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NEJM Journal Watch

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Course Description

After hearing and assimilating this program, the listener will be better able to: ( 1 ) Increase his/her basic knowledge of important advances in medicine; ( 2 ) Identify a broad range of clinical research reported in the medical literature; ( 3 ) Synthesize research findings through one-on-one interviews with authors and editorialists; ( 4 ) Integrate new treatments reviewed in the summaries into current practice; ( 5 ) Challenge oneself with thoughtful, clinically relevant questions. Disclosure In adherence to the ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, Dr. Neil Zakai, Dr. Peter Lindenauer, and the planning committee members reported that they had nothing to disclose. ELEVATED RISK FOR THROMBOTICEVENTS AFTER SUPERFICIAL VENOUS THROMBOSIS Recently, it was shown that 9% of patients with superficial venous thrombosis had an extension of thrombi to the deep veins ( www.jwatch.org /na32247 ), suggesting that patients with superficial venous thrombosis might be at risk for future thrombotic problems. To estimate the risk for venous and arterial thrombosis happening after superficial venous thrombosis, researchers in the Netherlands and Denmark studied data on 11,000 patients with superficial venous thrombosis and 500,000 age- and sex-matched controls. Details appear in the January8th, 2015 issue of Blood ( http:// dx.doi.org /10.1182/blood-2014-06-577783 ). At a median follow-up of 7years, the results were: The incidence of deep vein thrombosis was higher in the case patients than in the controls (13 vs . 1 per 1000 patient-years). The incidence of pulmonary embolism was also higher in the case patients than in the controls (5 vs . 1 per 1000 patient-years). The association of superficial venous thrombosis with subsequent deep vein thrombosis and pulmonary embolism was stronger in men than in women. Adverse arterial events (like acute myocardial infarction and ischemic stroke) were more common in the case patients than in the controls; mortality was higher as well. The rates of adverse venous and arterial events, and death, were highest in the first 3months after superficial venous thrombosis and gradually declined after that. This analysis shows that patients with superficial venous thrombosis are at risk for subsequent deep vein thrombosis, pulmonary embolism, myocardial infarction, and ischemic stroke. Whereas the extension of the superficial venous thrombosis to the deep veins might account for the heightened risk for venous thromboembolism, the higher incidence of arterial events suggests that arterial and venous thrombosis are different manifestations of an underlying thrombotic propensity. TWO-POINT COMPRESSION ULTRASOUND IS INADEQUATE TO RULEOUT DVT We know that isolated two-point compression ultrasound to detect clots in the common femoral or popliteal veins will miss some lower extremity deep vein thromboses. To quantify the miss rate, researchers retrospectively studied nearly 2500 patients with suspected deep vein thrombosis who underwent full-leg ultrasound at a single emergency department during a 6-year period. Details appear on the website of the Annals of Emergency Medicine ( http:// dx.doi.org /10.1016/ j. annemergmed.2014.10.032 ). Deep vein thrombosis was detected in 15% of the patients; of those patients, 6% had isolated thrombi in proximal veins other than common femoral and popliteal veins. This study doesnt change the current standard of care. If a patient has a positive d -dimer test and a negative two-point compression study, a repeat full lower-extremity venous ultrasound should be performed within a week. If adherence to follow-up is a concern, then a full study can be done in the emergency department. POSTOPERATIVE COMPLICATIONS AFTER CAROTID ENDARTERECTOMY Perioperative complications especially stroke or death are key considerations when patients contemplate carotid endarterectomy. In a study in the January2015 Journal of Vascular Surgery ( http:// dx.doi.org /10.1016/ j. jvs.2014.05.100 ), researchers used a national surgical database to determine the rates and the predictors of postoperative stroke and death among nearly 4000 patients who underwent carotid endarterectomy at 80 medical centers in the United States in 2012. Carotid stenosis was symptomatic in 40% of the patients and asymptomatic in the rest. The 30-day incidence of postoperative stroke or death was 3% overall nearly 5% in the patients with symptomatic stenosis and not quite 2% in those with asymptomatic stenosis. In multivariate analysis, the independent predictors of stroke or death among the symptomatic patients were emergency surgery, contralateral carotid stenosis of 80% or greater, a past stroke (as opposed to a transient ischemic attack), and one or more physiologic high-risk characteristics as defined