Question 1

A randomized, parallel-group, controlled clinical trial evaluates the effectiveness of an anti-inflammatory intervention as treatment for neuropathic pain following spinal cord injury.  Participants with varying levels and severities of spinal cord injury are randomly assigned to either a 24-week, anti-inflammatory diet treatment group or a control group.  Primary outcomes consist of changes in pain scores and markers of inflammation at 6 months.  Preliminary analyses reveal a significant reduction in pain scores in the treatment group from baseline to 6 months (p = 0.03).  There was a significant reduction in pain scores among nonobese subjects (p = 0.01) and a nonsignificant increase in pain scores among obese subjects (p = 0.06).  Which of the following is the best explanation for these differences in findings between obese and nonobese subjects?

Accepted Answer

Explanation: Effect modification (interaction bias) occurs when an extraneous variable (effect modifier) changes the direction or strength of the effect that the independent variable (exposure or treatment) has on the dependent variable (outcome). For instance, aspirin use is associated with Reye syndrome in children but not adults; therefore, age (effect modifier) modifies the effect of aspirin (exposure) on Reye syndrome development (outcome). Stratification based on the modifier (eg, analyzing the data by age group) can help detect effect modification as it typically shows different effects in each stratum (eg, children, adults); separate measures of effect should be reported for each stratum. In this case, the treatment group (ie, 24-week anti-inflammatory diet) had a significant reduction in pain scores from baseline to 6 months compared to the control group (p < 0.03). However, the effect was significant only among nonobese (nonsignificant among obese subjects), and went in opposite directions depending on weight status (reduced pain among nonobese versus increased pain among obese). Therefore, weight status is an effect modifier that changes the effect of the intervention diet on pain scores. A stratified analysis by weight group (nonobese and obese) helps to estimate the real effect. (Choices A and D) Effect modification is sometimes confused with confounding bias, which occurs when an extraneous variable (ie, confounder) associated with both the exposure and the outcome obscures the association between the exposure and the outcome. With confounding (unlike with effect modification), no change in the strength or direction of the effect is typically seen with stratification. Randomization usually helps remove confounder effects. If successful randomization has occurred, characteristics such as obesity, age, and sex should be similarly distributed between the treatment and the control groups, and confounding should be minimized. Because obesity was found to be an effect modifier and not a confounder, neither confounding bias nor randomization failure explain the differences seen between obese and nonobese groups. (Choice C) The Hawthorne (observer) effect is the tendency of study subjects to change their behavior as a result of their awareness of being studied. However, it is commonly seen in studies concerning behavioral outcomes or outcomes that can be influenced by behavioral changes. (Choice E) Selection bias can occur with inappropriate (random or nonrandom) selection methods or through selective attrition of the study participants. Randomization in a clinical trial reduces selection bias. Educational objective: Effect modification occurs when the magnitude or direction of the effect of the independent variable on the dependent variable (outcome) varies depending on the level of a third variable (effect modifier). Separate (stratified) analyses should be conducted for each level of the effect modifier.

Question 2

A group of graduate students conducted a case-control study to evaluate the association between sporadic frontotemporal dementia and thyroid disease.  A total of 80 patients with sporadic frontotemporal dementia along with 160 age and sex surrogate informant matched controls participated in the study.  Results showed that thyroid disease was associated with frontotemporal dementia with an odds ratio of 2.5 and a 95% confidence interval: 0.9-7.9.  The students reported that patients with sporadic frontotemporal dementia were 2.5 times more likely to have thyroid disease compared to patients with no sporadic frontotemporal dementia.  They concluded that there is a statistically significant association between sporadic frontotemporal dementia and thyroid disease.  Based on this information, which of the following is the best evaluation of the students' conclusion?

Accepted Answer

Explanation: This case-control study evaluated the association between sporadic frontotemporal dementia and thyroid disease in 80 patients with sporadic frontotemporal dementia and 160 age and sex surrogate informant matched controls. The results of the study showed that thyroid disease was associated with frontotemporal dementia with an odds ratio (OR) of 2.5 and a 95% confidence interval (CI): 0.9-7.9. The OR is a measure of association between an exposure to a risk factor and an outcome, usually defined as the odds of an exposure in cases divided by the odds of the same exposure in controls. The OR may also be defined as the odds of outcome among exposed patients relative to nonexposed patients. These OR definitions are mathematically equivalent. OR = (odds of outcome in exposed group) / (odds of outcome in nonexposed group) An OR > 1.0 indicates that the exposure is associated with an increase in odds of outcome. The CI of an OR indicates, with a certain confidence level, whether a given OR is statistically different from the null value (OR = 1.0). A CI that excludes the null value is statistically significant (at that confidence level). In this study, the 95% CI includes the null value (OR = 1.0). Based on these results, thyroid disease is not significantly associated (ie, OR is not significantly greater than 1) with sporadic frontotemporal dementia (Choice C). Therefore, the students' conclusion is incorrect. (Choice A) Wider CIs lead to less precise estimates. The width of the CI by itself does not determine statistical significance, which depends on whether the CI includes the null value. (Choice B) The students concluded that there is a statistically (rather than a clinically) significant association between sporadic frontotemporal dementia and thyroid disease. However, the statistical evidence shows that the association was not significant; therefore, the students' conclusion is incorrect. (Choice D) There is not enough information given to determine whether a power calculation was performed. A low statistical power may explain the lack of statistical significance for the association. Regardless, the association was not significant, and therefore the students' conclusion is incorrect. Educational objective: An odds ratio (OR) >1 indicates that the exposure is associated with an increase in the odds of an outcome. A confidence interval that excludes the null value (OR = 1) is statistically significant.

Question 3

A 65-year-old woman with a medical history significant for tobacco use, hypertension, and laparoscopic cholecystectomy is brought to the operating room for a lumbar discectomy. She is placed in the prone position. General anesthesia is induced with propofol and rocuronium, and the patient is intubated without complications. Anesthesia is maintained with sevoflurane. Five minutes later, prior to incision, the ventilator sounds an alarm. Peak pressures have increased to >40 mm Hg, and end-tidal CO₂ has decreased from 30 to 20 mm Hg. Blood pressure is 90/60 mm Hg and pulse is 114/min. On examination, the patient is sedated and paralyzed. Heart sounds are rapid and regular. Bilateral wheezing is noted on auscultation of the lungs. What is the next step in management?

