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HIGH YIELD NOTES
~5 min read
Core Concepts
Statistics & EBM:
- Study Design: RCT (intervention), Cohort (prognosis), Case-control (rare disease), Cross-sectional (prevalence).
- Bias: Selection, Information (recall, observer), Confounding.
- Hypothesis Testing: Null (H0) vs. Alternative (H1). P-value (<0.05 significant). Type I Error (alpha, false+), Type II Error (beta, false-).
- Measures: Sensitivity (TP rate), Specificity (TN rate), PPV, NPV, NNT (Number Needed to Treat). Likelihood Ratios.
- Evidence Hierarchy: Meta-analysis > RCT > Cohort > Case-control > Case series > Expert opinion.
- Pillars: Autonomy, Beneficence, Non-maleficence, Justice.
- Consent: Voluntary, Informed, Capacity (decision-specific). Presumed capacity in adults.
- Confidentiality: Duty to protect, but can be overridden (e.g., public interest, court order).
- GMC Guidance: Provides professional standards and ethical principles for doctors.
- Pharmacokinetics (PK): ADME (Absorption, Distribution, Metabolism - CYP450, Excretion). Half-life (t1/2).
- Pharmacodynamics (PD): Receptor interactions (agonist, antagonist), therapeutic index.
- ADRs: Type A (predictable, dose-dependent) vs. Type B (idiosyncratic, unpredictable).
- Mendelian: Autosomal Dominant (vertical), Autosomal Recessive (horizontal, consanguinity), X-linked (males affected, no male-male transmission).
- Concepts: Penetrance (proportion expressing phenotype), Expressivity (variation in phenotype), Anticipation.
- Chromosomal: Aneuploidy (e.g., Trisomy 21).
- Immunity: Innate (non-specific) vs. Adaptive (specific, memory – B/T cells).
- Hypersensitivity (Gell & Coombs): Type I (IgE, anaphylaxis), Type II (IgG/M, cell surface), Type III (Immune complexes), Type IV (T-cell, delayed).
- Cell Injury/Adaptation: Reversible/Irreversible. Atrophy, Hypertrophy, Hyperplasia, Metaplasia, Dysplasia. Necrosis, Apoptosis.
- Inflammation: Acute (neutrophils) vs. Chronic (lymphocytes, macrophages, fibrosis).
- Neoplasia: Benign vs. Malignant (invasion, mets). Oncogenes, Tumour Suppressors.
Clinical Presentation
- Statistics: Scenarios requiring interpretation of study results (p-values, CIs, NNT) or identification of methodological flaws/biases.
- Ethics: Dilemmas involving patient capacity, refusal of treatment, confidentiality breaches, or resource allocation.
- Pharmacology: Patients presenting with unusual adverse drug reactions, drug interaction symptoms, or therapeutic failure/toxicity due to PK/PD variations.
- Genetics: Pedigrees showing specific inheritance patterns, or descriptions of syndromes with known genetic bases.
- Immunology: Clinical cases involving allergic reactions (e.g., anaphylaxis), autoimmune disorders, or transplant rejection.
- Pathology: Descriptions of gross or microscopic findings from biopsies/autopsies, or clinical features of inflammation/neoplasia.
Diagnosis (Gold Standard)
- Statistics: Critical appraisal of research papers to identify study design, statistical methods, bias, and validity. Calculation/interpretation of NNT, likelihood ratios.
- Ethics: Application of ethical frameworks (e.g., 4 pillars) and GMC guidance to resolve clinical dilemmas. Assessment of patient capacity.
- Pharmacology: Detailed drug history and understanding of PK/PD principles to identify causative agents of ADRs or interactions. Therapeutic drug monitoring for narrow therapeutic index drugs.
- Genetics: Pedigree analysis, karyotyping (for chromosomal abnormalities), molecular genetic testing (PCR, sequencing) for specific gene mutations.
