MEDICINE MEDICINE Acute interstitial nephritis (AIN) AIN is characterized by AKI with pyuria and often WBC casts in the urine. AIN can be caused by a few medications (e.g., allopurinol) and may be accompanied by nonspecific systemic signs and symptoms (e.g., fever, malaise, polyarthralgia, skin rash). Acute kidney injury (AKI) Aminoglycosides (e.g., amikacin) can cause AKI in the form of acute tubular necrosis, usually after >5-7 days of use. - Fractional excretion of sodium (FENa) is typically >2%, and urinalysis usually shows muddy brown (granular) or epithelial cell casts. Prerenal AKI (BUN: Cr ratio >20:1, FENa <1%, bland sediment) can occur both in hypovolemic and volume-overloaded states. Prerenal AKI in an acute heart failure exacerbation is most likely due to cardiorenal syndrome, which involves central venous and renal venous pressures leading to a reduction in GFR. Postrenal AKI can be seen in patients with severe bladder outlet obstruction due to benign prostatic hyperplasia (classically, an elderly male with lower urinary tract symptoms and a smooth, enlarged prostate). - A renal ultrasound is advised for assessment of hydronephrosis in patients with worsening kidney function. - Placement of a urinary catheter in patients with hydronephrosis can provide quick relief of the obstruction. Acute pancreatitis Acute pancreatitis is most often due to alcohol use, gallstones, triglyceridemia, or medications. Commonly implicated drugs include diuretics (e.g., thiazides), anti-seizure drugs (e.g., valproic acid), and antibiotics (e.g., metronidazole). - Drug-induced pancreatitis is usually mild and resolves with supportive care. An abdominal CT scan can reveal diffuse or focal parenchymal changes, edema, necrosis, or liquefaction. Acute respiratory distress syndrome (ARDS) Oxygenation in mechanically-ventilated patients is determined by the fraction of inspired oxygen (FiO2) and positive end-expiratory pressure (PEEP). Increasing PEEP recruits collapsed alveoli in ARDS, reducing intrapulmonary shunting and allowing reduction of FiO2. Optimal PEEP settings may improve mortality rates in patients with severe ARDS. Alcohol-induced cardiomyopathy (AIC) AIC, a type of dilated cardiomyopathy, is a potential cause of decompensated heart failure in patients with heavy and prolonged alcohol use. Complete abstinence from alcohol is the optimal treatment as it can markedly improve LV dysfunction. Alcoholic hepatitis Alcoholic hepatitis is generally characterized by a ratio of AST:ALT >2, gammaglutamyltransferase (GGT), and ferritin. The absolute values of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are almost always <500 IU/L in alcoholic liver disease. Amyloidosis AA amyloidosis occurs in the setting of chronic inflammation and is most seen in patients with long-standing rheumatoid arthritis. - The most common manifestation is renal disease characterized by proteinuria and nephrotic syndrome; cardiac and GI disease may also occur. The diagnosis is confirmed with fat pad biopsy demonstrating amorphous hyaline material that stains with Congo red. - Green birefringence is noted on the polarized light. Aortic stenosis The 3 most common causes of aortic stenosis are: - age-related calcification of a normal valve - calcification of a bicuspid aortic valve - rheumatic heart disease A congenital bicuspid aortic valve is the most common cause of severe aortic stenosis in middle-aged adults (i.e., age 40-60) in medically resource-rich countries. Aortic stenosis can present with decreased exercise tolerance, exertional dyspnea, angina, or syncope. Physical examination typically reveals a delayed and diminished carotid pulse, soft S2, and mid- to late-peaking systolic murmur with maximal intensity at the second right intercostal space and radiation to the carotids. Ascites Evaluation of new-onset ascites includes diagnostic paracentesis for fluid analysis to help determine the etiology. Cell count and differential (PMNs, lymphocytes), albumin (SAAG), and total protein levels are typically ordered. Atelectasis Large-volume atelectasis can result from airway obstruction (e.g., mucus plug) and lead to mediastinal displacement toward the side of alveolar collapse. Dullness to percussion and decreased or absent breath sounds are expected over the area of atelectasis. Atrial fibrillation (A-fib) Chronic hypertension is the most common comorbidity associated with atrial fibrillation and is likely one of the strongest contributors to the predisposing atrial remodeling. Aging is also a strong contributor. A-fib is recognized on ECG by irregularly irregular R-R intervals and an absence of organized P waves. Hyperthyroidism is a potential trigger of AF; therefore, it should be ruled out with serum TSH and free T4 testing in all patients with new-onset AF. Atrial premature beat (premature atrial complex, PAC) Tobacco and alcohol are reversible risk factors for PACs. Beta blockers are often helpful in symptomatic patients. Autoimmune hepatitis Autoimmune hepatitis is characterized by a hepatocellular pattern of liver injury (elevations in aspartate aminotransferase and alanine aminotransferase with normal alkaline phosphatase and bilirubin), as well as high levels of autoantibodies, resulting in elevated serum globulins and a gamma gap. Positive serology (e.g., anti–smooth muscle, anti–liver/kidney microsomal type1, antinuclear antibodies) or hypergammaglobulinemia confirms the diagnosis. Benign prostatic hyperplasia (BPH) Patients with lower urinary tract symptoms (e.g., urinary frequency, nocturia, hesitancy) should have a urinalysis to evaluate for hematuria and infection. Prostate specific antigen should also be obtained in symptomatic patients to assess the risk for prostate cancer, unless predicted life expectancy is <10 years. Beta blockers Conventional beta blockers (e.g., metoprolol, atenolol, propranolol) are associated with impaired glucose control and weight gain, likely via effects on skeletal muscle that lead to insulin sensitivity. Therefore, these drugs are an unfavorable option for hypertension management in patients with, or at high risk for, type 2 diabetes mellitus. However, beta blockers with combined vasodilatory alpha-1 receptor—blocking properties (carvedilol, labetalol; the “not -olols”) are not associated with reduced insulin sensitivity, which provides further evidence of the importance of the hemodynamic effects on skeletal muscles. Bladder cancer Bladder cancer often causes hematuria, voiding symptoms (e.g., dysuria, urgency, frequency), and/or suprapubic pain (neural invasion). Patients who have no clear source (e.g., cystitis) for these symptoms require urgent workup with cystoscopy. Carbon monoxide (CO) poisoning CO poisoning disrupts oxygen delivery and usage, which can cause clinical manifestations of myocardial ischemia. carboxyhemoglobin levels confirm the diagnosis. Severe cases require hyperbaric oxygen therapy. Cardiac tamponade Patients with cardiac tamponade usually have clinical features of Beck's triad: - hypotension, distended neck veins, and muffled heart sounds. These symptoms are due to an exaggerated shift of the interventricular septum toward the left ventricular cavity, which reduces left ventricular preload, stroke volume, and cardiac output. Electrical alternans is a specific but poorly sensitive finding for pericardial effusion with cardiac tamponade; it results from the heart changing position within the fluid-filled pericardial sac with each heartbeat. Tamponade is treated with emergency