Accepted Answer

Explanation: This patient's hypotension, elevated peak pressures (eg, bronchospasm), and decreased end-tidal CO₂ (eg, decreased cardiac output and CO₂ delivery to the lungs) shortly after anesthetic induction are concerning for anaphylaxis. Anaphylaxis is classically caused by an acute IgE-mediated release of inflammatory mediators (eg, histamine) in response to an allergen. In the perioperative setting, the most common allergens are neuromuscular-blocking agents (eg, rocuronium), antibiotics, skin antisepsis products (eg, povidone-iodine, chlorhexidine), and blood products. caused Because anaphylaxis is a clinical diagnosis that depends on history and physical examination, the diagnosis can be challenging in surgical patients for several reasons, including the following: Patients' inability to communicate symptoms Ongoing physiologic stress, volume shifts, and medication effects, initially attributed to shock Concealment of skin findings under surgical drapes If there is concern for anaphylaxis, the next step is thorough physical examination, especially inspection under the surgical drapes for cutaneous signs (eg, rash, flushing), which are present in most patients. Once the diagnosis is made, epinephrine should be promptly administered. (Choice A) Albuterol may help relieve bronchospasm. Unlike epinephrine, it does not improve hypotension and prevent impending circulatory collapse. This patient's hypotension and ventilatory issues should be completely investigated and addressed prior to proceeding with surgery. (Choice C) Reverse Trendelenburg positioning tilts the body so that the head is elevated and the feet are lowered. However, this (or any upright) posture increases the risk of cardiac arrest in anaphylaxis by decreasing venous return and ventricular filling in the setting of ongoing peripheral vasodilation. Instead, patients should be placed supine with the feet elevated to increase venous return. Reverse Trendelenburg positioning (Choice D) Malpositioning of the endotracheal tube into a mainstem bronchus can cause increased peak pressures (ie, the smaller radius increases resistance) and hypoxemia (eg, from contralateral lung atelectasis). However, this typically causes unilaterally absent breath sounds (vs bilateral breath sounds [wheezing]). Educational objective: Anaphylaxis is a clinical diagnosis that can be difficult to recognize in surgical patients. Early recognition is dependent on thorough physical examination (eg, inspecting skin under the surgical drapes). References: Anaphylaxis during the perioperative period. (http://www.ncbi.nlm.nih.gov/pubmed/25885604)

Question 4

A 6-year-old boy is brought to the clinic for influenza vaccination in September.  He has been healthy and has no nasal congestion, rhinorrhea, or other symptoms.  The patient had 2 episodes of otitis media during infancy and has mild intermittent asthma treated with inhaled albuterol as needed.  He has no other respiratory problems and takes no other medications.  His older brother had cystic fibrosis and recently died at age 10 from a severe influenza infection; the patient's sweat test was negative.  The patient has no medication allergies but has developed a splotchy, itchy red rash to egg-containing products in the past.  Eggs have since been excluded from his diet.  He has no history of other reactions to egg or to immunizations.  Vital signs and physical examination are normal.  Which of the following is the best next step in management of this patient?

Accepted Answer

Explanation: 11ec2b69_bde0_a868_8f63_91bf320d5aa0_MD0005_00 Annual influenza vaccination is recommended for children age >6 months to prevent the acute respiratory viral illness and spread of infection to patients at risk for life-threatening outcomes (eg, asthma, chronic illness, age <2 years). Inactivated intramuscular influenza vaccines are recommended; live-attenuated influenza vaccines are less efficacious and are not currently recommended (Choice B). Influenza vaccines are manufactured using egg-based products. Therefore, all patients should be evaluated for history of egg allergy prior to the administration of egg-containing vaccines, such as the influenza and yellow fever vaccines. Egg proteins in these vaccines may cause immediate-type hypersensitivity reactions in susceptible recipients. Severe reactions are extremely rare, occurring once per million administrations. Children with prior urticarial reactions to egg ingredients can receive inactivated influenza vaccine normally and do not require additional observation. Those with more severe reactions to eggs, including anaphylaxis, angioedema, hypotension, or persistent emesis, should receive their vaccine in a health care setting, supervised by a provider who can recognize and treat severe allergic reactions. The only contraindication to influenza vaccination is severe allergic reaction to the vaccine itself. (Choices C, D, and E) Urticarial reactions to egg protein are not a reason to defer influenza vaccination and do not require additional testing or consultation. Referral for allergy consultation can be considered for patients with prior anaphylaxis to egg products. Educational objective: Children with only urticarial reactions to egg protein can receive the inactivated intramuscular influenza vaccine without restriction. Those with more severe egg reactions should be immunized in a health care setting under the supervision of a provider who can recognize and treat allergic reactions. References: Influenza vaccination and egg allergy: another step forward. (http://www.ncbi.nlm.nih.gov/pubmed/27012268) Establishing the safety of influenza vaccine in egg-allergic individuals. (http://www.ncbi.nlm.nih.gov/pubmed/23805959)

Question 5

A 13-year-old girl is brought to the emergency department by paramedics due to difficulty breathing that started 30 minutes ago.  She was at an amusement park with her family when she was stung by a bee on her left ear.  The patient experienced shortness of breath; itching; and a raised, red rash on her face and neck minutes after the sting.  Medical history includes asthma that is well controlled on budesonide.  Blood pressure is 80/40 mm Hg, pulse is 144/min, and respirations are 28/min.  Pulse oximetry shows 92% on a nonrebreather mask.  The patient is in obvious distress.  The oropharynx is patent and without swelling.  On auscultation of the lungs, severe bilateral wheezing is present.  Heart sounds are rapid without murmurs.  There are multiple raised erythematous papules on her face, neck, and upper chest.  The patient's vital signs normalize, and symptoms resolve completely an hour after a single dose of epinephrine and nebulized albuterol.  What is the appropriate disposition for this patient?

Accepted Answer

Explanation: This patient with a history of asthma developed severe anaphylaxis (eg, hypotension, hypoxia, severe wheezing) after a bee sting. Because of the severity of her initial symptoms and history of asthma (likely the single most important risk factor for fatal anaphylaxis), she should be admitted to the hospital for observation. Although there are no universal guidelines dictating which patients with anaphylaxis require hospital admission, it is generally accepted that those with protracted anaphylaxis (ie, symptoms lasting hours to days despite treatment) should be admitted. In addition, patients who experience complete resolution of symptoms with treatment should be admitted under the following circumstances: Severe symptoms (eg, hypotension, upper airway edema, respiratory distress) occurred at presentation, as in this patient. Multiple doses of epinephrine were required to achieve symptom resolution. These patients are believed to have a higher risk of biphasic anaphylaxis (ie, recurrence of symptoms after an initial period of resolution), which can be fatal. Because both the timing and severity of symptom recurrence are unpredictable, admission for extended observation is recommended. In addition to asthma, other risk factors for fatal anaphylaxis include older age, cardiovascular comorbidities, and delayed administration of epinephrine. (Choice A) Desensitization therapy for bee (and other Hymenoptera) stings takes months to years to achieve and is not performed in an inpatient setting. (Choices C, D, and E) In this patient with severe symptoms (eg, hypotension, hypoxia), biphasic anaphylaxis could be fatal; therefore, hospital admission (vs discharge home) is required. In contrast, those who have milder anaphylactic symptoms (eg, pruritus, rash, nausea) that resolve after a single dose of epinephrine may be considered for discharge. All patients should be discharged with an epinephrine autoinjector. Antihistamines may improve pruritus or hives, and corticosteroids may help suppress a further inflammatory response; however, there is no strong evidence that either medication prevents biphasic anaphylaxis, which is a concern in this patient. Educational objective: Patients with anaphylaxis should be admitted to the hospital when symptoms are protracted or severe (eg, hypotension, upper airway edema, respiratory distress), or require multiple doses of epinephrine to resolve. These patients are at increased risk of biphasic anaphylaxis (ie, recurrence of symptoms after an initial period of resolution), which can be fatal. References: Predictors of hospital admission for food-related allergic reactions that present to the emergency department. (http://www.ncbi.nlm.nih.gov/pubmed/21195944) Anaphylaxis risk factors for hospitalization and intensive care: a comparison between adults and children in an upstate New York emergency department. (http://www.ncbi.nlm.nih.gov/pubmed/30582495) Anaphylaxis diagnosis and management in the emergency department of a tertiary hospital in the Philippines. (http://www.ncbi.nlm.nih.gov/pubmed/32099823)

Question 6

A randomized controlled study of chronically sleep-deprived (<6.5 hr per night), morbidly obese subjects examined whether sleep extension is associated with weight loss and metabolic and endocrinal improvements. The intervention consisted of education regarding sleep hygiene and a gradual change to subjects' bedtimes to earlier in the evening. Participants underwent general screening at visit 1 with collection of baseline parameters; then, 2 months later, at visit 2, subjects were randomized into either an intervention group or a comparison group. Researchers evaluated several parameters, including sleep duration, sleepiness, and sleep quality. The following results were reported: Note: Data is reported as mean ± standard deviation. ^*p < 0.05. ¹ ESS (Epworth Sleepiness Scale [daytime sleepiness]) >10 = sleepy. ² PSQI (Pittsburgh Sleep Quality Index [subjective sleep quality]) >5 = abnormal. There were statistically significant differences in all 3 parameters between visit 1 and visit 2. Which of the following is the best explanation for the difference between findings at the screening and randomization visits?

