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NEJM Journal Watch

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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. Karina Davidson, Dr. Michael Fiore, and the planning committee members reported that they had nothing to disclose. GUIDELINE WATCH: USPSTFRECOMMENDATION ON SCREENING FOR DEPRESSION IN ADULTS The United States Preventive Services Task Force has revised its 2009 guideline on screening for depression in adults, which recommended screening in the general population when systems are in place to ensure accurate diagnosis, effective treatment, and appropriate follow-up ( www.jwatch.org /jw201001050000003 ). The new recommendation includes pregnant and postpartum women ( http:// dx.doi.org /10.1001/jama.2015.18948 ), based on research published since 2009. This grade B recommendation statement appears in the January26 issue of JAMA ( http:// dx.doi.org /10.1001/jama.2015.18392 ). The Affordable Care Act requires that Grade A or B recommendations by the Task Force be supported by health insurance coverage. The key points of the latest recommendation are: The Task Force found convincing evidence that screening improves the accurate identification of adults with depression in primary care settings. Commonly used depression screening instruments include the Patient Health Questionnaire in adults, the Geriatric Depression Scale in older adults, and the Edinburgh Postnatal Depression Scale in postpartum and pregnant women. Evidence is lacking on optimal screening intervals, but a reasonable approach might include screening all previously unscreened adults and using clinical judgment to see if more-frequent screening is warranted in high-risk patients. Patients with positive screening results should undergo additional evaluation for the severity of depression, comorbid conditions, and alternative diagnoses. The Task Force found adequate evidence that programs that combine depression screening with adequate support systems improve clinical outcomes in adults, including pregnant and postpartum women. Evidence is convincing that antidepressants, psychotherapy, or both are effective in adults with depression identified through screening. Given the potential harms of certain medications to fetuses and newborns, evidence-based counseling interventions should be considered for managing depression in pregnant and postpartum women. Evidence is adequate that cognitive behavior therapy improves clinical outcomes in pregnant and postpartum women. The Task Force found evidence of potential serious fetal harms (like congenital anomalies, neonatal seizures, and neonatal death) from the use of second-generation antidepressants (like selective serotonin reuptake inhibitors) during pregnancy, but the risk for these serious harms is very low. This updated recommendation from the United States Preventive Services Task Force reaffirms support for depression screening in adults, but the operative phrase here is with adequate systems in place to ensure accurate diagnosis, effective treatment, and appropriate follow-up . Lack of these systems in many communities and the lack of access to care for many patients make these recommendations difficult to implement. Adding pregnant and postpartum women to the list of adults who might benefit from screening is consistent with recommendations from several professional associations, including the American Academy of Family Physicians, the American Academy of Pediatrics, and the American College of Obstetricians and Gynecologists. BARIATRIC SURGERY IS ASSOCIATEDWITH POSTOPERATIVE IMPROVEMENTS IN DEPRESSION In a meta-analysis in the January12 issue of JAMA ( http:// dx.doi.org /10.1001/jama.2015.18118 ), researchers evaluated the prevalence of preoperative and postoperative mental illness and its association with weight-loss outcomes. In 60 studies (including 70,000 patients), researchers reported mental illness prevalence, and in 30 studies (including 50,000 patients), investigators evaluated the associations between preoperative mental illness and postoperative outcomes in patients who underwent bariatric surgery. The average age range of the patients was 40 to 50 and their average body-mass index was 45kg/m 2 to 50kg/m 2 . Before surgery, the prevalence of any mood disorder was 20%. The most common mood disorders were depression and binge eating disorder; their prevalences were substantially higher than those found in the general population. The estimated prevalence of depression declined postoperatively by 8% to 70%, and depression severity declined by 40% to 70%. Binge eating disorder was evaluated in two studies; this disorder declined postoperatively, but returned to baseline in one of the studies. There was no consistent association between the presence or the absence of preoperative mental illness and postoperative weight loss. This meta-analysis suggests that weight loss after bariatric surgery is similar among patients with or without preoperative depression and that bariatric surgery alleviates depression in many patients. OPIOID PRESCRIBING AFTER NONFATAL OVERDOSE In recent years, opioid misuse and overdose have risen dramatically. In a study in the January5 Annals of Internal