by the American College of Surgeons (these included cardiac, pulmonary, and renal comorbidities; www. ncbi.nlm.nih .gov /pmc/articles/PMC3728168/table/T1/ ). Among the asymptomatic patients, the independent predictors were contralateral stenosis of 80% or greater and an American Society of Anesthesiologists Physical Status Classification of 4 or 5. The 30-day incidence of nonstroke major complications was 5%. Ideally, patients undergoing carotid endarterectomy would have access to surgeon-specific and institution-specific rates of postoperative stroke and death. Because this information isnt often available, studies like this one are necessary to inform clinical decision-making. Interestingly, most endarterectomies in this database were done for asymptomatic carotid stenosis; with contemporary medical management, it isnt clear whether surgery confers any long-term benefit in these patients. (For an analysis of this topic see http:// dx.doi.org /10.1001/jamainternmed.2014.4920 ). HEALTHY LIFESTYLE MIGHT PREVENT CHD IN NEARLY 75% OF WOMEN Although mortality from coronary heart disease in the United States is declining, the disease remains the leading cause of death among American women. In an analysis in the January6th, 2015 Journal of the American College of Cardiology ( http:// dx.doi.org /10.1016/ j. jacc.2014.10.024 ), researchers evaluated six healthy lifestyle habits (namely, not smoking, 2.5hours /week of physical activity, a healthy diet, a normal body-mass index, an average of 1 or fewer alcoholic drinks /day , and only up to 7hours /week of television viewing); they studied 90,000 women between the ages of 27 and 44 to see what proportion of coronary heart disease (nonfatal myocardial infarction and coronary heart disease-related death) might be preventable. During 20years of follow-up, there were 460 cases of newly diagnosed coronary heart disease. The hazard ratio for coronary heart disease among the women who adhered to all six of the healthy habits was 0.08, compared with those who had none of the habits. For an individual woman, not smoking was by far the most beneficial of the six habits; conversely, a low level of television watching wasnt independently protective against coronary heart disease. Roughly three quarters of incident coronary heart disease was attributable to poor lifestyle habits. This analysis of data from the Nurses Health Study II suggests that most coronary heart disease in women is preventable through an adherence to healthy lifestyle habits. An editorialist points out ( http:// dx.doi.org /10.1016/ j. jacc.2014.10.023 ) that analyses of large cohort studies show that only a small minority of participants meet all of the healthy lifestyle metrics and that only modest progress in coronary heart disease prevention is projected if current trends continue. Even so, this study suggests that substantial reductions in clinical coronary heart disease are possible if clinicians can help their patients overcome the challenges of behavior change. HIGHER WHOLE-GRAIN INTAKE IS ASSOCIATED WITH LOWER MORTALITY A higher intake of whole grains is associated with improvements in a wide range of cardiovascular and metabolic disease risk factors and markers, but its influence on all-cause mortality isnt clear. In two prospective studies on the website of JAMA Internal Medicine ( http:// dx.doi.org /10.1001/jamainternmed.2014.6283 ), researchers examined data from healthcare professionals in the United States that included about 120,000 adults who were free of cancer and cardiovascular disease at enrollment (the average age of the patients at baseline was 50 for men and 53 for women). Intakes of whole grains (like wheat, oats, cornmeal, rye, bulgur, buckwheat, brown rice, and popcorn), plus other foods, were evaluated every 2 to 4years for 25years. After adjusting for age, smoking, and other potential confounders, cardiovascular-related mortality was 15% lower among the patients with the highest vs . the lowest intakes of whole-grains (the median intake during the study period was 33 g /day vs . 4 g /day in women and 48 g /day vs . 6 g /day in men), whereas cancer-related mortality was similar in all of the groups. Overall mortality was 9% lower in the group with the highest intake of whole grains. If the association shown in this study is causal, the results would extend the known benefits of whole-grain intake on cardiovascular risk factors to a reduction in cardiovascular-related mortality. The contrast with a lack of effect on cancer-related mortality reinforces the validity of the cardiovascular results. Clinicians now have another reason to counsel their patients to eat more whole grains. WOMEN AND MEN BENEFIT EQUALLY FROM STATIN THERAPY Statins safely lower the incidence of major adverse vascular events (like nonfatal myocardial infarctions or coronary death, any stroke, and coronary revascularization) by about 20% for every 40 mg/ dL reduction in LDL cholesterol, regardless of baseline cardiovascular risk. But women have been underrepresented in many trials of statins, and meta-analyses based on aggregate data have lacked the statistical power to reliably compare the effectiveness of statins in women and men. Back in 2012, a patient-level meta-analysis of 30 randomized trials of statin vs . control therapies or high- vs . low-dose statins included more than 170,000 patients (about a quarter were women); that review established the effectiveness of statins regardless of cardiovascular risk and suggested that statins were equally effective in both sexes in all risk strata ( www.jwatch.org /jw201206120000004 ). Now, on the website of The Lancet ( http:// dx.doi.org /10.1016/ S0140- 6736(14)61368-4 ), the researchers revisit those data to describe the effects of statins in women and men in greater detail. Statins had similar effects on lipid levels in women and men after a year of treatment. For each 40-mg/dL reduction in LDL cholesterol, women and men had comparable overall reductions in major vascular events and all-cause mortality, with similar results in each stratum of cardiovascular risk. Statins werent associated with differences in cancer incidence or noncardiovascular-related mortality in either sex. This analysis provides reassurance that recent risk-based guidelines on lipid management can be applied to both women and men with the expectation of equivalent benefits. IS COENZYME Q10 EFFECTIVE IN STATIN MYOPATHY? Statins interfere with the production of coenzyme Q10 (so-called CoQ10), which has a role in muscle metabolism. For that reason, CoQ10 supplementation has been proposed as a way to mitigate the myalgia that is associated with statin therapy. In a meta-analysis in the January2015 issue of Mayo Clinic Proceedings ( http://dx.doi.org/10.1016/ j.mayocp.2014.08.021 ), researchers examined six placebo-controlled, randomized trials that included 300 patients to determine the efficacy of CoQ10 supplementation. Five trials enrolled patients with muscle symptoms; the sixth trial enrolled asymptomatic patients, but looked at the effects of CoQ10 on creatine kinase blood levels (as did several of the other trials). Study durations ranged from 1 to 3months, and CoQ10 doses ranged from 100 to 400 mg/ day. CoQ10 regardless of the dose had no significant effect on muscle symptoms or creatine kinase levels. In a study in the February2015 issue of Atherosclerosis ( http:// dx.doi.org /10.1016/ j. atherosclerosis.2014.12.016 ), which wasnt included in the meta-analysis summarized above, researchers identified 40 patients with histories of statin myalgia who had muscle symptoms on simvastatin but not on placebo during a randomized, crossover, run-in phase. Next, these patients were randomized to simvastatin plus either 600 mg/ day of CoQ10 or placebo. During 2months of treatment, CoQ10 had no effect on muscle symptoms. A range of dosages of coenzyme Q10 supplementation isnt beneficial in patients with myalgia that is attributed to statin therapy. PREGABALIN IS INEFFECTIVE FOR PATIENTS WITH NEUROGENICCLAUDICATION Frequently, pregabalin and gabapentin are prescribed for the pain of sciatica or spinal stenosis, but we dont have strong evidence to support that practice. In a double-blind crossover study in the January20th, 2015 issue of Neurology ( http:// dx.doi.org /10.1212/WNL.0000000000001168 ), researchers tested the efficacy of pregabalin in 30 patients with radiographically confirmed lumbar spinal stenosis and neurogenic claudication for 3months or longer. Enrollment criteria included pain on ambulation, but not at rest. On baseline treadmill testing, the average time to a pain score of 4 or higher (on a 10-point scale) was 2.5minutes. The researchers randomized the patients to either 75mg of pregabalin or an active placebo (which was 6.25mg of diphenhydramine) initially twice /day , with doses doubled after 3days. (The low-dose diphenhydramine control was chosen to mimic the sedative effects of pregabalin and maximize blinding.) After 10days of treatment, a 3-day taper, and a 1-week washout period, the patients got the opposite treatment. On repeat treadmill testing, there were no significant differences between the pregabalin and the active-placebo periods in the time to the onset of a pain score of 4 or higher. One secondary outcome (namely, a standardized disability score) showed greater improvement with active placebo than with pregabalin. Side effects were reported more often with pregabalin than with placebo. In this trial, pregabalin wasnt effective and was associated with a high incidence of adverse effects (especially dizziness). Although the study was small, it was powered to show a 2-minute difference in the time to substantial pain. The benefits of anticonvulsants for painful diabetic or zoster neuropathy cant necessarily be extrapolated to pain caused by mechanical nerve