Accepted Answer

Explanation: The Hawthorne effect is related to subjects' participation in research, the subsequent awareness of being observed, and the possible impact on behavior. This type of bias is commonly seen in studies that concern behavioral outcomes. In this case, subjects reported substantial improvements in sleep in the 2-month period between the screening and randomization phases, when they were candidates for participation but not yet subject to the actual intervention being implemented. It is likely that their awareness of their potential for participation (prior to any intervention) had a significant effect on the outcome under study, a characteristic of the Hawthorne effect. Alterations in behavior due to participation (or potential for participation) awareness may significantly impact how subjects report on the outcomes under study. In most instances, an overestimation of the effect of the intervention will be reported, which is a threat to the internal validity of the study. To minimize the Hawthorne effect, subjects can be kept unaware they are being studied; however, at times this is not reasonably possible. (Choice A) Allocation bias can result from the way subjects are assigned to the treatment and control groups. It may occur when subjects are nonrandomly assigned to the treatment groups of a clinical trial (eg, physicians may preferentially enroll sicker patients into the treatment group). Allocation bias is different from selection bias, which occurs when the studied sample does not represent the target population. (Choice B) A confounder is an extraneous variable that is independently associated with both the dependent variable (ie, outcome) and the independent variable (ie, exposure). Confounding bias occurs when the study design or analysis does not control for the potential effect these confounders may have on the association under study. However, in this case, researchers observed substantial improvements in sleep prior to randomization and to any intervention. (Choice D) The placebo effect is a perceived outcome (eg, beneficial or harmful) resulting from a participant's personal expectations rather than from the treatment itself. In this case, the design did not include a placebo treatment group. Moreover, the observed improvements in sleep were not related to having any particular intervention. (Choice E) Selection bias can occur with inappropriate (eg, random or nonrandom) selection methods or through differential attrition rates between study groups. This would not be a likely source of bias in this case, as subjects were not yet participating in the study but rather were candidates for participation. Educational objective: The Hawthorne effect, which describes the impact on behavior from awareness of being observed, may result in an overestimation of an outcome not only among participants, but also among candidates for participation. Such overestimation of the effect of the intervention poses a threat to the internal validity of any study.

Question 7

A 40-year-old male is brought to the emergency room with confusion, lethargy, and decreased strength in his left arm.  He is HIV-positive.  He was diagnosed several months ago, but he refused any kind of therapy.  His most recent CD4 cell count was 40/μL.  A lumbar puncture is performed, but cerebral spinal fluid findings and cytology are inconclusive.  A CT scan reveals a well-defined small focal lesion in the right cerebral hemisphere.  Biopsy findings are consistent with primary CNS lymphoma.  You decide to proceed with radiation therapy and corticosteroids, and to institute HAART.  Which of the following is the best prognostic sign for this patient's condition?

Accepted Answer

Explanation: Primary CNS lymphoma (PCNSL) is a common malignancy in patients with advanced HIV infections, and is strongly related to the Epstein-Barr virus (EBV). It is usually associated with a significant degree of immunosuppression. Most patients with PCNSL have a persistently depressed CD4 count (< 50/μL). Institution of HAART therapy is associated with an improved prognosis, especially in patients who demonstrate an improvement in the immune status (e.g. increase in CD4 count and decrease in viral load), because the degree of immunosuppression seems to be the major determinant of these patients' survival. (Choice E)Radiation therapy, combined with corticosteroids, induces a rapid response in 20-50% of patients; however, this does not seem to significantly prolong the overall survival. (Choice B) The measurement of EBV DNA levels in the CSF can be used to monitor the therapy; however, its prognostic role is not clear. (Choice C) An increase in the level of soluble B-cell marker in the CSF has been suggested as a diagnostic tool for PCNSL. (Choice A) PCNSL is almost always confined to the CNS. Staging is of value only in a minority of patients. Educational objective: The degree of immunosuppression seems to be the major determinant of the survival in patients with PCNSL.

Question 8

A 25-year-old man comes to the emergency department after being stung by a wasp on his right arm 30 minutes ago.  He reports generalized itching and mild local pain.  He has no other medical conditions.  Temperature is 36.7 C (98.1 F), blood pressure is 122/81 mm Hg, pulse is 108/min, and respirations are 22/min.  Pulse oximetry is 94% on room air.  Examination shows a 2 × 2 cm, erythematous, elevated, warm, and mildly tender area on the right arm.  Multiple wheals are visible on the trunk and extremities.  There is no tongue swelling or stridor.  Bilateral wheezes are present on lung auscultation.  The remainder of the examination is normal.  Which of the following is the most appropriate next step in management of this patient?

Accepted Answer

Explanation: 11ec2b69_bdd0_a2d1_8f63_6dfb889e67f0_MD0005_00 This patient developed sudden-onset pruritus, urticaria (ie, wheals on the trunk and extremities), and wheezing following a wasp sting. This presentation is consistent with anaphylaxis, a severe IgE-mediated type I hypersensitivity reaction that may be diagnosed when acute allergic symptoms (eg, rash, wheezing) are present in ≥2 systems (eg, skin, respiratory) after allergen exposure (eg, wasp sting). Patients with normal blood pressure, like this one, can still experience anaphylaxis; hypotension is not required to make the diagnosis, although it is often present. diagnosed Even when initial symptoms are less severe (ie, no shock or respiratory distress), intramuscular (IM) epinephrine should be administered as soon as anaphylaxis is diagnosed because symptom progression can be unpredictable, rapid, and varied. Early administration of IM epinephrine is the most important step in management of anaphylaxis due to its immediate and broad systemic effects (eg, bronchodilation, decreased systemic release of inflammatory mediators, vasoconstriction). Failure to administer epinephrine early (vs after onset of hypotension) can result in cardiovascular collapse and is associated with a higher incidence of fatalities. management of anaphylaxis Patients should be educated about epinephrine autoinjector administration and the importance of carrying this potentially lifesaving medication at all times. In addition, they should be referred to an allergist for venom immunotherapy, which can reduce the risk for insect sting anaphylaxis from 35%-60% to <5%. (Choice A) Inhaled albuterol (a beta-2 agonist) may eventually be administered to improve this patient's bronchoconstriction (eg, wheezing). Unlike epinephrine, however, it does not address the patient's other anaphylactic symptoms (eg, pruritus, urticaria) or prevent potential further deterioration and shock. (Choices C and E) Intravenous diphenhydramine and oral hydroxyzine are antihistamines that can relieve pruritus and urticaria. Although they are appropriate as first-line therapy in local allergic reactions, they do not relieve airway obstruction or prevent shock in anaphylaxis. Therefore, they should be used only as adjuvant therapies following first-line treatment with IM epinephrine. (Choice D) Glucocorticoids (eg, intravenous methylprednisolone) may be administered as adjunct therapy due to their anti-inflammatory effect; however, they are not an appropriate first step because of their delayed onset of action. Educational objective: The diagnosis of anaphylaxis can be made based on acute allergic symptoms in ≥2 systems after allergen exposure. Hypotension is not required to make the diagnosis. Intramuscular epinephrine is first-line treatment, and early administration improves outcomes. References: 2012 update: World Allergy Organization guidelines for the assessment and management of anaphylaxis. (http://www.ncbi.nlm.nih.gov/pubmed/22744267) Epinephrine absorption in adults: intramuscular versus subcutaneous injection. (http://www.ncbi.nlm.nih.gov/pubmed/11692118) Venom immunotherapy for preventing allergic reactions to insect stings. (http://www.ncbi.nlm.nih.gov/pubmed/23076950)

