Differential diagnosis

Differential diagnosis US Medical PG Question 1: A scientist in Chicago is studying a new blood test to detect Ab to EBV with increased sensitivity and specificity. So far, her best attempt at creating such an exam reached 82% sensitivity and 88% specificity. She is hoping to increase these numbers by at least 2 percent for each value. After several years of work, she believes that she has actually managed to reach a sensitivity and specificity much greater than what she had originally hoped for. She travels to China to begin testing her newest blood test. She finds 2,000 patients who are willing to participate in her study. Of the 2,000 patients, 1,200 of them are known to be infected with EBV. The scientist tests these 1,200 patients' blood and finds that only 120 of them tested negative with her new exam. Of the patients who are known to be EBV-free, only 20 of them tested positive. Given these results, which of the following correlates with the exam's specificity?

• A. 82%
• B. 90%
• C. 84%
• D. 86%
• E. 98% (Correct Answer)

Differential diagnosis Explanation: ***98%*** - **Specificity** measures the proportion of **true negatives** among all actual negatives. - In this case, 800 patients are known to be EBV-free (actual negatives), and 20 of them tested positive (false positives). This means 800 - 20 = 780 tested negative (true negatives). Specificity = (780 / 800) * 100% = **98%**. *82%* - This value represents the *original sensitivity* before the scientist’s new attempts to improve the test. - It does not reflect the *newly calculated specificity* based on the provided data. *90%* - This value represents the *newly calculated sensitivity* of the test, not the specificity. - Out of 1200 EBV-infected patients, 120 tested negative (false negatives), meaning 1080 tested positive (true positives). Sensitivity = (1080 / 1200) * 100% = 90%. *84%* - This percentage is not directly derived from the information given for either sensitivity or specificity after the new test results. - It does not correspond to any of the calculated values for the new test's performance. *86%* - This percentage is not directly derived from the information given for either sensitivity or specificity after the new test results. - It does not correspond to any of the calculated values for the new test's performance.

Differential diagnosis US Medical PG Question 2: A group of neurologists develop a new blood test for Alzheimer's. They are optimistic about the test, as they have found that for any given patient, the test repeatedly produces very similar results. However, they find that the new test results are not necessarily consistent with the gold standard of diagnosis. How would this new test most accurately be described?

• A. Valid and reliable
• B. Reliable (Correct Answer)
• C. Valid
• D. Biased
• E. Neither valid nor reliable

Differential diagnosis Explanation: ***Reliable*** - The test produces **similar results repeatedly** upon repeated measures, indicating high **reliability** or **precision**. - Reliability refers to the **consistency** of a measure, even if it is not accurate. *Valid and reliable* - While the test is **reliable**, it is explicitly stated that the results are **not consistent with the gold standard**, meaning it lacks **validity**. - A test must be both **consistent** (reliable) and **accurate** (valid) to be described as valid and reliable. *Valid* - **Validity** refers to the **accuracy** of a test, or how well it measures what it is supposed to measure. - The test is explicitly stated to **not be consistent with the gold standard**, indicating a lack of agreement with the true measure of Alzheimer's. *Biased* - **Bias** refers to a **systematic error** in measurement that can lead to consistently high or low results compared to the true value. - While the test might be biased due to its lack of consistency with the gold standard, "biased" is not the most accurate single descriptor of its measurement properties given the information provided. *Neither valid nor reliable* - The test is described as producing **very similar results repeatedly**, which directly indicates it has **high reliability**. - Therefore, stating it is neither valid nor reliable is incorrect, as it possesses reliability.

Differential diagnosis US Medical PG Question 3: 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

Differential diagnosis 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.

Differential diagnosis US Medical PG Question 4: A mother presents to the family physician with her 16-year-old son. She explains, "There's something wrong with him doc. His grades are getting worse, he's cutting class, he's gaining weight, and his eyes are often bloodshot." Upon interviewing the patient apart from his mother, he seems withdrawn and angry at times when probed about his social history. The patient denies abuse and sexual history. What initial test should be sent to rule out the most likely culprit of this patient's behavior?