pericardiocentesis to relieve pericardial pressure. Chemotherapy Serotonin (5HT) antagonists (e.g., ondansetron) that block 5HT3 receptors are the drugs of choice for treating and preventing chemotherapy-induced nausea and vomiting. Chronic cough Asthma may present with chronic cough (> 8 weeks) that is predominantly nocturnal. These patients should be evaluated with spirometry (PFTs) to assess bronchodilator response. - A methacholine challenge test can be performed if no bronchodilator response is seen. - Nocturnal or early morning peak expiratory flow rate measurements can be used to diagnose patients with only nocturnal symptoms. - An alternate approach is to treat empirically with 2-4 weeks of inhaled glucocorticoids. If the cough improves, a diagnosis of asthma can be made. Other common causes of chronic cough include: - upper airway cough syndrome - GERD - ACE inhibitors Chronic obstructive pulmonary disease (COPD) Patients with advanced COPD are prone to oxygen-induced hypercapnia due to reversal of hypoxic pulmonary vasoconstriction, which increases alveolar dead space. Severe hypercapnia causes neurologic dysfunction (e.g., encephalopathy) and can be prevented by maintaining SaO2 at 88%-92%. Cirrhosis Cirrhosis should be suspected in patients with stigmata of chronic liver disease (e.g., spider angiomas, gynecomastia, ascites). Common causes include: - heavy alcohol use - nonalcoholic fatty liver disease - hemochromatosis - chronic viral hepatitis B (worldwide) or C (United States). Prior or current use of IV drugs is a strong risk factor for hepatitis C. Dermatomyositis Dermatomyositis is an inflammatory myopathy characterized by immune-mediated injury to muscle fibers that often occurs as a paraneoplastic syndrome in malignancy. Patients typically have symmetrical, proximal muscle weakness and an erythematous rash over the dorsum of the fingers (Gottron sign, pathognomonic) and/or upper eyelids (heliotrope rash). Diabetes insipidus (DI) Patients with polyuria and dilute urine who have normal serum Na + require water deprivation testing to distinguish primary polydipsia from an arginine vasopressin (AVP) disorder. Persistently dilute urine following water deprivation (i.e., serum osmolality >295 mEq/L and serum Na+ >145 mEq/L) suggests an AVP disorder. Chronic lithium therapy is commonly associated with nephrogenic DI, presenting with polyuria and persistently dilute urine. - Lithium-induced nephrogenic DI results from lithium accumulation in the renal collecting ducts, which leads to antidiuretic hormone resistance and impaired renal water reabsorption. Diabetes mellitus Obesity and cardiovascular disease are common comorbidities in patients with type 2 diabetes mellitus. - In these patients, glucagon-like peptide-1 (GLP-1) receptor agonists and/or certain sodium-glucose cotransporter-2 (SGLT-2) inhibitors can be added to decrease cardiovascular mortality, induce weight loss, and minimize the risk for hypoglycemia. Diabetic nephropathy Diabetic nephropathy is characterized by altered glomerular filtration (initial hyperfiltration and, later, decreased filtration) and increased protein (e.g., albumin) excretion. The most sensitive test is the urine albumin/creatinine ratio, which should be assessed regularly beginning at the diagnosis of type 2 diabetes mellitus. Diffuse alveolar hemorrhage (DAH) Cocaine (“crack lung”) can induce acute lung toxicity in the form of DAH. DAH presents with rapid onset of dyspnea. - Diffuse, bilateral airspace opacities; and hypoxemia soon after inhaled cocaine exposure. Digital clubbing Digital clubbing describes bulbous enlargement and broadening of the fingertips due to connective tissue proliferation at the nail bed and distal phalanx. Pathophysiology involves megakaryocytes that skip the normal route of fragmentation within pulmonary circulation (due to circulatory disruption from tumors, chronic lung inflammation) to enter systemic circulation. - Megakaryocytes become entrapped in the distal fingertips and release PDGF and VEGF. Digital clubbing is diagnosed when the angle between the nail fold and the nail plate is >180º (Lovibond angle). Lung malignancies, cystic fibrosis, and right-to-left cardiac shunts are the most common causes of secondary digital clubbing. COPD does not cause digital clubbing, and the presence of clubbing should prompt a search for occult malignancy. Hypertrophic osteoarthropathy refers to digital clubbing along with painful joint enlargement, periostosis of long bones, and synovial effusions. Digoxin toxicity Digoxin has a narrow therapeutic window and toxicity is common in elderly patients as they are susceptible to acute renal dysfunction (dehydration, AKI) with decreased clearance of the drug. Symptoms of acute toxicity include GI disturbances (e.g., anorexia, nausea, vomiting), lethargy and fatigue. - Chronic toxicity presents with neurologic disturbances (e.g., confusion, changes in color vision), and cardiac arrhythmias (sinus bradycardia, AV block). A blood digoxin level helps confirm the diagnosis. - However, toxicity can occur even with normal blood levels and, in such cases, should be recognized by consistent clinical features. Treatment involves drug discontinuation and IV hydration. - In severe cases, administer digoxin-specific antibody (Fab) fragments. Digoxin toxicity can cause a wide range of cardiac arrhythmias, typically resulting from increased automaticity of myocardial conduction and/or increased vagal tone. - Atrial tachycardia with AV block involves both mechanisms and is the most specific arrhythmia for digoxin toxicity. Discoid lupus erythematosus (DLE) DLE presents with scaly, erythematous plaques, leading to atrophy, hypopigmentation, and scarring. It most commonly affects sun-exposed areas of the head and neck. DLE is the most common form of chronic cutaneous lupus erythematosus. DLE can occur independently, although systemic lupus erythematosus (SLE) eventually develops in up to 30% of patients. Disseminated gonococcal infection (DGI) DGI can present with purulent monoarthritis and fever. Synovial fluid analysis typically shows a leukocyte count of approximately 50,000/mm3 with no organisms or crystals on microscopy. Diagnosis requires synovial fluid nucleic acid amplification testing (NAAT), blood cultures, and NAAT of samples from mucosal sites (e.g., urethra, rectum, pharynx, cervix). Drug-induced acne (steroid acne) Drug-induced acne is a common side effect of systemic glucocorticoids and is characterized by monomorphic papules without associated comedones, cysts, or nodules. Drug-induced acne does not respond to typical acne treatment but improves rapidly on discontinuation of the offending agent. Factitious diarrhea Diarrhea that is not explained after extensive evaluation suggests possible factitious diarrhea. Helpful studies include: - stool osmolality (hypoosmolality suggests addition of water or dilute fluid; hyperosmolality suggests addition of concentrated fluid [e.g., urine]) - stool electrolytes (elevated magnesium or phosphate suggests use of saline osmotic laxatives), and - stool osmotic gap (osmotic laxatives cause a high osmotic gap diarrhea). Familial hypocalciuric hypercalcemia (FHH) FHH is caused by a mutation in the calcium-sensing receptor (CaSR). It is a benign disorder characterized by asymptomatic hypercalcemia, /- normal PTH levels, and low urinary calcium excretion (typically <100 mg/24 hr). It can be differentiated from 1º hyperparathyroidism (which has increased urinary calcium