Question 9

A 16-year-old boy is brought to the office by his mother for a routine well visit.  The patient has been doing well in school and has not been in the office over the past year for any sick visits.  His mother says, "My son has had a girlfriend for the last few months, and I wonder if boys can receive the human papillomavirus vaccine.  I am friends with his girlfriend's mother and heard that she received the vaccine a few years ago."  The patient takes no daily medications and has no known drug allergies.  The mother leaves the room for the examination, and the patient says that he is considering vaginal intercourse with his girlfriend.  His parents have talked with him about abstinence and the importance of using a condom if having sex.  The patient was sexually active with a previous girlfriend and used condoms every time.  He is not sexually active with males and has never been tested for sexually transmitted infections.  There is no family history of cancer.  Physical examination shows no skin lesions, including in the genital area.  The penis is circumcised with no visible discharge.  The testes are descended bilaterally with no erythema or masses.  Counseling about the prevention of pregnancy and sexually transmitted infections is provided.  Which of the following is the most appropriate recommendation about the human papillomavirus vaccine in this patient?

Accepted Answer

Explanation: 11ec2b69_bddc_fee5_8f63_a55eeacbcaa0_MD0005_00 Human papillomavirus (HPV) is a common sexually transmitted infection responsible for nearly all cases of cervical cancer and many cases of other anogenital cancers (eg, vulvar, vaginal, anal, penile), oropharyngeal cancer, and genital warts. The HPV vaccine series targets 9 serotypes that cause either genital warts (eg, types 6 and 11) or cancer (eg, types 16 and 18), and routine vaccination has resulted in the decline of HPV infection and HPV-related cancers. The primary indication for vaccination in girls is reducing the risk for cervical cancer, and all boys should be vaccinated to decrease the risk for anogenital and oropharyngeal cancers. Vaccine administration in boys also contributes to herd immunity against cervical cancer in women. Genital warts are prevented in both sexes. The recommended time for the first dose is age 11-12 (as early as age 9) because it is most effective in those who are HPV-naive (ie, prior to sexual debut). Younger adolescents also produce a more robust immune response to the vaccine than older patients. However, all patients age <26 should be offered the vaccine to decrease the risk for HPV transmission and related cancers (Choice A). Patients from age 26 to 45 can also receive the vaccine, but its effectiveness may be decreased due to an increased likelihood of prior HPV exposure from previous sexual partners. (Choices B and C) HPV is spread by skin-to-skin contact. Condoms offer partial protection but do not cover the entire genital area, so HPV can still be transmitted. Although the vaccine may be less effective in sexually active patients due to the possibility of prior exposure to HPV, it can confer protection against other HPV strains. Therefore, HPV vaccination should be offered to patients age <26 regardless of sexual history or method of contraception. (Choice E) Most male patients with HPV are asymptomatic. Clinically significant HPV infections manifest as genital warts or anogenital/oropharyngeal cancer. Although some cervical cancer treatments in women can reduce fertility, HPV does not cause male infertility. Educational objective: The human papillomavirus vaccine series should be offered to all patients age 11-26. The vaccine reduces the risk of genital warts and anogenital and oropharyngeal cancers in both sexes. References: Human papillomavirus vaccination 2020 guideline update: American Cancer Society guideline adaptation. (http://www.ncbi.nlm.nih.gov/pubmed/32639044) Efficacy, effectiveness and safety of vaccination against human papillomavirus in males: a systematic review. (http://www.ncbi.nlm.nih.gov/pubmed/30016957)

Question 10

A pharmaceutical company plans to conduct a study to evaluate the efficacy of the addition of a novel conjugated anti-CD22 monoclonal antibody (mAb) to frontline therapy in adults age 18-39 with newly diagnosed precursor B-cell acute lymphoblastic leukemia (ALL).  Researchers will assess the adverse reactions associated with treatment with the anti-CD22 mAb.  A total of 1,200 patients newly diagnosed with CD22 positive B-cell ALL will be randomized to either frontline chemotherapy or intravenous infusion of the mAb given on days 1, 8, and 15.  All participants will undergo bone marrow aspirate and biopsy on day 28.  The study's primary outcome measure will be event-free survival, and its secondary outcome will include disease-free survival, overall survival, and complete response.  Which of the following best describes this type of study?

Accepted Answer

Explanation: 11ec2b69_bde5_8a6b_8f63_f92288b3d889_MD0005_00 The clinical trials process addresses whether new treatments are effective and safe for their intended use in the population of patients with the disease/condition of interest. New treatments go through several research phases: some phases involve no human subjects (ie, preclinical studies) (Choice A), and some involve few (ie, phase I and II trials) or many (ie, phase III and IV trials) human subjects. A phase III trial assesses treatment efficacy and human safety (eg, long-term or rare adverse reactions). It compares a new treatment to standard treatments (or placebo) in a large sample consisting of hundreds (eg, 300 to 3,000 subjects) who have the disease of interest. Most phase III trials are randomized and blind (ie, patients/researchers are unaware of treatment assignment), may compare ≥2 treatments, and last 1 to 4 years. Results determine whether a new treatment is approved by the FDA for a commercial market. In this question, the study will evaluate the efficacy and adverse reactions associated with the addition of a new conjugated anti-CD22 monoclonal antibody to frontline therapy in adults age 18-39 with newly diagnosed precursor B-cell acute lymphoblastic leukemia (ALL). A total of 1,200 patients newly diagnosed with CD22 positive B-cell ALL will be randomized to either frontline chemotherapy or the new antibody. This process is consistent with a phase III trial. (Choice B) A phase I trial assesses toxicity, maximum tolerated dose, adverse effects, pharmacokinetics, and pharmacodynamics of a new treatment, usually in a small sample consisting of 20 to 100 healthy subjects (or in some cases, patients with the disease/condition), and lasts several months. (Choice C) A phase II trial assesses efficacy, optimal dosing, and adverse effects of a new treatment in a small sample consisting of up to a few hundred people with the disease/condition, and lasts several months to 2 years. This study involved a large sample (ie, 1,200) of affected patients and was aimed at assessing efficacy and adverse reactions. (Choice E) A phase IV trial studies adverse effects caused over time by a new treatment after it has been approved and is on the market. Educational objective: Phase III trials evaluate the efficacy, risks, and benefits of a new treatment compared to current standard treatments (or placebo) in a large sample (eg, 300 to 3,000) of patients with the disease of interest. Most phase III trials are randomized, blind, and compare ≥2 treatments.

