Deck 2: Foundations of Independent Practice

Question 1

Over the course of 5 years, a pediatric endocrinologist has seen a marked increase in the prevalence of depression among patients with obesity in her practice.  She partners with a pediatric psychiatrist to devise a short screening test for depression for this specific population.  The new screening test is found to be 90% sensitive and 84% specific.  If this test is used on a sample of patients with obesity in which 35% are known to have depression The authors of the study decide to conduct an ancillary statistical analysis in which a second cohort of workers employed in the manufacture of domestic textiles is used as the population of reference.  Based on the study results from the first cohort of vinyl chloride workers, which of the following is the most likely reason for the ancillary analysis?

A)All-cause mortality among the vinyl chloride workers is statistically lower than among the general population.
B)Compared to the general population, vinyl chloride workers had a nonstatistically significant association with mortality due to melanoma and lung cancer.
C)Considering a cohort of domestic textile workers reduces the possibility of contamination bias.
D)Misdiagnosis of early angiosarcoma of the liver might have influenced the association between vinyl chloride exposure and hepatocellular carcinoma.
E)The expected number of deaths among domestic textile workers will be greater than in the general population.

Answer 1

A
Explanation:
Assessing the effect of exposure to a risk factor in a population of workers requires an appropriate unexposed group for comparison.  Working populations are generally healthier than the general population and often exhibit lower mortality rates.  This is commonly known as the healthy worker effect (HWE).
The HWE is a type of selection bias that may result from severely ill or disabled individuals being excluded from or not entering the workforce.  Consequently, mortality rates from the general population may not be appropriate as a reference.  Generally, standardized mortality ratios (SMRs) that consider the general population as reference will be biased and underestimate the effect of the exposure to a risk factor (eg, vinyl chloride) in a working population.  If available, a demographically similar working population (eg, domestic textile workers) without exposure to the risk factor of interest may serve as a better basis for comparison than the general population.  Considering another working population as the population of reference would give more valid estimates of the true effect of exposure to the risk factor.
In this case, the population of vinyl chloride workers had an all-cause mortality rate lower than that of the general population, given an SMR = 0.87 with a 95% confidence interval (CI) that does not cross the null value (95% CI [0.85, 0.89]).  This indicates that, in general, the population of workers was healthier than the general population.  Conducting an ancillary statistical analysis in which a second cohort of workers (eg, domestic textile workers) is employed as the population of reference increases the validity of the study.
(Choice B)  Study results show that vinyl chloride workers had a nonstatistically significant association with mortality due to melanoma (SMR = 1.09, 95% CI [0.73, 1.56]), but a statistically significant association with mortality due to lung cancer (SMR = 0.88, 95% CI [0.81, 0.95]).
(Choice C)  Contamination bias occurs when the control group in a controlled trial unintentionally receives the treatment or intervention, thereby reducing the difference in outcomes between the control and treatment groups.  This type of bias is not a concern in observational studies.
(Choice D)  Misdiagnosis of early liver angiosarcomas may have influenced findings in the initial study; however, this has no bearing on the decision to employ a different population of reference.
(Choice E)  Employing a cohort of workers unexposed to the risk factor of interest as the population of reference reduces the bias introduced by the HWE.  The assumption is that the expected number of deaths among domestic textile workers will be lower than in the general population, making the comparison between observed and expected deaths more valid.
Educational objective:
The healthy worker effect is a special type of selection bias that usually occurs in occupational cohort studies when the general population is used as the reference group.  The general population consists of healthy and unhealthy individuals; those who are unhealthy are less likely to be employed, whereas the employed workforce tends to have fewer sick individuals.  Consequently, comparisons of mortality rates between an employed population and the general population are usually biased.
References:
Commentary for the then and now forum: the healthy worker effect.
(http://www.ncbi.nlm.nih.gov/pubmed/28267105)

Question 2

The following advertisement is focused on LDL particle number (LDL-P) testing, a novel new screening method used for assessing LDL.
A 54-year-old man comes to the physician for a routine health examination.  He has no complaints and feels well.  He has a history of hypertension and his current medications include aspirin, hydrochlorothiazide, and lisinopril.  The patient has smoked 1 pack of cigarettes a day for the past 35 years but denies alcohol or illicit drug use.  He exercises twice a week and eats a low-fat diet.  His father died of a myocardial infarction at age 52.  His vital signs are within normal limits.  Physical examination shows a BMI of 26 kg/m² but is otherwise unremarkable.  The patient is concerned about having a heart attack because of his family history.  The physician considers obtaining the patient's LDL-P levels.  Based on the advertisement, 95% of patients will most likely have LDL-P levels that lie between which of the following limits?

A)250 and 550 nmol/L
B)250 and 500 nmol/L
C)300 and 500 nmol/L
D)350 and 500 nmol/L
E)350 and 450 nmol/L

Answer 2

C
Explanation:
The advertisement compares the levels of LDL-C and LDL-P and the risk of developing cardiovascular disease over a 5-year period.  According to the advertisement, the levels of LDL-P and LDL-C were normally distributed, with LDL-P having a mean of 400 nmol/L and a standard deviation of 50 nmol/L.
A normal distribution is defined as a symmetrical, bell-shaped distribution curve.  The degree of dispersion around the mean is given by the standard deviation.  Wider distributions have larger standard deviations, and narrower distributions have smaller standard deviation values.  Normal distributions have a fixed proportion of observations lying within a certain number of standard deviations from the mean.  For instance, 95% of all observations lie within 2 standard deviations of the mean.  In this case, 95% of patients would have an LDL-P value between 300 and 500 nmol/L (mean of 400 ± 2 standard deviations of 50).
(Choice A)  99.7% of all observations lie within 3 standard deviations from the mean.
(Choices B and D)  These limits are asymmetric and therefore do not correspond to the standard 68%, 95%, and 99.7% proportions given by symmetric standard deviation bounds.
(Choice E)  68% of all observations lie within 1 standard deviation from the mean.
Educational objective:
In a normal (bell-shaped) distribution curve, 68% of observations lie within 1 standard deviation of the mean, 95% of observations lie within 2 standard deviations of the mean, and 99.7% of observations lie within 3 standard deviations of the mean.

Question 3

A cross-sectional study is investigating the association between smoking and latent tuberculosis infection (LTBI) in adults age ≥21 in a rural community.  Interferon-γ release assay (IGRA) results are used to determine LTBI status; subjects with a positive IGRA result undergo chest x-ray to exclude active pulmonary tuberculosis.  Sociodemographic, lifestyle, and health-related information are collected by a standardized questionnaire administered by trained interviewers.  The reported results on IGRA positivity among smokers are as follows: Which of the following factors strongly suggests a potential causal relationship between smoking and LTBI?

A)Higher levels of risk for disease with higher levels of exposure to smoking
B)No residual confounding by unadjusted risk factors
C)Smoking occurred before LTBI
D)Statistical significance of the association between smoking and LTBI
E)Strength of the association between smoking and LTBI

Answer 3

A
Explanation:
A dose-response (biological gradient) relationship between an increased level of exposure to a risk factor and an increased probability of disease assumes that the more intense the exposure, the greater the risk of disease.  The presence of a dose-response relationship is one of the criteria to determine causality (although absence of a dose-response relationship should not be taken as evidence against causality).  Any statistically significant association is more likely to be causal if its strength (typically reflected by the absolute value of the statistical parameter, such as the odds ratio [OR]) increases as the exposure to the risk factor increases.
causality
In this example, compared to a history of smoking ≤10 years, for every 10 additional years of smoking, the OR for latent tuberculosis infection (LTBI) increased in the following manner:
Although the cross-sectional study design precludes making causal inferences, the results of the study suggest a potential dose-response relationship between smoking (risk factor) and LTBI (disease).  The dose-response relationship builds on the known significant association between smoking and tuberculosis (possibly because smoking depresses the immune system), thereby offering a stronger evidence of a potential cause-effect relationship.
(Choice B)  Confounding occurs when the association between an exposure and a disease is obscured by the effect of ≥1 extraneous variables that are associated with both.  In this case, the adjusted OR accounted for some of the potential confounding effects of several risk factors (eg, sex, age, education level).  However, additional confounders (residual confounders) may not have been considered, leading to residual confounding.
(Choice C)  Temporality (order of events) states that the cause (ie, risk factor) must precede the outcome (ie, disease).  Temporality is one of the most important criteria for establishing causality.  However, in this case, the study design (ie, cross-sectional study) assesses the association at a single point in time; therefore, it precludes inferring accurate temporal sequence between the risk factor and the disease.
(Choices D and E)  Statistical association, although always a required criterion to establish causality, by itself in no way implies causation.  Compared to weaker statistical associations, stronger ones are more likely to be causal as they are unlikely to be accounted for entirely by alternate explanations (eg, confounding, bias).  In this case, although there appears to be a strong, statistically significant association between smoking and LTBI, the presence of a dose-response relationship provides stronger evidence of a potential causal relationship.
Educational objective:
An association between a risk factor and a disease is more likely to be causal if its strength increases as the exposure level increases (ie, dose-response relationship or biological gradient).  Although a very strong factor in favor of causality, a dose-response relationship is not necessary to infer causation.