Medicine ( http:// dx.doi.org /10.7326/M15-0038 ), researchers used data from a large health insurer in the United States to examine opioid use after hospitalization or presentation to an emergency department for nonfatal opioid overdose in nearly 3000 patients with an average age of 44 who were getting long-term opioid therapy (a duration of at least 3months) for noncancer pain. During the 2months before overdose, opioids were prescribed at an average daily morphine-equivalent dosage of 100mg or higher, between 50mg and 100mg, or lower than 50mg. During a median follow-up of about 10months, 90% of the patients got one or more opioid dispensings; only 7% did not get opioids during the postoverdose period. Among the patients who continued to be prescribed opioids, about a third continued to get high daily dosages (100mg or higher). Among the patients for whom pre- and postoverdose prescribers could be identified, only 30% got their prescriptions from entirely new clinicians. In this study, nearly all of the patients who experienced nonfatal opioid overdoses continued to get prescriptions for opioids; for most of the patients, the same clinician issued both the pre- and the postoverdose prescriptions. Although no single process can be expected to resolve this complex issue, an editorialist discusses ( http:// dx.doi.org /10.7326/M15-2687 ) several potential interventions including: 1.Building on state prescription monitoring programs to ensure that prescribing clinicians are informed when their patients overdose 2.Increasing clinicians knowledge of managing chronic opioid use and dependency 3.Ensuring that hospitals and emergency departments have systems to identify patients who present with problems related to substance abuse 4.Ensuring the availability of programs for addiction treatment One final issue is worth mentioning: Many clinicians feel that they are being scrutinized not only for overprescribing opioids, but also for undertreating pain. LYME DISEASE IN THESOUTHEASTERNU.S. Lyme disease has been endemic to limited areas of the United States, including the northeast coastal states and the upper Midwest. In response to increasing numbers of cases reported in Virginia, including the southern border of Virginia which is outside of previously identified endemic areas researchers conducted spatial and spatiotemporal cluster analyses. Both probable and confirmed cases (based on surveillance definitions by the Centers for Disease Control and Prevention) that were reported to state health departments between 2000 and 2014 were included. Details appear on the website of Open Forum Infectious Diseases ( http:// dx.doi.org /10.1093/ofid/ofv143 ). More than 11,000 cases of Lyme disease were included in the analyses, 90% of which were registered by the Virginia health department; the rest were registered by the health department in North Carolina. A trend toward increasing numbers of cases was apparent only for Virginia; the most marked annual increase was in southwestern Virginia. New disease clusters were identified along the Appalachian chain between Charlottesville and the North Carolina border and along the southeastern border of older clusters in northern Virginia. Clinicians in the newer areas of expansion of Lyme disease might not be familiar with its varied presentations and potential complications. This lack of familiarity could result in misdiagnoses or delays in diagnosis, which could affect patient outcomes. CAN PROCALCITONIN DISTINGUISH PNEUMONIA FROM HF IN THE ED? Pneumonia and heart failure are among the most common diagnoses for patients hospitalized via the emergency department; they both have dyspnea as a presenting feature. Natriuretic peptide concentrations are widely used to help in diagnosing heart failure. To better explore the value of measuring procalcitonin to diagnose pneumonia in patients with acute dyspnea, researchers combined data from 450 patients who were enrolled in two past studies that were based in emergency departments; the names of the studies were: PRIDE and BIONICS-HF ( http:// dx.doi.org /10.1016/ j. amjcard.2004.12.032 and http:// dx.doi.org /10.1371/journal.pone.0112313 ). Details of the pooled analysis appear in the Januaryissue of The American Journal of Medicine ( http:// dx.doi.org /10.1016/ j. amjmed.2015.06.037 ). Half of the patients got a final diagnosis of acutely decompensated heart failure; 6% got a final diagnosis of pneumonia; and 6% were diagnosed with both heart failure and pneumonia. The median procalcitonin level was significantly higher in the patients with pneumonia than in those without pneumonia. Among the patients whose clinical likelihood of heart failure exceeded 75%, a procalcitonin cutoff value of 0.1 ng/ mL had a sensitivity of 95% for identifying pneumonia and a negative predictive value of 99%; for the patients with a less-than-25% likelihood of heart failure, that procalcitonin cutoff value had a specificity of 85% and a negative predictive value of95%. This analysis suggests that procalcitonin can help to distinguish between pneumonia and heart failure in patients who present to the emergency department with acute dyspnea; it might even assist in identifying the patients who have both conditions. Its not