Question 11

A 56-year-old woman in the emergency department waiting room develops shortness of breath and generalized itching.  She was eating a cookie when the symptoms started.  The patient is allergic to peanuts and believes the cookie contained them.  She has a history of emphysema and a 20-pack-year smoking history.  Temperature is 36.7 C (98.1 F), blood pressure is 88/60 mm Hg, pulse is 124/min, and respirations are 26/min.  Pulse oximetry is 92% on room air.  The patient is using the accessory muscles of her neck and shoulder girdle and is exhaling through pursed lips.  There is no tongue swelling or stridor.  Bilateral wheezes are present on lung auscultation.  Skin examination is shown in the exhibit.  The patient is given an intramuscular injection of epinephrine.  Ten minutes later, there is no significant change in her condition.  Which of the following is the best next step in management of this patient?

Accepted Answer

Explanation: 11ec2b69_bdcf_4340_8f63_c93fcd09c7c8_MD0005_00 This patient with urticaria, respiratory distress, and hypotension is experiencing anaphylaxis. First-line treatment is immediate administration of intramuscular (IM) epinephrine, a beta-2 and alpha-1 adrenergic receptor agonist that typically causes bronchial smooth muscle relaxation (decreasing wheezing and work of breathing) and vasoconstriction (increasing blood pressure and decreasing edema), respectively. However, some patients experience refractory symptoms (eg, no significant change after 10 minutes). These patients require additional IM doses of epinephrine or even intravenous epinephrine to achieve significant symptom resolution. When intravenous epinephrine is required, slow infusion is preferred to bolus dosing due to the risk of cardiovascular side effects (eg, ventricular arrhythmias, myocardial infraction). Adjunct management of anaphylaxis includes circulatory support measures such as large-volume fluid resuscitation in hypotensive patients; patients should also be positioned (eg, supine, semirecumbent) with the lower extremities elevated to improve venous return to the heart. Other medications (eg, albuterol, glucocorticoids, antihistamines) may be given to address isolated symptoms. However, titrating epinephrine administration to achieve symptom improvement and/or resolution always takes priority because these other medications do not address the broad-ranging systemic effects of anaphylaxis or prevent hypotension, cardiovascular collapse, and death. (Choice A) The beta-2 agonist effect from albuterol can relieve bronchoconstriction (eg, wheezing) but does not treat other dangerous symptoms of anaphylaxis such as hypotension. (Choice C) The antihistamine effect of intravenous diphenhydramine can help relieve symptoms of pruritus and urticaria. However, it does not treat bronchospasm or shock, which are ongoing in this patient. (Choice D) Glucocorticoids such as methylprednisolone may be helpful (although evidence is limited) in preventing prolonged or biphasic reactions. However, glucocorticoids need several hours to take effect and do not provide the immediate action required in this emergency situation. (Choice E) IM epinephrine administration into the thigh is the preferred route and location because peak plasma concentration (and therefore medication effect) is achieved faster than with subcutaneous injection, which has delayed absorption. Educational objective: Immediate administration of intramuscular epinephrine is the first-line treatment for anaphylaxis, and additional epinephrine administration (eg, intramuscular, intravenous) may be required for symptom resolution in some patients. Fluid resuscitation, bronchodilators, antihistamines, and glucocorticoids may be adjunct therapies but do not take priority over epinephrine. References: Management and Prevention of Anaphylaxis (http://www.ncbi.nlm.nih.gov/pubmed/26918144) 2012 update: World Allergy Organization guidelines for the assessment and management of anaphylaxis. (http://www.ncbi.nlm.nih.gov/pubmed/22744267)

Question 12

A 32-year-old Caucasian female presents to your office with persistent cough and shortness of breath.  She has had three episodes of pneumonia over the last year.  She had severe sinusitis one year ago, and an episode of bloody diarrhea that required hospitalization and IV antibiotic therapy six months ago.  She does not smoke or consume alcohol.  She denies any illicit drug use.  She is currently not taking any medications.  All her immunizations are up-to-date.  Her blood pressure is 130/80 mmHg and heart rate is 90/min.  Physical examination reveals fine crackles over the right lower lung lobe.  No lower extremity edema is present.  Neck palpation does not reveal any lymph node enlargement.  The chest x-ray shows right lower lobe infiltrates and left upper lobe fibrosis.  The ECG reveals non-specific ST segment and T wave changes.  What is the best next step in the management of this patient?

Accepted Answer

Explanation: This patient has a history of recurrent bacterial infections that is highly suggestive of immunodeficiency with involvement of humoral immunity. Selective immunoglobulin deficiency that includes IgA and/or IgG subfractions is a possible diagnosis. For example, selective deficiency of IgG3 alone is more common in adult females and is associated with recurrent sinopulmonary as well as gastrointestinal infections. Food allergies and autoimmune diseases may also be present. IgA deficiency and common variable immunodeficiency are also possible. The latter may be associated with suppressed cell immunity and increased risk of malignancy. Quantitative measurement of serum immunoglobulin levels helps to establish the diagnosis. (Choice D)Cystic fibrosis is also a possibility, but it usually manifests earlier in life and does not cause gastroenteritis. (Choice A)Alpha-1-antitrypsin deficiency is an inherited disorder that leads to emphysema and liver damage, but does not increase the risk of recurrent infections. (Choices B and E)Methacholine challenge is used to diagnose asthma, and V/Q testing is employed in patients suspected to have pulmonary thromboembolism; both these diagnoses are unlikely in this case. Educational Objective: Recurrent bacterial infections in an adult patient may indicate a humoral immunity defect. Quantitative measurement of serum immunoglobulin levels helps to establish the diagnosis.

Question 13

A 35-year-old man is brought to the emergency department after cutting his finger with a rusty knife while doing yard work.  It is a deep cut, and his wife had immediately applied a pressure dressing to stop the bleeding.  His immunization status is unknown.  The patient last saw his doctor about 10 years ago, and cannot recall if he received all of his childhood vaccinations.  He has a deep laceration on the palmar aspect of his right middle finger.  Cleaning of the wound and other wound-care measures are initiated.  Which of the following is the best next step in management of this patient?

Accepted Answer

Explanation: 11ec2b69_bde1_b9d9_8f63_49bb96d717b0_MD0005_00 Tetanus immune globulin (TIG) provides passive and immediate but temporary immunity. Tetanus toxoid-containing vaccines provide active and prolonged but delayed immunity. These vaccines are recommended once every 10 years and can be given as tetanus/diphtheria toxoids adsorbed (Td), tetanus toxoid/reduced diphtheria toxoid/acellular pertussis (Tdap), tetanus toxoid (TT), or diphtheria/tetanus toxoids adsorbed (DT). Patients with a clean or minor wound who have had >3 tetanus vaccinations and a booster within the past 10 years do not require an additional vaccine booster. A tetanus toxoid-containing vaccine is recommended for patients who received their last tetanus vaccine >10 years ago or who have an unimmunized, uncertain, or incomplete vaccination status (<3 doses). Incomplete vaccination status is more commonly encountered in intravenous drug users, immigrants, individuals from rural areas, and the elderly. Patients with dirty (eg, dirt, feces, saliva) or severe (eg, punctures, avulsions, crush injuries, burns, frostbite) wounds have a higher risk for Clostridium tetani due to a favorable anaerobic growth environment. These patients require a tetanus booster alone (no TIG) if their vaccination history is up to date but their last vaccination was >5 years ago. Patients with dirty or severe wounds who are significantly immunocompromised (eg, HIV), or have an unimmunized, uncertain, or incomplete tetanus vaccination status should receive TIG and tetanus vaccine booster. This is because the early doses of tetanus toxoid only prime the immune system but do not confer immunity. TIG provides immediate, temporary immunity in these patients. (Choices A, C, and D) This patient has a severe wound in his hand due to a rusty knife. He is at increased risk for developing tetanus and needs tetanus prophylaxis. His immunization status is unknown, and so he should be given both TIG and tetanus toxoid-containing vaccines. Educational objective: Tetanus/diphtheria toxoid vaccines should be given to patients with severe or dirty wounds who received their most recent tetanus vaccine >5 years ago and to those with minor, clean wounds who received a booster >10 years ago. In addition, tetanus immune globulin should be given to any individual with a severe or dirty wound who has an unimmunized, unclear, or incomplete immunization history. References: Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine from the Advisory Committee on Immunization Practices, 2010. (http://www.ncbi.nlm.nih.gov/pubmed/21228763)