excretion), by the urine calcium/creatinine ratio (UCCR). UCCR is usually <0.01 in FHH compared to >0.02 in 1º hyper-PTH. Fecal impaction Fecal impaction is common in older patients with impaired mobility, chronic constipation, or decreased sensation of stool in the rectal vault. Obstruction of fecal flow in the rectum can cause backup of stool; passage of liquid stool around the impaction can lead to incontinence. Initial management includes manual disimpaction and enemas to clear the rectal vault. - Following acute treatment, a bowel regimen, including laxatives (e.g., polyethylene glycol, lactulose) and dietary alterations (e.g., increased intake of fluid and fiber), should be instituted. Focal segmental glomerulosclerosis (FSGS) HIV-associated nephropathy (HIVAN) is caused by viral infection of podocytes that leads to nephrotic syndrome and a severe variant of FSGS with collapsing glomeruli. Suspected HIVAN requires confirmation of collapsing FSGS by biopsy because HIV can injure the kidneys by a variety of mechanisms. Antiretroviral therapy should be initiated or continued in patients with HIVAN to slow the progression of renal failure. - RAAS inhibitors (e.g., ACE inhibitors) reduce proteinuria and help delay kidney dysfunction. - Many patients develop end-stage renal disease even with optimal therapy. Folate deficiency Body stores of folate are minimal, and deficiency may occur quickly in the setting of significant alcohol use. Folate and cobalamin (vitamin B12) deficiencies both result in megaloblastic anemia with insufficient reticulocytosis, but folate deficiency is associated with normal (not high) methylmalonic acid levels. Gallstone disease Patients receiving total parenteral nutrition lack the normal enteral stimulus (CCK) for gallbladder contraction. This results in gallbladder stasis, which creates concentrated bile and promotes the formation of sludge and gallstones. Biliary colic occurs when the gallbladder contracts against a gallstone that is obstructing the cystic duct. - Increased intra-gallbladder pressure causes the characteristic intense, dull, RUQ or epigastric pain with nausea and vomiting. - Symptoms are often triggered by fatty meals and typically resolve completely within 4-6 hours (as the gallbladder relaxes and the stone falls back from the duct). - Abdominal ultrasound can confirm the diagnosis. Asymptomatic gallstones typically do not require treatment because the majority do not progress to symptomatic or complicated disease. Laparoscopic cholecystectomy is the treatment of choice for patients who develop symptomatic gallstone disease. - Elective for uncomplicated, typical symptoms - Within 72 hours for complicated disease (cholecystitis, choledocholithiasis, gallstone pancreatitis) Greater trochanteric pain syndrome (GTPS) GTPS (aka, trochanteric bursitis) presents with chronic lateral hip pain and tenderness over the greater trochanter during hip flexion or lying on the affected side. Greater trochanteric pain syndrome is an overuse syndrome involving the tendons of the gluteus medius and minimus at the greater trochanter. Physical examination shows local tenderness over the greater trochanter. Initial treatment includes heat, activity modification, and NSAIDs. Patients with persistent symptoms may benefit from local corticosteroid injection. Heart failure Decompensated heart failure typically presents with dyspnea on exertion, jugular venous distension, and peripheral edema. - Pulmonary edema may be absent in slowly progressive decompensation because of increased lymphatic drainage. Decompensated heart failure involves the activation of compensatory mechanisms in the form of the sympathetic nervous system and RAAS. These systems stimulate vasoconstriction and Na+ retention to maintain organ and tissue perfusion in the setting of reduced cardiac output. The compensatory mechanisms are ultimately maladaptive as they further decrease cardiac output and perpetuate a downward spiral of clinical decompensation. Hereditary hemochromatosis (HH) HH is characterized by intestinal iron absorption, tissue iron deposition, and multisystem end-organ damage (e.g., hepatotoxicity). The diagnosis is confirmed by testing for HFE genetic mutations. - However, patients with extreme hyperferritinemia (e.g., serum ferritin >1000 ng/mL) should receive urgent therapeutic phlebotomy without waiting for genetic testing results. Hemolytic anemia Anemia with reticulocytosis suggests that the bone marrow is responding appropriately to the anemia by generating new erythrocytes, and that sufficient levels of folate, vitamin B12, and iron are available for erythrocytosis. Anemia with reticulocytosis is commonly seen in acute bleeding conditions and hemolysis. Chronic lymphocytic leukemia is associated with warm autoimmune hemolytic anemia. Autoimmune hemolytic anemia (AIHA) and hereditary spherocytosis (HS) can cause extravascular hemolytic anemia. - A negative family history and positive Coombs test suggest AIHA. - A positive family history and negative Coombs test suggest HS. The peripheral blood smear in both conditions may show spherocytes without central pallor. Heparin-induced thrombocytopenia (HIT) In type 2 HIT, heparin induces a conformational change in a platelet surface protein which exposes a neoantigen. Antibodies are formed and bind to the surface of platelets, resulting in platelet activation, thrombocytopenia, and a prothrombotic state. Type 2 HIT typically occurs 5-10 days after heparin initiation but may occur sooner in patients previously exposed to heparin. Hepatic encephalopathy (HE) Treatment for hepatic encephalopathy involves identifying the underlying precipitant and lowering serum ammonia. - Non-absorbable disaccharides (e.g., lactulose, lactitol) are preferred for lowering serum ammonia. Patients with HE on diuretics can develop low intravascular volume despite having total volume overload, leading to a: - metabolic alkalosis ( serum conversion of NH4+ NH3 which can cross the BBB) - hypokalemia: the resultant intracellular acidosis (excreted intracellular K+ replaced by H+ to maintain electroneutrality) causes increased NH3 production (glutamine conversion) in renal tubular cells. - Treatment includes volume resuscitation and repletion of hypokalemia in addition to serum ammonia-lowering medications (e.g., lactulose). Hepatitis A Hepatitis A causes fever, vomiting, jaundice, hepatomegaly, and severe elevations in hepatic transaminases (e.g., aminotransferase levels >1,000 U/L). Unvaccinated individuals are at increased risk, as are: - day care workers (children often do not have jaundice and may go undiagnosed), - homeless shelter residents - international travelers - men who have sex with men Anti-HAV IgM serology confirms the diagnosis. Treatment is supportive; complete recovery typically occurs within 2-3 months. Hepatitis C virus (HCV) Patients with cirrhosis from any cause, including chronic hepatitis C virus, should be vaccinated against both hepatitis A virus (HAV) and hepatitis B (HBV) virus unless they have serologic evidence of immunity. Acute HAV or HBV infection in unvaccinated/nonimmune patients with cirrhosis can cause severe acute or chronic liver failure. Hepatojugular reflux Hepatojugular reflux is useful for differentiating between cardiac disease— and liver disease—related causes of ascites, splenomegaly, and lower extremity edema. Hepatojugular reflux (i.e., sustained > 3-cm rise in JVP elicited by compression of the upper abdomen) is highly specific for right ventricular