compression. This study was industry-funded. ICATIBANT IS EFFECTIVE IN PATIENTSWITH ACE-INHIBITORINDUCED ANGIOEDEMA Icatibant (trade name: Firazyr) is a selective bradykinin B 2 receptor antagonist that has been approved by the Food and Drug Administration for treating patients with hereditary angioedema. Like hereditary angioedema, angioedema caused by angiotensin-convertingenzyme inhibitors is bradykinin-mediated. Standard treatment with corticosteroids and antihistamines drugs that are typically directed at mast cellmediated angioedema dont benefit patients with ACE-inhibitorinduced angioedema. In theory, icatibant should be effective for ACE-inhibitorinduced angioedema, which occasionally results in airway obstruction and the need for intubation. In a study in the January29th, 2015 New England Journal of Medicine ( http:// dx.doi.org /10.1056/NEJMoa1312524 ), researchers in Germany randomized 30 adults who presented within 10hours of the onset of ACE-inhibitorinduced angioedema of the upper aerodigestive tract (namely, the face, lips, cheeks, tongue, soft palate or uvula, pharynx, and larynx) to either a 30-mg subcutaneous injection of icatibant or usual therapy consisting of intravenous prednisolone (500mg) plus clemastine (2mg). Median times to the full resolution of angioedema were 8hours in the icatibant group and 27hours in the usual-care group; 40% of the icatibant patients had full resolution of their symptoms within 4hours, compared with none of the usual-care patients. Three usual-care patients needed rescue therapy with icatibant; one of these patients also needed tracheotomy. The only side effects in the icatibant patients were injection-site reactions. Although this was a small phase II trial, the results of icatibant for ACE-inhibitorinduced angioedema were very impressive. Icatibant is extremely expensive (more than US$8000 per 30-mg dose), but if it can prevent tracheotomy or a stay in the intensive care unit, it will be worth the high cost. This study was partially industry-funded. HOSPITALIZATION FOR PNEUMONIA IS ASSOCIATED WITH RISK FOR SUBSEQUENT CVD In the short term, the risk for incident cardiovascular disease is higher after respiratory infections, but whether the long-term risk for cardiovascular disease is affected isnt clear. In a study in the January20th, 2015 issue of JAMA ( http:// dx.doi.org /10.1001/jama.2014.18229 ), researchers analyzed data from two prospective cohort studies of cardiovascular disease risk factors and compared the risk for incident cardiovascular disease in 1300 patients hospitalized with pneumonia and in 2600 age-matched controls. In both of the studies, the patients with pneumonia were more likely to have several traditional cardiovascular disease risk factors. In patients with an average age of 73, the adjusted risk for incident cardiovascular disease during the second and third months following their hospitalizations (after the known initial higher-risk period), was about three times higher in the patients hospitalized with pneumonia than in the controls; the excess risk was up to 80% higher during the ensuing 10years after hospitalization. In patients with an average age of 56, the risk for cardiovascular disease was about double for pneumonia patients in the first 2years, but wasnt significantly elevated in later years. The researchers believe that older patients hospitalized for pneumonia might have an excess risk for developing cardiovascular disease beyond that associated with traditional risk factors and therefore deserve additional preventive measures. But the researchers dont specify what additional risk-reducing interventions might be prescribed for these patients. Plus, because the pneumonia and the control patients in this study differed substantially in their baseline cardiovascular disease risk, whether statistical adjustment adequately minimized confounding isnt clear. NONINVASIVE VENTILATION FOR SEVERE COPD EXACERBATIONS Its been shown that noninvasive positive pressure ventilation is the only intervention that improves mortality in patients hospitalized for exacerbations of chronic obstructive pulmonary disease ( http:// dx.doi.org /10.1002/14651858.CD004104.pub3 ). But many patients who are eligible for this intervention go untreated, and the benefits of this type of noninvasive ventilation in routine clinical practice remain incompletely defined. Until now. In a study in the December2014 issue of JAMA Internal Medicine ( http:// dx.doi.org /10.1001/jamainternmed.2014.5430 ), researchers evaluated data from a retrospective cohort of nearly 30,000 patients (at 400 hospitals in the United States) who were admitted with COPD exacerbations and got either noninvasive positive pressure ventilation or invasive mechanical ventilation within the first 2days of hospital admission. In propensity-matched comparisons vs . invasive ventilation, noninvasive ventilation was associated with