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Answers and Critiques Item 1 Answer: C Educational Objective: Screen for depression in a e In patients with chronic pain, the incidence of patient with chronic pain. depression increases as pain symptoms magnify, and depression may manifest as pain. The most appropriate management is to screen for depression (Option C). In patients with chronic pain, the e Aggressive treatment of depression, with cognitive incidence of depression increases as pain symptoms behavioral therapy and pharmacologic therapy, can wn magnify, and depression may manifest as pain. Aggressive lead to substantial improvement in both chronic pain a 3 treatment of depression, with cognitive behavioral ther- and depressive symptoms. = apy and pharmacologic therapy, can lead to substantial = improvements in both chronic pain and depressive symp- Bibliography rs)

Item 1 Answer: C Educational Objective: Screen for depression in a e In patients with chronic pain, the incidence of patient with chronic pain. depression increases as pain symptoms magnify, and depression may manifest as pain. The most appropriate management is to screen for depression (Option C). In patients with chronic pain, the e Aggressive treatment of depression, with cognitive incidence of depression increases as pain symptoms behavioral therapy and pharmacologic therapy, can wn magnify, and depression may manifest as pain. Aggressive lead to substantial improvement in both chronic pain a 3 treatment of depression, with cognitive behavioral ther- and depressive symptoms. = apy and pharmacologic therapy, can lead to substantial = improvements in both chronic pain and depressive symp- Bibliography rs) toms. Iterative evaluation of depressive symptoms during s Finnerup NB. Nonnarcotic methods of pain management. N Engl J Med. = chronic pain treatment is critical to ensuring that patients 2019;380:2440-8. [PMID: 31216399] doi:10.1056/NEJMra1807061 cs wn sustain improvements. The PHQ-2 has been validated as a wd ® screening instrument for depression in older adults, with Item 2 Answer: C = wn similar sensitivity and specificity in this population com- = Educational Objective: Treat a patient with type 2 9 pared with its performance in younger adults. A positive diabetes mellitus with moderate-intensity statin therapy. screening result should prompt further assessment for depression. The most appropriate treatment is moderate-intensity rosu- This patient’s sleep disruption is probably related to vastatin (Option C). The 2018 American Heart Association his depressed mood. Treatment for the depression should (AHA)/American College of Cardiology (ACC) guideline take precedence before introducing a controlled substance on management of blood cholesterol recommends initiat- with risk for dependence, such as diazepam (Option A), a ing moderate-intensity statin therapy in adults aged 40 to benzodiazepine. 75 years with diabetes mellitus, regardless of the calculated Oral tramadol (Option B) is a weak u-opioid recep- atherosclerotic cardiovascular disease (ASCVD) risk. The tor agonist with serotonergic and noradrenergic activity. guideline also notes that risk assessment using the AHA/ Although tramadol is thought to carry less risk related to ACC Pooled Cohort Equations can be considered in patients chronic use than other opioids, a 2019 study examining the with diabetes to assess the need for high-intensity statin association of tramadol prescription with all-cause mor- therapy. This patient with type 2 diabetes has a 10-year tality among patients with osteoarthritis suggested that ASCVD risk of 3.8%, and high-intensity statin therapy is tramadol may be associated with a higher rate of mortality not indicated. The U.S. Preventive Services Task Force rec- over 1 year. The single study is far from conclusive; however, ommends that adults without a history of cardiovascular tramadol should be considered as similar to other opioids disease use a low- to moderate-intensity statin for the when assessing the risk for opioid use in the treatment of prevention of ASCVD events and mortality when all of the chronic pain. following criteria are met: (1) they are aged 40 to 75 years; The evidence for spinal manipulation (Option D) in the (2) they have one or more ASCVD risk factors (dyslipid- treatment of acute, subacute, or chronic nonspecific low emia, diabetes, hypertension, or smoking); and (3) they back pain is mixed. One systematic review reported that have a calculated 10-year risk for an ASCVD event of 10% spinal manipulation was associated with modest improve- or greater. ments in pain and function at up to 6 weeks, with transient High-intensity rosuvastatin therapy (Option A) should minor musculoskeletal harms. Other low-quality evidence be considered in patients with diabetes who have additional suggests that spinal manipulation was associated with a high-risk features for ASCVD. These features include a his- small effect on function compared with sham manipula- tory of type 2 diabetes for at least 10 years or type 1 diabetes tion, but evidence was insufficient to determine the effect for 20 years or more; complications of diabetes, such as on pain. Assessment for depression and subsequent treat- nephropathy, neuropathy, or retinopathy; or chronic kidney ment is more likely to have a positive effect on pain control disease. in this patient than would spinal manipulation. In addi- Icosapent ethyl (a highly purified fish oil) (Option B) tion, spinal manipulation will not help with this patient’s and omega-3 fatty acids (Option D) decrease triglyceride lev- chronic knee pain. els and, in the case of icosapent ethyl, cardiovascular death.

toms. Iterative evaluation of depressive symptoms during s Finnerup NB. Nonnarcotic methods of pain management. N Engl J Med. = chronic pain treatment is critical to ensuring that patients 2019;380:2440-8. [PMID: 31216399] doi:10.1056/NEJMra1807061 cs wn sustain improvements. The PHQ-2 has been validated as a wd ® screening instrument for depression in older adults, with Item 2 Answer: C = wn similar sensitivity and specificity in this population com- = Educational Objective: Treat a patient with type 2 9 pared with its performance in younger adults. A positive diabetes mellitus with moderate-intensity statin therapy. screening result should prompt further assessment for depression. The most appropriate treatment is moderate-intensity rosu- This patient’s sleep disruption is probably related to vastatin (Option C). The 2018 American Heart Association his depressed mood. Treatment for the depression should (AHA)/American College of Cardiology (ACC) guideline take precedence before introducing a controlled substance on management of blood cholesterol recommends initiat- with risk for dependence, such as diazepam (Option A), a ing moderate-intensity statin therapy in adults aged 40 to benzodiazepine. 75 years with diabetes mellitus, regardless of the calculated Oral tramadol (Option B) is a weak u-opioid recep- atherosclerotic cardiovascular disease (ASCVD) risk. The tor agonist with serotonergic and noradrenergic activity. guideline also notes that risk assessment using the AHA/ Although tramadol is thought to carry less risk related to ACC Pooled Cohort Equations can be considered in patients chronic use than other opioids, a 2019 study examining the with diabetes to assess the need for high-intensity statin association of tramadol prescription with all-cause mor- therapy. This patient with type 2 diabetes has a 10-year tality among patients with osteoarthritis suggested that ASCVD risk of 3.8%, and high-intensity statin therapy is tramadol may be associated with a higher rate of mortality not indicated. The U.S. Preventive Services Task Force rec- over 1 year. The single study is far from conclusive; however, ommends that adults without a history of cardiovascular tramadol should be considered as similar to other opioids disease use a low- to moderate-intensity statin for the when assessing the risk for opioid use in the treatment of prevention of ASCVD events and mortality when all of the chronic pain. following criteria are met: (1) they are aged 40 to 75 years; The evidence for spinal manipulation (Option D) in the (2) they have one or more ASCVD risk factors (dyslipid- treatment of acute, subacute, or chronic nonspecific low emia, diabetes, hypertension, or smoking); and (3) they back pain is mixed. One systematic review reported that have a calculated 10-year risk for an ASCVD event of 10% spinal manipulation was associated with modest improve- or greater. ments in pain and function at up to 6 weeks, with transient High-intensity rosuvastatin therapy (Option A) should minor musculoskeletal harms. Other low-quality evidence be considered in patients with diabetes who have additional suggests that spinal manipulation was associated with a high-risk features for ASCVD. These features include a his- small effect on function compared with sham manipula- tory of type 2 diabetes for at least 10 years or type 1 diabetes tion, but evidence was insufficient to determine the effect for 20 years or more; complications of diabetes, such as on pain. Assessment for depression and subsequent treat- nephropathy, neuropathy, or retinopathy; or chronic kidney ment is more likely to have a positive effect on pain control disease. in this patient than would spinal manipulation. In addi- Icosapent ethyl (a highly purified fish oil) (Option B) tion, spinal manipulation will not help with this patient’s and omega-3 fatty acids (Option D) decrease triglyceride lev- chronic knee pain. els and, in the case of icosapent ethyl, cardiovascular death. 133

syersene Gnas However, they are not indicated for primary prevention in associated with drug-induced diabetes. Statins are not this patient with diabetes and hypertriglyceridemia that known to increase peripheral edema. has not been treated with lifestyle interventions and statin Empagliflozin (Option C) is a sodium-glucose therapy. cotransporter-2 (SGLT2) inhibitor that decreases renal glu- cose reabsorption and increases urinary glucose excretion, resulting in lower blood glucose levels. SGLT2 inhibitors also e According to guidelines from the American Heart increase urinary sodium excretion, cause weight loss, and Association/American College of Cardiology, moderate- lower blood pressure. Empagliflozin is not associated with intensity statin therapy should be initiated in adults the formation of peripheral edema. aged 40 to 75 years with diabetes mellitus. The mechanism of glucose lowering with metformin

However, they are not indicated for primary prevention in associated with drug-induced diabetes. Statins are not this patient with diabetes and hypertriglyceridemia that known to increase peripheral edema. has not been treated with lifestyle interventions and statin Empagliflozin (Option C) is a sodium-glucose therapy. cotransporter-2 (SGLT2) inhibitor that decreases renal glu- cose reabsorption and increases urinary glucose excretion, resulting in lower blood glucose levels. SGLT2 inhibitors also e According to guidelines from the American Heart increase urinary sodium excretion, cause weight loss, and Association/American College of Cardiology, moderate- lower blood pressure. Empagliflozin is not associated with intensity statin therapy should be initiated in adults the formation of peripheral edema. aged 40 to 75 years with diabetes mellitus. The mechanism of glucose lowering with metformin e The U.S. Preventive Services Task Force recommends (Option D) is complex and not completely understood. Met- formin decreases hepatic glucose production and increases statin therapy for the primary prevention of athero- > secretion of glucagon-like peptide-1. Metformin also may sclerotic cardiovascular disease (ASCVD) events and = nm reduce intestinal absorption of glucose and increase periph- mortality when patients meet all of the following cri- = eral glucose uptake. Commonly reported adverse effects oO teria: (1) age 40 to 75 years, 2) one or more ASCVD risk = “ include a metallic taste in the mouth; nausea; diarrhea; factors, and (3) a calculated 10-year risk for an ASCVD gm vitamin B,, deficiency; and, rarely, lactic acidosis. Peripheral = event of 10% or greater. Qa edema is not associated with metformin. (=) = a. Bibliography 2 Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ [= e Medications are a common cause of bilateral lower © ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management n of blood cholesterol: a report of the American College of Cardiology/ extremity edema. American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139:e1082-143. [PMID: 30586774] doi:10.1161/CIR. e The drugs most commonly implicated in edema forma- 0000000000000625 tion are calcium channel blockers, gabapentin, NSAIDs, oral contraceptives, glucocorticoids, and thiazolidinedi- Item 3 Answer: A ones.

e The U.S. Preventive Services Task Force recommends (Option D) is complex and not completely understood. Met- formin decreases hepatic glucose production and increases statin therapy for the primary prevention of athero- > secretion of glucagon-like peptide-1. Metformin also may sclerotic cardiovascular disease (ASCVD) events and = nm reduce intestinal absorption of glucose and increase periph- mortality when patients meet all of the following cri- = eral glucose uptake. Commonly reported adverse effects oO teria: (1) age 40 to 75 years, 2) one or more ASCVD risk = “ include a metallic taste in the mouth; nausea; diarrhea; factors, and (3) a calculated 10-year risk for an ASCVD gm vitamin B,, deficiency; and, rarely, lactic acidosis. Peripheral = event of 10% or greater. Qa edema is not associated with metformin. (=) = a. Bibliography 2 Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ [= e Medications are a common cause of bilateral lower © ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management n of blood cholesterol: a report of the American College of Cardiology/ extremity edema. American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139:e1082-143. [PMID: 30586774] doi:10.1161/CIR. e The drugs most commonly implicated in edema forma- 0000000000000625 tion are calcium channel blockers, gabapentin, NSAIDs, oral contraceptives, glucocorticoids, and thiazolidinedi- Item 3 Answer: A ones. Educational Objective: Diagnose medication-related Bibliography peripheral edema. Ratchford EV, Evans NS. Approach to lower extremity edema. Curr Treat The most likely cause of the edema is amlodipine (Option A). Options Cardiovasc Med. 2017;19:16. [PMID: 28290004] doi:10.1007/ $11936-017-0518-6 Acute bilateral lower extremity edema has a broad differen- tial diagnosis. Most diagnoses can be established on the basis of the history or physical examination findings. Medications Item 4 Answer: B are a common cause of bilateral lower extremity edema. Educational Objective: Treat chronic low back pain. The most commonly implicated drugs are calcium channel blockers, gabapentin, NSAIDs, oral contraceptives, gluco- Exercise therapy (Option B) is the most appropriate treat- corticoids, and thiazolidinediones. Dihydropyridine calcium ment for this patient with chronic low back pain. Nonphar-

Educational Objective: Diagnose medication-related Bibliography peripheral edema. Ratchford EV, Evans NS. Approach to lower extremity edema. Curr Treat The most likely cause of the edema is amlodipine (Option A). Options Cardiovasc Med. 2017;19:16. [PMID: 28290004] doi:10.1007/ $11936-017-0518-6 Acute bilateral lower extremity edema has a broad differen- tial diagnosis. Most diagnoses can be established on the basis of the history or physical examination findings. Medications Item 4 Answer: B are a common cause of bilateral lower extremity edema. Educational Objective: Treat chronic low back pain. The most commonly implicated drugs are calcium channel blockers, gabapentin, NSAIDs, oral contraceptives, gluco- Exercise therapy (Option B) is the most appropriate treat- corticoids, and thiazolidinediones. Dihydropyridine calcium ment for this patient with chronic low back pain. Nonphar- channel blockers, such as amlodipine, are associated with macologic treatment is recommended as first-line therapy lower extremity edema in up to 30% of patients in a dose- for patients with acute (<4 weeks), subacute (4-12 weeks), dependent fashion. Lower extremity edema occurs because or chronic (>12 weeks) low back pain. Multiple nonphar- these drugs cause vasodilation, leading to increased cap- macologic options are available for chronic low back pain. illary hydrostatic pressure, which is exacerbated by grav- Evidence and systematic reviews endorse exercise, multidis- itational forces with standing. The swelling subsides with ciplinary rehabilitation, acupuncture, mindfulness-based dose reduction of the dihydropyridine calcium channel stress reduction (moderate-quality evidence), tai chi, yoga, blocker or switching to a different class of antihypertensive motor control exercise, progressive relaxation, electromyog- medication. raphy biofeedback, low-level laser therapy, operant condition- Statins, such as atorvastatin (Option B), are generally ing, cognitive behavioral therapy, and spinal manipulation. well tolerated. Although muscle pain and weakness with Varying levels of predominantly weak evidence support these or without increased creatine kinase levels are commonly approaches, but associated harms are minimal. reported by patients, muscle symptoms in randomized trials Tricyclic antidepressants (such as amitriptyline [Option appear to occur equally often in patients taking placebo. A]) and neuromodulators (such as gabapentin [Option C] Statins may be associated with increases in serum amino- and pregabalin) have not demonstrated effectiveness for transferase levels, but statin-induced liver injury is rare. chronic low back pain and should not be prescribed for this Statins also have been associated with the onset of diabe- patient.

channel blockers, such as amlodipine, are associated with macologic treatment is recommended as first-line therapy lower extremity edema in up to 30% of patients in a dose- for patients with acute (<4 weeks), subacute (4-12 weeks), dependent fashion. Lower extremity edema occurs because or chronic (>12 weeks) low back pain. Multiple nonphar- these drugs cause vasodilation, leading to increased cap- macologic options are available for chronic low back pain. illary hydrostatic pressure, which is exacerbated by grav- Evidence and systematic reviews endorse exercise, multidis- itational forces with standing. The swelling subsides with ciplinary rehabilitation, acupuncture, mindfulness-based dose reduction of the dihydropyridine calcium channel stress reduction (moderate-quality evidence), tai chi, yoga, blocker or switching to a different class of antihypertensive motor control exercise, progressive relaxation, electromyog- medication. raphy biofeedback, low-level laser therapy, operant condition- Statins, such as atorvastatin (Option B), are generally ing, cognitive behavioral therapy, and spinal manipulation. well tolerated. Although muscle pain and weakness with Varying levels of predominantly weak evidence support these or without increased creatine kinase levels are commonly approaches, but associated harms are minimal. reported by patients, muscle symptoms in randomized trials Tricyclic antidepressants (such as amitriptyline [Option appear to occur equally often in patients taking placebo. A]) and neuromodulators (such as gabapentin [Option C] Statins may be associated with increases in serum amino- and pregabalin) have not demonstrated effectiveness for transferase levels, but statin-induced liver injury is rare. chronic low back pain and should not be prescribed for this Statins also have been associated with the onset of diabe- patient. tes mellitus, but typically only in patients with preexisting In patients with chronic low back pain who continue to be risk factors for diabetes; the beneficial effects of statins on symptomatic with nonpharmacologic therapy, pharmacologic cardiovascular mortality appear to overshadow the risks treatment with NSAIDs is considered first-line therapy and

tes mellitus, but typically only in patients with preexisting In patients with chronic low back pain who continue to be risk factors for diabetes; the beneficial effects of statins on symptomatic with nonpharmacologic therapy, pharmacologic cardiovascular mortality appear to overshadow the risks treatment with NSAIDs is considered first-line therapy and 134

