Case-cohort studies US Medical PG Practice Questions and MCQs
Practice US Medical PG questions for Case-cohort studies. These multiple choice questions (MCQs) cover important concepts and help you prepare for your exams.
Case-cohort studies US Medical PG Question 1: A study is funded by the tobacco industry to examine the association between smoking and lung cancer. They design a study with a prospective cohort of 1,000 smokers between the ages of 20-30. The length of the study is five years. After the study period ends, they conclude that there is no relationship between smoking and lung cancer. Which of the following study features is the most likely reason for the failure of the study to note an association between tobacco use and cancer?
- A. Late-look bias
- B. Latency period (Correct Answer)
- C. Confounding
- D. Effect modification
- E. Pygmalion effect
Case-cohort studies Explanation: ***Latency period***
- **Lung cancer** typically has a **long latency period**, often **20-30+ years**, between initial exposure to tobacco carcinogens and the development of clinically detectable disease.
- A **five-year study duration** in young smokers (ages 20-30) is **far too short** to observe the development of lung cancer, which explains the false negative finding.
- This represents a **fundamental flaw in study design** rather than a bias—the biological timeline of disease development was not adequately considered.
*Late-look bias*
- **Late-look bias** occurs when a study enrolls participants who have already survived the early high-risk period of a disease, leading to **underestimation of true mortality or incidence**.
- Also called **survival bias**, it involves studying a population that has already been "selected" by survival.
- This is not applicable here, as the study simply ended before sufficient time elapsed for disease to develop.
*Confounding*
- **Confounding** occurs when a third variable is associated with both the exposure and outcome, distorting the apparent relationship between them.
- While confounding can affect study results, it would not completely eliminate the detection of a strong, well-established association like smoking and lung cancer in a properly conducted prospective cohort study.
- The issue here is temporal (insufficient follow-up time), not the presence of an unmeasured confounder.
*Effect modification*
- **Effect modification** (also called interaction) occurs when the magnitude of an association between exposure and outcome differs across levels of a third variable.
- This represents a **true biological phenomenon**, not a study design flaw or bias.
- It would not explain the complete failure to detect any association.
*Pygmalion effect*
- The **Pygmalion effect** (observer-expectancy effect) refers to a psychological phenomenon where higher expectations lead to improved performance in the observed subjects.
- This concept is relevant to **behavioral and educational research**, not to objective epidemiological studies of disease incidence.
- It has no relevance to the biological relationship between carcinogen exposure and cancer development.
Case-cohort studies US Medical PG Question 2: A research team develops a new monoclonal antibody checkpoint inhibitor for advanced melanoma that has shown promise in animal studies as well as high efficacy and low toxicity in early phase human clinical trials. The research team would now like to compare this drug to existing standard of care immunotherapy for advanced melanoma. The research team decides to conduct a non-randomized study where the novel drug will be offered to patients who are deemed to be at risk for toxicity with the current standard of care immunotherapy, while patients without such risk factors will receive the standard treatment. Which of the following best describes the level of evidence that this study can offer?
- A. Level 1
- B. Level 3 (Correct Answer)
- C. Level 5
- D. Level 4
- E. Level 2
Case-cohort studies Explanation: ***Level 3***
- A **non-randomized controlled trial** like the one described, where patient assignment to treatment groups is based on specific characteristics (risk of toxicity), falls into Level 3 evidence.
- This level typically includes **non-randomized controlled trials** and **well-designed cohort studies** with comparison groups, which are prone to selection bias and confounding.
- The study compares two treatments but lacks randomization, making it Level 3 evidence.
*Level 1*
- Level 1 evidence is the **highest level of evidence**, derived from **systematic reviews and meta-analyses** of multiple well-designed randomized controlled trials or large, high-quality randomized controlled trials.
- The described study is explicitly stated as non-randomized, ruling out Level 1.
*Level 2*
- Level 2 evidence involves at least one **well-designed randomized controlled trial** (RCT) or **systematic reviews** of randomized trials.
