An 89-year-old man is brought to a geriatric clinic by family members who are concerned that he is developing dementia due to recent worsening of his memory. The attending physician uses a new cognitive test (test X) to help rule out the possibility of dementia. The patient’s test result is negative. A study evaluating the efficacy of test X in a sample of 200 individuals age >85, in which the prevalence of dementia is 50%, has determined that the test has a specificity of 80% and a sensitivity of 90%. Assuming that this patient’s pretest probability of having dementia is equivalent to the disease prevalence in the study population, what is the probability that this patient truly does not have dementia?

A hospital wants to estimate the prevalence of diabetic nephropathy in the surrounding population of adults with type 2 diabetes. Kidney biopsy samples are obtained from 500 adult patients with diabetes who receive care at the hospital. The samples are then interpreted by 10 different pathologists, 5 of whom work at the hospital and 5 of whom work at nearby institutions. A preliminary analysis shows that the pathologists who work for the hospital are 3 times more likely to interpret the biopsy samples as diabetic nephropathy compared to those who do not work for the hospital. Which of the following most likely explains this difference in interpretation?

A researcher is interested in assessing the blood folate level of women who live in a population with a high incidence of neural tube defects. She takes a large random sample (n) of women age 18-45 and measures their blood folate levels. The researcher finds that the data are normally distributed, and she reports the mean and standard deviation (SD) of the sample. To account for sampling variation, she decides to calculate a 95% confidence interval to estimate the mean of the entire population. The researcher concludes that 2.4 to 4.6 ng/mL might be a likely range for the true, unknown population mean. Which of the following calculations was most likely used to compute this interval estimate of the population mean?

A research laboratory is evaluating a new dipstick test for diagnosing urinary tract infections (UTIs). The new test is compared to urinalysis of a midstream urine specimen (considered the diagnostic gold standard) to establish diagnostic test parameters. The study enrolls 300 patients, of which 100 have a UTI as determined by urinalysis. The new dipstick test is determined to be 70% sensitive and 90% specific for the diagnosis of UTIs. How many false positives are present in the study?

A 62-year-old man with diabetes, hypertension, and hyperlipidemia comes to the emergency department of an academic medical center with chest pain, nausea, vomiting, and diaphoresis. An electrocardiogram demonstrates ST elevation in the anterior leads, and cardiac enzymes are markedly elevated. Investigators at the center are designing a randomized control trial to test the hypothesis that drug B will decrease the mortality associated with acute ST-elevation myocardial infarction compared to standard of care. To ensure that investigators will not miss a difference between drug B and standard of care (if a difference truly exists), which of the following would they want to maximize?

A geneticist is interested in the potential causes of a congenital abnormality. She hypothesizes that acetaminophen use during the first trimester of pregnancy might be associated with the abnormality. In her study, a sample of mothers of children with and without the abnormality are randomly selected from government birth records. Personal interviews are then conducted with the mothers to determine fetal exposure to acetaminophen. Results show that mothers of children who do not have the abnormality did not take acetaminophen as frequently during the first trimester. This type of study is most susceptible to which of the following types of bias?

A large prospective study evaluates the relationship between alcohol consumption and breast cancer. A total of 4000 middle-aged women are enrolled in the study through a random selection of residential addresses. Daily alcohol consumption and breast cancer incidence are assessed through the use of periodic questionnaires. On five-year follow-up, the investigators report the association between alcohol consumption and breast cancer as a relative risk of 1.32 (95% confidence interval = 0.90-1.85); 800 subjects were lost to follow-up by the end of the study, the majority of whom were moderate to heavy alcohol consumers. According to this information, which of the following biases is most likely to be present and may have affected the results?

A new test to diagnose urinary tract infections in women is being evaluated.  The comparison gold standard is positive urine dipstick plus urine culture.  Results of the study are given below.

What is the new test’s specificity?

A prospective cohort study was conducted to assess the role of daily alcohol consumption in the occurrence of breast carcinoma. The investigators reported a 5-year relative risk of 1.4 for people who consume alcohol daily compared to those who do not. The 95% confidence interval was 1.02-1.85. Which of the following p-values is most consistent with the results described above?

