HARRISON 19TH Description: Nothing prepares you for exam success like Harrison’s Vibrant fullcolor presentation includes color atlas — 500 allnew questions Now you can add the unmatched authority of Harrison’s to your board review or test preparation. Based on the content of Harrison’s Principles of Internal Medicine, Nineteenth Edition, this rigorous study aid is essential for Internal Medicine Board certification or recertificationmaintenance of certification, or as a refresher for any internal medicine examination. Reflecting the accuracy, currency, and wide scope of Harrison’s, this complete review of internal medicine delivers more than 1,000 extremely challenging review questions, many of which utilize realistic patient scenarios, including radiographic and pathologic images. Each question is accompanied by explanations for correct and incorrect answers. These explanations — which are derived from and crossreferenced to Harrison’s Principles of Internal Medicine, Nineteenth Edition — are one of the most effective ways to learn and teach internal medicine. They are designed to bolster your understanding of pathophysiology, epidemiology, differential diagnosis, clinical decision making, and therapeutics. The format of the book has also been enhanced, allowing for a more effective use of color images throughout. Readers will appreciate the convenience of having color images next to their citations in the text. A great way to learn internal medicine: • Coverage spans the entire spectrum of internal medicine • Each topic is covered in proportion to its level of importance on the Internal Medicine Examination Blueprint • Approximately 500 NEW, neverbeforepublished QAs (more than 60% of the questions are NEW) • Includes fullcolor atlas • Content follows the organization of Harrison’s Principles of Internal Medicine, Nineteenth Edition — making it perfect for sidebyside study • Beautiful fullcolor presentation
19th Edition ‘HAISON’S P L E IN T 0E H N A0L M E D | C | N E SELF-ASSESSMENT AND BOARD REVIEW WIENER KASPER h ' Ml: ' Graw Hill Education by Dr Nigam Rashmi Dhar for free pdf ebooks notes mcq join free whatsapp medical grp LOSCALZO 009779804202884 SECTION I General Considerations in Clinical Medicine QUESTIONS DIRECTIONS: Choose the one best response to each question I-1 All of the following statements regarding practice guidelines set forth by governing agencies and professional organizations are true EXCEPT: A B C D E Clinical practice guidelines protect caregivers against inappropriate charges of malpractice, yet not provide protection for patients from receiving substandard care Practice guidelines have largely reached a stage of nuance allowing them to address every unique illness and patient presented to the modern physician Practice guidelines provide a legal constraint to physicians, and deviation from guideline-based care invariably leaves physicians vulnerable to legal action Where different organizations disagree regarding practice guidelines, a third-party agency has been appointed to mitigate these disagreements such that now all major organizations’ guidelines are consistent All of the above statements are not true I-2 Regarding molecular medicine, which of the following statements represents an INACCURATE example of the listed area of study: A Exposomics: An endocrinologist studies sunlight exposure and population risk of hip fracture B Metabolomics: A biochemist studies the rate of flux through the creatine kinase pathway during the cardiac cycle C Metagenomics: A biologist studies the genomic alterations in molds commonly found in human dwellings D Microbiomics: A microbiologist studies the genomic variation in thermophiles, bacteria that can survive extreme heat near deep ocean vents E Proteomics: A cardiologist studies desmosomal proteins and their posttranslational modifications in studying arrhythmogenic right ventricular dysplasia I-3 Which of the following is the best definition of evidence-based medicine? A B C D E A summary of existing data from existing clinical trials with a critical methodologic review and statistical analysis of summative data A type of research that compares the results of one approach to treating disease with another approach to treating the same disease Clinical decision-making support tools developed by professional organizations that include expert opinions and data from clinical trials Clinical decision making supported by data, preferably randomized controlled clinical trials One physician’s clinical experience in caring for multiple patients with a specific disorder over many years I-4 Which of the following is the standard measure for determining the impact of a health condition on a population? A B C D E Disability-adjusted life-years Infant mortality Life expectancy Standardized mortality ratio Years of life lost I-5 Which of the following statements regarding disease patterns worldwide is true? A Childhood undernutrition is the leading risk factor for global disease burden B In a 2006 publication, the World Health Organization (WHO) estimated that 10% of the total global burden of disease was due to modifiable environmental risk factors C In 2010, ischemic heart disease was the leading cause of death among adults D In the last two decades, mortality attributed to communicable diseases, maternal and perinatal conditions, and nutritional deficiencies has remained fairly stable, with the majority (76%) of mortality from these causes occurring in sub-Saharan Africa and southern Asia E While poverty status has been shown to be linked to health status on the individual level, the same relationship does not hold true when studying the link between national health indicators and gross domestic product per capita among nations I-6 You are appointed to a governmental healthcare advisory subcommittee concerned with addressing problems facing the global health community Your task is to draw general conclusions from the global fight against tuberculosis (TB) and human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) that may be applied in combatting other diseases, including noncommunicable diseases Which of the following conclusions is reasonable when considering HIV/AIDS and TB as chronic diseases? A B C D E Barriers to adequate healthcare and patient adherence imposed by extreme poverty must be concomitantly addressed to adequately treat and prevent chronic disease in developing nations Charging small fees for health services (e.g., AIDS prevention and care) supplies the patient with a sense of the treatment’s value and increases compliance and overall public health Despite adequate available tools to practice their trade locally in developing nations, many physicians and nurses emigrate to developed nations to practice their respective trades, a phenomenon called “brain drain.” In developed nations where physicians are abundant, community health worker supervision of the care of chronically ill patients is not effective In the case of chronic infectious diseases, switching from one drug to another through a prolonged course of treatment provides the highest cure rate by obviating the infectious agent’s ability to develop resistance to any single drug I-7 Mrs Jones, a 22-year-old African American woman, presents to Dr Smith, an internal medicine specialist, with a facial rash Mrs Jones states that the rash began after spending a day at the beach with her family She also notes that her metacarpophalangeal and proximal interphalangeal joints have been painful and swollen for the preceding weeks On examination, the joints are swollen and tender Laboratory analysis discloses reduced creatinine clearance, proteinuria, and hemolytic anemia Antinuclear antibodies (a test with a high negative predictive value for systemic lupus erythematosus) are detected at significant titer, and ultimately, the diagnosis of systemic lupus erythematosus is made Two weeks later, Mrs Johnson, a 24-year-old African American woman, presents with a facial rash and elbow pain to Dr Smith After a cursory interview and brief physical exam, Dr Smith sends blood work only testing for antinuclear antibodies When the test returns negative (no antibodies detected), Dr Smith presumes this to be a false-negative result and starts Mrs Johnson on hydroxychloroquine and prednisone for treatment of systemic lupus erythematosus Which heuristic(s) did Dr Smith likely employ in diagnosing Mrs Johnson with systemic lupus erythematosus? A B C D E Availability heuristic Anchoring heuristic Bayes’ rule Confirmation bias A and B I-8 You have invented a blood test, which you name “veritangin,” to determine if patients are having a myocardial infarction You devise an experiment to determine the performance of your veritangin assay by testing it versus the troponin assay, the currently accepted gold standard for determining myocardial infarction, in 100 random emergency department patients with chest pain You choose a veritangin result >1 ng/dL as positive for myocardial infarction Your results are listed in the table below Which of the following statements regarding the characteristics of the veritangin assay in this trial is true? A The posttest probability of the veritangin test does not depend on the population studied B The sensitivity of the veritangin assay depends on the population studied and the disease prevalence in that population C The sensitivity of the veritangin assay will decrease by 50% if you reduce the threshold for a positive result to >0.5 ng/dL D The sensitivity of the veritangin test cannot be calculated based on the above data E The specificity of the veritangin assay is 0.93 (70/75) I-9 You are designing a clinical trial to test the use of a novel anticoagulant, clotbegone, in the treatment of deep vein thrombosis Which of the following statements regarding the design of the trial is true? A B C D E An optimal study design would assign many patients to clotbegone and compare their outcomes to the outcomes of prior (historical) patients not taking clotbegone This would allow faster trial completion If the trial returns a positive result (clotbegone is superior to placebo), that means that any patient with a clot would benefit from clotbegone therapy Observing the outcomes of patients already taking clotbegone versus patients who are not is preferable to assigning patients