- Immunology: Specific IgE levels (Type I), direct/indirect Coombs test (Type II), immune complex assays (Type III), Mantoux/patch testing (Type IV). Autoantibody panels.
- Pathology: Histopathological examination (microscopy) of biopsy specimens, immunohistochemistry, molecular pathology.
Management (First Line)
- Statistics: Applying evidence-based medicine (EBM) principles to clinical practice, informed decision-making based on robust research.
- Ethics: Prioritising patient autonomy, ensuring informed consent, maintaining confidentiality (unless overridden), best interest decisions for those lacking capacity.
- Pharmacology: Rational drug choice based on efficacy, safety profile, patient factors (renal/hepatic function, age, comorbidities), potential drug interactions. Dose adjustments. ADR reporting.
- Genetics: Genetic counselling, prenatal diagnosis/screening, pre-implantation genetic diagnosis, family screening.
- Immunology: Avoidance of triggers (Type I), antihistamines/steroids (Type I/III/IV), immunosuppression (autoimmune), plasma exchange/IVIG (some Type II/III).
- Pathology: Informs clinical decisions on prognosis, treatment selection (e.g., targeted therapies for specific tumour mutations), and surgical margins.
Exam Red Flags
- Confusing Type I (alpha, false positive) and Type II (beta, false negative) errors.
- Misinterpreting a p-value as the probability of the null hypothesis being true.
- Overlooking common biases (e.g., recall bias in case-control, selection bias in non-randomised studies).
- Failing to recognise a patient’s capacity, or overriding autonomy without strong justification (public interest, severe harm).
- Incorrectly classifying hypersensitivity reactions (e.g., contact dermatitis is Type IV, not I).
- Ignoring significant drug-drug interactions, especially involving CYP450 enzymes or narrow therapeutic index drugs.
- Missing key features distinguishing benign vs. malignant pathology (e.g., invasion, metastasis, pleomorphism).
- Applying principles of positive feedback when negative feedback is the more common homeostatic mechanism.
Sample Practice Questions
Question 1
A 28-year-old male with Type 1 Diabetes Mellitus presents to the emergency department with polyuria, polydipsia, weight loss, and Kussmaul breathing. Blood tests reveal hyperglycemia (blood glucose 25 mmol/L), metabolic acidosis (pH 7.15, bicarbonate 8 mmol/L), and elevated plasma ketones. Which of the following best explains the metabolic acidosis in this patient?
A) Accumulation of beta-hydroxybutyrate and acetoacetate
B) Excessive lactic acid production due to tissue hypoperfusion
C) Renal tubular acidosis type 2
D) Ingestion of methanol
Question 2
A 68-year-old man presents with confusion and nausea. His serum sodium is 118 mmol/L (normal range 135-145), plasma osmolality 240 mOsm/kg (normal range 275-295), and urine osmolality 450 mOsm/kg with urine sodium 60 mmol/L (normal range >20 in euvolaemia). He has a history of small cell lung carcinoma. Clinical examination reveals euvolaemia. Which of the following is the most likely underlying physiological mechanism contributing to his hyponatremia?
A) Increased secretion of atrial natriuretic peptide (ANP)
B) Inappropriate secretion of antidiuretic hormone (ADH)
C) Primary adrenal insufficiency leading to aldosterone deficiency
D) Impaired renal tubular response to ADH
Question 3
A 70-year-old male with a history of small cell lung carcinoma presents with lethargy and confusion. His serum sodium is 122 mmol/L (normal range 135-145), serum osmolality is 250 mOsm/kg (normal 275-295), and urine osmolality is 450 mOsm/kg. He appears euvolemic on examination. Which of the following is the most likely underlying physiological disturbance?
A) Primary adrenal insufficiency leading to aldosterone deficiency
B) Excessive renal loss of sodium due to diuretic use
C) Inappropriate secretion of antidiuretic hormone (ADH)
D) Increased thirst and excessive free water intake
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