diarreah | * Watchful observation without antibiotic (investigations to be sent in 1st visit itself) * Mandatory follow up after every 24 hours (till culture report is available) * risk stratification to be done-Positive culture-🡪ip admission and antibiotics * LP to be done prior to starting antibiotics. **Non pharmacological Antipyresis** Environmental modification \-place in cool(21-22 C) and airy area \-Minimal clothing(Only 1 layer of clothing) Hydration \-Extra fluid intake is recommended \-For each 1 degree Celsius of increase in tempreture a 12% increase in fluid intake is advised Mechanical Cooling (hydrotherapy or sponging)-sponging should be done by continuous wiping of the body with tepid waterfrom head to toe for 15 minutes.

* Indication for sponging with luke warm water(28-30 C) 1. Febrile delirium 2. Febrile seizure 3. Fever\> 41.1 C(105.9 F) 4. Patient with neurologic disorder 5. Children with hypersensitivity to antipyretic 6. Children with severe liver disease * Sponging with cold water in heat stroke **Paracetamol-**15mg/kg/dose at 4-6 hour interval(not exceeding 60 mg/kg/day) \-Antipyeretic effect begins in 30-60 minutes \-Reduces temperature by 1-2 C after 2 hours of intake \-Not much effective for higher tempreture **Ibuprofen**\-10 mg/kg/dose every 8th hourly \-longer duration of antipyresis compared to PCM \-Combination of PCM+ibuprofen **effective but not recommended** **Mefenamic Acid**\- 5-7 mg/kg/dose in TID doses(max-20 mg/kg/day) \-Effective in high temperature \-Main side effects- Diarrhea, Hemolytic Anemia,Thrombocytopenia and drowsiness. **Choice of antipyretic-based on personal experience** Paracetamol is considered safest antipyeretic in therapeutic doses in children(hepatotoxicity is side effect) Ibuprofen has side effect of GI disturbance, Nephrotoxicity hence should be used with caution in dehydrated child Asthma PCM is preffered Cough syrup containing Antipyeretic is not recomended

Rectal suppositories used in children with febrile seizures, recurrent vomiting or unconscious patients I/V PCM is given in comatose patient **Antipyeretic at Immunisation episode** PCM and Ibuprofen both are not recommended(may interfere with immune reaction). Parental Education Cause considerable parental anxiety and concern Parent need to be explained that fever is a protective response Danger signs should be explained and clearly mentioned when to take medical help.

**Status in India:** Dengue is seen throughout the year particularly in warmer places. **Pathophysiology:** T cell mediated antibodies \- \- \- \- platelets, endothelium, cytokines, complements \- \- \- \- \- Coagulopathy, low platelets, organ dysfunction, endothelial dysfunction and capillary leak. **Natural history:** **Febrile Phase (Days 1–3)** **Critical Phase (Days 3–7): A**s the fever subsides, patients may feel they are recovering, but this is when capillary permeability can peak **Convalescence Phase (Days 7–10)** Dengue cases should be managed on an **outpatient basis** unless hospitalization is **medically necessary**. Hospitalization should only be considered under the following conditions:

* Persistent high fever (\>102°F) for more than 5 days * Severe abdominal pain, persistent vomiting, inability to maintain oral hydration * Lethargy and/or restlessness, sudden behavioral changes, syncope * Severe dehydration or signs of shock (hypotension, pulse pressure\<20) * Enlarged liver\>2 cms * Dyspnoea * **Dengue Hemorrhagic Fever (DHF) / Dengue Shock Syndrome (DSS):** * **Platelet count \< 50,000/cu.mm** or progressive fall ? * **Active bleeding tendencies** (petechiae, gum bleeding, epistaxis, hematuria, GI bleed,melena) **at any platelet count** * **Signs of plasma leakage:** Hypotension, pleural effusion, ascites, * **Hematocrit rise** : baseline/1st \>45 % in men and \>41% in women, children younger than 12 years OR drop of 10% or more over baseline * **Organ failure:** Liver dysfunction (SGOT/PT \>1000 ?), encephalopathy, renal failure * **DIC (Disseminated Intravascular Coagulation) suspected cases, deranged coagulation profile** * **Expanded Dengue syndrome:** * DF /DHF \+ unusual presentation. * CNS Involvement: Encephalopathy, seizures, IC bleed. * GI involvement: Hepatitis, cholecystitis, cholangitis, pancreatitis. * Renal involvement: ATN, ARF. * Cardiac involvement : arrhythmia, myocarditis, pericardial effusion, cardiomyopathy. * Pulmonary : ARDS, pulmonary haemorrhage. * Ocular: optic neuritis, macular bleed * **Special Category Patients:** * Pregnant women * Elderly (\> 60 years) with comorbidities (diabetes, hypertension, CKD, CAD etc.), people on anticoagulants * Immunocompromised patients (HIV, chemotherapy, post-transplant, immunosuppressants, oral steroids) * Infants,

* Platelet count\>50000 and/or rising * Vitally stable * A minimum of 2–3 days have elapsed after recovery from shock. • No respiratory distress from pleural effusion/ascites. * Afebrile for 24 hours without antipyretics * Reports: ?? * **Investigations to confirm diagnosis: NS1 antigen upto day 3-4 and Dengue serology from day 5 onwards in addition** **Investigations for prognosis/severity** : * **complete blood count** (**CBC)** \- from day 3 onwards daily, look at Platelets \- once a recovery begins in platelet count it can be stopped Haematocrit \- However this can be repeated as frequently as 2 to 4 hours when the patient is in shock and when you want to evaluate the response. * **CRP**: Can be used as a prognostic marker, appropriate on days 3 to 5\. Moderate to severe rise in CRP can be a marker of complications. Half life of CRP is 19 hours. A CRP of more than 21mg/dl has a high sensitivity for possible complications. This should never be used as a sole marker of severity. Raised AST and ALT \> 3\*ULN can be found in 60 to 65% of patients with dengue. 15-17% of people can have AST and ALT raised to \>10\* ULN. Most hepatitis spontaneously resolves without medication. However fulminant hepatic failure is seen in 0.3 to 0.55 % in most studies. * Paracetamol , avoid NSAIDs * Plenty of fluids * Rest

**When is platelet transfusion necessary?** Only If platelet count is \<10,000 **without** bleeding In case of moderate to severe bleeding **When is IVF necessary?** IVF : If PCV \>45% or if there is an increase in 20% from baseline \- 10ml/Kg/Hr NS/RL —------- repeat PCV and look for trend — If PCV is decreasing —-- reduce fluids to 5ml /Kg/hr ( progressively reduce to 1ml/kg/hr \- If PCV is stable and patient is taking orally). If a patient is not taking orally he will require higher fluid ( while monitoring PCV). **41.5 degree C= 106.7 degree F, 36 degree C= 96.8 F** [**National Guidelines for Clinical Management of Dengue Fever 2023**](https://ncvbdc.mohfw.gov.in/Doc/National%20Guidelines%20for%20Clinical%20Management%20of%20Dengue%20Fever%202023.pdf) Dengue cases should be managed on an **outpatient basis** unless hospitalization is **medically necessary**. Hospitalization should only be considered under the following conditions:

* Persistent high fever (\>102°F) for more than 5 days * Severe abdominal pain, persistent vomiting, inability to maintain oral hydration * Lethargy and/or restlessness, sudden behavioral changes, syncope * Severe dehydration or signs of shock (hypotension, pulse pressure\<20) * Enlarged liver\>2 cms * Dyspnoea * **Dengue Hemorrhagic Fever (DHF) / Dengue Shock Syndrome (DSS):** * **Platelet count \< 50,000/cu.mm** or progressive fall ? * **Active bleeding tendencies** (petechiae, gum bleeding, epistaxis, hematuria, GI bleed,melena) **at any platelet count** * **Signs of plasma leakage:** Hypotension, pleural effusion, ascites, * **Hematocrit rise** : baseline/1st \>45 % in men and \>41% in women, children younger than 12 years OR drop of 10% or more over baseline * **Organ failure:** Liver dysfunction (SGOT/PT \>500), encephalopathy, renal failure * **DIC (Disseminated Intravascular Coagulation) suspected cases, deranged coagulation profile** * **Special Category Patients:** * Pregnant women * Elderly (\> 60 years) with comorbidities (diabetes, hypertension, CKD, CAD etc.), people on anticoagulants * Immunocompromised patients (HIV, chemotherapy, post-transplant, immunosuppressants, oral steroids) * Infants,

* Platelet count\>50000 and/or rising * Vitally stable * A minimum of 2–3 days have elapsed after recovery from shock. • No respiratory distress from pleural effusion/ascites. * Afebrile for 24 hours without antipyretics * Other Reports: PCV, SGOt, SGPT \- 2\. Mandatory Documentation for Claim Approval * **Diagnostic Reports:** * **Dengue NS1 Antigen / IgM/ IgG ELISA test** (RAPID test not acceptable) * **Complete Blood Count (CBC):** * Platelet count trend (repeated tests showing a drop) and/or platelet count \<50,000 * Hematocrit (\> 10% rise indicating plasma leakage) * **Liver function test (LFT) & Kidney function test (KFT)** * **Coagulation profile (PT/INR, aPTT, D-dimer) in case of severe dengue** * **Hospital Admission Notes:** * Justification for hospitalization * Treatment details and IV fluid management * **Discharge Summary:** * Final diagnosis, duration of stay, and outcome * **Medication & Treatment Details:** * IV fluids, supportive care, platelet transfusion (if applicable) 3\. Exclusion & Red Flags (Cases That Should Not Be Approved)

* **Mild dengue fever cases** managed on OPD basis without complications * **Hospitalization without proper platelet count reports or diagnostics when s/s of severe dengue are not present** * **Non-severe dengue cases admitted for observation only** * **Repeated dengue claims from the same member (possible fraud)** * **Unverified laboratory reports** (only MD Pathologist-verified reports acceptable) * **Hospitalization due to anxiety about dengue rather than clinical necessity** 4\. Fraud Prevention & Additional Verification * **Cross-check past claims** for multiple dengue hospitalizations from the same patient or hospital * **Verify lab test authenticity** (avoid claims based on rapid dengue tests) * **Check for unnecessary admissions** by hospitals inflating claim costs

Different presentations mostly along the three manifestations 1. Common cold 2. Acute Pharyngitis 3. Acute Rhinosinusitis 4. Influenza The term "common cold" refers to a mild upper respiratory viral infection involving, to variable degrees, nasal congestion and discharge (rhinorrhea), sneezing, sore throat, cough, low-grade fever, headache, and malaise. * Allergic or seasonal rhinitis * LRTI * Pertussis * COVID-19 For most people and most colds, symptoms are self-limited. The common cold is usually an uncomplicated illness; however, occasionally, patients may develop complications: * Sinusitis * Lower respiratory tract disease * Asthma exacerbations * Acute otitis media * Serous otitis media

| Runny nose, sneezing | URI (Common cold) | | :---- | :---- | | Watering of eyes | URI (Common cold) | | Blocked nose | URI (Acute rhinosinusitis) | | Cough with very little phlegm or sputum | Rhinosinusitis/asthma R/o Pneumonia/Covid | | Cough with greenish or thick phlegm | Rhinosinusitis/asthma R/o Pneumonia/Covid | | Sputum discharge from nose | URI (Acute rhinosinusitis) | | Need to clear throat often | URI (Acute rhinosinusitis) | | Sputum flows in the back of throat (post nasal drip) | URI (Acute rhinosinusitis) | | Sore throat | Pharyngitis | | Pain in swallowing | Pharyngitis | | Ear pain without discharge, especially on swallowing | Pharyngitis | | Headache | Non Specific | | Severe body ache | Non Specific | | Shivering and body shaking | Malaria | | Joint pain | Nonspecific | * An acute upper or lower respiratory tract infection * Common cold/acute rhinosinusitis * CAP (Community acquired pneumonia) * Acute bronchitis * COVID-19 or * exacerbation of a chronic condition * Asthma, * Bronchiectasis * COPD * Chronic rhinosinusitis * Heart failure * Others * Reactive airways disease syndrome \[RADS\], * Tuberculosis, * Lung cancer **URTI claims should only be approved if the hospitalization is medically necessary and meets the following criteria:**

* **s/s/o Complicated rhinosinusitis- orbital cellulitis, meningitis, cranial abscess, sinus venous thrombosis, these include** * **Neck pain or stiffness along with an intense headache** * **Extreme lethargy** * **Confusion or change in consciousness** * **Swelling around your eyes** * **Difficulty moving the eyes, or severe pain on movement** * **Changes in vision** * **Any stroke-like symptoms** * **High fever persisting after 48 hours of starting appropriate antibiotics (cephalosprins/augmentin)** * **s/s/o Complicated pharyngitis/tonsillitis- peritonsillar abscess** * **Stridor or difficulty with breathing, progressive difficulty with swallowing, or severe systemic symptoms.** * **Patients who develop dysphagia and dehydration. \-** * **Patients with peritonsillar cellulitis or abscess (quinsy) that may require parenteral antibiotics \+/- drainage** * **High fever persisting after 48 hours of starting appropriate antibiotics (cephalosprins/augmentin)** * **Patients with high-risk conditions such as:** * **Uncontrolled diabetes** * **Chronic kidney disease (CKD)** * **Immunocompromised conditions (HIV, chemotherapy, post-transplant)** * **Infants and elderly patients (\>60 years)**

Subacute cough (present for three to eight weeks) D/ds * Postinfectious cough (eg, respiratory viruses, pertussis, COVID-19) and * Exacerbations of underlying diseases (eg, asthma, COPD, and chronic rhinitis) * Pulmonary TB Chronic cough (more than eight weeks) D/ds * Asthma, * Nonasthmatic eosinophilic bronchitis, * COPD * Gastroesophageal reflux disease, and * Upper airway cough syndrome (due to postnasal drip)

| Drooling of saliva | Red flag | R/o Peritonsillar abscess | | :---- | :---- | :---- | | Difficulty in opening mouth | Red flag | R/o Peritonsillar abscess | | Sound/noise in breathing | Red flag | R/o Peritonsillar abscess | | None of these | | | **Bacterial vs viral sore throat/acute pharyngitis** Centor criteria: [https://www.mdcalc.com/calc/104/centor-score-modified-mcisaac-strep-pharyngitis](https://www.mdcalc.com/calc/104/centor-score-modified-mcisaac-strep-pharyngitis) Please do not use this score if the patient does not have a recent onset acute pharyngitis (3 days or less). * Tonsillar exudate/swelling \- ask the patient to examine self/share a photograph \- if any suspicion assume \+ve \- especially if pain referred to the ear or every swallow is significantly painful * Tender anterior cervical lymphadenopathy or lymphadenitis \- Assume \+ve if tonsillar exudate/swelling \+ve * History of fever (over 38 degrees Celsius=100.4 degree F) * Absence of cough * Age : 3-14 add \+1, 15-44 add \-0,\>45 add \-1 Each of the Centor criteria scores 1 point (maximum score of 4). A score of 0, 1 or 2 is thought to be associated with a 3 to 17% likelihood of isolating streptococcus. A score of 3 or 4 is thought to be associated with a 32 to 56% likelihood of isolating streptococcus and antibiotics should be considered/given

| First choice of antibiotics No penicillin allergy | Amoxcillin/ Augmentin for 10 days (augmentin 7 days- add probiotics) | | :---- | :---- | | 2nd Choice: | If IgE mediated mild penicillin allergy suspected (urticaria or angioedema but NOT anaphylaxis) 2nd/3rd Gen Cephalosporins with a side chain that is dissimilar to penicillin **cefdinir, or cefpodoxime**. A 5-day treatment course is acceptable BUT For patients with mild, non-IgE-mediated reactions to penicillin (eg, maculopapular rash beginning days into therapy), select a first-generation cephalosporin such as [cephalexin](https://www.uptodate.com/contents/cephalexin-drug-information?search=pharngitis%20antibiotics%20&topicRef=8049&source=see_link) for 10 days because of its narrow spectrum and the low likelihood of cross-reactivity. | | 3rd choice: | For patients with a history of severe angioedema and/or anaphylaxis or with serious delayed reactions or for patients who cannot take cephalosporins Macrolides: Azithromycin 5 days course Erythromycin | | 4th choice: | Clindamycin | Fever and constitutional symptoms typically resolve within one to three days of starting treatment. But mild sore throat/discomfort/voice change may persist for weeks. ##### Criteria for ENT referral For tonsillectomy Most patients with recurrent pharyngitis secondary to GAS do not require a tonsillectomy.

**Paradise criteria,** although they were not developed for adults, for referring patients for tonsillectomy: FREQUENCY * three episodes yearly for ≥ three years; * five episodes yearly for two years; or * seven episodes in one year CHARACTERISTICS Each episode of pharyngitis should be clearly documented with one or more of the following clinical features: * temperature \>38.3°C= 100.94 C * cervical adenopathy, * tonsillar exudate, or * positive test for group A streptococcal (GAS) infection | Discharge/pus coming of ear | Red flag | R/o complicated CSOM/ASOM | | :---- | :---- | :---- | | H/o pus discharge from ear off and on | Red flag | R/o complicated CSOM/ASOM | | Headache | Red flag | R/o complicated CSOM/ASOM | | Confusion | Red flag | R/o complicated CSOM/ASOM | | None of these | | |

Pain persisting even after taking painkiller or patient needs round the clock pain killers and compliance on medicines steam confirmed Supportive care — General supportive measures that can be suggested for most patients with infectious pharyngitis include ● Getting adequate rest ● Consuming an adequate volume of fluids ● Avoiding cigarette smoke (including secondhand smoke) and other respiratory irritants ● Avoiding acidic foods and beverages (particularly for those with oral or pharyngeal ulcers) ● Eating a soft diet (may be more palatable for those with difficulty swallowing due to pain or enlarged tonsils) Prevention of complications — Complications of streptococcal pharyngitis can result from extension of infection beyond the oropharynx, termed suppurative complications, or as immune phenomena, termed nonsuppurative complications. Suppurative complications of GAS pharyngitis include otitis media, peritonsillar cellulitis or abscess, sinusitis, meningitis, bacteremia, and necrotizing fasciitis.

**Nonsuppurative complications of GAS** pharyngitis include acute rheumatic fever, post-streptococcal glomerulonephritis, and reactive arthritis. Acute rheumatic fever (ARF) is a nonsuppurative complication of pharyngeal infection with group A Streptococcus (GAS). Signs and symptoms of ARF develop two to three weeks following pharyngitis and include arthritis, carditis, chorea, subcutaneous nodules, and erythema marginatum

Acute rhinosinusitis (ARS) is defined as symptomatic inflammation of the nasal cavity and paranasal sinuses lasting less than four weeks. The term "rhinosinusitis" is preferred to "sinusitis" since inflammation of the sinuses rarely occurs without concurrent inflammation of the nasal mucosa It is difficult to distinguish viral and bacterial acute sinusitis. A bacterial cause may be more likely if several of the following are present: * symptoms for more than 10 days * discolored or purulent nasal discharge * severe localized unilateral pain (particularly pain over teeth and jaw) * fever * marked deterioration after an initial milder phase Treatment for acute viral rhinosinusitis (AVRS) focuses on symptomatic management as it typically resolves within 7 to 10 days. Bacterial infection occurs in only 0.5 to 2 percent of episodes of ARS. Acute bacterial rhinosinusitis (ABRS) may also be a self-limited disease. Patients may be treated symptomatically and observed or treated with antibiotics. Rarely, patients with ABRS develop serious complications. Complications of Acute Bacterial RhinoSinusitis:

| Swelling and/or redness around eyes | R/o Peri Orbital sinusitis | | :---- | :---- | | Popping forward of an eye | R/o Orbital sinusitis | | New onset double vision of diminished vision | R/o Orbital sinusitis | | Difficulty or pain in moving eye | R/o Orbital sinusitis | | Neurological symptoms/compromised consciousness/orientation | Meningitis/intracranial abscess | | Treatment | Antibiotic, dosage and course length | | :---- | :---- | | First-choice oral antibiotic | Co‑amoxiclav: 500/125 mg three times a day for 7 days, can be extended to 10 days in children | | Alternative first choices for penicillin allergy or intolerance (for people who are not pregnant) | Doxycycline: 200 mg on first day, then 100 mg once a day for 4 days (5-day course in total) Clarithromycin: 500 mg twice a day for 5-7 days | | Alternative first choice for penicillin allergy in pregnancy | Erythromycin: 250 mg to 500 mg four times a day or 500 mg to 1,000 mg twice a day for 5 days | Symptomatic care options for adults with acute rhinosinusitis

| Class | Selected medication options | Advantages | Disadvantages | | :---- | :---- | :---- | :---- | | Oral analgesics and antipyretics (preferred) | Acetaminophen NSAIDS (eg, ibuprofen, naproxen) | Provide systemic pain relief and fever control Generally well-tolerated | Acetaminophen use should be limited or avoided in patients with advanced-stage liver disease or decompensated cirrhosis NSAIDs are avoided or used with caution in patients with cardiovascular disease, chronic kidney disease, or advanced-stage liver disease or cirrhosis NSAIDs can be associated with increased risk of bleeding and gastrointestinal upset | | Intranasal glucocorticoid sprays (preferred) | Fluticasone propionate Mometasone Triamcinolone | Relieve congestion by reducing inflammation May be particularly helpful for patients with allergic rhinitis | Can cause epistaxis and sore throat | | Intranasal saline spray | Intranasal sterile saline | Moisturizes passages and loosens secretions May temporarily improve nasal passage patency Useful in combination with intranasal glucocorticoid sprays | Some patients may find this difficult or uncomfortable Saline must be sterile | | Intranasal anticholinergic spray | Ipratropium bromide | Significantly reduces rhinorrhea | May not improve congestion | | Intranasal decongestant sprays | Oxymetazoline | Can improve nasal patency and promote drainage | Ma

y cause rebound congestion or mucosal damage when used for long-periods Should not be used for \>3 days | | Oral decongestants | Pseudoephedrine Phenylephrine | Relieves congestion through vasoconstriction Pseudoephedrine may be more effective than phenylephrine May be particularly helpful for patients with Eustachian tube dysfunction (eg, ear pain, a sensation of ear fullness or pressure, hearing loss, and/or tinnitus) | Avoid or use with caution in patients with cardiovascular disease, hypertension, angle-closure glaucoma, or bladder neck obstruction due to sympathomimetic effects | | Oral antihistamines | First generation: Clemastine Diphendydramine Second generation: Fexofenadine Loratadine Cetirizine | First-generation agents can be useful for drying effect Second-generation agents can be useful in patients with allergies Available in combination with oral decongestants | Can lead to over-drying, thickened, difficult-to-mobilize secretions, and increased discomfort Can cause drowsiness, cognitive impairment, and anticholinergic effects | | Oral expectorants | Guaifenesin | Can promote drainage by thinning secretions | Side effects can include gastrointestinal upset and drowsiness | | Steam inhalation or “tenting” – | | | Inhalation of warm, humidified air (steam), may provide patients with a transient sense of relief of congestion, but there is no evidence that it wil

l shorten the duration or severity of symptoms. If steam is used, care should be taken to ensure that the source of steam is clean, without mold or other contaminants. |