to clotbegone or placebo in a blinded fashion The observational strategy is more “real world,” applicable to the general population, and free of bias Population selection for the trial enrollment is not important as long as careful attention to randomization and blinding is observed The advantage of performing a randomized clinical trial of clotbegone over a prospective observational study of clotbegone is the avoidance of treatment selection bias I-10 A receiver operating characteristic (ROC) curve is constructed for a new test developed to diagnose disease X All of the following statements regarding the ROC curve are true EXCEPT: A One criticism of the ROC curve is that it is developed for testing only one test or clinical parameter with exclusion of other potentially relevant data B ROC curve allows the selection of a threshold value for a test that yields the best sensitivity with the fewest false-positive tests C The axes of the ROC curve are sensitivity versus – specificity D The ideal ROC curve will have a value of 0.5 E The value of the ROC curve is calculated as the area under the curve generated from the truepositive rate versus the false-positive rate I-11 When considering a potential screening test, what end points should be considered to assess the potential gain from a proposed intervention? A B C D E Absolute and relative impact of screening on the disease outcome Cost per life-year saved Increase in the average life expectancy for the entire population Number of subjects screened to alter the outcome in one individual All of the above I-12 You are appointed to an advisory committee in the WHO tasked with making recommendations regarding breast cancer screening and prevention In regard to screening and preventing breast cancer in women, which of the following potential recommendations from your committee would be valid? A B C D E Any breast cancer detected by screening mammography and adequately treated represents a reduction in breast cancer mortality Screening is most effective when applied to relatively common diseases Breast cancer, with a lifetime risk of 10% in women, meets this criterion The presence of a latent (asymptomatic) stage of breast cancer renders it a less ideal disease candidate for screening at the population level When studying the effectiveness of breast cancer screening with mammography in a population, length of disease survival is the most important outcome to consider Women in the general population should undergo just as rigorous screening and prevention measures for breast cancer as women with the BRCA1 or BRCA2 mutations I-13 You are seeing Mr Brown today in the primary care clinic He has a long history of tobacco abuse, and you notice on his intake form that he wishes to discuss lung cancer screening today Which of the following statements regarding lung cancer screening can you truthfully make to Mr Brown? A B C D E “Recently, a large National Heart, Lung, and Blood Institute study demonstrated a significant reduction in mortality by employing low-dose chest computed tomography as a screening tool in patients with a significant smoking history.” “Screening for lung cancer has a long history of successful implementation given the ease of obtaining a chest x-ray and the fact that most lung cancers are curable at the time of screening detection.” “Screening for lung cancer is a ‘no-brainer’; there is really no harm in a false-positive test The only real worry is always that you might have a cancer that we don’t know about.” “Because the sensitivity and specificity of any screening test not depend on the population studied, your odds of having lung cancer after a positive chest x-ray not depend on his smoking history.” “There is really no evidence of benefit for lung cancer screening by any modality.” I-14 Which preventative intervention leads to the largest average increase in life expectancy for a target population? A B C D E A regular exercise program for a 40-year-old man Getting a 35-year-old smoker to quit smoking Mammography in women age 50–70 Pap smears in women age 18–65 Prostate-specific antigen (PSA) and digital rectal examination for a man >50 years old I-15 The U.S Preventive Services Task Force (USPSTF) recommends which of the following screening tests for the listed patients? A 16-year-old male: immunoassay for HIV if not performed before B 32-year-old sexually active woman: nucleic acid amplification on a cervical swab for chlamydia C 50-year-old woman with a smoking history: dual-energy x-ray absorptiometry (DEXA) scan for osteoporosis D 58-year-old prior smoker: ultrasound for abdominal aortic aneurysm E 80-year-old man: anti–hepatitis C virus (HCV) antibody for hepatitis C I-16 Patients taking which of the following drugs should be advised to avoid drinking grapefruit juice? A B C D E Amoxicillin Aspirin Atorvastatin Prevacid Sildenafil I-17 A 26-year-old woman received an allogeneic bone marrow transplantation months ago for acute myelogenous leukemia Her transplant course is complicated by graft-versus-host disease with diarrhea, weight loss, and skin rash She is immunosuppressed with tacrolimus mg twice a day (bid) and prednisone 7.5 mg daily She recently was admitted to the hospital with shortness of breath and fevers to 101.5°F She has a chest computed tomography (CT) showing nodular pneumonia, and fungal organisms are seen on a transbronchial lung biopsy The culture demonstrates Aspergillus fumigatus, and a serum galactomannan level is elevated She is initiated on therapy with voriconazole mg/kg IV every 12 hours for day, decreasing to mg/kg IV every 12 hours beginning on day Two days after starting voriconazole, she is no longer febrile but is complaining of headaches and tremors Her blood pressure is 150/92 mmHg, up from 108/60 mmHg on admission On examination, she has developed 1+ pitting edema in the lower extremities Her creatinine has risen to 1.7 mg/dL from 0.8 mg/dL on admission What is the most likely cause of the patient’s current clinical picture? A B C D E Aspergillus meningitis Congestive heart failure Recurrent graft-versus-host disease Tacrolimus toxicity Thrombotic thrombocytopenic purpura caused by voriconazole I-18 A 43-year-old woman is diagnosed with pulmonary blastomycosis and is initiated on therapy with oral itraconazole therapy All of the following could affect the bioavailability of this drug EXCEPT: A B C D E Coadministration with a cola beverage Coadministration with oral contraceptive pills Formulation of the drug (liquid vs capsule) pH of the stomach Presence of food in the stomach I-19 Mr Jonas is a 47-year-old truck driver with a history of HIV, hypertension, coronary artery disease, atrial fibrillation, and ischemic cardiomyopathy He is on antiretroviral therapy He presents today complaining of a new rash on his chest and axilla, which you astutely diagnose as tinea corporis You would like to prescribe a course of oral ketoconazole for therapy You should consider dose adjustment for all of the following medicines that he is already taking EXCEPT: A B C D E Carvedilol Lovastatin Mexiletine Ritonavir Saquinavir I-20 Which of the following pharmacokinetic concepts is accurate? A After four half-lives of a zero-order drug, 93.75% of drug elimination is achieved B Elimination half-life is the sole determinant of the time required for steady-state plasma concentrations to be achieved after any change in drug dosing C First-order elimination refers to the priority a drug has for its elimination enzyme versus drugs of alternative orders For example, a first-order drug will have a higher affinity for the enzyme than a second-order drug D Steady state describes the situation during chronic drug dosing when the plasma concentration of drug is identical from minute to minute One can only truly achieve steady state with continuous intravenous infusion E The only method by which a drug can be removed from the central compartment is by elimination I-21 Mr Brooks has been seeing you in the primary care clinic for over 20 years Recently, he was diagnosed with amyotrophic lateral sclerosis (ALS), an almost universally fatal degenerative neurologic condition In consultation with his neurologist, you have started him on a high dose of a new medication, Drug X, to alleviate muscle spasms However, although Mr Brooks’s muscle spasms have improved drastically, he is experiencing dry mouth and dry eyes, side effects that were not described in very large clinical trials of Drug X A recent postmarketing study of Drug X was released showing that patients with ALS taking it live, on average, 14 days less than patients not taking it As you discuss the plan regarding Drug X with Mr Brooks, which statement would be valid? A B C D E “A recent study shows that patients taking Drug X die sooner, on average, than those not taking it I want to discuss your thoughts on continuing Drug X, perhaps at a lower dose, versus stopping it.” “A recent study shows that patients taking Drug X die sooner, on average, than those not taking it I recommend stopping it, and I anticipate the drug will be discontinued soon.” “If you’re having side effects at the high dose, it’s certain that you’ll have the same side effects at a lower dose.” No discussion is needed given the postmarketing data You should stop Drug X and report the new side effect to the U.S Food and Drug Administration (FDA) “These side effects you describe were not described in clinical trials enrolling hundreds of patients with ALS They cannot be from Drug X Let’s figure out what other medication might be causing them.” I-22 The graph below represents a plasma time-concentration curve after a single dose of Drug A Which of the following statements regarding Figure I-22A is true? by Dr Nigam Rashmi Dhar for free pdf ebooks notes mcq join free whatsapp medical grp 009779804202884 FIGURE I-22A A This drug was likely administered orally B This drug demonstrates zero-order kinetics C The shift in rapid reduction in plasma concentration to a more gradual reduction (point B) likely represents a saturation of the eliminating enzyme D Point B represents the time when drug is distributed both to and from a peripheral compartment and eliminated from the central compartment E This drug does not have a half-life given the curvilinear shape of its elimination curve I-23 All of the following patients