_ answprs ane Gritiques duloxetine is considered second-line pharmacologic therapy. significant functional impairment. Therefore, changing to Opioids, such as oxycodone (Option D), should be consid- extended-release oxycodone (Option A) would be inappro- ered as an option only in patients whose symptoms have not priate at this time. responded to nonpharmacologic and first- and second-line Urine drug screening (Option B) is an important mon- pharmacologic therapies and only if the potential benefits out- itoring tool in patients using opioids to ensure adherence to weigh the risks for individual patients. Furthermore, a 2018 the prescribed agent and to evaluate for the presence of other randomized controlled trial demonstrated that opioids were controlled drugs or substances prohibited by the terms of the not superior to nonopioid medications for improving pain- treatment agreement. Optimal screening frequency is cur- related function for chronic back pain; pain intensity was sig- rently unclear, but in this patient who recently underwent nificantly improved in the nonopioid group. screening and has a low Opioid Risk Tool score, it would be Most patients with low back pain do not require sur- reasonable to consider repeat screening at least yearly or if gery (Option E). Emergent surgery is indicated for most aberrant opioid use behaviors develop. patients with suspected cord compression or cauda equina Naloxone (Option C) is an opioid blocker used to treat wn o syndrome. Nonurgent surgery may be considered in patients opioid overdose and respiratory compromise. It can be pre- = with neurologic deficits, progressively worsening spinal ste- scribed in an outpatient environment to patients at high risk = nosis, or chronic pain (with corresponding abnormalities on for overdose. This patient does not have additional major risk = (s) imaging) that has been refractory to conservative measures factors (such as concurrent benzodiazepine use, obstructive a=] and has the potential to respond to surgery. This patient has = sleep apnea, a history of substance use, or liver or kid- os] no lesion that will be amenable to surgical intervention. ney failure) and is taking less than 50 morphine milligram wn ed o equivalents per day, placing her at relatively low risk for S overdose. wn = e Nonpharmacologic treatment is recommended as first- < line therapy for patients with acute (<4 weeks), subacute (4-12 weeks), or chronic (>12 weeks) low back pain. e The state prescription monitoring database should be

duloxetine is considered second-line pharmacologic therapy. significant functional impairment. Therefore, changing to Opioids, such as oxycodone (Option D), should be consid- extended-release oxycodone (Option A) would be inappro- ered as an option only in patients whose symptoms have not priate at this time. responded to nonpharmacologic and first- and second-line Urine drug screening (Option B) is an important mon- pharmacologic therapies and only if the potential benefits out- itoring tool in patients using opioids to ensure adherence to weigh the risks for individual patients. Furthermore, a 2018 the prescribed agent and to evaluate for the presence of other randomized controlled trial demonstrated that opioids were controlled drugs or substances prohibited by the terms of the not superior to nonopioid medications for improving pain- treatment agreement. Optimal screening frequency is cur- related function for chronic back pain; pain intensity was sig- rently unclear, but in this patient who recently underwent nificantly improved in the nonopioid group. screening and has a low Opioid Risk Tool score, it would be Most patients with low back pain do not require sur- reasonable to consider repeat screening at least yearly or if gery (Option E). Emergent surgery is indicated for most aberrant opioid use behaviors develop. patients with suspected cord compression or cauda equina Naloxone (Option C) is an opioid blocker used to treat wn o syndrome. Nonurgent surgery may be considered in patients opioid overdose and respiratory compromise. It can be pre- = with neurologic deficits, progressively worsening spinal ste- scribed in an outpatient environment to patients at high risk = nosis, or chronic pain (with corresponding abnormalities on for overdose. This patient does not have additional major risk = (s) imaging) that has been refractory to conservative measures factors (such as concurrent benzodiazepine use, obstructive a=] and has the potential to respond to surgery. This patient has = sleep apnea, a history of substance use, or liver or kid- os] no lesion that will be amenable to surgical intervention. ney failure) and is taking less than 50 morphine milligram wn ed o equivalents per day, placing her at relatively low risk for S overdose. wn = e Nonpharmacologic treatment is recommended as first- < line therapy for patients with acute (<4 weeks), subacute (4-12 weeks), or chronic (>12 weeks) low back pain. e The state prescription monitoring database should be e For patients with chronic low back pain unresponsive reviewed before prescribing opioids to monitor

duloxetine is considered second-line pharmacologic therapy. significant functional impairment. Therefore, changing to Opioids, such as oxycodone (Option D), should be consid- extended-release oxycodone (Option A) would be inappro- ered as an option only in patients whose symptoms have not priate at this time. responded to nonpharmacologic and first- and second-line Urine drug screening (Option B) is an important mon- pharmacologic therapies and only if the potential benefits out- itoring tool in patients using opioids to ensure adherence to weigh the risks for individual patients. Furthermore, a 2018 the prescribed agent and to evaluate for the presence of other randomized controlled trial demonstrated that opioids were controlled drugs or substances prohibited by the terms of the not superior to nonopioid medications for improving pain- treatment agreement. Optimal screening frequency is cur- related function for chronic back pain; pain intensity was sig- rently unclear, but in this patient who recently underwent nificantly improved in the nonopioid group. screening and has a low Opioid Risk Tool score, it would be Most patients with low back pain do not require sur- reasonable to consider repeat screening at least yearly or if gery (Option E). Emergent surgery is indicated for most aberrant opioid use behaviors develop. patients with suspected cord compression or cauda equina Naloxone (Option C) is an opioid blocker used to treat wn o syndrome. Nonurgent surgery may be considered in patients opioid overdose and respiratory compromise. It can be pre- = with neurologic deficits, progressively worsening spinal ste- scribed in an outpatient environment to patients at high risk = nosis, or chronic pain (with corresponding abnormalities on for overdose. This patient does not have additional major risk = (s) imaging) that has been refractory to conservative measures factors (such as concurrent benzodiazepine use, obstructive a=] and has the potential to respond to surgery. This patient has = sleep apnea, a history of substance use, or liver or kid- os] no lesion that will be amenable to surgical intervention. ney failure) and is taking less than 50 morphine milligram wn ed o equivalents per day, placing her at relatively low risk for S overdose. wn = e Nonpharmacologic treatment is recommended as first- < line therapy for patients with acute (<4 weeks), subacute (4-12 weeks), or chronic (>12 weeks) low back pain. e The state prescription monitoring database should be e For patients with chronic low back pain unresponsive reviewed before prescribing opioids to monitor to nonpharmacologic treatment, pharmacologic ther- patient use patterns, identify requests for early refills

duloxetine is considered second-line pharmacologic therapy. significant functional impairment. Therefore, changing to Opioids, such as oxycodone (Option D), should be consid- extended-release oxycodone (Option A) would be inappro- ered as an option only in patients whose symptoms have not priate at this time. responded to nonpharmacologic and first- and second-line Urine drug screening (Option B) is an important mon- pharmacologic therapies and only if the potential benefits out- itoring tool in patients using opioids to ensure adherence to weigh the risks for individual patients. Furthermore, a 2018 the prescribed agent and to evaluate for the presence of other randomized controlled trial demonstrated that opioids were controlled drugs or substances prohibited by the terms of the not superior to nonopioid medications for improving pain- treatment agreement. Optimal screening frequency is cur- related function for chronic back pain; pain intensity was sig- rently unclear, but in this patient who recently underwent nificantly improved in the nonopioid group. screening and has a low Opioid Risk Tool score, it would be Most patients with low back pain do not require sur- reasonable to consider repeat screening at least yearly or if gery (Option E). Emergent surgery is indicated for most aberrant opioid use behaviors develop. patients with suspected cord compression or cauda equina Naloxone (Option C) is an opioid blocker used to treat wn o syndrome. Nonurgent surgery may be considered in patients opioid overdose and respiratory compromise. It can be pre- = with neurologic deficits, progressively worsening spinal ste- scribed in an outpatient environment to patients at high risk = nosis, or chronic pain (with corresponding abnormalities on for overdose. This patient does not have additional major risk = (s) imaging) that has been refractory to conservative measures factors (such as concurrent benzodiazepine use, obstructive a=] and has the potential to respond to surgery. This patient has = sleep apnea, a history of substance use, or liver or kid- os] no lesion that will be amenable to surgical intervention. ney failure) and is taking less than 50 morphine milligram wn ed o equivalents per day, placing her at relatively low risk for S overdose. wn = e Nonpharmacologic treatment is recommended as first- < line therapy for patients with acute (<4 weeks), subacute (4-12 weeks), or chronic (>12 weeks) low back pain. e The state prescription monitoring database should be e For patients with chronic low back pain unresponsive reviewed before prescribing opioids to monitor to nonpharmacologic treatment, pharmacologic ther- patient use patterns, identify requests for early refills apy with NSAIDs and duloxetine can be considered. as a warning sign of worsening pain or disordered use, and avoid multiple prescriptions.

to nonpharmacologic treatment, pharmacologic ther- patient use patterns, identify requests for early refills apy with NSAIDs and duloxetine can be considered. as a warning sign of worsening pain or disordered use, and avoid multiple prescriptions. Bibliography Skelly AC, Chou R, Dettori JR, et al. Noninvasive nonpharmacological treat- Bibliography ment for chronic pain: a systematic review update. Rockville, MD: Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for Agency for Healthcare Research and Quality; 2020. [PMID: 32338846] chronic pain—United States, 2016. JAMA. 2016;315:1624-45. [PMID: 26977696] doi:10.1001/jama.2016.1464

Bibliography Skelly AC, Chou R, Dettori JR, et al. Noninvasive nonpharmacological treat- Bibliography ment for chronic pain: a systematic review update. Rockville, MD: Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for Agency for Healthcare Research and Quality; 2020. [PMID: 32338846] chronic pain—United States, 2016. JAMA. 2016;315:1624-45. [PMID: 26977696] doi:10.1001/jama.2016.1464 Item 5 Answer: D Educational Objective: Monitor a patient on chronic item 6 Answer: A opioid therapy. Educational Objective: Recognize confounding bias in a case-control study design. The most appropriate risk mitigation step before refilling this patient’s opioid prescription is to review the state pre- The most important threat to the validity of this study’s scription monitoring database (Option D). Review of the conclusions is confounding by factors not included in the prescription monitoring database before authorizing refills analysis (Option A). Confounding occurs when factors allows the prescribing clinician to monitor patient use pat- other than the treatments being studied are independently terns and identify requests for early refills as a warning associated with the participants being studied and the sign of worsening pain or disordered use. It also serves an end point being assessed. For example, in this study, con- important function in identifying multiple prescriptions founding could have been introduced if another condition of opioids and other controlled substances. For this patient likely to influence survival, such as the presence of kidney with chronic pain who has several specialists involved in disease, determined whether patients received the new her care, close monitoring of the database is needed before treatment or usual care. Although design strategies, such each prescription. The regulations for checking prescrip- as matching, and statistical techniques, such as stratified tion monitoring databases before opioid prescribing vary by analyses or regression techniques, can account for known state, and physicians should be familiar with the regulations or anticipated confounders, no design strategy or analy- in the states in which they practice. sis technique can remove the effect of unanticipated or For most patients with chronic noncancer pain, unknown confounders. All observational study designs short-acting opioids are preferred. Extended-release or are thus vulnerable to this threat to validity. Only random long-acting opioids are typically prescribed for use in pal- assignment of the intervention being studied (i.c., a ran- liative care or to manage pain from cancer or other condi- domized controlled study design) protects against both tions characterized by persistent pain or disabling pain with known and unknown confounders.

Item 5 Answer: D Educational Objective: Monitor a patient on chronic item 6 Answer: A opioid therapy. Educational Objective: Recognize confounding bias in a case-control study design. The most appropriate risk mitigation step before refilling this patient’s opioid prescription is to review the state pre- The most important threat to the validity of this study’s scription monitoring database (Option D). Review of the conclusions is confounding by factors not included in the prescription monitoring database before authorizing refills analysis (Option A). Confounding occurs when factors allows the prescribing clinician to monitor patient use pat- other than the treatments being studied are independently terns and identify requests for early refills as a warning associated with the participants being studied and the sign of worsening pain or disordered use. It also serves an end point being assessed. For example, in this study, con- important function in identifying multiple prescriptions founding could have been introduced if another condition of opioids and other controlled substances. For this patient likely to influence survival, such as the presence of kidney with chronic pain who has several specialists involved in disease, determined whether patients received the new her care, close monitoring of the database is needed before treatment or usual care. Although design strategies, such each prescription. The regulations for checking prescrip- as matching, and statistical techniques, such as stratified tion monitoring databases before opioid prescribing vary by analyses or regression techniques, can account for known state, and physicians should be familiar with the regulations or anticipated confounders, no design strategy or analy- in the states in which they practice. sis technique can remove the effect of unanticipated or For most patients with chronic noncancer pain, unknown confounders. All observational study designs short-acting opioids are preferred. Extended-release or are thus vulnerable to this threat to validity. Only random long-acting opioids are typically prescribed for use in pal- assignment of the intervention being studied (i.c., a ran- liative care or to manage pain from cancer or other condi- domized controlled study design) protects against both tions characterized by persistent pain or disabling pain with known and unknown confounders. 135

Answers and Critiques _ Statistical power (Option B) refers to the ability of a Acetabular labrum tear (Option A) is found most particular study to detect a difference if one exists. Power commonly in young competitive athletes. It presents with depends on the size of the difference to be detected and the anterior hip pain, often localized to the groin. The FADIR sample size, or number of participants being studied. Lack of (Flexion, ADduction, and Internal Rotation) test will demon- statistical power is a concern when the results fail to achieve strate pain and restricted movement; these results were not statistical significance. This was not the case in this study. found in this older patient with posterior hip pain. Loss to follow-up (Option C) is a threat to the validity Patients with greater trochanteric pain syndrome of prospective study designs, particularly those with long (GTPS) (Option B) typically have pain localized to the greater follow-up times or long time to the outcome produced by trochanter that may radiate down the lateral leg to the knee. the treatment or exposure to the studied risk factor. For The pain is often exacerbated by lying on the affected side observational study designs, the prospective cohort study and climbing stairs. Pain onset is usually insidious. GTPS with long follow-up time is most vulnerable to this threat. A can be differentiated from hip joint pain in that GTPS does | retrospective study design would not be vulnerable because not usually radiate to the groin or posterior hip or limit hip = wn all patients receiving the treatment or exposed to the risk are range of motion. Diagnosis is made by the history and by = identified and included in the study. eliciting pain with palpation over the greater trochanter or oO = wn The case-control study is an observational study in which reproduction of the pain when the patient takes a step up. ie?) participants are initially classified or enrolled according to Hip osteoarthritis (Option C) tends to present as = a. the presence of the condition being studied—in this case, a pain of insidious onset in older patients. Physical exam- a =e treatment. Those with the condition are compared against ination typically reveals groin pain and restricted range of = participants who do not have the condition or, in this case, motion with internal rotation or with the FADIR test. This 2 < the treatment. Because sample size is a critical determinant patient’s posterior hip pain, normal FADIR test result, and @o an of study power, or the ability to detect differences between pain upon FABER testing are most compatible with sacroil- groups, a case-control study design is an optimal way to col- iac joint dysfunction. lect enough cases of a rare disorder to enable adequate power to allow meaningful conclusions to be drawn (Option D). e The diagnosis of sacroiliac joint dysfunction is sup- ported by posterior hip pain and a positive result on e All observational studies are subject to confounding, FABER (Flexion, ABduction, and Externally Rotation) which occurs when factors other than the treatments testing. being studied are independently associated with the end point being assessed. Bibliography Telli H, Telli S, Topal M. The validity and reliability of provocation tests in the diagnosis of sacroiliac joint dysfunction. Pain Physician. 2018;21: Bibliography E367-E376. [PMID: 30045603] Metlay JP, Armstrong KA. Annals clinical decision making: weighing evi- dence to inform clinical decisions. Ann Intern Med. 2020;172:599-603. [PMID: 32311735] doi:10.7326/M19-1941

Statistical power (Option B) refers to the ability of a Acetabular labrum tear (Option A) is found most particular study to detect a difference if one exists. Power commonly in young competitive athletes. It presents with depends on the size of the difference to be detected and the anterior hip pain, often localized to the groin. The FADIR sample size, or number of participants being studied. Lack of (Flexion, ADduction, and Internal Rotation) test will demon- statistical power is a concern when the results fail to achieve strate pain and restricted movement; these results were not statistical significance. This was not the case in this study. found in this older patient with posterior hip pain. Loss to follow-up (Option C) is a threat to the validity Patients with greater trochanteric pain syndrome of prospective study designs, particularly those with long (GTPS) (Option B) typically have pain localized to the greater follow-up times or long time to the outcome produced by trochanter that may radiate down the lateral leg to the knee. the treatment or exposure to the studied risk factor. For The pain is often exacerbated by lying on the affected side observational study designs, the prospective cohort study and climbing stairs. Pain onset is usually insidious. GTPS with long follow-up time is most vulnerable to this threat. A can be differentiated from hip joint pain in that GTPS does | retrospective study design would not be vulnerable because not usually radiate to the groin or posterior hip or limit hip = wn all patients receiving the treatment or exposed to the risk are range of motion. Diagnosis is made by the history and by = identified and included in the study. eliciting pain with palpation over the greater trochanter or oO = wn The case-control study is an observational study in which reproduction of the pain when the patient takes a step up. ie?) participants are initially classified or enrolled according to Hip osteoarthritis (Option C) tends to present as = a. the presence of the condition being studied—in this case, a pain of insidious onset in older patients. Physical exam- a =e treatment. Those with the condition are compared against ination typically reveals groin pain and restricted range of = participants who do not have the condition or, in this case, motion with internal rotation or with the FADIR test. This 2 < the treatment. Because sample size is a critical determinant patient’s posterior hip pain, normal FADIR test result, and @o an of study power, or the ability to detect differences between pain upon FABER testing are most compatible with sacroil- groups, a case-control study design is an optimal way to col- iac joint dysfunction. lect enough cases of a rare disorder to enable adequate power to allow meaningful conclusions to be drawn (Option D). e The diagnosis of sacroiliac joint dysfunction is sup- ported by posterior hip pain and a positive result on e All observational studies are subject to confounding, FABER (Flexion, ABduction, and Externally Rotation) which occurs when factors other than the treatments testing. being studied are independently associated with the end point being assessed. Bibliography Telli H, Telli S, Topal M. The validity and reliability of provocation tests in the diagnosis of sacroiliac joint dysfunction. Pain Physician. 2018;21: Bibliography E367-E376. [PMID: 30045603] Metlay JP, Armstrong KA. Annals clinical decision making: weighing evi- dence to inform clinical decisions. Ann Intern Med. 2020;172:599-603. [PMID: 32311735] doi:10.7326/M19-1941 Item 8 Answer: D Educational Objective: Treat dyspnea with pulmonary Item 7 Answer: D rehabilitation. Educational Objective: Diagnose sacroiliac joint Pulmonary rehabilitation (Option D) is the most appro- dysfunction. priate treatment. In patients with severe COPD, dyspnea is The most likely diagnosis is sacroiliac joint dysfunction a common problem that requires a multimodal approach (Option D). Sacroiliac joints are true synovial joints between to management. Pulmonary rehabilitation is one of the the sacrum and ilium of the pelvis. The sacroiliac joint may most effective interventions to improve dyspnea, exercise be involved as part of a systemic inflammatory syndrome, capacity, and quality of life in patients with severe COPD. such as spondyloarthritis (particularly ankylosing spondyli- Specifically, pulmonary rehabilitation has been shown to tis) but may also be involved as an isolated musculoskeletal improve fatigue, emotional function, dyspnea, and 6-minute condition. Biomechanical factors that predispose to sacroil- walk distance. In addition, noninvasive measures, such as iac joint injury include repetitive torsional forces or unidi- pursed lip breathing and use of a handheld fan, can improve rectional pelvic shear forces, as might occur with stepping dyspnea in patients already using maximal medical therapy. off a curb. The diagnosis of sacroiliitis in this patient is sup- Studies of guided relaxation training and acupuncture/ ported by the posterior location of his hip pain and a positive acupressure have yielded mixed results, but these therapies FABER (Flexion, ABduction, and External Rotation of the are safe and may be reasonable to consider for patients with hip) test result. This test has a high specificity but low sensi- refractory dyspnea. tivity for sacroiliitis. Therapy for sacroiliitis is similar to that Azithromycin (Option A) and other macrolide anti- for other joint pain and includes rest, anti-inflammatory biotics have been studied in COPD and may be an impor- medications, and possibly physical therapy. tant adjunctive medical therapy in selected populations.

