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Restless leg, Cardiology Which of the following agents is associated with exacerbations of restless legs syndrome (RLS)? A) Diphenhydramine B) Iron C) Zolpidem D) Gabapentin Answer • A) Diphenhydramine Diagnostic criteria for RLS include: A) Urge to move legs during periods of inactivity B) Symptoms that may be relieved by movement C) Symptoms that occur or worsen exclusively during evening or night D) All the above Answer • D) All the above Pathophysiology • • • • • • • • • • • • • • • • dopaminergic dysfunction related to decreased iron concentrations in substantia nigra Common descriptions of RLS: “creepy crawly” sensation (eg, sensation of worms crawling out of feet or ankles) sensation of running water often difficult for patients to describe sensations Diagnostic criteria: urge to move limbs, accompanied by uncomfortable or unpleasant sensations urge to move begins during periods of inactivity symptoms may be relieved by movement symptoms occur exclusively or worsen during evening or nigh Symptoms described as most troublesome by patients: disruption of sleep uncomfortable feeling inability to stay still Pain Jerking daytime fatigue • • • • • • • • • • • • • • • • • • • • Differential diagnosis attention-deficit/hyperactivity disorder agitated depression essential tremor Nocturnal leg cramps Radiculopathy peripheral neuropathy (starts at toes, with sensation often described as burning) arthritic disease (occurs more often with weight bearing) vascular disease Exacerbations: can involve other parts of body (eg, arms) always occurs in legs first often exacerbated by levodopa and carbidopa (eg, Parcopa, Sinemet-10/100, Sinemet-25/100) Laboratory tests: check serum ferritin level iron saturation <20% considered abnormal check metabolic panel and creatinine Common clinical features: positive family history response to dopaminergic therapy periodic leg movements in sleep (PLMS) often noticed by bed partner in 50% of RLS patients movements occur frequently (eg, every 40 sec) patients often prefer sleeping with feet uncovered symptoms generally do not respond to typical sleep hygiene (eg, refraining from watching television before bedtime) Nonpharmacologic strategies • • • • • physical activity Avoid caffeine and alcohol stimulate legs traveling on long flights —select aisle seat occupy mind with, eg, food, computer games, or movie Choose the correct statement about levodopa. A) Onset slow B) Best choice for intermittent usage when RLS symptoms occur occasionally C) No risk for augmentation D) Long duration of action Answer • B) Best choice for intermittent usage when RLS symptoms occur occasionally • • • • • • • • • • • • • • • • • • • • • • • • • • Pharmacotherapy dopaminergic agents (eg, levodopa, dopamine agonists) anticonvulsants (eg, gabapentin, carbamazepine) Opioids sedative-hypnotic agents (eg, clonazepam [Klonopin]) supplement iron to bring saturation to >20% (vitamin C may improve absorption; consider side effects of iron) Ropinirole (Requip); pramipexole (Mirapex; use lower doses than those used for Parkinson disease) levodopa —fast onset; best choice for intermittent usage when symptoms occur occasionally dopamine agonist recommended for daily symptoms Other drawbacks of dopaminergic agents: augmentation— exacerbation and increased intensity of symptoms spread of symptoms to arms associated with levodopa (>200 mg/day) and carbidopa effects less dramatic when medication stopped rebound —symptoms occur early in morning occurs with use of levodopa and carbidopa due to short action side effects—include increased gambling or sexual urges Gabapentin: start with 100 mg/day (recommended maximum dose 300 mg/day) side effects include dizziness Carbamazepine: monitoring levels not required secondor third-line therapy for patients with neuropathy Sedative-hypnotic agents: clonazepam may be less addictive than other agents Zolpidem use for RLS off Pharmacotherapy: label (more data needed) no evidence of augmentation patients may require higher doses Opioids: third-line agents tramadol recommended over hydrocodone for long-term us RLS is a: A) Neurodegenerative disorder B) Physical condition C) Mental condition D) Vascular disease Answer • B) Physical condition Children and RLS • “growing pains” may be manifestation of RLS • trials evaluating potential pharmacologic treatments under way • check family history • benzodiazepines, anticonvulsants, and opioids prescribed for children with other conditions, but levodopa should be used with caution • Summary of RLS: not