are correctly matched to the drug and dose adjustment that should be considered given their concomitant listed comorbidity EXCEPT: A B C D E A 57-year-old man with cirrhosis: reduced dose of sotalol A 35-year-old man with renal disease: reduced dose of meperidine A 97-year-old man with normal creatinine and bilirubin: reduced dose of diazepam A 42-year-old man with cirrhosis: reduced dose of meperidine A 35-year-old woman with a known loss-of-function allele in CYP2C9: reduced initial dose of warfarin I-24 Which of the following sets of drug–drug interaction and mechanism is accurately described? A Ibuprofen and warfarin: increased risk of GI bleeding; ibuprofen inhibition of CYP2C9 B Sotalol and furosemide: increased risk of QT prolongation and torsades de pointes; furosemideinduced inhibition of CYP3A4 C Sildenafil and sublingual nitroglycerin: increased risk of hypotension; sildenafil inhibition of the phosphodiesterase type isoform that inactivates cyclic guanosine monophosphate D Ritonavir and lovastatin: increased risk of myotoxicity; ritonavir inhibition of CYP2C19 E Allopurinol and azathioprine: increased risk of blood dyscrasias; allopurinol inhibition of Pglycoprotein I-25 Which of the following statements regarding coronary heart disease (CHD) in women when compared to men is true? A Angina is a rare symptom in women with CHD B At the time of diagnosis of CHD, women typically have fewer comorbidities when compared to men C Physicians are less likely to consider CHD in women and are also less likely to recommend both diagnostic and therapeutic procedures in women D Women and men present with CHD at similar ages E Women are more likely to present with ventricular tachycardia, whereas men more commonly have cardiac arrest or cardiogenic shock I-26 All of the following diseases are more common in women than men EXCEPT: A B C D E Depression Hypertension Obesity Rheumatoid arthritis Type diabetes mellitus I-27 Which of the following statements regarding sex differences in the United States is true? A B C D E Due to extensive public awareness campaigns, the majority of physicians are counseling their female patients about their risk for cardiovascular disease The leading causes of death are the same for women and men Women’s bone density and their risk for cardiovascular disease decline after menopause Women have a longer average life expectancy than men, and this difference has been unchanged for decades Women younger than age 65 correctly believe that breast cancer is their leading health risk I-28 You are seeing Mrs Robin today, a 58-year-old woman with a history of tobacco use, treated hypertension, and moderate obesity She is recently menopausal You note on her intake form that she has questions about hormone replacement therapy to reduce her risk of coronary heart disease and stroke Which of the following statements to Mrs Robin would be true? A B C D E “Most studies suggest that combined continuous equine estrogen combined with medroxyprogesterone acetate is superior to combined continuous equine estrogen alone in regard to risk for stroke or heart attack.” “Studies suggest that initiating hormone therapy can reduce the incidence of hot flashes, night sweats, mood, sexual function, and bone density, but there is no change in risk for stroke, myocardial infarction, or venous thromboembolism.” “The largest trial done on hormone therapy demonstrated a benefit for hormone therapy in reducing the risk for heart attack and stroke.” “What is truly important for hormone therapy is the timing of initiation Since you are recently menopausal, we know that starting hormone therapy now will reduce your risk of future heart attack.” “You should definitely take low-dose aspirin daily It has been shown to reduce the risk of coronary heart disease in women more than men.” I-29 Which of the following statements is true regarding sex differences in disease? A B C D E Most autoimmune diseases are more prevalent in women than men This is attributed to stimulatory actions of estrogens and the inhibitory actions of androgens on the cellular mediators of immunity, and hormone therapy with oral contraceptives increases the risk of autoimmune disease Obesity decreases the risk of endometrial cancer in women Testosterone administered to hypogonadal men will increase the incidence or severity of obstructive sleep apnea This does not occur with testosterone administered to hypogonadal women Women are more sensitive to insulin than are men, and thus, women’s risk for type diabetes mellitus is lower Women have a longer QT interval on average than men and are at higher risk for drug-induced torsades de pointes I-30 A 67-year-old man with hypertension and sleep apnea presents to your clinic for routine follow-up As you open your discussion with him, he says that he has seen some commercials advising him to ask his doctor about “low T” (low testosterone) He is interested in getting tested Which of the following statements to this patient is valid? A B C D E “If you are found to be testosterone deficient, therapy with exogenous testosterone may worsen your sleep apnea.” “It is recommended that every man above the age of 60 be tested for low total and bioavailable testosterone.” “Most studies show that testosterone concentration does not, on average, decline with advancing age Instead, the endogenous testosterone made is less potent.” “Testosterone levels are associated with a risk for dementia in men.” “While exogenous testosterone therapy can increase lean muscle mass, it also increases visceral fat mass.” I-31 A 29-year-old former competitive power-lifter who stopped competing months earlier due to a deltoid muscle tear confides that he and his wife have been unable to conceive despite over a year of sexual intercourse without contraception He wonders if there is a “shot or something that can, you know, help me out.” You suspect that the patient may be using anabolic-androgenic steroids (AAS) Which of the following statements is true regarding AAS use? A AAS users have the same mortality as the general population B An elevated hematocrit should increase suspicion for AAS abuse C Elevated luteinizing hormone levels and suppressed follicle-stimulating hormone levels are clues suggesting AAS abuse D Increased testicular volume is a clue for AAS abuse E Several prolonged clinical trials of AAS abuse have provided the medical community with a sophisticated understanding of the adverse effects of AAS abuse I-32 Mr Brooks returns to clinic in August for his yearly follow-up He is a 78-year-old former long-haul trucker who enjoys fishing and traveling During the spring and summer months, he takes diphenhydramine daily for seasonal allergies He has been generally feeling well, but has recently noticed some urinary urgency, straining to void, and even urinary incontinence You perform a complete physical examination including a digital prostate exam and confirm benign prostatic hypertrophy The International Prostate Symptom Score indicates that Mr Brooks’s symptoms are moderate Which of the following statements to Mr Brooks would be appropriate? A B C D E “I recommend primary therapy with tolterodine, an anticholinergic agent targeted at treated overactive bladder symptoms.” “Therapy with finasteride can reduce progression to acute urinary retention and need for prostate surgery.” “Urodynamic studies are warranted; I’ll refer you now.” “We should go straight to surgery Given the severity of your symptoms, medical therapy is unlikely to help much.” “Your use of diphenhydramine is probably working to improve your lower urinary tract symptoms given its anticholinergic properties.” I-33 A 24-year-old woman comes to clinic for a routine visit She is 28 weeks pregnant with her first child To date, her pregnancy has been unremarkable and she has no family history of complicated pregnancies Her past medical history is unremarkable except for a history of mitral valve prolapse A blood pressure greater than which of the following would be considered potentially abnormally elevated? A B C D 110/80 mmHg in the standing position 120/80 mmHg in the standing position minutes after rising from the supine position 130/85 mmHg in the left lateral recumbent position 130/85 mmHg in the seated position azathioprine, mycophenolate mofetil, or infliximab Presence of caseating granulomas typically signifies an infectious process, most commonly tuberculosis or fungal infection Atypical lymphocytes with clonality on flow cytometry are found in various types of lymphoma A biopsy with small round cells that often resemble lymphocytes and that demonstrate scant cytoplasm, indistinct nucleoli, and mitotic figures is typical of small-cell lung carcinoma Nonspecific chronic inflammation is nondiagnostic, and further workup would be required XI-35 The answer is D (Chap 456) Syringomyelia is a development disorder of the spinal cord that results in enlargement of the central cavity of the spinal cord More than half of all cases are associated with a concomitant Chiari I malformation of the brainstem with protrusion of the cerebellar tonsils through the foramen magnum and into the cervical spinal canal Although controversial, one theory for the pathogenesis of syringomyelia is impaired CSF flow with secondary enlargement of the central spinal cord, and the common coexistence with Chiari malformations may provide support of this theory Symptoms of syringomyelia develop gradually, often beginning in late adolescence or early adulthood The symptoms progress irregularly and may even arrest for a prolonged period The presentation of syringomyelia includes both sensory loss and muscle wasting and weakness The sensory disturbance is dissociative, with loss of pain and temperature sensation but preservation of vibration and touch Patients may present with injuries or burns that occur when the patient is unaware of a painful sensation in the affected limb The distribution of sensory loss is classically described as cape-like, affecting the nape of the neck, shoulders, upper arms, and hands Patients are areflexic in the upper limbs Symptoms may be asymmetric As the cavity enlarges, it can further lead to spasticity and weakness in the lower extremities as well There are no definitive treatment options for the disease If a Chiari malformation is also present, surgical decompression