Item 8 Answer: D Educational Objective: Treat dyspnea with pulmonary Item 7 Answer: D rehabilitation. Educational Objective: Diagnose sacroiliac joint Pulmonary rehabilitation (Option D) is the most appro- dysfunction. priate treatment. In patients with severe COPD, dyspnea is The most likely diagnosis is sacroiliac joint dysfunction a common problem that requires a multimodal approach (Option D). Sacroiliac joints are true synovial joints between to management. Pulmonary rehabilitation is one of the the sacrum and ilium of the pelvis. The sacroiliac joint may most effective interventions to improve dyspnea, exercise be involved as part of a systemic inflammatory syndrome, capacity, and quality of life in patients with severe COPD. such as spondyloarthritis (particularly ankylosing spondyli- Specifically, pulmonary rehabilitation has been shown to tis) but may also be involved as an isolated musculoskeletal improve fatigue, emotional function, dyspnea, and 6-minute condition. Biomechanical factors that predispose to sacroil- walk distance. In addition, noninvasive measures, such as iac joint injury include repetitive torsional forces or unidi- pursed lip breathing and use of a handheld fan, can improve rectional pelvic shear forces, as might occur with stepping dyspnea in patients already using maximal medical therapy. off a curb. The diagnosis of sacroiliitis in this patient is sup- Studies of guided relaxation training and acupuncture/ ported by the posterior location of his hip pain and a positive acupressure have yielded mixed results, but these therapies FABER (Flexion, ABduction, and External Rotation of the are safe and may be reasonable to consider for patients with hip) test result. This test has a high specificity but low sensi- refractory dyspnea. tivity for sacroiliitis. Therapy for sacroiliitis is similar to that Azithromycin (Option A) and other macrolide anti- for other joint pain and includes rest, anti-inflammatory biotics have been studied in COPD and may be an impor- medications, and possibly physical therapy. tant adjunctive medical therapy in selected populations. 136

_Answers and Critiques In patients with moderate or severe COPD who experience illness. Once initiated, sertraline should be titrated to effect, frequent COPD exacerbations (more than two exacerbations with close monitoring for adverse effects, such as diarrhea. per year), azithromycin given daily or three times weekly Lorazepam (Option A) is a commonly used benzodiaz- can reduce the frequency of exacerbations and sometimes epine, effective in the treatment of acute anxiety. Although positively affect quality of life. Risks associated with macro- this patient is experiencing symptoms of anxiety, they are lide use include reduced hearing and antibiotic resistance. probably part of his depressive symptom cluster, and an This patient is not a good candidate for macrolide therapy SSRI is the preferred treatment for depressive symptoms in because it would not be expected to improve his dyspnea in a patient with an intermediate life expectancy. the absence of frequent COPD exacerbations. Psychostimulants (dextroamphetamine, methylpheni- Continuous oxygen (Option B) can reduce mortality date [Option B], and pemoline) should be considered in the in patients with severe COPD when they are experienc- treatment of depression at the end of life because they take ing hypoxia. Data from a randomized controlled trial of effect quickly. Terminally ill patients may experience an palliative oxygen versus medical air in normoxic patients improvement in mood and energy within 24 hours of initi- wn @ demonstrated no improvement in quality of life or subjective ating treatment. However, this patient is not at the end of his =

In patients with moderate or severe COPD who experience illness. Once initiated, sertraline should be titrated to effect, frequent COPD exacerbations (more than two exacerbations with close monitoring for adverse effects, such as diarrhea. per year), azithromycin given daily or three times weekly Lorazepam (Option A) is a commonly used benzodiaz- can reduce the frequency of exacerbations and sometimes epine, effective in the treatment of acute anxiety. Although positively affect quality of life. Risks associated with macro- this patient is experiencing symptoms of anxiety, they are lide use include reduced hearing and antibiotic resistance. probably part of his depressive symptom cluster, and an This patient is not a good candidate for macrolide therapy SSRI is the preferred treatment for depressive symptoms in because it would not be expected to improve his dyspnea in a patient with an intermediate life expectancy. the absence of frequent COPD exacerbations. Psychostimulants (dextroamphetamine, methylpheni- Continuous oxygen (Option B) can reduce mortality date [Option B], and pemoline) should be considered in the in patients with severe COPD when they are experienc- treatment of depression at the end of life because they take ing hypoxia. Data from a randomized controlled trial of effect quickly. Terminally ill patients may experience an palliative oxygen versus medical air in normoxic patients improvement in mood and energy within 24 hours of initi- wn @ demonstrated no improvement in quality of life or subjective ating treatment. However, this patient is not at the end of his = dyspnea scores with palliative oxygen therapy, supporting life, and psychostimulants are not indicated for patients with = a prognosis that may extend a few years. Psychostimulants = the hypothesis that movement of air is more important in 's) reducing breathlessness in these patients. This patient is are best reserved for patients who have weeks to live. sc = normoxic, and continuous oxygen therapy is not indicated Olanzapine (Option C) is a second-generation anti- cs wn at this time. psychotic that is often used to treat nausea in patients with Bam @ Nebulized saline (Option C) can be used for secretion advanced cancer. Olanzapine has a diverse neurotransmitter = wn management in patients with sputum production, cough, profile, targeting dopamine, 5-hydroxytryptamine-3, his- < and problematic secretions, but nebulized saline would not taminic, and muscarinic receptors. It is also effective in the <=

dyspnea scores with palliative oxygen therapy, supporting life, and psychostimulants are not indicated for patients with = a prognosis that may extend a few years. Psychostimulants = the hypothesis that movement of air is more important in 's) reducing breathlessness in these patients. This patient is are best reserved for patients who have weeks to live. sc = normoxic, and continuous oxygen therapy is not indicated Olanzapine (Option C) is a second-generation anti- cs wn at this time. psychotic that is often used to treat nausea in patients with Bam @ Nebulized saline (Option C) can be used for secretion advanced cancer. Olanzapine has a diverse neurotransmitter = wn management in patients with sputum production, cough, profile, targeting dopamine, 5-hydroxytryptamine-3, his- < and problematic secretions, but nebulized saline would not taminic, and muscarinic receptors. It is also effective in the <= improve this patient’s dyspnea because it is not caused by treatment of resistant depression as an adjuvant medication problematic sputum production. and may be effective in the treatment of psychotic depres- sion. This patient has not yet tried first-line treatment for depression, and olanzapine would not be the best initial ¢ Pulmonary rehabilitation is one of the most effective agent. interventions to improve dyspnea, exercise capacity, and quality of life in patients with severe COPD. e Although grief and a period of adjustment are common

improve this patient’s dyspnea because it is not caused by treatment of resistant depression as an adjuvant medication problematic sputum production. and may be effective in the treatment of psychotic depres- sion. This patient has not yet tried first-line treatment for depression, and olanzapine would not be the best initial ¢ Pulmonary rehabilitation is one of the most effective agent. interventions to improve dyspnea, exercise capacity, and quality of life in patients with severe COPD. e Although grief and a period of adjustment are common Bibliography in patients diagnosed with serious illness, patients Cornelison SD, Pascual RM. Pulmonary rehabilitation in the management should be monitored for symptoms of clinical depres- of chronic lung disease. Med Clin North Am. 2019;103:577-84. [PMID: sion and treated promptly if they are present. 30955523] doi:10.1016/j.mena.2018.12.015

Bibliography in patients diagnosed with serious illness, patients Cornelison SD, Pascual RM. Pulmonary rehabilitation in the management should be monitored for symptoms of clinical depres- of chronic lung disease. Med Clin North Am. 2019;103:577-84. [PMID: sion and treated promptly if they are present. 30955523] doi:10.1016/j.mena.2018.12.015 Bibliography Swetz KM, Kamal AH. Palliative care. Ann Intern Med. 2018;168:ITC33-48. Item 9 Answer: D [PMID: 29507970] doi:10.7326/AITC201803060 Educational Objective: Treat depression in a patient with advanced illness. Item 10 Answer: A The most appropriate treatment for this patient’s depres- Educational Objective: Treat medically unexplained sion is sertraline (Option D). Although grief and a period of symptoms with cognitive behavioral therapy. adjustment are common for a few days to a few weeks after a cancer diagnosis, this patient shows symptoms of clinical The most appropriate management for this patient with depression, including sleep disruption and persistent feel- medically unexplained symptoms (MUS) is cognitive behav- ings of guilt and burden. Neurovegetative symptoms, such as ioral therapy (Option A). MUS are symptoms that cannot appetite loss and low energy level, are also common in the be attributed to a specific medical cause after a thorough setting of depression, but these symptoms may overlap with medical evaluation. Common symptoms in patients with or be caused in part by the patient’s underlying cancer and/ MUS include fatigue, headache, abdominal pain, musculo- or cancer treatment, making these diagnostic criteria less skeletal pain (back pain, myalgia, arthralgia), dizziness, par- specific in patients with advanced disease. Depression neg- esthesia, generalized weakness, transient edema, insomnia, atively affects quality of life and should be treated promptly dyspnea, chest pain, chronic facial pain, chronic pelvic pain, in patients with serious illness. Sertraline is a selective sero- and chemical sensitivities. The management of MUS focuses tonin reuptake inhibitor (SSRI) that is effective in the treat- on restoring function, decreasing symptom focus, and ment of depression. Sertraline carries less risk for secondary acquiring coping mechanisms rather than abating symp- orthostatic hypotension than other agents and is available toms. It should be made clear to patients that treatment of in a liquid formulation, making it a good option for the MUS will probably not be curative and that symptoms may treatment of depression in patients with advanced serious persist. A therapeutic alliance and a mutually respectful

Bibliography Swetz KM, Kamal AH. Palliative care. Ann Intern Med. 2018;168:ITC33-48. Item 9 Answer: D [PMID: 29507970] doi:10.7326/AITC201803060 Educational Objective: Treat depression in a patient with advanced illness. Item 10 Answer: A The most appropriate treatment for this patient’s depres- Educational Objective: Treat medically unexplained sion is sertraline (Option D). Although grief and a period of symptoms with cognitive behavioral therapy. adjustment are common for a few days to a few weeks after a cancer diagnosis, this patient shows symptoms of clinical The most appropriate management for this patient with depression, including sleep disruption and persistent feel- medically unexplained symptoms (MUS) is cognitive behav- ings of guilt and burden. Neurovegetative symptoms, such as ioral therapy (Option A). MUS are symptoms that cannot appetite loss and low energy level, are also common in the be attributed to a specific medical cause after a thorough setting of depression, but these symptoms may overlap with medical evaluation. Common symptoms in patients with or be caused in part by the patient’s underlying cancer and/ MUS include fatigue, headache, abdominal pain, musculo- or cancer treatment, making these diagnostic criteria less skeletal pain (back pain, myalgia, arthralgia), dizziness, par- specific in patients with advanced disease. Depression neg- esthesia, generalized weakness, transient edema, insomnia, atively affects quality of life and should be treated promptly dyspnea, chest pain, chronic facial pain, chronic pelvic pain, in patients with serious illness. Sertraline is a selective sero- and chemical sensitivities. The management of MUS focuses tonin reuptake inhibitor (SSRI) that is effective in the treat- on restoring function, decreasing symptom focus, and ment of depression. Sertraline carries less risk for secondary acquiring coping mechanisms rather than abating symp- orthostatic hypotension than other agents and is available toms. It should be made clear to patients that treatment of in a liquid formulation, making it a good option for the MUS will probably not be curative and that symptoms may treatment of depression in patients with advanced serious persist. A therapeutic alliance and a mutually respectful 137

ities LidlssMnles, physician-patient relationship are key features in the suc- Treatment. Combination NRT, which includes short-acting cessful management of the patient with MUS. In keeping (e.g., nicotine inhaler) and long-acting (e.g., nicotine patch) with a patient-centered approach, the patient should be forms, is more effective than nicotine replacement mono- engaged fully in the plan, focusing on physical, psycho- therapy and is recommended by the ACC as first-line ther- logical, and social aspects of health. Nonpharmacologic apy for hospitalized patients with ACS to decrease nicotine interventions, including cognitive behavioral therapy, phys- cravings. At the time of hospital discharge, either combi- ical therapy, occupational therapy, individual or group psy- nation NRT or varenicline is recommended; however, the chotherapy, social support, biofeedback therapy, graded ACC Expert Pathway notes that some committee members exercise therapy, stress management activities, and training would initiate either varenicline or combination NRT during in coping mechanisms, are the cornerstone of treatment. hospitalization. Combining behavioral counseling with Rather than pursuing further costly, low-value diagnos- pharmacotherapy is more effective than either modality tic evaluations, it may be more beneficial and value-driven alone. Effective counseling and behavioral resources include = to assess and treat any potential underlying psychological problem-solving guidance (such as developing a quit plan = wa symptoms and to educate patients with MUS on successful and overcoming barriers), motivational interviewing, social = coping skills based on the personal impact of their symp- support, and telephone quit lines. oO = wn toms. As such, ordering more advanced imaging, such as Bupropion (Option A) is a norepinephrine and dopa- *) MRI of the spine (Option B), or adding new tests, such as mine reuptake inhibitor with nicotinic receptor activity. = a. urine and plasma porphyrin measurement (Option D), is Evidence is clear that it enhances smoking cessation rates, oO me unlikely to be helpful and may perpetuate the symptom but bupropion is probably less effective than varenicline and =. complex. & equivalent to nicotine replacement monotherapy. The ACC = Oxycodone (Option C) is an inappropriate intervention recommends bupropion as third-line therapy for patients @o A] for this patient. Opioids introduce the potential of harm hospitalized with ACS. without corresponding benefit. Opioids are not well suited The nicotine patch (Option B) has efficacy similar to for the management of neuropathic pain syndromes and that of bupropion for tobacco cessation. For patients with are associated with the potential for overuse, overdose, and ACS, the ACC recommends a nicotine patch at the time of addiction. hospital discharge as a second-line therapy behind either combination NRT or varenicline. Nortriptyline (Option C) is not FDA approved for smok- e A therapeutic alliance and a mutually respectful ing cessation, and there are few data on its use in patients physician-patient relationship are key features in the with cardiovascular disease. It is a suggested third-line ther- successful management of the patient with medically apy for patients with stable coronary artery disease but is not unexplained symptoms. recommended for hospitalized patients with ACS.

