Quizz 3

A 24-year-old man who has had type 1 diabetes since age 7 has recently had erratic glucose readings. Since his diagnosis, he has been

taking fixed doses of neutral protamine Hagedorn (NPH) insulin before breakfast and at bedtime, along with fixed doses of rapid-acting

insulin before breakfast and dinner. An insulin pump has been discussed, but the patient prefers to continue with his regimen of multiple daily injections of insulin. He checks his blood sugar level before each meal and before bedtime.

Review of his blood sugar levels reveals that most premeal blood sugars are between 140 and 180 mg/dL. There are also 2 to 4 episodes

of hypoglycemia per week, occurring either in the middle of the night or around midday if he eats lunch later than usual. His most recent

glycated hemoglobin level was 8.3% (target, <7.0%). In addition to keeping his rapid-acting insulin with meals, which one of the following therapeutic strategies is most appropriate for this patient at this time?

• Discontinue the bedtime dose of NPH insulin

• Switch the NPH insulin to insulin degludec

• Continue the current regimen and request more-frequent blood sugar checks, including nightly at 2 a.m., with

  follow-up in 3 months

• Reduce the bedtime dose of NPH insulin

• Continue the current regimen and suggest that the patient eat a 20-gram carbohydrate snack before bedtime every night

Answer explanation

The primary goal of type 1 diabetes management is to achieve glycemic control while avoiding moderate-to-severe hypoglycemia.

Recommendations from the American Diabetes Association (ADA) include:

• Using multiple (≥3) daily injections of basal and prandial (premeal) insulin or continuous subcutaneous insulin infusion via insulin pump

• Matching the prandial insulin dose to anticipated carbohydrate intake and premeal glucose levels

• Using insulin analogues in most circumstances (Insulin analogues are synthetic insulin-like molecules. Rapid-acting analogues [aspart, glulisine, lispro] are used for prandial insulin, and long-acting analogues [glargine, detemir, and degludec] are used for basal insulin.)

The fact that this patient has nighttime hypoglycemia and hypoglycemia midday when his lunch is delayed suggests that the peak of the neutral protamine Hagedorn (NPH) insulin is causing his hypoglycemia. Despite frequent hypoglycemic episodes, his premeal blood sugar values are elevated precluding a simple dose increase in his insulin. This pattern may be best addressed initially by substituting a

long-acting insulin analogue, such as insulin degludec, detemir, or glargine, in place of NPH insulin; compared with NPH, the analogues are associated with reduced risk for hypoglycemia and may be associated with improved glucose control.

Key learning point: Compared with neutral protamine Hagedorn (NPH) insulin, long-acting insulin analogues are more effective at

preventing the adverse effect of hypoglycemia.

A 65-year-old man presents with a long-standing history of poorly controlled acid reflux symptoms. He uses over-the-counter

omeprazole, which partially relieves his symptoms. He reports consuming approximately 30 mL of whiskey per day.

His BMI is 35; otherwise, his physical examination is unremarkable. He had an upper endoscopy 6 months ago, which showed evidence of a hiatal hernia and Barrett esophagus with high-grade dysplasia. A carbon-13 urea breath test is positive. For which type of cancer is this patient most at risk?

• Pancreatic cancer

• Esophageal adenocarcinoma

• Mucosal-associated lymphoid tumor

• Squamous-cell carcinoma of the esophagus

• Gastric adenocarcinoma

Answer explanation

This patient has several risk factors for esophageal adenocarcinoma, including Barrett's esophagus, chronic reflux esophagitis, hiatal hernia, male sex, and obesity. In patients with Barrett's esophagus, the annual risk of esophageal cancer is approximately 6% for those with high-grade dysplasia and 0.25% for those without dysplasia.

Key learning point: The cancer most typically associated with Barrett's esophagus and hiatal hernia is esophageal adenocarcinoma.

A 55-year-old woman with a history of dry eyes and hypothyroidism is found to have an isolated elevated serum alkaline phosphatase

level. Her serum aminotransferase, total bilirubin, and albumin levels are normal. She does not have abdominal pain. Her only medication

is levothyroxine. She does not use over-the-counter medications or any complementary or alternative therapy. Examination reveals no hepatosplenomegaly or features of chronic liver disease. Her repeat serum alkaline phosphatase level is 180 U/liter (reference range, 30–120), and her level of bone-specific alkaline phosphatase is normal. Which one of the following tests is most likely to be diagnostic in this case?