may be required Surgeons have attempted direct decompression of the spinal canal with varied results XI-36 and XI-37 The answers are C and D, respectively (Chap 458) This patient presents with visual disturbance and weakness affecting the lower extremities with a past history of prior visual disturbance This suggests a diagnosis of multiple sclerosis (MS), an autoimmune demyelinating disorder of the central nervous system This disease affects about 350,000 individuals in the United States and has a variable clinical course, with some individuals experiencing limited symptoms and others becoming very incapacitated due to the disease MS is three times more common in women, with a typical age of onset between 20 and 40 years of age MS is more common in white individuals that those of African or Asian descent In addition, geographic variations in disease prevalence have also been demonstrated, with higher prevalence in the temperate zone areas of northern North America, northern Europe, and southern Australia and New Zealand In contrast, the tropics have a prevalence that is 10 to 20 times less Other well-established risk factors for development of MS include vitamin D deficiency, exposure to Epstein-Barr virus after early childhood, and cigarette smoking Despite the fact that this is an autoimmune disorder, there has not been an associated between MS and other autoimmune disorders The clinical manifestations of MS are varied The disease can present with an abrupt onset of symptoms or may develop gradually The most common initial presenting symptoms include sensory loss, optic neuritis, weakness, paresthesias, and diplopia Weakness of the limbs may be asymmetric and manifest as loss of strength, speed, dexterity, or endurance Symptoms are upper neuron in origin and have associated spasticity, hyperreflexia, and Babinski sign most commonly However, if there is a spinal cord lesion, lower motor neuron signs and loss of reflexes may also be seen The spasticity that is present may lead to spontaneous or movement-induced muscle spasms and affects up to 30% of patients with MS Optic neuritis presents with blurred vision, dimness, or decreased color perception in the central visual fields Visual symptoms typically only affect one eye Periorbital pain often precedes or accompanies visual loss Funduscopic examination may be normal or show optic disc swelling Other common symptoms that occur with MS include bladder dysfunction, ataxia, constipation, chronic pain, fatigue, and depression A diagnosis of MS can be difficult to confirm in some individuals There is no definitive test for MS The diagnostic criteria require two or more episodes of symptoms and two or more signs of dysfunction in noncontiguous white matter tracts MRI characteristically shows multiple hyperintense T2-weighted lesions that can be present in the brain, brainstem, and spinal cord More than 90% of lesions seen on MRI, however, are asymptomatic Approximately one-third of lesions that appear hyperintense on T2weighted images will be hypointense on T1-weighted images These “black holes” may be a marker of irreversible demyelination and axonal loss Evoked potentials are no longer commonly used in MS and are most useful in studying pathways that are not exhibiting clinical symptoms Evoked potentials are not specific to MS, although a marked delay in latency of transmission suggests demyelination The CSF may show an increased number of mononuclear cells, although CSF protein is typically normal Oligoclonal bands help to assess the intrathecal production of immunoglobulin (Ig) G The presence of two or more discrete oligoclonal bands in the CSF that are not present in serum is found in more than 75% of MS patients If a patient has a pleocytosis of >75 cells/µL, presence of polymorphonuclear cells, or protein concentration >100 mg/dL, an alternative diagnosis should be sought XI-38 The answer is D (Chap 458) Over the past two decades, 10 disease-modifying agents for the treatment of MS have been approved Due to these multiple options, it is preferred that a patient with MS be referred to a treatment center with experience in the disease The disease-modifying drugs approved for MS include interferon-β-1a, interferon-β-1b, glatiramer acetate, natalizumab, fingolimod, dimethyl fumarate, teriflunomide, mitoxantrone, and alemtuzumab Given this patient’s poor functional status, her disease should be treated as moderate disease Generally, in those with moderate disease, the preferred agents are dimethyl fumarate, fingolimod, teriflunomide, and natalizumab, with interferon-β-1a and -1b treatment being reserved for individuals with milder disease However, natalizumab is not recommended in this patient due to the presence of antibody to JC virus About half of the population is antibody positive for JC virus, indicating past exposure typically with an asymptomatic infection JC virus is implicated in the development of progressive multifocal leukoencephalopathy This life-threatening condition has occurred in 0.3% of all patients treated with natalizumab and in about 0.6% of patients who are positive for JC virus antibody The risk is lower in the first year of treatment and increases thereafter Thus, natalizumab should not be used in this patient unless she has failed alternative therapies or if the disease course has been particularly aggressive If natalizumab is ultimately chosen for a patient who is JC virus antibody positive, it should not be used for any longer than year In patients who are JC virus antibody negative, it is recommended to follow the patient for development of antibody approximately every months XI-39 The answer is C (Chap 459) When evaluating a patient with peripheral neuropathy, the clinician should consider the history and physical examination carefully to determine the location of the lesion, which will then further identify the cause and appropriate treatment However, in as many as 50% of patients presenting with peripheral neuropathy, no cause is ever found, and these patients generally have a predominate sensory polyneuropathy Seven keys questions in the history and physical examination can assist with the identification of the site of the lesion and the cause (Table XI-39) The first determination the clinician should make is which systems are involved—sensory, motor, autonomic, or some combination of these An isolated motor neuropathy without sensory involvement should lead to diagnostic possibilities that include myopathy, motor neuropathy, or disorder of the neuromuscular junction Autonomic symptoms can accompany a diabetic neuropathy and can also be seen in amyloid polyneuropathy Another important determination is the distribution of the weakness (proximal vs distal, symmetric vs asymmetric) A third determination is the nature of the sensory involvement Small-fiber neuropathy often has a burning or stabbing quality along with temperature loss, whereas a large-fiber sensory neuropathy will show loss of vibratory sense and proprioception One should also consider whether upper motor neuron symptoms are also present, which occurs with vitamin B12 deficiency most commonly, but also occurs with other causes of combined system degeneration such as human immunodeficiency virus (HIV) and copper deficiency The temporal evolution of symptoms further provides the clinician with clues as to the cause of the disease Most neuropathies have an insidious onset over weeks to months Acute development of symptoms points to causes such as Guillain-Barré syndrome vasculitis or Lyme disease Asking about symptoms in other family members will help to establish whether a hereditary neuropathy is present Finally, it is important to obtain a full medical history to assess whether any associated conditions could be contributing to the neuropathy Once a full history and physical examination is completed, a clinician will often order EMG and nerve conduction studies to complete the work up Autonomic studies may also be helpful in selected patients TALBLE XI-39 Approach to Neuropathic Disorders: Seven Key Questions XI-40 The answer is A (Chap 459) Charcot-Marie-Tooth (CMT) syndrome is the most common type of hereditary neuropathy CMT is comprised of several similar but genetically distinct conditions with different associated mutations CMT1 is the most common syndrome and is an inherited demyelinating sensorimotor neuropathy CMT1 most often affects patients in the first to third decades of life with distal leg weakness (ie, foot drop) There are several subtypes of CMT1, most of which are inherited in an autosomal dominant fashion However, the penetrance is variable, and some affected family members may remain asymptomatic even late in life The most common genetic defect in CMT1 (CMT1A) is a 1.5-megabase duplication in the gene for peripheral myelin production (PMP-22) on chromosome 17 This results in a patient having three copies of the gene rather than two Although patients generally not complain of sensory symptoms, these can be elicited often on physical examination Muscle stretch reflexes are unobtainable or reduced throughout, and muscles below the knee are often atrophied, which makes legs appear to have so-called inverted champagne bottle appearance There are no medical therapies for CMT, but patients are generally referred for physical and occupational therapy Bracing and other orthotic devices are frequently used Hereditary neuralgic amyotrophy is an autosomal dominant disorder characterized by recurrent attacks of pain, weakness, and sensory loss in the distribution of the brachial plexus that often begins in childhood Hereditary sensory and autonomic neuropathy is a rare group of hereditary neuropathies in which sensory and autonomic dysfunction predominates over muscle weakness This would not fit the clinical pattern described here Guillain-Barré syndrome generally presents acutely with rapid development of ascending paralysis The prolonged symptom period and distribution described here are not typical for Guillain-Barré syndrome Fabry disease is an X-linked disorder in which men are more commonly affected then women Patients have angiokeratomas, which are reddish-purple lesions usually found around the umbilicus, scrotum, and inguinal region Burning pain in the hands and feet often is found in late childhood or early adult life Patients also have