Question 4

A 30-month-old boy is admitted to the hospital due to a 3-day history of fever, cough, and dyspnea.  He has a history of recurrent infections, including 4 episodes of cervical lymphadenitis that responded slowly to treatment with clindamycin.  Temperature is 38.2 C (100.8 F), blood pressure is 90/60 mm Hg, pulse is 100/min, and respirations are 30/min.  The anterior cervical lymph nodes are palpated bilaterally with several firm, 1- to 1.5-cm nodes that are nontender, nonfluctuant, and without overlying erythema.  Breath sounds are diminished at the left lower lung base.  The abdomen is soft, nontender, and nondistended without hepatosplenomegaly.  A chest x-ray reveals a patchy infiltrate in the left lower lobe and a moderately sized pleural effusion.  A chest tube is placed, and cloudy fluid is obtained.  Laboratory results are as follows: Microscopy of pleural fluid shows numerous, intact gram-negative rods within neutrophils; cultures ultimately grow Burkholderia cepacia.  The patient's condition improves with appropriate treatment.  Which of the following is most appropriate for infection prophylaxis for this patient?

A)Azithromycin and palivizumab
B)Granulocyte colony-stimulating factor
C)Intravenous immunoglobulin
D)Trimethoprim-sulfamethoxazole and itraconazole

Question 5

A 2-month-old girl is brought to the office for a well-child checkup.  The patient is gaining weight appropriately and has met all developmental milestones.  Her mother plans to exclusively breastfeed her until age 6 months.  The patient has no medical conditions and is up to date on all recommended vaccinations.  She lives with her parents, grandmother, and older brother and will start attending day care next month.  No one in the household smokes, and the family has 2 dogs.  Family history includes atopic dermatitis in the patient's father and older brother.  The mother wants to know if she can do anything to lower the girl's risk for developing atopic dermatitis.  Which of the following is the most appropriate recommendation for this patient?

A)Attend day care as planned
B)Eliminate dairy and eggs from the maternal diet
C)Introduce patient to solid food at age 3 months
D)Introduce patient to solid food at age 9 months
E)Remove dogs from the household

Question 6

A large study examined the role of a new medication X in patients with known atherosclerotic vascular disease.  Study subjects were randomized into intervention (medication X) versus placebo groups and followed for a mean of 3.9 years.  The following results were reported: Which of the following is the most accurate statement about the study results?

A)Administration of medication X is associated with hemorrhagic cerebrovascular accident
B)Medication X can potentially prevent revascularization procedures
C)Number needed to treat to prevent 1 myocardial infarction is 25
D)The effect of the intervention is exaggerated due to intention-to-treat analysis
E)The intervention group had statistically significantly fewer major vascular events

Question 7

A 2-year-old boy is brought to the office due to fever, cough, and irritability lasting 3 days.  Medical history is significant for a perirectal abscess that was drained at age 9 months.  Temperature is 38.9 C (102 F), blood pressure is 100/70 mm Hg, pulse is 124/min, and respirations are 24/min.  Eyes, ears, nose, and throat examinations are normal.  Bilateral patchy crackles are auscultated in the lower lobes.  Chest x-ray confirms bilateral focal pneumonia.  The patient receives empiric antibiotic therapy; however, he is persistently febrile after 3 days.  CT scan of the chest reveals a small, left pleural effusion and enlarged paratracheal and hilar lymphadenopathy, in addition to the bilateral pneumonia.  Fine-needle biopsy of the lymph nodes and lung tissue shows an inflammatory reaction with granuloma formation.  Biopsy cultures grow Burkholderia (Pseudomonas) cepacia.  What is the mechanism most likely responsible for this patient's current infection?

A)Decreased immunoglobulin production
B)Decreased superoxide production
C)Defective opsonization
D)Impaired clearing of airway secretions
E)Impaired neutrophil chemotaxis

Question 8

A 14-year-old boy is brought to the office due to intermittent rhinorrhea, nasal congestion, and nasal itching for the past 2 months.  He has also had periodic itchy, watery eyes and an occasional daytime cough.  The boy's symptoms occur usually after he plays with a neighbor's cat, and they cause the boy to be more tired than usual and have difficulty sleeping.  He has had no fever, headache, weight loss, or sick contacts.  The patient has atopic dermatitis and was hospitalized for bronchiolitis at age 2.  He uses a topical corticosteroid ointment as needed, and his immunizations are up to date.  Family history is significant for a younger brother with asthma.  Vital signs are within normal limits.  Physical examination shows a well-appearing boy with dark, edematous lower eyelids and pale, boggy turbinates with clear rhinorrhea.  Lungs are clear to auscultation.  Skin examination shows dry, scaly patches in the antecubital fossae bilaterally with associated excoriations.  Which of the following is the most effective long-term strategy for relief of this patient's symptoms?

A)Avoidance of the cat
B)Intranasal cromolyn sodium
C)Intranasal decongestant
D)Oral corticosteroid
E)Second-generation antihistamine

Question 9

Researchers are interested in determining whether oral corticosteroid administration is a more effective treatment for patients with multiple sclerosis exacerbation than intravenous corticosteroid administration.  They plan to conduct a systematic review and meta-analysis to compare the efficacy of these 2 treatments for acute exacerbations in this population.  The primary outcome is defined as the proportion of patients with improvement on the Expanded Disability Status Scale at 4 weeks.  The table lists the studies that meet inclusion criteria for the meta-analysis: The researchers included only studies 2, 3, and 5 in their meta-analysis.  Which of the following statements concerning the possible results of the meta-analysis is most likely true?

A)Compared with intravenous administration, oral corticosteroid administration will be significantly associated with improvement in scores on the Expanded Disability Status Scale
B)Oral corticosteroid administration will not have a statistically significant benefit over intravenous administration for treating acute relapses
C)Patients on oral corticosteroids will have 70% increased odds of improvement compared with patients on intravenous corticosteroids
D)Results may overestimate the true effect size as they are based on a biased sample of the target population of studies
E)The sample size in the meta-analysis will be too small to detect a significant difference between the 2 treatments

Question 10

A study was conducted to assess the relationship between the use of an over-the-counter pain reliever during pregnancy and the development of a neural tube defect in the offspring.  Mothers whose children have neural tube defects, as well as age-matched controls (mothers whose children do not have such abnormalities), were interviewed using a standard questionnaire.  The study showed that the use of the pain reliever during pregnancy increases the odds of a neural tube defect, even after adjusting for race, other medication use, comorbidities, family history of congenital abnormalities, and serum folate levels.  The odds ratio is 1.5 (p = 0.03).  Which of the following should be the major concern when interpreting the results of this study?

A)Selection bias
B)Interviewer bias
C)Recall bias
D)Observer bias
E)Confounding

Question 11

A 71-year-old man comes to the office due to slowly progressive shortness of breath for the past year.  He enjoys working in his garden, but shortness of breath has forced him to reduce the time he spends there.  He also has a mild morning cough productive of whitish sputum.  He estimates that his physical activity level is <30 min/day.  The patient has a history of hypertension.  He is a retired middle school teacher.  He smoked 2 packs of cigarettes daily for 20 years and quit 15 years ago.  Blood pressure is 127/85 mm Hg, pulse is 78/min, respirations are 14/min, and pulse oximetry is 93% on room air.  BMI is 24 kg/m².  Occasional end-expiratory wheezes are present on lung examination, and the heart examination demonstrates a regular rate and rhythm.  Chest x-ray shows hyperinflation, and pulmonary function test results are consistent with an obstructive defect. Suppose that 115 of the 160 (71.9%) patients age >65 with chronic obstructive pulmonary disease in the study completed all the surveys and questionnaires.  Which of the following best explains the potential bias introduced by the nonresponse in the study?

A)Compared to respondents, nonrespondents represent an entirely different population
B)Nonrespondents caused a violation of the assumption of independence between observations
C)Nonrespondents reduced the sample size; therefore, the likelihood for type I error is increased
D)Respondents and nonrespondents come from the same population; therefore, the potential for bias is minimal
E)Respondents may differ in some important way from nonrespondents

Question 12

A 33-year-old woman comes to the clinic for a routine health maintenance examination.  She has no lower abdominal pain, vaginal bleeding, or vaginal discharge.  Her past medical history is remarkable for 1 episode of uncomplicated urinary tract infection treated with a short course of antibiotics.  She is currently not taking any medications.  She has had 5 sexual partners in her life and has used barrier contraception the majority of the time.  Her latest sexual relationship began 3 months ago.  Her last cervical cancer screening examination was a Pap smear performed at the age of 23 that showed no abnormalities.  She does not use tobacco, alcohol, or illicit drugs.  During her visit, she requests screening for cervical cancer and appears extremely concerned as her older sister was recently diagnosed with it.
Based on the study results, which of the following testing sequences would be most effective for ruling out cervical neoplasia in this patient?