physician-patient relationship are key features in the suc- Treatment. Combination NRT, which includes short-acting cessful management of the patient with MUS. In keeping (e.g., nicotine inhaler) and long-acting (e.g., nicotine patch) with a patient-centered approach, the patient should be forms, is more effective than nicotine replacement mono- engaged fully in the plan, focusing on physical, psycho- therapy and is recommended by the ACC as first-line ther- logical, and social aspects of health. Nonpharmacologic apy for hospitalized patients with ACS to decrease nicotine interventions, including cognitive behavioral therapy, phys- cravings. At the time of hospital discharge, either combi- ical therapy, occupational therapy, individual or group psy- nation NRT or varenicline is recommended; however, the chotherapy, social support, biofeedback therapy, graded ACC Expert Pathway notes that some committee members exercise therapy, stress management activities, and training would initiate either varenicline or combination NRT during in coping mechanisms, are the cornerstone of treatment. hospitalization. Combining behavioral counseling with Rather than pursuing further costly, low-value diagnos- pharmacotherapy is more effective than either modality tic evaluations, it may be more beneficial and value-driven alone. Effective counseling and behavioral resources include = to assess and treat any potential underlying psychological problem-solving guidance (such as developing a quit plan = wa symptoms and to educate patients with MUS on successful and overcoming barriers), motivational interviewing, social = coping skills based on the personal impact of their symp- support, and telephone quit lines. oO = wn toms. As such, ordering more advanced imaging, such as Bupropion (Option A) is a norepinephrine and dopa- *) MRI of the spine (Option B), or adding new tests, such as mine reuptake inhibitor with nicotinic receptor activity. = a. urine and plasma porphyrin measurement (Option D), is Evidence is clear that it enhances smoking cessation rates, oO me unlikely to be helpful and may perpetuate the symptom but bupropion is probably less effective than varenicline and =. complex. & equivalent to nicotine replacement monotherapy. The ACC = Oxycodone (Option C) is an inappropriate intervention recommends bupropion as third-line therapy for patients @o A] for this patient. Opioids introduce the potential of harm hospitalized with ACS. without corresponding benefit. Opioids are not well suited The nicotine patch (Option B) has efficacy similar to for the management of neuropathic pain syndromes and that of bupropion for tobacco cessation. For patients with are associated with the potential for overuse, overdose, and ACS, the ACC recommends a nicotine patch at the time of addiction. hospital discharge as a second-line therapy behind either combination NRT or varenicline. Nortriptyline (Option C) is not FDA approved for smok- e A therapeutic alliance and a mutually respectful ing cessation, and there are few data on its use in patients physician-patient relationship are key features in the with cardiovascular disease. It is a suggested third-line ther- successful management of the patient with medically apy for patients with stable coronary artery disease but is not unexplained symptoms. recommended for hospitalized patients with ACS. ¢ Nonpharmacologic interventions for medically unex- plained symptoms include cognitive behavioral therapy, ¢ Varenicline or combination nicotine replacement among many other options. therapy is the most appropriate treatment for hospi- talized patients with acute coronary syndrome. Bibliography Olde Hartman TC, Rosendal M, Aamland A, et al. What do guidelines and systematic reviews tell us about the management of medically unex- Bibliography plained symptoms in primary care? BJGP Open. 2017;1:bjgpopen Barua RS, Rigotti NA, Benowitz NL, et al. 2018 ACC expert consensus decision 17X101061. [PMID: 30564678] doi:10.3399/bjgpopen17X101061 pathway on tobacco cessation treatment: a report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol. 2018;72:3332-65. [PMID: 30527452] doi:10.1016/j.jacc. 2018.10.027 Item 11 Answer: D Educational Objective: Treat nicotine dependence in a patient hospitalized with acute coronary syndrome. item 12 Answer: A Educational Objective: Treat insomnia in an elderly Varenicline (Option D) or combination nicotine replacement patient. therapy (NRT) is the most appropriate treatment for this hospitalized patient with acute coronary syndrome (ACS). Cognitive behavioral therapy for insomnia (CBT-I) (Option Varenicline is a partial nicotinic receptor agonist that has A) is the best treatment option for this patient with prob- been shown to be more effective as monotherapy for tobacco lematic sleep-onset insomnia, characterized by difficulty cessation than either bupropion or nicotine replacement falling asleep. Decreased total sleep time, decreased rapid monotherapy. In addition, it is not associated with increased eye movement (REM) latency, reduced sleep efficiency, risk for cardiovascular events. Varenicline is one of two and earlier morning awakening are common physiologic first-line treatments recommended for hospitalized patients changes to the sleep cycle in older adults. Initial evaluation with ACS by the 2018 American College of Cardiology (ACC) of insomnia should consist of a thorough history and review Expert Consensus Decision Pathway on Tobacco Cessation of sleep hygiene. CBT-I is considered first-line treatment in

¢ Nonpharmacologic interventions for medically unex- plained symptoms include cognitive behavioral therapy, ¢ Varenicline or combination nicotine replacement among many other options. therapy is the most appropriate treatment for hospi- talized patients with acute coronary syndrome. Bibliography Olde Hartman TC, Rosendal M, Aamland A, et al. What do guidelines and systematic reviews tell us about the management of medically unex- Bibliography plained symptoms in primary care? BJGP Open. 2017;1:bjgpopen Barua RS, Rigotti NA, Benowitz NL, et al. 2018 ACC expert consensus decision 17X101061. [PMID: 30564678] doi:10.3399/bjgpopen17X101061 pathway on tobacco cessation treatment: a report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol. 2018;72:3332-65. [PMID: 30527452] doi:10.1016/j.jacc. 2018.10.027 Item 11 Answer: D Educational Objective: Treat nicotine dependence in a patient hospitalized with acute coronary syndrome. item 12 Answer: A Educational Objective: Treat insomnia in an elderly Varenicline (Option D) or combination nicotine replacement patient. therapy (NRT) is the most appropriate treatment for this hospitalized patient with acute coronary syndrome (ACS). Cognitive behavioral therapy for insomnia (CBT-I) (Option Varenicline is a partial nicotinic receptor agonist that has A) is the best treatment option for this patient with prob- been shown to be more effective as monotherapy for tobacco lematic sleep-onset insomnia, characterized by difficulty cessation than either bupropion or nicotine replacement falling asleep. Decreased total sleep time, decreased rapid monotherapy. In addition, it is not associated with increased eye movement (REM) latency, reduced sleep efficiency, risk for cardiovascular events. Varenicline is one of two and earlier morning awakening are common physiologic first-line treatments recommended for hospitalized patients changes to the sleep cycle in older adults. Initial evaluation with ACS by the 2018 American College of Cardiology (ACC) of insomnia should consist of a thorough history and review Expert Consensus Decision Pathway on Tobacco Cessation of sleep hygiene. CBT-I is considered first-line treatment in 138

tat i all adults, including the geriatric population. Therapy can as psychotherapy, is a candidate for intranasal esketamine. be individual, group, or internet based. There is a lack of Intranasal esketamine is approved as an adjunct to oral anti- evidence for or against any of these modes of CBT-I delivery depressant agents for treatment-resistant major depressive as being the most effective. An abbreviated version of CBT-I, disorder and major depressive disorder with suicidal ide- brief behavioral treatment for insomnia (BBT-I), focuses on ation. Esketamine is a glutamate receptor modulator, which the behavioral components of sleep restriction, stimulus offers a novel mechanism of action for depression treatment. control, and sleep hygiene only. BBT-I also has been shown to Unlike most other antidepressant therapies, treatment effect be effective in the treatment of chronic insomnia. In general, is almost immediate; however, there are several barriers to its pharmacotherapy for sleep should be pursued only after use. Labeling indications restrict the drug to patients whose shared decision making between the physician and patient. symptoms have failed to respond to two courses of appropri- Diphenhydramine (Option B) is an over-the-counter, ately prescribed antidepressant therapy, and patients cannot first-generation antihistamine with sedative-hypnotic drive or operate machinery for 24 hours after administration. effects. It can cause anticholinergic side effects that are espe- Esketamine must be administered intranasally in a physi- ” a cially concerning in older patients. The 2019 Beers Criteria cian’s office under direct supervision, and physicians must be =]

all adults, including the geriatric population. Therapy can as psychotherapy, is a candidate for intranasal esketamine. be individual, group, or internet based. There is a lack of Intranasal esketamine is approved as an adjunct to oral anti- evidence for or against any of these modes of CBT-I delivery depressant agents for treatment-resistant major depressive as being the most effective. An abbreviated version of CBT-I, disorder and major depressive disorder with suicidal ide- brief behavioral treatment for insomnia (BBT-I), focuses on ation. Esketamine is a glutamate receptor modulator, which the behavioral components of sleep restriction, stimulus offers a novel mechanism of action for depression treatment. control, and sleep hygiene only. BBT-I also has been shown to Unlike most other antidepressant therapies, treatment effect be effective in the treatment of chronic insomnia. In general, is almost immediate; however, there are several barriers to its pharmacotherapy for sleep should be pursued only after use. Labeling indications restrict the drug to patients whose shared decision making between the physician and patient. symptoms have failed to respond to two courses of appropri- Diphenhydramine (Option B) is an over-the-counter, ately prescribed antidepressant therapy, and patients cannot first-generation antihistamine with sedative-hypnotic drive or operate machinery for 24 hours after administration. effects. It can cause anticholinergic side effects that are espe- Esketamine must be administered intranasally in a physi- ” a cially concerning in older patients. The 2019 Beers Criteria cian’s office under direct supervision, and physicians must be =] for Potentially Inappropriate Medication Use in Older Adults enrolled in an FDA-mandated Risk Evaluation and Mitigation aoe from the American Geriatrics Society recommends avoid- Strategies (REMS) program. Esketamine carries a black box = oO ance of diphenhydramine in elderly patients such as this warning for dissociation, sedation, and suicidal thoughts. The sc = one, except in the acute treatment of severe allergic reaction. cost of the month-long induction is very expensive. ce

for Potentially Inappropriate Medication Use in Older Adults enrolled in an FDA-mandated Risk Evaluation and Mitigation aoe from the American Geriatrics Society recommends avoid- Strategies (REMS) program. Esketamine carries a black box = oO ance of diphenhydramine in elderly patients such as this warning for dissociation, sedation, and suicidal thoughts. The sc = one, except in the acute treatment of severe allergic reaction. cost of the month-long induction is very expensive. ce Gabapentin (Option C) should generally be avoided in Lithium (Option B) is indicated for the treatment of = o geriatric populations owing to increased risk for sedation. bipolar 1 disorder and schizoaffective disorder. It is not an = 2] Use of gabapentinoids is sometimes acceptable in an older approved therapy for major depressive disorder. This patient S patient transitioning off opioid treatment for pain. Gabapen- reports no symptoms of mania that would justify the use of 4

Gabapentin (Option C) should generally be avoided in Lithium (Option B) is indicated for the treatment of = o geriatric populations owing to increased risk for sedation. bipolar 1 disorder and schizoaffective disorder. It is not an = 2] Use of gabapentinoids is sometimes acceptable in an older approved therapy for major depressive disorder. This patient S patient transitioning off opioid treatment for pain. Gabapen- reports no symptoms of mania that would justify the use of 4 tin is not approved for the treatment of insomnia. this therapy. Melatonin (Option D) is an over-the-counter sleep aid. It Risperidone (Option C), an antipsychotic agent, is not is often tried by patients and recommended by clinicians, but indicated for the treatment of major depressive disorder. no conclusive evidence supports its effectiveness for sleep-on- However, the addition of other antipsychotic medications set insomnia. Evidence shows an approximately 7-minute to SGAs is an appropriate strategy for treatment failure. decrease in sleep latency, an 8-minute increase in total sleep Approved regimens include olanzapine plus fluoxetine, and time, and a very small improvement in sleep quality. aripiprazole or quetiapine plus any SGA. Pramipexole (Option E) can be used for restless legs Selective serotonin reuptake inhibitors (SSRIs) are one syndrome (RLS) when nonpharmacologic treatments and of four classes of SGAs considered first-line therapy for major iron deficiency correction are ineffective. RLS is a movement depressive disorder. Other SGAs include serotonin-norepi- disorder characterized by an uncomfortable urge to move nephrine reuptake inhibitors, serotonin modulators, and the legs and is transiently relieved by movement. RLS is atypical antidepressants. Sertraline (Option D) is an SSRI. worse at rest and at night and may prevent sleep or interrupt This patient’s symptoms have already failed to respond to sleep. This patient does not have symptoms consistent with treatment with one SSRI (fluoxetine) at maximum doses. In RLS, and pramipexole should not be used for management addition, the sexual side effects he experienced can occur of insomnia in patients who do not have RLS. with all SSRIs and are likely to recur with sertraline; there- fore, this drug is not a good option for the patient.

tin is not approved for the treatment of insomnia. this therapy. Melatonin (Option D) is an over-the-counter sleep aid. It Risperidone (Option C), an antipsychotic agent, is not is often tried by patients and recommended by clinicians, but indicated for the treatment of major depressive disorder. no conclusive evidence supports its effectiveness for sleep-on- However, the addition of other antipsychotic medications set insomnia. Evidence shows an approximately 7-minute to SGAs is an appropriate strategy for treatment failure. decrease in sleep latency, an 8-minute increase in total sleep Approved regimens include olanzapine plus fluoxetine, and time, and a very small improvement in sleep quality. aripiprazole or quetiapine plus any SGA. Pramipexole (Option E) can be used for restless legs Selective serotonin reuptake inhibitors (SSRIs) are one syndrome (RLS) when nonpharmacologic treatments and of four classes of SGAs considered first-line therapy for major iron deficiency correction are ineffective. RLS is a movement depressive disorder. Other SGAs include serotonin-norepi- disorder characterized by an uncomfortable urge to move nephrine reuptake inhibitors, serotonin modulators, and the legs and is transiently relieved by movement. RLS is atypical antidepressants. Sertraline (Option D) is an SSRI. worse at rest and at night and may prevent sleep or interrupt This patient’s symptoms have already failed to respond to sleep. This patient does not have symptoms consistent with treatment with one SSRI (fluoxetine) at maximum doses. In RLS, and pramipexole should not be used for management addition, the sexual side effects he experienced can occur of insomnia in patients who do not have RLS. with all SSRIs and are likely to recur with sertraline; there- fore, this drug is not a good option for the patient. ¢ Cognitive behavioral therapy for insomnia is first-line treatment in all adults with chronic insomnia, including e Intranasal esketamine can be added to oral antidepressant the geriatric population. agents for treatment-resistant major depressive disorder.

¢ Cognitive behavioral therapy for insomnia is first-line treatment in all adults with chronic insomnia, including e Intranasal esketamine can be added to oral antidepressant the geriatric population. agents for treatment-resistant major depressive disorder. ¢ Unlike most other antidepressant therapies, esketamine Bibliography has an almost immediate effect on depression symptoms. Patel D, Steinberg J, Patel P. Insomnia in the elderly: a review. J Clin Sleep Med. 2018;14:1017-24. [PMID: 29852897] doi:10.5664/jcsm.7172 Bibliography Daly EJ, Singh JB, Fedgchin M, et al. Efficacy and safety of intranasal esketa- mine adjunctive to oral antidepressant therapy in treatment-resistant Item 13 Answer: A depression: a randomized clinical trial. JAMA Psychiatry. 2018;75:139-48. [PMID: 29282469] doi:10.1001/jamapsychiatry.2017.3739 Educational Objective: Treat resistant depression with esketamine. The most appropriate treatment is the addition of intra- Item 14 Answer: B nasal esketamine (Option A). This patient, who has severe Educational Objective: Manage high-risk syncope. major depressive disorder that is unresponsive to maxi- mal combination oral therapy with a second-generation this patient with syncope and features suggestive of aortic antidepressant (SGA) and an antipsychotic agent as well Stenosis should undergo inpatient cardiac monitoring and 139

Answers and Critiques evaluation (Option B). In patients with syncope, the pres- Item 15 Answer: D ence of high-risk clinical characteristics should prompt CONT. Educational Objective: Screen for cognitive impairment consideration of hospitalization. This patient has sev- in an elderly patient. eral risk factors that are associated with a higher 30-day mortality rate (male sex, age >60 years, no syncopal pro- This older patient has symptoms suggestive of cognitive drome, concern for structural heart disease based on impairment and should be tested using a screening clinical examination findings, and syncope during exer- instrument, such as the Mini-Cog (Option D). Cogni- tion). Other symptoms or findings on the history and tive impairment, defined as a progressive decline in at physical examination that indicate a need for inpatient least two cognitive domains (memory, attention, lan- evaluation include cardiac arrhythmias (sustained or symp- guage, visuospatial function, and executive function) tomatic ventricular tachycardia); symptomatic or high- that negatively affects patient functioning, is increas- risk bradycardia or heart block; pacemaker/implantable ingly common with older age. Cognitive impairment

evaluation (Option B). In patients with syncope, the pres- Item 15 Answer: D ence of high-risk clinical characteristics should prompt CONT. Educational Objective: Screen for cognitive impairment consideration of hospitalization. This patient has sev- in an elderly patient. eral risk factors that are associated with a higher 30-day mortality rate (male sex, age >60 years, no syncopal pro- This older patient has symptoms suggestive of cognitive drome, concern for structural heart disease based on impairment and should be tested using a screening clinical examination findings, and syncope during exer- instrument, such as the Mini-Cog (Option D). Cogni- tion). Other symptoms or findings on the history and tive impairment, defined as a progressive decline in at physical examination that indicate a need for inpatient least two cognitive domains (memory, attention, lan- evaluation include cardiac arrhythmias (sustained or symp- guage, visuospatial function, and executive function) tomatic ventricular tachycardia); symptomatic or high- that negatively affects patient functioning, is increas- risk bradycardia or heart block; pacemaker/implantable ingly common with older age. Cognitive impairment > cardioverter-defibrillator malfunction; other structural is associated with increased risk for falls and loss of J n heart abnormalities, such as hypertrophic cardiomyopa- independence and is a barrier to appropriate control = thy; or severe anemia. of chronic medical conditions. Screening for cognitive @ = wn When cardiac syncope is suspected, the evaluation impairment is an important component of comprehen- Qe sive geriatric assessment. Objective in-office screening = should be tailored to the specific concern. Electrophysiology a. consultation can be useful for suspected arrhythmias. For should be performed when patients or family members a patients with exertional syncope, cardiac stress testing may report symptoms concerning for cognitive impairment. = = help to evaluate for ischemia. In this case, echocardiography The Mini-Cog, which consists of a three-item recall test 2 = is warranted to evaluate for severe aortic stenosis, given the followed by a clock-drawing test if three-item recall is @o 72) history of a syncopal event and the physical examination abnormal, has appropriate test characteristics to reli- findings (late-peaking systolic murmur heard best at the ably identify cognitive impairment. On the basis of this right upper sternal border). patient’s symptoms, it is most appropriate to perform

> cardioverter-defibrillator malfunction; other structural is associated with increased risk for falls and loss of J n heart abnormalities, such as hypertrophic cardiomyopa- independence and is a barrier to appropriate control = thy; or severe anemia. of chronic medical conditions. Screening for cognitive @ = wn When cardiac syncope is suspected, the evaluation impairment is an important component of comprehen- Qe sive geriatric assessment. Objective in-office screening = should be tailored to the specific concern. Electrophysiology a. consultation can be useful for suspected arrhythmias. For should be performed when patients or family members a patients with exertional syncope, cardiac stress testing may report symptoms concerning for cognitive impairment. = = help to evaluate for ischemia. In this case, echocardiography The Mini-Cog, which consists of a three-item recall test 2 = is warranted to evaluate for severe aortic stenosis, given the followed by a clock-drawing test if three-item recall is @o 72) history of a syncopal event and the physical examination abnormal, has appropriate test characteristics to reli- findings (late-peaking systolic murmur heard best at the ably identify cognitive impairment. On the basis of this right upper sternal border). patient’s symptoms, it is most appropriate to perform Extended outpatient cardiac monitoring with an Mini-Cog testing.