premature atherosclerosis from the underlying mutation in the αgalactosidase gene with accumulation of ceramide in nerves and blood vessels XI-41 The answer is E (Chap 459) One of the most common side effects of isoniazid treatment is peripheral neuropathy The elderly, malnourished patients, and “slow acetylators” are at increased risk for developing the neuropathy Isoniazid inhibits pyridoxal phosphokinase, resulting in pyridoxine (vitamin B6) deficiency and the neuropathy Prophylactic administration of pyridoxine can prevent the neuropathy from developing Symptoms are generally dysesthesias and sensory ataxia Impaired large-fiber sensory modalities are found on examination Cobalamin (vitamin B12) is not reduced in this condition and unaffected by isoniazid Neurontin and pregabalin may alleviate symptoms but will not reverse the neuropathy There is no indication that hypothyroidism is present XI-42 The answer is C (Chap 459) Diabetes mellitus is the most common cause of peripheral neuropathy in developed countries and is associated with several different types of polyneuropathy including distal symmetric sensory or sensorimotor polyneuropathy, autonomic neuropathy, diabetic neuropathic cachexia, polyradicular neuropathies, cranial neuropathies, and other mononeuropathies Risk factors for development of neuropathy include long-standing and poorly controlled diabetes and the presence of retinopathy or nephropathy The patient here appears to have diabetic distal symmetric sensory and sensorimotor polyneuropathy (DSPN), which is the most common form of diabetic neuropathy DSPN presents with sensory loss beginning in the toes and gradually progressives over time up the legs and into the fingers and arms Symptoms also may include tingling, burning, and deep aching pains Nerve biopsy, although rarely indicated, often shows axonal degeneration, endothelial hyperplasia, and occasionally perivascular inflammation Tight glucose control prevents development of disease but does not reverse established disease Diabetic autonomic neuropathy is often seen in combination with DSPN and manifests by abnormal sweating, dysfunctional thermoregulation, dry eyes and mouth, postural hypotension, gastrointestinal abnormalities including gastroparesis, and genitourinary dysfunction XI-43 and XI-44 The answers are B and B, respectively (Chap 460) Guillain-Barré syndrome (GBS) is an acute demyelinating polyneuropathy that can be severe and life-threatening if not immediately recognized and treated Each year, there are about 5000–6000 cases in the United States, with an incidence of about 1–4 cases per 100,000 population annually Men are slightly more commonly affected than women, and GBS is more commonly diagnosed in adulthood The typical presentation is a rapid ascending paralysis that may be first noticed as weak or “rubbery” legs The weakness can evolve over hours to a few days, with the legs being more affected than the arms Tingling dysesthesias are also frequently present, although sensory neuropathy is always present Facial paresis occurs in about 50% of patients, and other lower cranial nerves may also be affected Pain is a frequent complaint, with pain in the neck, shoulders, back, and diffusely over the spine In addition, vague sensation of deep aching pain in the weakened muscles may also be present Up to 30% of patients will require mechanical ventilation due to weakness of the respiratory muscles Moreover, bulbar involvement increases the risk of aspiration and subsequent pneumonia Deep tendon reflexes are decreased or disappear entirely within the first few days of onset Cutaneous sensory deficits are usually only mild if present at all Bladder dysfunction only rarely occurs and is transient Persistent or severe bladder dysfunction should stimulate a workup for other causes Autonomic symptoms are common Blood pressure may be quite labile with marked postural changes Cardiac dysrhythmias may also occur and require continuous monitoring Typically within weeks of onset or sooner, there is a plateau in symptoms with no further progression Diagnosis of GBS relies upon a high degree of clinical suspicion because there is no one test that is diagnostic for the disorder Typical CSF findings include a high CSF protein without pleocytosis The presence of a high CSF white blood cell count should prompt a search for an alternative diagnosis Early in the disease process, electrodiagnostic testing may be normal or only show mild findings of demyelination Approximately 70% of GBS cases occur within 1–3 weeks of an antecedent infectious illness Most commonly, the illness is respiratory or gastrointestinal in nature About 20%–30% of all cases in North America, Europe, and Australia are preceded by infection or reinfection with Campylobacter jejuni A similar proportion of individuals will have had an infection with a human herpes virus, most often cytomegalovirus or Epstein-Barr virus Less frequently, HIV, hepatitis E, or Mycoplasma pneumoniae may be implicated Recent immunizations are a rare cause of GBS, with a risk of 3× upper limit of normal), and myoglobinuria are indications for stopping After cessation, improvement generally occurs in up to several weeks XI-49 The answer is E (Chap 462e) A number of endocrinologic conditions are associated with myopathy Both hypo- and hyperthyroidism are associated with proximal muscle weakness Hypothyroidism is associated with an elevated CK frequently, even with minimal clinical evidence of muscle disease Thyrotoxic patients may have fasciculations in addition to proximal myopathy, but in contrast to hypothyroid patients, CK is not generally elevated Hyperparathyroidism is associated with muscle weakness, generally proximal Muscle wasting and brisk reflexes are also generally present Serum CK levels may be normal or slightly elevated Serum calcium and phosphate levels show no correlation with clinical weakness Hypoparathyroid patients also often have myopathy due to hypocalcemia Patients with acromegaly usually have mild proximal weakness without atrophy The duration of acromegaly, not the serum growth hormone levels, correlates with the degree of myopathy Diabetes mellitus is a rare cause of myopathy, generally due to ischemic infarction of muscle, and not a primary myopathy Finally, vitamin D deficiency is associated with muscle weakness, as are glucocorticoid excess states (e.g., Cushing disease) XI-50 The answer is D (Chap 462e) There are two recognized clinical forms of myotonic dystrophy, both of which are characterized by autosomal dominant inheritance Myotonic dystrophy type (DM1) is the most common form and the most likely disorder in this patient Characteristic clinical features of this disorder include a “hatchet-faced” appearance, due to wasting of the facial muscles, and weakness of the neck muscles In contrast to the muscular dystrophies (Becker and Duchenne), distal limb muscle weakness is more common in DM1 Palatal, pharyngeal, and tongue involvement are also common and produce the dysarthric voice that is frequently heard The failure of relaxation after a forced hand grip is characteristic of myotonia Myotonia can also be elicited by percussion of the thenar eminence In most individuals, myotonia is present by age 5, but clinical symptoms of weakness that lead to diagnosis may not be present until adulthood Cardiac conduction abnormalities and heart failure are also common in myotonic dystrophy Diagnosis can often be made by clinical features alone in an individual with classic symptoms and a positive family history An EMG would confirm myotonia Genetic testing for DM1 would show a characteristic trinucleotide repeat on chromosome 19 Genetic anticipation occurs with an increasing number of repeats and worsening clinical disease over successive generations Myotonic dystrophy type (DM2) causes proximal muscle weakness primarily and is also known by the name proximal myotonic myopathy Other features of the disease overlap with DM1 Acid maltase deficiency (glucosidase deficiency, or Pompe disease) has three recognized forms, only one of which has onset in adulthood In the adult-onset form, respiratory muscle weakness is prominent and often is the presenting symptom As stated previously, Becker and Duchenne muscular dystrophies present with primarily proximal muscle weakness and are X-linked recessive disorders Becker muscular dystrophy presents at a later age than Duchenne muscular dystrophy and has a more prolonged course Otherwise, features are similar to one another Nemaline myopathy is a heterogeneous disorder marked by the threadlike appearance of muscle fibers on biopsy Nemaline myopathy usually presents in childhood and has a striking facial appearance similar to myotonic dystrophy with a long, narrow face This disease is inherited in an autosomal dominant fashion XI-51 The answer is E (Chap 464e) Chronic fatigue syndrome (CFS) is a disorder characterized by persistent and unexplained fatigue resulting in severe impairment in daily functioning Besides intense fatigue, most patients with CFS report concomitant symptoms such as pain, cognitive dysfunction, and unrefreshing sleep Additional symptoms can include headache, sore throat, tender lymph nodes, muscle aches, joint aches, feverishness, difficulty sleeping, psychiatric problems, allergies, and abdominal cramps Criteria for the diagnosis of CFS have been developed by the U.S Centers for Disease Control and Prevention (Table XI-51) CFS is seen worldwide, with adult prevalence rates varying between 0.2% and 0.4% In the United States, the prevalence is higher among women (~75% of cases), members of minority groups (African and Native Americans), and individuals with lower levels of education and occupational status The mean age of onset is between 29 and 35 years Many patients probably go undiagnosed and/or not seek help There are numerous hypotheses about the etiology of CFS; there is no definitively identified cause Physical inactivity and trauma in childhood tend to increase the risk of CFS in adults Neuroendocrine dysfunction may be associated with childhood trauma, reflecting a biological correlate of vulnerability Psychiatric illness and physical hyperactivity in adulthood raise the risk of CFS in later life Twin studies suggest a familial predisposition to CFS, but no causative genes have been identified