A)Perform HPV testing → if positive (≥1 pg HPV DNA/mL), perform Pap smear → if positive (ASCUS or worse), refer for biopsy
B)Perform HPV testing → if positive (≥1 pg HPV DNA/mL), refer for biopsy
C)Perform Pap smear → if positive (ASCUS or worse), perform HPV testing → if positive (≥1 pg HPV DNA/mL), refer for biopsy
D)Perform Pap smear → if positive (ASCUS or worse), refer for biopsy

Question 13

The following advertisement is focused on LDL particle number (LDL-P) testing, a novel new screening method used for assessing LDL. Based on the study shown in the advertisement, initial levels of LDL-C and LDL-P were obtained in 5584 individuals and the cumulative incidence of cardiovascular events was tracked.  Which of the following choices best identifies the study design used in the advertisement?

A)Case-control study
B)Cross-sectional study
C)Prospective cohort study
D)Randomized clinical trial
E)Retrospective cohort study

Question 14

A 24-year-old man comes to the emergency department with palpitations.  He has had short-lived episodes of palpitations for several years, but this one is persistent.  He has no past medical history and takes no medications.  ECG shows regular narrow-complex tachycardia (QRS duration of 90 msec) at a rate of 175/min.  His blood pressure is 135/80 mm Hg and physical examination is notable for tachycardia but otherwise unremarkable.  Vagal maneuvers are ineffective in breaking the tachycardia.  The patient receives a rapid intravenous push of adenosine (6 mg) followed by saline chaser.  Soon after the bolus, his heart rate becomes 230/min and irregular, and the rhythm rapidly degenerates into ventricular fibrillation.  The patient loses consciousness, and the pulse is not palpable.  He is immediately defibrillated and regains consciousness.  He has poor recollection of the recent events but has no other complaints.  Repeat ECG shows normal sinus rhythm at a rate of 89/min, short PR interval of 110 msec, prolonged QRS complex of 130 msec, and delta waves in multiple leads.  Which of the following best classifies this patient's encounter?

A)Medicolegal error
B)Near-miss
C)Negligent adverse event
D)Non-preventable adverse event
E)"Save" event

Question 15

A randomized controlled trial investigated the effect of body awareness therapy (BAT) and aerobic exercises on pain and quality of life in patients with tension-type headache.  Participants were randomly assigned to 1 of 3 groups:  BAT group, aerobic exercise (AE) group, and control group.  Main outcomes were pain severity evaluated by a Visual Analog Scale (VAS); pain-related disability measured by the Pain Disability Index (PDI); impact of headaches measured by the Headache Impact Tests (HIT); and quality of life measured by the Short Form Health Survey (SF-36).  Baseline characteristics concerning age, weight, height, BMI, VAS, and HIT were not statistically different among the groups (p > 0.05).  However, there was a statistically significant difference among the groups (p < 0.05) in mean baseline PDI values.  Further evaluation of baseline PDI values revealed the following: Which of the following is likely to be the most valid measure of central tendency for baseline PDI data?

A)Mean and median both equally valid
B)Mean, median, and mode all equally valid
C)Mean only
D)Median only
E)Mode only

Question 16

A 19-year-old male presents to the emergency department with acute onset of breathlessness.  He was feeling short of breath for the last few weeks, but it was not that severe.  He denies any chest pain or cough.  He is a non-smoker and non-alcoholic.  His father has asthma. His respiratory rate is 22/min and pulse rate is 98/min.  There is diffuse wheezing all over the lung fields.  PEFR is 230 L/min, and this improves markedly after bronchodilator therapy.  Which of the following is the most frequent cause of this disorder?

A)House dust mite
B)Cat allergen
C)Dog allergen
D)Cockroach allergen
E)Air pollution

Question 17

A large-scale clinical trial is being planned to evaluate the effect of a nonselective beta blocker, propranolol, on the clinical course of portal hypertension.  The comparison is with placebo.  The primary outcomes of the study are all-cause mortality and major gastrointestinal hemorrhage.  Secondary outcomes are minor gastrointestinal hemorrhage and the number of hospitalizations.  Classification of the episodes of gastrointestinal hemorrhage into "major" and "minor" is based on clinical assessment as well as laboratory data such as change in hemoglobin level.  The investigators are concerned about the possibility that major gastrointestinal hemorrhage events could be over-reported in the placebo group.  Which of the following is the most useful technique to reduce this possibility?

A)Blinding
B)Matching
C)Randomization
D)Restriction
E)Stratified analysis

Question 18

A 56-year-old man with exertional chest pain comes to the office because his exercise stress echocardiogram showed evidence of mild ischemia in the posterior wall.  He was recently diagnosed with type 2 diabetes mellitus and hypertension.  He is a current smoker but is willing to quit.  His father died of a heart attack at age 51.  Physical examination is unremarkable. Laboratory results are as follows:
Based on the information in the drug advertisement,
According to the drug advertisement, the investigators reported the median value and the median percentage change from baseline for triglyceride levels in the study patients.  Which of the following best explains the reason for reporting median values as opposed to mean values?

A)High number of missing values
B)Narrow range of values
C)Skewed distribution
D)Small sample size

Question 19

A group of researchers wants to investigate an outbreak of acute diarrhea that occurred in a coastal town in northern Massachusetts.  Approximately 50 people who were from the town or were visiting the surrounding area had severe hemorrhagic diarrhea, in most cases requiring hospitalization for several days.  A fatal case was reported.  The researchers believe that the outbreak is related to seafood prepared at one of the coastal restaurants.  Which of the following study designs is most appropriate to test this hypothesis?

A)Case-control study
B)Correlational study
C)Cross-sectional study
D)Longitudinal study
E)Randomized clinical trial

Question 20

A 54-year-old man comes to the office for follow-up of type 2 diabetes mellitus.  The patient also has a history of hypertension, obesity, and chronic kidney disease (CKD).  Medications include an antihyperglycemic agent and insulin.  Blood pressure is 148/92 mm Hg and pulse is 81/min and regular.  BMI is 34 kg/m².  Physical examination is otherwise unremarkable.  Laboratory results are as follows:
Based on his serum creatinine level, his CKD has progressed, and the calculated glomerular filtration rate (eGFR) is now 42 mL/min/1.73 m², down from 55 mL/min/1.73 m² as measured 6 months ago.
As stated in the ad, the proportion of subjects reaching A1c <7.0% was one of the prespecified secondary endpoints evaluated at week 26.  Compared to the placebo group, a greater proportion of subjects in the 2 kanebaflozin groups achieved A1c <7.0%; however, researchers did not perform or report tests for the statistical significance of the differences in secondary endpoints among the 3 groups.  Which of the following is the most likely reason that these statistical tests were not conducted?

A)At baseline, there was no difference in mean A1c among the 3 groups
B)No statistical test is necessary as the large intergroup differences are clinically significant
C)Testing for multiple secondary endpoints increases the likelihood of a type I error
D)The overlap of confidence intervals among the 3 groups implies the results were statistically significant
E)The placebo group had an adjusted mean increase rather than a mean decrease in A1c

Question 21

A graduate student conducting research on the association between vitamin D₃ supplementation and cancer is reviewing the abstract of a recently published journal article.
Which of the following conclusions can be drawn from the results of the study?

A)BMI modifies the effect of vitamin D₃ on metastatic cancer
B)Only BMI ≥30 kg/m² is significantly associated with an increase in metastatic cancers
C)The effect of vitamin D₃ on cancer mortality is significant only for certain individuals
D)Vitamin D₃ is significantly associated with a reduction in cancer mortality regardless of BMI level

Question 22

A systematic review examines the effect of drug X, a commonly used medication, on all-cause mortality in patients with a chronic pulmonary problem.  A systematic search identified 12 retrospective cohort studies.  The pooled odds ratio of mortality with drug X use was 0.72 (95% confidence interval: 0.61-0.79).  The authors also reported the following funnel plot of the 12 studies, centered around the log of the pooled odds ratio: The graphical findings suggest the presence of which of the following?

A)Lead-time bias
B)Placebo effect
C)Publication bias
D)Small samples in drug X treatment arms

Question 23

Investigators want to explore a possible association between the use of nonsteroidal antiinflammatory drugs (NSAIDs) and the development of Crohn disease.  They plan to administer a standardized questionnaire on NSAID use over the past year to patients with newly diagnosed Crohn disease and to age- and sex-matched healthy volunteers.  The study design is most concerning for which of the following?

A)Lack of external validity
B)Lack of statistical power
C)Length time bias
D)Misclassification of exposure
E)Misclassification of outcome

Question 24

A study investigates the prevalence of ischemia in 512 patients with chest pain undergoing stress testing.  Only patients with negative cardiac enzymes and nondiagnostic electrocardiogram changes are included.  Myocardial perfusion imaging for ischemia and coronary artery calcification (CAC) score are obtained for each participant.  The following results are reported: Which of the following best describes the study design?