> cardioverter-defibrillator malfunction; other structural is associated with increased risk for falls and loss of J n heart abnormalities, such as hypertrophic cardiomyopa- independence and is a barrier to appropriate control = thy; or severe anemia. of chronic medical conditions. Screening for cognitive @ = wn When cardiac syncope is suspected, the evaluation impairment is an important component of comprehen- Qe sive geriatric assessment. Objective in-office screening = should be tailored to the specific concern. Electrophysiology a. consultation can be useful for suspected arrhythmias. For should be performed when patients or family members a patients with exertional syncope, cardiac stress testing may report symptoms concerning for cognitive impairment. = = help to evaluate for ischemia. In this case, echocardiography The Mini-Cog, which consists of a three-item recall test 2 = is warranted to evaluate for severe aortic stenosis, given the followed by a clock-drawing test if three-item recall is @o 72) history of a syncopal event and the physical examination abnormal, has appropriate test characteristics to reli- findings (late-peaking systolic murmur heard best at the ably identify cognitive impairment. On the basis of this right upper sternal border). patient’s symptoms, it is most appropriate to perform Extended outpatient cardiac monitoring with an Mini-Cog testing. ambulatory ECG monitor (Option A) or an implantable A major risk factor for Alzheimer disease is the presence loop recorder is appropriate for individuals with syncope of the apolipoprotein-E ¢4 (ApoE-e4) allele. However, genetic of probable arrhythmic origin who do not have high-risk testing (Option A) is not recommended in the diagnostic features. Patients with intermediate-risk syncope (stable evaluation of dementia, and testing for specific causes of structural heart disease with no family history of sudden dementia is not indicated until the presence of cognitive cardiac death) may benefit from extended monitoring in an impairment is established.

ambulatory ECG monitor (Option A) or an implantable A major risk factor for Alzheimer disease is the presence loop recorder is appropriate for individuals with syncope of the apolipoprotein-E ¢4 (ApoE-e4) allele. However, genetic of probable arrhythmic origin who do not have high-risk testing (Option A) is not recommended in the diagnostic features. Patients with intermediate-risk syncope (stable evaluation of dementia, and testing for specific causes of structural heart disease with no family history of sudden dementia is not indicated until the presence of cognitive cardiac death) may benefit from extended monitoring in an impairment is established. observation unit if one is available. Noncontrast MRI of the brain is preferred to CT of the Tilt-table testing (Option C) is primarily used with sus- head (Option B) in the evaluation of cognitive impairment. pected vasovagal syndrome. It can also be helpful when Before obtaining neuroimaging, the diagnosis of dementia orthostatic hypotension is suspected but the evaluation should be established, and the initial step is an office-based is inconclusive. Tilt-table testing is not indicated for this cognitive assessment. patient. Advanced neuroimaging is helpful in the assessment of Reassurance and discharge home (Option D) are cognitive impairment. When neuroimaging is performed, appropriate when a benign cause of syncope, such as neu- noncontrast MRI of the brain is preferred. When the MRI is rally mediated syncope, is suspected. Neurally mediated normal and the diagnosis is in question, or a non-Alzheimer syncope occurs most commonly in younger individuals disease process is being considered, functional brain scans, and is associated with a prodrome of symptoms that may such as fluorodeoxyglucose PET (Option C), can be used to include nausea and diaphoresis. Patients with neurally evaluate for specific patterns of decreased brain function. mediated syncope can receive a limited evaluation, includ- However, this patient first requires documentation of cog- ing physical examination and ECG; all findings are typically nitive impairment before either MRI or functional PET is normal. obtained.

observation unit if one is available. Noncontrast MRI of the brain is preferred to CT of the Tilt-table testing (Option C) is primarily used with sus- head (Option B) in the evaluation of cognitive impairment. pected vasovagal syndrome. It can also be helpful when Before obtaining neuroimaging, the diagnosis of dementia orthostatic hypotension is suspected but the evaluation should be established, and the initial step is an office-based is inconclusive. Tilt-table testing is not indicated for this cognitive assessment. patient. Advanced neuroimaging is helpful in the assessment of Reassurance and discharge home (Option D) are cognitive impairment. When neuroimaging is performed, appropriate when a benign cause of syncope, such as neu- noncontrast MRI of the brain is preferred. When the MRI is rally mediated syncope, is suspected. Neurally mediated normal and the diagnosis is in question, or a non-Alzheimer syncope occurs most commonly in younger individuals disease process is being considered, functional brain scans, and is associated with a prodrome of symptoms that may such as fluorodeoxyglucose PET (Option C), can be used to include nausea and diaphoresis. Patients with neurally evaluate for specific patterns of decreased brain function. mediated syncope can receive a limited evaluation, includ- However, this patient first requires documentation of cog- ing physical examination and ECG; all findings are typically nitive impairment before either MRI or functional PET is normal. obtained. ¢ Patients with syncope and high-risk clinical charac- ¢ Objective in-office evaluation for cognitive impairment teristics should be considered for hospitalization and should be performed when patients or their family inpatient monitoring. members report concerning symptoms, such as con- fusion, forgetfulness, and memory impairment. Bibliography Shen WK, Sheldon RS, Benditt DG, et al. 2017 ACC/AHA/HRS guideline for the evaluation and management of patients with syncope: executive Bibliography summary: a report of the American College of Cardiology/American Seematter-Bagnoud L, Biila C. Brief assessments and screening for geriat- Heart Association Task Force on Clinical Practice Guidelines and the ric conditions in older primary care patients: a pragmatic approach. Heart Rhythm Society. Circulation. 2017;136:e25-59. [PMID: 28280232] Public Health Rev. 2018;39:8. [PMID: 29744236] doi:10.1186/s40985- doi:10.1161/CIR.0000000000000498 018-0086-7

¢ Patients with syncope and high-risk clinical charac- ¢ Objective in-office evaluation for cognitive impairment teristics should be considered for hospitalization and should be performed when patients or their family inpatient monitoring. members report concerning symptoms, such as con- fusion, forgetfulness, and memory impairment. Bibliography Shen WK, Sheldon RS, Benditt DG, et al. 2017 ACC/AHA/HRS guideline for the evaluation and management of patients with syncope: executive Bibliography summary: a report of the American College of Cardiology/American Seematter-Bagnoud L, Biila C. Brief assessments and screening for geriat- Heart Association Task Force on Clinical Practice Guidelines and the ric conditions in older primary care patients: a pragmatic approach. Heart Rhythm Society. Circulation. 2017;136:e25-59. [PMID: 28280232] Public Health Rev. 2018;39:8. [PMID: 29744236] doi:10.1186/s40985- doi:10.1161/CIR.0000000000000498 018-0086-7 140

Item 16 Answer: 8B and examination findings concerning for vertebrobasilar stroke. About 20% of patients with vertebrobasilar stroke Educational Objective: Diagnose bunion. present with isolated vertigo, and these symptoms can be The most likely diagnosis is a bunion (Option B). A bunion is misclassified as peripheral vertigo. Clues to the diagnosis a valgus malformation of the great toe that may result in pain are the patient’s advanced age, vascular disease risk fac- and disability. The cause is unknown but has been attributed tors, and constant vertigo. An abnormal result on any one to wearing shoes with a narrow toe box; however, it can occur of the three HINTS (Head Impulse, Nystagmus, and Test of in patients who do not customarily wear such shoes. Bunion is Skew) examination components suggests a central rather diagnosed by inspection of the foot that demonstrates lateral than peripheral cause of acute vertigo; this patient demon- deviation of the toe at the first metatarsal phalangeal (MTP) strated vertical skew. Patients with central vertigo secondary joint. In some cases, erythema of the joint is observed. A bun- to vertebrobasilar stroke frequently, but not invariably, dis- ion deformity can be associated with several painful compli- play neurologic findings in addition to vertigo, such as this cations involving the first MTP joint. The most common cause patient’s ataxia and postural instability. Urgent brain MRI w AF) of pain is bursitis medial to the MTP joint. Other sources of would confirm the diagnosis. For acute stroke, either non =

Item 16 Answer: 8B and examination findings concerning for vertebrobasilar stroke. About 20% of patients with vertebrobasilar stroke Educational Objective: Diagnose bunion. present with isolated vertigo, and these symptoms can be The most likely diagnosis is a bunion (Option B). A bunion is misclassified as peripheral vertigo. Clues to the diagnosis a valgus malformation of the great toe that may result in pain are the patient’s advanced age, vascular disease risk fac- and disability. The cause is unknown but has been attributed tors, and constant vertigo. An abnormal result on any one to wearing shoes with a narrow toe box; however, it can occur of the three HINTS (Head Impulse, Nystagmus, and Test of in patients who do not customarily wear such shoes. Bunion is Skew) examination components suggests a central rather diagnosed by inspection of the foot that demonstrates lateral than peripheral cause of acute vertigo; this patient demon- deviation of the toe at the first metatarsal phalangeal (MTP) strated vertical skew. Patients with central vertigo secondary joint. In some cases, erythema of the joint is observed. A bun- to vertebrobasilar stroke frequently, but not invariably, dis- ion deformity can be associated with several painful compli- play neurologic findings in addition to vertigo, such as this cations involving the first MTP joint. The most common cause patient’s ataxia and postural instability. Urgent brain MRI w AF) of pain is bursitis medial to the MTP joint. Other sources of would confirm the diagnosis. For acute stroke, either non = pain may include entrapment of the dorsal cutaneous nerve, contrast CT or MRI is recommended to exclude hemorrhage = hod

Item 16 Answer: 8B and examination findings concerning for vertebrobasilar stroke. About 20% of patients with vertebrobasilar stroke Educational Objective: Diagnose bunion. present with isolated vertigo, and these symptoms can be The most likely diagnosis is a bunion (Option B). A bunion is misclassified as peripheral vertigo. Clues to the diagnosis a valgus malformation of the great toe that may result in pain are the patient’s advanced age, vascular disease risk fac- and disability. The cause is unknown but has been attributed tors, and constant vertigo. An abnormal result on any one to wearing shoes with a narrow toe box; however, it can occur of the three HINTS (Head Impulse, Nystagmus, and Test of in patients who do not customarily wear such shoes. Bunion is Skew) examination components suggests a central rather diagnosed by inspection of the foot that demonstrates lateral than peripheral cause of acute vertigo; this patient demon- deviation of the toe at the first metatarsal phalangeal (MTP) strated vertical skew. Patients with central vertigo secondary joint. In some cases, erythema of the joint is observed. A bun- to vertebrobasilar stroke frequently, but not invariably, dis- ion deformity can be associated with several painful compli- play neurologic findings in addition to vertigo, such as this cations involving the first MTP joint. The most common cause patient’s ataxia and postural instability. Urgent brain MRI w AF) of pain is bursitis medial to the MTP joint. Other sources of would confirm the diagnosis. For acute stroke, either non = pain may include entrapment of the dorsal cutaneous nerve, contrast CT or MRI is recommended to exclude hemorrhage = hod synovitis, and generalized metatarsalgia as the patient shifts = before administration of alteplase. However, this patient has (=) the distribution of pressure away from the great toe while exceeded the 3-hour window for thrombolytic therapy, and Ss = walking. Radiography is not necessary for the diagnosis of hemorrhagic stroke in the territory of the posterior circula- Li]

synovitis, and generalized metatarsalgia as the patient shifts = before administration of alteplase. However, this patient has (=) the distribution of pressure away from the great toe while exceeded the 3-hour window for thrombolytic therapy, and Ss = walking. Radiography is not necessary for the diagnosis of hemorrhagic stroke in the territory of the posterior circula- Li] bunion but may be needed to assess for underlying articular tion is an unlikely cause of persistent and isolated vertigo. wn Ben wo damage. Conservative treatment includes orthotic devices, MRI is more sensitive than CT in the diagnosis of ischemic = wearing toe separators at night, and analgesics. The evidence stroke and is the preferred imaging test in this situation. wn = supporting the efficacy of these measures is sparse. In some Audiometry (Option A) would be important to obtain <x

bunion but may be needed to assess for underlying articular tion is an unlikely cause of persistent and isolated vertigo. wn Ben wo damage. Conservative treatment includes orthotic devices, MRI is more sensitive than CT in the diagnosis of ischemic = wearing toe separators at night, and analgesics. The evidence stroke and is the preferred imaging test in this situation. wn = supporting the efficacy of these measures is sparse. In some Audiometry (Option A) would be important to obtain <x cases of severe pain and disability, surgery may be beneficial. if Meniere disease were suspected in order to document Osteochondritis of the metatarsal head of the second, sensorineural hearing loss, but Meniere disease is unlikely third, or fourth MTP joints leading to avascular necrosis (Option to present with acute vertigo. Initial symptoms of Meniere A) is known as Freiberg infraction. It presents as plantar pain in disease are typically peripheral vertigo with hearing loss and the region of the affected metatarsal head. Patients may indicate tinnitus, making it unlikely in this patient. that it feels like walking with a pebble in the shoe. It is not asso- A canalith repositioning maneuver (Option B) would ciated with pain and deformity of the first MTP joint. be effective for benign paroxysmal positional vertigo, char- Morton neuroma (Option C) most commonly affects the acterized by sudden-onset, short-lasting peripheral ver- second or third interdigital web spaces. It is associated with tigo occurring with abrupt head movement. This patient's localized pain and also with the sensation of walking on a constant central vertigo symptoms are not consistent with pebble. On examination, there are usually no obvious abnor- benign paroxysmal positional vertigo. malities, but some patients may have tenderness to direct Meclizine (Option C) may offer some symptom relief in palpation of the involved interspace. It is not associated with the setting of motion sickness and Meniere disease. It has no valgus deformity or MTP joint inflammation. role in the treatment of central vertigo. Stress fractures (Option D) are associated with localized Vestibular and balance rehabilitation (Option E) can be pain but are not associated with joint deformity or inflam- useful for persistent vertiginous symptoms, but it would not mation. aid in the diagnosis or acute management of this patient.

cases of severe pain and disability, surgery may be beneficial. if Meniere disease were suspected in order to document Osteochondritis of the metatarsal head of the second, sensorineural hearing loss, but Meniere disease is unlikely third, or fourth MTP joints leading to avascular necrosis (Option to present with acute vertigo. Initial symptoms of Meniere A) is known as Freiberg infraction. It presents as plantar pain in disease are typically peripheral vertigo with hearing loss and the region of the affected metatarsal head. Patients may indicate tinnitus, making it unlikely in this patient. that it feels like walking with a pebble in the shoe. It is not asso- A canalith repositioning maneuver (Option B) would ciated with pain and deformity of the first MTP joint. be effective for benign paroxysmal positional vertigo, char- Morton neuroma (Option C) most commonly affects the acterized by sudden-onset, short-lasting peripheral ver- second or third interdigital web spaces. It is associated with tigo occurring with abrupt head movement. This patient's localized pain and also with the sensation of walking on a constant central vertigo symptoms are not consistent with pebble. On examination, there are usually no obvious abnor- benign paroxysmal positional vertigo. malities, but some patients may have tenderness to direct Meclizine (Option C) may offer some symptom relief in palpation of the involved interspace. It is not associated with the setting of motion sickness and Meniere disease. It has no valgus deformity or MTP joint inflammation. role in the treatment of central vertigo. Stress fractures (Option D) are associated with localized Vestibular and balance rehabilitation (Option E) can be pain but are not associated with joint deformity or inflam- useful for persistent vertiginous symptoms, but it would not mation. aid in the diagnosis or acute management of this patient. e A bunion is recognized as a lateral deviation of the e Patients with central vertigo should be urgently evalu- great toe at the metatarsal phalangeal joint. ated for vertebrobasilar stroke using MRI of the brain.