Question 14

A 5-year-old boy is brought to the office for his annual well-child visit.  The boy was briefly hospitalized a month ago for an asthma exacerbation, which was treated with albuterol and oral corticosteroids.  He has been well since then except for a runny nose and cough for the past 2 days.  He takes an inhaled corticosteroid daily and albuterol as needed, most recently 3 weeks ago.  The patient lives at home with his mother, who is 38 weeks pregnant, and his father and 2-year-old sister.  He recently started kindergarten and is doing well.  Temperature is 36.7 C (98 F).  The patient is tracking along the 40th and 60th percentiles for weight and height, respectively.  Physical examination shows a well-appearing boy who speaks clearly in full sentences, counts to 12, and can hop on one foot.  The lungs are clear to auscultation, and the remainder of the examination is unremarkable.  He is scheduled to receive the second dose of measles-mumps-rubella (MMR) vaccine today.  The parents say, "After his first MMR shot a few years ago, he had a fever up to 39.4 C (103 F), and we almost took him to the emergency department."  Which of the following is the most appropriate next step in management of this patient?

Accepted Answer

Explanation: 11ec2b69_bdde_d3a7_8f63_c986f262a842_MD0005_00 The measles-mumps-rubella (MMR) vaccine is a live-attenuated vaccine typically administered at ages 1 and 4. Common adverse effects include fever, rash, and transient lymphadenopathy. These adverse effects are not contraindications to receiving a subsequent MMR vaccine dose. Contraindications include anaphylaxis (eg, respiratory compromise, hypotension, angioedema) to neomycin or gelatin (which are components of the vaccine) or after prior administration of the MMR vaccine. Patients who are pregnant or attempting to become pregnant should also not receive the MMR vaccine due to the risk of congenital rubella syndrome in the fetus. Finally, immunodeficient patients, such as those who have HIV with CD4 <200/mm³, congenital immunodeficiency, or hematologic/solid tumors, should not receive the MMR vaccination due to the risk of life-threatening disseminated infection from the attenuated virus. Household contacts of these patients, including children of pregnant women, can safely receive live vaccines (Choice D). (Choice A) Administering antipyretics (eg, acetaminophen) prior to vaccination has not been shown to prevent high fever and could decrease immunogenicity. (Choice C) The MMR vaccine does not contain a significant amount of egg protein, and a history of egg allergy is not a contraindication to administration. The yellow fever vaccine is contraindicated in patients with egg allergy. (Choice E) Mild illness (eg, acute otitis media, upper respiratory infection) is not a contraindication for administering vaccines. Delay of vaccination increases time of potential exposure to vaccine-preventable disease. This child is afebrile, has a normal physical examination, and should be given the MMR vaccine. Educational objective: Measles-mumps-rubella (MMR) vaccination is contraindicated in patients with anaphylaxis to prior MMR vaccination, anaphylaxis to neomycin or gelatin, severe immunodeficiency, or pregnancy. It can be given to patients who had fever after prior vaccination and to those who are household contacts of immunodeficient or pregnant individuals. References: Prevention of measles, rubella, congenital rubella syndrome, and mumps, 2013: summary recommendations of the Advisory Committee on Immunization Practices (ACIP). (http://www.ncbi.nlm.nih.gov/pubmed/23760231)

Question 15

A 45-year-old woman with a history of chronic menorrhagia is hospitalized for an elective hysterectomy.  Her preoperative hemoglobin is 7 g/dL.  She is transfused with 2 units of packed red blood cells.  Two hours after starting the transfusion, the patient reports chills and malaise.  Her temperature is 38.8 C (102 F), blood pressure is 120/76 mm Hg, pulse is 100/min, and respirations are 18/min.  The transfusion is stopped, and she receives acetaminophen.  Direct antiglobulin test and plasma free hemoglobin level are negative.  Urinalysis is within normal limits.  The reaction resolves 6 hours after the transfusion began.  Which of the following actions could have prevented this reaction?

Accepted Answer

Explanation: 11ec2b69_bddb_0313_8f63_3bc82e4f14f7_MD0005_00 11ec2b69_bddb_0314_8f63_7d546f01a142_MD0005_00 This patient most likely has a febrile nonhemolytic transfusion reaction, the most common adverse reaction that occurs within 1-6 hours of transfusion. When red cells and plasma are separated from whole blood, small amounts of residual plasma and/or leukocyte debris may remain in the red cell concentrate. During blood storage, these leukocytes release cytokines, which when transfused can cause transient fevers, chills, and malaise without hemolysis. Management includes stopping the transfusion to exclude other serious reactions, administering antipyretics, and using leukoreduced blood products for future transfusions. Leukoreduction involves reducing the number of transfused leukocytes through filtering or other methods such as saline washing, freezing and deglycerolizing, or buffy coat removal. It also reduces the risk of human leukocyte antigen alloimmunization and transmission of cytomegalovirus (which typically resides in leukocytes). Premedication with antipyretics and antihistamines has not been shown to significantly reduce transfusion reactions. (Choice A) Careful cross-matching of blood prevents acute hemolytic reactions, which present with fever, chills, flank pain and hemoglobinuria within an hour of transfusion. These can progress to renal failure and disseminated intravascular coagulation. The direct antiglobulin test (Coombs) is positive and plasma free hemoglobin is >25 mg/dL. Urinalysis also shows hemoglobinuria. (Choice C) Whole blood contains numerous leukocytes and increases the risk of febrile reaction. Therefore, it is rarely used except in cases of acute massive hemorrhage (eg, trauma). (Choice D) Warming blood is recommended only during rapid massive transfusion to prevent hypothermia. (Choice E) Residual plasma in red cell concentrates contains proteins, including immunoglobulin A (IgA). IgA-deficient patients develop antibodies against IgA. These antibodies can react with IgA-containing donor products and induce an anaphylactic reaction (angioedema, hypotension, and respiratory distress) that can progress rapidly to loss of consciousness, shock, and respiratory failure. To reduce this risk, red cells should be washed to remove as much of the plasma as possible for patients with IgA deficiency or prior allergic transfusion reaction. Educational objective: Febrile nonhemolytic transfusion reaction is the most common adverse reaction that occurs within 1-6 hours of transfusion. Patients usually develop fever, chills, and malaise without hemolysis. Leukoreduction of donor blood can prevent febrile nonhemolytic reaction and reduce the risk of human leukocyte antigen alloimmunization and cytomegalovirus transmission. References: Leukoreduced blood components: Advantages and strategies for its implementation in developing countries. (http://www.ncbi.nlm.nih.gov/pubmed/20376259) Universal leukoreduction decreases the incidence of febrile nonhemolytic transfusion reactions to RBCs. (http://www.ncbi.nlm.nih.gov/pubmed/14692963)