Physical or psychological stress may elicit the onset of CFS Most patients report an infection (usually a flulike illness or infectious mononucleosis) as the trigger of their fatigue Relatively high percentages of CFS cases occur after Q fever and Lyme disease TALBLE XI-51 Diagnostic Criteria for Chronic Fatigue Syndrome XI-52 The answer is B (Chap 464e) Cognitive behavioral therapy (CBT) and graded exercise therapy (GET) have been found to be the only beneficial interventions in CFS Some patient groups argue against these approaches because of the implication that CFS is a purely mental disorder CBT is a psychotherapeutic approach directed at changing unhealthy disease-perpetuating patterns of thoughts and behaviors It includes educating the patient about the etiologic model, setting goals, restoring fixed bedtimes and wake-up times, challenging and changing fatigue and activity-related concerns, reducing a focus on symptoms, spreading activities evenly throughout the day, gradually increasing physical activity, planning a return to work, and resuming other activities The intervention, which typically consists of 12–14 sessions spread over months, helps CFS patients gain control over their symptoms GET targets deconditioning and exercise intolerance and usually involves a home exercise program that continues for 3–5 months Walking or cycling is systematically increased, with set goals for maximal heart rates CBT and GET appear to improve fatigue primarily by changing the patient’s perception of the fatigue and also by reducing the focus on symptoms In general, CBT studies tend to yield better improvement rates than GET trials Not all patients benefit from CBT or GET Predictors of poor outcome are medical (including psychiatric) comorbidities, current disability claims, and severe pain CBT offered in an early stage of the illness reduces the burden of CFS for the patient as well as for society in terms of decreased medical and disability-related costs Full recovery from untreated CFS is rare: the median annual recovery rate is 5% (range, 0%–31%), and the median improvement rate is 39% (range, 8%–63%) Patients with an underlying psychiatric disorder and those who continue to attribute their symptoms to an undiagnosed medical condition have poorer outcomes The other listed therapies have been tried in patients with CFS with no proven lasting benefit XI-53 The answer is A (Chap 466) Generalized anxiety disorder (GAD) has a lifetime prevalence of about 5%–6% and presents with persistent, excessive, and/or unrealistic worry occurring on most days that persists for at least months The worry typically pervades most aspects of life and is to a degree that it is uncontrollable and causes impairment in social, work, or interpersonal functioning Associated physical symptoms include tension, restlessness, impaired concentration, insomnia, autonomic arousal, and feeling of being “on edge.” Typical onset of symptoms is before the age of 20, although patients may not seek treatment for many years A history of childhood fears may be present More than 80% of patients with GAD have a concomitant mood disorder such as major depression or dysthymia or social phobia, but panic attacks (e.g., 10–30 minute episodes including palpitations, shortness of breath, and feelings of impending doom) generally not occur Comorbid substance abuse, most often with alcohol or sedative/hypnotics, is also common, perhaps as an attempt to self-treat anxiety Treatment of GAD is most effective when psychotherapy is combined with medications, although complete relief of symptoms is rare Initial intervention with benzodiazepines is often required for a period of 4–6 weeks Other medications that are FDA-approved for the treatment of GAD are escitalopram, paroxetine, and venlafaxine, although other SSRIs have been demonstrated in clinical trials to be effective as well, typically at doses comparable to the effective dose for major depression Buspirone is another anxiolytic agent that is nonsedating, does not produce tolerance or dependence, and has no abuse potential However, it generally has mild effects and takes several weeks to produce results It has demonstrated best results in individuals with dementia or head injury who develop agitation and/or anxiety Anticonvulsants with GABAergic properties such as gabapentin, oxcarbazepine, tiagabine, pregabalin, and divalproex also may have efficacy against anxiety XI-54 The answer is C (Chap 466) There are an estimated 300,000 episodes of acute schizophrenia in the United States annually This disorder has a high degree of morbidity, with many individuals failing to achieve their premorbid level of functioning after an episode of acute schizophrenia Symptoms of schizophrenia are heterogeneous with perturbations in language, thinking, perception, social activity, affect, and volition The most typical age of onset is late adolescence and young adulthood Onset is insidious as individuals progressively experience social withdrawal and perceptual distortion and often progress to experience frank delusions and hallucinations As individuals age, the positive symptoms of delusions and hallucinations tend to recede, and the negative symptoms of anhedonia, decreased emotional expression, and loss of function become more predominant In a first episode, antipsychotic agents are effective about 70% of the time Symptoms may improve within hours or days of dosing, but full remission often takes 6–8 weeks If medications are discontinued, relapse will occur in 60% of patients within months The long-term prognosis of most individuals with schizophrenia is somewhat grim Prognosis of schizophrenia depends not on symptom severity at initial diagnosis but on the response to antipsychotic medication A permanent remission rarely occurs About 10% of schizophrenic patients commit suicide XI-55 The answer is D (Chap 466) This patient is experiencing her first episode of a panic attack and does not meet criteria for panic disorder In this situation, no specific treatment is required The patient should be reassured that she does not have any evidence of a serious medical disorder in a manner that is empathetic and supportive Panic disorder is a frequently occurring mental disorder with a lifetime prevalence of about 2%–3% Panic attacks begin abruptly, most commonly without an immediate precipitating cause, and peak in severity over 10 minutes The first episode of panic attack is most often outside the home The symptoms usually subside spontaneously over the course of an hour Panic attacks are often accompanied by intense fear and a variety of physical symptoms, including palpitations, dizziness, sweating, shortness of breath, chest pain, and a feeling of impending doom or death Gastrointestinal distress, paresthesias, and syncope may occur Panic disorder could be diagnosed if the patient developed recurrent attacks lasting at least month or exhibited excessive worry or change in behavior related to these attacks If the patient subsequently develops panic disorder, a variety of treatment options can be pursued The goals of therapy for panic attacks are to decrease the frequency of attacks and severity of symptoms during the attack Antidepressant medications are the cornerstone of therapy with SSRIs being the most frequently used class of medication The dose of medication for panic disorder is typically lower than the antidepressant dose For fluoxetine, this would be 5–10 mg daily Because these medications take 2–6 weeks to become effective, they are often combined with benzodiazepines early in the course of treatment to alleviate anticipatory anxiety and provide immediate relief of panic symptoms Alprazolam and clonazepam are common agents used for panic disorder, although alprazolam may have more associated dependence with need for escalating doses of medications In combination with pharmacologic therapy, psychotherapy and education are also useful for the treatment of panic disorder The therapy often includes breathing techniques, cognitive behavioral therapy, and even homework assignments XI-56 The answer is A (Chap 466) There are an increasing number of antidepressant medications available in a variety of classes SSRIs are the most commonly used antidepressant drugs This class of medications includes fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, and escitalopram These medications are taken once daily and have side effects including sexual dysfunction, headache, and insomnia Tricyclic antidepressants were commonly used in past decades for treatment of depression However, overdoses can be lethal, and anticholinergic side effects including dry mouth, constipation, and urinary retention can limit the dose Medications in the tricyclic class of antidepressants include amitriptyline, nortriptyline, imipramine, desipramine, doxepin, and clomipramine Mixed norepinephrine/serotonin reuptake inhibitors and receptor blockers are a newer class of medications These medications are increasing in use because they are quite effective and not have the same frequency of sexual dysfunction Medications in this class includes venlafaxine, desvenlafaxine, duloxetine, and mirtazapine Monoamine oxidase inhibitors were once a common antidepressant class of medication, but these medications are now only rarely used because of a wide range of drug and food interactions that can lead to hypertensive crises Examples of medication in this class include phenelzine, tranylcypromine, and isocarboxazid A final class of antidepressants, called simply mixed-action, and includes trazodone, bupropion, and nefazodone XI-57 The answer is E (Chap 466) Posttraumatic stress disorder (PTSD) was only added as a discrete disorder in 1980 The diagnostic criteria for PTSD are long and require that an individual experiences an event where there was an actual or perceived threat of death or serious injury and that the individual’s reaction included intense fear or helplessness Following the event, the individual continues to reexperience the event and avoids stimuli associated with the trauma In association with this, there is also often a generalized withdrawal and decrease in responsiveness At the same time, the patient exhibits an increase in arousal that is often exhibited by insomnia, irritability, hypervigilance, and difficulty concentrating Treatment of PTSD is