neurodegenerative disorder; physical rather than mental condition Patients with _______ have muscle aches or weakness without elevations in creatinine kinase (CK). A) Myalgia B) Myositis C) Rhabdomyolysis D) All the above Answer • A) Myalgia Definitions • • • • • • • • • • • • • • • • myalgia—ache or weakness without elevation of creatine kinase (CK) myositis —ache or weakness with elevation of CK rhabdomyolysis —muscle symptoms with marked elevation of CK (>10 times normal) and elevated serum creatinine Incidence of myalgias: higher in clinics than in trials, possibly due to increased direct-to-consumer advertising of medications, voluntary nature of Food and Drug Administration (FDA) Adverse Event Reporting System, and exclusion from clinical trials of patients with myalgias, extremes of age or lifestyle, or use of drugs that could cause myalgias study —looked at 7900 patients on high-dose statin for 3 mo, or with decreased dose or discontinuation of statin in last 3 mo medications included atorvastatin (Lipitor; 40-80 mg/day), fluvastatin (extended-release; 80 mg/day), pravastatin (40 mg/day), or simvastatin (Zocor; 40-80 mg/day) 10% had muscle symptoms incidence highest (20%) with simvastatin and lowest with fluvastatin 60% had widespread pain most patients had pain in thighs and calves 25% had tendonitis 27% regarded pain as minor distraction 26% reported that pain interfered with major exertion, and 20% with minor exertion 20% of patients discontinued therapy 17% wanted reduced dose myalgia generally occurred within first or second month (time of onset may be affected by other medications that increase plasma levels Which of the following statins appears least associated with high plasma levels due to high firstpass metabolism? A) Simvastatin B) Atorvastatin C) Fluvastatin D) Pravastatin Answer • C) Fluvastatin • • • • • • • • • • • • • • • • • • • Risk factors for myalgias alcohol use heavy exercise primary muscle disease increased statin levels— use of high doses low body mass index drug interactions (eg, cytochrome P450 3A4 inhibitors) verapamil, diltiazem, SSRIs, amiodarone, and colchicine tend to increase plasma levels (especially in older patients, who may have altered kidney or liver function) Pharmacogenomics: SLCO1B1 gene —encodes for organic transporter that brings statin to liver and enhances uptake deficiency in transporter results in higher plasma levels of statin and higher risk for complications Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) — 12,000 patients in United Kingdom randomized to 20 mg or 80 mg of simvastatin after myocardial infarction (MI) isolated 120 patients who had myalgic complaints and elevations of CK genome-wide scanning found C allele defect associated with 5- to 6-fold higher risk patients with more complaints of myalgia had less reduction in cholesterol due to low uptake of drug Management: no recommendation for routine monitoring of CK before therapy (consider in higherrisk patients [eg, patients who exercise heavily]) change statin or statin dose fluvastatin associated with high first-pass metabolism (ie, less likely to result in high plasma levels) ezetimibe (Zetia) and colesevelam expensive, with modest benefits niacin may be beneficial Alternative statin dosing • • • • • • • • • • • • • • • based on small studies Rosuvastatin (Crestor) —tolerability of 80% and lipid reduction of 29% seen with 5 to 20 mg/wk similar results seen in other studies with 2.5 to 20.0 mg/wk, or dosing every other day (average dose 5 mg) studies—1) looked at patients on ezetimibe (10 mg/day) for few months, followed by addition of atorvastatin (10 mg twice weekly) for 3 mo saw good tolerability and reduction in low-density lipoprotein (LDL) 2) looked at rosuvastatin (5 or 10 mg twice weekly) and saw reasonable LDL Reduction atorvastatin and rosuvastatin (drugs with long half-lives) could potentially be used every other day, or 1 to 2 times/wk with reasonable reductions in LDL 3) looked at patients with previous coronary disease and myalgia on different statins average LDL 175 mg/dL; after 3 mo, 16% LDL reduction seen with ezetimibe (10 mg/day), 33% with fluvastatin (extended release; 80 mg/day), and greater reduction seen with combination of both agents myalgia complaints highest with ezetimibe, and lower with combination therapy small number of patients discontinued therapy 4) small studies of ezetimibe and colesevelam saw 42% reduction in LDL 5) niacin (homeopathic dose, 500 mg; therapeutic dose, 2-3 g) shown to reduce LDL by 5% to 25%; plant stanols can be used Xuezhikang • study in