Question 16

A 68-year-old man undergoing hemodialysis is being evaluated due to "difficulty breathing and chest tightness."  He has not had any chest pain.  The patient was feeling well when he arrived at his hemodialysis appointment.  He was started on hemodialysis 15 minutes ago after a heparin flush; an intravenous iron infusion was started 5 minutes ago for iron deficiency anemia.  Medical history is significant for end-stage renal disease due to uncontrolled hypertension, a small pericardial effusion, and small, bilateral pleural effusions.  He has been on hemodialysis treatment for the past year.  Temperature is 35.6 C (96.1 F), blood pressure is 90/60 mm Hg, pulse is 112/min, and respirations are 24/min.  Pulse oximetry is 93% on room air.  The patient is alert but in mild distress.  Conjunctivae are pale.  Lungs sounds are decreased at both bases.  Bilateral wheezing is noted on auscultation of the lungs.  Heart sounds are slightly muffled and rapid but without murmurs or rubs.  Abdomen is soft and nontender.  Skin is flushed.  Mild, bilateral pitting pedal edema is present.  What is the most likely cause of this patient's symptoms?

Accepted Answer

Explanation: 11ec2b69_bdd1_db52_8f63_d3ad9f67a307_MD0005_00 Determining the cause of dyspnea during hemodialysis can be challenging, in part because large, physiologic shifts (eg, fluid shifts) are occurring, but also because hemodialysis patients often have multiple comorbidities (eg, cardiovascular disease) that can manifest with dyspnea. Dyspnea prior to initiation of hemodialysis often results from volume overload and is common. However, dyspnea that begins after initiation of hemodialysis may reflect another medical condition (eg, acute coronary syndrome, anaphylaxis) that warrants further workup. This patient developed dyspnea with wheezing, hypotension, and flushing shortly after intravenous (IV) iron infusion. This is concerning for anaphylaxis, which may be diagnosed when cutaneous symptoms (eg, flushing) and either hypotension or respiratory distress (this patient has both) occur after exposure to a possible allergen (eg, IV iron). Allergic symptoms in ≥2 systems (eg, skin, respiratory, cardiovascular) after possible allergen exposure is another diagnostic criterion for anaphylaxis. IV iron is a recognized allergen. Although anaphylaxis is rare, IV iron infusions are common as the preferred treatment for anemia in hemodialysis patients (~70% of patients). Anaphylaxis may also be triggered by other medications (eg, antibiotics) administered during hemodialysis or by the dialysate itself. Early recognition and treatment with epinephrine can be lifesaving. (Choice A) Hemodialysis patients have an increased incidence of coronary artery disease and can develop acute myocardial infarction (AMI), causing chest tightness and dyspnea. However, AMI causing hypotension (eg, cardiogenic shock) would likely lead to pale skin (vs flushing) due to hypoperfusion and crackles (vs wheezing) due to acute pulmonary edema. This patient's lack of chest pain and his symptom onset after IV iron infusion make anaphylaxis more likely. (Choice B) Venous air embolism can cause dyspnea and hypotension, particularly if the air embolus travels to pulmonary circulation. However, flushing and wheezing would be unexpected. (Choice D) Dialysis patients can have small pericardial effusions (eg, slightly muffled heart sounds) due to volume overload. Large uremic effusions can lead to cardiac tamponade presenting with symptoms of cardiogenic shock (eg, dyspnea, hypotension) and impaired venous return (eg, peripheral edema). However, distended neck veins are also frequently present, and skin flushing and wheezing are not expected. (Choice E) Pulmonary embolism can cause dyspnea, chest tightness, hypotension, and tachycardia; however, flushing and bilateral wheezing are more suggestive of anaphylaxis. Educational objective: Although anaphylaxis can be difficult to recognize in hemodialysis patients due to large fluid shifts and confounding patient comorbidities, it should be considered as a potential cause of dyspnea in patients receiving intravenous iron infusions or other medications during hemodialysis. References: 84-year-old woman with hemodialysis-associated shortness of breath. (http://www.ncbi.nlm.nih.gov/pubmed/19181653) Diagnosis, treatment, and prevention of hemodialysis emergencies. (http://www.ncbi.nlm.nih.gov/pubmed/27831511) Safety of intravenous iron in hemodialysis patients. (http://www.ncbi.nlm.nih.gov/pubmed/28370957)

Question 17

A group of rheumatologists wants to investigate 8 candidate rheumatoid arthritis (RA) susceptibility loci to identify whether single nucleotide polymorphisms (SNPs) are associated with RA in a given population.  Eight SNPs (MTHFR C677T, MTHFR A1298C, TGFβ1 T869C, TNFB A252G, VDR ApaI, VDR BsmI, VDR FokI, VDR TaqI) are tested by genotyping patients with RA (n = 105) and unrelated patients without RA (n = 80) as controls.  Which of the following is the most appropriate null hypothesis for this study?

Accepted Answer

Explanation: 11ec2b69_bde4_03ca_8f63_d94546e4fec0_MD0005_00 A statistical hypothesis is an initial assumption, which may or may not be true, regarding population parameters (eg, mean values in two different groups) or the relationship between variables within a population (eg, association between an exposure and a disease). The null hypothesis (H₀) is a statement of no difference or no association. The alternative hypothesis (H_a) is a statement of difference or association. _a In this case, patients are initially identified based on their disease status (ie, cases: patients with rheumatoid arthritis [RA]; controls: patients without RA). The frequency of exposure (ie, 8 different single nucleotide polymorphisms [SNPs]) is subsequently compared between cases and controls; therefore, this is a case-control study. The most appropriate measure of association between exposure and disease in case-control studies is the odds ratio (OR), which represents the odds of exposure among cases relative to controls. The OR may be interpreted as follows: OR = 1.0 (null value) indicates that the odds of exposure among cases are the same as the odds of exposure among controls; therefore, exposure is not associated with the disease. OR ≠ 1.0 indicates that the odds of exposure among cases are lower (OR < 1) or higher (OR > 1) than among controls; therefore, exposure is associated with the disease. The OR is sometimes described as the odds of disease among exposed patients relative to nonexposed patients. These two OR definitions are mathematically equivalent. Because H₀ is a statement of no association, the most appropriate H₀ for this study is that the OR = 1 (Choice B). Researchers can compare patients with controls to evaluate which of the 8 SNPs are associated with RA in this population. (Choices C and D) Measures of association based on risk/incidence (eg, relative risk) are calculated in cohort studies and experimental designs, in which participants are initially selected based on exposure status (ie, exposed or nonexposed to a risk factor or treatment) and then followed over time to assess development of disease. However, in case-control studies, cases (by definition) already have the disease, so case-control studies cannot calculate and compare the risk/incidence of disease between the case and control groups. Instead, they must compare the odds of exposure (to a risk factor) between cases and controls. Educational objective: The odds ratio (OR) is a measure of association used in case-control studies. It quantifies the relationship between an exposure and a disease; its null value (ie, null hypothesis) is always OR = 1.

Question 18

A randomized study assigned patients with sickle cell anemia and silent stroke to either monthly transfusion therapy (transfusion group of 110 patients) or usual care (observation group of 105 patients).  An excerpt of the study results is provided below: Which of the following adverse event estimates is most subject to selection bias?