failure. - Hepatojugular reflux is not expected with liver cirrhosis. High-output heart failure High-output heart failure is caused by decreased systemic vascular resistance that leads to an increase in stroke volume, cardiac output, and venous return and is recognized by a wide pulse pressure and prominent point of maximal impulse. Hyperthyroidism is a common cause of high-output heart failure. HIV HIV patients with CD4 ≤200/mm3 require primary prophylaxis with TMP-SMX to prevent Pneumocystis pneumonia. - TMP-SMX is also used for primary prophylaxis against toxoplasmosis in those with positive serology and CD4 ≤100/mm3. Primary prophylaxis against mycobacterium avium complex (azithromycin) is no longer required. No other primary prophylaxis is routinely given. - However, patients in Histoplasma-endemic areas with CD4 ≤150/mm3 are sometimes given prophylactic itraconazole. Hypercalcemia Causes of hypercalcemia (differential: C-H-I-M-P-A-N-Z-E-E-S) should be categorized based on parathyroid hormone (PTH) levels. - PTH-independent hypercalcemia (suppressed PTH) is usually due to malignancy. - PTH-dependent hypercalcemia (elevated or inappropriately normal PTH) is usually due to 1º hyper-PTH (differential: 3º hyper-PTH, FHH, lithium) CHIMPANZEEES = - Ca intake - Hyper-PTH (2º/3º) - Immobilization - Multiple myeloma/Milk-alkali/Medication (thiazides, lithium) - Parathyroid hyperplasia or adenoma (1º) - Alcohol/Adrenal insufficiency - Neoplasm (breast cancer, lung cancer // PTHrP in squamous cell lung cancer, renal cell carcinoma, bladder cancer) - Zollinger-Ellison syndrome - Excessive vitamin D ( 25-(OH) vitamin D) - Excessive vitamin A - Endocrine (thyrotoxicosis, adrenal insufficiency) - Sarcoidosis ( 1,25-(OH)2 vitamin D) – also histoplasmosis, TB, and lymphoma. Hypercalcemia can occur in prolonged immobilization due to increased osteoclastic activity, especially in individuals with a high baseline rate of bone turnover (e.g., younger individuals, Paget disease). - Bisphosphonates can reduce this hypercalcemia and prevent bone loss. Humoral hypercalcemia of malignancy is characterized by severe, symptomatic hypercalcemia. It is due to the release of parathyroid hormone-related protein (PTHrP) by tumor cells, leading to increased bone resorption and reabsorption of calcium in the distal renal tubule. Hyperosmolar hyperglycemic state (HHS) In HHS, severely elevated glucose (>600 mg/dL) and plasma osmolality are present, causing altered mentation and focal neurological signs. Due to osmotic diuresis and insulin deficiency, total body potassium is often depleted despite normal or slightly elevated serum potassium values. Therefore, in addition to insulin and intravenous fluids, potassium repletion should be given when serum K+ is <5.3 mEq/L. Hypersensitivity pneumonitis Acute hypersensitivity pneumonitis classically presents with recurrent episodes of abrupt-onset fever, dyspnea, nonproductive cough, and fatigue that coincide with intermittent exposure to an inhaled antigen. The condition is often mistaken for bacterial pneumonia but self-resolves within a few days after removal of antigen exposure. Hyperthyroidism Treatment options for Graves disease include radioactive iodine (RAI) therapy, antithyroid drugs (e.g., methimazole, propylthiouracil), and thyroidectomy. - RAI therapy can induce or worsen thyroid eye disease and is contraindicated in patients with moderate or severe eye disease. Untreated hyperthyroid patients are at risk for rapid bone loss from increased osteoclastic activity in the bone cells. Untreated hyperthyroid patients are also at risk for cardiac tachyarrhythmias, including atrial fibrillation. Hypocalcemia Patients with hypoalbuminemia can have decreased total serum calcium. The serum calcium concentration decreases by 0.8 mg/dL for every 1 g/dL decrease in serum albumin; the corrected calcium level can be calculated using the following formula: - Corrected Ca++ = (measured total Ca++) + 0.8 × (4.0 g/dL − serum albumin in g/dL) However, ionized calcium (physiologically active form) is hormonally regulated and remains stable. Hypothyroidism Hypothyroidism is an important cause of reversible changes in memory and mentation. It will be accompanied by systemic changes such as weight gain, fatigue, and constipation. Subclinical hypothyroidism may be diagnosed in a patient with elevated TSH and normal free T4. Infective endocarditis (IE) IE following dental or respiratory tract procedures is most often caused by viridans streptococci. Enterococcus is the most common cause of IE following manipulation of infected areas of the GI or GU tract. IE following skin or soft tissue infection or in users of IV drugs is most often due to Staphylococcus aureus or coagulase-negative Staphylococcus. IE often causes several weeks of nonspecific symptoms, complications related to septic emboli (e.g., brain abscess), and new heart murmur. Initial workup includes 3 sets of blood cultures (from 3 different venipuncture sites) and echocardiography. Irritable bowel syndrome (IBS) Irritable bowel syndrome is characterized by recurrent abdominal pain and changes in stool frequency or form in the absence of an organic cause. Management includes dietary modification, physical activity, and soluble fiber supplementation (e.g., psyllium) for all patients initially. Kaposi sarcoma (KS) KS is the most common cancer in patients with untreated HIV. All individuals with suspected KS should undergo HIV testing, particularly when other symptoms (e.g., unintentional weight loss, lymphadenopathy) of HIV infection are present. Klinefelter syndrome Klinefelter syndrome (47, XXY) is characterized by a eunuchoid habitus, gynecomastia, small testes, and decreased virilization. It can lead to infertility due to testicular fibrosis with seminiferous tubule dysgenesis, azoospermia, hypogonadism, and elevated FSH and LH levels. Lichen planus Drug-induced lichen planus (lichenoid drug reaction) is associated with a number of medications, including ACE inhibitors, thiazide diuretics, beta blockers, and hydroxychloroquine. Whereas idiopathic lichen planus occurs most commonly at the wrists and ankles, druginduced lichen planus can have a more diffuse presentation. Treatment includes topical glucocorticoids and discontinuation of the suspected medication. Lupus nephritis Lupus nephritis is a common manifestation of systemic lupus erythematosus (SLE) and should be suspected in patients with glomerulonephritis, hypocomplementemia ( C3, C4), and findings suggesting SLE (e.g., pancytopenia). Metabolic acidosis In patients with anion gap metabolic acidosis (AGMA), calculating the serum osmolal gap (measured osmolality − calculated osmolality) can narrow the differential diagnosis. - A high serum osmolal gap suggests ingestion of a toxic alcohol (e.g., methanol, ethylene glycol). AGMA in a patient with altered mental status, sweet-smelling breath, envelope-shaped urinary crystals (e.g., calcium oxalate crystals), and acute kidney injury is consistent with a toxic ingestion of ethylene glycol. Methotrexate Methotrexate is a disease-modifying antirheumatic drug (DMARD) used in treatment of rheumatoid arthritis. Its effects are mediated largely by inhibition of dihydrofolate reductase, which causes folate depletion and leads to impaired DNA synthesis. Side effects include oral ulcers, macrocytic anemia, and hepatotoxicity. - Much of the toxicity of methotrexate can be mitigated by the administration of folic acid (e.g., leucovorin), which does not reduce the