**(**Pneumonia, acute bronchitis, and exacerbation of COPD) * An acute illness (present for 21 days or less), * usually with cough as the main symptom, * And with at least 1 other lower respiratory tract symptom * Fever, * Sputum production, * Breathlessness, * Wheeze * Chest discomfort or pain, * Respiratory rate 24 breaths per minute or more * AND without alternative explanations (sinusitis, asthma) Diagnosis is unlikely if there are no focal chest signs and heart rate, respiratory rate and temperature are normal. The elderly may present with mainly systemic complaints of malaise, fatigue, anorexia and myalgia. Young children may present with nonspecific symptoms or abdominal pain. | Difficulty in breathing even at rest | SevereSOB | | :---- | :---- | | Not able to speak normally because of breathlessness | SevereSOB | | Oxygen saturation \<92% | SevereSOB | WORKUP: CBC, CHEST X RAY PA VIEW, CRP, KFT, SPUTUM R/M AND CULTURE, tests for Sepsis workup \- LDH when required: [https://www.mdcalc.com/calc/1096/sirs-sepsis-septic-shock-criteria](https://www.mdcalc.com/calc/1096/sirs-sepsis-septic-shock-criteria) CRB65 score OR CURB 65 for mortality risk assessment in primary care in LRTIs CRB65 score is calculated by giving 1 point for each of the following prognostic features:

* Confusion (abbreviated Mental Test score 8 or less, or new disorientation in person, place or time). * Raised respiratory rate (30 breaths per minute or more) * Blood pressure low(diastolic 60 mmHg or less, or systolic less than 90 mmHg) * age 65 years or more. CURB65 score when labs done includes Blood Urea Nitrogen (BUN), if BUN \>19.6 \- score 1 otherwise 0 Patients are stratified for risk of death as follows: | CRB 65 score | Mortality risk | CURB65 score | Mortality risk | Care recommendation | | :---- | :---- | :---- | :---- | :---- | | 0 | \<1% | 0-1 | 1.5% | Home based with possible reach within 4 hours to a hospital, follow up every 12 hours, define red flags | | 1-2 | 1-10% | 2 | 9.2% | Hospital, Blood and sputum culture and pneumococcal and legionella urinary antigen tests would be required | | 3-4 | \>10% | 3-5 | \>22% | Hospital, Blood and sputum culture and pneumococcal and legionella urinary antigen tests would be required Potentially ICU | Another more exhaustive score calculator is [PSI/PORT Score: Pneumonia Severity Index for CAP](https://www.mdcalc.com/calc/33/psi-port-score-pneumonia-severity-index-cap#why-use). Criteria for Safe discharge from hospital (proxy for favorable response in our set up) Do not routinely discharge people with community‑acquired pneumonia if in the past 24 hours they have had 2 or more of the following findings:

* temperature higher than 37.5°C * respiratory rate 24 breaths per minute or more * heart rate over 100 beats per minute * systolic blood pressure 90 mmHg or less * oxygen saturation under 90% on room air * abnormal mental status * inability to eat without assistance. While many pneumonias are actually viral in nature, typical practice is to provide a course of antibiotics given the pneumonia may be bacterial. Disposition (inpatient vs. outpatient) often dictates further care and management \-- including lab testing, blood cultures, etc.

| Treatment LOW SEVERITY (based on clinical judgement AND CRB65 score 0 ) | Antibiotic, dosage and course length | | :---- | :---- | | First choice oral antibiotic | Amoxicillin \+clavulate (Augmentin): 500 (625) mg three times a day for 5 days or 1000 mg BD OR Beta-lactamase stable beta-lactam: cefotaxime,cefuroxime axetil | | Alternative for penicillin allergy or if amoxicillin unsuitable (for example, if atypical pathogens suspected) | Doxycycline: 200 mg on first day, then 100 mg once a day for 4 days (5‑day course in total) OR Clarithromycin: 500 mg twice a day for 5 days OR Erythromycin (in pregnancy): 500 mg four times a day for 5 days | | MODERATE SEVERITY First-choice oral antibiotics (based on clinical judgement and guided by a CRB65 score 1 or 2, guided by microbiological results when available) | Amoxicillin/Augmentin: 625 mg three times a day /1000 mg BD for 5 days **With** (if atypical pathogens suspected) Clarithromycin: 500 mg twice a day for 5 days Or Erythromycin (in pregnancy): 500 mg four times a day for 5 days | | Alternative for penicillin allergy (guided by microbiological results when available) | Doxycycline: 200 mg on first day, then 100 mg once a day for 4 days (5‑day course in total) Clarithromycin: 500 mg twice a day for 5 days | | HIGH SEVERITY (based on clinical judgement and guided by a CRB65 score 3 or 4, guided by microbiological results when available) | Co‑amoxiclav: 500/125 mg three times a day orally **or 1.2 g three times a day intravenously for 5 days** With Clarithromycin: 500 mg twice a day orally or intravenously for 5 days Or Erythromycin (in pregnancy): 500 mg four times a day orally for 5 days | | Alternative, for penicillin allergy (guided by microbiological results when available; consult a local microbiologist if fluoroquinolone not appropriate) | Levofloxacin (consider safety issues): 500 mg twice a day orally or intravenously for 5 days |

* Fever and constitutional symptoms typically resolve within one to three days of starting treatment. But the cough may persist for weeks. * Watch out for SpO2, every 6 hours for first 3 days if pulse ox is available and any suspicion of breathlessness * Ask the patient to do 6 minutes walk test twice daily if pulse oximeter not available Patient information on Expected course of resolution Explain to people with community‑acquired pneumonia that after starting treatment their symptoms should steadily improve, although the rate of improvement will vary with the severity of the pneumonia, and most people can expect that by: * 1 week: fever should have resolved * 4 weeks: chest pain and sputum production should have substantially reduced * 6 weeks: cough and breathlessness should have substantially reduced * 3 months: most symptoms should have resolved but fatigue may still be present * 6 months: most people will feel back to normal.

DEFINITION: Inflammation to the mucosal lining of the nose caused by inappropriate hypersensitivity reaction to an aeroallergen. IgE mediated immune response, with mast cell activation and release of cytokines. it is uncommon in children under two years of age. After the age of two, the prevalence of allergic rhinitis steadily increases, demonstrating a bimodal peak in the early school and early adult years. Allergic rhinitis uncommonly presents for the first time in older adults, unless there is a significant change in exposures (eg, a new pet or a move to a different climate) Allergic rhinitis is a diagnosis associated with a group of symptoms affecting the nose. * Sneezing, runny nose , post nasal drip * Cough * Itchy eyes * Sore/itchy throat * Headache/congestion * Ear pain/itching/hearing loss * Snoring/mouth breathing * Dark circles * Young children typically do not blow their noses, and instead, they may repeatedly snort, sniff, cough, and clear their throats. Some scratch their itchy palates with their tongues, producing a clicking sound (palatal click) * Sinsusitis/nasal polyps/loss of sense of smell * Chronic ear infections, Serous otitis media and ASOM

* Allergic conjunctivitis – Up to 60 percent of patients with allergic rhinitis have concomitant allergic conjunctivitis * Asthma – Up to 50 percent of patients with asthma have allergic rhinitis. * Atopic dermatitis (eczema) * In children, atopic dermatitis presents with intensely pruritic erythematous patches with papules and some crusting, usually affecting the face, scalp, extremities, or trunk, with sparing of the diaper areas. * In older individuals with more chronic disease, atopic dermatitis presents with thickened skin, increased skin markings (lichenification), and excoriated and fibrotic papules. The flexural areas (neck, antecubital fossae, and popliteal fossae) are most commonly involved in adults. Oral allergy syndrome * Oral allergy syndrome is a form of food allergy that develops in individuals who are sensitized to pollen. Patients report itching and/or mild swelling of the mouth and throat immediately following ingestion of certain uncooked fruits (such as apples, peaches, plums, cherries, and some nuts) or raw vegetables. The symptoms result from contact with urticaria in the oropharynx caused by pollen-related proteins in these foods.

**Differential diagnosis of allergic rhinitis** **Acute infectious rhinitis** **Rhinitis medicamentosa –** Rhinitis medicamentosa is a complication of vasoconstrictor nasal sprays (which may develop with as little as five days of use) or intranasal cocaine abuse. Chronic nasal obstruction and nasal inflammation develop and are manifested as beefy red nasal membranes on physical examination. Diagnosis depends almost entirely on the appropriate history, characteristic physical examination findings, and positive response to treatment with topical nasal glucocorticoids, which is usually required to withdraw successfully from the culprit medication **Rhinitis due to systemic medications** Classes of medications that can cause nasal symptoms include birth control pills, antihypertensive drugs (alpha-adrenergic blockers, beta-adrenergic blockers, angiotensin-converting enzyme \[ACE\] inhibitors), erectile dysfunction drugs, and nonsteroidal anti-inflammatory drugs (NSAIDs). Psychiatric medications that have been implicated include chlorpromazine, thioridazine, perphenazine, chlordiazepoxide, amitriptyline, and alprazolam. Lastly, the immunosuppressants cyclosporine and mycophenolic acid can cause nasal symptoms. Rhinitis symptoms caused by these medications generally subside within a few weeks of discontinuation. **Atrophic rhinitis** Atrophic rhinitis is a syndrome of prog

ressive atrophy of the nasal mucosa usually seen in older adults. Such individuals report chronic nasal congestion and perceive a persistent bad odor. This condition is associated with mucosal colonization with Klebsiella ozaenae. **Unilateral rhinitis or nasal polyps** – Unilateral rhinitis or nasal polyps are uncommon in uncomplicated allergic rhinitis. Unilateral rhinitis suggests the possibility of nasal obstruction by a foreign body, tumor, or polyp, and the presence of nasal polyps suggests nonallergic rhinitis with eosinophilia syndrome (NARES), chronic bacterial sinusitis, allergic fungal sinusitis, aspirin hypersensitivity, cystic fibrosis, or primary ciliary dyskinesia (immotile cilia syndrome). Fiberoptic rhinoscopy may be helpful in this settin, so ENT referral for physical consultation is warranted Rhinitis with immunologic disorders – The most common presenting symptoms of **granulomatosis with polyangiitis** include persistent rhinorrhea, purulent/bloody nasal discharge, oral and/or nasal ulcers, polyarthralgias, myalgias, or sinus pain. **With relapsing polychondritis**, symptoms of stuffiness, crusting, rhinorrhea, and on occasion, epistaxis, may accompany nasal cartilage inflammation, which can also compromise olfaction. Cartilage destruction associated with sustained or recurrent episodes of inflammation can result in a characteristic saddle-nose

**Chronic nonallergic rhinitis** caused by irritants such as smoke, air pollution, strong odours such as perfume etc, spicy cuisines, alcohol, pregnancy, even hypothyroidism, weather, stress Investigation: CBC, AEC (eosinophil count), Immunocap IGE testing for common allergens \- Phadiotop or (rarely skin prick test- it is contraindicated on antihistamines \- need to be stopped for 3 weeks, or for patients on beta blockers * **Intermittent:** Symptoms occur \< 4 days per week OR for \< 4 consecutive weeks. * **Persistent:** Symptoms occur ≥ 4 days per week AND for ≥ 4 consecutive weeks. * **Mild:** Patients experience **all** of the following: normal sleep, no impairment of daily activities/sports/leisure, normal work/school performance, and symptoms are **not** troublesome. * **Moderate to Severe:** Patients experience **any one or more** of the following: sleep impairment, impairment of daily activities/sports/leisure, abnormal work/school performance, or symptoms that are considered troublesome. PREFERRED ANTIHISTAMINICS LEVOCETORIZINE AND FEXOFENADINE BEFORE IMMUNOTHERAPY \- CONFIRMATION WITH ALLERGY TESTING WILL BE REQUIRED

Allergen avoidance Allergen immunotherapy Immunotherapy can be given as subcutaneous injections or as sublingual tablets (available for a limited number of allergens) or drops. Indications for immunotherapy include severe symptoms that are only partially controlled with medications, a preference on the part of the patient to minimize the use or cost of medications, and, particularly in an older child or young adult, prevention of progression to asthma

Chronic Sinusitis (12 weeks or more) There are four cardinal signs/symptoms of CRS in adults, The diagnosis requires at least two of four cardinal signs/symptoms: * Anterior and/or posterior **nasal mucopurulent drainage:** The typical anterior and/or posterior nasal drainage of CRS is usually opaque white or light yellow, although there is considerable variability among patients. Thick yellow, green, or brown mucus can occur, although it is more characteristic of recurrent acute rhinosinusitis, allergic fungal rhinosinusitis, and eosinophilic mucin rhinosinusitis * **Nasal obstruction**/nasal blockage/congestion * **Facial pain**, pressure, and/or fullness * Reduction or loss of sense of smell, In children, the fourth cardinal sign/symptom is **cough** rather than reduction/loss of smell Several other symptoms are reported by patients with CRS, including fatigue, malaise, cough, sleep disturbance, ear pain or pressure, dizziness, halitosis, dental pain, dysphonia, or nasal or throat irritation. However, none of these are specific enough to be clinically useful in diagnosis. When patients have 4 or more annual episodes of ABRS, *without* persistent symptoms in between, the condition is termed *recurrent* ARS (RARS) 1. CRS without nasal polyposis (CRS without NP) 2. CRS with nasal polyposis (CRS with NP) 3. Allergic fungal rhinosinusitis (AFRS)

CRS cannot be "cured" in most patients, and therapy is intended to reduce symptoms and improve quality of life. Thus, the goals of CRS therapy include the following: * Control of mucosal inflammation and edema * Maintenance of adequate sinus ventilation and drainage * Treatment of colonizing or infecting micro-organisms, if present * Reduction in the number of acute exacerbations The clinician should confirm a clinical diagnosis of CRS with objective documentation of sinonasal inflammation, which may be accomplished using anterior rhinoscopy, nasal endoscopy, or computed tomography. CT scan is also necessary for surgical planning and evaluation of unique patient anatomy to prevent complications. Sinus CT scans are generally not recommended for evaluation of acute rhinosinusitis or acute flares of CRS, as common respiratory viral infections can cause extensive mucosal thickening, sinus ostial occlusion, and air-fluid levels that may persist for weeks . In children, sinus CT is generally not performed during the initial diagnostic evaluation in an effort to minimize radiation exposure . In a consensus document regarding appropriate use of CT in the management of CRS, the majority of otolaryngology experts believed that CT in children should be reserved for evaluation of those who have failed medical treatment and/or adenoidectomy or are experiencing complications

**Intranasal saline:** Saline irrigations can be used immediately prior to administration of other intranasal medications, so that the mucosa is freshly cleansed when the medications are introduced. We encourage patients with CRS to perform nasal **irrigation in preference to using saline nasal sprays**, Systematic reviews of studies employing various forms of saline sprays and irrigation (performed one to four times daily) found that nasal saline is an effective adjunctive treatment for CRS although is less effective as monotherapy than intranasal corticosteroids A variety of over-the-counter devices including squeeze bottles, syringes, and pots are available. Nasal lavage (with at least 200 mL warmed saline per side) can be performed as needed only, daily, or multiple times daily, depending on the severity of symptoms. Care should be taken to ensure that the irrigation bottles do not become contaminated. **Oral corticosteroids** Oral corticosteroids, such as [prednisone](https://www.uptodate.com/contents/prednisone-drug-information?search=chronic+rhinosinusitis&topicRef=7534&source=see_link), may be administered to patients with CRS for the following purposes: * Relieving severe and refractory mucosal edema in CRS without NP * Reducing the size of polyps in CRS with NP * Minimizing mucosal inflammation in allergic fungal rhinosinusitis (AFRS)

| Name | Type of preparation (alcohol content)¶ | strength | Available without a prescription (OTC) | Usual adult dose per nostril | Lower age limit when used in children (years)\* | Usual pediatric dose per nostril | | :---- | :---- | :---- | :---- | :---- | :---- | :---- | | Second-generation (systemic bioavailability \<1% or undetectable) | | | | | | | | Ciclesonide | Aqueous suspension pump spray | (50 mcg/spray) | No | Two sprays once daily | 2 years | 2 to 11 years: One or two sprays once daily ≥12 years: Two sprays once daily | | | Pressurized aerosol spray (3.4% alcohol) | (37 mcg/spray) | No | One spray once daily | 12 years | ≥12 years: One spray once daily | | Fluticasone furoate | Aqueous suspension pump spray | (27.5 mcg/spray) | Yes | Two sprays once daily | 2 years | One or two sprays once daily; in children 2 to 11 years, start with one spray once daily | | Fluticasone propionate | Aqueous suspension pump spray (0.25% alcohol) | (50 mcg/spray) | Yes | Two sprays once daily or one spray twice daily | 4 years | 4 to 11 years: One spray once daily ≥12 years: Two sprays once daily or one spray twice daily | | Mometasone | Aqueous suspension pump spray | (50 mcg/spray) | Yes | Two sprays once daily | 2 years | 2 to 11 years: One spray once daily ≥12 years: Two sprays once daily | | First-generation (systemic bioavailability 10 to 50%) | | | | | | | | Bec

lomethasone | | (42 mcg/spray) | No | One or two sprays twice daily | 6 years | One or two sprays twice daily; in children 6 to 11 years, start with one spray twice daily | | | | Pediatric: 40 mcg/spray) Adolescent/adult: (80 mcg/spray) | No | Two sprays once daily using 80 mcg/spray product | 4 years | 4 to 11 years: One spray once daily using 40 mcg/spray product ≥12 years: Two sprays once daily using 80 mcg/spray product | | Budesonide | | (32 mcg/spray) | Yes | One to two sprays once daily | 6 years | One to two sprays once daily; in children 6 to 11 years, start with one spray twice daily | | Triamcinolone | | (55 mcg/spray) | Yes | Two sprays once daily | 2 years | 2 to 5 years: One spray once daily ≥6 years: One to two sprays once daily; in children 6 to 11 years, start with one spray once daily |

**Antileukotriene agents** montelukast or zafirlukast and the 5-lipoxygenase inhibitor zileuton- may be used as an adjunct therapy to intranasal corticosteroids in patients with CRS with concomitant allergic rhinitis or in patients with NP * in the setting of an acute flare (eg, sudden worsening of symptoms). * in situations when infection is possible and cannot be excluded, such as CRS without nasal polyposis that does not respond to several months of topical glucocorticoids Approach to categorizing UTI in adults and adolescents

| Acute simple cystitis\* | Acute UTI that is presumed to be confined to the bladder: The classic clinical manifestations of cystitis consist of dysuria, urinary frequency, urinary urgency, suprapubic pain, and hematuria is also often observed. In elderly women There are no signs or symptoms that suggest an upper tract or systemic infection (refer to below) | | :---- | :---- | | Acute complicated UTI | Acute UTI accompanied by signs or symptoms that suggest extension of infection beyond the bladder: Fever (\>99.9°F/37.7°C)¶ Chills, rigors, significant fatigue or malaise beyond baseline, or other features of systemic illness Flank pain Costovertebral angle tenderness Pelvic or perineal pain in men | | Special populations with unique management considerations | Pregnant women Renal transplant recipients | | Underlying condition which can be considered to be complicated UTI | Underlying urologic abnormalities nephrolithiasis strictures stents urinary diversions Immunocompromising conditions (such as neutropenia or advanced HIV infection) Poorly controlled diabetes mellitus to have a complicated UTI if they have no concerning symptoms for upper tract or systemic infection | Definition of asymptomatic — Asymptomatic bacteriuria refers to patients who have no symptoms specifically referable to a UTI (eg, dysuria, urinary frequency or urgency, suprapubic pain

NO screening or treatment required for asymptomatic bacteriuria in the general population Asymptomatic bacteriuria in a few patient populations that may warrant screening and treatment. These populations include: * Pregnant persons * Patients undergoing urologic procedures in which mucosal bleeding is anticipated * Patients who recently received a renal transplant

**Women**: Pregnant and nonpregnant females have a similar prevalence (2 to 7 percent). In young healthy women, asymptomatic bacteriuria is transient; it rarely lasts longer than a few weeks. Prevalence among females with diabetes mellitus is 8 to 14 percent and is usually correlated with duration and presence of long-term complications of diabetes, rather than with metabolic parameters of diabetes control **Males** Asymptomatic bacteriuria is rare among healthy young males . Among males older than 75 years residing in the community, prevalence is 6 to 15 percent \[[16](https://www.uptodate.com/contents/asymptomatic-bacteriuria-in-adults/abstract/16)\]. Males with diabetes mellitus do not appear to have a higher prevalence of bacteriuria than those without Patients with diabetes mellitus Although diabetes mellitus is associated with asymptomatic bacteriuria in females, which in turn is associated with subsequent UTI, including severe U**TI, available evidence suggests that treating asymptomatic bacteriuria in patients with diabetes mellitus does not improve outcomes.**

Although cystitis in males is generally classified in the literature as a complicated urinary tract infection (UTI), it is reasonable to consider a healthy man without a neurogenic bladder who has mild to moderate dysuria, urinary frequency and/or urgency, with no symptoms or signs of infection outside the bladder, as having simple cystitis

Differentials **Acute bacterial prostatitis** The presence of fever, chills, malaise, myalgias, pelvic or perineal pain, or obstructive symptoms such as dribbling and hesitancy (due to acute urinary retention) in a man with symptoms of cystitis suggests acute bacterial prostatitis. Pain radiating to the tip of the penis Digital Rectal examination urine showing nitrite positive, clinically suspecting prostatitis \- start fluroquinolone and send culture. Underlying chronic prostatitis particularly in those males who have recurrent UTIs caused by the same strain of bacteria **Urethritis** must be considered in sexually active males; Dysuria, or discomfort with urination, is usually the chief complaint Pruritus at meatus Discharge at the urethral meatus: can range from mucoid or watery to frankly purulent , morning An acute presentation of a frankly purulent urethral discharge is suggestive of, but not definitive for, gonorrhea. Patients with dysuria alone are more likely to have chlamydial infection. These patients should be treated for urethritis with therapy that provides coverage for both gonococcal and chlamydial infections. **Dysuria that is accompanied by painful genital ulcers** is most likely due to genital herpes simplex virus (HSV); patients with primary HSV infection may also complain of fever, tender local inguinal lymphadenopathy, and

headache. **Vaginitis** In females with dysuria, the presence of vaginal discharge or odor, pruritus, dyspareunia, and absence of urinary frequency or urgency should prompt consideration of vaginitis. Causes of vaginitis include yeast infection, trichomoniasis, and bacterial vaginosis. **Urethritis** Evaluation for urethritis is warranted in sexually active females with dysuria, particularly those with pyuria on urinalysis but no bacteriuria. Causes of urethritis in females include chlamydia, gonorrhea, trichomoniasis, Candida species, herpes simplex virus, and noninfectious irritants, such as a contraceptive gel. **Pelvic inflammatory disease** Lower abdominal or pelvic pain and fever are the most common clinical findings in patients with pelvic inflammatory disease (PID), although dysuria may also be present. The findings of mucopurulent endocervical discharge or cervical motion tenderness on pelvic examination are strongly suggestive of PID. **Painful bladder syndrome** This is a diagnosis of exclusion in females who have ongoing discomfort related to the bladder with symptoms of dysuria, frequency, and/or urgency but no evidence of infection or other identifiable cause.