A)Case-control study
B)Case series
C)Cross-sectional study
D)Prospective cohort study
E)Randomized clinical trial

Question 25

Gastric adenocarcinoma is typically diagnosed using upper endoscopy and managed with radical gastrectomy and, in some cases, chemoradiation; nevertheless, long-term survival is poor.  Researchers in a region with a relatively high incidence of gastric adenocarcinoma are evaluating a novel screening test for early detection of the malignancy in high-risk patients.  The novel test is based on the measurement of a recently discovered serologic marker of gastric adenocarcinoma, MGAc.  Based on results of a large study sample of representative high-risk patients screened with MGAc and diagnosed with gastric adenocarcinoma, the mean survival of patients since time of diagnosis is 8.2 months.  A review of records shows that, compared to these patients, similar high-risk patients who were diagnosed using the traditional endoscopic modality had a statistically significant lower mean survival of 7.1 months, with no statistically significant differences in the rates of radical gastrectomy or in the average number or intensity of chemoradiation cycles.  Which of the following best explains these results?

A)Lead-time bias
B)Length-time bias
C)Low sensitivity
D)Recall bias
E)Selection bias

Question 26

A large longitudinal study examined the association between obesity (defined as BMI >30 kg/m²) and risk of ischemic stroke in a cohort of patients.  After assessing participant baseline characteristics, researchers followed 2,300 patients for a mean of 2.7 years and determined the incidence of major cardiovascular events.  Within the entire cohort, the crude relative risk (RR) of ischemic stroke was 2.4 in obese patients as compared to nonobese patients, with a 95% confidence interval (CI) of 1.8-2.6.  When the cohort patients were divided into those with diabetes mellitus and those without, among patients with diabetes, the RR of ischemic stroke was 1.1 in obese as compared to nonobese patients (CI, 0.9-1.6) whereas among patients without diabetes, the RR was 1.0 (CI, 0.7-1.5).  Which of the following is the best interpretation of this study's findings?

A)Diabetes confounds the association between stroke and obesity.
B)Obesity increases the risk of stroke in patients with diabetes only.
C)Obesity independently increases the risk of stroke in the study population.
D)Obesity is confounding the association between stroke and diabetes.
E)The same relative rate of stroke is seen in obese and nonobese patients.

Question 27

A 33-year-old woman comes to the clinic for a routine health maintenance examination.  She has no lower abdominal pain, vaginal bleeding, or vaginal discharge.  Her past medical history is remarkable for 1 episode of uncomplicated urinary tract infection treated with a short course of antibiotics.  She is currently not taking any medications.  She has had 5 sexual partners in her life and has used barrier contraception the majority of the time.  Her latest sexual relationship began 3 months ago.  Her last cervical cancer screening examination was a Pap smear performed at the age of 23 that showed no abnormalities.  She does not use tobacco, alcohol, or illicit drugs.  During her visit, she requests screening for cervical cancer and appears extremely concerned as her older sister was recently diagnosed with it. During the study, women with abnormal Pap test results or a positive HPV test underwent colposcopy and biopsy, as did a random sample of women with negative test results.  The purpose of performing a colposcopy and a biopsy on women with negative test results is to reduce which type of bias?

A)Contamination bias
B)Observer bias
C)Selection bias
D)Susceptibility bias
E)Verification bias

Question 28

Researchers are conducting a clinical trial to assess the effect of erythropoietin on the survival of patients with end-stage renal disease receiving dialysis.  Statistical analysis of the data shows that, after adjustment for age, sex, and duration of disease, patients who did not receive erythropoietin were at increased risk of mortality compared with those who did; the calculated relative risk (RR) of survival and corresponding p-value for patients treated with erythropoietin were RR = 2.4 with p = 0.005.  Among patients with diabetes, erythropoietin use was associated with higher survival rates, with an RR of 6.2 and p < 0.001.  Among patients without diabetes, however, the corresponding RR was 0.94 with p = 0.56.  The researchers are preparing a manuscript for publication of their findings.  Which of the following recommendations is most appropriate for the manuscript?

A)Diabetes status of patients could be ignored.
B)Only the p-value for patients with diabetes should be reported.
C)Overall relative risk (RR; RR = 2.4) is the best measure of outcome to report.
D)Overall RR (RR = 2.4) should be adjusted for diabetes status.
E)Separate RRs for patients with and without diabetes should be reported.

Question 29

Women with inflammatory bowel disease (IBD) appear to be at greater risk for human papillomavirus (HPV) infection and HPV-related malignancies compared to healthy counterparts.  A new study evaluated knowledge about HPV infection among women with IBD.  Potential participants were identified from among patients seeking care at local clinics, and all women age ≥15 with an established diagnosis of IBD from 2009 to 2010 were invited to participate in the study.  A questionnaire was used to collect information on demographics, lifestyle, sexual behavior, and HPV-related knowledge; simultaneously, the association between HPV-related knowledge and the other factors was analyzed.  Which of the following best describes the study design?

A)Case series
B)Case-control
C)Cross-sectional
D)Prospective cohort
E)Retrospective cohort

Question 30

The drug advertisement suggests that BoXeva should be added to metformin for the treatment of patients with type 2 diabetes mellitus. A 56-year-old woman comes to the office for follow-up.  She has a history of type 2 diabetes mellitus and hypertension.  The patient has been on metformin therapy for the past 6 months.  Despite adhering to a diabetic diet and increasing her level of physical activity, she has been unable to lose weight.  At the current visit, her blood pressure is 145/90 mm Hg, and heart rate is 72/min.  Her weight is 82 kg (180 lb).  HbA_1c is 7.6%, and serum creatinine is 0.9 mg/dL.
The section of the drug advertisement shown does not mention side effects.  BoXeva inhibits sodium-glucose cotransporter 2 (SGLT2), which is expressed in the proximal renal tubules.  Based on this mechanism of action, which of the following side effects would be expected for the SGLT2 inhibitor class of medications?

A)Acute inflammatory pancreatitis
B)Acute lactic acidosis
C)Angioedema
D)Flatulence and diarrhea
E)Vulvovaginal candidiasis

Question 31

The proportion of colonoscopies performed by a physician with at least 1 detected adenoma is called the adenoma detection rate.  A study examined the association between the adenoma detection rate and the risk of colorectal cancer 6 months to 10 years after colonoscopy.  In the graph below, physicians were sorted into quintiles based on their adenoma detection rate, with quintile 1 being the lowest rate of detection and quintile 5 being the highest.  There were no significant differences in rates of complications.  The hazard ratios (HRs), shown along with their corresponding 95% confidence intervals (CIs), were adjusted for other variables including patient age, sex, comorbidities, and indication for colonoscopy. Which of the following statements best describes the study results?

A)Adenoma detection rate could be a useful quality measure of a physician's colonoscopy performance
B)Adenoma detection rate is not associated with the incidence of colorectal cancer
C)Patients with no adenomas can be safely followed for 10 years without repeat colonoscopy
D)Physicians in quintile 3 prevent significantly more colorectal cancers than those in quintile 1
E)The risk of colorectal cancer appears to increase with higher adenoma burden

Question 32

A 45-year-old man is diagnosed with dilated nonischemic cardiomyopathy.  Late gadolinium enhancement cardiac magnetic resonance (CMR) imaging shows a left ventricular ejection fraction (LVEF) of 20% and evidence of extensive midwall myocardial scarring.  A recent study determined prognosis in patients with dilated cardiomyopathy using CMR-derived LVEF and evidence of midwall myocardial scarring (fibrosis).  Two models were assessed: one model was based on LVEF alone, and the other incorporated the presence or absence of fibrosis.  The following 5-year prediction curves were reported: Based on the study results, what is the approximate predicted 5-year all-cause mortality for this patient?

A)10%
B)20%
C)30%
D)40%
E)50%

Question 33

A three-arm, randomized crossover trial is conducted to determine whether the profile of circulating micro RNAs (miRNAs) is altered after acute resistance training with blood flow restriction (BFR), as compared with unrestricted low- and high-volume training.  Eighteen healthy volunteers (mean age 25) are enrolled.  The arms are single bouts of leg flexion/extension resistance training at: 70% of the individual single-repetition maximum (1RM)30% of the 1RM30% of the 1RM with BFR (artificially applied by a cuff at 300 mm Hg)
During each training intervention, load-associated outcomes (fatigue, heart rate, and exhaustion) are monitored.  Acute effects (circulating miRNAs and lactate) are determined using pre- and postintervention measurements.  Preliminary results show that lower lactate concentrations tend to correspond with lower miR-143-3p expression, and that the relationship is very strong and statistically significant.  Based on this information, which of the following statements is most correct about the correlation coefficient r for this relationship?

A)r is negative and probably closer to −1 than to 0
B)r is negative and probably closer to 0 than to −1
C)r is positive and probably closer to 0 than to 1
D)r is positive and probably closer to 1 than to 0

Question 34

A 5-day-old girl is brought to the office by her adoptive parents for her first newborn visit.  The girl has been doing well.  The parents are concerned about her risk of having hemophilia A.  The birth father and his brother (the paternal uncle) have hemophilia A.  The birth mother does not, and there is no history of bleeding in her family, including in male relatives.  The girl is well-appearing and has no abnormalities on examination.  Which of the following is the most appropriate response?