significantly lower in-hospital mortality and hospital-acquired pneumonia, shorter length of stay, and lower hospital costs. Although a mortality benefit with noninvasive positive pressure ventilation for patients with exacerbations of chronic obstructive pulmonary disease has already been proven in randomized trials, this large study confirms that benefit in routine clinical practice. Noninvasive positive pressure ventilation is a guideline-recommended intervention ( www. goldcopd .org /Guidelines/ guidelines-resources.html ), which should be considered for any patient admitted with a COPD exacerbation who has respiratory acidosis (a pH of 7.35 or lower) or severe dyspnea with signs of respiratory fatigue or increased work of breathing. OBSTRUCTIVE SLEEP APNEA IS MORECOMMON IN ASTHMA PATIENTS Its been shown that obstructive sleep apnea is more prevalent in patients with asthma than in those without it. A cohort study in the January13th, 2015 issue of JAMA ( http:// dx.doi.org /10.1001/jama.2014.17822 ) provides additional evidence for that association. In the Wisconsin Sleep Cohort Study, 1500 randomly chosen state employees were followed from 1988 to 2013; the participants underwent overnight polysomnography every 4years. Among the 80 participants with asthma whose sleep studies were normal at baseline, 30% developed obstructive sleep apnea (defined by an apnea-hypopnea index of 5 or more events /hour ), whereas 17% of the participants without asthma developed sleep apnea. The relative risk for new-onset obstructive sleep apnea was 1.4 in the participants with asthma and was independent of body-mass index. Asthma is associated with an excess risk for new-onset obstructive sleep apnea. Clinicians should routinely ask all patients with asthma about snoring, apnea, and daytime somnolence and consider sleep studies based on current guidelines ( www.jwatch.org /NA35439 ). But routine sleep studies in patients with asthma arent indicated, and it isnt known if treating asthma patients with obstructive sleep apnea can improve asthma control. CLINICAL CHARACTERISTICS OF ACUTEENCEPHALITIS Due to its relatively low incidence, acute encephalitis remains poorly characterized. To better define the etiology, clinical presentation, and outcomes of this condition, researchers retrospectively analyzed all of the confirmed cases at a tertiary care medical center in Minnesota between 2000 and 2012. Details appear in the January27th, 2015 issue of Neurology ( http:// dx.doi.org /10.1212/WNL.0000000000001190 ). Of 200 patients with an average age of 58, half were men. Viral encephalitis accounted for 100 cases, most commonly herpes simplex virus, followed by varicella zoster virus, West Nile virus, Epstein-Barr virus, and HIV. Autoimmune disease was responsible for 20% of the cases, with disease mainly due to anti N -methyl- d -aspartate receptors or voltage-gated potassium channel antibodies. Etiology wasnt identified in 30% of the cases. Overall, outcomes were good (that is to say, mild or no disability) in half of the patients at discharge and among those with available follow-up information approximately 60% at a year. Mortality was 9% during hospitalization and 17% at a year. The factors that were associated with poor outcome (defined as moderate-to-severe disability or death) were being older than 65, being immunocompromised, being in a coma, having acute thrombocytopenia, and having the need for mechanical ventilation. Although the relative frequency of viral, autoimmune, and other or unknown etiologies is certainly related to the geographic location of this medical center, the review provides clinically helpful data on the natural history and prognosis of acute encephalitis. Its important to note that the etiology remained unknown in almost a third of the cases. ATYPICAL ANTIPSYCHOTIC USE IS ASSOCIATED WITH RISK FOR FALLSAND FRACTURES IN ELDERS Antipsychotic medications, often used inappropriately for managing dementia and behavioral disturbances in nursing home residents, have been linked to fractures in elderly patients; whether this association encompasses newer atypical antipsychotics isnt as clear. To examine this issue, researchers in Canada used linked administrative and healthcare databases to study nearly 100,000 patients with an average age of 81 who got new outpatient prescriptions for atypical antipsychotic drugs (namely, quetiapine, risperidone, or olanzapine); a quarter of the patients were in long-term care facilities, and more than half had dementia. These patients were matched on 90 clinical and demographic factors with an equal number of controls who didnt get these prescriptions. Details appear on the website of JAMA Internal Medicine ( http:// dx.doi.org /10.1001/jamainternmed.2014.6930 ). During 3months of follow-up, the patients who got prescriptions for atypical antipsychotics, compared with those who didnt, had significantly higher risks for falls and