Urine R/M and C\&S indicated in India as drug resistnace is high E. coli should not necessarily be considered a contaminant if it grows in mixed flora since almost any growth of E. coli in voided urine in a symptomatic patient reflects bladder growth . Growth of organisms generally thought to be contaminants (such as lactobacilli, enterococci, Group B streptococci, and non-saprophyticus coagulase-negative staphylococci) may be considered causative when found in voided midstream urine at high counts and with pure growth IF Clinically pyelonephritis IS SUSPECTED 1) Recurrent (more than 2 episodes in a year), in sepsis, anatomical abnormality, previous/suspected stones, urogenital surgery \- urine C/S , imaging ( CT \- KUB is preferred) \- Out patient or inpatient \- depending on CT report. 2) Other cases \- urine C/S \- start oral antibiotics (fluroquinolones) \- If responding in 24 to 48 hours \- no imaging needed. #### TREATMENT of uncomplicated UTI/cystitis

**First-line regimens recommended for females:** Nitrofurantoin 100 mg BD for 7 days It should be avoided if there is suspicion for early pyelonephritis or if the creatinine clearance is \<30 mL/minute. Fosfomycin (3 grams of powder mixed in water as a single dose) Oral: Always mix with 3 to 4 oz (90 to 120 mL) cool water before ingesting; do not administer in its dry form or mix with hot water. May be administered without regard to meals. ADD COVER FOR MDR gram-negative organism , Use of a fluoroquinolone, [trimethoprim-sulfamethoxazole](https://www.uptodate.com/contents/trimethoprim-sulfamethoxazole-co-trimoxazole-drug-information?search=fosfomycin&topicRef=8063&source=see_link), or broad-spectrum beta-lactam (eg, third or later generation cephalosporin) if they have any of the following occurring in the prior three months: * An MDR gram-negative urinary isolate (ie, nonsusceptible to at least one agent in three or more antimicrobial classes; this includes extended-spectrum beta-lactamase \[ESBL\]-producing isolates) * Inpatient stay in a health care facility (eg, hospital, nursing home, long-term acute care facility). **If pregnant \-** 1st trimester \- prefer \- amoxicillin/cephalexin. Nitrofurantoin(avoid in 1st trimester) and fosfomycin can be used.

**Suspected ACUTE prostatitis in men:** severe cystitis symptoms or concern about early involvement of the prostate Ciprofloxacin 500 mg orally twice daily or 1000 mg extended release once daily (10 DAYS), or Levofloxacin 750 mg orally once daily) **clinically chronic prostatitis** \- obstructive symptoms \+ chronic pelvic pain \+/- systemic symptoms for 3 months or more \- need per rectal examination and C/S or urine ( 2 samples) \- fluroquinoloes/Septran for 6 weeks or more. **FOLLOW-UP** Follow-up urine cultures are not needed in males with acute simple cystitis whose symptoms resolve on antimicrobials. For patients who had hematuria on initial presentation, a urinalysis should be repeated several weeks following antimicrobial therapy to evaluate for persistent hematuria. **Urethritis:** Syndromic approach: Gonorrhoea: The preferred regimen for gonococcal infections is a single intramuscular dose of ceftriaxone (500 mg for individuals \<150 kg or 1 g for individuals ≥150 kg) or Cefixime 400 mg/800 mg Chlamydia: doxycycline 100 mg twice daily for seven days OR azithromycin given as a single 1 g oral dose is an alternative Additionally Metronidazole 2 gm one dose

**Symptomatic therapy** Symptoms of acute simple cystitis should respond to antimicrobial therapy within 48 hours. In the interim, for some patients with severe dysuria, **Pyridium**: phenazopyridine three times daily for two days Patients with urologic abnormalities a longer duration of therapy (eg, one to two weeks, depending on the agent chosen) is reasonable. **Incidental pyuria (10 or More pus cells in uncentrifuged sample)** 1) Asymptomatic/Sexually inactive \- no further testing needed. 2) Sexually active- treat for STI 3) Pregnant \- Urine C/S \- significant if colony count \>105

Allergies are described as abnormal harmful immune responses to harmless substances,or allergens. The term ‘allergy testing’, in general, refers to evaluation for suspected type I or type IV hypersensitivity reactions that occur because of exogenous allergens. Type IV (delayed) reaction present with **purely cutaneous symptoms such as pruritic skin lesions: eczema/contact dermatitis** * A personal or family history of atopy is essential because individuals with these histories are genetically predisposed to produce IgE toward certain environmental allergens. * These are evaluated using the skin patch test method. On the contrary, type II hypersensitivity reactions occur because of the presence of endogenous IgM or IgG antibodies, for example, in acute haemolytic transfusion reaction, rheumatic fever and pemphigus vulgaris. Type III reactions, in turn, are due to antigen-antibody complexes that result in hypersensitivity reactions, as in systemic lupus erythematosus, serum sickness, reactive arthritis, IgA vasculitis and nephropathy. Type II and III reactions are not evaluated via allergy testing. Common dilemmas concerning allergy testing include the indication for allergy testing, selection of the appropriate test,interpretation of the results and application of this information in patient management.

**Type I (immediate) reaction** : Also known as the immediate hypersensitivity reaction, occurs because of IgE activation of mast cells in the skin as well as the gastrointestinal and respiratory mucosal linings. * Previous exposure to the allergen is necessary for this reaction to manifest. Firrst exposure produces sensitization (Presence of IgE at levels significantly high for a particular antigen) * Subsequent exposure to the same allergen triggers a cascade of events that produces a reaction within minutes (immediate reaction) and up to 1 to 3 days afterward (late phase reaction).

* Urticaria * Angioedema: Angioedema is a sudden, localized swelling of the deep layers of the skin or mucous membranes. It most commonly affects the lips, eyelids, face, hands, feet, and genitals. While it resembles hives, it affects deeper tissues and often presents as tightness or burning rather than itching Angioedema is a medical emergency if it affects the throat, tongue, or larynx, as it can lead to severe airway obstruction and breathing difficulties. The severe most form is Anaphylaxis which is highly likely when *either* of the following is met 1\. **Acute onset (minutes–hours**) with skin/mucosal involvement (urticaria, angioedema, flushing) plus ≥1 of: \- Respiratory compromise (dyspnea, wheeze, stridor, hypoxemia) \- Reduced blood pressure or signs of end‑organ hypoperfusion (collapse, syncope, incontinence) \- Severe gastrointestinal symptoms (crampy pain, repetitive vomiting; especially with non‑food triggers in WAO criteria) 2\. **Acute hypotension, bronchospasm, or laryngeal involvement** after exposure to a known or highly probable allergen, even without skin involvement Meeting formal criteria is **not required before giving epinephrine** **History taking during anaphylaxis workup** When evaluating anaphylaxis (including idiopathic or exercise‑associated forms), history should systematically document:

**Timing and content of food ingestion** in the 4–6 hours before onset; note specific high‑risk foods (wheat, peach/other LTP‑rich fruits, shellfish, nuts).14 **Exercise around the event**: type/intensity, onset relative to eating or drug intake; ask explicitly about mild exertion (walking, running for a bus) vs vigorous activity.25 **NSAID and alcohol use** in the preceding hours (including “as‑needed” analgesics); identify specific NSAID and whether reactions recur only with food \+ NSAID.156 Other cofactors: **menstruation, intercurrent viral illness, fasting, sleep deprivation, stress**. Asthma and peanut trigger further increased risk of grade 4 reactions **Acute management** Management of Anaphylaxis is centered on immediate intramuscular epinephrine plus aggressive supportive care; diagnostic tests support but must not delay treatment. **Initial ED/prehospital steps** \- Position supine (or position of comfort if vomiting/dyspneic) with legs elevated. \- High‑flow oxygen; continuous cardiac and pulse oximetry monitoring. \- Large‑bore IV with isotonic crystalloid; give 1 L bolus in adults (20 mL/kg in children) for hypotension, repeat as needed.

**Epinephrine (first‑line**) \- IM epinephrine 1:1000(1mg/ml) into mid‑anterolateral thigh; repeat q5–10 min as needed (doses per local protocol). More than two dosages should be given in clinical settings only **Dose of intramuscular epinephrin 1mg/ml strength** * Adult IM: 0.3–0.5 mg (0.3–0.5 mL of 1 mg/mL) thigh * Pediatric IM: 0.01 mg/kg up to 0.3–0.5 mg per dose * Repeat IM q5–10 min as needed based on response * Use anterolateral thigh (vastus lateralis); IM preferred over SC * No absolute contraindication in life‑threatening anaphylaxis * Reserve IV epinephrine for profound hypotension/CPA refractory to IM \+ fluids * IV bolus: 0.1 mg over \~5 min * IV infusion: \~0.05–2 mcg/kg/min; typical 1–4 mcg/min (4–60 mL/hr of 4 mcg/mL) * Use central/large vein, pump, continuous BP/ECG * Beta-blockers blunt response; epi still indicated; ↑arrhythmia/HTN risk * Continuous **ECG and frequent BP**; rapid IV administration can precipitate fatal arrhythmias or cerebrovascular hemorrhage * Avoid extravasation; if it occurs, infiltrate with **phentolamine 5–10 mg in 10–15 mL NS**. **Glucagon:** Consider glucagon if poor response and patient is on beta‑blockers.

**Adjunctive medications** **H1 ± H2 antihistamines** for cutaneous/systemic symptoms **Systemic corticosteroids** commonly used in moderate–severe reactions; they do not treat acute symptoms but may (theoretically) reduce protracted reactions, though high‑quality data are lacking Patients taking beta-adrenergic blockers (e.g., for hypertension or migraine prophylaxis) can develop **refractory anaphylaxis that responds poorly to standard epinephrine dosing**.1 Beta-blockade attenuates epinephrine’s β₁/β₂ effects (cardiac inotropy/chronotropy and bronchodilation), reducing its ability to reverse hypotension and bronchospasm. 1\. **Do not withhold epinephrine** \- Give standard IM thigh epinephrine; repeat as needed.4 2\. **Aggressive volume resuscitation and vasopressors** \- Hypotension is primarily distributive; give large-volume crystalloids, often several liters, titrated to BP and urine output.1 \- For persistent shock, escalate to **IV epinephrine infusion** or **dopamine** with invasive monitoring as required.1 3\. **Glucagon for patients on beta-blockers** \- In BB-treated patients with **refractory anaphylaxis**, **glucagon may be effective** because it increases intracellular cAMP via a non–β-adrenergic pathway, providing **inotropic, chronotropic, and bronchodilatory effects** independent of blocked β-receptors.1

4\. **Ongoing caution with nonselective BBs** \- Avoid or minimize nonselective BB use in patients at significant risk for recurrent anaphylaxis where possible; if continued, counsel regarding potentially more severe reactions and need for early epinephrine and EMS activation. **Airway and breathing** \- Early airway assessment; provide bag‑valve‑mask ventilation as needed \- Prompt endotracheal intubation if progressive laryngeal edema; epinephrine may reverse edema but do not delay if not rapidly improving \- Cricothyrotomy or jet ventilation if intubation/BVM fails \- Inhaled β‑agonists for wheeze/bronchospasm; consider aminophylline or systemic corticosteroids for refractory bronchospasm (onset delayed). \- Observe at least **4–6 hours** after symptom resolution; longer/ admission for severe or refractory reactions (cardiovascular or severe respiratory involvement) or if multiple epinephrine doses were required, given risk of biphasic reactions up to 12–48 h **Acute phase biomarkers** \- Draw **acute serum tryptase** as early as possible, ideally within \~2 h of symptom onset; obtain a second (baseline) level later to detect a significant rise. \- These tests support but do not replace a clinical diagnosis and should not delay treatment. **Later allergy workup (identifying the trigger**) Performed electively, usually by an allergist

\- **Venom anaphylaxis**: Hymenoptera venom skin testing and/or in vitro specific IgE **4–6 weeks** after the sting to maximize sensitivity (same timing for imported fire ant extracts). \- **Drug allergy (e.g., penicillin**): skin testing with standardized reagents (Pre‑Pen, penicillin G ± minor determinants) once the patient is stable; no fixed waiting interval is given. \- **Perioperative anaphylaxis**: perform immediate‑type skin tests and/or in vitro specific IgE to all plausible culprit agents, but **delay testing after the event when feasible**, unless re‑operation cannot be postponed. \- **Food allergy**: targeted SPT and serum specific IgE guided by history; double‑blind or supervised open food challenges used when necessary. \- Prescribe and train in the use of **epinephrine autoinjectors**,(NOT AVAILABLE IN INDIA- HENCE SYRINGE AND AMPULE) routinely for patients at higher risk of recurrent anaphylaxis; consider \>1 device in those needing multiple doses or with biphasic history. \- Arrange allergist referral for **trigger identification and desensitization** where indicated (e.g., venom immunotherapy, drug desensitization). #### Treatment of non anaphylactic allergic reaction **Treatment of non-anaphylactic cutaneous/systemic reactions** **Acute urticaria/limited angioedema without systemic compromise**

\- **Second-generation H1 antihistamines** are first-line (eg, cetirizine, loratadine, fexofenadine) and may be dose-escalated in refractory cases in line with urticaria guidance. **Adults/adolescents ≥12 y:** 5 mg PO once daily in the evening **Pediatrics** \- 6 months–5 years: **1.25 mg PO once daily** in the evening \- 6–11 years: **2.5 mg PO once daily** in the evening **Renal impairment (≥12 y**) 1 \- CrCl 50–80 mL/min: 2.5 mg qDay \- CrCl 30–50 mL/min: 2.5 mg q48h \- CrCl 10–30 mL/min: 2.5 mg 2×/week \- CrCl \<10 mL/min or hemodialysis: contraindicated **Adults/adolescents ≥12 y**: 180 mg PO once daily **or** 60 mg PO twice daily **Pediatrics – oral suspension/tablets** \- 6 months–\<2 years (chronic idiopathic urticaria): **15 mg PO BID** \- 2–11 years: **30 mg PO BID**. **Renal impairment (CrCl \<80 mL/min, ≥12 y**) \- 60 mg PO once daily initially. Avoid grapefruit/apple/orange juice around dosing due to reduced bioavailability (separate by ≥4 h). If inadequate control, **increase dose up to fourfold** before moving to next‑line agents (mainly relevant for chronic urticaria) \- **Sedating H1 agents** \- **Diphenhydramine PO**: adults 25 mg q6h for 2–5 days; children 1 mg/kg q6h for 2–5 days.6 \- **Hydroxyzine PO**: adults 25 mg q8h for 2–5 days; children 1 mg/kg q8h for 2–5 days.

\- **H2 blockers** **Cimetidine PO (adult**): 300 mg qid for 2–5 days. \- Pediatric H2 dosing is not specified in the supplied data; use only if you have an appropriate pediatric reference. \- **Short systemic corticosteroid course** (e.g., prednisone 20–80 mg PO daily for 2–5 days in adults; 0.5–1 mg/kg in children) can be considered in more extensive reactions or to reduce risk of late-phase recurrence after significant systemic symptoms, recognizing that benefit is largely theoretical and long-term use is discouraged. \- Observe patients for several hours if symptoms were extensive, there is diagnostic uncertainty, or progression risk (e.g., facial/oropharyngeal swelling without airway compromise). \- Discharge once stable with oral H1 (± H2, short steroids) for 5 days, clear return precautions for respiratory or systemic symptoms, and counseling on trigger avoidance. Would you like a concise protocol-style order set (ED and outpatient) for these non-anaphylactic reactions, including pediatric dosing ranges?

**Common Allergens:** Dust, pollen/plant components, animal components \- dander, mite etc. \- **Symptom pattern** – seasonal vs perennial, indoor vs outdoor, relation to exposures (pets, house dust, workplace). \- **Symptom type** – rhinitis, conjunctivitis, asthma (wheeze, cough), lower vs upper airway; urticaria/anaphylaxis after stings/meds/foods. \- **Atopic background** – personal/family history of asthma, allergic rhinitis, atopic dermatitis. \- **Medication use** – antihistamines, TCAs, H2 blockers, beta‑blockers/ACEIs before testing. \- **Nasal/ocular**: clear rhinorrhea, pale swollen turbinates, conjunctival injection/chemosis, allergic shiners in rhinitis.3 \- **Chest**: wheeze, prolonged expiration; confirm obstructive pattern and reversibility on spirometry if asthma suspected. \- **Skin**: eczema, urticaria, dermatographism (may cause false-positive SPT). Rhinoscopy can document polyps/structural disease when needed. For a patient-reported food allergy, use a structured history-first algorithm, **True allergy (IgE mediated)**

* **Clarify reaction type**: Ask which food, form (raw/cooked), amount, and timing of symptom onset after ingestion; IgE-mediated reactions usually occur within minutes to 2 hours, whereas non–IgE-mediated allergic reactions can be delayed or chronic * **Characterize systems involved**: Skin (urticaria, angioedema), GI (nausea, vomiting, pain, diarrhea), respiratory, cardiovascular; hypotension/syncope suggests anaphylaxis * **Assess reproducibility**: Determine whether similar symptoms recur with repeated exposure; reproducibility strongly supports food allergy * **High-risk features**: Prior anaphylaxis, respiratory compromise, cardiovascular symptoms, or coexistence of asthma—particularly poorly controlled—increase risk of severe reactions **Non–IgE and mixed-mechanism food allergy syndromes** are largely pediatric, but adults are affected, particularly for FPIES and eosinophilic GI disease.

* **FPIES, food protein–induced allergic proctocolitis (FPIAP), and food protein–induced enteropathy** are described as non–IgE-mediated GI food allergies that “primarily affect the gastrointestinal tract” in infancy, with typical features of vomiting, diarrhea, poor weight gain or blood‑streaked stools. These infant non–IgE-mediated food allergies (FPIES, FPIAP) “typically resolve within the first years of life.” Epidemiologic series from the UK/Ireland and Sweden describe FPIES almost exclusively in children (incidence 0.006% in England, triggers mainly cow’s milk, fruits/vegetables, egg, fish in infants; median first reaction in early months) **Adult contribution**: A Japanese adult cohort of food‑allergic patients found **48 of 288 adults (16.7%) met criteria for adult FPIES**, with seafood as the commonest trigger. 5 This quantifies FPIES *within* an adult food‑allergy population, not its share of all FPIES cases; comparative pediatric vs adult proportions at the population level are not provided in the supplied data. * **Eosinophilic gastrointestinal diseases (mixed IgE/cell-mediated**) : **chronic, relapsing conditions** often requiring long‑term management

Eosinophilic esophagitis and other eosinophilic GI disorders are characterized by chronic eosinophilic inflammation and are described as **Global EGID symptom profile** They are not confined to infancy; persistence into adolescence and adulthood is typical * **Eosinophilic gastritis/enteritis/colitis**: Eosinophilic infiltration can extend through mucosa, muscularis, and serosa, leading to malabsorption, obstruction, and other complications. Diarrhea, sometimes with weight loss or malnutrition, is thus a **prominent symptom** in many non‑esophageal EGIDs, particularly when the colon or diffusely the small bowel are involved. In **eosinophilic colitis (EoC**), some patients present with **bloody diarrhea**, mimicking inflammatory bowel disease * **Eosinophilic esophagitis (EoE**) Isolated Eosinophilic Esophagitis (EoE) is defined by esophageal dysfunction (dysphagia, vomiting, chest/epigastric pain, food impaction) with eosinophilic inflammation restricted to the esophagus. Chronic dysphagia, food impaction, abdominal pain, growth issues; biopsy with eosinophil-predominant inflammation

* H/o Angioedema/Anaphylaxis * Recurrent/persistent Allergic rhinitis * Recurrent Asthma * ? Recurrent Allergic conjunctivitis * ? Recurrent/chronic Urticaria: acute- post viral \- 6 weeks \- no need to skin/patch test,What do the guidelines say * Prior to immunotherapy, environmental control counseling, unclear triggers * When a specific cause is established in history and avoidance results in resolution and re-exposure reproduces symptoms, then no further testing is necessary, unless the impact on the patient’s quality of life from the restriction will be severe The best entry-level approach is **a medical consultation paired with an automated screening blood test or a Skin Prick Test (SPT)**, r**ather than immediately buying a massive, expensive panel.** **The single best step depends directly on whether you are experiencing respiratory symptoms (like sneezing or asthma) or digestive/skin symptoms.**

**Serum allergen-specific IgE (sIgE**) Modern assays (e.g., ImmunoCAP) have near-comparable sensitivity/specificity to SPT for inhalant allergens. **What patient should know before testing? How will the result impact management?** 1) **Allergic tests include a limited number of allergens.** 2) **In addition to those specific IgE tested patients can be allergic to antigens which are not tested.** 3) **A positive test need not necessarily indicate that the person is allergic as false positives are common.** 4) **Even though the allergen is identified at certain situations, it might not be possible to completely eliminate the allergen.** 5) **These tests are more sensitive and specific for airborne allergens.** **1\. For Respiratory Symptoms: Phadiatop Adult Screen OR children Screen as appropriate** If you suffer from unexplained sneezing, runny nose, or wheezing, this is the most efficient baseline option * **Why it is best:** It uses genuine ImmunoCAP technology to deliver a highly accurate "Yes/No" answer on whether your symptoms are actually caused by an environmental allergy (like dust mites, molds, or dander) * **The Benefit:** If it comes back negative, you instantly save thousands of rupees by ruling out an environmental allergy, proving that you do not need expensive specialized treatment.