A)The girl has a 25% chance of having hemophilia and a 75% risk of being a carrier
B)The girl has a 50% chance of having hemophilia and a 50% risk of being a carrier
C)The girl has a 75% chance of having hemophilia and a 25% risk of being a carrier
D)The girl has hemophilia
E)The girl will be a carrier

Question 35

A 62-year-old man with a history of dyslipidemia and type 2 diabetes mellitus comes to the emergency department due to severe substernal chest pain and diaphoresis that began 2 hours ago.  His ECG shows ST- segment elevation in leads V1 to V4.  He is taken to the cardiac catheterization lab and a complete occlusion of the mid-left anterior descending artery (LAD) is diagnosed.  A drug-eluting stent is placed in the LAD with complete restoration of flow, and the patient is started on aspirin and clopidogrel.  On the third day of hospitalization, the option of adding rivaroxaban is discussed with the patient.  He asks about the benefits and risks of the added therapy.  Based on the research abstract, The statistical methods section of the full research paper indicates that the analysis was performed using an "intention-to-treat" approach.  The primary purpose of such an approach is most likely which of the following?

A)Decrease the placebo effect
B)Eliminate observer bias
C)Enhance external validity
D)Preserve randomization
E)Reduce type II errors

Question 36

A cohort study of 4,000 patients examines the role of vitamin D supplements on the incidence of colon cancer.  Relative risk (RR) calculations with their corresponding 95% confidence intervals (CI) are reported for subjects taking vitamin D versus controls after a 5-year follow-up period: A separate double-blind randomized clinical trial assigns 3,900 subjects to vitamin D supplementation or placebo.  The following results are reported for subjects taking vitamin D versus placebo after a 5-year follow-up period:
Which of the following best describes the results of both studies?

A)Cancer prevention using vitamin D lacks biological plausibility
B)Lead-time bias best explains the discrepancy in study results
C)Residual confounding best explains the discrepancy in study results
D)Results of both studies support using vitamin D for colon cancer prevention
E)The clinical trial was underpowered to detect any difference in outcomes

Question 37

Several clinical trials studied the effect of a new antiviral agent on symptomatic relief of genital herpes simplex virus infection.  All trials were based on physician report of symptom improvement; valacyclovir was used as a comparator.  The pooled analysis of studies that blinded only patients favored valacyclovir with an odds ratio for valacyclovir of 1.65 (95% confidence interval, 1.53-1.75).  The pooled analysis of studies that blinded both patients and treating physicians favored the new agent with an odds ratio for valacyclovir of 0.64 (95% confidence interval, 0.38-0.79).  Which of the following best explains the difference in the reported odds ratios?

A)Effect modification
B)Lead-time bias
C)Observer bias
D)Publication bias
E)Randomization failure

Question 38

A 71-year-old man comes to the office due to slowly progressive shortness of breath for the past year.  He enjoys working in his garden, but shortness of breath has forced him to reduce the time he spends there.  He also has a mild morning cough productive of whitish sputum.  He estimates that his physical activity level is <30 min/day.  The patient has a history of hypertension.  He is a retired middle school teacher.  He smoked 2 packs of cigarettes daily for 20 years and quit 15 years ago.  Blood pressure is 127/85 mm Hg, pulse is 78/min, respirations are 14/min, and pulse oximetry is 93% on room air.  BMI is 24 kg/m².  Occasional end-expiratory wheezes are present on lung examination, and the heart examination demonstrates a regular rate and rhythm.  Chest x-ray shows hyperinflation, and pulmonary function test results are consistent with an obstructive defect.
Based on the results of the study, which of the following is most likely to occur if the patient increases his physical activity level to >60 min/day?

A)A statistically significant decrease in anxiety and depression based on HADS scores.
B)A statistically significant decrease in anxiety based on HADS-A score.
C)A statistically significant decrease in dyspnea based on MMRC scale score.
D)A statistically significant increase in 6MWD.
E)A statistically significant increase in physical functioning based on SF-36 score.

Question 39

A clinical trial was conducted to compare the effects of ACE inhibitors and diuretics in elderly patients with hypertension.  The investigators believed that ACE inhibitors provide some additional survival benefits over diuretics use in elderly subjects because of their neurohumoral effects.  The study lasted 5 years and the investigators presented the following results after the completion of the study: According to the information given, which of the following is the best interpretation of the study results?

A)ACE inhibitors have no overall advantage over diuretics
B)ACE inhibitors are associated with higher risk of heart failure
C)ACE inhibitors may protect from some cardiovascular events
D)ACE inhibitors decrease the risk of mortality
E)ACE inhibitors should be used with caution in elderly patients

Question 40

A 65-year-old man comes to the clinic for follow-up treatment of hypertension.  He is on 2 antihypertensive agents and says he is compliant with his medication regimen.  The patient has no other medical problems.  Blood pressure is 134/88 mm Hg and pulse is 78/min and regular.  BMI is 32 kg/m².  Physical examination is otherwise unremarkable.  His fasting blood glucose levels on 2 recent laboratory workups were 108 mg/dL and 111 mg/dL.  He is concerned about his risk of dementia because his father suffers from Alzheimer dementia. After excluding from the analysis participants with diabetes who had an unusual clinical course such as high fluctuations in reported glucose levels, the investigators repeat their calculations of the hazard ratio of dementia.  This analytical step is best referred to as which of the following?

A)Blinding
B)Linear regression
C)Matching
D)Propensity scoring
E)Sensitivity analysis

Question 41

A 42-year-old woman comes to the office for a routine follow-up.  She was diagnosed with multiple sclerosis 3 months ago and has had no relapses since.  She had previously preferred not to take any medications for multiple sclerosis, but she is now interested in finding out about different treatments.  The patient has no other medical problems.  She does not use tobacco, alcohol, or illicit drugs.  Examination shows no abnormalities.  A new treatment A is available that is apparently highly effective in preventing multiple sclerosis relapses.  A randomized trial shows that the incidence of relapses was 20% after 6 months of treatment A.  Patients managed with placebo had an incidence of 25% during the same time period.  Considering this information, how many patients will need to be treated with treatment A in order to prevent 1 episode of relapse of multiple sclerosis during the first 6 months of therapy?

A)Four patients
B)Eight patients
C)Twenty patients
D)Ten patients
E)Five patients

Question 42

Two independent research groups are studying the effect of a new anticoagulant on the incidence of deep-vein thrombosis after hip replacement surgery.  The first group designs a 1:1 randomized trial with 1000 patients comparing the new drug with the standard of care (500 patients in each group).  The second group designs a similar randomized trial but intends to recruit 500 patients (250 patients in each group).  Assuming similar populations for patient recruitment, the small study has a higher chance of which of the following?

A)Early termination
B)Outcome misclassification
C)Selection bias
D)Type I error
E)Type II error

Question 43

A 46-year-old woman comes to the office due to persistent joint pains.  She has a history of rheumatoid arthritis and, for the past 6 months, has been on methotrexate (Mtx) therapy.  However, her symptoms have shown little improvement.  She has morning stiffness that lasts for >1 hour, and her erythrocyte sedimentation rate is 40 mm/hr.  A discussion is initiated regarding modifying her therapy to include either subcutaneous (SC) tocilizumab (TCZ_SC) or SC abatacept (ABT_SC) in addition to Mtx.  The patient expressed wanting to attempt the most effective treatment and avoid having to modify her treatment again. The mean cost of treatment per number needed to treat (NNT), obtained by multiplying the yearly individual cost by the NNT, is considered an indicator of the clinical benefits and costs linked to the use of the therapies.  Based on the results of the meta-analysis, which of the following best describes the clinical benefits and costs of rheumatoid arthritis therapies per NNT in patients previously treated with Mtx?

A)ABT_sc and TCZ_sc have very similar mean cost per NNT
B)Mean cost per NNT for ABT_sc is approximately $42,000
C)Mean cost per NNT for TCZ _sc is approximately $41,333
D)TCZ_sc represents a more cost-effective therapy per NNT than ABT_sc
E)TCZ _sc represents a more effective but also more costly therapy per NNT than ABT_sc

Question 44

A 46-year-old woman comes to the office due to persistent joint pains.  She has a history of rheumatoid arthritis and, for the past 6 months, has been on methotrexate (Mtx) therapy.  However, her symptoms have shown little improvement.  She has morning stiffness that lasts for >1 hour, and her erythrocyte sedimentation rate is 40 mm/hr.  A discussion is initiated regarding modifying her therapy to include either subcutaneous (SC) tocilizumab (TCZ_SC) or SC abatacept (ABT_SC) in addition to Mtx.  The patient expressed wanting to attempt the most effective treatment and avoid having to modify her treatment again.
Based on the study results, compared to Mtx therapy alone, what is the approximate number needed to treat over 1 year to prevent 1 additional clinical response of <70% improvement with (ABT_SC + Mtx) and (TCZ_SC + Mtx) ?

Question 45

A 26-year-old woman comes to the office due to several weeks of fatigue, headaches, joint pain and swelling, light sensitivity, and occasional periods of low-grade fever.  The patient has no other medical issues.  She works as a systems engineer for a major airline.  Family history is unremarkable.  The diagnosis of systemic lupus erythematosus (SLE) is considered, and an antinuclear antibody (ANA) assay is obtained.  The prevalence of SLE in patients from whom an ANA test is obtained is 3.2%.  The sensitivity of ANA for SLE is 96%, and the specificity is 91%.  Assuming that this patient has SLE, how likely is she to have a positive ANA result compared with a patient without SLE having a positive ANA result?

