July Answers
1. The answer is B.
The goal of a meta-analysis is often to summarize the treatment benefit conferred by an intervention. Risk reduction is frequently expressed by relative risk or odds ratios; however, clinicians also find it useful to be familiar with the absolute risk reduction (ARR). This is the difference in mortality (or another endpoint) between the treatment and the placebo arms. In this case, the absolute risk reduction is 10% – 2% = 8%. From this number, one can calculate the number needed to treat (NNT), which is 1/ARR. The NNT is the number of patients who must receive the intervention to prevent one death (or another outcome assessed in the study). In this case the NNT is 1/8% = 12.5 patients.
2. The answer is B.
Newly refined criteria for classifying fever of unknown origin (FUO) subdivide FUO into four subcategories: classic, nosocomial, neutropenic, and HIV-associated. This patient has nosocomial FUO, which is defined by a temperature >38.2°C (100.7°F) on several occasions in a hospitalized patient receiving acute care in whom infection was not evident at admission. Further, a specific etiology is not identified after 3 days of evaluation and at least 48 h of culture incubation. More than 50% of cases of nosocomial FUO have an infectious etiology; suspect sources include intravascular catheterization, urinary tract infections, Clostridium difficile colitis, and septic phlebitis. However, approximately 25% of these patients have a noninfectious etiology, examples of which include alcohol withdrawal, drug fever, pancreatitis, and adrenal insufficiency. In this case, the patient has been hospitalized and on broad-spectrum antibiotics for over 1 week with new development of an erythematous truncal rash and acute renal failure. Standard cultures are unrevealing. The presence of a rash and the development of fever 1 week into antibiotic therapy suggest drug fever. The acute renal failure probably is secondary to allergic interstitial nephritis, and the white blood cell count may indicate significant eosinophilia. In light of the absence of positive culture data and the patient's clinical stability and lack of underlying immunodeficiency, it is not necessary at this time to add either amphotericin B or vancomycin. Hemodialysis is unlikely to address the patient's fevers. An 111In-labeled white blood cell scan would be indicated if no source of fever could be localized, but a drug fever is a fitting hypothesis. The most appropriate treatment would be to discontinue the most likely offending drug: imipenem-cilastatin. In the case of drug fever, the fevers should cease after 2 to 3 days.
3. The answer is E.
Vitamin K is a fat-soluble vitamin that plays an essential role in hemostasis. It is absorbed in the small intestine and stored in the liver. It serves as a cofactor in the enzymatic carboxylation of glutamic acid residues on prothrombin-complex proteins. The three major causes of vitamin K deficiency are poor dietary intake, intestinal malabsorption, and liver disease. The prothrombin complex proteins (factors II, VII, IX, and X and protein C and protein S) all decrease with vitamin K deficiency. Factor VII and protein C have the shortest half-lives of these factors and therefore decrease first. Therefore, vitamin K deficiency manifests with prolongation of the prothrombin time first. With severe deficiency, the aPTT will be prolonged as well. Factor VIII is not influenced by vitamin K.
4. The answer is E.
The peripheral blood smear showing schistocytes (fragmented red blood cells) and the clinical picture, including the evidence of hemolysis and the absence of coagulopathy, are typical for thrombotic thrombocytopenic purpura (TTP). TTP and hemolytic-uremic syndrome (HUS) are often considered distinct syndromes. However, in adult patients their overlapping symptoms and signs, as well as their common treatment with plasma exchange, make the clinical distinction imprecise and sometimes challenging. TTP is classically defined by a pentad of abnormalities: microangiopathic hemolytic anemia, thrombocytopenia, renal failure, neurologic abnormalities, and fever. However, this fulminant classic presentation is rare. Indeed, the only two criteria required now are thrombocytopenia and microangiopathic hemolytic anemia without another clinically apparent etiology. HUS was initially described in children with acute renal failure who also had thrombocytopenia. This was recognized to have an association with enteric infection with a Shiga toxin–producing bacteria. TTP has been recognized to be a congenital or acquired deficiency in a von Willebrand factor protease, resulting in increased platelet activation. Acquired TTP may be idiopathic (after a viral infection?) or secondary to diseases (e.g., HIV infection, rheumatologic conditions) or drugs (clopidogrel, cyclosporine). Because it is often clinically difficult to distinguish the two entities at first presentation, the term TTP-HUS is often used. Plasma exchange has dramatically changed the natural history of these diseases from one of 85% mortality to one of 85% recovery. In the congenital form of TTP plasma replacement may be sufficient as opposed to exchange. Additional treatments, such as prednisone, splenectomy, and immunosuppression, are unproven but often are used in refractory cases. The blood smear showing microangiopathy with schistocytes excludes ITP, autoimmune hemolytic anemia, and paroxysmal nocturnal hemoglobinuria as the sole diagnosis. The presence of normal coagulation factors makes DIC unlikely.