**2\. For Unclear/GI Symptoms: Total IgE \+ Absolute Eosinophil Count (AEC)** If patient has generalized symptoms—such as alternating skin rashes, mild digestive issues, or chronic congestion—but aren't sure if it's an allergy, start with a basic **Total IgE & CBC**, **Why it is best:** It does not name the specific trigger, but it measures the body's overall baseline allergic response and immune cells. **3**. **In suspected food allergies :** only testing for specific suspected allergen’s for which history is strong is advised Food SPT and serum sIgE have **high false‑positive rates (\~50–60%)**, but negative results have high negative predictive value (\>95%) for IgE‑mediated reactions and **and unnecessary dietary restriction** **4\. Consider component-resolved diagnostics (e**.g., Ara h 2\) selectively when cross-reactivity is suspected, especially for peanut/tree nuts. **5.IF choosing comprehensive panels : Match Symptoms to the Panel rather than type of allergen** If you decide to go straight to a specific panel, pick a targeted option like the Dust Allergy Panel **(\~₹3,900)** or **Asthma/Rhinitis Panel (\~₹11,500)** rather than a generic food panel, ensuring it matches the patient’s day-to-day physical discomfort **6\. The Clinical Alternative: Skin Prick Test (SPT)**

* **Why it is theoritically the best:** IStandardized extracts for dust mites, cat, dog, grass/trees/weeds, molds; accuracy \>85% sensitivity/specificity for these. It is cost-effective, immediate, and maps exact reactions to local Indian grasses and dust. * **The draw backs**: it has to be done at a Hospital \- ICU set up required, between 26-54 pricks \- each prick with separate needle and it has many contraindications that include: * On antihistamines: Hold oral/nasal antihistamines and other H1/H2‑blocking or TCA drugs 3–7 days pre-test * Avoid in unstable asthma, recent major cardiac/cerebrovascular events due to small anaphylaxis risk * Skin inflamed: False positives with dermatographism/chronic urticaria; test on unaffected skin in atopic dermatitis * Pregnant * Child \< 2 years * Steroids with 7-10 days \- **Spirometry/bronchoprovocation**: to confirm obstruction and hyperresponsiveness; methacholine challenge helpful when baseline spirometry is normal. \- **Sputum or peripheral eosinophils, serum IgE**: characterize allergic/eosinophilic phenotype and guide therapy selection in moderate–severe asthma, but not diagnostic alone. **Conceptual role of food‑specific IgG/IgG4 intolerance tests**

\- The immune system normally generates IgG to many dietary proteins; **specific IgG to foods is common in healthy individuals** and reflects exposure, not pathology.1 \- In non‑IgE cow’s‑milk protein intolerance, **IgG/IgG‑subclass antibodies to cow’s‑milk protein “have no role in diagnosing CMPA and therefore are not recommended.”** \- In the workup of protein intolerance and non‑IgE GI disease, position statements from AAAAI, NIAID, and ESPGHAN explicitly categorize **cytotoxic tests and IgG tests as of “unproven value.”** \- The Diagnostic allergy testing overview lists **IgG/IgG4 food testing among unvalidated diagnostics** alongside provocation/neutralization, kinesiology, cytotoxic, and electrodermal tests, noting they lead to unnecessary testing and inappropriate advice. \- A Medscape review of social‑media allergy myths identifies **IgG testing as a major source of misinformation**, emphasizing that results are broad, nonspecific, and often label dozens of foods as “positive,” confusing patients and driving them to unnecessary restriction. \- Studies in eosinophilic esophagitis and eosinophilic gastroenteritis show **elevated food‑specific IgG/IgG4 and mucosal IgG4 deposition** but these are **pathophysiologic markers**, not validated diagnostic tools; even active vs inactive disease groups have overlapping IgG/IgG4 levels.

**How clinicians should interpret IgG results** \- A positive IgG/IgG4 to a food **does not demonstrate allergy or intolerance** and should not be used to justify avoidance on its own. \- If a patient presents with a commercial IgG panel: \- Emphasize that **tolerated foods remain safe regardless of IgG positivity**. \- Focus on **symptom‑linked foods**, using history, targeted IgE testing for suspected IgE‑mediated reactions, and structured elimination/re‑challenge and/or supervised oral food challenges for non–IgE phenotypes.

\- Define **acute urticaria** (wheals/angioedema ≤6 weeks) vs **chronic urticaria** (\>6 weeks; chronic spontaneous or inducible). \- Detailed history (onset, duration of individual wheals, triggers including NSAIDs, physical stimuli, infections, stress) and physical exam are first steps. **Screen for clinical red flags (at each visit**) **Typical Chronic spontaneous urticaria CSU (no immediate extended workup):** \- Wheals pruritic, evanescent (\<24 h), no bruising; \+/- histaminergic angioedema; no systemic symptoms; respond to H1 antihistamines. **Red flags for mimics**: \- Wheals **\>24 h**, painful/burning, **residual purpura or hyperpigmentation** \- Recurrent fever, arthralgia/arthritis, GI pain, eye inflammation, lymphadenopathy, fatigue, bone pain \- **Recurrent angioedema without wheals**, non‑pruritic, poor response to antihistamines/steroids \- Strong family history of angioedema or ACE‑inhibitor association **Baseline labs for all chronic urticaria** For patients labelled “chronic urticaria,” obtain once:261 \- **CBC with differential** (eosinophilia, anemia, cytopenias) \- **ESR and/or CRP** \- **TSH** (± thyroid antibodies in specialist care) **Targeted panels when red flags present** **A. Urticarial vasculitis / systemic autoimmune or autoinflammatory disease** If wheals \>24 h, painful, bruising, or systemic features:521

\- Already done: **CBC, ESR/CRP** \- Add: \- **ANA ± RF** \- **Hepatitis B and C serologies** (vasculitis/cryoglobulinemia context) \- **Stool O\&P** if eosinophilia, GI symptoms, or travel risk2 \- Consider skin biopsy when lesions are purpuric, non‑blanchable, or leave pigment change to evaluate for urticarial vasculitis.45 \- Refer to rheumatology/immunology when systemic inflammatory/autoinflammatory syndrome suspected (e.g., recurrent fevers, bone pain, monoclonal gammopathy **B. Bradykinin‑mediated angioedema (HAE/acquired**) Bradykinin‑mediated [Angioedema](https://emedicine.medscape.com/article/135208-overview) typically presents as recurrent, nonpruritic swelling without urticaria, with a particular risk for abdominal and airway complications.

\- **Swelling characteristics**: Nonpitting, usually nonpruritic, often painful or with burning/tightness; involves deep dermis, subcutaneous or submucosal tissue rather than superficial skin.1 \- **Common sites**: Face (lips, eyelids), tongue, hands, feet, genitalia; bowel wall and larynx are classic in hereditary and acquired C1‑INH deficiency and ACE‑inhibitor angioedema.12 \- **Time course**: Attacks evolve over hours and typically last **1–7 days**, with symptom‑free intervals between episodes.34 \- **Absence of wheals**: Angioedema occurs **without urticaria** in HAE and most ACEI/AAE cases; pruritus is usually absent.14 \- **Poor drug response**: Little or no response to H1 antihistamines, corticosteroids, or epinephrine, in contrast to histaminergic angioedema.54 \- **Airway**: Tongue/laryngeal edema causing throat tightness, dysphonia/hoarseness, stridor, or air hunger; airway obstruction is the leading cause of death in anaphylaxis‑like presentations and in untreated HAE.67 \- **Gastrointestinal**: Severe, colicky abdominal pain with nausea, vomiting, distension, or ascites from bowel wall edema; may mimic an acute surgical abdomen.134 \- **Peripheral/genital**: Disfiguring, painful swelling impairing function (e.g., hands/feet, scrotum).1

\- **Life‑threatening laryngeal obstruction**: Unpredictable; historical untreated HAE mortality up to \~30% from asphyxiation. \- **Severe abdominal attacks**: Risk of hypovolemia from third‑spacing and unnecessary laparotomy if misdiagnosed. \- **Quality‑of‑life impairment**: Recurrent painful, disabling swelling and procedure‑triggered crises (e.g., dental, ENT surgery). **Key differentiators from histaminergic angioedema/urticaria** \- No wheals; nonpruritic, deeper, longer‑lasting swellings (2–5+ days) vs rapid‑onset, itchy hives and AE resolving \<48 h. \- Prominent abdominal attacks and recurrent isolated angioedema; family history or ACE‑inhibitor exposure often present. If *recurrent angioedema without wheals*, non‑pruritic, poor antihistamine response, or strong family history: \- Order: \- **C4** \- **C1 esterase inhibitor level and functional activity** \- ± **C3** in the broader complement panel2 \- Continue basic inflammation/autoimmunity screen (CBC, ESR/CRP, ANA) as above.2 \- Refer to allergy/immunology for interpretation and long‑term HAE/ACEI‑AE management. \- If targeted workup is negative and clinical pattern remains typical, manage as CSU per guideline algorithm (stepwise 2nd‑gen H1, then biologics if refractory).31 \- Reassess disease activity and need for ongoing therapy every 3–6 months.

**Second‑generation H1 antihistamines (daily, not PRN**) Guidelines recommend a **standard‑dose modern 2nd‑generation H1 antihistamine as first‑line** in both acute and chronic disease. \- **Levocetirizine**: adults/≥12 y 5 mg PO qDay; children 6–11 y 2.5 mg qDay; 6 mo–5 y 1.25 mg qDay. \- **Fexofenadine**: adults/≥12 y 180 mg qDay or 60 mg BID; 2–11 y 30 mg BID; 6–23 mo 15 mg BID. In chronic cases can be given for 6 weeks and evaluated again after 7-10 days or SOS If inadequate control, **increase dose up to fourfold** before moving to next‑line agents (mainly relevant for chronic urticaria). Management of acute exacerbation covered in treatment for non anaphylactic allergic reaction For CSU uncontrolled on high‑dose 2nd‑generation H1 1\. **Omalizumab** 150–300 mg SC q4wk (CU indication) 2\. **Dupilumab** SC q2wk for antihistamine‑refractory chronic spontaneous urticaria 3\. **Remibrutinib** (oral BTK inhibitor) for CSU inadequately controlled with H1 antihistamines 4\. **Cyclosporine** 3.5–5 mg/kg/day for severe disease refractory to antihistamines and omalizumab, under specialist supervision

\- Advise avoidance of individually relevant triggers (NSAIDs, alcohol, overheating, pressure/friction, stress) where feasible. \- Consider pseudoallergen‑reduced or low‑histamine diet trial for CSU (2–3 weeks) in selected patients. \- Re‑evaluate treatment need and step‑up/step‑down every 3–6 months, as activity fluctuates and spontaneous remission is common.

**Cervical radiculopathy \- signs and symptoms** **Pain- radiating along the nerve distribution** **Pins and needles sensations** **Spurling's maneuver and modified Spurling's maneuver** can be used to reproduce radicular pain. The specificity of the Spurling's maneuver was consistently high, ranging from 0.89 to 1.00; sensitivity varied from 0.38 to 0.97 Spurling's maneuver – The Spurling's maneuver (also called the neck compression test) is performed by keeping the head in a neutral position and tapping or pressing down on the top of the head. This should reproduce the pain beyond the shoulder, in a positive test Modified Spurling's maneuver: The procedure is repeated with the head extended and rotated and tilted to the affected side. The modified Spurling's maneuver is most likely to provoke symptoms in patients with foraminal stenosis, central stenosis, or disc herniation.

* For most other patients in whom imaging is indicated, cervical spine radiography is usually the initial study. If radiography suggests an underlying abnormality other than age-appropriate degenerative changes, an MRI with contrast should be obtained. * The most common view for Cervical spine X-ray: is AP and Lateral * For evaluation of suspected infection or malignancy, an MRI of the cervical spine with contrast is the appropriate choice. * In patients presenting with symptoms and signs of myelopathy or progressive radiculopathy, MRI without contrast is the appropriate choice. If MRI is contraindicated or unavailable, CT myelography is an acceptable alternative. * MRI Findings of severe neuro-compression: Hyperintensity in T2 images in cord- cord edema, Severe compromise in neural foramen \- no CSF visualised. Laboratory studies are not necessary for the routine evaluation of neck pain, particularly if a musculoskeletal aetiology is suspected. Laboratory testing may be helpful when non-spinal causes of neck pain are suspected.

* ESR and CRP: may be elevated in patients with chronic inflammatory conditions (eg, polymyalgia rheumatica, giant cell arteritis, rheumatoid arthritis). * Complete blood cell count (CBC) with differential \+ appropriate culture ( in addition to tests mentioned in 1): obtained in patients with suspected infection * CBC, urinalysis, and basic serum chemistries may be appropriate in initial tests in patients with suspected malignancy. * Electrocardiogram and troponin are appropriate if myocardial ischemia is suspected. 1) **Progressive radiculopathy** Proposed indications for surgery in patients with cervical radiculopathy are unremitting radicular pain despite 6 to 12 weeks of conservative treatment, progressive motor weakness, Requires the presence of all of the following criteria * Symptoms and signs of cervical radiculopathy ( nerve root dysfunction, pain, or both) * Evidence of cervical nerve root compression by magnetic resonance imaging (MRI) or computed tomography (CT) myelography at the appropriate side and level(s) to explain the clinical symptoms and signs * Progressive motor weakness

2) **Presence of myelopathy**: refers to spinal cord injury or dysfunction caused by degenerative changes narrowing the spinal canal * Lower extremity weakness * Gait or coordination difficulties, * Bladder or bowel dysfunction. * Upper motor neuron signs in the arms and/or legs. * Lhermitte's sign * MRI scan showing cervical spinal canal narrowing, spinal cord compression, and signal abnormality TREATMENT OF ACUTE NECK PAIN – DURATION OF PAIN LESS THAN 6 WEEKS * Minimise pain, muscle irritability, and spasm * Reestablish normal cervical lordosis * Restore maximum function For all patients: parts of management include * Postural (mechanical) modification * Heat or cold application * Early mobilization through participation in a home exercise program * Adjunctive pharmacologic therapy **Postural modification** For those who carry heavy purses or backpacks (particularly ones that are worn over one shoulder), minimization of weight or discontinuation of use may help alleviate acute neck pain A preferred sleep position is to have the patient lie flat on their back with thighs elevated on pillows with a relatively small pillow under the head and neck, thereby flattening the long spinal muscles. For side sleepers, the use of a slightly larger pillow may help maintain proper cervical spine alignment

Heat or/and (alternate) cold application Heat or cold can be applied every two to three hours as needed. Limit exposure to 15 minutes at a time. [Exercise](https://www.youtube.com/watch?v=w51vrWJs2zA) **Pharmacologic therapy** The goal of medications is to provide symptomatic relief of pain symptoms while allowing the patient to participate in a home exercise program. **First-line pharmacotherapy** NSAIDs or acetaminophen for acute non-radicular neck pain.  One is not preferred over the other. Look at individual responses and risk factors to decide **Ibuprofen **400 to 600 mg orally three times daily as needed **Naproxen **250 to 500 mg orally twice daily as needed , better cardiovascular safety profile than Etoricoxib **Etrocoxib :** 60-90 mg once daily better GI profile but careful use in :

* **Heart and Circulation Conditions:** It is contraindicated for patients with ischemic heart disease, peripheral arterial disease, or cerebrovascular disease. Because of the risk of exacerbating or triggering heart attacks and strokes, its use is heavily restricted in patients with cardiovascular risk factors. * **Uncontrolled Hypertension:** It is unsafe for people with persistently high blood pressure (typically above 140/90 mmHg) that is not adequately managed by medication. Blood pressure should be monitored closely when starting the drug * **Renal and Hepatic Impairment:** It is unsafe for patients with severe kidney disease (creatinine clearance below 30 mL/min) or severe liver disease (e.g., cirrhosis with a Child-Pugh score ≥ 10). * **Allergies and Aspirin Sensitivity:** Individuals with a history of bronchial asthma, hives, or severe allergic reactions triggered by aspirin or other NSAIDs should avoid it. * **Pregnancy and Breastfeeding:** Etoricoxib should not be taken during pregnancy or by those attempting to conceive, as it can affect fertility and harm the fetus.

* patients who are unable to take NSAIDs * (eg, due to allergy or other intolerance, * chronic kidney disease, * hypertension, * peptic ulcer disease, * cardiovascular disease * who have previously tried with good pain relief –\> use acetaminophen 500 to 1000 mg orally TID as needed. Use a Lower total daily dose for older adult patients and those with any hepatic impairment. **Skeletal muscle relaxant if NSAID or acetaminophen therapy is inadequate **Chlorxoxazone is preferred because of its less sedating effect, Tizanidine is faster and more effective **Oral glucocorticoids** — A short course of high-dose oral glucocorticoid therapy may be used as initial treatment for patients with severe cervical radicular pain. The evidence supporting the effectiveness of oral glucocorticoids for cervical radiculopathy is limited Prednisone 60 to 80 mg/day for five days, followed by a taper off the medication over the ensuing 5 to 14 days, is a typical regimen. **Second line therapy:** Tramadol or duloxetine If NSAID or acetaminophen and muscle relaxants are insufficient  **Tramadol**

* For patients with pain symptoms almost controlled: add tramadol 25 to 50 mg orally three times daily as needed to their regimen. Caution patients regarding the risk of sedation, particularly when used with muscle relaxants. * For patients with significant pain despite an NSAID or acetaminophen plus a skeletal muscle relaxant, discontinue the muscle relaxant and prescribe tramadol. If additional pain control is needed, increase the dose if necessary to 50 to 100 mg orally three times daily as needed. When tramadol therapy is prescribed, the dose is reduced and tapered to off as quickly as symptoms allow. **Duloxetine ** Duloxetine, an SNRI, is started at 30 mg PO OD and is increased to 60 mg PO OD after one to two weeks if tolerated. May cause nausea, drowsiness, headache, and dizziness and may not be tolerated by all patients, particularly at the higher dose. If tramadol therapy is continued with duloxetine, a lower dose should be used (eg, 25 to 50 mg orally three times daily standing or as needed), and the patient should be monitored for the development of serotonin syndrome ( look for shivering, diarrhea, vomiting, fever, rigidity) OR

**Tricyclic antidepressants ** Prefer nortriptyline due to its tolerability, although bedtime dosing is still preferred to its sedating effects. Start at 10 mg PO HS and increase the dose by 10 mg per week to a maximum dose of 50 mg PO HS. Adverse effects include sedation, dry mouth, dizziness, constipation, and urinary retention; may be more pronounced in older adults, and use this medication with caution in these patients. **Third-line pharmacotherapy** Gabapentin: discontinue antidepressants and tramadol and begin treatment with gabapentin. **Gabapentin:** initiated at 300 mg PO OD at bedtime and titrated up to a goal dose of 600 mg PO TID daily as tolerated Titration starts at 100mg OD at night and uptitrate every 4- 7 days after watching for side effects. - **Prefer Pregabalin** to Gabapentin for better side effect profile: Start at 75mg HS upto but no more than 330mg/day - Continue therapy for atleast 4-6 weeks for effective management. Side effects of gabapentin may include dizziness and sedation, particularly in older patients; a slower titration or lower doses may be used if side effects occur TREATMENT OF SUBACUTE AND CHRONIC NECK PAIN

* Self-care advice for all patients as per previous advice. * Physical therapy/physiotherapy referral \- for all patients with neck pain for more than 6 weeks. * In-house physiotherapy referral: * Radiculopathy * All people who have had a history of similar pain in the past * Patients who at 15 days follow up with pharmacological therapy and general advice (including suggested exercises) report that pain has not subsided fully * In cases of chronic neck pain \> 12 weeks: Physiotherapy \+ Particular exercises that were found to be beneficial include mind-body exercise therapies, such as Tai Chi and yoga OFFLINE PHYSIOTHERAPY INTERVENTIONS: WHICH ARE THOSE **Cervical traction** is a reasonably safe alternative for patients with persistent or refractory pain who do not want epidural glucocorticoid injections or surgery Traction should not be used unless neuroimaging has been performed and should be discontinued if symptoms worsen with the application of distracting force. Traction is not recommended in the presence of spinal cord compression or large disc protrusion. **Persisting severe radicular pain \- non progressive**

Epidural Glucocorticoid Injections For patients with confirmed cervical radiculopathy who have severe or disabling pain despite a reasonable course (six to eight weeks) of conservative therapy, and who do not have a progressively worsening neurologic deficit, Uptodate suggests the use of epidural glucocorticoid injections rather than surgery, provided that the injections are performed by experienced centers and interventionalists under fluoroscopic guidance using test contrast injection to identify accidental vessel injection.