A)0)04
B)0)26
C)1)00
D)10.67
E)12.82

Question 46

A large study evaluated a rapid toxin-based stool assay for diagnosing Clostridium difficile colitis.  It evaluated the test against polymerase chain reaction, which served as the gold standard.  The following values of the new test were obtained from a hospitalized symptomatic patient population with 50% prevalence of Clostridium difficile colitis: Which of the following is the positive likelihood ratio for the new test?

A)0)2
B)2
C)5
D)6
E)8

Question 47

A 65-year-old man is scheduled for hip replacement surgery.  He is worried about possible complications of the surgery, particularly the risk of heart attack.  A retrospective cohort study identified 98,102 patients who underwent total knee replacement (TKR) or total hip replacement (THR) surgery and compared their rates of myocardial infarction (MI) with those of controls matched by age, sex, and geographic region.  The following curves for hazard ratios (HR) were obtained. Based on the study results and assuming statistical significance, which of the following provides the best explanation to the patient?

A)Although there is no risk of heart attack immediately following surgery, the risk increases after hospital discharge.
B)There is an increased risk of heart attack after surgery, which is best explained by risk factors and comorbidities.
C)There is an increased risk of heart attack right after surgery, but it returns to baseline after 4 weeks.
D)There is an increased risk of heart attack up to approximately 8-10 weeks after the surgery.
E)There is no substantial proof that the surgery is associated with a higher risk of heart attack.

Question 48

A 33-year-old woman comes to the clinic for a routine health maintenance examination.  She has no lower abdominal pain, vaginal bleeding, or vaginal discharge.  Her past medical history is remarkable for 1 episode of uncomplicated urinary tract infection treated with a short course of antibiotics.  She is currently not taking any medications.  She has had 5 sexual partners in her life and has used barrier contraception the majority of the time.  Her latest sexual relationship began 3 months ago.  Her last cervical cancer screening examination was a Pap smear performed at the age of 23 that showed no abnormalities.  She does not use tobacco, alcohol, or illicit drugs.  During her visit, she requests screening for cervical cancer and appears extremely concerned as her older sister was recently diagnosed with it. A national government agency is reviewing data from this paper to decide which screening method to recommend and fund.  However, agency officials realize that the prevalence of cervical cancer varies throughout the country.  For this reason, a reliable epidemiological parameter is needed to compare the significance of negative and positive results obtained in individual patients, irrespective of prevalence.  Which of the following epidemiological parameters would be the most useful in comparing these screening tests when applied to individual patients?

A)False positive and negative rates
B)Likelihood ratios
C)Odds ratio
D)Predictive values
E)Relative risk

Question 49

A retrospective cohort study examines the long-term risk of ischemic stroke in patients with perioperative atrial fibrillation following cardiac and noncardiac surgery.  The following data are reported: Which of the following best describes the study results?

A)Cardiac surgery carries a lower risk of atrial fibrillation than noncardiac surgery
B)Patients with perioperative atrial fibrillation following cardiac surgery should not receive anticoagulation
C)Perioperative atrial fibrillation increases the risk of stroke with either type of surgery
D)Perioperative atrial fibrillation is not predictive of stroke in patients undergoing cardiac surgery
E)The risk of stroke after noncardiac surgery is significantly higher compared to that after cardiac surgery

Question 50

Researchers are interested in further investigating the side effects of a relatively recent hypolipidemic drug.  A literature review showed several studies in which patients who took this drug reported severe acute myositis as an adverse event.  In many instances, affected patients experienced life-threatening complications from myositis, including rhabdomyolysis leading to acute renal failure and profound electrolyte abnormalities.  However, none of these studies documented a statistically significant difference in the occurrence of severe acute myositis between the treatment and placebo groups.  Which of the following is the best method to further investigate the association between use of this hypolipidemic drug and development of severe acute myositis?

A)Conduct a new large-scale clinical trial.
B)Perform stratified analysis on multiple risk factors.
C)Pool the data from several trials.
D)Review the medical charts to re-ascertain the events.
E)There is no need to further study this statistically nonsignificant association.

Question 51

The abstract applies to the next 2 items.Over the course of 5 years, a pediatric endocrinologist has seen a marked increase in the prevalence of depression among patients with obesity in her practice.  She partners with a pediatric psychiatrist to devise a short screening test for depression for this specific population.  The new screening test is found to be 90% sensitive and 84% specific.  If this test is used on a sample of patients with obesity in which 35% are known to have depression
Based on the data, which of the following statements is most accurate concerning exposure to vinyl chloride in the cohort of 10,250 workers?

A)Brain cancer, melanoma, and non-Hodgkin lymphoma mortality were significantly elevated among workers.
B)Exposure to vinyl chloride significantly reduces the risk for Hodgkin disease among workers.
C)Mortality from laryngeal cancer and lung cancer among workers is not statistically lower than expected.
D)The expected number of deaths from liver cancer among workers was significantly higher than the observed number.
E)The observed number of deaths among workers was significantly higher for cancers of the connective and soft tissues.

Question 52

An epidemiologic study is conducted to evaluate the long-term complications of coronary stent placement.  10,000 patients who underwent emergency or elective percutaneous coronary intervention at tertiary care centers around the nation were randomly selected and monitored for the development of adverse events.  According to the study results, 2% of patients who received bare metal stents developed stent thrombosis within a year.  40% of the patients who developed stent thrombosis died as a result.  The risk of death in a patient who develops stent thrombosis is best described by which of the following epidemiologic parameters?

A)Attack rate
B)Case fatality rate
C)Median survival time
D)Mortality rate
E)Standardized mortality ratio

Question 53

A randomized controlled trial assigned patients with diabetes to a new combination antihypertensive pill or placebo group for blood pressure control.  Routine administration of the combination pill was associated with a reduction in the risk for some macrovascular or microvascular events at the end of the trial.  The investigators decided to follow-up with patients after the end of the study to see if the benefits of therapy were sustained.  They report the following hazard ratio curves comparing the combination pill to placebo from the end of the trial (T1) to 6 years afterward. Administration of the combination pill resulted in a statistically significant sustained reduction in events for which of the following outcomes (setting α = 0.05)?

A)Cardiovascular mortality and all-cause mortality
B)Cardiovascular mortality and stroke
C)Major clinical microvascular events and myocardial infarction
D)Major clinical microvascular events and stroke
E)Major macrovascular events and myocardial infarction

Question 54

A 46-year-old man comes to the office due to loose teeth and inflammation in his gums.  After periodontal evaluation, the diagnosis of localized aggressive chronic periodontitis (CP) is suspected.  Laboratory results, including C-reactive protein (CRP) results, are pending.  Results from a recent cross-sectional study evaluating serum CRP levels in 100 subjects with aggressive CP has found that the mean CRP concentration among these subjects is 6 mg/dL ± 1 mg/dL.  If the population has a normal distribution, what is the probability that this patient has a CRP ≥9 mg/dL?

A)0)0015
B)0)003
C)0)025
D)0)05
E)0)16

Question 55

A graduate student conducting research on the association between vitamin D₃ supplementation and cancer is reviewing the abstract of a recently published journal article. The graduate student is interested in conducting further studies among individuals with BMI <25 kg/m².  Which of the following statements regarding these individuals is best supported by the abstract?

A)Having a BMI <25 kg/m² decreases the risk of cancer mortality by 58%
B)Supplementation with vitamin D₃ significantly reduces the risk of metastatic cancer in individuals with BMI <25 kg/m²
C)The risk of cancer mortality is significantly reduced in individuals with BMI <25 kg/m² who supplement their diets with vitamin D₃
D)Vitamin D₃ supplementation is not significantly associated with metastatic cancer or cancer mortality in individuals with BMI <25 kg/m²

Question 56

A randomized controlled trial is conducted to evaluate the safety and efficacy of high-dose protovastatin compared with low-dose protovastatin in patients with stable coronary artery disease (CAD) in the prevention of CAD-related complications.  A total of 12,780 patients with stable CAD who achieved low-density lipoprotein cholesterol (LDL-C) <120 mg/dL during a run-in period (protovastatin 1 mg/d) are randomized (1:1) to high-dose (protovastatin 4 mg/d; n = 6,392) or low-dose (protovastatin 1 mg/d; n = 6,388) statin therapy.  The primary endpoint is a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergency hospitalization.  With a median follow-up of 4 years, the risk of the primary endpoint is 4.3% in the high-dose group and 5.4% in the low-dose group.  The difference in the risk of the primary endpoint is statistically significant.  Which of the following is the most accurate interpretation of these results?