A large cohort study is conducted to assess the association between smoking and squamous cell carcinoma of the esophagus among middle-aged Chinese men. During 10 years of follow-up, smokers have 5 times the risk of esophageal carcinoma compared to non-smokers (relative risk = 5.0, 95% confidence interval = 2.9-7.1). According to the study results, what percentage of squamous cell carcinoma of the esophagus in smokers can be attributed to smoking?

A 65-year-old man with a history of congestive heart failure is hospitalized with chest pain and hypotension requiring admission to the cardiac care unit. An intra-arterial line is placed for direct blood pressure monitoring. Consecutive readings of his intra-arterial blood pressure are 75, 110, 80, 90, 75, and 110 mm Hg. Which of the following represents the median of these blood pressure readings?

A study compared drug A versus standard therapy in preventing recurrent pulmonary embolism (PE). The absolute risk reduction for drug A versus standard therapy was 4%. The incidence of recurrent PE in the standard therapy group was 6%. There were 24 patients who developed recurrent PE in the drug A group. How many total subjects were there in the drug A group?

Researchers conduct a prospective study that demonstrates an association between alcohol consumption and transitional bladder carcinoma, with a relative risk (RR) of 1.81 and a p-value of 0.03.  They then divide the study subjects into 2 groups, smokers and non-smokers, and again examine the association between alcohol consumption and bladder cancer:

The discrepancy between the overall results and the stratified results is best explained by which of the following?

An epidemiological study is initiated to assess the impact of type II diabetes mellitus in a large population with little migration.  Disease incidence and prevalence are monitored and recorded as the number of cases per 1,000 individuals over a 30-year period.

Which of the following is the most likely explanation for the change in disease prevalence seen in the graph?

A residency program organized a barbecue at the beginning of the academic year to welcome the new class of first-year residents.  The total number of attendees was 100, including faculty, administrative staff, and residents.  Hamburgers, hotdogs, and potato salad were served.  The following day, 28 of the attendees had diarrhea and vomiting.  All of the attendees were questioned about what they had eaten, and the following table was obtained:

Which of the following best describes the attack rate among all of the attendees who had potato salad?

A 34-year-old man is admitted to the hospital with acute chest pain. An ECG is obtained in the emergency department and shows ST segment elevation in leads II, III, and aVF. A sample of blood is taken from the patient, and a new test is used to measure plasma homocysteine levels. The test is repeated 3 times with his blood sample, and the results are 11.8 µmol/L, 9.2 µmol/L, and 13.7 µmol/L (laboratory reference range: 4-14). Which of the following parameters is most likely to be low based on the results of the new test?

A suburban hospital is undergoing an annual review by a health care accreditation organization.  As part of the process, iatrogenic infection rates are assessed for all major hospital services.  Inpatient surgical infection statistics for the last year are shown below.

What is the case-fatality rate for methicillin-resistant S aureus surgical infections in this hospital?

A study is designed to evaluate the efficacy of a new drug, KM28. The study will compare KM28 plus standard care versus standard care alone with regard to decreasing the incidence of recurrent breast cancer. The Food and Drug Administration (FDA) will approve the new drug if KM28 plus standard care decreases the rate of breast cancer recurrence by at least 40% compared to standard therapy alone. The recurrence rate on standard therapy is found to be 8%. In order for the FDA to approve KM28, what is the maximal incidence of recurrent disease acceptable for women treated with KM28 plus standard therapy?

A study evaluated the role of angiotensin-converting enzyme (ACE) inhibitors in the prevention of coronary events in patients with diabetes. During 5 years of follow-up, 120 out of 400 diabetic patients who had taken an ACE inhibitor developed an acute coronary event. Over the same time, 100 out of 300 diabetic patients who had not taken an ACE inhibitor experienced coronary events. What was the relative risk of developing a coronary event in diabetic patients who were taking ACE inhibitors compared to diabetic patients who were not taking ACE inhibitors?

A 54-year-old man with hypertension and hyperlipidemia who came to the emergency department with chest pain wants to know if he is having a heart attack.  Test A is newly available for diagnosing myocardial infarction (MI).  In a recent study, the results of test A (compared to a gold standard diagnosis of MI) were as follows:

The patient has a positive result on test A.  Assuming his pre-test probability is equivalent to the prevalence of MI in the study, what is the probability that the patient has an MI?