cases of severe pain and disability, surgery may be beneficial. if Meniere disease were suspected in order to document Osteochondritis of the metatarsal head of the second, sensorineural hearing loss, but Meniere disease is unlikely third, or fourth MTP joints leading to avascular necrosis (Option to present with acute vertigo. Initial symptoms of Meniere A) is known as Freiberg infraction. It presents as plantar pain in disease are typically peripheral vertigo with hearing loss and the region of the affected metatarsal head. Patients may indicate tinnitus, making it unlikely in this patient. that it feels like walking with a pebble in the shoe. It is not asso- A canalith repositioning maneuver (Option B) would ciated with pain and deformity of the first MTP joint. be effective for benign paroxysmal positional vertigo, char- Morton neuroma (Option C) most commonly affects the acterized by sudden-onset, short-lasting peripheral ver- second or third interdigital web spaces. It is associated with tigo occurring with abrupt head movement. This patient's localized pain and also with the sensation of walking on a constant central vertigo symptoms are not consistent with pebble. On examination, there are usually no obvious abnor- benign paroxysmal positional vertigo. malities, but some patients may have tenderness to direct Meclizine (Option C) may offer some symptom relief in palpation of the involved interspace. It is not associated with the setting of motion sickness and Meniere disease. It has no valgus deformity or MTP joint inflammation. role in the treatment of central vertigo. Stress fractures (Option D) are associated with localized Vestibular and balance rehabilitation (Option E) can be pain but are not associated with joint deformity or inflam- useful for persistent vertiginous symptoms, but it would not mation. aid in the diagnosis or acute management of this patient. e A bunion is recognized as a lateral deviation of the e Patients with central vertigo should be urgently evalu- great toe at the metatarsal phalangeal joint. ated for vertebrobasilar stroke using MRI of the brain. e Bunions can be associated with inflammation and significant pain and disability. Bibliography Venhovens J, Meulstee J, Verhagen WI. Acute vestibular syndrome: a critical review and diagnostic algorithm concerning the clinical differentiation Bibliography of peripheral versus central aetiologies in the emergency department. J Federer AE, Tainter DM, Adams SB, et al. Conservative management of Neurol. 2016;263:2151-7. [PMID: 26984607] metatarsalgia and lesser toe deformities. Foot Ankle Clin. 2018;23:9-20. [PMID: 29362036] doi:10.1016 /j.fel.2017.09.003 Item 18 Answer: D

e Bunions can be associated with inflammation and significant pain and disability. Bibliography Venhovens J, Meulstee J, Verhagen WI. Acute vestibular syndrome: a critical review and diagnostic algorithm concerning the clinical differentiation Bibliography of peripheral versus central aetiologies in the emergency department. J Federer AE, Tainter DM, Adams SB, et al. Conservative management of Neurol. 2016;263:2151-7. [PMID: 26984607] metatarsalgia and lesser toe deformities. Foot Ankle Clin. 2018;23:9-20. [PMID: 29362036] doi:10.1016 /j.fel.2017.09.003 Item 18 Answer: D Educational Objective: Treat escalating pain in a Item 17 Answer: D patient with advanced cancer. Educational Objective: Diagnose the cause of central The most appropriate treatment for this patient’s pain is vertigo. to start sustained-release morphine sulfate (Option D). MRI of the brain (Option D) is the most appropriate next step The patient is experiencing escalating pain in the setting in management. This patient presents with a clinical history of known metastatic cholangiocarcinoma. He was started 141

Answers and Critiques on appropriate immediate-release opioid therapy for severe MRI or CT is indicated. Several studies suggest that imme- cancer-associated pain and is now experiencing end-dose diate MRI or CT is more cost-effective than splinting and failure, which should prompt the initiation of a sustained- repeat radiography when follow-up care, missed fracture, release opioid while continuing the short-acting opioid for and lost productivity are taken into account. If diagnosed breakthrough pain flares. Because the patient is currently immediately, nondisplaced or minimally displaced scaphoid tolerating morphine, there is no reason to change to an fractures may be managed with immobilization of the wrist alternative opioid. In addition, nonopioid adjuvant therapies in a cast or with splinting for 4 to 12 weeks. Undiagnosed, should be considered for this patient; he would benefit from untreated scaphoid fracture may develop into scaphoid non- an evaluation for targeted interventional options by a pain union with degeneration of the distal radius, leading to medicine specialist. progressive arthritis months to years after the initial injury. Duloxetine (Option A) is commonly used as an adju- Bone scintigraphy (Option A) has the greatest sensitivity vant in the treatment of bony cancer-associated pain and of all advanced imaging modalities for acute scaphoid frac- > neuropathic pain. The primary analgesic mode of action ture. However, to maximize sensitivity, scintigraphy must be = wn may be modulation of the descending pain pathway through delayed for 72 hours after the event. Scintigraphy also has the = inhibition of norepinephrine reuptake, as well as serotoner- lowest specificity of all advanced imaging modalities, result- oO = wn gic and dopaminergic effects. However, the onset to efficacy ing in overtreatment of patients with positive scan results my is at least 1 week, and the best next step in the setting of but no fracture. Bone scintigraphy is not the best option for s 2. metastatic cancer is to increase the patient’s current opioid this patient. (@) =e regimen with a basal analgesic agent. Repeat radiography without splinting (Option C) would = Tramadol (Option B) is a weak opioid agonist, making be insufficient in this patient, who probably has a nondis- 2 c it a less effective analgesic in the treatment of cancer-related placed or minimally displaced scaphoid fracture. The frac- oO wi pain than agents such as morphine. Its use should be avoided ture may become displaced without splinting and could in patients with kidney and/or liver failure because of accu- potentially require surgical fixation with screws or pinning. mulation of active metabolites. In addition, tramadol carries Splinting alone (Option D) can result in a missed diag- risk for significant drug-drug interactions. nosis of scaphoid fracture. In some cases, pain will resolve Changing the opioid agent to oral oxycodone (Option C) despite fracture, only to recur in the form of degenerative would not solve the end-dose failure this patient is experi- arthritis. Advanced imaging with CT or MRI is preferred to encing. He is tolerating immediate-release morphine sulfate splinting alone. with improvement in his pain, but the improvement is not Reassurance and acetaminophen (Option E) would sustained, making a long-acting formulation a more appro- be inappropriate in this patient with a high likelihood of priate treatment in this situation. scaphoid fracture based on demographics and mechanism of injury. Radiographs are not sufficiently reassuring in this instance. e Ina patient taking an immediate-release opioid for severe cancer pain, escalating pain should prompt the addition of a sustained-release formulation. e Ifscaphoid fracture is suspected and radiographs are normal, thumb splinting and repeat radiography in 1 Bibliography to 2 weeks or immediate advanced imaging (MRI or Scarborough BM, Smith CB. Optimal pain management for patients with CT) is recommended. cancer in the modern era. CA Cancer J Clin. 2018;68:182-96. [PMID: 29603142] doi:10.3322/caac.21453 Bibliography Mawdsley MJ, Harrison J. Conservative interventions for treating scaphoid fractures in adults. Cochrane Database Syst Rev. 2018;2018:CD010713. Item 19 Answer: B doi:10.1002/14651858.CD010713.pub2

on appropriate immediate-release opioid therapy for severe MRI or CT is indicated. Several studies suggest that imme- cancer-associated pain and is now experiencing end-dose diate MRI or CT is more cost-effective than splinting and failure, which should prompt the initiation of a sustained- repeat radiography when follow-up care, missed fracture, release opioid while continuing the short-acting opioid for and lost productivity are taken into account. If diagnosed breakthrough pain flares. Because the patient is currently immediately, nondisplaced or minimally displaced scaphoid tolerating morphine, there is no reason to change to an fractures may be managed with immobilization of the wrist alternative opioid. In addition, nonopioid adjuvant therapies in a cast or with splinting for 4 to 12 weeks. Undiagnosed, should be considered for this patient; he would benefit from untreated scaphoid fracture may develop into scaphoid non- an evaluation for targeted interventional options by a pain union with degeneration of the distal radius, leading to medicine specialist. progressive arthritis months to years after the initial injury. Duloxetine (Option A) is commonly used as an adju- Bone scintigraphy (Option A) has the greatest sensitivity vant in the treatment of bony cancer-associated pain and of all advanced imaging modalities for acute scaphoid frac- > neuropathic pain. The primary analgesic mode of action ture. However, to maximize sensitivity, scintigraphy must be = wn may be modulation of the descending pain pathway through delayed for 72 hours after the event. Scintigraphy also has the = inhibition of norepinephrine reuptake, as well as serotoner- lowest specificity of all advanced imaging modalities, result- oO = wn gic and dopaminergic effects. However, the onset to efficacy ing in overtreatment of patients with positive scan results my is at least 1 week, and the best next step in the setting of but no fracture. Bone scintigraphy is not the best option for s 2. metastatic cancer is to increase the patient’s current opioid this patient. (@) =e regimen with a basal analgesic agent. Repeat radiography without splinting (Option C) would = Tramadol (Option B) is a weak opioid agonist, making be insufficient in this patient, who probably has a nondis- 2 c it a less effective analgesic in the treatment of cancer-related placed or minimally displaced scaphoid fracture. The frac- oO wi pain than agents such as morphine. Its use should be avoided ture may become displaced without splinting and could in patients with kidney and/or liver failure because of accu- potentially require surgical fixation with screws or pinning. mulation of active metabolites. In addition, tramadol carries Splinting alone (Option D) can result in a missed diag- risk for significant drug-drug interactions. nosis of scaphoid fracture. In some cases, pain will resolve Changing the opioid agent to oral oxycodone (Option C) despite fracture, only to recur in the form of degenerative would not solve the end-dose failure this patient is experi- arthritis. Advanced imaging with CT or MRI is preferred to encing. He is tolerating immediate-release morphine sulfate splinting alone. with improvement in his pain, but the improvement is not Reassurance and acetaminophen (Option E) would sustained, making a long-acting formulation a more appro- be inappropriate in this patient with a high likelihood of priate treatment in this situation. scaphoid fracture based on demographics and mechanism of injury. Radiographs are not sufficiently reassuring in this instance. e Ina patient taking an immediate-release opioid for severe cancer pain, escalating pain should prompt the addition of a sustained-release formulation. e Ifscaphoid fracture is suspected and radiographs are normal, thumb splinting and repeat radiography in 1 Bibliography to 2 weeks or immediate advanced imaging (MRI or Scarborough BM, Smith CB. Optimal pain management for patients with CT) is recommended. cancer in the modern era. CA Cancer J Clin. 2018;68:182-96. [PMID: 29603142] doi:10.3322/caac.21453 Bibliography Mawdsley MJ, Harrison J. Conservative interventions for treating scaphoid fractures in adults. Cochrane Database Syst Rev. 2018;2018:CD010713. Item 19 Answer: B doi:10.1002/14651858.CD010713.pub2 Educational Objective: Diagnose scaphoid fracture.

on appropriate immediate-release opioid therapy for severe MRI or CT is indicated. Several studies suggest that imme- cancer-associated pain and is now experiencing end-dose diate MRI or CT is more cost-effective than splinting and failure, which should prompt the initiation of a sustained- repeat radiography when follow-up care, missed fracture, release opioid while continuing the short-acting opioid for and lost productivity are taken into account. If diagnosed breakthrough pain flares. Because the patient is currently immediately, nondisplaced or minimally displaced scaphoid tolerating morphine, there is no reason to change to an fractures may be managed with immobilization of the wrist alternative opioid. In addition, nonopioid adjuvant therapies in a cast or with splinting for 4 to 12 weeks. Undiagnosed, should be considered for this patient; he would benefit from untreated scaphoid fracture may develop into scaphoid non- an evaluation for targeted interventional options by a pain union with degeneration of the distal radius, leading to medicine specialist. progressive arthritis months to years after the initial injury. Duloxetine (Option A) is commonly used as an adju- Bone scintigraphy (Option A) has the greatest sensitivity vant in the treatment of bony cancer-associated pain and of all advanced imaging modalities for acute scaphoid frac- > neuropathic pain. The primary analgesic mode of action ture. However, to maximize sensitivity, scintigraphy must be = wn may be modulation of the descending pain pathway through delayed for 72 hours after the event. Scintigraphy also has the = inhibition of norepinephrine reuptake, as well as serotoner- lowest specificity of all advanced imaging modalities, result- oO = wn gic and dopaminergic effects. However, the onset to efficacy ing in overtreatment of patients with positive scan results my is at least 1 week, and the best next step in the setting of but no fracture. Bone scintigraphy is not the best option for s 2. metastatic cancer is to increase the patient’s current opioid this patient. (@) =e regimen with a basal analgesic agent. Repeat radiography without splinting (Option C) would = Tramadol (Option B) is a weak opioid agonist, making be insufficient in this patient, who probably has a nondis- 2 c it a less effective analgesic in the treatment of cancer-related placed or minimally displaced scaphoid fracture. The frac- oO wi pain than agents such as morphine. Its use should be avoided ture may become displaced without splinting and could in patients with kidney and/or liver failure because of accu- potentially require surgical fixation with screws or pinning. mulation of active metabolites. In addition, tramadol carries Splinting alone (Option D) can result in a missed diag- risk for significant drug-drug interactions. nosis of scaphoid fracture. In some cases, pain will resolve Changing the opioid agent to oral oxycodone (Option C) despite fracture, only to recur in the form of degenerative would not solve the end-dose failure this patient is experi- arthritis. Advanced imaging with CT or MRI is preferred to encing. He is tolerating immediate-release morphine sulfate splinting alone. with improvement in his pain, but the improvement is not Reassurance and acetaminophen (Option E) would sustained, making a long-acting formulation a more appro- be inappropriate in this patient with a high likelihood of priate treatment in this situation. scaphoid fracture based on demographics and mechanism of injury. Radiographs are not sufficiently reassuring in this instance. e Ina patient taking an immediate-release opioid for severe cancer pain, escalating pain should prompt the addition of a sustained-release formulation. e Ifscaphoid fracture is suspected and radiographs are normal, thumb splinting and repeat radiography in 1 Bibliography to 2 weeks or immediate advanced imaging (MRI or Scarborough BM, Smith CB. Optimal pain management for patients with CT) is recommended. cancer in the modern era. CA Cancer J Clin. 2018;68:182-96. [PMID: 29603142] doi:10.3322/caac.21453 Bibliography Mawdsley MJ, Harrison J. Conservative interventions for treating scaphoid fractures in adults. Cochrane Database Syst Rev. 2018;2018:CD010713. Item 19 Answer: B doi:10.1002/14651858.CD010713.pub2 Educational Objective: Diagnose scaphoid fracture. The most appropriate next step in management is MRI of Item 20 Answer: B the right wrist (Option B). Falls onto outstretched hands Educational Objective: Recognize heterogeneity as a resulting in pain in the anatomic snuffbox, especially in male limitation of a meta-analysis. athletes in the second or third decade of life, should raise high clinical suspicion for scaphoid fracture. The location The most important limitation to this meta-analysis is het- of the scaphoid bone, articulating with the distal radius and erogeneity (Option B). Meta-analysis is a statistical method four carpal bones, makes it prone to fracture. Because of that combines the results from different studies included the complexity of the anatomy, scaphoid fractures are often in systematic reviews. Systematic reviews are systematic missed on initial radiographs, which are normal in up to literature searches performed by using predefined criteria 20% of patients. If scaphoid fracture is suspected and initial to collect all relevant studies. The systematic selection of the radiographs are normal, either splinting with repeat radiog- included studies minimizes bias. The resultant larger sample raphy in 1 to 2 weeks or immediate advanced imaging with size has greater power to discriminate differences between

The most appropriate next step in management is MRI of Item 20 Answer: B the right wrist (Option B). Falls onto outstretched hands Educational Objective: Recognize heterogeneity as a resulting in pain in the anatomic snuffbox, especially in male limitation of a meta-analysis. athletes in the second or third decade of life, should raise high clinical suspicion for scaphoid fracture. The location The most important limitation to this meta-analysis is het- of the scaphoid bone, articulating with the distal radius and erogeneity (Option B). Meta-analysis is a statistical method four carpal bones, makes it prone to fracture. Because of that combines the results from different studies included the complexity of the anatomy, scaphoid fractures are often in systematic reviews. Systematic reviews are systematic missed on initial radiographs, which are normal in up to literature searches performed by using predefined criteria 20% of patients. If scaphoid fracture is suspected and initial to collect all relevant studies. The systematic selection of the radiographs are normal, either splinting with repeat radiog- included studies minimizes bias. The resultant larger sample raphy in 1 to 2 weeks or immediate advanced imaging with size has greater power to discriminate differences between 142

pnewiers. and Gritigues groups; thus, meta-analysis increases sample size and sta- sacroiliac joint dysfunction, and gluteal tendinopathy. Pain tistical power. Meta-analysis of high-quality randomized associated with radiation down the leg suggests lumbar controlled trials is considered one of the highest levels of radiculopathy, whereas concomitant exertional leg pain or clinical evidence. Factors that limit the ability to combine peripheral vascular disease suggests vascular claudication. study results meaningfully include differences in the study These causes of posterior hip pain are not associated with populations, research measures, and statistical techniques. positive results on the FADIR test. Acetabular labrum injury These differences are termed heterogeneity. This systematic (labrum tear) is an example of an extra-articular cause of review had differences in patient populations that included anterior hip pain; osteoarthritis and avascular necrosis are more advanced disease, sicker patients, and variability in examples of intra-articular causes. Anterior or posterior hip previous treatment before inclusion in the study. pain that starts insidiously and worsens with standing and Confounding (Option A) occurs when factors other than activity in older patients suggests osteoarthritis. The same the treatments being studied are independently associated pain characteristics in a younger person with anterior hip with the participants being studied and the end point being pain raise concern for a labral tear, especially when accom- wv rH assessed. Although statistical techniques can account for panied by painful clicking or catching. Gradual onset of =

groups; thus, meta-analysis increases sample size and sta- sacroiliac joint dysfunction, and gluteal tendinopathy. Pain tistical power. Meta-analysis of high-quality randomized associated with radiation down the leg suggests lumbar controlled trials is considered one of the highest levels of radiculopathy, whereas concomitant exertional leg pain or clinical evidence. Factors that limit the ability to combine peripheral vascular disease suggests vascular claudication. study results meaningfully include differences in the study These causes of posterior hip pain are not associated with populations, research measures, and statistical techniques. positive results on the FADIR test. Acetabular labrum injury These differences are termed heterogeneity. This systematic (labrum tear) is an example of an extra-articular cause of review had differences in patient populations that included anterior hip pain; osteoarthritis and avascular necrosis are more advanced disease, sicker patients, and variability in examples of intra-articular causes. Anterior or posterior hip previous treatment before inclusion in the study. pain that starts insidiously and worsens with standing and Confounding (Option A) occurs when factors other than activity in older patients suggests osteoarthritis. The same the treatments being studied are independently associated pain characteristics in a younger person with anterior hip with the participants being studied and the end point being pain raise concern for a labral tear, especially when accom- wv rH assessed. Although statistical techniques can account for panied by painful clicking or catching. Gradual onset of = known or anticipated confounders, random assignment of anterior hip pain can also occur with avascular necrosis (or = osteonecrosis), which should be considered in the presence = the intervention being studied (i.e., a randomized controlled rs) study) best protects against both known and unknown con- of alcohol abuse, glucocorticoid use, systemic lupus erythe- sc = founders. This protection should also apply to meta-analysis matosus, or sickle cell anemia. ©

known or anticipated confounders, random assignment of anterior hip pain can also occur with avascular necrosis (or = osteonecrosis), which should be considered in the presence = the intervention being studied (i.e., a randomized controlled rs) study) best protects against both known and unknown con- of alcohol abuse, glucocorticoid use, systemic lupus erythe- sc = founders. This protection should also apply to meta-analysis matosus, or sickle cell anemia. © of randomized controlled trials. Acetabular labrum tear (Option A) is most commonly wn thon 7 Meta-analysis, as previously stated, combines the seen in a young person, often an athlete, with anterior hip = wn results of multiple studies, thus effectively increasing sample pain. Labrum tears are exacerbated by athletic activity, par- = size. The associated increase in statistical power (Option C) ticularly sprinting or jumping. The FADIR test will reproduce 9

of randomized controlled trials. Acetabular labrum tear (Option A) is most commonly wn thon 7 Meta-analysis, as previously stated, combines the seen in a young person, often an athlete, with anterior hip = wn results of multiple studies, thus effectively increasing sample pain. Labrum tears are exacerbated by athletic activity, par- = size. The associated increase in statistical power (Option C) ticularly sprinting or jumping. The FADIR test will reproduce 9 to detect differences is a strength of this technique. the pain. This older man with posterior hip pain does not Random error (Option D) is introduced by random vari- have a labrum tear. ability or chance and is expressed by the P value or confi- Sciatic nerve irritation from lumbar radiculopathy dence interval. All study designs, including meta-analysis, (Option C) is less likely to be the cause of this patient’s pain, are subject to random error, but random error is not a given the lack of radiation down the leg. unique vulnerability of this design compared with others. Sacroiliac joint dysfunction (Option D) can cause pos- Random error can be decreased by increasing the sample terior hip pain but would be associated with a positive result size (a strength of meta-analysis) and using precise measure- on the FABER (Flexion, ABduction, and External Rotation) ment strategies. test rather than a positive result on the FADIR test, as seen in this patient.