almost always multifactorial, including both pharmacotherapy and psychotherapy It is not uncommon for an individual with PTSD to develop dependence on drugs or alcohol as an attempt to control the symptoms, and any substance abuse issues need to be treated simultaneously as well This patient’s treatment would include avoidance of alcohol and intensive substance abuse treatment, as needed Treatment with antidepressant medications can decrease anxiety and avoidance behaviors Trazodone is often given at night for its sedating properties Psychotherapeutic strategies include cognitive behavioral therapy to overcome avoidance behaviors XI-58 The answer is B (Chap 466) Fifteen percent of the population will experience at least one episode of major depression over the course of a lifetime, and most episodes of major depression are treated by primary care practitioners Treatment can be with any of a number of medications across a variety of classes Despite the popularity of newer antidepressants, there is no evidence that these medications are more efficacious than older drugs like tricyclic antidepressants Indeed, 60%–70% of patients will respond to any drug chosen if given in a sufficient dose for 6–8 weeks However, up to 40% of patients treated at primary care offices discontinue treatment if there has not been a response within month Once a patient has been on treatment for ~2 months, the response should be evaluated, and if there has been an insufficient response, a dose increase should be considered In this patient, a dose increase yielded control of depressive symptoms at months Once control of symptoms has been achieved, the drug should be continued for an additional 6–9 months to prevent relapse If a patient experiences any additional episodes of major depression, he will likely require indefinite maintenance treatment because it is recommended that anyone with more than two episodes of major depression continue treatment indefinitely XI-59 The answer is F (Chap 467) About 20% of all patients have an alcohol use disorder, even in affluent locales Patients should be screened for an alcohol use disorder by asking specific questions regarding alcohol consumption, although many patients may minimize their alcohol use The patient in the scenario presented reports daily alcohol consumption and some symptoms of an alcohol use disorder, including blackouts from drinking and frequent hangovers while working Laboratory tests may be helpful in this situation as they can be elevated in individuals who regularly consume six or more drinks daily The two tests with the greatest sensitivity and specificity (≥60%) are γ-glutamyl transferase (GGT) >35 U/L and carbohydratedeficient transferrin (CDT) Using both of these tests combined is more likely to be accurate than using either test alone Other blood tests that may be useful include high-normal MCV >91 µm3 and serum uric acid >7 mg/dL Elevations in AST or ALT are neither sensitive nor specific XI-60 The answer is A (Chap 467) Alcohol is primarily absorbed through the proximal small intestine, but small amounts can also be absorbed in the mouth, esophagus, stomach, and large intestines as well Several factors can increase the rate of absorption One factor that increases absorption is rapid gastric emptying, which can be induced by concurrent consumption of carbonated beverages Another factor that increases absorption from the gut to the blood is the ingestion of alcohol in the absence of other calorie sources such as proteins, fat, or carbohydrates A final factor that can increase absorption is to drink alcohol that is diluted to a modest concentration (~20% or less) At high alcohol concentrations, absorption is decreased, although high blood levels may be achieved because the amount of alcohol ingested is high XI-61 The answer is C (Chap 467) Alcohol has effects on many neurotransmitters in the brain The predominant effect of alcohol lies in its ability to cause release of γ-aminobutyric acid (GABA), and it acts primarily at the GABAA receptors GABA is the primary inhibitory neurotransmitter in the brain and is associated with the sedative effects of alcohol Many other drugs affect the GABA system including benzodiazepines, nonbenzodiazepine sleep aids such as zolpidem, anticonvulsants, and muscle relaxants The euphoric effects of alcohol consumption are related to increases in dopamine, which is common to all pleasurable activities The effects on dopamine are thought to be important in alcohol craving and relapse In addition, alcohol alters opioid receptors and can lead to a release of β-endorphins during acute ingestion In addition to these effects, alcohol also inhibits postsynaptic NMDA excitatory glutamate receptors Glutamate is the primary excitatory neurotransmitter of the brain, and its inhibition further contributes to the sedative effects of alcohol Additional important effects on neurotransmitters include increased serotonin activity and decreased nicotinic acetylcholine receptors XI-62 The answer is D (Chap 467) The acute effects of any drug depend on many factors including amount consumed and absorbed, presence of other drugs, and past experience with the drug In an individual who is naïve to alcohol, levels as low as 0.02 g/dL can lead to a decrease in inhibitions and a slight feeling of intoxication In the United States, “legal” intoxication occurs at a blood alcohol level of 0.08 g/dL in most states At this level, decreases in cognitive and motor abilities are seen Once an alcohol level of 0.20 g/dL is achieved, an individual is obviously impaired with slurred speech, poor judgment, and impaired coordination Light coma and depression of respiratory rate, blood pressure, and pulse occur at levels around 0.30 g/dL, and death is likely to occur at levels of 0.40 g/dL However, in individuals who drink heavily, tolerance begins to develop to alcohol After a period of 1–2 weeks of daily alcohol consumption, liver metabolism of alcohol increases by as much as 30%, but disappears quite quickly with abstinence Cellular or pharmacodynamic tolerance also occurs and refers to the neurochemical changes that allow an individual to maintain more normal physiologic function despite the presence of alcohol XI-63 The answer is C (Chap 467) In the most recent fifth edition of Diagnostic and Statistical Manual of Mental Disorders, the term alcohol use disorder replaced the two terms used to describe problem areas with alcohol use: alcohol abuse and alcohol dependence Under the new terminology, alcohol use disorder is defined as repeated alcohol-related difficulties in at least of 11 life areas that cluster together in the same 12-month period, and this disorder combines many of the criteria of dependence and abuse into a single diagnosis The diagnosis of alcohol use disorder is further characterized as mild, moderate, or severe based on how many criteria a person fulfills Examples of these criteria include failure to fulfill obligations, drinking in hazardous situations, tolerance, withdrawal, craving, and inability to control drinking behaviors The lifetime risk of an alcohol use disorder in most Western countries is about 10%–15% in men and 5%–8% in women However, there may be higher rates in Ireland, France, and Scandinavian countries In addition, native cultures appear to be especially susceptible to problems with alcohol use This has been seen in Native Americans, Maoris, and the aboriginal tribes of Australia About 60% of the risk for alcohol use disorders is attributed to genetic influences Children of alcoholics have a higher risk of an alcohol use disorder; however, this risk is about times higher, not 10 times higher This risk is conferred even when the children are adopted early and raised by nonalcoholics Identical twins also exhibit a higher risk of concurrent alcoholism when compared to fraternal twins The genetic factors that appear to be most strongly linked to alcohol use disorders include genes that are linked to impulsivity, schizophrenia, and bipolar disorder In addition, genes that affect alcohol metabolism or sensitivity to alcohol also contribute to the genetics of alcoholism A mutation in aldehyde dehydrogenase that is more common in individuals of Asian descent results in intense flushing when alcohol is consumed and confers a decreased risk of alcohol dependence Conversely, genetic variants that lead to a low sensitivity to alcohol increase the risk of a subsequent alcohol use disorder as higher doses of alcohol are required to achieve the same effects It is estimated that 20% of all patients have at least mild alcohol use disorder The age at first drink is similar between alcoholics and nonalcoholics However, alcoholics report a slightly earlier onset of regular drinking and drunkenness In most individuals with alcoholism, the course of the disease is one of remissions and relapse, but most individuals require treatment to be able to sustain abstinence The chance of spontaneous remission is about 20% If drinking continues without remission, the lifespan will decrease by about 10 years, with leading causes of death including heart disease, cancer, suicide, and accidents XI-64 The answer is B (Chap 467) Individuals with alcohol dependence are susceptible to alcohol withdrawal when alcohol intake is stopped abruptly The individual in this case scenario is likely alcohol dependent given his large amount of alcohol intake on a daily basis Symptoms of alcohol withdrawal can range from mild tremulousness to hallucinations, seizures, or development of delirium tremens Other clinical features of alcohol withdrawal include anxiety, insomnia, and autonomic nervous system overactivity manifested as tachycardia, tachypnea, elevated blood pressure, and fever This patient exhibits symptoms of the more severe delirium tremens, with mental confusion, agitation, and fluctuating levels of consciousness Although minor symptoms of alcohol withdrawal may begin as soon as 5–10 hours after cessation of alcohol intake, the symptoms not peak for 48–72 hours, putting this patient in the appropriate time frame for alcohol withdrawal The best approach to the alcohol-dependent patient who abruptly stops all alcohol intake is a prophylactic approach, and the patient should be screened early for symptoms of alcohol withdrawal Tools such as the Revised Clinical Institute for