China in 4800 patients with previous MI saw significant reduction in event rates • supplement combines other substances (eg, plant stanols) with red yeast rice (fermented form of mold) • active ingredient (monacolin K) same as that of lovastatin • 4800 mg equal to 10 mg of lovastatin; concerns raised by questionable manufacturing standards and lack of approval by FDA • available in China, but not in United States • tolerability appears similar to that of statins; some cases of renal failure reported Statins with long half-lives (eg, atorvastatin, rosuvastatin) could potentially be used every other day or 1 to 2 times weekly, with reasonable reductions in lowdensity lipoprotein. A) True B) False Answer • A) True Red yeast rice A) Active ingredient (monacolin K) same as that of lovastatin B) Absorption increased by vitamin C; associated with marked CK elevations C) Blood levels shown to be reduced by pravastatin; data inconclusive D) Immediate-release form generally associated with more side effects and hepatotoxicity than extended-release form Answer • A) Active ingredient (monacolin K) same as that of lovastatin Coenzyme Q10 A) Active ingredient (monacolin K) same as that of lovastatin B) Absorption increased by vitamin C; associated with marked CK elevations C) Blood levels shown to be reduced by pravastatin; data inconclusive D) Immediate-release form generally associated with more side effects and hepatotoxicity than extended-release form Answer • C) Blood levels shown to be reduced by pravastatin; data inconclusive Niacin A) Active ingredient (monacolin K) same as that of lovastatin B) Absorption increased by vitamin C; associated with marked CK elevations C) Blood levels shown to be reduced by pravastatin; data inconclusive D) Immediate-release form generally associated with more side effects and hepatotoxicity than extended-release form Answer • D) Immediate-release form generally associated with more side effects and hepatotoxicity than extended-release form • • • • • • • • • • • • • • Vitamin D and coenxyme Q10 epidemiologic markers suggest hypovitaminosis D associated with myalgia nuclear receptors for vitamin D present in myocytes study —looked at >600 patients in lipid clinic 120 had statin myalgia, and 82 had vitamin D levels <32 ng/mL (mean level, 28 ng/mL) significant number of patients improved with statin plus vitamin D (50,000 IU for 3 mo 92% myalgia-free); problems with study include subject reporting and lack of placebo arm Coenzyme Q10 (coQ10): blood levels shown to be reduced by pravastatin studies —1) study saw 40% reduction in pain with coQ10 (100 mg/day), compared to vitamin E and statin therapy 2) Japanese study compared coQ10 to placebo in patients on atorvastatin (10 mg/day) no difference in CK levels no reports on symptoms 3) study compared coQ10 (200 mg/day) to placebo in 44 patients on simvastatin (40 mg/day) No difference in pain scores summary —data about coQ10 inconclusive • • • • • • • • • • • • • • • • • Conclusion muscle complaints with statin use common mechanisms unclear treat patients symptomatically No outcome data suggest any other strategy reduces events Questions and answers: ezetimibe —not likely harmful renal disease —ezetimibe plus simvastatin (Vytorin) beneficial no studies comparing combination drug to ezetimibe or simvastatin alone Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial —ezetimibe plus simvastatin reduced risk for MI, compared to placebo no good outcome data for ezetimibe alone niacin —outcome data modest (mostly surrogate data) Small amount of mortality data available mortality data about ezetimibe limited over-the-counter or flush-free niacin (inositol) —not beneficial in reducing cholesterol Slow niacin may be effective “if it doesn’t flush, it’s not niacin” speaker prefers extended-release formulation (Niaspan; expensive) immediate-release niacin formulations generally associated with greater flushing and more side effects and hepatotoxicity, compared to extended-release niacin Which of the following should be used initially to identify gastroesophageal reflux disease (GERD) in a patient who presents with heartburn and no alarm symptoms? A) Empiric trial of acid suppression for 4 to 8 wk B) Esophagogastroduodenoscopy C) Barium radiography D) pH probing Answer • A) Empiric trial of acid suppression for 4 to 8 wk • • • • • • • • • • • • • • • • • • • • • • • Dyspepsia and peptic ulcer disease (PUD) differentiated from gastroesophageal reflux disease (GERD) intermittent epigastric pain (gnawing or aching) may improve with meals absence of heartburn