- The current study is *non-randomized*, which means it cannot be classified as Level 2 evidence, as randomization is a key criterion for this level.
*Level 4*
- Level 4 evidence includes **case series**, **case-control studies**, and **poorly designed cohort or case-control studies**.
- While the study is non-randomized, it is a controlled comparative trial rather than a case series or retrospective case-control study, placing it at Level 3.
*Level 5*
- Level 5 evidence is the **lowest level of evidence**, typically consisting of **expert opinion** without explicit critical appraisal, or based on physiology, bench research, or animal studies.
- While the drug was initially tested in animal studies, the current human comparative study offers a higher level of evidence than expert opinion or preclinical data.
Case-cohort studies US Medical PG Question 3: A 25-year-old man with a genetic disorder presents for genetic counseling because he is concerned about the risk that any children he has will have the same disease as himself. Specifically, since childhood he has had difficulty breathing requiring bronchodilators, inhaled corticosteroids, and chest physiotherapy. He has also had diarrhea and malabsorption requiring enzyme replacement therapy. If his wife comes from a population where 1 in 10,000 people are affected by this same disorder, which of the following best represents the likelihood a child would be affected as well?
- A. 0.01%
- B. 2%
- C. 0.5%
- D. 1% (Correct Answer)
- E. 50%
Case-cohort studies Explanation: ***Correct Option: 1%***
- The patient's symptoms (difficulty breathing requiring bronchodilators, inhaled corticosteroids, and chest physiotherapy; diarrhea and malabsorption requiring enzyme replacement therapy) are classic for **cystic fibrosis (CF)**, an **autosomal recessive disorder**.
- For an autosomal recessive disorder with a prevalence of 1 in 10,000 in the general population, **q² = 1/10,000**, so **q = 1/100 = 0.01**. The carrier frequency **(2pq)** is approximately **2q = 2 × (1/100) = 1/50 = 0.02**.
- The affected man is **homozygous recessive (aa)** and will always pass on the recessive allele. His wife has a **1/50 chance of being a carrier (Aa)**. If she is a carrier, she has a **1/2 chance of passing on the recessive allele**.
- Therefore, the probability of an affected child = **(Probability wife is a carrier) × (Probability wife passes recessive allele) = 1/50 × 1/2 = 1/100 = 1%**.
*Incorrect Option: 0.01%*
- This percentage is too low and does not correctly account for the carrier frequency in the population and the probability of transmission from a carrier mother.
*Incorrect Option: 2%*
- This represents approximately the carrier frequency (1/50 ≈ 2%), but does not account for the additional 1/2 probability that a carrier mother would pass on the recessive allele.
*Incorrect Option: 0.5%*
- This value would be correct if the carrier frequency were 1/100 instead of 1/50, which does not match the given population prevalence.
*Incorrect Option: 50%*
- **50%** would be the risk if both parents were carriers of an autosomal recessive disorder (1/4 chance = 25% for affected, but if we know one parent passes the allele, conditional probability changes). More accurately, 50% would apply if the disorder were **autosomal dominant** with one affected parent, which is not the case here.
Case-cohort studies US Medical PG Question 4: A 21-year-old woman is diagnosed with a rare subtype of anti-NMDA encephalitis. During the diagnostic workup, she was found to have an ovarian teratoma. Her physician is curious about the association between anti-NMDA encephalitis and ovarian teratomas. A causal relationship between this subtype of anti-NMDA encephalitis and ovarian teratomas is suspected. The physician aims to identify patients with anti-NMDA encephalitis and subsequently evaluate them for the presence of ovarian teratomas. Which type of study design would be the most appropriate?
- A. Case-control study
- B. Retrospective cohort study (Correct Answer)
- C. Cross-sectional study
- D. Case series
- E. Randomized controlled trial
Case-cohort studies Explanation: ***Retrospective cohort study***
- This is the **most appropriate design** because the physician starts with a defined group of patients **with anti-NMDA encephalitis** (the exposure/condition) and then evaluates them for the **presence of ovarian teratomas** (the outcome).