to detect differences is a strength of this technique. the pain. This older man with posterior hip pain does not Random error (Option D) is introduced by random vari- have a labrum tear. ability or chance and is expressed by the P value or confi- Sciatic nerve irritation from lumbar radiculopathy dence interval. All study designs, including meta-analysis, (Option C) is less likely to be the cause of this patient’s pain, are subject to random error, but random error is not a given the lack of radiation down the leg. unique vulnerability of this design compared with others. Sacroiliac joint dysfunction (Option D) can cause pos- Random error can be decreased by increasing the sample terior hip pain but would be associated with a positive result size (a strength of meta-analysis) and using precise measure- on the FABER (Flexion, ABduction, and External Rotation) ment strategies. test rather than a positive result on the FADIR test, as seen in this patient. ¢ Meta-analysis is a statistical method that combines the results from different studies included in syste- e Anterior or posterior hip pain and positive results on matic reviews; meta-analysis increases sample size the FADIR (Flexion, ADduction, and Internal Rotation) and statistical power. test suggest osteoarthritis.

¢ Meta-analysis is a statistical method that combines the results from different studies included in syste- e Anterior or posterior hip pain and positive results on matic reviews; meta-analysis increases sample size the FADIR (Flexion, ADduction, and Internal Rotation) and statistical power. test suggest osteoarthritis. e Heterogeneity refers to factors that limit the ability to Bibliography meaningfully combine study results in a meta-analysis Buckland AJ, Miyamoto R, Patel RD, Slover J, Razi AE. Differentiating hip because of differences in study populations, research pathology from lumbar spine pathology: key points of evaluation and measures, or statistical techniques. management. J Am Acad Orthop Surg. 2017;25:e23-e34. [PMID: 28045713] doi:10.5435/JAAOS-D-15-00740

e Heterogeneity refers to factors that limit the ability to Bibliography meaningfully combine study results in a meta-analysis Buckland AJ, Miyamoto R, Patel RD, Slover J, Razi AE. Differentiating hip because of differences in study populations, research pathology from lumbar spine pathology: key points of evaluation and measures, or statistical techniques. management. J Am Acad Orthop Surg. 2017;25:e23-e34. [PMID: 28045713] doi:10.5435/JAAOS-D-15-00740 Bibliography Lee YH. An overview of meta-analysis for clinicians. Korean J Intern Med. Item 22 Answer: C 2018;33:277-83. [PMID: 29277096] doi:10.3904/kjim.2016.195 Educational Objective: Evaluate syncope with orthostatic blood pressure measurement. Item 21 Answer: 8B The most appropriate diagnostic test to perform next is Educational Objective: Evaluate posterior hip pain. orthostatic blood pressure measurement (Option C). The The most likely diagnosis is hip osteoarthritis (Option B). American Heart Association/American College of Cardiol Pain in the hip can be predominantly anterior, lateral, or pos- ogy/Heart Rhythm Society concluded that the history and terior. Anterior and posterior hip pain can be intra-articular physical examination are the most important tools in strat or extra-articular. Posterior hip pain associated with posi- ifyving risk in patients with syncope. All additional testing tive results on the FADIR (Flexion, ADduction, and Internal can be based on this initial evaluation. Important aspects to Rotation) test, as seen in this patient, strongly suggests osteo- obtain in the history include the presence of reversible fac arthritis. Examples of extra-articular causes of posterior hip tors, the situation in which the syncopal event occurred, and pain include lumbar radiculopathy, vascular claudication, any symptoms present before and after the syncopal event.

Bibliography Lee YH. An overview of meta-analysis for clinicians. Korean J Intern Med. Item 22 Answer: C 2018;33:277-83. [PMID: 29277096] doi:10.3904/kjim.2016.195 Educational Objective: Evaluate syncope with orthostatic blood pressure measurement. Item 21 Answer: 8B The most appropriate diagnostic test to perform next is Educational Objective: Evaluate posterior hip pain. orthostatic blood pressure measurement (Option C). The The most likely diagnosis is hip osteoarthritis (Option B). American Heart Association/American College of Cardiol Pain in the hip can be predominantly anterior, lateral, or pos- ogy/Heart Rhythm Society concluded that the history and terior. Anterior and posterior hip pain can be intra-articular physical examination are the most important tools in strat or extra-articular. Posterior hip pain associated with posi- ifyving risk in patients with syncope. All additional testing tive results on the FADIR (Flexion, ADduction, and Internal can be based on this initial evaluation. Important aspects to Rotation) test, as seen in this patient, strongly suggests osteo- obtain in the history include the presence of reversible fac arthritis. Examples of extra-articular causes of posterior hip tors, the situation in which the syncopal event occurred, and pain include lumbar radiculopathy, vascular claudication, any symptoms present before and after the syncopal event. 143

Answers and Critiques A thorough medical history and medication history should as hyperglycemia) and hyperlipidemia. The fasting blood be obtained, with an emphasis on history of cardiac disease. glucose level should be measured upon initial medication CONT. A family history also should be obtained, focusing on any initiation and at 3 months. Thereafter, the fasting glucose history of syncope or sudden unexplained death, including level should be checked at least annually. More frequent drowning. Physical examination should include a thorough monitoring can be considered in patients with risk factors cardiovascular examination, with orthostatic blood pressure for diabetes. Lipid monitoring should be performed at base- measurement in three positions and cardiac auscultation. line, at 3 months, and at least every 5 years thereafter. A basic neurologic examination should also be performed. Complete blood count monitoring (Option A) is ECG should be included in the initial evaluation of syncope required for patients who take clozapine owing to its asso- as a tool to identify potentially life-threatening causes of ciation with agranulocytosis. Routine complete blood count cardiac syncope. monitoring is not required with olanzapine use. The usefulness of cardiac enzyme measurement Periodic monitoring of liver chemistries (Option C) is bt (Option A) is uncertain in patients for whom a cardiac cause required with use of some first-generation antipsychotics, = wn of syncope is suspected, and these tests should not be a part such as fluphenazine, but it is not needed with olanzapine. = of the routine evaluation of syncope. No laboratory values First-generation (typical) antipsychotic agents have a © higher risk for extrapyramidal symptoms (parkinsonism, = wa obtained in a routine metabolic profile are linked to the » mechanism of syncope. akathisia), tardive dyskinesia, and hyperprolactinemia = 2. In the absence of neurologic symptoms or findings, than do second-generation (atypical) antipsychotic agents. se) = MRI of the brain or CT of the head (Option B) is not recom- Regardless of whether the patient is treated with typical 5 mended as part of the routine evaluation of patients who or atypical agents, in the absence of side effects, such as 2 c present with syncope. Such imaging adds significant cost to nipple discharge, routine monitoring of the prolactin level oO wn the evaluation with minimal benefit. (Option D) is not indicated. Transthoracic echocardiography (Option D) is useful Second-generation antipsychotic agents, including olan- in evaluating patients for whom there is suspicion of struc- zapine, have been associated with a prolonged QT interval. tural heart disease. If no physical examination findings sug- However, the incidence of prolonged QT interval with olanza- gest structural heart disease, routine cardiac imaging is not pine alone is less than 2%. When combined with other agents recommended. that can prolong the QT interval (quinidine, selective serotonin reuptake inhibitors, tricyclic antidepressants, ondansetron), QT should be monitored. In a patient with a previously nor- e All patients with syncope should be evaluated with mal QT interval and no new medications, routinely obtaining orthostatic blood pressure measurement and ECG. an ECG for QT interval monitoring (Option E) is not required. e Laboratory evaluation of syncope with cardiac enzyme testing and comprehensive metabolic assessment is of ¢ The most common adverse effects of second-generation uncertain value. antipsychotic agents are weight gain (and sequelae of weight gain, such as hyperglycemia) and hyperlipidemia. Bibliography Shen WK, Sheldon RS, Benditt DG, et al. 2017 ACC/AHA/HRS guideline for e Weight, blood glucose level, and lipid levels should be the evaluation and management of patients with syncope: executive monitored in patients taking second-generation summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the antipsychotic drugs. Heart Rhythm Society. Circulation. 2017;136:e25-59. [PMID: 28280232] doi:10.1161/CIR.0000000000000498 Bibliography American Diabetes Association; American Psychiatric Association; American Association of Clinical Endocrinologists; North American Item 23 Answer: B Association for the Study of Obesity. Consensus development conference

A thorough medical history and medication history should as hyperglycemia) and hyperlipidemia. The fasting blood be obtained, with an emphasis on history of cardiac disease. glucose level should be measured upon initial medication CONT. A family history also should be obtained, focusing on any initiation and at 3 months. Thereafter, the fasting glucose history of syncope or sudden unexplained death, including level should be checked at least annually. More frequent drowning. Physical examination should include a thorough monitoring can be considered in patients with risk factors cardiovascular examination, with orthostatic blood pressure for diabetes. Lipid monitoring should be performed at base- measurement in three positions and cardiac auscultation. line, at 3 months, and at least every 5 years thereafter. A basic neurologic examination should also be performed. Complete blood count monitoring (Option A) is ECG should be included in the initial evaluation of syncope required for patients who take clozapine owing to its asso- as a tool to identify potentially life-threatening causes of ciation with agranulocytosis. Routine complete blood count cardiac syncope. monitoring is not required with olanzapine use. The usefulness of cardiac enzyme measurement Periodic monitoring of liver chemistries (Option C) is bt (Option A) is uncertain in patients for whom a cardiac cause required with use of some first-generation antipsychotics, = wn of syncope is suspected, and these tests should not be a part such as fluphenazine, but it is not needed with olanzapine. = of the routine evaluation of syncope. No laboratory values First-generation (typical) antipsychotic agents have a © higher risk for extrapyramidal symptoms (parkinsonism, = wa obtained in a routine metabolic profile are linked to the » mechanism of syncope. akathisia), tardive dyskinesia, and hyperprolactinemia = 2. In the absence of neurologic symptoms or findings, than do second-generation (atypical) antipsychotic agents. se) = MRI of the brain or CT of the head (Option B) is not recom- Regardless of whether the patient is treated with typical 5 mended as part of the routine evaluation of patients who or atypical agents, in the absence of side effects, such as 2 c present with syncope. Such imaging adds significant cost to nipple discharge, routine monitoring of the prolactin level oO wn the evaluation with minimal benefit. (Option D) is not indicated. Transthoracic echocardiography (Option D) is useful Second-generation antipsychotic agents, including olan- in evaluating patients for whom there is suspicion of struc- zapine, have been associated with a prolonged QT interval. tural heart disease. If no physical examination findings sug- However, the incidence of prolonged QT interval with olanza- gest structural heart disease, routine cardiac imaging is not pine alone is less than 2%. When combined with other agents recommended. that can prolong the QT interval (quinidine, selective serotonin reuptake inhibitors, tricyclic antidepressants, ondansetron), QT should be monitored. In a patient with a previously nor- e All patients with syncope should be evaluated with mal QT interval and no new medications, routinely obtaining orthostatic blood pressure measurement and ECG. an ECG for QT interval monitoring (Option E) is not required. e Laboratory evaluation of syncope with cardiac enzyme testing and comprehensive metabolic assessment is of ¢ The most common adverse effects of second-generation uncertain value. antipsychotic agents are weight gain (and sequelae of weight gain, such as hyperglycemia) and hyperlipidemia. Bibliography Shen WK, Sheldon RS, Benditt DG, et al. 2017 ACC/AHA/HRS guideline for e Weight, blood glucose level, and lipid levels should be the evaluation and management of patients with syncope: executive monitored in patients taking second-generation summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the antipsychotic drugs. Heart Rhythm Society. Circulation. 2017;136:e25-59. [PMID: 28280232] doi:10.1161/CIR.0000000000000498 Bibliography American Diabetes Association; American Psychiatric Association; American Association of Clinical Endocrinologists; North American Item 23 Answer: B Association for the Study of Obesity. Consensus development conference Educational Objective: Monitor a patient taking on antipsychotic drugs and obesity and diabetes. Diabetes Care. 2004;27: 596-601. [PMID: 14747245] doi:10.2337/diacare.27.2.596 antipsychotic medication.

Educational Objective: Monitor a patient taking on antipsychotic drugs and obesity and diabetes. Diabetes Care. 2004;27: 596-601. [PMID: 14747245] doi:10.2337/diacare.27.2.596 antipsychotic medication. Lipid levels (Option B), weight, and blood glucose level Item 24 Answer: C should be monitored in this patient who has schizophrenia Educational Objective: Initiate statin therapy for and takes olanzapine, a second-generation antipsychotic secondary prevention of myocardial infarction. medication. Schizophrenia is associated with an increased risk for diabetes mellitus, cardiovascular disease, and obe- The most appropriate treatment is high-intensity rosuva- sity, and undertreatment of medical disease is common in statin (Option C). Patients aged 75 years or younger with a this population. Metabolic effects of antipsychotic therapy history of atherosclerotic cardiovascular disease (ASCVD) also can contribute to these conditions, which significantly should be prescribed high-intensity statin therapy (rosu- increase mortality in patients with schizophrenia. The most vastatin or atorvastatin) as secondary prevention. Clinical common adverse effects of second-generation antipsychotic ASCVD is defined as acute coronary syndrome, myocar- agents are weight gain (and sequelae of weight gain, such dial infarction, stable or unstable angina, coronary artery 144

Answers and Critiques revascularization, stroke, transient ischemic attack, or periph- pharmacologic therapy for depression with a low dosage of eral artery disease. The goal of drug therapy is to decrease the the selected medication, the medication should be gradu- LDL cholesterol level by 50% or more; however, therapy in this ally titrated to achieve a clinical response while monitoring patient population should be started regardless of initial LDL for adverse effects. Therapeutic response can be measured cholesterol level. LDL cholesterol should be measured again objectively with the PHQ-9 by comparing scores before and in approximately 6 to 8 weeks to ensure adherence to the during treatment. A decrease in the score of at least 50% medication regimen and successful lowering of cholesterol indicates a response to treatment; a decrease to a score of levels. If the patient does not tolerate high-intensity statin less than 5 indicates remission. Ifa partial response occurs, therapy because of statin-associated adverse effects, moder- as it did in this case, increasing the dosage of the chosen ate-intensity statin therapy should be initiated, with the aim medication or adding psychotherapy, such as cognitive of decreasing LDL cholesterol by 30% to 49%. behavioral therapy (CBT), may be appropriate. Approxi- Despite a theoretical and basic science benefit to col- mately half of patients who respond to appropriate initial chicine (Option A) in improving cardiovascular outcomes, therapy develop recurrent depression after 1 year with- wn cH a meta-analysis showed no effect on all-cause mortality. out continued treatment. Continuation therapy (treatment 3

revascularization, stroke, transient ischemic attack, or periph- pharmacologic therapy for depression with a low dosage of eral artery disease. The goal of drug therapy is to decrease the the selected medication, the medication should be gradu- LDL cholesterol level by 50% or more; however, therapy in this ally titrated to achieve a clinical response while monitoring patient population should be started regardless of initial LDL for adverse effects. Therapeutic response can be measured cholesterol level. LDL cholesterol should be measured again objectively with the PHQ-9 by comparing scores before and in approximately 6 to 8 weeks to ensure adherence to the during treatment. A decrease in the score of at least 50% medication regimen and successful lowering of cholesterol indicates a response to treatment; a decrease to a score of levels. If the patient does not tolerate high-intensity statin less than 5 indicates remission. Ifa partial response occurs, therapy because of statin-associated adverse effects, moder- as it did in this case, increasing the dosage of the chosen ate-intensity statin therapy should be initiated, with the aim medication or adding psychotherapy, such as cognitive of decreasing LDL cholesterol by 30% to 49%. behavioral therapy (CBT), may be appropriate. Approxi- Despite a theoretical and basic science benefit to col- mately half of patients who respond to appropriate initial chicine (Option A) in improving cardiovascular outcomes, therapy develop recurrent depression after 1 year with- wn cH a meta-analysis showed no effect on all-cause mortality. out continued treatment. Continuation therapy (treatment 3 Although this analysis did demonstrate a decreased risk for after resolution of a major depressive episode) for 4 to = myocardial infarction, colchicine should not be used as first- 9 months is recommended in patients who responded to + rs line therapy before initiation of proven medications, such as acute therapy. The antidepressant dosage that was effective a=] = low-dose aspirin, statins, B-blockers, and ACE inhibitors or in acute treatment should be maintained in the continu- © w angiotensin receptor blockers. ation phase, and if psychotherapy was used, it should be — 7 If patients with clinical ASCVD continue to have an continued. = elevated LDL cholesterol level (>70 mg/dL [1.81 mmol/L]) CBT (Option A) is an appropriate therapeutic choice wn Ss despite maximally tolerated statin therapy, ezetimibe for patients with mild to moderate depression. In patients Pe