effectiveness of the drug. Mitral valve prolapse (MVP) Myxomatous degeneration of the mitral valve leading to MVP is the most common cause of chronic mitral regurgitation in medically resource-rich countries. It can occur as an isolated valvular process or in association with syndromic connective tissue disease (e.g., Marfan syndrome, Ehlers-Danlos syndrome). Multifocal atrial tachycardia (MAT) MAT is a supraventricular tachyarrhythmia characterized by distinct P waves with 3 different morphologies, atrial rate > 100/min, and an irregular rhythm. It is usually precipitated by acute respiratory illness in patients with underlying lung disease (e.g., COPD). Treatment should be directed at treating the underlying inciting disturbance. - Persistent MAT can be treated with verapamil (AV nodal blockade). Myocardial infarction (MI) Right ventricular MI is confirmed by ST-segment elevation in the right-sided precordial ECG leads (e.g., V4R). - Increased RV preload, decreased LV preload, and reduced cardiac output with hypotension and a compensatory increase in systemic vascular resistance are expected. ST-segment elevation myocardial infarction (STEMI) can present with atypical symptoms in elderly patients. Patients with STEMI should undergo emergency cardiac catheterization and percutaneous coronary intervention. Nonbacterial thrombotic endocarditis (NBTE) NBTE results from a hypercoagulable state that is usually due to advanced cancer or SLE. It typically presents with systemic embolization of valvular vegetation (e.g., stroke) in the absence of evidence of infective endocarditis (i.e., no fever or leukocytosis, negative blood cultures). Evaluation should include hypercoagulable work-up and investigation for malignancy (CT scan of the chest and abdomen). Non-Hodgkin lymphoma (NHL) Patients with chronic autoimmune diseases (e.g., SLE, Sjögren syndrome) are at increased risk for NHL due to persistent B-cell stimulation, immune dysregulation, and use of immunosuppressive agents (e.g., hydroxychloroquine). NHL often presents with progressive, painless lymphadenopathy and B symptoms (e.g., weight loss, fever, night sweats). Laboratory evaluation often reveals elevated LDH, likely due to tumor burden, liver involvement, or occasional hemolysis. Confirmation is usually made by excisional lymph node biopsy. Obstructive sleep apnea (OSA) OSA is caused by episodic obstruction of the upper airway die to laxity of pharyngeal tissue, resulting in nocturnal hypoventilation. Common manifestations include daytime sleepiness, snoring, and a choking or gagging sensation while sleeping. OSA can present without symptoms of snoring or witnessed apneic events. Not all patients have obvious respiratory symptoms (e.g., snoring, gasping for air); the sequelae of OSA (e.g., erectile dysfunction, arterial hypertension) may be what prompts the initial evaluation. OSA causes transient periods of hypoxemia. The kidneys respond by increasing erythropoietin, which can result in erythrocytosis. Obesity (particularly BMI >35 kg/m2) is the strongest risk factor for OSA. Paroxysmal nocturnal hemoglobinuria (PNH) PNH should be suspected in patients who have a combination of hemolytic anemia, cytopenias (impaired hematopoiesis), and hypercoagulable state (intraabdominal or cerebral venous thrombosis). Flow cytometry tests are used to confirm the diagnosis by assessing for absence of the CD55 and CD59 proteins on the surface of red blood cells. Parvovirus B19 Viral arthritis due to parvovirus B19 is characterized by acute, symmetric, small-joint arthralgias, mild joint swelling, and a benign, self-limited course. It is usually seen in adults, whereas erythema infectiosum due to parvovirus B19 is more common in children. Peptic ulcer disease (PUD) PUD can be complicated by perforation, which typically causes acute-onset, severe pain; a systemic inflammatory response (e.g., fever, tachycardia); and peritonitis. Upright x-ray of the chest and abdomen can confirm the diagnosis of perforation by revealing subdiaphragmatic free air. Pericarditis Patients with acute viral (or idiopathic) pericarditis should be initially treated with a combination of NSAIDs (e.g., ibuprofen) and colchicine, as colchicine lowers the rate of recurrent pericarditis. - Corticosteroids (e.g., prednisone) are second-line therapy for these patients. Uremic pericarditis can occur in patients with BUN >60 mg/dL. - It presents like other etiologies of acute pericarditis except that classic ECG findings (i.e., diffuse ST-segment elevation and PR-segment depression) are typically absent (because the inflammation from uremic pericarditis does not involve the myocardium). - Dialysis is the best treatment. Peripheral artery disease (PAD) The pathophysiology of PAD and coronary artery disease (CAD) is similar, and the presence of PAD is considered a CAD risk equivalent. Therefore, patients diagnosed with PAD should undergo aggressive management—antiplatelet, highintensity statin and lifestyle modification—of cardiovascular risk factors to reduce the risk of MI and stroke. Both low-dose aspirin and statin therapy are indicated for secondary prevention of cardiovascular events in all patients with known atherosclerotic cardiovascular disease (ASCVD). PAD is a manifestation of ASCVD, as is MI, stable or unstable angina, coronary or other arterial revascularization, and stroke or TIA. Pertussis Pertussis manifests as a stepwise illness beginning with 1-2 weeks of nonspecific symptoms and progressing to a paroxysmal cough. A normal lung exam and absence of fever are typical. Rib fractures can occur with vigorous coughing episodes, and lymphocytepredominant leukocytosis (in response to B pertussis cytotoxin) is classic. Pill esophagitis Pill esophagitis is due to a direct effect of certain medications on esophageal mucosa. Tetracyclines, potassium chloride, bisphosphonates, and NSAIDs are common causes. Patients experience sudden-onset odynophagia and retrosternal pain that can sometimes cause difficulty swallowing. Pleural effusion Undiagnosed pleural effusion is best evaluated with thoracentesis, except in patients with clear-cut evidence of congestive heart failure (trial of a diuretic). *Extremely HY question for USMLE!!! Lung carcinoma, breast carcinoma, and lymphoma are the three tumors that cause ~75% of all malignant pleural effusions. Pleural effusion insulates sound and vibration originating within the lung parenchyma. - Physical exam of patients with a pleural effusion typically shows breath sounds, tactile fremitus, and dullness to percussion over the effusion. Pneumocystis pneumonia (PCP) Manifestations of Pneumocystis pneumonia (PCP) in patients with HIV are usually indolent and include nonproductive cough, exertional dyspnea, fever, hypoxia, elevated lactate dehydrogenase, and bilateral interstitial infiltrates. TMP-SMX is the first-line treatment. - Concomitant corticosteroids are administered to reduce risk of respiratory decompensation for those with: o PaO2 ≤70 mm Hg, o A-a gradient ≥35 mm Hg, or o Pulse oximetry <92% on room air. Polymyalgia rheumatica Polymyalgia rheumatica is an inflammatory disorder that occurs in patients age 50. It is characterized by aching pain and stiffness in the hips and shoulders, along with systemic symptoms (fever, malaise, fatigue, weight loss). The diagnosis is suggested by inflammatory markers (e.g., ESR, CRP) The condition responds rapidly to low-dose glucocorticoid therapy (e.g., prednisone 20 mg daily). ~10% of cases are associated with giant cell