and regurgitation reflux should not be bloody Infantile GERD: concerns—increased or persistent forceful vomiting (rule out pyloric stenosis) green, yellow, or bloody vomit difficulty breathing after vomiting food refusal that causes weight loss or poor weight gain pain related to eating or swallowing “test and treat”—start with H2–receptor antagonist or proton pump inhibitor (PPI) if ineffective, can try erythromycin, antacids, or cytoprotective agents (and consult pediatric gastroenterologist) diagnostic studies—barium swallow or upper gastrointestinal (GI) series to rule out congential abnormalities pH probe upper endoscop (esophagogastroduodenoscopy [EGD]) gastric emptying study parental education—smaller or more frequent feedings Elevate head of infant’s crib or bassinet hold infant upright burp child appropriately use bottles that minimize swallowing of air thickening formulas with cereal and introduction of solid food should be discussed with physician involve pediatric gastroenterologist if conventional measures fail need for surgery rare Categorization of GERD • • • • • • • • • • • nonerosive reflux disease (NERD)— 90% of cases erosive esophagitis—Los Angeles classification system based on size and extent of erosions across esophagus other—Barrett esophagus esophageal adenocarcinoma (EAC) GERD algorithm: initiate treatment for heartburn with PPI or H2receptor antagonist if initial response good and patient symptom- free, maintain with lowest effective dose screen high-risk patients (eg, white men >50 yr of age with long-term symptoms who smoke) for Barrett esophagus if no initial response, use step-up therapy (ie, start with lowest effective dose, then increase to twice-daily dosing if patient on H2-receptor antagonist, switch to PPI if patient on PPI, increase to maximum dose or twice-daily dosing) if still no response, confirm diagnosis with pH probing or endoscopy if alarm symptoms present, or 8-wk trial of PPI fails, refer for endoscopy In patients with atypical GERD and moderate to severe persistent asthma, twice-daily proton pump inhibitor (PPI) therapy for 24 wk is most likely to: A) Reduce asthma exacerbations B) Reduce albuterol use C) Cause chest pain D) Improve pulmonary function Answer • A) Reduce asthma exacerbations • • • • • • • • • • • • • • • • • Diagnosis no gold standard 50% of patients who undergo EGD have normal findings sensitivity and specificity of pH probing high, but false-positive and false-negative results occur sensitivity of EGD for pathologic reflux low Usefulness of barium radiography limited empiric trial of acid suppression for 4 to 8 wk can identify GERD in patients without alarm symptoms recommend lifestyle modifications (eg, avoid eating 3-4 hr before recumbency) Alarm symptoms: black or bloody stools Choking Chronic cough Dysphagia early satiety Hematemesis Hoarseness Iron deficiency anemia Odynophagia unexplained weight loss Pharmacologic treatment for atypical GERD • • • • • • • • • • • • • • • • • • • • • H2-receptor antagonists, PPIs, and prokinetic agents PPIs should be taken 30 to 60 min before meals NERD—step-up therapy (H2-receptor antagonist followed by PPI if no improvement) and step-down therapy (PPI followed by lowest dose of acid suppression) equally effective step-down therapy does not necessarily change natural history of disease, but can decrease pharmacy costs erosive esophagitis—PPI treatment of choice for acute and maintenance therapy on-demand therapy—patients take medications as needed minimizes pharmacy costs efficacious Newer pharmacologic agents: baclofen—gama-aminobutyric acid agonist works on smooth muscle frequent dosing often required (may be sedating or cause central nervous system side effects) arbaclofen—R-isomer of baclofen small trials showed efficacy in reducing number of heartburn events at all dose levels studied cisapride (Propulsid)—effective in minimizing GERD symptoms, but associated with cardiac effects mosapride—small study saw decrease in GERD symptoms and improved gastric emptying when given with omeprazole to patients resistant to omeprazole alone Laryngeal symptom and asthma exacerbations: no significant long-term benefits shown with twice-daily PPI for laryngealinduced cough or chronic hoarseness twice-daily PPI therapy for 24 wk shown to reduce asthma exacerbations in patients with moderate to severe persistent asthma treatment may improve quality of life, but may not reduce symptoms or albuterol use no improvement in pulmonary function Patients with chronic cough should be prescribed antisecretory therapy, even with no