Use of a nonparticulate glucocorticoid such as [dexamethasone](https://www.uptodate.com/contents/dexamethasone-drug-information?search=surgical%20management%20of%20cervical%20nerve%20compression&topicRef=5263&source=see_link) may reduce the risk of ischemic complications **Surgery** Benefits: ​​Indications for surgery — Proposed indications for surgery in patients with cervical radiculopathy are unremitting radicular pain despite 6 to 12 weeks of conservative treatment, progressive motor weakness, or the presence of myelopathy As part of a presurgical evaluation, flexion and extension plain films are necessary to assess the stability of the cervical spine **Anterior cervical discectomy and fusion** : most commonly used The advantages of **ACDF** are that it requires little manipulation of the spinal cord or cervical roots and allows for removal of both lateral and midline disc herniation and osteophytes. Disadvantages include a small perioperative risk of damage to the carotid artery, trachea, esophagus, or recurrent laryngeal nerve. There is also a risk of pseudoarthrosis and further degenerative changes of adjacent segments **Posterior laminoforaminotomy** — A posterior surgical approach may be used when a single lateral disc herniation is present. A **PLF** is frequently performed, although many variations have been described. Midline pathology is not easily a

ccessible with PLF. As a result, this approach is not useful in patients with midline disc herniation or osteophytes. The main advantages of PLF are that it involves no alteration of the architecture of the cervical spine and no risk of damage to anterior neck structures. The main disadvantage is that there may be more postoperative pain with PLF than with ACDF, although this is controllable with medications **Artificial disc replacement** — Artificial cervical disc replacement surgery or **cervical disc arthroplasty (CDA)** is a developing technique for the treatment of cervical radiculopathy that has been used in situations when an ACDF would otherwise be appropriate. Mounting evidence suggests that CDA is equal or superior to ACDF in terms of clinical outcomes **Complications** — Complications of surgery for cervical radiculopathy and/or myelopathy are uncommon but include spinal cord injury (\<1 percent of cases), nerve root injury (2 to 3 percent), and instrumentation or device failure (≤4 percent). Additional complications seen with anterior surgical approaches in retrospective studies include transient dysphagia (10 percent), recurrent laryngeal nerve injury (2 to 3 percent), esophageal perforation (\<1 percent), vertebral artery injury (\<1 percent), and superficial wound infection (\<1 percent)

| Neck pain | | :---- | | | | DO | | Do regular neck exercises and stretches https://www.youtube.com/watch?v=5lbe9oZbpDs ; other activities such as walking, swimming, yoga ( Avoid handstands & headstands) and pilates may also be helpful | | Avoid sitting for long periods, take a break every 40-60 minutes to walk around for 2-3 minutes | | Use hot or cold compression packs for short-term relief – you can buy these from a pharmacy, or a hot water bottle or a bag of frozen vegetables wrapped in a cloth or towel will work just as well | | Avoid sitting for long periods, take a break every 40-60 minutes to walk around for 2-3 minutes | | check your posture when sitting, using computers or tablets and watching television – find out how to sit correctly and get tips for laptop users: https://www.ccohs.ca/oshanswers/ergonomics/sitting/sitting\_position.html | | Use a low, firm pillow (which supports the nape of neck not to high of low ) | | Ensure the mattress on your bed supports you properly | | DON’T | | | | Do not wear a neck collar unless it is suggested by your health care personnel– it's better to keep your neck moving | | Do not do anything that could be dangerous because you cannot move your neck – for example, driving or cycling | | | [Back to top](https://docs.google.com/document/d/1b6OiQKFaX45DRPQZyBTldhbT-CO2LbjBxN5d5DwuzZQ/edit#heading=h.k0kbah3jmaha)

To perform this test, have the patient flex their arms and elbows to 90 degrees with their elbows braced somewhat posteriorly. Have the patient open and close their fists at a moderate speed for 3 minutes. A positive test reproduces the patient’s usual symptoms within 3 minutes. Neurogenic TOS — Symptoms of neurogenic thoracic outlet syndrome (nTOS) include pain, dysesthesia, numbness, and weakness, which may not be localized in specific peripheral nerve distribution. Symptoms are reproducibly aggravated by any activity that requires elevation or sustained use of the arms or hands. These activities include reaching overhead (eg, brushing the hair, holding a telephone to the ear, getting objects from a cabinet), overhead lifting, and prolonged typing or working at a computer, or driving. Venous TOS — Symptoms of venous compression are the second most common clinical finding of TOS, accounting for about 3 percent of cases. Venous TOS (vTOS) typically occurs in individuals who perform vigorous repetitive exertion of the upper extremities, usually with the arms above shoulder level \[[1](https://www.uptodate.com/contents/overview-of-thoracic-outlet-syndromes/abstract/1)\]. Forearm fatigue within minutes of using the arm may be present in vTOS. Swelling can be accompanied by pain and cyanosis of the affected extremity;

Arterial TOS — Symptoms of arterial compression are the least common type of thoracic outlet syndrome, accounting for only about 1 percent of cases. Symptoms develop spontaneously unrelated to work or trauma. Arterial TOS (aTOS) is almost always associated with a cervical rib or anomalous rib. It occurs in young patients without typical atherosclerotic risk factors distinguishing it from peripheral artery disease Hand ischemia with symptoms of pain, pallor, paresthesia, and coldness is the most common presentation **Differential diagnosis of cervical nerve neuropathy** Carpal tunnel syndrome is the most common mononeuropathy, although the prevalence varies with the population studied. The disorder is much more common in female M:F::3:1 The hallmark of classic CTS is pain or paresthesia (numbness and tingling) in a distribution that includes the median nerve territory, with involvement of the first three digits and the lateral half of the fourth digit The symptoms of CTS may be noted initially at night and the pain or paresthesias may awaken patients from sleep. As they progress, symptoms may also be noted during waking hours, especially during activities that require sustained arm positions or repetitive movements.

Electrodiagnostic testing with nerve conduction studies and electromyography is performed to confirm the clinical diagnosis of CTS and to define the extent of median nerve injury in moderate to sever cases For patients with a clinical diagnosis of CTS with mild symptoms, we suggest initial nonsurgical therapy. We also treat other patients with moderate to severe symptoms and electrodiagnostic features consistent with mild or moderate CTS (without axon loss) with initial nonsurgical measures. Nonsurgical interventions include splinting, glucocorticoids, physical and occupational therapy techniques (eg, carpal bone mobilization and nerve-gliding exercises), yoga, and therapeutic ultrasound. Up to two-thirds of patients with mild to moderate CTS symptoms have successful outcomes with nonsurgical therapy

| Suspicion of cancer H/o cancer in the past 10 years Spinal involvement from metastatic disease should be considered in patients with a current or recent (within 5 years) history of cancer. Cancers that are particularly concerning for spinal involvement include multiple myeloma and cancer of the breast, lung, prostate, thyroid, or kidney. While the majority of these cancer recurrences occur within the first 5 years of diagnosis, some cancers can occur much later (up to 10 years or longer). Cancers at particular risk for late recurrence include breast cancer and prostate cancer. Moderate or high suspicion of cancer Factors to consider include the patient's age, smoking history, family history, physical examination findings, and any associated concerning symptoms (eg, recent weight loss). Vertebral metastases are often associated with localized pain and focal tenderness on examination. It is likely that patients having more than one such finding or feature are at higher risk than those with a single risk factor. Suspicion of spinal infection Signs, symptoms, and risk factors for spinal infection include: Current: Objective fever Immunosuppression Hemodialysis Current or recent (eg, within the past 3 to 6 months\*): Injection drug use Endocarditis Invasive epidural/spinal procedure Bacteremia with an organism associated with vertebral osteomyelitis, for example: Staphylococcus a

ureus Enteric gram-negative bacilli, particularly following urinary tract instrumentation Nonpyogenic streptococci, including viridans and milleri groups, Streptococcus bovis, and enterococci Pyogenic streptococci, including groups B and C/G Pseudomonas aeruginosa, coagulase-negative staphylococci, or Candida spp, especially in association with intravascular access, sepsis, or injection drug use Prior epidural/spinal infection S/o vertebral compression \* The time frame given for "recent" is a rough estimate only. Risk factors for osteoporosis that have been associated with an increased risk of fracture include: Advanced age (eg, \>70 years)\* Previous fracture\* Long-term glucocorticoid therapy Low body weight (less than 127 lb/58 kg) Parental history of hip fracture Cigarette smoking Excess alcohol intake Spondyloarthritis (ankylosing spondylitis) If a person has low back pain that started before the age of 45 years and has lasted for longer than 3 months, refer the person to a rheumatologist for a spondyloarthritis assessment if 4 or more of the following additional criteria are also present: low back pain that started before the age of 35 years (this further increases the likelihood that back pain is due to spondyloarthritis compared with low back pain that started between 35 and 44 years) waking during the second half of the night because of symptoms buttock pain improve

ment with movement improvement within 48 hours of taking non-steroidal anti-inflammatory drugs (NSAIDs) a first-degree relative with spondyloarthritis current or past arthritis current or past enthesitis current or past psoriasis. If exactly 3 of the additional criteria are present, perform an HLA‑B27 test. If the test is positive, refer the person to a rheumatologist for a spondyloarthritis assessment. This may be especially appropriate if the person has current or past inflammatory bowel disease (Crohn's disease or ulcerative colitis), psoriasis or uveitis (eye pain, eye redness, sensitivity to light or blurred visionsee recommendation 1.1.12 for guidance on referral for immediate \[same‑day\] ophthalmological assessment for people with acute anterior uveitis). Imaging for suspected axial spondyloarthritis Initial investigation using X‑ray Offer plain film X‑ray of the sacroiliac joints for people with suspected axial spondyloarthritis, unless the person is likely to have an immature skeleton. Diagnose radiographic axial spondyloarthritis (ankylosing spondylitis) if the plain film X‑ray shows sacroiliitis meeting the modified New York criteria (bilateral grade 2–4 or unilateral grade 3–4 sacroiliitis). If the plain film X‑ray does not show sacroiliitis meeting modified New York criteria), or an X‑ray is not appropriate because the person's skeleton is not fully mature, reque

Includes inspection, palpation, the range of motion, strength testing, provocative maneuvers, and neurologic (limb strength and sensation,) assessments. A straight leg raise (SLR) can be completed by raising the patient’s leg to 30 to 70 degrees. Ipsilateral leg pain at less than 60 degrees is a positive test for lumbar disk herniation One leg hyperextension test/stork test: Have the patient stand on one leg and (while being supported by the provider) have them hyper-extend their back. Repeat this maneuver on both sides. Pain with hyperextension is positive for a pars intercularis defect . Dermatomes and myotomes for radiculopathy assessment * CRP and ESR * CBC and blood cultures may assist in the diagnosis of inflammatory, infectious, or malignant etiologies as well. * LDH and uric acid may assist in diagnosing a condition with rapid marrow turnover such as leukemia **Imaging** **We recommend urgent neuroimaging by MRI Lumbosacral spine in the initial assessment for patients with any of the following conditions** * Acute radiculopathy with progressive neurologic deficits * Radiculopathy with urinary retention, saddle anesthesia, or bilateral neurologic symptoms or signs * Suspected neoplasm * Suspected epidural abscess

As an example, one study of 98 people without back pain found MRI evidence of disc herniation in 27 percent. Furthermore, lumbar spine abnormalities on MRI in asymptomatic patients do not appear to be predictive for the future development or duration of low back pain

OFFLINE PHYSIOTHERAPY INTERVENTIONS AND WHICH ARE THOSE Physiotherapy Patient Flow Algorithm & Treatments Flow Chart The following conditions may be candidates for surgical treatment: * Cauda equina syndrome advises surgery right away to ease the pain and prevent more problems. * Herniated or ruptured discs, in which one or more of the disks that cushion the bones of the spine are damaged * Spinal stenosis, a narrowing of the spinal column that puts pressure on the spinal cord and nerves * Spondylolisthesis, in which one or more bones in the spine slip out of place * Vertebral fractures caused by injury to the bones in the spine or by osteoporosis * Degenerative disc disease, or damage to spinal discs as a person gets older Surgical Indications for Disc Herniation : * In all levels of disc herniations the absolute surgical indications include deteriorating neurological deficits with myelopathy or cauda equina syndrome (new urinary retention, fecal or urinary incontinence, or saddle anesthesia) or if there are severe neurologic deficits (progressive motor weakness or significant motor deficits not localized to a single nerve root, such as foot drop).

* In thoracic disc herniation (TDH: in addition, giant calcified thoracic disc herniations or myelopathy signs on magnetic resonance imaging, even in the absence of neurological symptoms, may benefit from surgical treatment as a preventive measure. * In lumbar disc herniation (LDH), the indications for surgery include imaging confirmation of LDH, consistent with clinical findings, and failure to improve after six weeks of conservative care and not more than 3 months to try and avoid the chronic pathologic changes that occur within the nerve root * Recurrent Sciatica: Conservative treatment can also fail in that the patient experiences recurrences of the sciatica syndrome * Significant Neurological Deficit with Significant SLR Reduction : These patients are in extreme pain and often cannot wait for the benefits of conservative care. These patients on rare occasion can present with severe pain that has resolved as the neurological deficit has increased, they should also go to surgery when MRI demonstrates large HNP.( Herniation of Nucleus Pulposus) * A Disc rupture into a Stenotic Canal : A quick surgical intervention maybe warranted when the neurologic deficit is shown on MRI to be associated with a narrowed spinal canal such as acquired canal stenosis or subarticular stenosis or congenital stenosis.

* Recurrent Neurologic Deficit: If a patient with sciatica and a neurologic deficit has been successfully treated with conservative care, only to have neurologic deficits reappear with recurrent symptoms, operate. * **The use of transforaminal epidural steroid injection (TFESI)** as the initial invasive treatment was similarly effective to surgical microdiscectomy (SM) at reducing pain and disability for sciatica secondary to herniated lumbar disc, with symptom duration between 6 weeks and 12 months.

| DO | | :---- | | | | Stay as active as possible and try to continue your daily activities – this is 1 of the most important things you can do, as resting for long periods is likely to make the pain worse | | Do regular back exercises and stretches Basic: https://www.youtube.com/watch?v=VDf43fOTH1E Advanced: https://www.youtube.com/watch?v=EIyx7FlUNyo ; other activities such as walking, swimming, yoga and pilates may also be helpful | | Use hot or cold compression packs for short-term relief – you can buy these from a pharmacy, or a hot water bottle or a bag of frozen vegetables wrapped in a cloth or towel will work just as well | | | | Avoid sitting for long periods, take a break every 40-60 minutes to walk around for 2-3 minutes | | Take care when lifting things | | Keep a wide base of support. ... | | Squat down, bending at the hips and knees only. ... | | Keep good posture. ... | | Slowly lift by straightening your hips and knees (not your back). ... | | Hold the load as close to your body as possible, at the level of your belly button. | | | | check your posture when sitting, using computers or tablets and watching television – find out how to sit correctly and get tips for laptop users: https://www.youtube.com/watch?v=K88q\_oEwRS8 | | Ensure the mattress on your bed supports you properly and place a pillow below the knees when sleeping on your back. | | Lose weight through a combination of a healthy diet and regular exercise if you're overweight – being overweight can increase your risk of developing back pain | | | | DON’T | | do not stay in bed or sit for long periods of time | | | | |

**Anemia evaluation in outpatients (nonpregnant adults)** ACD/AI: anemia of chronic disease/anemia of inflammation; TSAT: transferrin saturation; MDS: myelodysplastic syndrome This algorithm addresses anemia in healthy outpatients, which is often an incidental finding or may be identified when a CBC is performed to evaluate mild symptoms such as fatigue. It is not appropriate for individuals who are acutely ill with fever, bleeding, neurologic symptoms, or any severe cytopenia (hemoglobin \<7 to 8 g/dL; platelet count \<50,000/microL, absolute neutrophil count \[ANC\] \<1000/microL).

| IDA | | | | :---- | :---- | :---- | | Cut off and prevalence | Severity | Classification | | Hb\<13 in men of age \>15 years, \<12 in nonpregnant women of age \>15 years, \<11 in pregnant women Children: See latest WHO chart below Prevalence in India The prevalence of anaemia among six groups as per the National Family Health Survey 5 (2019-21), is 25.0 percent in men (15-49 years) and 57.0 percent in women (15-49 years). 31.1 percent in adolescent boys (15-19 yrs), 59.1 percent in adolescent girls,52.2 percent in pregnant women (15-49 years) and 67.1percent in children (6-59 months). [https://pib.gov.in/PressReleasePage.aspx?PRID=1795421](https://pib.gov.in/PressReleasePage.aspx?PRID=1795421) | See latest WHO chart below | **Work up: Even Basic HCU/Complete Blood Profile** What we get usually Mean cell haemoglobin (MCH; a marker of hypochromia) mean cell volume (MCV; a marker of microcytosis or abnormally small red blood cells \[RBCs\]) ESR LFT KFT Vit B12 Vit D 25 OH **Classify as** Anaemia \+ other cell lines deranged ? pancytopenia **If there is Only anaemia, classify as one of** MCHC type microcytic hypochromic NCNC type normocytic normochromic Macrocytic Mixed **Then work up** If MCHC or NCNC \- **check for IDA** order iron study \+ferritin , peripheral smear/HPLC is Mentzer Index is \<13 or **haemolysis** (raised indirect bilirubin), reticulocyte count \- raised (further work up: LDH increased, Haptoglobulindecreased , Coomb’s test \= negative in inherited, positive in acquired) H/s/o acquired causes : h/o recent transfusion, drug intake, sickness **RED FLAG:** ALWAY ASK ABOUT BLOOD LOSS \- menses, blood in stool/melena, change in bowel habits, blood in urine: **Stool for occult blood, especially in men or postmenopausal women Urine R/M for blood/RBC USG abdomen and pelvis \- in women with h/o irregular menses** **IF Macrocytic** order/check Vitamin B12 levels TSH Alcohol intake Ofcourse LFT To r/o pernicious anaemia \- parietal cell AB (in which cases?) |

[https://www.guidelinecentral.com/guideline/3534081/\#section-3534099](https://www.guidelinecentral.com/guideline/3534081/#section-3534099) #### HB cut off for severity of anaemia gm/L Serum ferritin level, a measure of iron stores in the liver, is the most specific marker of iron deficiency in the absence of inflammation—a level of less than 30 mcg/l is indicative of low body iron stores, whereas less than 15 mcg/l is indicative of absent iron stores However, ferritin is an acute-phase protein (often raised in the presence of inflammation), so it can be high as a result of inflammation even when a patient is iron deficient. Therefore, Iron deficiency can be masked by inflammation : ferritin will be high, but other blood tests (for example, transferrin saturation) can be helpful if false-normal ferritin is suspected, when ESR/CRP are high

* 100 mg elemental iron/day is the desired dose for elemental Iron * It requires 2-3 capsules/tablets a day typically * Common brands: * **DEXORANGE (Ferric ammonium citrate)** HAS 32.5 mg/capsule/15 ml syrup, ferric ammonium citrate , poor bioavailability with not great tolerance, but risk of Iron toxicity is low * **FEFOL Z (carbonyl/elemental Iron)** HAS 50 mg, better than Dexorange in tolerance as well * **Orofer XT (Ferrous ascorbate+Folic acid, no Zinc and B12)** has 100 mg /table, best bioavailability, because of inbuilt Vitamin C, but best on empty stomach, tolerance is good, Hb correction is fast * **Feroze XT has 60 mg** (Elemental Iron,Zinc,Folic Acid,Vitamin B12, no vitamin C), best GI tolerability and can be taken with or without food, but rate of correction slower * **Vitamin C supplements/ rich foods** should be taken along with the Iron tablets/capsules to increase intestinal absorption * **Do not take iron within two hours of** coffee, tea, dairy (calcium), high-fiber foods, or antacids, as they can inhibit absorption * Patients should be monitored in the first 4 weeks for an Hb response to oral iron, and treatment should be continued for a period of around 3 months after normalisation of the Hb level, to ensure adequate repletion of the marrow iron stores * A good response to iron therapy (Hb rise 1 gm/Dlitre or greater within a 2-week timeframe) in patients with anaemia is highly suggestive of absolute iron deficiency, even if the results of iron studies are equivocal * **The target for therapy is restoration of Hb and Ferritin both, Hb\> 13/14 g/dL and Ferritin \> 30** * **Strategies to Improve Tolerance** * Alternate-Day Dosing * Take With a small amount of food * Avoid Certain Foods

* **Parenteral/intravenous iron** should be considered when oral iron is contraindicated, ineffective, or not tolerated. This consideration should be at an early stage if oral IRT is judged unlikely to be effective, and/or the correction of IDA is particularly urgent * Iron deficit and dose calculator for intravenous Iron: [Ganzoni Equation for Iron Deficiency Anemia Calculator](https://www.mdcalc.com/calc/10139/ganzoni-equation-iron-deficiency-anemia) * [**Ferric Carboxymaltose (50mg/ml)**](https://www.1mg.com/generics/ferric-carboxymaltose-212463) **: PREFERRED:** Ferinject 50mg/ml Solution for Injection 20 ml contains 1000 mg, allowing for one time hospital visit * Only IV, typically given slow I/V mixed with Normal Saline over 15-60 minutes * Should be given in set ups equipped with anaphylaxis management: reported as 8/10000 anaphylaxis to 108/10000 for any hypersensitivity reactions * **Iron Sucrose (20 mg/ml):** Iron Sucrose is the most commonly used formulation in India, particularly for patients with chronic kidney disease (CKD) or anemia in pregnancy. It typically requires a slower infusion or a series of smaller doses * Hemodialysis-Dependent CKD: 100 mg administered over 2-5 minutes per dialysis session, up to 300 mg per week. * Non-Dialysis-Dependent CKD: 200 mg given as slow IV injections over 2-5 minutes on 5 different days within a 14-day period. * Other Indications (Off-Label): Total cumulative doses up to 1,000 mg may be divided and administered over several weeks.

* **hemoglobin (Hb) level less than 7 g/dL** is widely accepted as a standard threshold for packed red blood cell (PRBC) transfusion in hemodynamically stable adults * **Age & Comorbidities:** Patients with active cardiovascular disease, acute coronary syndrome, or severe pulmonary disease often require a higher threshold (typically \<8 to 9 g/dL) * **Symptoms:** Clinical signs of tissue hypoxia (e.g., severe fatigue, shortness of breath, or chest pain) are heavily weighed alongside the lab value. * **Chronicity:** Patients with chronic, well-compensated anemia can often tolerate much lower Hb levels without acute intervention * After the restoration of Hb and iron stores with IRT, it is recommended that the blood count should be monitored periodically (perhaps every 6 months initially) to detect recurrent IDA. * Endoscopy UGI or Colonoscopy or both * In those with negative bidirectional endoscopy of acceptable quality and either an inadequate response to IRT or recurrent IDA, further investigation of the small bowel and renal tract is recommended to exclude other causes * After negative capsule endoscopy of acceptable quality, further GI investigations need to be considered only if there is ongoing IDA after IRT * Long-term IRT may be an appropriate strategy when the cause of recurrent IDA is unknown or irreversible.