A 28-year-old woman comes to the office to establish care. She recently moved to New York to begin a job as a copy editor at a major newspaper. She has no known medical problems. The patient is in a monogamous relationship with her husband. She usually eats fast food for lunch, and she and her husband cook in the evenings. She goes to the gym about once every 2 weeks. The patient’s temperature is 36.7 C (98 F), blood pressure is 118/64 mm Hg, pulse is 60/min, and respirations are 14/min. Her BMI is 24.6 kg/m2. Physical examination is unremarkable. Laboratory results are within the normal range. Counseling this patient regarding diet and exercise habits would be an example of which of the following?

A new serologic test has been developed for the detection of active pulmonary tuberculosis and is compared to the gold standard of sputum mycobacterial culture.  A total of 1000 subjects are randomly selected for testing from a population with a high prevalence of tuberculosis.  Results of the study are given below:

Which of the following is the positive predictive value of the test under study?

A 73-year-old man comes to the office for follow-up. He was diagnosed with chronic lymphocytic leukemia (CLL) 3 years ago when routine laboratory testing revealed a markedly elevated leukocyte count. He feels well. On examination, he has stable lymphadenopathy. He has been reading about management options should his CLL progress and inquires about an experimental drug that selectively binds malignant lymphocytes. The drug has been shown to significantly prolong survival in patients with stage 3 and 4 CLL, without curing the malignancy. If this new drug were widely used, what changes would be expected in the number of incident and prevalent cases of CLL?

Researchers are interested in the association between colorectal carcinoma and nonsteroidal anti-inflammatory drug use. They first interview a group of patients with biopsy-proven colorectal carcinoma and then interview a group consisting of the patients’ neighbors who are of similar age and race. The analysis is based on comparing the results of pairs of individuals (one from each of the 2 groups) who have similar characteristics. This design technique best helps address which of the following potential problems with this study?

A new tumor marker is being investigated for its usefulness in diagnosing ovarian cancer.  A sample of 400 women is stratified into 2 groups based on the presence or absence of BRCA mutations.  Serum levels of the new marker are obtained in the 2 groups; in addition, both groups of women undergo conventional screening to determine their disease status.  The curves on the top represent the distribution of the new serum marker in women with BRCA mutations, and the curves on the bottom represent the distribution of the new serum marker in women without the BRCA mutations.

The proposed serum marker cutoff value for both populations is shown.  Use of the new serum marker in women with BRCA mutations, compared with those without BRCA mutations, is associated with which of the following?

A physician research group is evaluating the efficacy of a new lipid-lowering drug, Superstatin, which is being marketed directly to consumers as a groundbreaking new therapy to prevent heart attacks.  The drug manufacturer claims that the drug is more effective than existing hypolipidemic agents for primary prevention of myocardial infarction.  Results of a 5-year, randomized, double-blinded, controlled study to evaluate the efficacy of Superstatin are shown below.

Compared to the control medication, how many patients need to be treated with Superstatin to prevent one additional myocardial infarction?

The graph below shows the yearly incidence of viral hepatitis per 100,000 population from 1982-2012 in the United States (US).

During this period, the total population in the US continued to increase, as shown in the table below:

At any given time point, the number of individuals at risk for hepatitis infection is assumed to be equal to the total US population.  Based on these data, which of the following is most likely to be true?

A study determines that the mean blood cholesterol level is 195 mg/dL in 200 non-diabetic hospitalized patients and 210 mg/dL in 180 diabetic hospitalized patients. The probability that the observed difference is due to chance alone is reported to be 5%. There is also a 20% probability of concluding that there is no difference in blood cholesterol level when there is one in reality. What is the power of the study?

A novel serum biomarker, UWRLD99, is being evaluated for early detection of pancreatic cancer.  The concentration of UWRLD99 (measured in international units [IU] per dL) has been found to be elevated in patients with pancreatic adenocarcinoma.  Test results in 200 volunteers (“healthy”) and 190 patients with biopsy-proven pancreatic cancer (“diseased”) are given in the figure below.  The investigators determined the sensitivity and specificity of UWRLD99 for pancreatic cancer using a cutoff of 200 IU/dL (indicated by the solid vertical line).

If they had instead used a lower cutoff as indicated by the dashed vertical line, which of the following would most likely be seen?