reportable GI symptoms PPI therapy reduces symptoms of noncardiac chest pain, and can be used as diagnostic test for abnormal reflux Classic GERD • consider twice-daily PPI, or confirm diagnosis with 24-hr pH monitoring • if patient improves, taper treatment • if symptoms recur, observe and use maintenance therapy • if pH test positive while patient taking PPI, increase dose • (if negative, reconsider diagnosis) • • • • • • • • • • • • • • Surgical treatment fundoplication; nearly 50% of patients require PPI therapy within 1 yr after surgery Stretta procedure endoscopic treatment destroys top layer of mucosa to decrease acid exposure trial showed BARRX procedure may minimize dysplastic transformation to EAC Complementary and alternative medicine: licorice, marshmallow root, and slippery elm (demulcents); ginger; apple cider vinegar probiotics (controversial may be better for lower GI issues) digestive enzymes relaxation, meditation, biofeedback, and acupuncture Follow-up and surveillance: if symptoms remain unchanged in patient with previous normal endoscopy, repeating endoscopy not recommended for 10 yr refer patients with warning signs and symptoms that suggest complications further diagnostic testing should be considered in patients who do not respond to acid suppression, and in patients with history of chronic GERD at risk for complications chronic reflux plays role in development of Barrett esophagus (unclear whether outcomes can be changed) antisecretory therapy reduces need for recurrent dilatation due to formation of esophageal strictures Which of the following are the 2 most common prognosticators for progression of Barrett esophagus to esophageal adenocarcinoma (EAC)? A) Smoking and age of patient B) Degree of disease and age of patient C) Presence of heartburn and male sex D) Age of patient and male sex Answer • B) Degree of disease and age of patient Barrett esophagus • • • • • • • • • • • • • • • • • • • • • • • change in distal esophageal epithelium of any length that can be recognized as columnar-type mucosa on endoscopy, and intestinal metaplasia on biopsy of tubular esophagus screening controversial degree of Barrett esophagus and age of patient most common prognosticators for progression to EAC can present without heartburn any grade of dysplasia should be confirmed by expert pathologist Pharmacologic acid suppression controversial Esophageal adenocarcinoma: screening should not be performed in men <50 yr of age, or in women, due to low incidence of cancer (regardless of frequency of symptoms) incidence in white men >60 yr of age with weekly GERD symptoms substantial and warrants screening PPI issues: end points in PPI treatment unclear many patients begin self-directed trial of over-the-counter PPIs patients often left on PPI therapy without adequate follow-up cost of inappropriate PPI use significant risks—hip fractures related to osteoporosis vitamin B12, calcium, zinc, vitamin C, and magnesium deficiencies interactions with clopidogrel (particularly with omeprazole) spontaneous bacterial peritonitis contraindicated in pregnancy Clostridium difficile diarrhea— associated with use of PPIs with antibiotics 43-fold increase in risk with PPIs, antibiotics, and chemotherapy Protocols suggest stopping PPI therapy on hospital admission, unless PPI specifically indicated or if symptoms extreme 6-fold risk for community-acquired pneumonia associated with current PPI therapy started within 2 days of diagnosis some conflicting data about risks antiplatelet interactions Regardless of the frequency of symptoms, screening for EAC in men <50 yr of age is not recommended. A) True B) False Answer • A) True Risks of PPI therapy include: A) Calcium deficiency B) Interactions with antiplatelet agents C) Clostridium difficile diarrhea D) All the above Answer • D) All the above Most patients with peptic ulcer disease (PUD) do not complain about: A) Gnawing or burning pain B) Pain several hours after a meal C) Heartburn D) Waking between 12 am and 3 am due to pain Answer • C) Heartburn • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • Functional dyspepsia EGD normal patients do not have heartburn or regurgitation, but have stomach pain difficult to treat may overlap with other diagnoses no proven effective pharmacotherapy may be caused by, eg, acid secretion, delayed or accelerated emptying of stomach, hypersensitivity to stomach acid or expansion, abnormal processing of internal organ activity by brain and nerves, infections, or altered neurohormonal responses to meals many patients respond symptomatically to PPIs (no significant proven superiority over placebo) Peptic ulcer disease: common symptoms—most patients do not complain about heartburn and regurgitation gnawing, burning, or “hunger-like” pain nonradiating, epigastric pain several hours after meal when stomach empty and transit time normal pain often relieved by food or antacids pain commonly awakens patient between 12 AM and 3 AM etiologies—nonsteroidal anti-inflammatory drugs (NSAIDs) Cyclooxygenase (COX)-2 inhibitors Aspirin antiplatelet agents corticosteroids Helicobacter pylori upper GI cancer Advanced age previous upper GI bleeding Zollinger-Ellison syndrome (hypergastrinemia; rare) Management of dyspepsia or PUD: heartburn and/or regurgitation—manage as GERD with PPI or H2-receptor antagonist newer data suggest greater improvement of symptoms with lower doses than with higher doses if no response to therapy, confirm diagnosis with, eg, pH probing EGD does not diagnose GERD or dyspepsia, but can diagnose complications if alarm symptoms present, then treat for 8 wk and consider EGD NSAID and COX-2 inhibitor use—consider discontinuing medication, switching to other agent, or adding PPI symptoms usually resolve 10 to 14 days after stopping agent GI complications shown to be minimally reduced with COX-2 inhibitors relative to standard NSAIDs and aspirin over short term (ie, few weeks) risk for ulcer increased in patients on long-term COX-2 inhibitors Avoid NSAIDs in high-risk patients (particularly patients >65 yr of age), patients with history of PUD, and patients taking long-term corticosteroids and/or anticoagulants Nonsteroidal anti-inflammatory drugs (NSAIDs) should be avoided in which of the following groups of patients? A) Patients >65 yr of age B) Patients with history of PUD C) Patients taking long-term corticosteroids and/or anticoagulants D) All the above Answer • D) All the above Risk for upper GI bleeding and antiplatelet agents • • • • • • • • • • • • • • • • • • • • • • Clopidogrel alone, aspirin alone, NSAIDs alone, and combinations associated with increased risk patients with history of upper GI bleeding at highest risk PPIs appropriate in patients with multiple risk factors who require antiplatelet therapy routine use of PPI or H2-receptor antagonist not recommended for patients at lower risk who have less potential to benefit from prophylactic therapy patients with recurrent GI symptoms shown to benefit from PPI while on NSAID observational studies and one randomized trial showed inconsistent effects of cardiovascular outcomes when clopidogrel and PPI used together Study saw use of clopidogrel and PPI (omeprazole) reduced antiplatelet effects of clopidogrel (requires individualized therapy) Dyspepsia without obvious GERD or NSAID use: if patient >65 yr of age or has alarm symptoms, refer for EGD if patient <55 yr of age with no alarm symptoms, consider testing for H pylori and treat if positive (if treatment fails, give trial of PPI for 4 wk if PPI fails, reassess diagnosis) if test negative, give trial of PPI for 4 to 6 wk (if PPI fails, reassess diagnosis) alarm symptoms—GI bleeding heme-positive stools melena Hematemesis Anemia Penetration Perforation plain film radiography best study barium studies or EGD contraindicated obstruction; signs of cancer (eg, weight loss, anorexia) Choose the correct statement about Helicobacter pyloriinfection and NSAID use. A) H pylori eradication eliminates risk for ulcer development in patients taking NSAIDs B) H pylori eradication in patients taking NSAIDs is more effective than PPI therapy in reducing recurrence of PUD C) Recurrence of ulcer bleeding is significantly lower 6 mo after H pylori eradication, compared to that in patients taking low-dose aspirin D) H pylori eradication alone is not sufficient for minimizing risk for upper gastrointestinal bleeding due to PUD in patients taking NSAIDs Answer • D) H pylori eradication alone is not sufficient for minimizing risk for upper gastrointestinal bleeding due to PUD in patients taking NSAIDs • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • H pylori Infection H pylori and NSAIDs: H pylori eradication does not eliminate risk for ulcer development in patients taking NSAIDs Eradication in patients taking NSAIDs less effective than PPI therapy in reducing recurrence of PUD or rebleeding recurrence of ulcer bleeding in patients taking low-dose (81 mg/day) aspirin similar to 6 mo after H pylori eradication H pylori reduction alone not sufficient for minimizing risk for upper GI bleeding due to PUD in patients taking NSAIDs Diagnosis and treatment of H