• Anti-thyroid peroxidase antibody

• Antinuclear antibody

• Anti-smooth-muscle antibody

• Antimitochondrial antibody

• Anti-liver-kidney microsomal type 1 antibody

Answer explanation

A diagnosis of primary biliary cholangitis (PBC) should be considered in all patients with abnormal serum liver enzymes in a cholestatic pattern (elevated serum alkaline phosphatase of liver origin out of proportion to the serum aminotransferases), especially in older

women. In this case, the patient has dry eyes, a symptom of Sjögren syndrome that is associated with a higher incidence of PBC. The antimitochondrial-antibody test has 95% sensitivity for the diagnosis of PBC and very high specificity; it should be the first test ordered.

Key learning point: The most specific antibody associated with primary biliary cholangitis (previously referred to as primary biliary

cirrhosis) is antimitochondrial antibody.

A 66-year-old man with hypertension, hyperlipidemia, and documented coronary artery disease returns to discuss the results of a fasting

lipid panel. He is feeling well. His current medications include aspirin 81 mg once daily, simvastatin 40 mg once daily, atenolol 50 mg

once daily, and lisinopril 20 mg once daily. Laboratory testing reveals lipid values of 203 mg/dL for total cholesterol, 125 mg/dL for LDL cholesterol, 40 mg/dL for HDL cholesterol, and 190 mg/dL for triglycerides.

In addition to reinforcing recommended therapeutic lifestyle changes, which one of the following management approaches is most

appropriate for this patient?

• Continue simvastatin 40 mg once daily and add ezetimibe 10 mg once daily

• Increase the dose of simvastatin to 80 mg once daily

• Replace simvastatin with atorvastatin 80 mg once daily

• Continue simvastatin 40 mg once daily and add gemfibrozil 600 mg twice daily

• Replace simvastatin with pravastatin 40 mg once daily

Answer explanation

Current cholesterol treatment guidelines from the American College of Cardiology (ACC) and the American Heart Association (AHA) recommend a high-intensity statin (atorvastatin 40–80 mg or rosuvastatin 20–40 mg daily) as first-line therapy in adults ≤ 75 years of age who have clinical atherosclerotic cardiovascular disease (ASCVD). The evidence supports high-intensity statin therapy for this group

to achieve a ≥ 50% reduction in LDL-cholesterol levels. This patient is currently taking a moderate-intensity statin (simvastatin 40 mg daily), which is expected to achieve only a 30% to 49% reduction in LDL-cholesterol levels; he should therefore be switched to a high-intensity statin.

Key learning point: The first-line lipid management approach for patients ≤75 years of age with established coronary artery disease is treatment with a high-intensity statin.

A 64-year-old woman with hypertension and osteoarthritis reports 2 weeks of epigastric pain that worsens with eating, as well as

several episodes of dark stools. She has been restricting her oral intake because of the pain and has lost 2.7 kg of body weight. She takes

hydrochlorothiazide regularly and has been taking ibuprofen 600 to 800 mg three times daily for the past 3 months for pain related to

her arthritis. She smokes a half-pack of cigarettes daily, drinks no alcohol, and identifies as non-Hispanic white on the patient intake questionnaire. She is not aware of any family history of peptic ulcer disease or gastric cancer. On physical examination, she is afebrile with a blood pressure of 120/65 mm Hg, a heart rate of 75 beats per minute, and an oxygen saturation of 98% while she breathes ambient air. She has tenderness to palpation in the epigastric area without rebound or guarding. Rectal examination reveals black stool and no masses.

Which one of the following diagnoses is most likely in this case?

• Viral gastroenteritis

• Peptic ulcer disease related to ibuprofen use

• Helicobacter pylori -associated peptic ulcer disease

• Gastroparesis

• Functional dyspepsia

Answer explanation

The combination of epigastric pain and dark stool (suggesting melena) in a patient with long-term ibuprofen use should raise suspicion for peptic ulcer disease (PUD). Most cases of PUD are caused by either Helicobacter pylori infection or nonsteroidal antiinflammatory drug (NSAID) use; the remainder are typically classified as idiopathic. The clinical presentation of PUD is similar whether it is caused by

H. pylori or by NSAID use. Risk factors for developing PUD while taking an NSAID include a history of PUD, a high daily dosage of the NSAID, chronic NSAID use, advanced age (>75 years), use of other medications that enhance NSAID toxicity, and concurrent cardiovascular disease. Risk factors for H. pylori infection include lower socioeconomic status, living in a developing country as a child, Black or Hispanic race/ethnicity, and family history of PUD or gastric cancer. This patient has no clear risk factors for H. pylori infection, but she does have several risk factors for an NSAID-related ulcer, making this the more likely diagnosis. However, she should still undergo evaluation for H. pylori infection, as the combination of H. pylori infection and NSAID use increases the risk for PUD.