A 45-year-old man comes to the office for a routine visit.  The patient has a first-degree relative with Alzheimer dementia and is concerned about his chances of developing the disease.  He has read in the newspaper that decreased consumption of yellow and orange fruits and vegetables has been associated with Alzheimer disease and would like to know how likely he is to develop the disease.  A medical literature review uncovers a recent cohort study that evaluated the association between blood carotene concentration and Alzheimer disease.  The development of the disease was evaluated in a 20-year follow-up study of 200 middle-aged subjects who have a first-degree relative with Alzheimer disease.  The results are as follows:

Assuming the patient has low carotene levels, what is his 20-year risk of developing Alzheimer disease?

A meta-analysis of several trials on the effect of cocoa intake on systolic blood pressure (SBP) revealed the following results:

All the trials evaluated the difference in SBP at 2 weeks.  Based on the data, which of the following is the most appropriate conclusion?

Pulmonary capillary wedge pressure (PCWP) measurements can be used to estimate left atrial pressure; the normal range is between 6-12 mm Hg, and recorded values are whole numbers. A patient in the intensive care unit has 20 serial PCWP measurements taken over the course of 2 hours. Among these 20 observations, the maximal recorded value is 12 mm Hg and the minimal recorded value is 10 mm Hg. If the next measurement is 26 mm Hg, which of the following is most likely to remain unchanged?

Zeracizumab is an experimental angiogenesis inhibitor targeting vascular endothelial growth factor that is being tested for the treatment of advanced, chemotherapy-naive, non-squamous non-small cell lung cancer (NSCLC).  Part of the drug company’s evaluation process is to analyze the 1-year survival after treatment to determine the clinical efficacy of the experimental treatment.  The results are given in the table below.

Which of the following best represents the number needed to harm for the zeracizumab-containing regimen?

A research laboratory develops a new serologic test for detecting prostate cancer. The new assay is compared to transrectal ultrasound-guided prostate biopsy to determine sensitivity and specificity parameters. It is found that the test result is negative in 95% of patients who do not have the disease. If the new assay is used on 8 blood samples taken from patients without prostate cancer, what is the probability of all 8 test results coming back negative?

A new portable cholesterol-measuring device is being developed for use in medically underserved communities. During clinical trials of an early prototype, a patient’s cholesterol level is found to be 200 mg/dL, 201 mg/dL, and 200 mg/dL on 3 separate measurements of the same blood sample. Using the gold standard measurement method, the same sample is found to have a cholesterol level of 260 mg/dL. Which of the following descriptions best characterizes the new cholesterol-measuring device?

A prospective study evaluates the relationship between regular antioxidant supplement use (vitamins C and E) and the risk of stroke in healthy and physically active men age 40-60. The study compares the risk of stroke among men who consumed antioxidant supplements for ≥5 years and among men who consumed antioxidant supplements for <5 years, as compared to a reference group of men who never consumed antioxidant supplements. According to the study results, men who consumed antioxidant supplements for <5 years and men who consumed antioxidant supplements for ≥5 years have stroke relative risks of 0.95 (p = 0.45) and 0.75 (p < 0.01), respectively, when compared to the reference group. The results of the study were adjusted to account for baseline differences related to healthy behaviors and overall health. Which of the following factors most likely explains why the relative risk of stroke is lower with longer antioxidant use?

A medical student is conducting a chart review of patients admitted to the local emergency department with acute pancreatitis. He is interested in comparing blood glucose levels between mild and severe cases. Before attempting to compare the mean blood glucose levels between the 2 groups of patients, he decides to conduct a descriptive analysis of the variables in each group. Blood glucose levels in patients with severe acute pancreatitis were found to have a strong positively skewed distribution. Which of the following is most likely to be true regarding the data for the severe acute pancreatitis group?

Researchers are studying the relationship between essential hypertension and a common mutation in the structure of a sodium channel protein. A study population is randomly selected and blood samples are obtained for leukocyte genotyping. The prevalence of hypertension is determined based on mean blood pressure measurements obtained using standardized ambulatory blood pressure monitoring conducted over 1 week. Based on the analysis results, the researchers conclude that the sodium channel structure mutation is associated with hypertension. Which of the following best describes the study design used by the investigators?

A new biomarker has been shown to allow for the early detection of non-small cell lung carcinoma. A preliminary analysis on a cohort study of this new test demonstrates that its use prolongs survival of lung cancer patients by 3 months when compared to the survival of patients diagnosed by conventional methods. A secondary analysis reveals no difference in 6-month mortality rates between the 2 groups. Which of the following factors most likely explains the study results?