All practice questions

A 48-year-old man is evaluated in the emergency department for sudden-onset right-sided chest pain and mild shortness of breath that began earlier this morning. His medical history is significant for hypertension and severe alcohol use disorder. He is currently unhoused and sleeps at a local congregate shelter. Vital signs are temperature $37.2^\circ\text{C}$ ($99.0^\circ\text{F}$), blood pressure $135/85\text{ mmHg}$, pulse $92\text{/min}$, and respiratory rate $18\text{/min}$. Oxygen saturation is $96\%$ on room air. On physical examination, he is alert and oriented but appears mildly disheveled. The lungs are clear to auscultation bilaterally, and there is no right ventricular heave.

Computed tomography pulmonary angiography demonstrates a segmental pulmonary embolism in the right lower lobe. Laboratory studies show a serum troponin I level of $< 0.01\text{ ng/mL}$ (normal $< 0.04\text{ ng/mL}$), an NT-proBNP level of $80\text{ pg/mL}$ (normal $< 125\text{ pg/mL}$), and a serum creatinine of $0.9\text{ mg/dL}$. His Pulmonary Embolism Severity Index (PESI) score is calculated to be $58$ (Class I, very low risk).

During the evaluation, the patient admits to drinking approximately one pint of vodka daily. He also mentions that his backpack, which contained his hypertension medications, was stolen at the shelter two days ago. He states that he feels much better after receiving a dose of intravenous acetaminophen and expresses a strong desire to leave the emergency department immediately to secure a bed at the shelter for the night.

Which of the following is the most appropriate next step in the disposition of this patient?

A randomized, double-blind, placebo-controlled clinical trial is conducted to evaluate the efficacy and safety of Agent Z, a novel biologic therapy, in adults with severe plaque psoriasis. The primary efficacy endpoint is the proportion of patients achieving a $75\%$ reduction in the Psoriasis Area and Severity Index (PASI 75) at week 16. The primary safety endpoint is the incidence of serious infections over the same period. The trial enrolls $800$ patients, randomized equally to receive either Agent Z or a placebo.

The trial results at 16 weeks are shown in the table below:

*\*Note: Absolute difference is calculated as the incidence in the Agent Z group minus the incidence in the placebo group.*

Based on these results, which of the following statements most accurately describes the clinical impact of Agent Z compared to placebo?

A 52-year-old woman comes to the clinic for a routine health maintenance examination. She has a history of mild hypertension well-controlled on lisinopril. She has no gastrointestinal symptoms, no changes in bowel habits, and no family history of cancer. The physician recommends initiating colorectal cancer screening. The patient appears visibly anxious and states, "I really do not want to have a colonoscopy or any other screening test. My neighbor had a colonoscopy last year and ended up in the hospital with a punctured bowel. Can I just skip this? I eat a very healthy diet and feel perfectly fine."

Which of the following is the most appropriate initial response by the physician?

To evaluate the efficacy of a novel immunomodulator in preventing clinical relapses among patients with relapsing-remitting multiple sclerosis, researchers conduct a phase III, placebo-controlled, double-blind trial. A total of $2,000$ enrolled patients are randomized in a 1:1 ratio to receive either the novel immunomodulator or a placebo. After two years of continuous follow-up, $140$ patients in the placebo arm and $95$ patients in the intervention arm experienced at least one clinical relapse. In their primary analysis, the investigators report the absolute risk reduction alongside a 95% confidence interval of $0.021$ to $0.069$.

Determine the number of patients that must be treated with the novel immunomodulator to prevent one additional clinical relapse, and appropriately characterize the statistical significance based on the reported absolute risk reduction confidence interval.

A $54$-year-old woman is evaluated in the hospital on day 3 of admission for severe fatigue, jaundice, and right upper quadrant discomfort. She has a history of metastatic melanoma and received her third cycle of ipilimumab and nivolumab three weeks prior to admission.

