Recurrent Ischemic Stroke: Strategies for Prevention.

Recurrent strokes make up almost 25% of the nearly 800,000 strokes that occur annually in the United States. Risk factors for ischemic stroke include hypertension, diabetes mellitus, hyperlipidemia, sleep apnea, and obesity. Lifestyle modifications, including tobacco cessation, decreased alcohol use, and increased physical activity, are also important in the management of patients with a history of stroke or transient ischemic attack. Antiplatelet therapy is recommended to reduce the risk of recurrent ischemic stroke. The selection of antiplatelet therapy should be based on timing, safety, effectiveness, cost, patient characteristics, and patient preference. Aspirin is recommended as initial treatment to prevent recurrent ischemic stroke. Clopidogrel is recommended as an alternative monotherapy and in patients allergic to aspirin. The combination of clopidogrel and aspirin is not recommended for long-term use (more than two to three years) because of increased bleeding risk. Aspirin/dipyridamole is at least as effective as aspirin alone, but it is not as well tolerated. Warfarin should not be used for prevention of recurrent ischemic stroke.

Nonpharmacologic management of hypertension: what works?

Hypertension is one of the most common conditions encountered in primary care. Nonpharmacologic strategies have been shown to help lower blood pressure. Lifestyle modifications are recommended for all patients with hypertension. The American Heart Association/American College of Cardiology lifestyle management guideline recommends a diet emphasizing vegetables, fruits, and whole grains; limiting sodium intake to less than 2,400 mg per day; and exercising three or four times per week for an average of 40 minutes per session. Other nonpharmacologic strategies include weight loss, tobacco cessation, decreased alcohol consumption, biofeedback, and self-measured blood pressure monitoring. For patients with obstructive sleep apnea, the use of continuous positive airway pressure has been shown to improve blood pressure. Dietary supplements such as garlic, cocoa, vitamin C, coenzyme Q10, omega-3 fatty acids, and magnesium have been suggested for lowering blood pressure, but evidence is lacking.

Outpatient diagnosis of acute chest pain in adults.

Approximately 1 percent of primary care office visits are for chest pain, and 1.5 percent of these patients will have unstable angina or acute myocardial infarction. The initial goal in patients presenting with chest pain is to determine if the patient needs to be referred for further testing to rule in or out acute coronary syndrome and myocardial infarction. The physician should consider patient characteristics and risk factors to help determine initial risk. Twelve-lead electrocardiography is typically the test of choice when looking for ST segment changes, new-onset left bundle branch block, presence of Q waves, and new-onset T wave inversions. For persons in whom the suspicion for ischemia is lower, other diagnoses to consider include chest wall pain/costochondritis (localized pain reproducible by palpation), gastroesophageal reflux disease (burning retrosternal pain, acid regurgitation, and a sour or bitter taste in the mouth), and panic disorder/anxiety state. Other less common but important diagnostic considerations include pneumonia (fever, egophony, and dullness to percussion), heart failure, pulmonary embolism (consider using the Wells criteria), acute pericarditis, and acute thoracic aortic dissection (acute chest or back pain with a pulse differential in the upper extremities). Persons with a higher likelihood of acute coronary syndrome should be referred to the emergency department or hospital.

Total synthesis of (+)-ambruticin S: probing the pharmacophoric subunit.

An enantioselective synthesis of the antifungal natural product (+)-ambruticin S has been accomplished starting with the readily available methyl alpha-d-glucopyranoside, (R)-Roche ester, and (S)-glycidol as chirons, which encompassed seven of the 10 stereogenic centers of the target molecule. The remaining three centers were set by a highly diastereoselective, asymmetric cyclopropanation employing a chiral, nonracemic phosphonamide reagent. Our strategy for the construction of the dihydropyran subunit involved a highly syn-selective Lewis acid catalyzed 6-endo-trig cyclization. Other key steps in the synthesis featured an epoxide opening with a dithiane anion, two efficient phosphonamide-anion based olefinations, and a late-stage C-glycosylation.

Caring for patients with co-occurring mental health & substance use disorders.

Consider substance abuse if Tx for mood or anxiety disorders is ineffective. Don't defer treating a mental health issue until a substance use disorder is resolved.

Academic family medicine physicians' confidence and comfort with opioid analgesic prescribing for patients with chronic nonmalignant pain.

OBJECTIVE: To examine academic family medicine physicians' current practices, experiences, beliefs, level of concern about negative outcomes, and confidence and comfort when prescribing opioid analgesics for chronic nonmalignant pain management. DESIGN: Electronic cross-sectional survey. PARTICIPANTS: This study was part of the Council of Academic Family Medicine (CAFM) Educational Research Alliance omnibus survey of active academic US family physicians. MAIN OUTCOME MEASURES: Respondents completed survey items addressing their 1) sociodemographic and practice characteristics, 2) current opioid prescribing practices, 3) experiences and beliefs toward prescribing opioid analgesics for chronic nonmalignant pain management, 4) level of concern about negative opioid-related outcomes, and 5) confidence and comfort when prescribing opioid analgesics. RESULTS: The majority of the sample (n=491) were male (57.8 percent) with 84.1 percent identifying themselves as non-Hispanic white. Nearly all respondents (91.0 percent) reported currently prescribing opioids to patients with chronic nonmalignant pain. Most respondents reported being confident (88.4 percent) and comfortable (76.2 percent) in their prescribing for patients with chronic nonmalignant pain. Family physicians who were comfortable in their opioid prescribing skills were more likely to report satisfaction in prescribing opioids to patients with chronic pain (ρ=0.494, p<0.001), while those who were confident in their opioid prescribing skills were more likely to identify pain management as high priority (ρ=-0.287, p<0.001). CONCLUSIONS: Most academic family physicians currently prescribed opioid analgesics to patients with chronic nonmalignant pain. There was a strong inverse relationship between confidence regarding opioid prescription and concern about negative consequences. Similarly, comfort level was tied to increased satisfaction with the overall process of opioid prescription.

Total synthesis of jerangolid A.

The first total synthesis of the antifungal polyketide jerangolid A has been accomplished. Starting with the readily available (R)-Roche ester and (S)-glycidol as chirons, the synthesis involved a highly syn-selective Lewis acid catalyzed 6-endo-trig cyclization for the construction of the dihydropyran subunit. The lactone segment was built through a tandem NaOMe conjugate addition-lactonization reaction, and further functionalized through a sequence consisting of iodination, I-Mg exchange, and hydroxymethylation. Other key steps in the synthesis featured a novel application of a phosphonamide-anion based olefination and a Julia-Kocienski reaction.