5. The answer is B.
Trichinella spp. are members of the nematode phylum (roundworms). Trichinosis occurs after a person eats meat containing Trichinella nematode oocytes. After the consumption of affected meat, the encysted larvae are released by the action of gastric acid and pepsin. The larvae penetrate the small interstitial mucosa and rapidly mature into adult worms. In 1 week female worms release newborn larvae that travel via the circulation to striated muscle and then encyst. Clinical symptoms follow each of these phases. Initially gut invasion may be marked by abdominal pain, nausea, and constipation or diarrhea. Larval migration, which occurs during the second week after infection, produces a local and systemic hypersensitivity reaction manifested by fever, hypereosinophilia, and periorbital and facial edema. Myocarditis, encephalitis, and pneumonitis are rare but potentially life-threatening complications that may occur during this phase. After larval encystment in muscle for 2 to 3 weeks, edema and symptoms of myositis, including muscle edema and weakness, develop. The symptoms subside gradually during what may be a prolonged convalescence. Antihelminthic drugs are ineffective against the encysted larvae. Trichinosis, which typically is associated with eosinophilia and an elevated IgE level, may be prevented by cooking pork until it is no longer pink or freezing it at –15°C for 3 weeks. Ocular larva migrans, another nematode infection, is caused by the invasion of Toxocara larvae into the eye, typically producing a granulomatous mass, usually in the posterior pole of the retina.
6. The answer is B.
Hospital-acquired pneumonia accounts for approximately 20% of nosocomial infections. In patients in intensive care units an attributable mortality rate of 6 to 14% has been associated with ventilator-associated pneumonia (VAP). Aspiration is felt to be a common contributor to the development of VAP. Three trials have demonstrated a decreased incidence of VAP with a semirecumbent position more than 45-degrees. Stress ulcer prophylaxis does not prevent VAP; instead, it may increase the incidence because of its effect in changing the microbial gastric flora to gram-negative organisms. This is especially true in the case of H2 blockers and proton pump inhibitors. Sucralfate has been demonstrated to have less associated VAP compared with H2 blockers but offers less protection against gastrointestinal (GI) bleed and is no better than placebo for the prevention of VAP. Increasing the frequency of ventilator circuitry changes has also been associated with an increased frequency of VAP. Finally, there are insufficient data to support selective gut decontamination, and in light of worries about the selection of resistant organisms, it is not recommended.
7. The answer is E.
Approximately 3000 heart transplants are performed each year
in the
8. The answer is B.
The patient has an ischemic cardiomyopathy with an ejection fraction below 35%. In this patient population mortality benefit has clearly been demonstrated with ACE inhibitors and beta blockers, namely, metoprolol XL and carvedilol. Because of her history of myocardial infarction, aspirin is indicated. In patients with ischemic cardiomyopathy and a depressed ejection fraction, there is now good evidence that implantable defibrillators confer a mortality benefit. No data suggest a mortality benefit with the long-acting oral nitrate isosorbide mononitrite. There is a mortality benefit of isosorbide dinitrite and hydralizine versus placebo, but this regimen is still not as beneficial as ACE inhibitors.
9. The answer is D.
Ventilatory function can be easily measured with lung volume measurement and the FEV1/FVC ratio. A decreased FEV1/FVC ratio diagnoses obstructive lung disease. Alternatively, low lung volumes, specifically decreased TLC, and occasionally decreased RV diagnose restrictive lung disease. With extensive air trapping in obstructive lung disease, TLC is often increased and RV may also be increased. VC is proportionally decreased. MIP measures respiratory muscle strength and is decreased in patients with neuromuscular disease. Thus, myasthenia gravis will produce low lung volumes and decreased MIP, whereas patients with idiopathic pulmonary fibrosis will have normal muscle strength and subsequently a normal MIP but decreased TLC and RV. In some cases of pulmonary parenchymal restrictive lung disease, the increase in elastic recoil results in an increased FEV1/FVC ratio. The hallmark of obstructive lung disease is a decreased FEV1/FVC ratio.
10. The answer is E.
Multiple drugs have been associated with eosinophilic pulmonary reactions. They include nitrofurantoin, sulfonamides, NSAIDs, penicillins, thiazides, tricyclic antidepressants, hydralazine, and chlorpropramide, among others. Amiodarone can cause an acute respiratory distress syndrome with the initiation of the drug as well as a syndrome of pulmonary fibrosis. Eosinophilic pneumonia is not caused by amiodarone.