On admission, her viral hepatitis panel and autoimmune markers (antinuclear antibody, anti-smooth muscle antibody) were negative. A right upper quadrant ultrasound showed normal liver echotexture with no biliary dilation and normal flow in the portal and hepatic veins. She was diagnosed with Grade 3 immune-checkpoint inhibitor-induced hepatitis. Immunotherapy was permanently discontinued, and intravenous methylprednisolone $2\text{ mg/kg/day}$ was initiated.

Currently, 72 hours later, the patient reports no improvement in her symptoms. Her vital signs are temperature $37.1^\circ\text{C}$ ($98.8^\circ\text{F}$), pulse $88/\text{min}$, and blood pressure $118/74\text{ mmHg}$.

Serial laboratory values are shown below:

Which of the following is the most appropriate next step in the management of this patient?

A consortium of community hospitals initiates a prospective, randomized controlled study evaluating an early-ambulation protocol for postoperative orthopedic patients. The primary outcome is the mean length of hospital stay. Initial statistical modeling determined that 450 participants are needed to achieve $80\%$ power to detect a 1.5-day difference between the intervention and standard care groups, utilizing a two-tailed $\alpha$ of $0.05$.

Halfway through the enrollment period, an independent data monitoring committee conducts a blinded interim audit. They discover that the standard deviation for the length of hospital stay across all enrolled patients is nearly double the estimate originally derived from preliminary pilot data. The trial sponsors mandate that the study must conclude precisely when the original enrollment target of 450 participants is reached, and no alterations to the predetermined significance threshold are permitted.

Based on the newly discovered population parameters, which of the following is the most accurate statement regarding the trial's operating characteristics?

During an outpatient consultation, a 42-year-old woman discusses the possibility of undergoing BRCA1/2 genetic testing due to a profound family history of early-onset breast and ovarian cancer. Throughout the encounter, she voices several specific hesitations. Match each of the patient's expressed barriers to testing (left) with the most targeted and appropriate physician counseling strategy (right).

A 62-year-old woman presents to the emergency department on a Saturday evening with chills and a temperature of 38.6°C (101.5°F). She is currently undergoing chemotherapy for stage II breast cancer and received her last cycle of doxorubicin and cyclophosphamide 10 days ago. Her temperature in the emergency department is 38.7°C (101.7°F), blood pressure is 122/78 mm Hg, pulse is 92/min, and respirations are 16/min. Physical examination reveals a well-appearing woman with no localizing source of infection; her central venous port site has no erythema, tenderness, or fluctuance. Laboratory studies show a white blood cell count of 0.8 × 10^9/L with 20% neutrophils (absolute neutrophil count of 160/µL). A comprehensive metabolic panel is normal. The patient is evaluated using the Multinational Association for Supportive Care in Cancer (MASCC) risk index and scores a 24. When discussing the care plan, the patient notes she lives alone in a rural community 90 miles away. Her primary caregiver, her daughter, is currently out of the country for two weeks. The patient does not drive and relies on a community shuttle that only operates on weekdays. Which of the following is the most appropriate disposition and management plan for this patient?

Review the following clinical quality and patient safety initiatives. Pair each specific hospital scenario with the most appropriate quality improvement methodology or analytical framework utilized in that context.

A consortium of neuroscientists is planning a study to evaluate whether elevated levels of a newly identified structural neurofilament protein in the serum of healthy young adults increases the risk of developing a rare variant of early-onset frontotemporal dementia (FTD) later in life. The incidence of this specific FTD variant is approximately $1$ in $250,000$ person-years. The investigators have obtained approval to access a national military biobank that contains baseline serum samples and $40$ years of continuous, comprehensive electronic health records for over $3$ million service members. However, the novel mass spectrometry assay required to quantify the neurofilament protein is highly resource-intensive and prohibitively expensive, preventing the analysis of all available biobank samples. Which of the following study designs is most appropriate to efficiently investigate this association while minimizing selection bias?