pylori: established indications— active PUD confirmed history of PUD in patients not previously treated for H pylori gastric mucosa-associated lymphoid tissue lymphoma (especially low-grade) endoscopic resection of early gastric cancer uninvestigated dyspepsia Controversial indications—nonulcer dyspepsia GERD NSAID use Unexplained iron deficiency anemia populations at higher risk for gastric cancer; antibody testing—inexpensive widely available good negative predictive value positive predictive value dependent on background H pylori prevalence not recommended after H pylori therapy treat if positive, but do not retest with serologic study fecal antigen testing and urease breath testing—identify active infection excellent positive and negative predictive values regardless of prevalence useful before and after therapy first-line therapy—standard dose of PPI twice daily (once daily if using esomeprazole [Nexium]), clarithromycin (500 mg twice daily), and amoxicillin (or metronidazole [500 mg twice daily]) eradication rate 70% to 85% quadruple therapy with bismuth subsalicylate (BSS), metronidazole, tetracycline, and ranitidine (or standard dose of PPI) results in slightly higher eradication rate (may be useful in patients allergic to penicillin; intolerance and noncompliance high) sequential therapy—PPIs could increase effectiveness of amoxicillin no amoxicillin-resistant H pylori Up to one-third of cases resistant to metronidazole Salvage therapy—7-day regimen eradication rate low quadruple therapy with BSS, daily PPI, tetracycline, and metronidazole High pill count results in side effects triple therapy using PPI, amoxicillin, and levofloxacin to be approved Which of the following tests for H pylori is not recommended after eradication therapy? A) Fecal antigen testing B) Serologic antibody testing C) Urease breath testing D) Culture Answer • B) Serologic antibody testing Treatment of H pylori should not be withheld due to concerns that it might worsen GERD symptoms. A) True B) False Answer • A) True • • • • • • • • • • • • • • • • • • • • • • • • • Reassessing diagnosis if EGD normal, consider rapid urease testing and/or histology for H pylori culture and sensitivity testing for patients previously treated for H pylori (if detected, use salvage therapy some patients may receive 1 round of salvage therapy) EGD—based on histology, sensitivity and specificity excellent often expensive requires trained pathologist Rapid urease breath testing—generally inexpensive rapid results specificity excellent and sensitivity good sensitivity reduced in posttreatment setting culture—specificity excellent helps determine antibiotic sensitivity Expensive not widely available Polymerase chain reaction testing—sensitivity and specificity excellent allows for determination of antibiotic sensitivity Difficult to standardize due to variety of methodologies Persistent symptoms with no other established cause: usually functional dyspepsia consider antidepressant therapy, hypnotherapy, behavioral therapy, and prokinetic agents (ie, erythromycin or metoclopramide [eg, Octamide, Reclomide, Reglan]) controversies—clinical benefit seen in small percentage of patients after H pylori eradication no clear evidence that H pylori consistently worsens or improves GERD symptoms treatment of H pylori not shown to worsen GERD symptoms (do not withhold) available data support association between H pylori and iron deficiency, but no proven cause and effect no population-based data suggest H pylori eradication reduces incidence of gastric adenocarcinoma Transmission of HIV by which of the following modes makes up 75% of diagnoses? A) Man-to-woman sexual contact B) Man-to-man sexual contact C) Mother-to-child transmission D) Injection drug use Answer • B) Man-to-man sexual contact According to the Centers for Disease Control and Prevention, which of the following groups of patients should be screened for HIV? A) All patients 13 to 64 yr of age B) All patients initiating treatment for tuberculosis C) All pregnant women D) All the above Answer • D) All the above Which of the following symptoms is most common in patients with HIV? A) Oral lesions B) Fever C) Sore throat D) Maculopapular rash Answer • B) Fever Magnetic resonance imaging (MRI) suggests HIV infection ages brain blood flow by 15 to 20 yr. A) True B) False Answer • A) True The Veterans Aging Cohort Study concluded that non-HIV biomarkers (eg, anemia, liver disease, inflammatory markers) were of no value in estimating risk for death, compared to HIV biomarkers. A) True B) False Answer • B) False Choose