• A. Complete blood count
• B. Sexually transmitted infection (STI) testing
• C. Blood culture
• D. Urine toxicology screen (Correct Answer)
• E. Slit lamp examination

Differential diagnosis Explanation: ***Urine toxicology screen*** - The patient's presentation with **declining grades**, **cutting class**, **weight gain**, **bloodshot eyes**, and **irritability** are classic signs of **substance abuse** in an adolescent. - A **urine toxicology screen** is the most appropriate initial test to detect common illicit substances, especially given the clear signs pointing towards drug use. *Slit lamp examination* - This test is used to examine the **anterior segment of the eye**, including the conjunctiva, cornea, iris, and lens. - While the patient has **bloodshot eyes**, this specific test would be more relevant for ruling out ocular infections or injuries, not for diagnosing the underlying cause of systemic behavioral changes. *Complete blood count* - A **complete blood count (CBC)** measures different components of the blood, such as red blood cells, white blood cells, and platelets. - A CBC is a general health indicator and while it can detect infections or anemia, it is not specific or sensitive enough to identify the cause of the behavioral changes described. *Sexually transmitted infection (STI) testing* - Although the patient denies sexual history, all adolescents presenting with certain risk factors or symptoms may warrant STI testing in a broader health assessment. - However, in this scenario, the primary cluster of symptoms (poor grades, cutting class, bloodshot eyes, irritability) points more directly to substance abuse than to an STI. *Blood culture* - A **blood culture** is used to detect the presence of bacteria or other microorganisms in the bloodstream, indicating a systemic infection (sepsis). - The patient's symptoms are not indicative of an acute bacterial bloodstream infection, and a blood culture would not be the initial test for the presented behavioral changes.

Differential diagnosis US Medical PG Question 5: A 52-year-old man comes to the physician because of a 3-week history of a cough and hoarseness. He reports that the cough is worse when he lies down after lunch. His temperature is 37.5°C (99.5°F); the remainder of his vital signs are within normal limits. Because the physician has recently been seeing several patients with the common cold, the diagnosis of a viral upper respiratory tract infection readily comes to mind. The physician fails to consider the diagnosis of gastroesophageal reflux disease, which the patient is later found to have. Which of the following most accurately describes the cognitive bias that the physician had?

• A. Framing
• B. Anchoring
• C. Visceral
• D. Confirmation
• E. Availability (Correct Answer)

Differential diagnosis Explanation: ***Availability*** - The physician recently seeing several patients with the common cold led to this diagnosis readily coming to mind, demonstrating how easily recalled examples can disproportionately influence diagnosis. - This bias occurs when easily recalled instances or information (like recent cases of common cold) are used to estimate the likelihood or frequency of an event, even if other more relevant data exist. *Framing* - This bias occurs when the way information is presented (e.g., as a gain or a loss) influences a decision, rather than the intrinsic characteristics of the options themselves. - The scenario does not involve the presentation of information in different ways to sway the physician's judgment. *Anchoring* - This bias involves relying too heavily on an initial piece of information (the "anchor") when making subsequent judgments, often leading to insufficient adjustment away from that anchor. - While the physician initially considered a viral URI, the setup is more about the ease of recall influencing the decision rather than being stuck on an initial data point. *Visceral* - This is not a commonly recognized cognitive bias in the context of medical decision-making; "visceral" largely refers to emotional or intuitive feelings rather than a structured cognitive bias. - Cognitive biases describe systematic patterns of deviation from norm or rationality in judgment, not merely emotional responses. *Confirmation* - This bias involves seeking, interpreting, favoring, and recalling information in a way that confirms one's pre-existing beliefs or hypotheses. - The physician did not actively seek information to confirm the common cold diagnosis; rather, the diagnosis came to mind due to recent encounters, which aligns with availability bias.