arteritis (e.g., headache, jaw claudication, visual symptoms). Primary adrenal insufficiency (PAI) Autoimmune adrenalitis is the most common cause (>90%) of PAI in developed countries. The key differentiating features of PAI from central/secondary adrenal insufficiency are the hyperpigmentation and hyperkalemia seen in PAI. Chronic PAI presents with weight loss, fatigue, and GI symptoms. - Volume depletion and reduced vascular tone can cause hypotension and syncope. - Most patients have hyponatremia due to renal Na loss and increased secretion of ADH (non-osmotic stimulus for release from volume loss + reduced inhibition by cortisol). - Hyperkalemia is also common due to renal K retention in the setting of aldosterone deficiency. Primary hyperaldosteronism (Conn syndrome) In 1º hyperaldosteronism, autonomous aldosterone secretion results in an elevated plasma aldosterone/renin ratio. Hypokalemia is often present, and serum Na+ is typically in the high end of normal range. Patients with an adrenal adenoma who are not surgical candidates and those who decline surgery are treated with a mineralocorticoid receptor antagonist (e.g., spironolactone, eplerenone). Primary sclerosing cholangitis (PSC) PSC is characterized by fibrosis and stricturing of the medium and large intra- and extrahepatic bile ducts, promoting cholestasis and acute cholangitis. It occurs most commonly in men and is strongly associated with ulcerative colitis. Patients may have normal ultrasonography because intrahepatic bile ducts are not easily visible. Magnetic resonance cholangiopancreatography (MRCP) overcomes this limitation and is the preferred test to confirm the diagnosis in these patients. Management of PSC includes endoscopic interventions for strictures, therapy for coexisting ulcerative colitis, antibiotics for cholangitis (with some patients maintained on long-term antibiotic therapy), and, in some cases, ursodeoxycholic acid. Pseudofolliculitis barbae (PB) PB presents with small, painful papules in the beard area. It is caused by penetration of the hair shaft into interfollicular skin, often due to shaving of tightly curled hair. Complications include hyperpigmentation, secondary bacterial infection, and keloid formation. Management includes discontinuation of shaving or use of alternative shaving techniques. Pseudogout (acute calcium pyrophosphate crystal arthritis) Pseudogout is an acute inflammatory arthritis caused by calcium pyrophosphate dihydrate (CPPD) crystals. It often occurs in the setting of surgery or medical illness. Pseudogout is diagnosed with synovial fluid showing rhomboid-shaped, positively birefringent crystals and radiographic evidence of chondrocalcinosis (calcified articular cartilage). Pulmonary embolism (PE) The manifestations of PE are nonspecific and variable. The diagnosis should be suspected in any patient who presents with sudden-onset shortness of breath (~73%) and pleuritic chest pain (~66%). - Tachypnea (~55%), tachycardia, hypoxemia, low-grade fever (~5%) and jugular venous distension (~15%) are common exam findings. - Classic (but infrequent) ECG finding is the S1-Q3-Tinv3. - Classic (but infrequent) CXR findings include the Hampton hump and Westermark sign. Atrial fibrillation is commonly associated with PE, either as a cause (emboli from right atrial appendage) or a result (PE-induced right atrial dilation or sympathetic tone). A normal D-dimer result is useful in excluding pulmonary venous thromboembolism (VTE) in patients with unlikely pretest probability. - However, a normal D-dimer result is not useful in patients with likely pretest probability. An elevated D-dimer result in any patient is not diagnostic of VTE and must be followed by more specific studies. Patients with massive pulmonary embolism usually present with signs of low arterial perfusion (e.g., hypotension, syncope) and acute dyspnea, pleuritic chest pain, and tachycardia. - The thrombus increases pulmonary vascular resistance and right ventricular pressure, causing right ventricular hypokinesis and dilation and hypotension. Pulmonary emboli classically present with sudden-onset pleuritic chest pain, cough, and dyspnea. Hemoptysis can occur as a result of pulmonary infarction. Chest CT scan showing a peripheral, wedge-shaped infarction is virtually pathognomonic for pulmonary embolism. Rheumatoid arthritis (RA) RA can cause exudative pleural effusions (inflammatory disruption of vascular permeability) characterized by low glucose, very high LDH, and (often) low pH and is associated with interstitial lung disease and pulmonary nodules. Patients with rheumatoid arthritis are at increased risk of developing osteopenia, osteoporosis, and bone fractures. - Management includes adequate physical activity, optimization of calcium and vitamin D intake, steroids, and bisphosphonate treatment. Sjögren syndrome The diagnosis of Sjögren syndrome requires evidence of dry mouth and eyes (e.g., positive Schirmer test result for decreased lacrimation) with either histologic evidence of lymphocytic infiltration of the salivary glands or serum autoantibodies against SSA (Ro) and/or SSB (La). Sjögren syndrome is an autoimmune disorder characterized by inflammation of the exocrine glands. Typical features include dry mouth, autoimmune sialadenitis, and keratoconjunctivitis sicca. Extraglandular features include arthritis, Raynaud phenomenon, dyspareunia, cutaneous vasculitis, interstitial lung disease, and non-Hodgkin lymphoma. Solitary pulmonary nodule Evaluation of a solitary pulmonary nodule detected on chest x-ray includes comparison with old imaging studies, if available, followed usually by chest CT. The decision to observe, biopsy, or surgically resect the nodule is based on its size and characteristics as well as the patient's age and smoking history. Stevens-Johnson syndrome/Toxic epidermal necrolysis (SJS/TEN) SJS/TEN represents an inflammatory reaction to drugs or certain infections and is characterized by coalescing erythematous macules, bullae, desquamation, and mucositis. Systemic signs include fever, hemodynamic instability, and altered level of consciousness. Supraventricular tachycardia Patients with persistent tachyarrhythmia (narrow or wide complex) causing hemodynamic instability with a pulse should undergo immediate synchronized cardioversion. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) Pulmonary pathology may lead to SIADH, which is characterized by hypotonic hyponatremia in a euvolemic patient. Infusion of normal saline may worsen hyponatremia in patients with SIADH. Syncope Patients with syncope not clearly attributable to a benign etiology (e.g., reflex or orthostatic syncope) should undergo further cardiac workup to determine whether a cardiac etiology is present. Syncope that occurs while supine or sitting, at rest, and without warning symptoms suggests an arrhythmic etiology. Continuous ECG monitoring can evaluate for transient arrhythmia (e.g., ventricular tachycardia) that may not be detected on initial ECG. - In relatively young patients (e.g., age <40) without structural heart disease, ambulatory ECG monitoring (e.g., Holter monitor, insertable cardiac monitor) is usually appropriate. - In contrast, patients likely need hospital admission for closer monitoring and expedited cardiac evaluation when they have/are: o Older o Underlying structural heart disease (e.g., prior MI), or o An abnormal ECG Syphilis A single dose of intramuscular benzathine penicillin G is the treatment of choice for early syphilis. However, patients