Evaluation of unexplained hemolytic anemia TMA: thrombotic microangiopathy (eg, thrombotic thrombocytopenic purpura \[TTP\], hemolytic uremic syndrome \[HUS\], drug-induced TMA); AIHA: autoimmune hemolytic anemia; DAT: direct antiglobulin (Coombs) test; G6PD: glucose-6-phosphate dehydrogenase; PK: pyruvate kinase; PNH: paroxysmal nocturnal hemoglobinuria; PCH: paroxysmal cold hemoglobinuria; DIC: disseminated intravascular coagulation; LDH: lactate dehydrogenase. \* Evidence of hemolysis includes increased reticulocyte count that is not due to active bleeding, recent correction of iron deficiency or nutritional anemia, or erythropoietin administration; spherocytosis; low haptoglobin; high LDH and indirect (unconjugated) bilirubin. ¶ Inherited intracorpuscular defects include hemoglobinopathies such as thalassemia or sickle cell disease; enzymopathies such as G6PD or PK deficiency; and membrane defects such as hereditary spherocytosis, elliptocytosis, or stomatocytosis. **Conceptual framework for inherited hemolytic anaemia** Hemoglobinopathies and membrane disorders tend to have characteristic abnormalities of RBC morphology on the peripheral blood smear.

Membrane disorders may have nonspecific findings or bite cells on the blood smear. Refer to UpToDate for other distinguishing features among these conditions and the approach to diagnostic testing. \* Hemoglobinopathies can often coexist (eg, sickle-beta thalassemia; Hb E-beta thalassemia; Hb SC disease). Not all forms of thalassemia cause hemolysis; hemolysis is seen with hemoglobin H disease and transfusion-dependent beta thalassemia, but not with milder forms of thalassemia such as one or two alpha globin gene deletions or heterozygous beta thalassemia.

**Acquired, non-immune haemolytic anaemia** •Membrane defects (liver disease, acquired acanthocytosis) •Infections (malaria, babesiosis, clostridial sepsis, Bartonellosis, trypanosomiasis, visceral leishmaniasis) •Drug-induced (oxidant stress) •Severe burns •Thrombotic microangiopathies (thrombotic thrombocytopenic purpura \[TTP\], hemolytic uremic syndrome \[HUS\], drug-induced TMA) •Mechanical (intravascular devices, artificial heart valve, giant hemangioma, footstrike hemolysis) •Hypersplenism (may have a component of phagocytosis but is not antibody mediated) •Vasculitis •Severe hypertension •Heavy metals (Wilson disease, copper toxicity, arsine toxicity) •Envenomation (snake, brown recluse spider, hobo spider) •Hypophosphatemia Acquired, immune-mediated •Autoimmune (warm autoimmune hemolytic anemia \[AIHA\], cold agglutinin disease, paroxysmal cold hemoglobinuria) •Hemolytic transfusion reactions •Drug-induced **Management of haemolytic anaemia : GPs refer to Internal Medicine Specialist**

**Incidental finding of mild anemia, macrocytosis \[MCV\] \>100 fL, but if a patient has concomitant microcytosis due to iron deficiency or thalassemia, the macrocytosis may be masked** **An MCV value \>115 fL is more specific to vitamin B12 or folate deficiency than other conditions in the differential diagnosis such as hypothyroidism or myelodysplastic syndrome** **Confirm true macrocytosis and screen for megaloblastosis** * **CBC with indices and reticulocyte count** (MCV \>100 fL defines macrocytosis; correct retic for anemia) * **Peripheral Smea**r can show on eof the two pictures * **Megaloblastic (defective DNA synthesis):** macro‑ovalocytes and hypersegmented neutrophils strongly suggest B12/folate deficiency * **Vitamin B12 deficiency**: pernicious anemia, gastrectomy/IF lack, ileal disease/resection, malabsorption, dietary veganism; may present with neurologic and psychiatric symptoms * **Folate deficiency**: poor intake, pregnancy, sprue, alcohol use disorder, **increased turnover (hemolysis, sickle cell disease)**, drugs affecting folate

**Pernicious anemia** is an autoimmune disorder causing destruction of gastric parietal cells and/or intrinsic factor (IF) antibodies, leading to failure of IF-mediated cobalamin transport to the terminal ileum and B12 malabsorption. 1 It is a major cause of vitamin B12 deficiency and megaloblastic anemia and has strong associations with other autoimmune diseases and atrophic gastritis.

* Onset is typically insidious and often presents via non-hematologic complaints. * **General**: fatigue, weakness, weight loss, low-grade fever. * **Yellowed skin** (caused by combined anemia and jaundice), * **Cardiac**: high-output state, heart failure or coronary insufficiency in severe anemia. * **GI/oral**: atrophic glossitis with smooth, beefy-red painful tongue, anorexia, constipation or diarrhea, dyspepsia/pyrosis. * **Neurologic**: paresthesias, weakness, gait ataxia, sensory loss (posterior column), cognitive decline, psychiatric features (“megaloblastic madness”), subacute combined degeneration; may occur without anemia, especially with folate supplementation. * **GU**: urinary retention, UTIs from cord involvement. * **Thrombotic**: venous thrombosis via hyperhomocysteinemia. * **Causes of folate deficiency** * Increased requirements due to pregnancy, hemolytic anemia * Decreased intake, especially in individuals with excessive alcohol use and corresponding reductions in dietary intake of folate-rich foods such as fresh vegetables and fortified grains * Decreased absorption in the setting of gastric bypass surgery. * Increased requirements, such as exfoliative dermatitis * Medications and drugs that interfere with metabolism * Methotrexate, * Sulfasalazine * Rare genetic disorders

* Lhermitte sign, a shock-like sensation that radiates to the feet during neck flexion * Ataxia or positive Romberg test * Abnormal deep tendon reflexes * Extrapyramidal signs (eg, dystonia, dysarthria, rigidity) * **Non‑megaloblastic:** round macrocytes (liver/marrow infiltrative disease); reticulocytosis with polychromatophilic macrocytes in hemolysis * Hemolytic anemia/reticulocytosis * Hypoproliferative marrow * Alcohol use disorder (direct marrow toxicity), * liver disease, hypothyroidism, * COPD * Aplastic and myelodysplastic anemias, * Marrow infiltrative disorders, * Drug‑induced (e.g., **methotrexate, AZT, hydroxyurea, imatinib, valproate, phenytoin, metformin, CDK4/6 inhibitors**) * Genetic syndromes **Reticulocyte/hemolysis assessment** Reticulocyte count: \<1% suggests hypoproliferative/marrow failure; \>4% suggests hemolysis or blood loss **Hemolysis labs** Elevated LDH and unconjugated bilirubin, low haptoglobin; Coombs test if retic ↑ to evaluate immune hemolysis **Vitamin assays and metabolites** **Low serum B12 and/or RBC folate** in respective deficiencies; both may show hypersegmented neutrophils and macro‑ovalocytes * Confirmed deficiency: total B12 \<180 ng/L or active B12 \<25 pmol/L. * Indeterminate: 180–350 ng/L or 25–70 pmol/L (possible deficiency).4

**Second-line tests for vitamin B12 deficiency: MMA (± homocysteine**) If symptoms/signs fit B12 deficiency but B12 is **indeterminate**, measure **serum MMA** (± homocysteine).3564 \- ↑ MMA (+/− ↑ homocysteine) → functionally confirm B12 deficiency and treat as such. **Intrinsic factor antibodies (IF‑Ab**) **to test for pernicious anemia in megaloblastic picture**; specific, present in \~50–60% of cases **Parietal cell antibodies (PCA**) are more sensitive but not specific; use if autoimmune gastritis suspected and IF‑Ab negative IF‑Ab/PCA negative but strong suspicion of autoimmune gastritis/PA (macrocytosis, low B12/MMA+, chronic gastritis history): measure serum gastrin to assess for achlorhydria and support autoimmune gastritis; If autoimmune gastritis is still suspected despite negative IF‑Ab/PCA and nondiagnostic gastrin, proceed to endoscopic/biopsy evaluation per guideline pathways. **Vitamin B12 deficiency macrocytic anaemia** **1\. Neurologic symptoms/signs present** (e.g. SACD, peripheral neuropathy, cognitive/psychiatric changes attributable to B12) \- **Route**: **IM (or SC) cobalamin is mandatory; avoid oral-only.**123 \- **Regimen**: 1000 µg IM daily × 1–2 weeks → weekly until Hb/Hct normal → monthly for life or until a reversible cause is clearly corrected.1 Choose a route based on etiology/absorption.

**A. Irreversible or strong malabsorption (IM first‑line, usually lifelong**) \- Examples: confirmed/suspected [Pernicious Anemia](https://emedicine.medscape.com/article/204930-overview) / autoimmune gastritis, total gastrectomy, complete terminal ileal resection. \- **Route**: IM for life.52 \- **Regimen**: As above (IM loading then monthly).12 \- **Oral role**: Possible for maintenance in selected adherent patients after parenteral loading (≥250–1000 µg/d), with biochemical monitoring, but guidelines still favor IM when malabsorption is definite.215 **B. Malabsorption likely but potentially reversible / partial** (e.g. coeliac disease, partial gastrectomy, some bariatric procedures, drug‑induced from metformin/PPI) **Route**: Either IM or oral ≥1 mg/day; many guidelines “consider” IM if malabsorption is the main concern or adherence uncertain.51 \- **Strategy**: Often reasonable to **start with IM**, then switch to oral once cause is treated and response stable. **C. Adequate absorption / pure dietary deficiency (vegans, low intake), older adults without clear malabsorption** \- **Route**: **Oral cobalamin** (cyanocobalamin) at ≥1 mg/day is appropriate first‑line.265 \- **Escalate to IM** if: poor biochemical/clinical response, adherence doubtful, or new neurologic features develop.5 **D. Unknown cause, no neurologic signs**

\- Start with **oral ≥1 mg/day** or IM based on patient preference/comorbidities; review at 3 months.5 \- Switch to IM if symptoms persist, MMA/homocysteine remain elevated, or an irreversible malabsorptive cause is later identified

Presenting complaints The term “fatigue” can be used to describe: * Difficulty or inability to initiate activity (subjective sense of weakness) * Reduced capacity to maintain activity (easy fatigability) * Difficulty with concentration, memory, and emotional stability (mental fatigue) * Daytime sleepiness or an uncontrollable need to sleep * Less than one month (Acute) * One to six months (Sub acute) * More than six months (Chronic) The cause of chronic fatigue can be identified in approximately two-thirds of patients **What to cover in 1st consult- History**

* Duration- acute vs subacute/chronic * In Severe acute cases: * Recovering from any recent infective episode * A history should be obtained regarding dark colored urine or hematuria as a clue regarding rhabdomyolysis. * Any lifestyle change/stressor events/Work out related exhaustion and muscle soreness (FAS scale can be added Katch test(anaerobic fatigue) * Blood lactate test * In subacute/chronic cases: LOOK FOR LOCALISING SYMPTOMS * Muscle weakness /neuromuscular /rheumatological symptoms * Cramps at rest (usually not a neuromuscular disorder) * Benign nocturnal leg cramps. * Diurnal cramps related to exercise. * Cramps occurring with exertion, relieved by rest (may be associated with myoglobinuria) * Muscular dystrophy, Duchenne, Becker, limb girdle muscular dystrophy. * Myopathy: Rippling Muscle Syndromes * Metabolic disorders * Toxic myoglobinuria * Inflammatory myositis * Acute extracellular volume depletion * perspiration * diarrhea, vomiting * diuretic therapy * hemodialysis * Low grade fever * Cough * Weight loss, appetite loss, malena (black tarry stools) and or change in bowel habits * Sleep disturbance, snoring, daytime sleepiness * Substance abuse * Pedal edema, orthopnea/PND to assess for CVD risk * Jaundice, k/c/o hepa

titis, family h/o liver disease * Sexual history * Known anaemia, thyroid disorder and/or Vitamin B12/ D deficiency, kidney problems in the past, HT * Medicine intake: beta blockers, benzodiazepines, antidepressants, muscle relaxants, first generation antihistamines, opioids, GABA analogues * Stress/somatisation- stress can be coexisting or an independent condition with fatigue. Diagnosis of somatization to be considered as an exclusion if all medical parameters are WNL. Coexisting anxiety or stress can be treated independently too * **Assessment of neuromuscular weakness in tele consult** * **Wekness:** * Anatomic distribution / pattern of weakness and focal wasting or hypertrophy of muscle groups (arms versus legs, proximal versus distal, symmetric versus asymmetric).: Myopathies have weakness that is usually proximal greater than distal with rare exceptions * Course of weakness * Acute onset (days to weeks) * chronic (months to years) * episodic * Is the weakness getting worse, staying the same, or getting better? * Ascertain the rate of progression (days, weeks, months, or years). * Muscle cramps or stiffness: if they come only after physical exhaustion \- red flag, otherwise not neurological * A history of twitching of muscles may reflect fasciculations *

Lack of sensory loss * Gait characteristics: Toe walking, excessive lordosis, trendelenburg or gluteus maximus lurch, etc. * Functional difficulties * ambulatory distances * frequency of falls * transitions from the floor to standing * problems climbing stairs * problems dressing * problems reaching overhead * difficulty lifting * running ability, problems in physical education, and recreational or athletic performance.

**What to cover in 1st consult- Physical examination** * General appearance – Level of alertness, psychomotor agitation or retardation, grooming-CAN BE DONE ONLINE * Evidence of thyroid disease – Bradycardia, tachycardia, goiter, skin changes, ophthalmopathy \- TFT \+ ONLINE OBSERVATIONS SHOULD SUFFICE * Hepatosplenomegaly \- USG ABDOMEN * Cardiopulmonary examination – ECHO, ECG * Lymphadenopathy \- LDH as a substitute * Neuromuscular examination – Muscle bulk, tone, and strength; deep tendon reflexes; sensory and cranial nerve evaluation; cognitive function **What to cover in 1st consult \- HCU/tests/previous treatment** * Last HCU done- when and reports * CBC * LFT * KFT * Serum electrolytes * TFT * HbA1c * Urine R/M * Vitamin D 25 OH * Vitamin B12 * ESR * USG abdomen * Check the duration of treatment and compliance for known anaemia, vitamin deficiencies etc.

* If no localising symptoms are there on history, reports of HCU was done within last 6 months and the patient is known ℅ vitamin B12 and/or D deficiency, treat for 3 weeks at least before working up again * If tests were done more than 6 months ago, repeat as per requirement : CBC, ESR, Vitamins or Even Complete Blood Profile as required * LDH \- we will consider LDH in severe cases where everything is normal including ESR. if there are obvious lab findings pointing to some cause, we shall not use it. * USG abdomen for hepatosplenomegaly * If LFT is deranged \- work up as per our clinical protocol for viral markers- HBsAg+Anti HCV * **HIV Rapid/Even STD panel if high risk sexualt history/or HIV ELISA anti HIV1 and HIV 2+p24 antigen if very high risk sexual encounter in past one month and VDRL** * ECHO and ECG if CVS symptoms present * If KFT is deranged or urine R/M shows proteins, cast, hematuria, refer to IHS

Overt vitamin D deficiency: is characterised by * hypocalcemia and/or * hypophosphatemia and * rickets and osteomalacia in children and osteomalacia in adults With prolonged, severe vitamin D deficiency, there is reduced intestinal absorption of calcium and phosphorus and hypocalcemia occurs, causing secondary hyperparathyroidism, which leads to phosphaturia, demineralization of bones, and when prolonged, osteomalacia in adults and rickets and osteomalacia in children. Associated symptoms may then include bone pain and tenderness, muscle weakness, fracture, and difficulty walking Subclinical vitamin D deficiency: is associated with * osteoporosis and possibly fractures * possibly even extraskeletal health, including the immune and cardiovascular systems The majority of groups currently use the following values to categorise the vitamin D status in adults:

* Vitamin D deficiency is defined as a 25(OH)D level less than 12 ng/mL (30 nmol/L) * Vitamin D insufficiency is defined as a 25(OH)D concentration of 12 to 20 ng/mL (30 to 50 nmol/L) * Vitamin D sufficiency is defined as a 25(OH)D concentration greater than 20 ng/mL (50 nmol/L) * What is the optimal level for metabolic/cardiovascular health ??? But there are no prospective studies to define optimal 25(OH)D levels for extraskeletal health Uptodate does not suggest vitamin D supplementation above and beyond what is required for osteoporosis management * A "risk" of vitamin D toxicity is defined as a 25(OH)D level \>100 ng/mL (\>250 nmol/L) in adults ingesting substantial amounts of calcium . More studies are needed to define the upper level of serum 25(OH)D that is safe, not only with respect to the risk of kidney stones but also for falls and chronic diseases. TOXICITY — The first measurable consequences of vitamin D toxicity are hypercalciuria and hypercalcemia, which have been observed only at 25(OH)D levels above 88 ng/mL (220 nmol/L) . In addition, chronically high levels of 25(OH)D (exceeding 40 and 50 ng/mL) have been found in some association studies to be linked to a modest increase in the risk of some cancers (eg, pancreatic), mortality, and falls

SUPPLEMENTATION The majority of healthy adults with serum 25\[OH\]D of 12 to 20 ng/mL do not require any additional evaluation. Patients with serum 25(OH)D levels \<12 ng/mL are at risk for developing osteomalacia. In such patients, measure * Serum calcium, phosphorus, parathyroid hormone (PTH) : Patients with low vitamin D and secondary elevations in PTH are at increased risk for having accelerated bone loss, as evidenced by low bone mass on bone densitometry (dual-energy x-ray absorptiometry \[DXA\]) and fractures * LFT: alkaline phosphatase * KFT: electrolytes, blood urea nitrogen (BUN), creatinine * Celiac disease tests: tissue transglutaminase antibodies (to assess for celiac disease). * Radiographs are necessary in certain settings, such as the presence of bone pain Adult Vitamin D deficiency treatment For patients with serum 25(OH)D \<12 ng/mL:

* Treat with 60,000 IU [vitamin D2](https://www.uptodate.com/contents/vitamin-d2-ergocalciferol-drug-information?search=adult+vitamin+d+supplement&topicRef=2022&source=see_link) or D3 orally once per week for six to eight weeks, * Then 800 IU of vitamin D2 or D3 daily thereafter. * However, the efficacy of this practice compared with daily, weekly, or monthly dosing has not been rigorously established. Except * [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6024703/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6024703/) \- no side effects of monthly dosing up to one year * Supplement with 800 to 1000 IU daily. The American Geriatrics Society (AGS) and the National Osteoporosis Foundation (NOF) recommend a slightly higher dose of vitamin D supplementation (at least 1000 IU) to older adults (≥65 years) to reduce the risk of fractures and falls * A repeat serum 25(OH)D level should be obtained after approximately three months of therapy to assure obtaining the goal serum 25(OH)D level. If goal level is not achieved, higher doses may be necessary. For levels of 20 to 30 ng/mL: 600 to 800 units of [vitamin D2](https://www.uptodate.com/contents/vitamin-d2-ergocalciferol-drug-information?search=adult+vitamin+d+supplement&topicRef=2022&source=see_link) or D3 daily may be sufficient to maintain levels in the target range OR MONTHLY DOSAGE OF 60 K

Uprise D3 syrup: cholecalciferol 400 IU/ml DV 400 syrup DEFINITION-(IAP 2017\) 25(OH)D \>20ng/ml \- SUFFICIENT 12-20 ng/ml-insufficient \<12ng/ml- Deficient Vitamin D deficiency, prevention (eg, Rickets prevention) (AAP \[Golden 2014\]; Abrams 2020; Munns 2016): Breastfed infants (fully or partially): Oral: 400 units daily beginning in the first few days of life; continue supplementation unless the infant is transitioned to full formula intake. Children and Adolescents without adequate intake: Oral: 600 units daily. Note: Children with an increased risk of vitamin D deficiency (chronic fat malabsorption, maintained on chronic antiseizure medications) may require higher doses Vitamin D deficiency (severe, symptomatic), treatment: Note: Treatment should also include calcium supplementation Infants, children, adolescents: Oral: 2,000 units daily for 6 weeks to achieve a serum 25(OH)D level \>20 ng/mL; followed by a maintenance dose of 400 to 1,000 units daily. Monitoring Patients being treated specifically for serum 25(OH)D \<20 ng/mL (50 nmol/L) require a repeat 25(OH)D measurement approximately three to four months after initiating therapy. The dose of vitamin D may require further adjustment and additional measurements of 25(OH)D.

* High doses of vitamin D of 10,000 to 50,000 international units daily may be necessary to treat patients with gastrectomy or malabsorption. * Patients who remain deficient or insufficient on such doses will need to be treated with hydroxylated vitamin D metabolites because they are more readily absorbed, or with sun or sunlamp exposure. * All patients should maintain a daily total calcium intake (diet plus supplement) of 1000 mg (for ages 19 to 70 years) to 1200 mg (for women ages 51 through 70 years and all adults 71 years and older). * The Upper Level (UL) of intake for calcium in most adults is 2000 to 2500 mg daily. * However, a higher calcium dose (up to 4 g/day) may be necessary in patients with malabsorption. | Food | Calcium in milligrams | | :---- | :---- | | Milk (skim, 2%, or whole; 8 oz \[240 mL\]) | 300 | | Yogurt (6 oz \[168 g\]) | 250 | | Orange juice (with calcium; 8 oz \[240 mL\]) | 300 | | Tofu with calcium (0.5 cup \[113 g\]) | 435 | | Cheese (1 oz \[28 g\]) | 195 to 335 (hard cheese \= higher calcium) | | Cottage cheese (0.5 cup \[113 g\]) | 130 | | Ice cream or frozen yogurt (0.5 cup \[113 g\]) | 100 | | Non-dairy milks (soy, oat, almond; 8 oz \[240 mL\]) | 300 to 450 | | Beans (0.5 cup cooked \[113 g\]) | 60 to 80 | | Dark, leafy green vegetables (0.5 cup cooked \[113 g\]) | 50 to 135 | | Almonds (24 whole) | 70 | | Orange (1 medium) | 60 |

**Pathology:** Low bone mass with microarchitectural deterioration → increased fragility; often asymptomatic until fracture.1 **WHO BMD-based definitions (postmenopausal women, men ≥50):** DXA (hip/spine) is reference standard; peripheral DXA mainly for low-risk rule-out.1 \- Normal: T ≥ \-1 \- Osteopenia: T between \-1 and \-2.5 \- Osteoporosis: T \< \-2.5 \- Severe osteoporosis: T \< \-2.5 plus fragility fracture.1 In premenopausal women, men \<50, and children, use **Z-scores**, with Z ≤ \-2.0 “below expected for age”; diagnosis must not be densitometry-based alone.2 **Fragility fracture:** Fracture from trauma ≤ fall from standing height; characteristic of osteoporosis. #### **When to do DXA screening for osteoporosis** Use the FRAX TOOL: [https://www.fraxplus.org/calculation-tool/\#risk-factors](https://www.fraxplus.org/calculation-tool/#risk-factors) Major guidelines (NOGG, BHOF, AACE, USPSTF) recommend FRAX for **initial fracture risk assessment** in postmenopausal women and men ≥50 with risk factors, to decide on DXA and pharmacologic therapy It covers age 40-90 years, for people \<40, it takes the age at 40 to calculate a score **Low Risk:** \<10% (Major) or \<1.5% (Hip). Lifestyle changes (diet, exercise, fall prevention) are usually recommended.