- A **cohort study** follows this directional approach: identify individuals with a specific exposure or condition, then assess the frequency or presence of an outcome within that group.
- **Retrospective** cohort studies use **existing medical records** to identify the exposed cohort and determine outcome status, making this practical for studying a rare condition like anti-NMDA encephalitis.
- This design allows calculation of the **prevalence** of ovarian teratomas among anti-NMDA encephalitis patients and can suggest an association between the two conditions.
*Cross-sectional study*
- Cross-sectional studies assess **both exposure and outcome simultaneously** at a single point in time in a population, rather than starting with one condition and looking for another.
- This design would be appropriate if the physician surveyed a population and assessed both anti-NMDA encephalitis and ovarian teratomas at the same time, but the question describes a **directional evaluation** (first identify encephalitis patients, then evaluate for teratomas).
- While cross-sectional studies can identify associations, they do not follow the sequential approach described in the clinical scenario.
*Case series*
- A **case series** is a descriptive study that reports characteristics or outcomes in a group of patients with a particular condition but lacks a comparison group and does not systematically evaluate associations.
- While it could describe ovarian teratoma findings in anti-NMDA encephalitis patients, it does not provide the structured framework for assessing prevalence or association that a cohort study offers.
*Case-control study*
- **Case-control studies** work in the **opposite direction**: they start with the outcome (e.g., ovarian teratoma cases) and look backward for the exposure (e.g., anti-NMDA encephalitis).
- The physician's approach starts with the **exposure first** (anti-NMDA encephalitis), making a case-control design inappropriate.
- Case-control studies are efficient for studying rare outcomes but are not aligned with the described study plan.
*Randomized controlled trial*
- **RCTs** are experimental studies that randomly assign participants to different interventions to evaluate treatment efficacy or causation.
- This is an **observational research question** about naturally occurring associations, not an intervention study, making RCTs inappropriate and unethical for this scenario.
Case-cohort studies US Medical PG Question 5: Study X examined the relationship between coffee consumption and lung cancer. The authors of Study X retrospectively reviewed patients' reported coffee consumption and found that drinking greater than 6 cups of coffee per day was associated with an increased risk of developing lung cancer. However, Study X was criticized by the authors of Study Y. Study Y showed that increased coffee consumption was associated with smoking. What type of bias affected Study X, and what study design is geared to reduce the chance of that bias?
- A. Observer bias; double blind analysis
- B. Selection bias; randomization
- C. Lead time bias; placebo
- D. Measurement bias; blinding
- E. Confounding; randomization (Correct Answer)
Case-cohort studies Explanation: ***Confounding; randomization***
- Study Y suggests that **smoking** is a **confounding variable** because it is associated with both increased coffee consumption (exposure) and increased risk of lung cancer (outcome), distorting the apparent relationship between coffee and lung cancer.
- **Randomization** in experimental studies (such as randomized controlled trials) helps reduce confounding by ensuring that known and unknown confounding factors are evenly distributed among study groups.
- In observational studies where randomization is not possible, confounding can be addressed through **stratification**, **matching**, or **multivariable adjustment** during analysis.
*Observer bias; double blind analysis*
- **Observer bias** occurs when researchers' beliefs or expectations influence the study outcome, which is not the primary issue described here regarding the relationship between coffee, smoking, and lung cancer.
- **Double-blind analysis** is a method to mitigate observer bias by ensuring neither participants nor researchers know who is in the control or experimental groups.
*Selection bias; randomization*
- **Selection bias** happens when the study population is not representative of the target population, leading to inaccurate results, which is not directly indicated by the interaction between coffee and smoking.
- While **randomization** is used to reduce selection bias by creating comparable groups, the core problem identified in Study X is confounding, not flawed participant selection.