Differential diagnosis US Medical PG Question 6: A 27-year-old woman presents to the emergency department complaining of a left-sided headache and right-sided blurry vision. She states that 2 weeks ago she developed dark urine and abdominal pain. She thought it was a urinary tract infection so she took trimethoprim-sulfamethoxazole that she had left over. She planned on going to her primary care physician today but then she developed headache and blurry vision so she came to the emergency department. The patient states she is otherwise healthy. Her family history is significant for a brother with sickle cell trait. On physical examination, there is mild abdominal tenderness, and the liver edge is felt 4 cm below the right costal margin. Labs are drawn as below: Hemoglobin: 7.0 g/dL Platelets: 149,000/mm^3 Reticulocyte count: 5.4% Lactate dehydrogenase: 3128 U/L Total bilirubin: 2.1 mg/dL Indirect bilirubin: 1.4 mg/dL Aspartate aminotransferase: 78 U/L Alanine aminotransferase: 64 U/L A peripheral smear shows polychromasia. A Doppler ultrasound of the liver shows decreased flow in the right hepatic vein. Magnetic resonance imaging of the brain is pending. Which of the following tests, if performed, would most likely identify the patient’s diagnosis?

• A. Flow cytometry (Correct Answer)
• B. Glucose-6-phosphate-dehydrogenase levels
• C. Anti-histone antibodies
• D. Bone marrow biopsy
• E. Hemoglobin electrophoresis

Differential diagnosis Explanation: ***Flow cytometry*** - The patient's symptoms (headache, blurry vision, dark urine, abdominal pain, hepatomegaly) along with laboratory findings of **hemolytic anemia** (low hemoglobin, elevated reticulocyte count, high LDH, elevated indirect bilirubin) and signs of **thrombosis** (decreased hepatic vein flow, neurological symptoms) are highly suggestive of **paroxysmal nocturnal hemoglobinuria (PNH)**. - **Flow cytometry** is the gold standard for diagnosing PNH by detecting the absence of **CD55** and **CD59** on red blood cells, granulocytes, and monocytes, indicating a deficiency in the **GPI anchor protein**. *Glucose-6-phosphate-dehydrogenase levels* - **G6PD deficiency** typically presents with hemolytic anemia triggered by **oxidant stressors** (like trimethoprim-sulfamethoxazole) but does not typically cause **thrombosis** or widespread organ involvement (e.g., hepatic vein thrombosis, neurological symptoms) as seen in this patient. - Measuring G6PD levels would be appropriate if G6PD deficiency was suspected, but the clinical picture points more strongly to PNH due to the thrombotic events. *Anti-histone antibodies* - **Anti-histone antibodies** are primarily associated with drug-induced **lupus erythematosus**, which can manifest with various systemic symptoms, but not typically with severe hemolytic anemia and thrombotic microangiopathy in this specific pattern. - While drug exposure is present (trimethoprim-sulfamethoxazole), the overall clinical and lab findings (especially the severe hemolytic picture and thrombosis) are not characteristic of drug-induced lupus in this context. *Bone marrow biopsy* - A **bone marrow biopsy** might show findings consistent with increased erythropoiesis due to hemolysis but is not a primary diagnostic test for PNH or its associated thrombotic complications. - While it could be part of an evaluation for underlying bone marrow disorders, it would not directly confirm a diagnosis of PNH, which requires specific surface marker detection. *Hemoglobin electrophoresis* - **Hemoglobin electrophoresis** is used to diagnose **hemoglobinopathies** such as **sickle cell disease** or **thalassemia**. The patient's brother has sickle cell trait, but the patient's symptoms, particularly the prominent hemolytic anemia and thrombotic events, are not typical of a hemoglobinopathy in this acute presentation. - While it could rule out a hemoglobinopathy, it wouldn't explain the full spectrum of symptoms, especially the thrombosis and the specific pattern of hemolysis (e.g., elevated LDH, indirect bilirubin).

Differential diagnosis US Medical PG Question 7: A student health coordinator plans on leading a campus-wide HIV screening program that will be free for the entire undergraduate student body. The goal is to capture as many correct HIV diagnoses as possible with the fewest false positives. The coordinator consults with the hospital to see which tests are available to use for this program. Test A has a sensitivity of 0.92 and a specificity of 0.99. Test B has a sensitivity of 0.95 and a specificity of 0.96. Test C has a sensitivity of 0.98 and a specificity of 0.93. Which of the following testing schemes should the coordinator pursue?