**Intermediate Risk: 10% \- 20% (Major) or 1.5% \- 3% (Hip). Clinicians often recommend a DXA scan for better clarity or recalculate the risk if BMD was previously unknown.** **High Risk:** \>20% (Major) or \>3% (Hip). Medical treatment to prevent bone loss is generally advised. A previous fracture denotes more accurately a previous fracture in adult life occurring spontaneously, or a fracture arising from trauma which, in a healthy individual, would not have resulted in a fracture. Enter yes or no (see also notes on risk factors). **A special situation pertains to a prior history of vertebral fracture.** A fracture detected as a radiographic observation alone (a morphometric vertebral fracture) counts as a previous fracture. **A prior clinical vertebral fracture or a hip fracture is an especially strong risk factor, and the probability of fracture may therefore be underestimated. A fracture within the past 2 years is a particularly strong risk factor for subsequent fracture, and fracture probability is also likely to be underestimated with multiple prior fractures**.

* These include * type I (insulin-dependent) diabetes, * osteogenesis imperfecta in adults, * untreated long-standing hyperthyroidism, * hypogonadism * premature menopause (\<45 years), * chronic malnutrition or malabsorption, * chronic renal failure (dialysis independent) and * chronic liver disease. * Cushing’s syndrome **Lifestyle:** Weight-bearing and strengthening exercise; smoking cessation; limit alcohol; fall-risk reduction; adequate Ca and Vit D. In postmenopausal osteoporosis, 1200 mg of calcium daily (total diet plus supplement) and 800 international units of vitamin D daily are advised. In premenopausal osteoporosis or in males with osteoporosis, 1000 mg of calcium (total of diet and supplement) and 600 international units of vitamin D daily are generally suggested. **Pharmacologic indications (postmenopausal women, men ≥50)** * Hip or vertebral fragility fracture * T ≤ \-2.5 at hip, spine, or 33% radius * Osteopenia (T \-1 to \-2.5) with FRAX 10‑yr hip ≥3% or major fragility ≥20%

* Antiresorptive therapy: Oral bisphosphonates (alendronate, risedronate) * For high risk patients: Denosumab or IV zoledronate if oral intolerance/contraindications * **Anabolic therapy (very high risk or multiple vertebral fractures):** teriparatide, abaloparatide (≤2 years), or romosozumab (12 months), followed by antiresorptive maintenance * **Glucocorticoid-induced osteoporosis:** start bone-protective therapy concomitantly in high-risk patients (e.g., ≥7.5 mg prednisolone ≥3 months, prior fragility fracture, age ≥70) * Abaloparatide approved in 2024 by NICE, is a synthetic peptide analog of parathyroid hormone-related protein (PTHrP). It works by stimulating new bone formation, thereby increasing bone density and reducing the risk of fracture.

Calcium – The most widely available calcium supplements are [calcium carbonate](https://www.uptodate.com/contents/calcium-carbonate-drug-information?search=adult+vitamin+d+supplement&topicRef=2023&source=see_link) and [calcium citrate](https://www.uptodate.com/contents/calcium-citrate-drug-information?search=adult+vitamin+d+supplement&topicRef=2023&source=see_link). In most individuals, calcium carbonate taken with meals is adequate for supplementation and is inexpensive. However, we recommend calcium citrate in patients taking proton pump inhibitors (PPIs) or H2 blockers or who have achlorhydria Vitamin D – We suggest [cholecalciferol](https://www.uptodate.com/contents/vitamin-d3-cholecalciferol-drug-information?search=adult+vitamin+d+supplement&topicRef=2023&source=see_link) (vitamin D3), when available, rather than [ergocalciferol](https://www.uptodate.com/contents/vitamin-d2-ergocalciferol-drug-information?search=adult+vitamin+d+supplement&topicRef=2023&source=see_link) (vitamin D2) for vitamin D supplementation **Calcium carbonate** **Shelcal has** 500 mg+250 IU (Carbonate) Shelcal HD has 500 mg+500 IU Shelcal HD 12 has 500 mg+500 IU \+ 15 mcg Vit B12 Shelcal M has 500 mg \+250 IU \+ minerals **Calcimax** has 500 mg+ 200 IU \+ minerals Calcimax forte \+ has 400 mg+ 500 IU \+ minerals **Calcium Citrate** **Supracal tablet:**Calcium citrate (1000mg) \+ Vitamin D3 (200IU) \+ Zinc Sulfate (4mg) \+ Magnesium Sulphate (100mg) **Supracal Pro:** Calcium citrate (1250mg) \+ Vitamin D3 (1000IU) \+ Zinc Sulfate (4mg) \+ Magnesium Sulphate (100mg)+ manganese+Boron

| Food | Amount per serving | | | :---- | :---- | :---- | | | In international units (IU) | In micrograms | | Cod liver oil, 1 tablespoon (15 mL) | 1360 | 34 | | Salmon (sockeye), cooked, 3 ounces (85 g) | 380 to 570\* | 9.5 to 14\* | | Mushrooms that have been exposed to ultraviolet light to increase vitamin D, 3 ounces (85 g) (not yet commonly available) | 889 | 22.3 | | Mackerel, cooked, 3 ounces (85 g) | 388 | 9.7 | | Tuna fish, canned in water, drained, 3 ounces (85 g) | 40 to 68 | 1 to 2 | | Milk, nonfat, reduced fat, and whole, vitamin D-fortified, 8 ounces (240 mL) | 100 | 2.5 | | Orange juice fortified with vitamin D, 8 ounces (240 mL) (check product labels, as amount of added vitamin D varies) | 100 | 2.5 | | Yogurt, fortified with vitamin D, 6 ounces (180 mL) (more heavily fortified yogurts provide more of the DV) | 80 | 2 | | Margarine, fortified, 1 tablespoon (15 g) | 60 | 1.5 | | Sardines, canned in oil, drained, 2 sardines | 46 | 1 | | Liver, beef, cooked, 3.5 ounces (100 g) | 46 | 1 | | Ready-to-eat cereal, fortified with vitamin D, 6 to 8 ounces (227 g) (more heavily fortified cereals might provide more of the DV) | 40 | 1 | | Egg, 1 whole (vitamin D is found in yolk) | 25 | 0.6 | | Cheese, Swiss, 1 ounce (29 g) | 6 | 0 |

* Decreased intake (eg, reduced intake of animal products, strict vegan diet, breastfeeding by a vitamin B12-deficient mother). * Decreased absorption (eg, **Pernicious anaemia,** gastrectomy, bariatric surgery, resection of the terminal ileum, Crohn disease, celiac disease, pancreatic insufficiency, bacterial overgrowth, fish tapeworm infection, gastric atrophy associated with aging) * Other autoimmune conditions, such as thyroid disease or vitiligo, in individuals with pernicious anemia. * Medications and drugs that interfere with absorption or stability * Metformin * H2 receptor antagonists * Proton pump inhibitors * Rare genetic disorders. **Symptoms:** Classic symptoms of severe B12 and/or folate deficiency are rarely seen , check out macrocytic anaemia * Macrocytic anaemia * Fatigue, irritability, cognitive decline * Neurological symptoms in the elderly: symmetric paresthesias or numbness and gait problems * glossitis (including pain, swelling, tenderness, and loss of papillae and/or hyperpigmentation of the tongue), and folate deficiency can cause oral ulcers * gastrointestinal symptoms related to the underlying condition that caused the deficiency, such as pain or diarrhea related to inflammatory bowel disease, celiac disease, or other malabsorptive states * Restless legs syndrome

* Incidental finding of mild anemia, macrocytosis \[MCV\] \>100 fL, but if a patient has concomitant microcytosis due to iron deficiency or thalassemia, the macrocytosis may be masked **An MCV value \>115 fL is more specific to vitamin B12 or folate deficiency than other conditions in the differential diagnosis such as hypothyroidism or myelodysplastic syndrome.** However, a normal MCV does not exclude vitamin B12 or folate deficiency * Pancytopenia (Mild leukopenia and/or thrombocytopenia), * Hypersegmented neutrophils Vitamin B12 normal ranges — The following reflects typical serum vitamin B12 levels and their interpretation Above 300 pg/mL – Normal; deficiency unlikely 200 to 300 pg/mL- Borderline deficiency is possible and additional testing is useful. Additional testing can be used to determine the clinical significance. Below 200 pg/mL – Low; consistent with deficiency. In most laboratories, serum vitamin B12 levels are measured using a competitive chemiluminescence assay that has an estimated sensitivity of approximately 95 percent in symptomatic patients (a specificity of approximately 80 percent or less) **Further testing:** Peripheral blood smear and ruling out secodary causes In case of macrocytic anaemia or frank neurological signs and symptoms \- covered in macrocytic anaemia, especially if peripheral smear shows megaloblastic picture

**TREATMENT** Urgency of correction — Most individuals with vitamin B12 or folate deficiency present asymptomatically with an incidental laboratory finding or with the slow development of symptoms. Repletion of the deficient vitamin can be instituted over a period of weeks in these instances. However, in certain cases it may be prudent to intervene more urgently: * Symptomatic anemia or neurologic or neuropsychiatric findings, due to the risk of adverse events and irreversibility of neurologic deficits * Pregnancy, as the developing fetus may be affected * Neonates and infants, whose development may be impacted

**Route of administration** A 2018 Cochrane review that included three small trials (153 participants in total) comparing oral versus intramuscular vitamin B12 in individuals with vitamin B12 deficiency suggested that both routes were effective in raising vitamin B12 levels A 2006 systematic review found data from two randomized trials (108 participants) that compared oral versus intramuscular vitamin B12 and found that **oral vitamin B12 at high doses was equivalent to or better than intramuscular vitamin B12 for raising serum vitamin B12 levels, correcting anemia**, **BUT in Symptomatic patients, pregnancy, neonates – Initial parenteral administration (vitamin B12 or folic acid) is suggested for those who have severe symptomatic anemia or any neurologic findings associated with deficiency.** **DOSE** **Parenteral** Adults – If there are symptoms of anemia and/or neurologic symptoms, 1000 mcg can be administered one to three times per week or daily, followed by once weekly for 5 weeks, check levels, and continue weekly until corrected, then then once per month (cyanocobalamin) or once every other month (hydroxocobalamin). Children –While doses of 1000 mcg parentally are appropriate in adolescents, some experts have suggested that in infants and young children, parenteral doses of 50 to 100 mcg are sufficient. Once the deficiency is corrected, maintenance dosing can be given once per month (cyanocobalamin) or once every other month (hydroxocobalamin) if the underlying cause of the deficiency persists **Oral** 1000-2000 mcg daily for 4-8 weeks Repeat testing: After 4 weeks, then 6 months check vitamin B12 levels and then manually Maintenance: 1000 mcg daily in nondietary/ GI causes, otherwise as per table

**Adverse effects/overdos**e — Vitamin B12 and folate are water-soluble vitamins that are excreted when stores are adequate. Rare cases of hypersensitivity or **acneiform eruptions** with vitamin B12 have been reported Reports of serious adverse effects from administration or intake of greater-than-recommended doses have not been observed **Causes of spuriously low vitamin B12** Certain conditions or medications may be associated with spuriously low serum vitamin B12 levels and thus might cause the appearance of vitamin B12 deficiency when the patient is not deficient. Examples include: ● Multiple myeloma ● HIV infection ● Pregnancy ● Oral contraceptives ● Diphenylhydantoin **Causes of spuriously high vitamin B12** — Certain conditions may be associated with spuriously increased vitamin B12 levels and thus might cause the appearance of normal vitamin B12 levels when the patient is deficient. Examples include : * Occult malignancy * Myeloproliferative neoplasm * Alcoholic liver disease * Kidney disease * Certain inborn errors of metabolism * Nitrous oxide exposure (which can also cause vitamin B12 deficiency, as evidenced by clinical symptoms and high methylmalonic acid \[MMA\] levels)

* This can be achieved by the use of norethisterone 5mg three times daily starting 3 days before the anticipated onset of menstruation. Menstruation will occur 2-3 days after stopping taking the norethisterone (NET). Brand: Primolut-N * Ideally 5 days prior to period and to continue till the day of postponement * Obese * Personal h/o VTE * Strong FH of VTE * Immobile/wheelchair bound * Carriers of thrombophilia * Any other condition predisposing to VTE * use Medroxyprogesterone acetate (Brand: Meprate)10mgs bd or tds **(SAFER)** instead of NET particularly in women who are overweight, smokers, aged over 35 or any other woman at risk of VTE.

| Frequent | Occasionally | Not reported | | :---- | :---- | :---- | | Dogs | Cats Monkey Cattle & buffaloes Mongoose Foxes, wolves & jackals Sheep & goat Bears Pigs Donkeys Horses Camels Spotted Deer \[14\] Squirrel\*\* | Bats\* Rodents\* Birds | | Note: All exposures in the wild are considered as Category III exposures. \* Bite by bats or rodents do not ordinarily necessitate rabies vaccination in India. However, bites by bats or rodents in unusual circumstances may be considered for vaccination in consultation with an expert in the field of rabies. \*\*One case reported from India. | | | | MODES OF TRANSMISSION | | | :---- | :---- | | Common | Rare | | Bites from infected animals Licks on broken skin and mucous membrane Scratches | Inhalation Organ transplantation (Cornea) Ingestion |

1. Wound management : * Local wound care.Wash the wound with soap and water immediately and thoroughly (minimum 15 minutes). Wound washing is essential even after the patient presents long after exposure. Directed at decreasing infection, reducing scar formation, restoring function. * Irrigate the wound with normal saline or povidone-iodine solution (Do not use surgical povidone-iodine scrub ) and then serial irrigation with saline. * Antibiotics to cover S.aureus and Streptococcus e.g.Cloxacillin, Cephalexin, and in Penicillin allergic patients \- Erythromycin or Trimethoprim \+ Sulfamethoxazole. IN WHICH CATEGORIES * Tetanus prophylaxis as per protocol: * For children \<7 yrs, DPT preferred to TT alone * \* If only 3 doses of toxoid have been given a fourth dose of TT may be given. * Yes, If \>10 years since the last dose * Yes if \>5 years since the last dose * Bite wounds should not be sutured immediately. If suturing is necessary, it should be done 24-48 hours later, applying minimum possible stitches, under cover of anti-rabies serum locally. * Dog bites to the hand or those causing extensive crush injuries are not sutured primarily. CAN THE ANIMAL BE ASSUMED TO BE RABIES FREE OR BE OBSERVED 1. Does the offending animal have rabies/could have rabies or not? 2. Can the offending animal be kept under observation for 10 days?

Post-exposure prophylaxis may be discontinued if the animal involved remains healthy for an observation period of 10 days after the exposure occurred; or if the animal is dead and proven to be negative for rabies by a reliable diagnostic laboratory using a prescribed test. If the animal inflicting the wound is suspected of being rabid and is not apprehended, post-exposure prophylaxis should be instituted immediately. In areas where canine or wildlife rabies is enzootic, adequate laboratory surveillance is in place, and data from laboratory and field experience indicate that there is no infection in the species involved, local health authorities may not recommend anti-rabies prophylaxis. IN SOME SITUATIONS such as exposure of infants or mentally disabled persons and other circumstances where a reliable history cannot be obtained, particularly in areas where rabies is enzootic, even though the animal is considered to be healthy at the time of exposure. Such cases may be treated as category II or III. FOR A RABIES VACCINATED DOG/CAT WHAT TO DO? CATEGORY OF WOUNDMinor scratch \- from nails (vaccine not required), teeth (vaccination rec.) IN WOUND Administration of rabies immunoglobulin (RIG): * Infiltration of wounds with RIG is of utmost importance in category 3 exposure management.

* In wound suturing: Infiltrate into the depth of the wound and around the wound, as much as anatomically feasible. The rest of the immunoglobulin, if any should be injected at an intramuscular site distant from that of vaccine inoculation. * * The dose of RIG: 20IU/ kg for Human RIG (HRIG) or 40 IU/ kg of Equine RIG (ERIG). * If RIG is unavailable on the first visit of vaccine injection its administration can be delayed by a maximum of 7days from the date of that first injection. * If the calculated dose is insufficient to infiltrate all wounds, sterile saline may be used to dilute it 2 to 3 fold to permit thorough infiltration RABIES VACCINE FOR NOT VACCINATED Intramuscular regimens for rabies VACCINE for category II and III exposures The 5 doses intramuscular regime: one dose of the vaccine should be administered on days 0, 3, 7, 14, and 28 in the deltoid region or, in small children, into the anterolateral area of the thigh muscle. The 2-1-1 regimen may also be used. Two doses are given on day 0 in the deltoid muscle, right and left arm. In addition, one does in the deltoid muscle on day 7 and one on day 21\.

Intradermal regimen for rabies PEP (DO WE WANT TO RECOMMEND IT? ) As a PEP regimen provided by the intradermal route require considerably less vaccine than the intramuscular regimens, the method is particularly appropriate where vaccine or money is in short supply. * Where the ID route has been endorsed by National Health Authorities and the intradermal route is used, staff training, instructions regarding conditions and duration of vaccine storage after reconstitution, use of appropriate 1 mL syringe, and short hypodermic needles are provided by the governing body. The regimen that is used in some places in India is 2 sites intradermal regimen. * It is also known as the 2-2-2-0-1-1 regimen. It consists of one dose (0.1 ml or 0.2 ml) of vaccine given at every of two sites on days 0, 3, and 7 and at one site on days 28 and 90\. * Two PEP schedules (vaccines fulfilling WHO requirements): * 2 DOSE \- 2 DAYS one dose on days 0 and 3\. The dose is either one standard intramuscular dose (which may be 1 ml or 0.5 ml depending on vaccine type) or one intradermal dose of 0.1 ml per site or as an alternative, * 4-site- ONE DAY (one visit only) intradermal PEP consisting of 4 injections of 0.1 mL distributed on each arm and thigh or suprascapular region on days 0\. * RIG is not indicated in CAT I and II. Exposure categories.BUT IN CATEGORY 3 IS INDICATED

* Full PEP should be given to : * patients who have received pre-or post-exposure prophylaxis with vaccines of unproven potency * patients in whom immunological memory is no longer assured as a result of HIV/ AIDS or other immunosuppressive causes. Pre-exposure prophylaxis Recommended for Pre-exposure prophylaxis may be offered to high-risk group like laboratory staff handling the virus and infected material, clinicians and para-medicals attending to hydrophobia cases, veterinarians, animal handlers and catchers, wildlife wardens, quarantine officers and travellers from rabies free areas to rabies endemic areas. Total three doses are recommended for pre-exposure prophylaxis. * In case of IM route 1 full vial to be given on days 0, 7, and day 21 or 28\. * In case of ID route, 0.1 ml on one site to be given on days 0, 7, and on either day 21

**Asymptomatic newly diagnostic stones**— Patients with asymptomatic stones or past history of renal calculi — Some patients are found to have an asymptomatic kidney stone or stones by imaging performed for a different indication. **Approximately one-third** of such patients will develop symptoms related to their kidney stones within three years, **and as many as one-half of these symptomatic patients may require surgical treatment for their stones.** **Monitoring for newly diagnosed stones by imaging** — Radiologic monitoring, is warranted for the detection of new stones. Monitoring and, in asymptomatic patients with a single stone who do not warrant a complete metabolic evaluation, active surveillance with repeat imaging is a reasonable approach. * should be performed initially at one year * If repeat imaging shows no evidence of stone growth, imaging can be repeated every two years * if there is no stone growth after four to five years, active surveillance may be discontinued. * If repeat imaging shows an increase in stone size or new stones, we perform a complete metabolic evaluation.