Complications of PUD from any cause include gastrointestinal bleeding and gastric outlet obstruction, which is typically related to an ulcer in the pyloric channel or the duodenum. Nausea and vomiting are the most common symptoms of gastric outlet obstruction, but the obstruction may also cause bloating, abdominal pain, loss of appetite, and weight loss.

Key learning point: The most likely diagnosis in a woman who takes high-dose ibuprofen and reports 2 weeks of epigastric pain and dark

stools is peptic ulcer disease related to ibuprofen use.

A 50-year-old man with a history of mild chronic obstructive pulmonary disease presents to the emergency department during influenza

season with 2 days of fever, chills, myalgias, dry cough, and dyspnea. On examination, he has a temperature of 38.5°C, a blood pressure of 140/90 mm Hg, a heart rate of 104 beats per minute, a respiratory rate of 24 breaths per minute, and an oxygen saturation of 93% while he is breathing ambient air. Pulmonary examination reveals scattered expiratory wheezes and fine crackles in the right upper lobe. Rapid testing for influenza A is positive. A chest radiograph reveals no focal opacities. The patient is given prednisone and inhaled bronchodilators.

Which one of the following treatments is most appropriate for this patient's influenza?

• Zanamivir

• Amantadine

• Amoxicillin-clavulanate

• Ribavirin

• Oseltamivir

Answer explanation

Influenza is typically characterized by an acute onset of fever, chills, myalgias, headache, and upper respiratory symptoms; the infection can also cause lower respiratory tract disease. During influenza season, especially in patients with respiratory disease, antiviral therapy with a neuraminidase inhibitor is indicated and should be started promptly (within 48 hours of symptom onset). Therapy may be considered beyond 48 hours for severe or progressive infections and in certain patient populations, such as immunocompromised individuals.

In this case, the patient’s underlying chronic obstructive pulmonary disease (COPD) puts him at increased risk for influenza complications or severe disease. Treatment with antivirals should be initiated in an attempt to limit his COPD exacerbation. Current recommendations for influenza therapy include the use of oral oseltamivir, inhaled zanamivir, or intravenous peramivir.

Oseltamivir should be dosed twice daily for 5 days for the treatment of influenza. It can also be dosed once daily as prophylaxis in those with a history of influenza exposure. Intravenous peramivir is most appropriate for hospitalized patients.

Key learning point: The appropriate treatment for influenza in a patient with underlying respiratory disease is oseltamivir 75 mg twice

daily for 5 days.

A 77-year-old man returns for follow-up after a workup for dyspnea and weight loss revealed diffusely metastatic lung cancer. Three

days earlier, his oncologist informed him that his prognosis was poor, estimating his survival at “weeks to months.” Since that

appointment, he has been tearful, thinking about the things that he will never get a chance to experience. He reports some difficulty

sleeping, low energy, difficulty concentrating, and a loss of appetite. He has not informed his wife or children of his diagnosis or

prognosis.

Which one of the following statements is most appropriate to facilitate the coping process and minimize distress in this patient?

• It’s important to make the most of the time you have left. Would you consider starting an antidepressant

  now?

• I’m glad you shared your feelings with me. Let’s talk more about the impact of this painful news; then we can see how best to get your family’s support.

• It must be very difficult to keep this information private. Would you be willing to take a medication to help

  you relax?

• Symptoms of depression are to be expected after hearing a prognosis like yours. Anyone in your position

  would feel sad.

• Your survival could be much longer than your oncologist has predicted. I would encourage you not to be sad

  but to focus on enjoying the time you have left

Answer explanation

Painful emotions are a normal, expected reaction in patients and caregivers facing a life-threatening illness. Interventions to facilitate the coping process include listening empathically, providing a supportive presence for patients and their families, validating feelings, encouraging open communication, fostering hope, allowing opportunities to discuss fears, and educating patients and their families about ways to manage their responses.

Fluctuating emotions are expected components when facing limited survival, but prolonged or debilitating levels of distress may indicate an episode of a mood disorder or suggest limited psychological resources for bearing painful emotions. In the context of a new diagnosis of an aggressive illness, more active treatments for depressive symptoms, including psychotherapy and medication, may help the patient manage his distress. If the patient survives long enough (for example, 6 months or longer), it may become clear whether his mood symptoms are a transient reaction or if they are the early phase of a complicated grief disorder or a mood disorder.

Key learning point: Interventions to facilitate the coping process include listening empathically, providing a supportive presence for patients and their families, validating feelings, encouraging open communication, fostering hope, allowing opportunities to discuss fears, and educating patients and their families about coming to terms with mortality.