A 68-year-old man presents to the emergency department with a 3-day history of productive cough, fever, and shortness of breath. Over the past 24 hours, he has also developed severe nausea and has vomited 6 times. He has not been able to keep any food or liquids down, including his daily medications. Medical history includes hypertension and type 2 diabetes mellitus.

On physical examination, he appears fatigued. Temperature is 38.4°C (101.1°F), blood pressure is 118/76 mm Hg, pulse is 98/min, and respiratory rate is 22/min. Pulse oximetry shows 94% on ambient air. He is alert and fully oriented. Mucous membranes are dry. Lung auscultation reveals crackles in the right lower lobe. There is no accessory muscle use.

Laboratory results:

Chest radiograph demonstrates a right lower lobe infiltrate without a pleural effusion. The patient is given an initial dose of intravenous ceftriaxone and azithromycin, as well as 1 L of normal saline. He continues to have severe nausea and dry heaves despite receiving intravenous ondansetron.

Which of the following is the most appropriate disposition for this patient?

An infectious disease epidemiology unit is investigating an outbreak of carbapenem-resistant *Enterobacteriaceae* (CRE) bacteremia. They aim to evaluate whether prior exposure to specific broad-spectrum antibiotics is a risk factor. Over a 3-year period, the researchers identify $120$ patients who developed CRE bacteremia during their hospitalization. For each of these patients, they select three control patients from the same hospital who did not develop CRE bacteremia, matching them exactly by age, admission date, and hospital ward. The investigators then retrospectively review the electronic medical records to compare the duration and types of antibiotics administered to both groups prior to the index date.

Which of the following statements correctly describe the methodological characteristics or appropriate analytical requirements for this study design? (Select all that apply)

A randomized controlled trial is evaluating a novel intensive lifestyle intervention against standard care for reducing fasting blood glucose in adults with prediabetes. The primary outcome is the mean change in fasting blood glucose after 6 months. Initial sample size calculations indicate that 300 participants are required to provide 80% statistical power to detect a 10 mg/dL difference between groups, using a two-sided $\alpha$ of 0.05 and an anticipated standard deviation (SD) of 20 mg/dL.

Prior to patient enrollment, the central laboratory transitions to a new, highly precise point-of-care assay. A pilot validation study confirms that this new assay reduces the anticipated SD of the fasting blood glucose measurements from 20 mg/dL to 10 mg/dL. The investigators decide to proceed with the originally planned sample size of 300 participants without altering the $\alpha$ level.

Assuming the true effect size remains 10 mg/dL, which of the following best describes the statistical impact of utilizing the new laboratory assay?

A 66-year-old biological male presents to a community clinic to review his preventive health needs. He recently moved to the area and wants to ensure he is up to date with his required medical care. His past medical history includes well-controlled essential hypertension, hyperlipidemia, and mild osteoarthritis. His daily medications are amlodipine, rosuvastatin, and as-needed acetaminophen. Review of his social history reveals that he smoked half a pack of cigarettes daily from age 20 to 50 but successfully quit 16 years ago. He is a retired teacher and consumes one glass of wine weekly. Medical records indicate he had a normal screening colonoscopy four years ago, a negative hepatitis C virus antibody test, and completed the two-dose recombinant zoster series. Last year, he received the 20-valent pneumococcal conjugate vaccine and his annual high-dose influenza vaccine. Today, his blood pressure is $124/76$ mmHg and his body mass index is $26$ $kg/m^2$. Physical examination is unremarkable. Which of the following is the most appropriate health maintenance intervention for this patient at this time?

A physician is reviewing a pharmaceutical advertisement for a newly approved oral anticoagulant, 'Novanoxaban,' indicated for stroke prevention in non-valvular atrial fibrillation. The promotional material highlights a recent randomized, double-blind, non-inferiority trial comparing Novanoxaban to the standard of care. The advertisement includes a forest plot showing a primary efficacy endpoint hazard ratio (HR) of $1.10$ with a $95\%$ confidence interval (CI) of $0.95$ to $1.25$. The pre-specified non-inferiority margin ($\Delta$) is set at an HR of $1.30$. The bolded text in the brochure concludes: 'Novanoxaban is highly effective, demonstrating non-inferiority to standard of care based on a robust intention-to-treat (ITT) analysis, despite a $20\%$ loss to follow-up in both arms.' Which of the following is the most significant methodological concern regarding the interpretation of this drug advertisement?