*Lead time bias; placebo*
- **Lead time bias** occurs in screening programs when early detection without improved outcomes makes survival appear longer, an issue unrelated to the described association between coffee, smoking, and lung cancer.
- A **placebo** is an inactive treatment used in clinical trials to control for psychological effects, and its relevance here is limited to treatment intervention studies.
*Measurement bias; blinding*
- **Measurement bias** arises from systematic errors in data collection, such as inaccurate patient reporting of coffee consumption, but the main criticism from Study Y points to a third variable (smoking) affecting the association, not just flawed measurement.
- **Blinding** helps reduce measurement bias by preventing participants or researchers from knowing group assignments, thus minimizing conscious or unconscious influences on data collection.
Case-cohort studies US Medical PG Question 6: A physician attempts to study cirrhosis in his state. Using a registry of admitted patients over the last 10 years at the local hospital, he isolates all patients who have been diagnosed with cirrhosis. Subsequently, he contacts this group of patients, asking them to complete a survey assessing their prior exposure to alcohol use, intravenous drug abuse, blood transfusions, personal history of cancer, and other medical comorbidities. An identical survey is given to an equal number of patients in the registry who do not carry a prior diagnosis of cirrhosis. Which of the following is the study design utilized by this physician?
- A. Randomized controlled trial
- B. Case-control study (Correct Answer)
- C. Cross-sectional study
- D. Cohort study
- E. Meta-analysis
Case-cohort studies Explanation: ***Case-control study***
- This study design **identifies subjects based on their outcome (cases with cirrhosis, controls without cirrhosis)** and then retrospectively investigates their past exposures.
- The physician selected patients with cirrhosis (cases) and patients without cirrhosis (controls), then assessed their prior exposures to risk factors like alcohol use and intravenous drug abuse.
*Randomized controlled trial*
- This design involves randomly assigning participants to an **intervention group** or a **control group** to assess the effect of an intervention.
- There is no intervention being tested or randomization occurring in this study; it is observational.
*Cross-sectional study*
- A cross-sectional study measures the **prevalence of disease and exposure at a single point in time** in a defined population.
- This study collects retrospective exposure data and compares two distinct groups (cases and controls), rather than assessing prevalence at one time point.
*Cohort study*
- A cohort study **follows a group of individuals over time** to see if their exposure to a risk factor is associated with the development of a disease.
- This study starts with the outcome (cirrhosis) and looks backward at exposures, which is the opposite direction of a cohort study.
*Meta-analysis*
- A meta-analysis is a statistical method that **combines the results of multiple independent studies** to produce a single, more powerful estimate of treatment effect or association.
- This is an original research study collecting new data, not a systematic review or synthesis of existing studies.
Case-cohort studies US Medical PG Question 7: A 28-year-old male presents to his primary care physician with complaints of intermittent abdominal pain and alternating bouts of constipation and diarrhea. His medical chart is not significant for any past medical problems or prior surgeries. He is not prescribed any current medications. Which of the following questions would be the most useful next question in eliciting further history from this patient?
- A. "Does the diarrhea typically precede the constipation, or vice-versa?"
- B. "Is the diarrhea foul-smelling?"
- C. "Please rate your abdominal pain on a scale of 1-10, with 10 being the worst pain of your life"
- D. "Are the symptoms worse in the morning or at night?"
- E. "Can you tell me more about the symptoms you have been experiencing?" (Correct Answer)
Case-cohort studies Explanation: ***Can you tell me more about the symptoms you have been experiencing?***
- This **open-ended question** encourages the patient to provide a **comprehensive narrative** of their symptoms, including details about onset, frequency, duration, alleviating/aggravating factors, and associated symptoms, which is crucial for diagnosis.
- In a patient presenting with vague, intermittent symptoms like alternating constipation and diarrhea, allowing them to elaborate freely can reveal important clues that might not be captured by more targeted questions.
*Does the diarrhea typically precede the constipation, or vice-versa?*
- While knowing the sequence of symptoms can be helpful in understanding the **pattern of bowel dysfunction**, it is a very specific question that might overlook other important aspects of the patient's experience.