A 44-year-old man with HIV infection seeks advice about HIV treatment and initiation of antiretroviral therapy. He feels well, has never taken antiretrovirals, and has a CD4 count of 450 cells per mm (reference range, 400–1600) and an HIV viral load of 10,000 copies/mL. An HIV genotype shows no resistance mutations. Baseline laboratory results are normal.

Which one of the following management approaches is most appropriate for this patient?

• Initiate antiretroviral therapy if the CD4 count drops below 350 cells per mm3

• Initiate trimethoprim-sulfamethoxazole now for prophylaxis

• Initiate antiretroviral therapy when the HIV viral load is >100,000 copies/mL

• Initiate antiretroviral therapy if toxoplasmosis develops

• Initiate antiretroviral therapy now

Answer explanation

Both the U.S. Department of Health and Human Services and the International AIDS Society-USA recommend antiretroviral therapy (ART) for all patients with HIV, regardless of CD4-cell count. This strategy is supported by evidence from large observational studies as well as randomized controlled trials. Moreover, data from the international HPTN 052 trial showed that in HIV-serodiscordant couples, ART initiation in people with HIV and CD4 counts between 350 and 550 cells per mm reduced sexual transmission of the virus to their

uninfected partners and also reduced the frequency of HIV-related clinical events, such as extrapulmonary tuberculosis.

Key learning point: Antiretroviral therapy is recommended for all with HIV infection regardless of CD4-cell count.

A young man, 18 years of age, presents 2 days after feeling a pop along the back of his thigh while running. The pain, which prevented

him from returning to activity, is exacerbated by ambulation. Nonsteroidal antiinflammatory medications have provided some relief.

He has tenderness and visible ecchymosis along the posterior-medial aspect of his upper leg; there is no tenderness at the ischial

tuberosity. Resisted knee flexion demonstrates minor weakness and reproduces the pain.

Which one of the following next steps is most appropriate for this patient?

• Urgent MRI

• Platelet-rich plasma therapy

• Application of an immobilizing cast

• Referral to an orthopedic surgeon

• Rest, ice, and compression

Answer explanation

This patient has an acute, uncomplicated hamstring strain. The typical injury that provokes a hamstring strain is due to acute loading that occurs during hip flexion and knee extension, such as when running. Affected patients often describe experiencing a popping sensation when the injury occurs. In the acute setting, the pain often prevents patients from returning to activity.

Moderate-severity (grade II) hamstring strains, as seen in this patient, may manifest with posterior thigh ecchymosis as well as diminished strength and pain provoked by resisted knee flexion on physical examination. A mild (grade I) hamstring strain would manifest with slight pain, no reduction in strength, and no ecchymosis.

Appropriate initial management for a hamstring strain includes rest, ice, compression, and antiinflammatory medications. Therapy should begin with a strengthening program, and the return to activity should be gradual (4 to 6 weeks) because these injuries heal slowly.

Key learning point: The most appropriate initial management for an acute, uncomplicated hamstring strain is rest, ice, and compression.

A 59-year-old man with gout who has been prescribed allopurinol, 300 mg daily, for 5 years reports 2 days of pain and swelling in his

right first metatarsophalangeal joint and generally throughout his right foot. This is his typical location for gout. He reports feeling well,

except for the localized pain and swelling, and has had no fevers or chills. This is his first gout flare in 3 years. Laboratory testing 6

months ago identified a uric acid level of 4.2 mg/dL (reference range, 2.5–8.0). Physical examination reveals swelling, erythema, limited range of motion of the right first metatarsophalangeal joint, swelling and erythema in the midfoot, difficulty with eversion and inversion of the foot, and pain on ambulation. The patient is afebrile and has normal vital signs.

The flare resolves with colchicine treatment. When the patient returns for follow-up 2 weeks later, his uric acid level is 10.2 mg/dL.

Which one of the following factors is most likely to have caused this patient’s flare?

• Increased alcohol consumption

• Recent change in diet

• Nonadherence to the colchicine regimen

• Nonadherence to the allopurinol regimen

• Development of tophi

Answer explanation

When a patient whose gout was previously well controlled with allopurinol experiences a flare and has a newly elevated uric acid level, the clinician should determine the status of allopurinol adherence before deciding whether to raise the allopurinol dose or to add colchicine or a nonsteroidal antiinflammatory drug. Sudden discontinuation or recent initiation of allopurinol can trigger attacks of gout by causing abrupt increases or decreases in serum uric acid. Development of resistance to allopurinol has not been reported. Some medications, particularly diuretics, frequently raise uric acid levels.

Key learning point: When a patient with long-standing gout that is generally well controlled on allopurinol has a newly elevated uric acid level, the first possible explanation to explore is nonadherence to the allopurinol treatment regimen