fractures, especially hip fractures. These results provide further support for restricting the use of any antipsychotic medications conventional or atypical in elderly patients, especially for the purpose of controlling the agitation and the behavioral disturbances associated with dementia. Unfortunately, recent studies suggest that inappropriate antipsychotic use continues at a high rate ( http://www.jwatch.org/jw201302120000003/2013/02/12/antipsychotic-prescribing-us-nursing-homes ). COMPARATIVE EFFECTIVENESS OF PHARMACOLOGIC INTERVENTIONS FOR KNEE OA Initial options for treating patients with knee osteoarthritis include acetaminophen, nonsteroidal anti-inflammatory drugs, intra-articular corticosteroids, or intra-articular hyaluronic acid. But which agent should be tried first? Using a network meta-analysis of data from 140 studies (with more than 30,000 patients), researchers evaluated these agents (including 4 NSAIDs), both head-to-head and vs . oral or intra-articular placebos. Findings appear in the January6th, 2015 Annals of Internal Medicine ( http:// dx.doi.org /10.7326/M14-1231 ). For pain outcomes, intra-articular placebo was more effective than oral placebo. Acetaminophen was the least effective and failed to produce a clinically significant improvement, followed by (in ascending order of effectiveness) intra-articular placebo, celecoxib, naproxen, ibuprofen, diclofenac, and intra-articular corticosteroids; intra-articular hyaluronic acid was the most effective treatment. Notably, no oral NSAID was statistically better for pain than intra-articular placebo. For functional outcomes, all of the treatments (except intra-articular corticosteroids) were more effective than placebo. Naproxen, ibuprofen, diclofenac, and celecoxib were all significantly better than acetaminophen. This network analysis showed some surprising results: Acetaminophen failed to produce a clinically significant improvement in pain, no oral NSAID was better than intra-articular placebo, and intra-articular hyaluronic acid was the most effective agent for pain. This study suggests that acetaminophen is overprescribed and, at first glance, intra-articular hyaluronic acid is underused. But if one subtracts the placebo effect of intra-articular injection itself (which was shown in this analysis), hyaluronic acid becomes less attractive; plus, hyaluronic acid injections are expensive. ESOPHAGEAL CANCER RISK WITH BARRETT ESOPHAGUS Endoscopic screening and surveillance strategies for Barrett esophagus have been justified by the hypothesis that recognizing and monitoring precancerous conditions can change clinical outcomes. The estimated annual risk for progression from no dysplasia to esophageal adenocarcinoma in patients with Barrett esophagus in the United States was as high as 2% in early studies from tertiary referral centers. But in more recent, large national cohort studies from the Netherlands, Ireland, and Denmark, the annual risks were lower. In a population-based, retrospective cohort study in the December2014 American Journal of Gastroenterology ( http:// dx.doi.org /10.1038/ajg.2014.324 ), researchers evaluated the risk for esophageal cancer in 30,000 patients with Barrett esophagus and an average age of 62 (nearly all were white men) from 120 centers in the United States Veterans Health Administration. During almost 150,000 patient-years of follow-up, the annual incidence of esophageal adenocarcinoma was 0.3%. Excluding the patients with esophageal cancer diagnosed within a year of getting a diagnosis of Barrett esophagus (presumed to be incident cancers, accounting for half of all esophageal adenocarcinoma cases), the annual incidence was under 0.2%. Including the patients who underwent endoscopic ablation or esophagectomy for high-grade dysplasia or esophageal cancer, the annual incidence was 0.5%. This is the first national cohort study in the United States in which the risk for esophageal adenocarcinoma with Barrett esophagus was evaluated, and its estimates are more in line with those from the recent international studies than with the earlier American studies. Given that ablation is now used more often in the U.S. and esophagectomy is being performed for high-grade dysplasia, the inclusion of these patients is justified in defining the overall incidence rate. Limitations of this study include the lack of a systematic surveillance definition, standardized biopsy protocols, and the stratification for dysplasia or covariates (like obesity, smoking, and alcohol use). The Veterans Health Administration population also limits the generalizability of these results. Even so, these incident rates will be helpful for clinicians when counseling patients and evaluating strategies for surveillance or ablation. REASSESSING CHLORHEXIDINEBATHING One recently developed strategy to prevent hospital-acquired infections in intensive care units has been unit-wide patient bathing