• A. Test A on the entire student body followed by Test B on those who are positive
• B. Test A on the entire student body followed by Test C on those who are positive
• C. Test C on the entire student body followed by Test B on those who are positive
• D. Test C on the entire student body followed by Test A on those who are positive (Correct Answer)
• E. Test B on the entire student body followed by Test A on those who are positive

Differential diagnosis Explanation: ***Test C on the entire student body followed by Test A on those who are positive*** - To "capture as many correct HIV diagnoses as possible" (maximize true positives), the initial screening test should have the **highest sensitivity**. Test C has the highest sensitivity (0.98). - To "capture as few false positives as possible" (maximize true negatives and confirm diagnoses), the confirmatory test should have the **highest specificity**. Test A has the highest specificity (0.99). *Test A on the entire student body followed by Test B on those who are positive* - Starting with Test A (sensitivity 0.92) would miss more true positive cases than starting with Test C (sensitivity 0.98), failing the goal of **capturing as many cases as possible**. - Following with Test B (specificity 0.96) would result in more false positives than following with Test A (specificity 0.99). *Test A on the entire student body followed by Test C on those who are positive* - This scheme would miss many true positive cases initially due to Test A's lower sensitivity compared to Test C. - Following with Test C would introduce more false positives than necessary, as it has a lower specificity (0.93) than Test A (0.99). *Test C on the entire student body followed by Test B on those who are positive* - While Test C is a good initial screen for its high sensitivity, following it with Test B (specificity 0.96) is less optimal than Test A (specificity 0.99) for minimizing false positives in the confirmation step. - This combination would therefore yield more false positives in the confirmatory stage than using Test A. *Test B on the entire student body followed by Test A on those who are positive* - Test B has a sensitivity of 0.95, which is lower than Test C's sensitivity of 0.98, meaning it would miss more true positive cases at the initial screening stage. - While Test A provides excellent specificity for confirmation, the initial screening step is suboptimal for the goal of capturing as many diagnoses as possible.

Differential diagnosis US Medical PG Question 8: A trauma 'huddle' is called. Morphine is administered for pain. Low-flow oxygen is begun. A traumatic diaphragmatic rupture is suspected. Infusion of 0.9% saline is begun. Which of the following is the most appropriate next step in management?

• A. Chest fluoroscopy
• B. Barium study
• C. CT of the chest, abdomen, and pelvis (Correct Answer)
• D. MRI chest and abdomen
• E. ICU admission and observation

Differential diagnosis Explanation: ***CT of the chest, abdomen, and pelvis*** - A suspected **traumatic diaphragmatic rupture** requires a comprehensive imaging study to assess the diaphragm, surrounding organs, and potential associated injuries. - **CT scan** of the chest, abdomen, and pelvis provides detailed anatomical information, can identify herniated abdominal contents, and is essential for surgical planning in trauma settings. *Chest fluoroscopy* - While fluoroscopy can detect diaphragmatic motion, it is **less sensitive** for identifying tears or herniated contents in the **acute trauma setting**. - It does not provide the comprehensive view of surrounding organs and associated injuries often needed in trauma. *Barium study* - A barium study is primarily used to evaluate the **gastrointestinal tract**, but it is generally **not the initial imaging modality** for diaphragmatic rupture due to its limited ability to visualize the diaphragm itself or other solid organ injuries. - It would be performed after suspicion is increased or for very specific indications, not as a primary diagnostic tool. *MRI chest and abdomen* - While MRI offers excellent soft tissue contrast, its use in **acute trauma** is limited by **longer acquisition times**, potential contraindications with metallic implants (though less common in acute trauma), and lower availability compared to CT. - CT remains the **gold standard** for rapid, comprehensive imaging in unstable trauma patients. *ICU admission and observation* - While observation in the ICU is important for monitoring and supportive care, it is **not the next step for diagnosis** of a suspected diaphragmatic rupture. - Definitive diagnosis through imaging (CT) is crucial before determining specific management strategies, including potential surgical intervention.