with severe penicillin allergy (who do not have neurosyphilis) generally require an alternate regimen such as oral doxycycline or IV/IM ceftriaxone. All patients with syphilis should have pretreatment serology with a nontreponemal test (e.g., rapid plasma reagin) to quantitate antibody titers. - A 4-fold decrease in antibody titers at 6-12 months indicates treatment success. Systemic sclerosis Scleroderma renal crisis typically presents with acute renal failure (without previous kidney disease) and malignant hypertension (e.g., headache, blurry vision, nausea). Urinalysis may show mild proteinuria. Peripheral blood smear can show microangiopathic hemolytic anemia or DIC with fragmented RBCs (e.g., schistocytes) and thrombocytopenia. Temporomandibular joint disorder (TMD) TMD can result in referred pain to the ear that is worse with chewing and on awakening. Patients typically have a history of nocturnal teeth grinding (joint trauma). Patients with psychiatric illness (e.g., GAD) may be at increased risk. Management includes education, a soft diet, warm compresses, and avoidance of triggers. NSAIDs (e.g., naproxen) are the first-line medication. - Muscle relaxants (e.g., cyclobenzaprine) can be added for patients with associated muscle spasm. Tertiary hyperparathyroidism Patients with long-standing chronic kidney disease often have hypocalcemia and hyperphosphatemia, which can lead to chronic parathyroid stimulation. Over time, this can cause parathyroid hyperplasia and autonomous parathyroid hormone (PTH) secretion. The net effect, termed tertiary hyperparathyroidism, is characterized by hypercalcemia, hyperphosphatemia, and extremely high serum PTH levels. Treatment is parathyroidectomy (usually unresponsive to medical therapy). Tinea Tinea corporis (“ringworm”) is a cutaneous dermatophyte infection that causes a pruritic rash with a scaly, erythematous border and central clearing. - Patients often have concurrent infection elsewhere on the body, hands, groin, or feet. - Those with immunocompromising conditions (e.g., HIV, diabetes mellitus) can have severe or widespread disease. Tinea pedis most commonly involves the skin between the toes but can extend to involve the souls and sides of the feet (moccasin pattern), often with significant hyperkeratosis and flaking. A KOH preparation of skin scrapings showing branched, segmented hyphae is diagnostic. Treatment includes topical antifungals (e.g., miconazole, terbinafine, tolnaftate). Torsade de pointes (TdP) TdP is a type of polymorphic ventricular tachycardia precipitated by a prolonged QT interval. Immediate electrical cardioversion is indicated for hemodynamically unstable patients with TdP. IV magnesium is first-line therapy for stable patients. Tuberculosis (TB) Mycobacterium tuberculosis takes several (3-8) weeks to grow in culture (gold standard). To reduce the risk of transmission and progression, patients with a high pretest probability of pulmonary TB require empiric 4-drug treatment with RIPE (rifampin, isoniazid, pyrazinamide, and ethambutol) while awaiting culture results. Although rapid testing (e.g., acid fast bacilli stain) supports the diagnosis, several samples are required to achieve adequate sensitivity (1 sample ~50%, 3 spaced samples ~85%). Tuberculin skin testing can be used to identify patients with latent tuberculosis infection. - In the US, an induration size <15 mm is considered negative (i.e., ≥15 mm is considered positive) in healthy patients with a low likelihood of TB infection. Ulcerative colitis (UC) UC most commonly develops between ages 15 and 40, but it can be diagnosed at any age. Symptoms include abdominal pain, bloody diarrhea, tenesmus, and fecal incontinence. Colonoscopy or flexible sigmoidoscopy demonstrates continuous colonic involvement with ulcers and erythematous, friable mucosa. Urinary tract infection (UTI) Uncomplicated UTI refers to infection confined within the bladder and is confirmed with urinalysis. - Patients can be treated empirically without a urine culture; effective first-line treatment options include oral TMP-SMX, nitrofurantoin, and fosfomycin. Complicated UTI refers to infections that extend beyond the bladder, but these infections require urine culture prior to treatment initiation. Vasovagal syncope Vasovagal syncope is a type of reflex syncope typically preceded by a trigger (e.g., strong emotion) and a prodrome (e.g., pallor, light-headedness). A neurally mediated reflex response (cardioinhibitory and vasodepressor) leads to brief (e.g., <1-2 min) loss of consciousness, followed by rapid and complete recovery. SOCIAL SCIENCES/ETHICS SOCIAL SCIENCES/ETHICS Advance directive/surrogate decision maker In the absence of an advance directive, decision-making for an incapacitated patient is based on the principle of the substituted judgment standard. The surrogate decision maker is obligated to base medical decisions on his or her best judgment of what the patient would have chosen. Cesarean delivery Patients may desire a cesarean delivery in the absence of maternal or fetal indications. Physicians who are uncomfortable performing cesarean deliveries on maternal request should refer these patients to another OB-GYN. Complementary and alternative medicine The US FDA has only limited regulatory authority regarding complementary and alternative medicine supplements, which often have poor manufacturing standards. Third-party review organizations (e.g., US Pharmacopeia) may have independent information for some products and can be used to guide patient choice. When discussing a patient's use of nonstandard therapies that are known to be harmful, the physician should clearly explain the risks to the patient. If the patient insists on using such therapies, the physician should schedule close follow-up to strengthen the therapeutic alliance and monitor for toxicity. Cultural considerations Cross-cultural care improves health outcomes and communication in diverse populations. It involves components of high-value care common to all populations, including patient-centeredness (i.e., exploring an individual patient's beliefs), avoidance of stereotyping, and cultural sensitivity (responding to a patient's sociocultural paradigm). Disclosing adverse events When a serious adverse event occurs during treatment, all physicians involved in the patient’s care should collectively disclose the event to the family. A cooperative discussion can increase transparency, promote continuity of care, and facilitate an efficient response to patient and family questions and concerns. End of life care Some patients and families have the misconception that hospice enrollment hastens death. However, hospice does not shorten life expectancy but allows patients to die a natural death, usually at home and with a better quality of life than without hospice services. The hospice model of care is designed to optimize comfort and quality of life for patients with terminal illness. Patients enrolling in hospice services may continue treatments that are intended for relief of symptoms (e.g., palliative radiotherapy), but not those that are curative or intended to prolong life. Although dialysis extends life expectancy in younger patients with limited comorbidity, that benefit becomes negligible in elderly patients with significant comorbidity and functional decline. - In elderly patients with end-stage renal disease, especially those with advanced comorbidities and functional decline, chronic dialysis does not significantly extend life expectancy