A)Number needed to treat with high-dose protovastatin is 9
B)Number needed to treat with high-dose protovastatin is 91
C)Relative risk reduction for high-dose protovastatin is 1%
D)Relative risk reduction for high-dose protovastatin is 80%

Question 57

A randomized, double-blinded clinical trial was conducted to assess the role of a multidrug chemotherapy regimen for the treatment of newly diagnosed stage III and IV stomach cancer.  In the study, 150 patients were enrolled in the treatment group and received the new multidrug treatment, and 100 patients were enrolled in the control group and were treated with standard first-line therapy.  All patients were followed for 24 months.  A total of 120 patients in the treatment group (80%) and 80 patients in the control group (80%) died during this follow-up period.  Despite these calculations, the investigators concluded that the new multidrug regimen was more effective than standard therapy.  Which of the following most likely accounts for the conclusion reached by the study investigators?

A)2-year mortality risk was calculated
B)Observer bias may be present
C)Selective survival bias may be an issue
D)The results were confounded
E)Time-to-event data was analyzed

Question 58

A follow-up study was conducted to assess the effect of circumcision on the incidence of penile carcinoma.  A large cohort was investigated.  The rate in uncircumcised males was 8/1000, and the rate in circumcised males was 6/1000.  The investigators concluded that circumcision may be markedly effective in reducing the incidence of the disease in the population.  According to the study results, how many patients should be circumcised to prevent one case of penile carcinoma?

A)100
B)250
C)500
D)1000
E)5000

Question 59

A 62-year-old man with a history of dyslipidemia and type 2 diabetes mellitus comes to the emergency department due to severe substernal chest pain and diaphoresis that began 2 hours ago.  His ECG shows ST- segment elevation in leads V1 to V4.  He is taken to the cardiac catheterization lab and a complete occlusion of the mid-left anterior descending artery (LAD) is diagnosed.  A drug-eluting stent is placed in the LAD with complete restoration of flow, and the patient is started on aspirin and clopidogrel.  On the third day of hospitalization, the option of adding rivaroxaban is discussed with the patient.  He asks about the benefits and risks of the added therapy.  Based on the research abstract, which of the following measures would best reflect the net clinical benefit of rivoraxaban?

A)"Death from any cause/myocardial infarction/stroke" and "intracranial hemorrhage"
B)"Death from cardiovascular causes" and "fatal bleeding"
C)"Death from myocardial infarction" and "TIMI bleeding requiring medical attention"
D)"Intracranial hemorrhage" and "fatal bleeding"
E)"Primary efficacy endpoint" only

Question 60

An orthotics and prosthetics company conducts a single-blind, randomized, parallel group trial to investigate the effects of custom foot orthoses with motion control shoes versus the effects of motion control shoes alone in individuals with patellofemoral joint osteoarthritis.  Eligible subjects are randomized to receive either custom foot orthoses with motion control shoes or motion control shoes alone, to be worn for 4 months.  A significant number of patients are lost to follow-up or are noncompliant to the assigned intervention during the study.  However, results for the patients who completed the protocol are encouraging.  Which of the following techniques is most appropriate to estimate the real effect of custom foot orthoses in the population?

A)As-treated analysis
B)Intention-to-treat analysis
C)Noninferiority analysis
D)Per-protocol analysis
E)Stratified analysis

Question 61

Case reports indicate that exposure to manganese among miners may lead to central nervous system damage, particularly a Parkinson-like syndrome.  This syndrome, thought to be associated with increased mortality, is characterized by cogwheel rigidity, neuropsychiatric and cognitive manifestations, balance and speech changes, dystonia more pronounced than that seen with Parkinson disease, and resting tremors less pronounced than those seen with Parkinson disease.  A group of investigators are further investigating the association between exposure to manganese and increased mortality among miners.  As part of their statistical analysis, they calculate a standardized mortality ratio of 1.75 among manganese miners compared to the general population.  Which of the following statements is most applicable to this study result?

A)Manganese miners are 75% more likely to develop Parkinson-like syndrome.
B)The crude rate of death is 75 times higher among miners compared to the general population.
C)The observed number of deaths among miners is 75% higher than expected.
D)The standardized mortality ratio is an unadjusted measure of overall mortality.
E)The standardized mortality ratio is not generally applicable to occupational studies.

Question 62

A randomized, double-blinded clinical trial was conducted to evaluate the effect of a new hypolipidemic drug on the survival of patients after percutaneous coronary intervention (PCI).  1000 patients undergoing PCI were randomly assigned to the drug or placebo group.  500 patients were in each group.  The 2 groups were then followed for 3 years for the development of acute coronary syndromes.  Severe acute myositis was reported as a rare side effect of the drug therapy, but the difference between the 2 groups in the occurrence of this side effect was not statistically significant (p = 0.09).  A review of the literature shows that, in prior clinical trials and case reports, the same side effect was noted in some patients taking this drug.  Which of the following is the most likely cause for the failure to detect a significant statistical difference in the occurrence of acute myositis between the treatment and placebo groups in this randomized trial?

A)Ascertainment bias
B)Limited follow-up period
C)Inappropriate patient selection
D)Small sample size
E)Observer bias

Question 63

A 54-year-old man comes to the office for follow-up of type 2 diabetes mellitus.  The patient also has a history of hypertension, obesity, and chronic kidney disease (CKD).  Medications include an antihyperglycemic agent and insulin.  Blood pressure is 148/92 mm Hg and pulse is 81/min and regular.  BMI is 34 kg/m².  Physical examination is otherwise unremarkable.  Laboratory results are as follows:
Based on his serum creatinine level, his CKD has progressed, and the calculated glomerular filtration rate (eGFR) is now 42 mL/min/1.73 m², down from 55 mL/min/1.73 m² as measured 6 months ago.
Based on the ad, which of the following is the most accurate statement concerning the use of kanebaflozin in this patient?

A)Adding kanebaflozin 300 mg will increase by 0.46% the patient's probability of lowering mean A1c
B)Because his A1c is 8.0%, the patient would likely benefit more from 100 mg than 300 mg of kanebaflozin
C)Either dose of kanebaflozin will likely lead to a statistically significant reduction in the patient's mean A1c level
D)The patient is unlikely to derive any significant benefit from kanebaflozin due to the decline in kidney function
E)The study was underpowered to detect any statistically significant benefit from kanebaflozin

Question 64

A team of neurologists and psychologists researching intellectual function is reviewing the results of a study on the association between childhood lead exposure and adult intellectual function.
Based on the abstract, which of the following is the most concerning factor regarding the design of the study?

A)Contamination bias
B)External validity
C)Lack of statistical power
D)Measurement error
E)Selection bias

Question 65

A 62-year-old man with a history of dyslipidemia and type 2 diabetes mellitus comes to the emergency department due to severe substernal chest pain and diaphoresis that began 2 hours ago.  His ECG shows ST- segment elevation in leads V1 to V4.  He is taken to the cardiac catheterization lab and a complete occlusion of the mid-left anterior descending artery (LAD) is diagnosed.  A drug-eluting stent is placed in the LAD with complete restoration of flow, and the patient is started on aspirin and clopidogrel.  On the third day of hospitalization, the option of adding rivaroxaban is discussed with the patient.  He asks about the benefits and risks of the added therapy.  Based on the research abstract, After a pharmaceutical drug is approved by the Food and Drug Administration, phase IV or post-marketing surveillance is conducted to detect fatal and serious side effects.  The failure to detect such events in earlier phases of clinical testing is most likely due to which of the following?

A)Biased allocation of patients
B)Hidden confounders
C)Inadequate power
D)Measurement bias
E)Use of placebo

Question 66

The drug advertisement suggests that BoXeva should be added to metformin for the treatment of patients with type 2 diabetes mellitus. A 56-year-old woman comes to the office for follow-up.  She has a history of type 2 diabetes mellitus and hypertension.  The patient has been on metformin therapy for the past 6 months.  Despite adhering to a diabetic diet and increasing her level of physical activity, she has been unable to lose weight.  At the current visit, her blood pressure is 145/90 mm Hg, and heart rate is 72/min.  Her weight is 82 kg (180 lb).  HbA_1c is 7.6%, and serum creatinine is 0.9 mg/dL.
Compared to adding BoXeva, adding glimepiride to this patient's current regimen will most likely lead to which of the following at 52 weeks of treatment?

A)Higher chance of sustained glycemic control
B)Higher insulin resistance
C)Higher risk of stroke
D)Lower compliance rate
E)Similar effect on glycemic control

Question 67

A study assesses the length of stay in the intensive care unit after common surgical procedures.  The following graph is obtained by plotting the number of admissions against length of stay (in days). Which of the following corresponds to the measures of central tendency on the graph?

A)Line 1: Mean; Line 2: Median; Line 3: Mode
B)Line 1: Median; Line 2: Mean; Line 3: Mode
C)Line 1: Median; Line 2: Mode; Line 3: Mean
D)Line 1: Mode; Line 2: Mean; Line 3: Median
E)Line 1: Mode; Line 2: Median; Line 3: Mean

Question 68

The following advertisement is focused on LDL particle number (LDL-P) testing, a novel new screening method used for assessing LDL. The patient's fasting serum lipid profile and LDL-P levels are as follows:
Given these results combined with the patient's risk factors for cardiovascular disease, the physician discusses lifestyle modifications with the patient and decides to start him on a statin.  The treatment of his lipids for the prevention of myocardial infarction is an example of which of the following?