Differential diagnosis US Medical PG Question 9: In a randomized controlled trial studying a new treatment, the primary endpoint (mortality) occurred in 14.4% of the treatment group and 16.7% of the control group. Which of the following represents the number of patients needed to treat to save one life, based on the primary endpoint?

• A. 1/(0.144 - 0.167)
• B. 1/(0.167 - 0.144) (Correct Answer)
• C. 1/(0.300 - 0.267)
• D. 1/(0.267 - 0.300)
• E. 1/(0.136 - 0.118)

Differential diagnosis Explanation: ***1/(0.167 - 0.144)*** - The **Number Needed to Treat (NNT)** is calculated as **1 / Absolute Risk Reduction (ARR)**. - The **Absolute Risk Reduction (ARR)** is the difference between the event rate in the control group (16.7%) and the event rate in the treatment group (14.4%), which is **0.167 - 0.144**. *1/(0.144 - 0.167)* - This calculation represents 1 divided by the **Absolute Risk Increase**, which would be relevant if the treatment increased mortality. - The **NNT should always be a positive value**, indicating the number of patients to treat to prevent one adverse event. *1/(0.300 - 0.267)* - This option uses arbitrary numbers (0.300 and 0.267) that do not correspond to the given **mortality rates** in the problem. - It does not reflect the correct calculation for **absolute risk reduction** based on the provided data. *1/(0.267 - 0.300)* - This option also uses arbitrary numbers not derived from the problem's data, and it would result in a **negative value** for the denominator. - The difference between event rates of 0.267 and 0.300 is not present in the given information for this study. *1/(0.136 - 0.118)* - This calculation uses arbitrary numbers (0.136 and 0.118) that are not consistent with the reported **mortality rates** of 14.4% and 16.7%. - These values do not represent the **Absolute Risk Reduction** required for calculating NNT in this specific scenario.

Differential diagnosis US Medical PG Question 10: 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)

Differential diagnosis 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.

Differential diagnosis Flashcard 1 of 10

Question: A positive _____ sign is when minor pressure induces skin separation

Answer: Nikolsky

Differential diagnosis Flashcard 2 of 10

Question: What is the differential diagnosis (2) in a Cushing syndrome patient with elevated ACTH?_____

Answer: 1. Cushing disease (ACTH-secreting pituitary adenoma) 2. Ectopic ACTH secretion

Differential diagnosis Flashcard 3 of 10

Question: What pathologies (2) are characterized by hematuria with no casts? _____

Answer: Bladder cancer, Kidney stones

Differential diagnosis Flashcard 4 of 10

Question: The following signs and symptoms are characteristic of what diesase: broad-based ataxia, positive Romberg, Argyll-Robertson pupil, Charcot joint, stroke

Answer: tertiary syphilis

Differential diagnosis Flashcard 5 of 10

Question: The following signs and symptoms are characteristic of what diesase: constitutional symptoms, maculopapuar rash (especially on palms and soles)

Answer: secondary syphilis

Differential diagnosis Flashcard 6 of 10

Question: What are the signs and symptoms of stage 3 Lyme disease?

Answer: arthritis, encephalopathy, polyneuropathy

Differential diagnosis Flashcard 7 of 10

Question: What kinds of things could cause anergy in a PPD test?

Answer: steroid therapy, malnutrition, immunocompromise

Differential diagnosis Flashcard 8 of 10

Question: Transillumination of the testes can help distinguish _____ from _____.

Answer: benign lesions of the tunica vaginalis

Differential diagnosis Flashcard 9 of 10

Question: testosterone-secreting tumor

Answer:

Extra Information: increased: testosterone decreased: LH 

Differential diagnosis Flashcard 10 of 10

Question: Double Y syndrome

Answer:

Extra Information: male, tall stature, severe acne, antisocial behaviorXYY