when compared to conservative kidney care; it is associated with increased hospitalizations and diminished quality of life. These factors should be discussed prior to initiation of dialysis. Ethical principles in healthcare Ethical principles (i.e., autonomy, beneficence, nonmaleficence, justice) can often conflict with each other in patient care. Typically, respect for patient autonomy does not supersede the ethical principle of nonmaleficence, or a physician's duty to first do no harm. Therefore, patient requests for a specific treatment should not be fulfilled if the treatment is medically inappropriate or causes unacceptable patient harm. Handling distractions Distractions (e.g., interruptions) are unavoidable in health care, and they increase cognitive overload and risk of error. Whenever possible (e.g., non-emergency situations), physicians should manage interruptions in a way that minimizes unnecessary task-switching and multitasking. Informed consent Patients with psychiatric diagnoses can give informed consent provided they have capacity, meaning that their judgment and decision-making abilities are determined to be intact at the time of treatment. When caring for an unemancipated minor, informed consent from one parent or guardian is considered legally sufficient to justify proceeding with therapy. - Physicians should also provide care in urgent situations without waiting for parental consent. Genetic testing in children should consider the best interests of the child. When there is no impact on the child's medical management or prognosis, genetic testing to predict future disease risk should be deferred until adulthood to ensure informed consent. Medication prescribing in elderly patients The number of physicians prescribing medications for an elderly patient should be minimized, when possible, to lower the risk for adverse drug events. Primary care providers should work closely with specialists and often can prescribe majority of their patients' medications. Psychological safety Psychological safety refers to team members' comfort in taking actions (e.g., openly voicing concerns, asking for help) for safe patient outcomes. Psychological safety is hindered by strict hierarchy or fear of retribution and can be promoted by organizational initiatives such as change management (i.e., engaging front-line personnel in improving organizational culture). Reducing antibiotic use in viral infections & chronic bronchitis The clinician should express awareness of patients’ symptoms and concern for their well-being and probe their understanding of the illness and the self-limited nature of the infection. Referring to the illness as a “chest cold” may alleviate patients’ anxiety that their infection requires antibiotics. The clinician should also discuss the risks and adverse effects of antibiotics. Reducing errors in patient handoffs Verbal handoffs during transfers of care necessitate exchanging the large amount of information in the limited time. To minimize communication errors, handoff discussions should: - prioritize patients with highest medical acuity. - confirm accurate comprehension of critical information (e.g., selective readback), and - follow a structured (checklist) and interactive (ask questions as you go) approach. Refusal of treatment Patients have the right to refuse treatment except when doing so poses a serious threat to public health. In these cases, the physician is justified in restricting individual liberties until the public's health is no longer at risk. In general, adult patients with intact decision-making capacity have the right to refuse treatment, even if it would be life-saving. However, protection of individual patient rights (patient autonomy) must be balanced with a physician's duty to protect the health of the public by mandating hospitalization and isolation of patients with a communicable disease. Research ethics Special considerations apply to research involving minors (age <18). Research protocols should address how the investigators will obtain informed consent from parents and legal guardians as well as age-appropriate assent to participate from minors. QUALITY IMPROVEMENT QUALITY IMPROVEMENT BIOSTATISTICS BIOSTATISTICS Confounding, Effect modification, Bias, Errors Randomization is used to control for confounders during the design stage of a study. It helps to control for known, unknown, and difficult-to-measure confounders. Berkson bias is a type of selection bias that occurs when controls are chosen from among hospitalized patients only, resulting in a potential bias (e.g., hospitalized controls may have an exposure related to the outcome of interest) and limiting generalizability. Differential loss to follow-up is a subtype of selection bias and represents a threat to the internal validity of a study. Confounding refers to the bias that can result when the exposure-disease relationship is mixed with the effect of extraneous factors (i.e., confounders). Number needed to treat (NNT) The interpretation of the NNT should always include information about the comparison group, the specific outcome, and the period of observation for the outcome. NNT values for the same intervention or treatment will vary depending on the outcome, the period of observation, and the comparison group used. For example, “compared with placebo, 10 patients need to be treated with mercaptopurine after surgical resection to prevent 1 additional clinical recurrence within 3 years of treatment.” Power and sample size Power describes a study’s ability to detect an effect (e.g., difference between groups) when one truly exists. Power is influenced by 4 factors, as follows: - sample size, power - outcome variability, power - effect size, power - significance level (alpha value), power P-value and confidence interval A confidence interval (CI) always contains the sample value at the center of the interval. A CI that excludes a null value is statistically significant. Receiver operating characteristic (ROC) The ROC curve of a quantitative diagnostic test demonstrates the trade-off between the test's sensitivity and specificity at various cutoff points. Changing the cutoff point to increase the true-positive rate (directly proportional to sensitivity) will also increase the false-positive rate (inversely proportional to specificity). Risk Risk is the probability of developing a disease over a certain period of time. To calculate the risk, divide the number of exposed subjects with the disease by the total number of exposed subjects (i.e., all subjects at risk). Sensitivity and specificity Changing the cutoff point of a quantitative diagnostic test will inversely affect its sensitivity and specificity. Typically, raising the cutoff value will increase specificity (fewer false positives) and decrease sensitivity (more false negatives). Screening tests need high sensitivity. Confirmatory tests need high specificity. Study designs In ecological studies, the unit of observation is the population. Disease rates and exposures are measured in each of a series of populations, and their association is determined. Therefore, results about associations at the population level may not translate to the subject level. The ecological fallacy assumes that individuals of a population all have the average characteristics of the population as whole, but any association observed between variables at the population level does not necessarily mean that the same association exists for any individual selected from the population.