A)Primordial prevention
B)Primary prevention
C)Secondary prevention
D)Tertiary prevention
E)Quaternary prevention

Question 69

The drug advertisement suggests the addition of Zettiga (extended-release niacin) to low-dose simvastatin for the treatment of high-risk patients with type 2 hyperlipidemia or mixed dyslipidemia.
A 56-year-old man with exertional chest pain comes to the office because his exercise stress echocardiogram showed evidence of mild ischemia in the posterior wall.  He was recently diagnosed with type 2 diabetes mellitus and hypertension.  He is a current smoker but is willing to quit.  His father died of a heart attack at age 51.  Physical examination is unremarkable.
Laboratory results are as follows:
Based on the information in the drug advertisement, which of the following changes in HDL and LDL cholesterol would be expected if this patient was started on combined Zettiga and simvastatin compared to simvastatin alone?

Question 70

A group of researchers is designing a study to investigate the role of a new diet in treating patients with mild hypertension.  The researchers are using the following parameters to calculate the sample size required for the study: Expected change (decrease) in systolic blood pressure (SBP) with the new diet:  8 mm HgExpected standard deviation for SBP in the population:  10 mm HgValue for α:  0.01Power:  0.85
Based on these parameters, they estimate the minimum sample size required for a 2-tailed test to be 21.  In which of the following situations would a sample size >21 be needed to appropriately address the research question?

A)If actual decrease in systolic blood pressure with the new diet is 5 mm Hg rather than 8 mm Hg
B)If actual standard deviation for systolic blood pressure is 7 mm Hg rather than 10 mm Hg
C)If α is set at 0.05 rather than at 0.01
D)If power is set at 0.75 rather than at 0.85
E)If the 2-tailed test is replaced by a 1-tailed test

Question 71

Two groups of investigators are interested in the problem of esophageal cancer in a population that has a high prevalence of hot beverage consumption.  One group conducted study A, which showed that hot beverage consumption is associated with esophageal cancer, with an odds ratio (OR) of 1.51 and a 95% confidence interval of 1.19 to 1.81.  The other group conducted study B, which demonstrated an OR of 1.46 and a 95% confidence interval of 0.95 to 1.97.  Which of the following statements is most likely true concerning the results of these 2 studies?

A)The odds ratio estimate obtained in study A is likely not valid.
B)The p-value for the odds ratio estimate in study B is likely < 0.05.
C)The results of study A are not statistically significant.
D)The sample in study B is likely poorly selected.
E)The sample size in study B is likely too small to detect a difference.

Question 72

A 65-year-old man comes to the clinic for follow-up treatment of hypertension.  He is on 2 antihypertensive agents and says he is compliant with his medication regimen.  The patient has no other medical problems.  Blood pressure is 134/88 mm Hg and pulse is 78/min and regular.  BMI is 32 kg/m².  Physical examination is otherwise unremarkable.  His fasting blood glucose levels on 2 recent laboratory workups were 108 mg/dL and 111 mg/dL.  He is concerned about his risk of dementia because his father suffers from Alzheimer dementia.
Based on the study results, which of the following is the best response to this patient's concerns?

A)"Glucose toxicity causes dementia in a dose-response manner."
B)"Only uncontrolled diabetes is associated with a risk of dementia."
C)"We need to control your blood glucose level to prevent dementia."
D)"Your family history of dementia increases your risk of dementia; diabetes does not."
E)"Your risk of dementia may be increased, even with borderline blood glucose levels."

Question 73

A group of investigators is exploring trends in the incidence of coronary heart disease (CHD) in a large population.  The investigators studied several factors in relation to the incidence of the disease.  The relationships between cigarette sales in the population (in average number of cigarette packs sold per person per day) and the incidence of CHD (per 1000 people) over time are given on the figure below: Which of the following is the best statement concerning the results of the study?

A)Coronary heart disease (CHD) incidence shows no stable trend over time
B)Individuals from this population who quit smoking have a decreased risk of CHD
C)Sales of cigarettes in the population increased over time
D)The plot cannot provide individual-level conclusions
E)There are discordant changes in cigarette sales and CHD incidence

Question 74

A study examines the association between benzodiazepine use and hip fracture in elderly patients >70 years of age.  A total of 180 patients admitted to 20 hospitals with hip fracture were included in the analysis; 10 patients used benzodiazepines in the week before admission.  For comparison, the investigators selected 200 patients who were admitted for a different reason; 7 of them used benzodiazepines in the week before admission.  Which of the following is the best measure of association to be reported for this study?

A)(10 / 180) / (7 / 200)
B)(10 *193) / (7 * 170)
C)(10 / 170) − (7 / 193)
D)(10 * 200) / (7 * 180)
E)(10 + 7) / (180 + 200)

Question 75

A 56-year-old man is hospitalized in the intensive care unit due to community-acquired pneumonia with resultant multiorgan failure.  His trachea is intubated and mechanical ventilation is initiated.  His family wants to "do everything possible" to make him better and save his life. Based on the study results, which of the following is the best statement concerning the use of glutamine and antioxidants in this patient?

A)It does not appear to be safe to use antioxidants in critically ill patients
B)Mortality benefit should be balanced against longer hospital stay and associated costs
C)Oxidative stress may not play an important role in critical illness
D)There could be a marginal mortality benefit that is not clinically significant
E)Use of glutamine may be associated with harm

Question 76

A large-scale clinical trial was conducted to assess the effect of carvedilol (a mixed alpha- and beta-blocker) on the clinical course of New York Heart Association class III-IV chronic heart failure.  The study reported that serum noradrenaline levels (a marker of the degree of neurohumoral activation) were correlated with serum sodium levels with correlation coefficient r = -0.39 (p = 0.005).  Which of the following statements best describes the observed relationship between serum noradrenaline levels and serum sodium levels?

A)Serum noradrenaline levels increase as serum sodium levels decrease
B)Serum noradrenaline levels increase as serum sodium levels increase
C)The measure of association does not reach statistical significance
D)There is a strong correlation between serum noradrenaline and serum sodium levels
E)Variations in serum noradrenaline levels change serum sodium levels

Question 77

Glycine (Gly) has been implicated in several neurological disorders, including malignant brain tumors.  However, the precise measurement of Gly has been difficult, primarily due to the spectral overlap with myo-inositol (mI).  A novel approach to measuring Gly and mI in healthy and tumorous human brains provides more reliable spectral differentiation between Gly and mI, such that alterations of Gly in brain tumors can now be evaluated more precisely.  A group of researchers plans to conduct 2 parallel studies to measure and compare Gly levels among healthy and tumorous brains.  Study A will use the current approach to measure Gly in the brain, whereas study B will use the novel approach.  All other factors being equal, which of the following statements is most likely true concerning these 2 studies?

A)Compared to study A, study B will have a higher probability of establishing a difference in Gly that does not exist between groups
B)Differences in Gly levels between groups in study A will be statistically different from the differences in Gly levels between groups in study B
C)Study B will have a higher probability of establishing a true difference in Gly between groups than study A
D)The confidence interval for the difference in Gly levels among healthy and tumorous brains will most likely include the null value in study A
E)The difference in Gly levels among healthy and tumorous brains will be statistically significant only in study B

Question 78

A phase 3, randomized controlled trial was conducted to evaluate the effect of Drug X and Drug Y on serum parathyroid hormone (PTH) concentrations in patients receiving hemodialysis with severe secondary hyperparathyroidism.  A total of 508 patients were randomly assigned to Drug X or Drug Y after each hemodialysis session for 26 weeks.  The primary efficacy endpoint was the percentage of patients achieving >30% reduction in mean PTH from baseline during weeks 20-27.  A secondary efficacy endpoint was the percentage of patients achieving mean PTH <300 pg/mL.  An excerpt of the study results is as follows: Based on these results, which of the following is a possible 95% confidence interval for the difference in the percentage of patients who achieved the primary efficacy endpoint between Drug X and Drug Y?

A)(−13.9% to −8.9%)
B)(−15.5% to −5.2%)
C)(−19.3% to −12.7%)
D)(−10.2% to 9.7%)
E)(−21.6% to 0.8%)

Question 79

A study examines the relationship between urine sodium excretion and systolic blood pressure in a large cohort of patients from several countries.  The following results are reported for change in systolic blood pressure for every 1-g increase in urine sodium excretion: Which of the following best describes the study results?

A)High sodium excretion causes susceptibility to hypertension
B)In non-hypertensive individuals, there is no association between  systolic blood pressure and increase in sodium excretion
C)The slope of association is steeper for patients with hypertension than those without hypertension
D)Younger individuals (age <45) are more susceptible to the effect of sodium on blood pressure
E)Younger individuals (age <45) have higher sodium excretion

Question 80

A study examines participation in cardiac rehabilitation in patients following their first-ever episode of myocardial infarction in Oakland County, Michigan, from 1991-2010.  The following graphs are reported: Which of the following is the best statement based on the information presented?

A)Cardiac rehabilitation participation declined sharply for all age categories
B)Cardiac rehabilitation participation of women increased over time
C)Elderly patients benefited most from cardiac rehabilitation participation
D)There were gender differences in the trend of cardiac rehabilitation participation
E)Young male patients showed higher motivation than young female patients