- It prematurely narrows the focus without first obtaining a broad understanding of the patient's overall symptomatic picture.
*Is the diarrhea foul-smelling?*
- Foul-smelling diarrhea can indicate **malabsorption** or **bacterial overgrowth**, which are important to consider in some gastrointestinal conditions.
- However, this is a **specific symptom inquiry** that should follow a more general exploration of the patient's symptoms, as it may not be relevant if other crucial details are missed.
*Please rate your abdominal pain on a scale of 1-10, with 10 being the worst pain of your life*
- Quantifying pain intensity is useful for assessing the **severity of discomfort** and monitoring changes over time.
- However, for a patient with intermittent rather than acute, severe pain, understanding the **character, location, and triggers** of the pain is often more diagnostically valuable than just a numerical rating initially.
*Are the symptoms worse in the morning or at night?*
- Diurnal variation can be relevant in certain conditions, such as inflammatory bowel diseases where nocturnal symptoms might be more concerning, or functional disorders whose symptoms might be stress-related.
- This is another **specific question** that should come after gathering a more complete initial picture of the patient's symptoms to ensure no key information is overlooked.
Case-cohort studies US Medical PG Question 8: In recent years, psoriasis has been identified as a risk factor for cardiovascular disease. A researcher conducted a study in which he identified 200 patients with psoriasis and 200 patients without psoriasis. The patients were followed for 10 years. At the end of this period, participants' charts were reviewed for myocardial infarction during this time interval.
Myocardial infarction No myocardial infarction Total
Psoriasis 12 188 200
No psoriasis 4 196 200
Total 16 384 400
What is the 10-year risk of myocardial infarction in participants with psoriasis?
- A. 0.75
- B. 0.04
- C. 0.5
- D. 0.06 (Correct Answer)
- E. 0.02
Case-cohort studies Explanation: ***0.06***
- The **risk of myocardial infarction** in participants with psoriasis is calculated by dividing the number of psoriasis patients who had a myocardial infarction by the total number of psoriasis patients.
- This calculation is 12 (myocardial infarctions in psoriasis group) / 200 (total psoriasis patients) = **0.06 or 6%**.
- This represents the **cumulative incidence** or **absolute risk** in the exposed cohort over 10 years.
*0.75*
- This value represents the **proportion of all MI cases that occurred in the psoriasis group**: 12/16 = 0.75.
- This is not the same as risk, which requires the denominator to be the total at-risk population (all psoriasis patients), not just those with the outcome.
*0.04*
- This value represents the **risk of myocardial infarction in the control group** (no psoriasis): 4/200 = 0.02, not 0.04.
- However, 0.04 could represent 2 × 0.02, which has no meaningful epidemiological interpretation for this study.
*0.5*
- This value does not correspond to any standard epidemiological measure from the given data.
- It might represent a miscalculation or confusion with other statistical concepts.
*0.02*
- This value represents the **risk of myocardial infarction in the unexposed group** (no psoriasis): 4/200 = 0.02 or 2%.
- The question specifically asks for the risk in the psoriasis group, not the control group.
Case-cohort studies US Medical PG Question 9: A population is studied for risk factors associated with testicular cancer. Alcohol exposure, smoking, dietary factors, social support, and environmental exposure are all assessed. The researchers are interested in the incidence and prevalence of the disease in addition to other outcomes. Which pair of studies would best assess the 1. incidence and 2. prevalence?
- A. 1. Prospective cohort study 2. Cross sectional study (Correct Answer)
- B. 1. Prospective cohort study 2. Retrospective cohort study
- C. 1. Cross sectional study 2. Retrospective cohort study
- D. 1. Case-control study 2. Prospective cohort study
- E. 1. Clinical trial 2. Cross sectional study
Case-cohort studies Explanation: ***1. Prospective cohort study 2. Cross sectional study***
- A **prospective cohort study** is ideal for measuring **incidence** (new cases over time) because it follows a group of individuals forward in time to observe who develops the disease.