Accepted Answer

Explanation: 11ec2b69_bde6_26ac_8f63_69fe65e5c35c_MD0005_00 Selection bias occurs when the sample is unrepresentative of the target population. This may lead to a different measure of association (eg, rate ratio, odds ratio) in the sample than in the target population. In this example, for 4 out of 5 adverse events studied (acute chest syndrome, avascular hip necrosis, headache, vasooclusive crisis), data are provided for all 105 participants in the observation group and 110 participants in the transfusion group. However, only 35 out of 105 participants (= 33%) in the observation group had their ferritin level measured, so the results may be unrepresentative of the entire group. This makes it difficult to determine whether the calculated incidence rate ratio is reflective of the true difference between the observation and transfusion groups. One possible explanation for the low proportion compared to the transfusion group (91 / 110 = 83%) is that participants who received transfusions were more likely to have iron levels measured. Selection bias is often seen in surveys and polls. A high rate of nonresponse may lead to selection bias as the nonresponders may differ in some way from the responders. Other types of selection bias are seen in the table. (Choices A, B, C, and E) The entire sample (patients in both observation [N = 105] and transfusion groups [N = 110]) was analyzed for the other adverse effects (acute chest syndrome, avascular necrosis, headache, and vasoocclusive crisis); this minimized the risk of selection bias. Educational objective: Selection bias occurs when the sample is unrepresentative of the target population and may lead to incorrect measures of association.

Question 19

A 64-year-old man comes to the emergency department complaining of facial swelling.  He has not had such symptoms before and has no associated itching or rash.  The patient's medical problems include type 2 diabetes mellitus, hypertension, and coronary artery disease.  He had a myocardial infarction 7 years ago.  He was recently diagnosed with congestive heart failure with systolic dysfunction.  The patient's medications include ramipril, metoprolol, furosemide, spironolactone, aspirin, glyburide, and simvastatin.  Physical examination shows prominent lip and tongue swelling without stridor.  His symptoms subside within 24 hours after he is admitted.  Which of the following is the best statement concerning the management of this patient?

Accepted Answer

Explanation: The facial swelling with prominent lip and tongue swelling in this patient are consistent with angioedema, an uncommon (<1%) but well-recognized side effect of angiotensin-converting-enzyme (ACE) inhibitors such as ramipril. Some patients may also develop abdominal pain due to intestinal swelling. ACE catalyzes the degradation of bradykinin; inhibition of ACE leads to elevated levels of bradykinin that can cause angioedema as well as a dry cough. Angioedema associated with ACE inhibitors is usually self-limited, lasts 24-48 hours, and, unlike allergic angioedema, is not associated with itching or urticaria. Half of all cases of ACE inhibitor-related angioedema occur in the first few weeks of therapy, although it can occur even in patients who have been on the medication for several years. ACE inhibitor-related angioedema affecting the airway can be life- threatening. Patients who develop angioedema should not receive ACE inhibitors again (Choices A and D). Angiotensin-receptor blockers (ARBs) are generally used as a replacement for ACE inhibitors in this situation as they do not affect the bradykinin system and otherwise have the same general benefits. Some patients may have a recurrence of angioedema during the first few months after discontinuing the ACE inhibitor and still need monitoring on the ARB. It is not clear whether this is a direct effect of the ARB, residual effect of the ACE inhibitors, or an underlying tendency of the patient to develop angioedema. (Choice C) Although ACE inhibitors and ARBs are structurally related, the angioedema is not immune mediated and does not involve cross-reactivity. Angioedema is due to the bradykinin pathway. (Choice E) Antihistamines such as diphenhydramine are effective in histamine-mediated angioedema (ie, allergic angioedema) but have no effect on the bradykinin-mediated angioedema of ACE inhibitors. Educational objective: Angioedema is a possible side effect of angiotensin-converting-enzyme inhibitors that occurs in <1% of patients. Those with this reaction should discontinue the drug or switch to an angiotensin-receptor blocker (ARB) if needed. The risk of angioedema with ARBs is low, and ARBs have benefits similar to those of ACE inhibitors. References: Meta-analysis of randomized trials of angioedema as an adverse event of renin-angiotensin system inhibitors. (http://www.ncbi.nlm.nih.gov/pubmed/22521308) Comparative risk for angioedema associated with the use of drugs that target the renin-angiotensin-aldosterone system. (http://www.ncbi.nlm.nih.gov/pubmed/23147456)

Question 20

A 4-month-old boy is brought to the office for a well-child visit.  The boy is rolling over and cooing.  He reaches for toys and mouths them frequently.  He is breastfed exclusively and takes a multivitamin with iron.  Last week, the patient was diagnosed with acute otitis media and croup, which were treated with a 10-day course of amoxicillin and a single dose of dexamethasone.  He is currently on day 6 of antibiotics and is no longer irritable or coughing.  His last fever was 4 days ago.  The patient lives at home with his parents and sister age 3.  His sister has a seizure disorder of unclear etiology that is well controlled on antiepileptic medication.  Temperature is 36.7 C (98.1 F).  Physical examination is normal for his age.  The infant is scheduled to receive several immunizations today as part of the recommended schedule.  The parents express concern about their son receiving the diphtheria-tetanus-acellular pertussis vaccination.  The father says, "After he got his shots the first time, he had a fever of 103 and was so fussy that we had to take him to the urgent care clinic to make sure he was okay.  I'm not sure I can go through that again."  Based on this child's history, which of the following is the most appropriate step regarding DTaP administration in this patient?

Accepted Answer

Explanation: 11ec2b69_bddd_e946_8f63_495d01165a1c_MD0005_00 Diphtheria-tetanus-acellular pertussis (DTaP) immunization virtually eliminated diphtheria and tetanus in the United States and markedly reduced the incidence and severity of pertussis. DTaP is composed of conjugated acellular pertussis antigen (pertactin) as well as diphtheria and tetanus toxoid. The DTaP vaccine has an excellent safety profile. Either of 2 serious complications is an absolute contraindication to future DTaP immunization: anaphylaxis immediately after the vaccination or encephalopathy within 7 days. The latter reaction is due to the pertussis components, and children who can no longer receive pertussis immunization can still receive tetanus and diphtheria toxoid (Td) vaccines. Relative contraindications (eg, situations in which immunizations are normally given but might be deferred if risks are perceived to outweigh benefits) include extremely high fever (>40.6 C [105 F]) or seizures following previous DTaP vaccination or ongoing evaluation for a neurologic condition. Since this child has no absolute or relative contraindications, he should receive DTaP as scheduled. (Choice A) Fever <40.6 C (105 F) and local site reactions (eg, erythema, swelling) are common following DTaP administration and are not contraindications to future doses. (Choice B) A family history of encephalopathy, seizures, or other central nervous system disorders is not a contraindication to immunization for this child, whose development is normal and who has had no seizures. (Choice D) Immunosuppression of any kind is not a contraindication to DTaP immunization. The immune dysfunction following a single dose of dexamethasone is mild and short-lived. (Choice E) Minor illnesses such as acute otitis media and croup are not contraindications to the DTaP immunization. There is no benefit to waiting until antibiotic therapy has been completed. Educational objective: Anaphylaxis or encephalopathy following diphtheria-tetanus-acellular pertussis vaccine is an absolute contraindication to receiving additional doses. Minor illnesses, local site reactions, and immunosuppression are not contraindications. References: Update on child and adolescent immunizations: selected review of US recommendations and literature. (http://www.ncbi.nlm.nih.gov/pubmed/22572761)

Exam 1: Advanced Clinical Medicine