the correct statement about the pneumococcal vaccine. A) Overall efficacy, 25% B) Patients >65 yr of age should receive second dose to boost immunity C) Less effective in older patients with longer time since immunization D) Not cost effective when given at age 65 yr Answer • C) Less effective in older patients with longer time since immunization Compared to the standard influenza vaccine, Fluzone HighDose influenza vaccine: A) Should be used only in adults ≥65 yr of age B) Is associated with lower antibody levels C) Contains less protein D) Causes fewer side effects Answer • A) Should be used only in adults ≥65 yr of age Choose the correct statement about herpes zoster vaccine. A) Multiple studies show high efficacy in immunocompromised hosts B) More effective in patients ≥80 yr of age C) Protection against postherpetic neuralgia persists until age 80 yr D) Data suggest immunity lasts 3 yr Answer • C) Protection against postherpetic neuralgia persists until age 80 yr Which of the following should be considered when providing other vaccines concomitant with herpes zoster vaccine? A) Concomitant vaccines should always be avoided B) Acceptable to give pneumococcal or influenza vaccine C) Vaccines should be injected in the same arm D) Vaccines should be injected from the same syringe Answer • B) Acceptable to give pneumococcal or influenza vaccine Which of the following can be used for the treatment of pertussis? A) Azithromycin B) Clarithromycin C) Trimethoprimsulfamethoxazole D) Any of the above Answer • D) Any of the above The CHA2DS2-VASc scoring system for predicting risk for stroke assigns 2 points to which of the following? A) Age 65 to 74 yr B) Aortic plaques C) History of stroke D) Female sex Answer • C) History of stroke Choose the correct statement about dabigatran. A) 150 mg twice daily shown to reduce risk for stroke and intracerebral hemorrhage B) Should be taken on empty stomach C) Preferred in patients with renal failure or valvular heart disease D) No known drug interactions Answer • A) 150 mg twice daily shown to reduce risk for stroke and intracerebral hemorrhage Choose the correct statement about rivaroxaban. A) Should be taken 2 to 3 times daily B) Half-life longer than that of dabigatran C) Superior to warfarin in reducing risk for major bleeding D) Shown to reduce intracranial hemorrhage by 60% Answer • D) Shown to reduce intracranial hemorrhage by 60% In patients with atrial fibrillation (AF), risk of developing dementia within 5 to 7 yr is increased 2- to 3-fold. A) True B) False Answer • A) True Compared to amiodarone, dronedarone: A) Is associated with greater neurotoxicity B) Is associated with more thyroid problems C) Has a shorter half-life D) Is superior in increasing median time to recurrence of AF Answer • C) Has a shorter half-life Dronedarone is contraindicated in patients with: A) Hypertension and insignificant left ventricular hypertrophy B) Decompensated heart failure C) Coronary disease D) All the above Answer • B) Decompensated heart failure Oxygen radical absorbance capacity is: A) A measure of antioxidant capacity of foods B) The sum of vitamins C and E in foods C) Based on measurements of samples from vascular tissue D) Not affected by water content in foods Answer • A) A measure of antioxidant capacity of foods A study looking at the antioxidant effects of active strawberry compounds after ingestion of a high-fat meal found: A) Protective benefits against lowdensity lipoprotein (LDL) oxidation B) Improvements in C-reactive protein levels C) Need for lower amounts of insulin to maintain glucose D) All the above Answer • D) All the above Which of the following statements about the benefits of chocolate is correct? A) For reduction of blood pressure (BP), 8 g/day of dark chocolate is as effective as 100 g/day of white chocolate B) Meta-analysis found decrease in BP of ≈10 mm Hg in hypertensive patients who regularly consumed dark chocolate C) Meta-analysis found decrease in BP of ≈5 mm Hg in normotensive patients who regularly consumed dark chocolate D) Regular consumption of dark chocolate may decrease risk of experiencing a cardiovascular (CV) event over 5 yr by 20% Answer • D) Regular consumption of dark chocolate may decrease risk of experiencing a cardiovascular (CV) event over 5 yr by 20% National Health and Nutrition Examination Survey data show a lower incidence of stroke and CV disease mortality (when adjusted for other CV risk factors) with the consumption of fruits and vegetables >3 times daily, compared to consumption <1 time daily. A) True B) False Answer • A) True