Withdrawal Assessment for Alcohol (CIWA-Ar) may help clinicians and nurses screen for early development of symptoms and allow intervention before symptoms escalate In this setting, most experts recommend use of oral long-acting benzodiazepines such as chlordiazepoxide or diazepam beginning on the first day However, in this case, the patient received no such treatment and is now experiencing severe alcohol withdrawal and delirium tremens IV medications that have a rapid onset of action and can be titrated for more aggressive symptom management are often employed in this setting Thus, use of IV lorazepam or diazepam is preferred in this patient Following an initial bolus, repeated doses can be used in short intervals until the patient is calm but arousable In some instances, a continuous infusion may be required, although bolus dosing is preferred In the most severe cases, propofol or barbiturates may be required, although the patient would most likely need to be intubated for airway protection with use of these medications The other options listed are not appropriate for initial management of this patient IV fluids and thiamine had been administered since hospital admission Administration of glucose-containing fluids without thiamine in the alcoholdependent patient can precipitate Wernicke encephalopathy, which would present with ophthalmoparesis, ataxia, and encephalopathy Given the patient’s fever, an infectious etiology can be considered, and it would be appropriate to perform blood cultures in this patient However, given the clear symptoms of alcohol withdrawal and lack of necrotizing pancreatitis on abdominal CT, empiric treatment with antibiotics is not required Likewise, without focal neurologic findings, a head CT would be a low-yield diagnostic procedure that would be difficult to perform in the patient’s current agitated condition and would only delay appropriate therapy Finally, restraints are best avoided if the patient’s safety can be ensured through appropriate use of benzodiazepines because restraints are only likely to make the patient’s agitation worse and may lead to iatrogenic harm Haloperidol may have some sedative effect on the patient but could lead to torsades de pointes arrhythmia because this patient is at risk for electrolyte deficiencies from his alcoholism and pancreatitis XI-65 The answer is D (Chap 467) In individuals recovering from alcoholism, several medications may have a modest benefit in increasing abstinence rates The two medications with the best risk-benefit ratio are acamprosate and naltrexone Acamprosate inhibits NMDA receptors, decreasing symptoms of prolonged alcohol withdrawal Naltrexone is an opioid antagonist that can be administered orally or as a monthly injection It is thought to act by decreasing activity in the dopamine-rich ventral tegmental area of the brainstem and subsequently decreasing the pleasurable feelings associated with alcohol consumption There is some research to suggest that the use of these medications in combination may be more effective than either one alone Disulfiram is an aldehyde dehydrogenase inhibitor that has been used for many years in the treatment of alcoholism However, it is no longer a commonly used drug due to its many side effects and risks associated with treatment The primary mechanism by which it acts is to create negative effects of vomiting and autonomic nervous system hyperactivity when alcohol is consumed concurrently with use of the medication Because it inhibits an enzyme that is part of the normal metabolism of alcohol, it allows the buildup of acetaldehyde, which creates these unpleasant symptoms As a result of the autonomic side effects, it is contraindicated in individuals with hypertension, a history of stroke, heart disease, or diabetes mellitus XI-66 The answer is B (Chap 470) Although declining in prevalence, cigarette smoking and use of other nicotine-containing products remain a significant contributor to premature death in the United States and account for about one out of every five deaths in the United States, for a total of 400,000 deaths annually Approximately 40% of cigarette smokers will die prematurely due to the habit unless they are able to quit The primary causes of premature death related to cigarette smoking are cardiovascular diseases, including both myocardial infarction and stroke; chronic obstructive pulmonary disease (COPD); and myriad cancers including lung, oral, esophageal, urogenital, and pancreatic cancer Cigarette smoking promotes both large- and small-vessel vascular disease Approximately 90% of peripheral vascular disease in the nondiabetic population can be attributed to cigarette smoking In addition, 50% of aortic aneurysms, 20%–30% of coronary artery diseases, and 10% of ischemic and hemorrhagic strokes are caused by cigarette smoking Moreover, if additional cardiac risk factors are present, the incremental risk added by cigarette smoking is multiplicative As mentioned earlier, cigarette smoking increases the risk of many different cancers, not just those of the respiratory tract The digestive tract appears to be particularly susceptible to the effects of cigarette smoking because cigarette smoking has been linked to esophageal, stomach, pancreatic, liver, and colorectal cancer Urogenital cancers are also increased in cigarette smokers, with increases in both kidney and bladder cancer In women, cervical cancer is also increased among smokers Interestingly, however, uterine cancer may be decreased among postmenopausal woman who smoke Cigarette smoking is responsible for 90% of COPD Cigarette smoking induces chronic inflammation in the small airways, although most smokers not develop symptomatic respiratory disease Chronic inflammation, narrowing of the small airways, and destruction of the alveoli lead to symptoms of COPD and emphysema in 15%–25% of smokers In any given year, more than half of smokers would like to quit smoking However, only 6% quit for months, and less than 3% remain abstinent at years Most individuals have to make multiple attempts to quit before being successful, and they are more likely to be successful if advised to quit by a physician Other triggers for smoking cessation include an acute illness, the cost of cigarettes, media campaigns, and workplace smoking restrictions XI-67 The answer is E (Chap 470) Smoking cessation is more likely to be successful when an individual is advised to quit by a physician and has a supervised smoking cessation plan At every medical visit, all patients should be asked whether they smoke, how much they smoke, and whether they are interested in quitting Even patients who state that are not interested in quitting should receive a clear message from their provider that smoking is an important health hazard and be offered assistance with quitting in the future For those interested in quitting, negotiating a quit date is an important step in the process, and close follow-up with office contact near the quit date is an important part of the process In addition, sometimes a more intensive counseling approach may be necessary Current recommendations are to offer pharmacologic therapy with either nicotine replacement therapy (NRT) or varenicline A variety of NRTs are available, including transdermal patches, nasal inhaler, gum, oral inhaler, or lozenge, with success rates of 1.5–2.7 times greater than no intervention Varenicline is an oral partial agonist of the nicotinic acetylcholine receptor that has a published success rate of 2.7 times greater than no intervention There has been some concern regarding use of varenicline in individuals with severe psychiatric illness, including suicidal ideation, but this individual does not meet this level of concern With planned close follow-up, varenicline should be considered an available option for this patient XI-68 The answer is D (Chap 470) Varenicline is a partial agonist of the nicotinic acetylcholine receptor and has been demonstrated to be more effective than placebo in promoting smoking cessation Severe psychiatric symptoms including suicidal ideation have been reported, prompting a warning by the FDA In addition, closer therapeutic supervision has been recommended, but at this time, the true frequency of these responses remains unclear A recent publication retrospectively reviewed the use of varenicline in over 69,000 individuals in Sweden When compared to the general population, there was no increased risk of suicide or psychosis in individuals prescribed varenicline even though these individuals were twice as likely to have had a prior psychiatric diagnosis (Thomas KH et al BMJ 347:f5704, 2013) However, the FDA is currently continuing its surveillance of the drug until more data are available Alternative agents such as bupropion in combination with nicotine replacement therapy should be considered XI-69 The answer is B (Chap 470) Smokers regulate their blood levels of nicotine by adjusting the frequency and intensity of their tobacco use Smokers can compensate for the lower levels of nicotine in low-yield cigarettes by smoking more cigarettes or by adjusting their smoking technique with a deeper inhalation and breathhold Therefore, smoking low-yield cigarettes is not a reasonable alternative to smoking cessation Moreover, there is no difference in the harmful physical effects of smoking or in the potential for drug interactions Finally, although not definitively proven, there is some thought that the rise in adenocarcinoma of the lung over the past 50 years is associated with introduction of the low-tar cigarette and the resultant change in smoking behavior associated with this introduction by Dr Nigam Rashmi Dhar for free pdf ebooks notes mcq join free whatsapp medical grp 009779804202884 ... and initiation of total parenteral nutrition D Placement of a nasogastric tube and initiation of enteral nutrition E Placement of a nasojejunal tube and initiation of enteral nutrition I-81 All... occurred between the treatment of the control and intervention arms of the trial Population selection of any randomized trial is crucial to determining the external validity (generalizability) of the... a macrosomic fetus, and attention to fetal growth via clinical and ultrasound examination is important Fetal macrosomia is associated with an increased risk of maternal and fetal birth trauma,