Although this analysis did demonstrate a decreased risk for after resolution of a major depressive episode) for 4 to = myocardial infarction, colchicine should not be used as first- 9 months is recommended in patients who responded to + rs line therapy before initiation of proven medications, such as acute therapy. The antidepressant dosage that was effective a=] = low-dose aspirin, statins, B-blockers, and ACE inhibitors or in acute treatment should be maintained in the continu- © w angiotensin receptor blockers. ation phase, and if psychotherapy was used, it should be — 7 If patients with clinical ASCVD continue to have an continued. = elevated LDL cholesterol level (>70 mg/dL [1.81 mmol/L]) CBT (Option A) is an appropriate therapeutic choice wn Ss despite maximally tolerated statin therapy, ezetimibe for patients with mild to moderate depression. In patients Pe (Option B) may be considered as an addition to the statin who have a partial response to pharmacologic therapy, it medication. Shared decision making considering the risks is not unreasonable to add CBT in an attempt to achieve and benefits of adding a medication should occur. remission. If remission was achieved using both pharma- In patients with clinical ASCVD who are judged to be cologic therapy and CBT, both should be continued during at very high risk and who are receiving maximally tolerated the continuation phase. However, there is no compelling LDL cholesterol-lowering therapy with a statin and ezetimibe reason to add CBT to pharmacologic therapy after remis- but in whom the LDL cholesterol level exceeds 70 mg/dL sion has been achieved. (1.81 mmol/L) or the non-HDL cholesterol level is greater This patient has achieved remission on a stable dos- than 100 mg/dL (2.59 mmol/L), it is reasonable to add a pro- age of fluoxetine, and that dosage should be continued for protein convertase subtilisin/kexin type 9 (PCSK9) inhibitor an additional 4 to 9 months. Reducing the dosage by half (Option D), after a clinician-patient discussion about the net (Option B) may result in relapse of depression and is not benefit, safety, and cost. appropriate in this patient. Fluoxetine should not be discontinued (Option D) because depression may relapse. Furthermore, the sud- e Patients aged 75 years or younger with clinical athero- den discontinuation of antidepressant medications can sclerotic cardiovascular disease should be prescribed cause discontinuation syndrome. Discontinuation syn- a high-intensity statin as secondary prevention. drome is most frequently seen in patients who abruptly e If patients with clinical atherosclerotic cardiovascular stop selective serotonin reuptake inhibitors. The most com-

(Option B) may be considered as an addition to the statin who have a partial response to pharmacologic therapy, it medication. Shared decision making considering the risks is not unreasonable to add CBT in an attempt to achieve and benefits of adding a medication should occur. remission. If remission was achieved using both pharma- In patients with clinical ASCVD who are judged to be cologic therapy and CBT, both should be continued during at very high risk and who are receiving maximally tolerated the continuation phase. However, there is no compelling LDL cholesterol-lowering therapy with a statin and ezetimibe reason to add CBT to pharmacologic therapy after remis- but in whom the LDL cholesterol level exceeds 70 mg/dL sion has been achieved. (1.81 mmol/L) or the non-HDL cholesterol level is greater This patient has achieved remission on a stable dos- than 100 mg/dL (2.59 mmol/L), it is reasonable to add a pro- age of fluoxetine, and that dosage should be continued for protein convertase subtilisin/kexin type 9 (PCSK9) inhibitor an additional 4 to 9 months. Reducing the dosage by half (Option D), after a clinician-patient discussion about the net (Option B) may result in relapse of depression and is not benefit, safety, and cost. appropriate in this patient. Fluoxetine should not be discontinued (Option D) because depression may relapse. Furthermore, the sud- e Patients aged 75 years or younger with clinical athero- den discontinuation of antidepressant medications can sclerotic cardiovascular disease should be prescribed cause discontinuation syndrome. Discontinuation syn- a high-intensity statin as secondary prevention. drome is most frequently seen in patients who abruptly e If patients with clinical atherosclerotic cardiovascular stop selective serotonin reuptake inhibitors. The most com- disease continue to have an elevated LDL cholesterol mon discontinuation symptoms include dizziness, fatigue,

(Option B) may be considered as an addition to the statin who have a partial response to pharmacologic therapy, it medication. Shared decision making considering the risks is not unreasonable to add CBT in an attempt to achieve and benefits of adding a medication should occur. remission. If remission was achieved using both pharma- In patients with clinical ASCVD who are judged to be cologic therapy and CBT, both should be continued during at very high risk and who are receiving maximally tolerated the continuation phase. However, there is no compelling LDL cholesterol-lowering therapy with a statin and ezetimibe reason to add CBT to pharmacologic therapy after remis- but in whom the LDL cholesterol level exceeds 70 mg/dL sion has been achieved. (1.81 mmol/L) or the non-HDL cholesterol level is greater This patient has achieved remission on a stable dos- than 100 mg/dL (2.59 mmol/L), it is reasonable to add a pro- age of fluoxetine, and that dosage should be continued for protein convertase subtilisin/kexin type 9 (PCSK9) inhibitor an additional 4 to 9 months. Reducing the dosage by half (Option D), after a clinician-patient discussion about the net (Option B) may result in relapse of depression and is not benefit, safety, and cost. appropriate in this patient. Fluoxetine should not be discontinued (Option D) because depression may relapse. Furthermore, the sud- e Patients aged 75 years or younger with clinical athero- den discontinuation of antidepressant medications can sclerotic cardiovascular disease should be prescribed cause discontinuation syndrome. Discontinuation syn- a high-intensity statin as secondary prevention. drome is most frequently seen in patients who abruptly e If patients with clinical atherosclerotic cardiovascular stop selective serotonin reuptake inhibitors. The most com- disease continue to have an elevated LDL cholesterol mon discontinuation symptoms include dizziness, fatigue, level despite maximally tolerated statin therapy, addi- headache, and nausea. Other symptoms include agitation, anxiety, dysphoria, and irritability. Onset of the syndrome tion of ezetimibe may be considered. is within 1 to 4 days of abruptly stopping antidepressant therapy or after a rapid taper. Although fluoxetine has the Bibliography lowest incidence of discontinuation syndrome, if therapy Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management must be discontinued, it should be tapered rather than of blood cholesterol: a report of the American College of Cardiology/ abruptly stopped. American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139:e1082-143. [PMID: 30586774] doi:10.1161/CIR. 0000000000000625

level despite maximally tolerated statin therapy, addi- headache, and nausea. Other symptoms include agitation, anxiety, dysphoria, and irritability. Onset of the syndrome tion of ezetimibe may be considered. is within 1 to 4 days of abruptly stopping antidepressant therapy or after a rapid taper. Although fluoxetine has the Bibliography lowest incidence of discontinuation syndrome, if therapy Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management must be discontinued, it should be tapered rather than of blood cholesterol: a report of the American College of Cardiology/ abruptly stopped. American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139:e1082-143. [PMID: 30586774] doi:10.1161/CIR. 0000000000000625 e Continuation therapy after resolution of a major Item 25 depressive episode is recommended for 4 to 9 months Answer: C in patients who responded to acute therapy. Educational Objective: Treat depression with mainte- nance pharmacologic therapy. Bibliography The most appropriate management is to continue fluoxe- Park LT, Zarate CA Jr. Depression in the primary care setting. N EnglJ Med. tine for an additional 6 months (Option C). After starting 2019;380:559-68. [PMID: 30726688] doi:10.1056/NEJMcp1712493 145

snes ate rience Item 26 Answer: C Item 27 Answer: 6B Educational Objective: Treat binge eating disorder with Educational Objective: Treat a venous stasis ulcer. lisdexamfetamine. The most appropriate treatment is compression therapy Lisdexamfetamine (Option C) is the most appropriate treat- (Option B). Treatment of venous stasis ulcers consists ment for this patient with binge eating disorder, which is of local wound care and compression therapy. Infection characterized by binge eating and feelings of loss of control should be eliminated as a contributing cause of nonheal- around food that occur an average of at least once weekly ing venous ulceration. Necrotic tissue should be debrided, for 3 months. Binging episodes include at least three of the and the wound should be covered with a dressing. Various following characteristics: abnormally rapid consumption, dressings are available, and none stand out as superior in eating until uncomfortably full, consuming large amounts of direct comparisons; however, dry gauze should be avoided food when not hungry, eating alone due to embarrassment, because it disrupts the formation of granulation tissue and feelings of guilt related to overconsumption. These char- when removed. Many patients prefer hydrocolloidal dress- P= = ings because of ease of application and reduction in pain, wn acteristics distinguish binge eating disorder from overeating. = The main treatment for binge eating disorder is cognitive when present. oO = wn behavioral therapy (CBT). Because this patient’s symptoms Compression therapy is an essential component of the oo have persisted while she is engaged in CBT, medical therapy treatment of venous stasis ulcers. Before application of com- = Qa. can be considered. A systematic review found that CBT, pression therapy, measurement of the ankle-brachial index a lisdexamfetamine, selective serotonin reuptake inhibitors (ABI) is recommended to avoid inappropriate application of oe =. (SSRIs), and topiramate all reduced binge eating. Lisdexam- lower extremity compression in a patient with peripheral 2 S fetamine and topiramate reduced weight in adults with artery disease. An absolute contraindication to compression © wn binge eating disorder and should be considered for this therapy is an ABI of 0.5 or less, although cautious use is patient, who has partial response to CBT and an SSRI. Side advised for any patient with an ABI less than 0.9. There are effects are common with lisdexamfetamine and include many options for compression therapy, including multilay- headache, gastrointestinal upset, and sleep disturbance. Lis- ered elastic bandage systems, elastic compression stock- dexamfetamine has been shown to reduce the frequency of ings, and intermittent pneumatic compression (dynamic binge eating days and is FDA approved to treat binge eating compression). Static compression with a zinc oxide paste disorder. Topiramate is not FDA approved for this indication. bandage (e.g., Unna boot) is not as effective as elastic com- In addition to initiating lisdexamfetamine, CBT should be pression or dynamic compression in venous ulcer healing. continued in this patient. At times, the choice is determined by the ability of the For patients who are severely underweight or at risk for compression system to accommodate the bulk of the wound life-threatening complications, admission to an inpatient facil- dressing. Specialty compression stockings that include a ity specializing in eating disorders (Option A) is indicated. Treat- zipper may increase patient adherence and, like multilay- ment should continue on an outpatient basis for this patient ered elastic bandage systems, may be easier to apply in the who has overweight and no features of anorexia nervosa. presence of bulky dressings. Although antidepressant therapy is appropriate to con- Routine use of antibiotics (topical or systemic) does sider in binge eating disorder, this patient is concerned not aid in venous ulcer healing. Antibiotic therapy is indi- about weight gain, and lisdexamfetamine or topiramate cated only if the ulcer is infected. Clues to infection include should be considered in this situation rather than switching increasing pain, exudate, erythema, or nonresponse to to a second SSRI (fluoxetine) (Option B). appropriate ulcer-directed therapy. There is no indication Monitored dietary intake (Option D) and concurrent that this patient’s ulcer is infected and requires antibiotic psychotherapy are the mainstays of treatment for anorexia therapy, such as cephalexin (Option A). nervosa. This patient’s symptoms of binge eating with no Current evidence does not support the use of honey purging behavior are not consistent with anorexia. (Option C) in the treatment of chronic wounds. No definite conclusion can be reached regarding the effectiveness of topical antiseptics, such as peroxide-based ¢ Cognitive behavioral therapy is the cornerstone of preparations (Option D) or povidone-iodine (Option E), in treatment for binge eating disorder. the healing of venous ulcers. Even if effective, topical ther- apy for venous ulcers would be an adjunct to compression e Lisdexamfetamine reduces the frequency of binge eating therapy. days and can be added as an adjunctive treatment for patients with persistent symptoms of binge eating disorder. ¢ Compression therapy is an essential component in the treatment of venous stasis ulcers. Bibliography Brownley KA, Berkman ND, Peat CM, et al. Binge-eating disorder in adults: e Routine administration of antibiotics has no role in a systematic review and meta-analysis. Ann Intern Med. 2016;165:409- the treatment of chronic venous stasis ulcers. 20. [PMID: 27367316] doi:10.7326/M15-2455

Educational Objective: Treat binge eating disorder with Educational Objective: Treat a venous stasis ulcer. lisdexamfetamine. The most appropriate treatment is compression therapy Lisdexamfetamine (Option C) is the most appropriate treat- (Option B). Treatment of venous stasis ulcers consists ment for this patient with binge eating disorder, which is of local wound care and compression therapy. Infection characterized by binge eating and feelings of loss of control should be eliminated as a contributing cause of nonheal- around food that occur an average of at least once weekly ing venous ulceration. Necrotic tissue should be debrided, for 3 months. Binging episodes include at least three of the and the wound should be covered with a dressing. Various following characteristics: abnormally rapid consumption, dressings are available, and none stand out as superior in eating until uncomfortably full, consuming large amounts of direct comparisons; however, dry gauze should be avoided food when not hungry, eating alone due to embarrassment, because it disrupts the formation of granulation tissue and feelings of guilt related to overconsumption. These char- when removed. Many patients prefer hydrocolloidal dress- P= = ings because of ease of application and reduction in pain, wn acteristics distinguish binge eating disorder from overeating. = The main treatment for binge eating disorder is cognitive when present. oO = wn behavioral therapy (CBT). Because this patient’s symptoms Compression therapy is an essential component of the oo have persisted while she is engaged in CBT, medical therapy treatment of venous stasis ulcers. Before application of com- = Qa. can be considered. A systematic review found that CBT, pression therapy, measurement of the ankle-brachial index a lisdexamfetamine, selective serotonin reuptake inhibitors (ABI) is recommended to avoid inappropriate application of oe =. (SSRIs), and topiramate all reduced binge eating. Lisdexam- lower extremity compression in a patient with peripheral 2 S fetamine and topiramate reduced weight in adults with artery disease. An absolute contraindication to compression © wn binge eating disorder and should be considered for this therapy is an ABI of 0.5 or less, although cautious use is patient, who has partial response to CBT and an SSRI. Side advised for any patient with an ABI less than 0.9. There are effects are common with lisdexamfetamine and include many options for compression therapy, including multilay- headache, gastrointestinal upset, and sleep disturbance. Lis- ered elastic bandage systems, elastic compression stock- dexamfetamine has been shown to reduce the frequency of ings, and intermittent pneumatic compression (dynamic binge eating days and is FDA approved to treat binge eating compression). Static compression with a zinc oxide paste disorder. Topiramate is not FDA approved for this indication. bandage (e.g., Unna boot) is not as effective as elastic com- In addition to initiating lisdexamfetamine, CBT should be pression or dynamic compression in venous ulcer healing. continued in this patient. At times, the choice is determined by the ability of the For patients who are severely underweight or at risk for compression system to accommodate the bulk of the wound life-threatening complications, admission to an inpatient facil- dressing. Specialty compression stockings that include a ity specializing in eating disorders (Option A) is indicated. Treat- zipper may increase patient adherence and, like multilay- ment should continue on an outpatient basis for this patient ered elastic bandage systems, may be easier to apply in the who has overweight and no features of anorexia nervosa. presence of bulky dressings. Although antidepressant therapy is appropriate to con- Routine use of antibiotics (topical or systemic) does sider in binge eating disorder, this patient is concerned not aid in venous ulcer healing. Antibiotic therapy is indi- about weight gain, and lisdexamfetamine or topiramate cated only if the ulcer is infected. Clues to infection include should be considered in this situation rather than switching increasing pain, exudate, erythema, or nonresponse to to a second SSRI (fluoxetine) (Option B). appropriate ulcer-directed therapy. There is no indication Monitored dietary intake (Option D) and concurrent that this patient’s ulcer is infected and requires antibiotic psychotherapy are the mainstays of treatment for anorexia therapy, such as cephalexin (Option A). nervosa. This patient’s symptoms of binge eating with no Current evidence does not support the use of honey purging behavior are not consistent with anorexia. (Option C) in the treatment of chronic wounds. No definite conclusion can be reached regarding the effectiveness of topical antiseptics, such as peroxide-based ¢ Cognitive behavioral therapy is the cornerstone of preparations (Option D) or povidone-iodine (Option E), in treatment for binge eating disorder. the healing of venous ulcers. Even if effective, topical ther- apy for venous ulcers would be an adjunct to compression e Lisdexamfetamine reduces the frequency of binge eating therapy. days and can be added as an adjunctive treatment for patients with persistent symptoms of binge eating disorder. ¢ Compression therapy is an essential component in the treatment of venous stasis ulcers. Bibliography Brownley KA, Berkman ND, Peat CM, et al. Binge-eating disorder in adults: e Routine administration of antibiotics has no role in a systematic review and meta-analysis. Ann Intern Med. 2016;165:409- the treatment of chronic venous stasis ulcers. 20. [PMID: 27367316] doi:10.7326/M15-2455 146