- A **cross-sectional study** is suitable for measuring **prevalence** (existing cases at a specific point in time) as it surveys a population at one moment to determine the proportion with the disease.
*1. Prospective cohort study 2. Retrospective cohort study*
- A **retrospective cohort study** assesses past exposures and outcomes and can measure incidence, but it is not the primary choice for prevalence.
- While a prospective cohort study is appropriate for incidence, a retrospective cohort study is less suited for determining current prevalence.
*1. Cross sectional study 2. Retrospective cohort study*
- A **cross-sectional study** measures prevalence, not incidence, as it captures disease status at a single point in time.
- A **retrospective cohort study** looks back in time to identify past exposures and subsequent outcomes, which is not the best method for current prevalence.
*1. Case-control study 2. Prospective cohort study*
- A **case-control study** compares exposures between individuals with a disease (cases) and those without (controls) and is best for studying rare diseases and estimating odds ratios, not incidence or prevalence directly.
- A **prospective cohort study** is suitable for incidence, but a case-control study is not for incidence or prevalence.
*1. Clinical trial 2. Cross sectional study*
- A **clinical trial** is an experimental study designed to test the efficacy of interventions and is not primarily used to measure disease incidence or prevalence in a general population.
- While a cross-sectional study is appropriate for prevalence, a clinical trial is not designed for incidence measurement.
Case-cohort studies US Medical PG Question 10: A 44-year-old woman presents to her primary care physician’s office with episodes of pain in her right hand. She says that the pain is most significant at night and awakens her from sleep numerous times. When she experiences this pain, she immediately puts her hand under warm running water or shakes her hand. She has also experienced episodes of numbness in the affected hand. Driving and extending the right arm also provoke her symptoms. She denies any trauma to the hand or associated weakness. Medical history is notable for hypothyroidism treated with levothyroxine. She works as a secretary for a law firm. On physical exam, when the patient hyperflexes her wrist, pain and paresthesia affect the first 3 digits of the right hand. Which of the following is the confirmatory diagnostic test for this patient?
- A. Magnetic resonance imaging
- B. Needle electromyography
- C. Nerve conduction studies (Correct Answer)
- D. Nerve biopsy
- E. Tinel test
Case-cohort studies Explanation: ***Nerve conduction studies***
- **Nerve conduction studies (NCS)** are the most sensitive and specific diagnostic test for **carpal tunnel syndrome**, definitively confirming median nerve compression.
- They measure the speed and amplitude of electrical signals through the **median nerve** at the wrist, identifying slowed conduction across the carpal tunnel.
*Magnetic resonance imaging*
- While MRI can visualize soft tissues and nerve pathology, it is not typically the **first-line confirmatory test** for carpal tunnel syndrome due to its lower sensitivity compared to NCS.
- MRI is more useful for identifying **structural abnormalities** like tumors or synovitis, which might cause secondary nerve compression.
*Needle electromyography*
- **Electromyography (EMG)** involves inserting a needle into muscles to assess their electrical activity; it helps evaluate for **axonopathy** and muscle denervation.
- While EMG is often performed alongside NCS, it primarily assesses muscle function and nerve damage severity, rather than directly confirming nerve compression itself, which is best done by NCS.
*Nerve biopsy*
- **Nerve biopsy** is an invasive procedure generally reserved for diagnosing demyelinating or infiltrative neuropathies when less invasive tests are inconclusive.
- It carries risks and is **unnecessary** and inappropriate for diagnosing a common compressive neuropathy like carpal tunnel syndrome.
*Tinel test*
- The **Tinel test** is a clinical provocative maneuver where percussion over the median nerve at the wrist elicits tingling or pain.
- It is a **screening tool** and part of the physical exam for carpal tunnel syndrome, but it is not a confirmatory diagnostic test due to its variable sensitivity and specificity.
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