* If stones were previously visible by ultrasonography, then using this modality will minimize cumulative radiation exposure; this is particularly important in patients of childbearing age. Ultrasound should not be used for radiologic monitoring if prior stones were **only quantifiable** with noncontrast CT or abdominal radiographs * Noncontrast CT remains the most sensitive test for detecting stones, particularly small stones, but is an expensive option for routine monitoring of stone burden . * Digital tomosynthesis, a high-resolution radiograph-based imaging technique that is used routinely for breast cancer screening, may be an effective and lower cost alternative to noncontrast CT. It has also been shown to have lower radiation exposure compared with noncontrast CT , NOT COMMON IN INDIA **Symptomatic case \-evaluation and Initial Imaging** \- Adults with suspected renal colic: offer *urgent (≤24 h) low‑dose non‑contrast CT*; use ultrasound instead in pregnancy. \- Children/young people: ultrasound first‑line; CT only if diagnosis remains uncertain. \- NSAID (any route) as *first‑line*; IV paracetamol second‑line; opioids only if these are insufficient or contraindicated. **Conservative Management and Medical Expulsive Therapy**

\- Spontaneous passage: \~80% for stones \<4 mm; \~20% for \>8 mm \- Observation appropriate for small, uncomplicated stones with controlled pain and no infection/solitary kidney \- Consider *alpha‑blockers* as medical expulsive therapy (MET) for distal ureteric stones \<10 mm in adults, children, and young people (off‑label) **Definitive Interventions (SWL, URS, PCNL, Others**) \- **Renal stones \<10 mm (adults**): offer shock‑wave lithotripsy (SWL); consider ureteroscopy (URS) if SWL contraindicated/failed; PCNL if SWL/URS not options. \- **Renal 10–20 mm (adults**): consider URS or SWL; PCNL if these fail. \- **Renal \>20 mm / staghorn (adults**): offer percutaneous nephrolithotomy (PCNL); consider URS if PCNL is not possible. \- **Ureteric \<10 mm (adults**): offer SWL; consider URS if SWL is not feasible or fails. \- **Ureteric 10–20 mm (adults**): offer URS; consider SWL if timely clearance; PCNL for impacted proximal stones when URS fails. In older adults, URS yields \~70% stone‑free (zero fragments) and \~16% overall complication rate; ASA ≥3, emergency surgery, and \>60‑minute operative time increase complications **When to Seek Urgent/Urgent‑Surgical Care** Hospital admission/urgent urologic consultation is indicated for

\- Intractable pain not controlled with oral analgesia \- Obstruction in a solitary or transplanted kidney \- Obstruction with UTI, fever, sepsis, or pyonephrosis (infected hydronephrosis) – requires IV antibiotics and *immediate drainage* (stent or percutaneous nephrostomy). \- Significant renal dysfunction, dehydration requiring IV fluids, pregnancy, immunocompromise, or poor social support. **Favor URS** when: need maximal single‑procedure SFR (e.g., frail patient where repeated anesthetics are undesirable), larger ureteric stones (10–20 mm), complex anatomy, or SWL‑unfavorable factors (dense stones, long skin‑to‑stone distance, lower‑pole anatomy) **Favor SWL** when: stones are small/moderate, renal or proximal ureteric, anatomy favorable, and the patient is high‑risk for GA or prolonged endoscopy; SWL offers noninvasive, usually outpatient treatment with lower immediate morbidity but higher retreatment risk. **When to do metabolic evaluation and which** **Urinalysis** **pH:** A pH greater than 7.5 raises the possibility of a stone due to urease-producing bacteria, whereas a pH less than 5.5 favors uric acid lithiasis. **Uric acid crystals**:

* Uric acid crystals are observed in acid urine (usually pH \<5.5), a milieu that favors the conversion of the relatively soluble urate salt into the insoluble uric acid * Calcium phosphate \- calcium phosphate crystals only form in a relatively alkaline urine (usually pH ≥6.5) * Calcium oxalate crystals – The formation of calcium oxalate crystals is not dependent upon the urine pH, * Cystine crystals – Cystine crystals, with their characteristic hexagonal shape, are diagnostic of cystinuria , a urinary screening test for cystine * Magnesium ammonium phosphate crystals – Magnesium ammonium phosphate (struvite) and calcium carbonate apatite are the constituents of struvite stones Normal urine is undersaturated with magnesium ammonium phosphate, and struvite stone formation occurs only when ammonia production is increased and the urine pH is elevated. Both of these requirements are only met when an upper urinary tract infection occurs with a urease-producing bacterium, such as Proteus or Klebsiella. **Serum potassium, creatinine, phosphate, calcium, vitamin D, oxalate, and uric acid, are extremely helpful.** **The serum calcium concentration** should be measured looking for hypercalcemia

* If high-normal (which we define as above the midpoint of the normal range), the serum calcium should be repeated. * A measurement of intact parathyroid hormone is warranted in patients with serum calcium values in the high-normal range or if the urine calcium is high since primary hyperparathyroidism is often associated with only intermittent and mild elevations in the serum calcium concentration * High or high-normal serum calcium levels and hypercalciuria observed in 24-hour urine testing suggest possible hyperparathyroidism for which specific testing * Elevated serum uric acid levels suggest hyperuricemia * Low serum phosphate levels might indicate renal phosphate leak, which causes a vitamin D–dependent form of hypercalciuria that only responds to oral phosphate supplementation. * Elevated vitamin D could suggest sarcoidosis. **24 H Urine metabolic panel** An optimal 24-hour urine test should include calcium, citrate, oxalate, phosphate, sodium, sulfate, uric acid, creatinine, urea, and volume values It is indicated in cases of

* Multiple or recurrent stones * Single stone * Occupation (airline pilots, frequent business travelers) * Complexity (neurologic disease, anatomic abnormalities of the urinary tract, such as urinary diversion or solitary kidney), previous surgery for renal stones, renal disease, High risk for anesthesia or surgery * **The need for surgical stone removal, meaning for every operated case \- it should be done ideally** * **Stone composition of cystine, calcium phosphate, or uric acid** * Patients taking medication that may put them at higher risk (eg, topiramate, acetazolamide, atazanavir, sulfadiazine, and triamterene) * **First stone before 21 years** * Family history of kidney stones * Morbid obesity * **Chronic diarrheal states** Highly motivated patients should be offered testing and prophylactic treatment. [24-Hour Urine Testing for Nephrolithiasis: Interpretation and Treatment Guidelines \- StatPearls \- NCBI Bookshelf](https://www.ncbi.nlm.nih.gov/books/NBK482448/)

**Focused history for stone risk factors — Dietary habits** ● Low fluid intake or a high fluid loss (eg, from sweating or gastrointestinal losses), ● A very high animal protein diet, which can lead to higher excretion of calcium and uric acid and lower excretion of urine citrate . ● Higher sodium diet, which increases urinary calcium excretion ● Increased intake of higher oxalate-containing foods, particularly spinach. The magnitude of the contribution of dietary oxalate to urinary oxalate is controversial and likely varies considerably from person to person due to differences in gastrointestinal absorption. ● Lower calcium intake, which acts by increasing the absorption of dietary oxalate and subsequent higher excretion of oxalate in the urine due to decreased calcium oxalate complex formation within the intestinal lumen. The effect of lower calcium intake on raising urine oxalate more than counterbalances the decrease in calcium absorption and excretion. ● Excessive vitamin C and D supplementation, which may increase urinary oxalate or calcium, respectively. ● Excessive sugar (sucrose and fructose) intake, which may increase calcium and/or oxalate excretion.

SCr: serum creatinine; AKI: acute kidney injury; CKD: chronic kidney disease; UA: urinalysis; eGFR: estimated glomerular filtration rate; CBC: complete blood count; ECG: electrocardiogram; NSAID: nonsteroidal antiinflammatory drug; IV: intravenous; GFR: glomerular filtration rate; ACE: angiotensin-converting enzyme; ARB: angiotensin II receptor blocker; UTI: urinary tract infection. \* The normal mean SCr varies according to gender, race, and body size in part related to muscle mass. Interpretation of a specific abnormal test result should be based upon the reference range reported with that result. ¶ Examples of drugs associated with nephrotoxicity: * Acyclovir, aminoglycosides, amphotericin B, cephalosporins, penicillins, sulfonamides, vancomycin * NSAIDs * Omeprazole, other proton pump inhibitors * Allopurinol * Recent IV contrast * Zoledronic acid Examples of drugs that may reduce GFR without causing kidney damage: Examples of drugs that increase SCr independent of GFR: * Trimethoprim, dronedarone, H2 blockers, cobicistat

Δ CKD is defined by the presence of kidney damage (urinary albumin excretion of ≥30 mg/day) or decreased kidney function (eGFR \<60 mL/min) for 3 or more months. ◊ When the creatinine is stable, GFR-estimation equations provide a more accurate reflection of renal function than the SCr. GFR-estimating equations are not reliable in the setting of unstable serum creatinine. § AKI may be defined as an increase in SCr ≥0.3 mg/dL or \>50% increase in SCr within 48 hours or decrease in urine output \<0.5 mL/kg/hour for \>6 hours. AKI typically occurs in hospitalized patients or after a procedure. ¥ Subacute kidney injury may be defined as worsening SCr developing more slowly than AKI over \<3 months duration or an elevated SCr of unknown duration. Subacute kidney injury may overlap with AKI. ‡ Obtain nephrology consultation, even if "stable" SCr, if any of the following are present in a patient with CKD: * High-grade proteinuria (≥1 g) and/or hematuria to evaluate the possibility of glomerular disease * eGFR \<30 mL/min, GFR stage 4 to anticipate the need for renal replacement * Evidence of progressive renal disease or increased risk of developing future kidney or cardiovascular complications (eg, uncontrolled diabetes or hypertension) * Difficulty implementing the appropriate management plan by the primary care team

* Diabetes, high blood pressure, cardiovascular disease * UTI, kidney stones, obstruction * Autoimmune diseases * Systemic infections, drug toxicity, procedures

Prevention and treatment of altitude sickness * HAI is the collective term for the unique cerebral and pulmonary syndromes that can occur following an initial ascent to high altitude (generally above 2000 to 2500 m, 6500 to 8200 feet) or following a further ascent while already at high altitude. * HAI includes acute mountain sickness (AMS) and high altitude cerebral edema (HACE), which afflict the brain, and high altitude pulmonary edema (HAPE), which afflicts the lungs. * Acute Mountain Sickness (AMS): is the most common form of HAI and may occur following rapid ascent. It is characterized by headache in combination with other nonspecific symptoms, such as malaise and anorexia * Gradual ascent is the best strategy for the prevention of High Altitude Illness HAI * Early recognition of symptoms and prompt treatment are critical to reducing the risk of progression to serious HAI such as HAPE and HACE.

* HACE: Early symptoms of HACE may be missed or mistaken for exhaustion. Lethargy and irritability may manifest initially as diminished exercise performance, lack of participation in group activities, and the desire to be left alone. Even ataxia, the earliest physical sign of HACE, may be missed if the patient is lying in bed, insisting that he is well and simply wants to be left alone. The clinician may observe papilledema. A working diagnosis of HACE can be made presumptively and treatment started in any patient with a history of recent ascent (especially above 3500 m) and signs of encephalopathy. HAPE generally begins with a subtle, nonproductive cough, and shortness of breath with exertion, often when walking uphill * HAPE: HAPE generally begins with a subtle, nonproductive cough, and shortness of breath with exertion, often when walking uphill. Such nonspecific symptoms are easily mistaken for a benign upper respiratory tract infection or attributed to normal breathlessness at high altitudes or exhaustion. Initial symptoms typically appear two to four days after arrival at a new altitude. Occasionally, HAPE develops precipitously * Past history of HAI (strongly predictive if conditions are similar) * Rate of ascent and lack of acclimatization * Vigorous exertion at altitude before adequate acclimatization

Risk for high altitude illness per rate of ascent and other risk factors | Risk of HAI | Description | | :---- | :---- | | Low | No prior history of altitude illness and planning ascent to \<2800 m=9148 feet | | | Taking two days or more to arrive at 2500 to 3000 m \= 9842 feetfrom low altitude | | | Ascending no more than 500 m=1640 feet/day (sleeping altitude) once over 2500 m and taking one extra day to acclimatize for every additional 1000 m=3280 feet of ascent | | Moderate | Prior history of AMS and ascending to 2500 to 2800 m in less than two days | | | No history of AMS and ascending to 2800 m or higher in less than two days | | | Ascending \>500 m/day (increase in sleeping elevation) at altitudes above 3000 m with one extra day for acclimatization for every additional 1000 m of ascent | | High | History of severe altitude illness (HACE, HAPE) | | | History of AMS and ascending to 2800 m or higher in less than two days | | | Ascending over 3500 m in less than two days | | | Ascending \>500 m/day (increase in sleeping elevation) above 3000 m without extra days for acclimatization; rapid guided ascents (eg, Mt. Kilimanjaro in \<7 days) | | | Persons with medical conditions predisposing to altitude illness |

* Additional risk factors of developing AMS/HACE * Substances (eg, alcohol) or conditions that interfere with acclimatization * Comorbidities that interfere with respiration: * Of note, neither anemia nor asthma is associated with an increased risk for HAI (in fact, asthma generally improves at high altitude). * Sickle cell disease is exacerbated by hypoxic environments. * All forms of HAI respond to descent, oxygen therapy, or both. * For mild AMS, rest, halt ascent, and symptomatic treatment (eg, acetaminophen or NSAID for headache and ondansetron for nausea/vomiting) may be sufficient. * Reserve pharmacologic prophylaxis for patients who have a history of HAPE or recurrent Acute Mountain Sickness (AMS) and patients at high risk (as well as selected patients at moderate risk) * The provision of these medications for "rescue" treatment is also reasonable. Consider a kit of Acetazolamide, Dexamethasone and Nifedipine and make an escalation plan with the person seeking advice Pharmacologic treatment and prevention of high altitude illness (HAI)

| Condition | | Preferred agent | | :---- | :---- | :---- | | AMS/ HACE | Prevention\* | Acetazolamide: 125 mg orally every 12 hours Children: 2.5 mg/kg (maximum single dose: 125 mg) orally every 12 hours Duration: Start day before ascent and continue 2 to 3 days at maximum altitude; may use once at night thereafter to improve sleep | | | Treatment of mild AMS | Acetazolamide: 125 to 250 mg orally every 12 hours Children: 2.5 mg/kg (maximum single dose: 250 mg) orally every 12 hours¥ Duration: Continue for 24 hours after symptoms resolve or descent completed | | | Treatment of moderate to severe AMS | Dexamethasone:Δ 4 mg orally every 6 hours Children: 0.15 mg/kg (maximum single dose: 4 mg) orally every 6 hours Duration: Continue for 24 hours after symptoms resolve or descent completed but for no more than 7 days total | | | Treatment of HACE | Dexamethasone:Δ 8 to 10 mg orally /IM/IV once, then 4 mg orally/IM/IV every 6 hours Children: 0.15 mg/kg (maximum single dose: 4 mg) every 6 hours Duration: Continue until 24 hours after symptoms resolve or descent completed but for no more than 7 days total |

| HAPE | Prevention | Nifedipine: 60 mg extended-release orally divided daily (30 mg orally every 12 hrs; or 20 mg orally every 8 hours) Children: 0.5 mg/kg (maximum single dose: 20 mg) extended-release orally every 8 hours Duration: Start day before ascent and continue for 5 days at maximum altitude | | :---- | :---- | :---- | | | Treatment | Nifedipine: 60 mg extended-release orally divided daily (30 mg orally every 12 hours or 20 mg orally every 8 hours) Children: 0.5 mg/kg (maximum single dose: 20 mg) extended-release orally every 8 hours Duration: Continue until descent completed, symptoms resolved, and SpO2 normal for altitude | Δ Treatment with dexamethasone alleviates symptoms of AMS/HACE but does not improve acclimatization. Dexamethasone is not a substitute for immediate descent in HACE.

1. **When is asthma confirmed?** 2. **Important potentially dangerous d/ds that could get missed?** 3. **How to assess asthma control in non attack settings?** 4. **How to convince patients for better control \- long term difference between well controlled vs not well controlled asthma?** 5. **How to assess asthma exacerbation for severity and start treatment /refer dependening on patient’s location, willingness?** 6. **Association of other conditions?**

**What is the role of reversibility testing in asthma?** This can be easily done after performing baseline spirometry, by administering 400 g of inhaled salbutamol (or equivalent) and repeating the test after 15-20 minutes. **An improvement in FEV1 and/ or FVC of at least 12% and 200 mL compared to the baseline value indicates a positive bronchodilator response.** When spirometry is not available, response to bronchodilator can be assessed using peak expiratory flow (PEF) measurements. An increase in baseline peak expiratory flow by 60 L/min (and/or 20%) following inhalation of 400 g of salbutamol or equivalent is considered a positive bronchodilator response. **Quantification of eosinophil count in sputum** (\<2% normal, \>2% suggestive of eosinophilic inflammation) can guide inhaled corticosteroid (ICS) therapy, thereby reducing the risk of exacerbations in adults with moderate to severe asthma.

**Preferred : ICS+LABA as both releiver and controller medicines** SABA (Short‑Acting Beta‑2 Agonists) is the agent of choice for rescue medication in asthma. LABA monotherapy (Long‑Acting Beta‑2 Agonists) should be avoided due to safety concerns with the use of LABA monotherapy SAMA i(Short-Acting Muscarinic Antagonists) is a less preferred alternative/add-on to SABA as reliever medication. Ipratropium Bromide , Oxitropium Bromide **CONTROLLERS** Inhalational Corticosteroids (ICS) ICS+LABA ICS+LABA+ oral LAMA (long‑acting methylxanthines) ICS+LABA \+ oralLTRA Omalizumab

**Summary of asthma treatment \- Step approach when not adequately controlled** **Omalizumab** may be considered as an adjunctive therapy to ICS in patients with moderate to severe asthma who have elevated serum IgE levels and a positive skin test to at least one perennial aero-allergen.Most of these trials used omalizumab for a duration of 16-28 weeks in asthmatics who had elevated **serum IgE levels (140-1300 IU/mL in various trials)** **and a positive skin test to aero-allergens**. Analysis of pooled data from seven trials showed that most patients who responded to omalizumab therapy did so by the end of 12 weeks The most common and well-documented adverse effect with omalizumab is injection site reaction. Considering the possibility of increased risk of parasitic infections and malignancy, more data is needed on the safety of long-term therapy with omalizumab before its widespread adoption **What is the role of inhaled corticosteroids (ICSs) in asthma?** * **Most of the clinical benefit from ICS is obtained at low to moderate doses**. Only a minority of patients benefit from increasing the dose beyond this. * High-dose ICS use should preferably be avoided to decrease the risk of side effects, both local and systemic. (1A) • * We recommend the use of valved holding chambers/ spacers whenever using moderate to high-dose ICS.

**What is the role of long‑acting beta‑2 agonists (LABA) in asthma?** * LABA monotherapy should not be used in the management of stable asthma. (1A) * Addition of LABA to ICS is the preferred choice when symptoms are uncontrolled despite ICS monotherapy in moderate doses. **What is the role of leukotriene receptor antagonists (LTRAs) in asthma?** * Monotherapy with LTRA is inferior to monotherapy with ICS. (1A) * Monotherapy with LTRA might be an alternative to ICS in patients with mild asthma if they are unwilling to use ICS or if they are not suitable for ICS therapy. (1B) * As an add-on to ICS, LTRAs are inferior to LABA. (1A) * Addition of LTRA might be beneficial in patients whose asthma remains uncontrolled despite the ICS/LABA combination. **What is the role of long‑acting methylxanthines in the management of asthma?**

* Methylxanthine monotherapy is inferior to ICS monotherapy. (1A) * When stepping up from ICS monotherapy, addition of methylxanthine to ICS is as effective as doubling the dose of ICS (1A) but inferior to the ICS/LABA combination. (2A) * Methylxanthines may be used as an add-on therapy in patients who remain uncontrolled on a moderate to high ICS/LABA combination. (2B) * Whenever used as an add-on to ICS, we recommend using low dose (200-400 mg/day) sustained release formulations of theophylline. * **Acebrophylline:** An airway mucolytic and bronchodilator derivative of theophylline that functions via sustained release. * **Etofylline & Theophylline Combinations:** A synergistic combination often prescribed for chronic airflow limitation

**What is the benefit of using a single inhaler for maintenance and reliever therapy? ICS+LABA** The SiT approach has several advantages over conventional therapy. It is more patient friendly as the patient needs to use only a single inhaler. As the ICS and LABA components are combined through a single delivery device, patients cannot use LABA alone, thus reducing the complications of LABA monotherapy. Use of the SiT approach is also associated with reduction in asthma exacerbations.During periods of worsening asthma control which precede an asthma exacerbation, patients tend to take increasing doses of reliever medication. In SiT, an extra dose of ICS is also delivered with each reliever dose used. These additional doses of ICS delivered at the time of worsening prevent the impending asthma exacerbation. Also, the SiT approach is more cost effective. It decreases the cumulative corticosteroid dose used, by decreasing the daily dose requirement of ICS and by decreasing the exposure to systemic steroids during exacerbations by decreasing the frequency of exacerbations

The most common local side effects are oral candidiasis and dysphonia. Other less frequent side effects include perioral dermatitis, pharyngitis, reflex cough, sensation of thirst, and tongue hypertrophy. Using ICS at the lowest possible dose and frequency, rinsing mouth and oropharynx by gargling every time after ICS inhalation, and using a spacer device are important measures to reduce local side effects from ICS use. Ciclesonide, being a prodrug (not in active form in the pharynx), has been shown to have the least incidence of oro-pharyngeal side effects among all ICS.

When used in high doses, ICS can cause systemic side effects, the most worrisome being the suppression of hypothalamo-pituitary-adrenal (HPA) axis.\[200,201\] Current use of high-dose ICS (beclomethasone dipropionate \[BDP\] equivalent ≥ 1000 g/day) increases the risk of developing adrenal crisis.\[201\] Because of its unique pharmacokinetic properties (such as extensive first pass metabolism, extra hepatic metabolism and high protein binding), ciclesonide has an oral bio-availability of \< 1% and has not been shown to cause significant HPA axis suppression.\[202,203\] In a large retrospective cohort study, a dose–response relationship between the dose of ICS and risk of pneumonia, lower respiratory infection and tuberculosis was noted.\[204,205\] Other systemic side effects reported with ICS include suppression of growth (a serious concern when ICS are used in children), reduced bone mineral density, ocular side effects (glaucoma and cataract), skin thinning and bruising, and increased risk of infections.

The dose of inhaled steroids (in patients already on inhaled steroids) should be hiked up for 2-4 weeks at discharge from ED in addition to oral steroids. Leukotriene modifiers have no role in the management of patients with acute asthma. (1A)

ACUTE NEW ONSET HEADACHE VS NEW DAILY PERSISTENT HEADACHE (patient can vividly recall the day of onset, it evolves over max 3 days) VS CHRONIC DAILY/NEAR DAILY HEADACHE * SERIOUS: meningitis, SAH, EDH/SDH, glaucoma, tumor * NONSERIOUS : purulent sinusitis (without complications), URTI, fever Low CSF: CSF leak \- LP history Raised CSF: obese women, or pregnant women, eye symptoms, papilloedema ICH: maximises in 5 minutes, neck stiffness may be there Temporal arteritis: in old age, women , headache, polymyalgia rheumatica, jaw pain/claudication, fever, weight loss Migraine: average age of onset \~ 12 years Headache intensity can peak in 20s and 30s One in 5 women, one in 16 men and one in 11 children Migraine vs Tension type vs TACs (Trigeminal autonomic cephalgias) TACs: Short lasting , lateralised autonomic cranial autonomic symptoms- eye injection, tears, nasal congestion, fullness of ear, severe headache Migraine: Look of associated symptoms: nausea, photo/phonophobia, auar, prodrome/postdrome if not there \- clear cut migraine likely, if there confusion still remains Prevention in migraine: at least 8 days a month or 4 if high MIDAS score ?