with chlorhexidine gluconate. But chlorhexidine is relatively expensive, and theres concern that its ongoing use could lead to the emergence of resistant organisms. In a cluster-randomized, crossover trial in the January27th, 2015 issue of JAMA ( http:// dx.doi.org /10.1001/jama.2014.18400 ), researchers compared once-daily bathing with 2% chlorhexidineimpregnated cloths vs . nonantimicrobial cloths in more than 9000 evaluable patients in five adult ICUs at a single medical center. The incidence of the primary outcome (which was a composite of central lineassociated bloodstream infections, ventilator-associated pneumonia, catheter-associated urinary tract infections, and Clostridium difficile infections) was identical during both the chlorhexidine and the control bathing periods (3 per 1000 patient-days). In secondary analyses, the incidence of ventilator-associated pneumonia was significantly higher during the chlorhexidine bathing periods, but the rates of the other individual infections, hospital-acquired bloodstream infections, the acquisition of multidrug-resistant organisms, and in-hospital mortality were similar during the two periods. Although the initial rationale for chlorhexidine bathing in intensive care units was to prevent the transmission of multidrug-resistant organisms, this effect wasnt incorporated into the primary study outcome nor was active surveillance performed to evaluate it. Plus, the small number of central lineassociated bloodstream infections in this trial suggests that the bacteremia rate was already lower than that at which the study could detect an effect. These findings suggest that institutions should evaluate the potential benefits of chlorhexidine bathing in the context of their overall infection-prevention programs and their rates of multidrug-resistant organism acquisition and hospital-acquired infection. TREATING HYPERTENSION DURING PREGNANCY Almost 10% of pregnancies are affected by hypertension, yet many clinicians remain reluctant to prescribe antihypertensives during pregnancy. In an open-label multicenter trial in the January29th, 2015 New England Journal of Medicine ( http:// dx.doi.org /10.1056/NEJMoa1404595 ), researchers randomized 1000 women with singleton pregnancies to either less-tight blood pressure control (a diastolic target of 100mmHg) or tight control (a diastolic target of 85mmHg) to evaluate the effects of the two targets during pregnancy. The patients had mild, nonproteinuric preexisting hypertension or gestational hypertension (with a diastolic blood pressure between 90 and 105mmHg without medication or between 85 and 105mmHg with medication). In both of the groups, labetalol was the most commonly used antihypertensive, but more women needed medication to reach the tighter goal. The rates of pregnancy loss, low birth weight, and the need for neonatal intensive care were similar in the two groups. But significantly fewer women treated with tighter control developed abnormally low platelet counts or elevated liver function tests, with a trend toward less of a need for blood transfusion. Although optimal approaches to managing hypertension during pregnancy still need to be identified, this rigorous trial should reassure clinicians that the benefits of treating maternal hypertension with labetalol during pregnancy seem to outweigh the risks. WORKING LONG HOURS IS ASSOCIATED WITH RISKYALCOHOLUSE Working long hours has been linked to risks for injury, depression, and anxiety. In a meta-analysis on the website of The BMJ ( http:// dx.doi.org /10.1136/bm j. g7772 ), researchers systematically reviewed 60 studies from 14 countries to see if long work hours were associated with risky alcohol use. In a cross-sectional analysis of data on more than 300,000 patients, working long hours (55hours /week or more) was associated with a greater likelihood of high alcohol use. In a prospective analysis of data on more than 100,000 patients, the risk for new-onset risky alcohol use (more than 14 drinks /week for women and more than 21 drinks /week for men) for people who worked 49hours /week or longer was elevated, compared with the risk for people who worked between 35 and 40hours /week . These associations didnt vary between men and women or by age, socioeconomic group, geographical region, or by the type of the study sample (for example, population-based vs . an occupational cohort). Working long hours is associated with a greater likelihood of high alcohol use and new-onset risky alcohol use. The researchers speculate that long working hours and work-related factors, like high demands and a lack of control, contribute to stress at work; affected workers might use alcohol to alleviate that stress.

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Learning Format 6 Hours
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Internal Medicine Gastroenterology Emergency Medicine Vascular Surgery Neurology Cardiology