Match each clinical research scenario with the specific epidemiological concept or type of bias it best illustrates.

A 64-year-old man with chronic hepatitis C virus infection is evaluated for abdominal distension, fatigue, and a $5\text{-kg}$ ($11\text{-lb}$) weight loss over the past two months. Three weeks ago, he was admitted to the hospital for an episode of hematemesis. Esophagogastroduodenoscopy at that time revealed large esophageal varices with red wale signs; he received endoscopic band ligation and was discharged on nadolol.

Vital signs today are within normal limits. Physical examination shows scleral icterus, palmar erythema, and a palpable, hard liver edge $4 \text{ cm}$ below the right costal margin.

Laboratory studies show:
Total bilirubin: $2.4 \text{ mg/dL}$
Aspartate aminotransferase (AST): $95 \text{ U/L}$
Alanine aminotransferase (ALT): $88 \text{ U/L}$
Platelet count: $85,000/\mu\text{L}$
Alpha-fetoprotein: $2,100 \text{ ng/mL}$

A multiphase abdominal CT scan reveals a $7\text{-cm}$ hypervascular mass in the right hepatic lobe that demonstrates avid arterial phase enhancement and rapid portal venous washout. The mass invades the right main branch of the portal vein. There is no evidence of extrahepatic metastasis.

The multidisciplinary tumor board considers initiating the preferred first-line systemic combination regimen consisting of atezolizumab and bevacizumab. However, the oncologist determines that this specific regimen is currently contraindicated for this patient.

This contraindication is primarily due to the drug-induced impairment of which of the following physiological processes?

A 65-year-old woman who underwent an uncomplicated total knee arthroplasty two weeks ago collapses suddenly at a rehabilitation center and is transported to the emergency department. On arrival, she is cyanotic and lacks a palpable pulse. The cardiac monitor shows pulseless electrical activity (PEA) at a rate of 110/min. Advanced cardiovascular life support is initiated. A rapid point-of-care echocardiogram obtained during a pulse check reveals a massively enlarged right ventricle, a severely compressed left ventricle, and a plethoric inferior vena cava. Despite aggressive resuscitation with intravenous fluids, epinephrine, and CPR, the patient succumbs. Autopsy confirms a massive saddle pulmonary embolus.

Arrange the following pathophysiological and hemodynamic events in the correct chronological sequence that led to this patient's fatal obstructive shock.

A variety of clinical scenarios demonstrating different forms of cellular responses to stress or injury are presented below. Match each patient presentation to the most precise underlying cellular adaptation or mechanism of cell death.

A 48-year-old woman with a history of injection drug use is admitted to the hospital with high fevers, chills, and pleuritic chest pain. Blood cultures drawn on admission grow methicillin-resistant *Staphylococcus aureus* (MRSA). A transesophageal echocardiogram reveals a $1.6 \text{ cm}$ mobile vegetation on the tricuspid valve. Intravenous vancomycin therapy is initiated. On hospital day 5, the patient's serum creatinine increases from a baseline of $0.7 \text{ mg/dL}$ to $2.2 \text{ mg/dL}$. Due to concern for vancomycin-induced nephrotoxicity, her antimicrobial regimen is switched to intravenous daptomycin. The patient initially defervesces and improves, but $12$ days later, she develops recurrent fevers and bacteremia. Susceptibility testing of the new isolate demonstrates a daptomycin minimum inhibitory concentration (MIC) of $4.0 \text{ } \mu\text{g/mL}$, indicating resistance. Which of the following best describes the molecular mechanism responsible for this pathogen's newly acquired resistance to the current antimicrobial therapy?