clear whether measuring procalcitonin in patients with acute dyspnea will ultimately affect their outcomes. A maker of procalcitonin assays funded this analysis. DIET AND EXERCISE PROGRAM IN PATIENTS WITH HF AND PRESERVEDEJECTION FRACTION Most patients with heart failure and preserved ejection fraction are overweight or obese, and effective pharmacologic therapies are limited. In a study in the January5 issue of JAMA ( http:// dx.doi.org /10.1001/jama.2015.17346 ), researchers randomized 100 such patients without substantial comorbidities to 20weeks of diet only, exercise only, both interventions, or an attention control group (which got telephone calls every 2weeks). The patients average age was 67 and 80% were women. Heart failure was symptomatic in all of the patients. Exercise capacity, as measured by peak oxygen consumption during cardiopulmonary exercise testing, significantly increased from baseline in both single-intervention groups; the combination group achieved additive effects. Body weight decreased by 7% with diet only, 3% with exercise only, 10% with exercise plus diet, and 1% in the controls. There were no statistically significant changes in health-related quality of life as measured by the Minnesota Living with Heart Failure Questionnaire ( www. queri.research.va .gov /chf/products/hf_toolkit/Minnesota-HF-Questionnaire_Rector.pdf ), but two other standardized measures (defined as exploratory in this study) showed significant improvement in some groups. Diet, exercise, and particularly the combination reduced body weight and significantly improved peak oxygen consumption during stress testing. The lack of a consistent improvement in measures of quality of life could be explained by the small cohort size, varying sensitivity among the quality of life instruments, a disconnect between physiologic measures and quality of life, or, as an editorialist notes ( http:// dx.doi.org /10.1001/jama.2015.17347 ), patients continuing to push themselves until symptoms occurred. The researchers emphasize that future studies should be designed to examine clinical events, particularly because some trials have reported lower mortality for overweight and obese patients with heart failure (the so-called heart failure obesity paradox ). In the meantime, clinicians should continue to advocate for a healthy diet and physical activity in patients with heart failure and preserved ejection fraction. SODIUM RESTRICTION IN HF: MOREQUESTIONS AND FEW ANSWERS Dietary sodium restriction is a traditional component of caring for patients with heart failure, but only sparse and conflicting data are available about its effect on outcomes. The American College of Cardiology and the American Heart Association guidelines support some degree of sodium restriction in patients with symptomatic heart failure ( http:// dx.doi.org /10.1161/CIR.0b013e31829e8776 ). Now, in a study in the Januaryissue of JACC: Heart Failure ( http:// dx.doi.org /10.1016/ j. jchf.2015.08.007 ), researchers analyzed observational data from a study sponsored by the National Institutes of Health in which food-frequency questionnaires were used to evaluate sodium intake every year for 3years in patients with symptomatic heart failure. The cohort contained 130 patients with restricted sodium intake (an average of less than 2500 mg/ day) and 130 propensity-matched patients with unrestricted sodium intake. Restricted intake was associated with a significantly higher risk for the combined primary endpoint, death or hospitalization for heart failure, due to a significantly higher hospitalization rate. One hypothetical explanation for worse outcomes with low sodium intake is deleterious neurohormonal activation induced by sodium restriction. But reaching conclusions from this observational study is difficult, because sodium intake was based only on patient report and because of possible unmeasured confounding. A large randomized trial of clinical outcomes with a low-sodium diet is in progress (its called SODIUM-HF https://clinicaltrials .gov /ct2/show/NCT02012179 ). But for now, the benefit of recommending strict sodium restriction to patients with heart failure is simply unknown. MORE INFORMATION ON TAVR FOR AORTIC STENOSIS Increasingly, transcatheter aortic valve replacement for aortic stenosis is being performed in North America and Europe, usually in patients deemed to be at high risk for complications with surgical valve replacement. In a study in the December29, 2015 Journal of the American College of Cardiology ( http:// dx.doi.org /10.1016/ j. jacc.2015.10.021 ), researchers in the United States reviewed national registry data that showed that transcatheter aortic valve replacement was performed in about 5000 patients in 2012, 9000 patients in 2013, and 13,000 patients in 2014 (the registry excludes 10,000 additional procedures done investigationally). In 2014, the patients median age was 83, and their overall health status was generally poor. Periprocedural complications included the need for a pacemaker, atrial fibrillation, major bleeding, vascular complications, and stroke. In-hospital mortality was 4%. At discharge, 5% of the patients had moderate-to-severe aortic regurgitation. In a study in the November2015 issue of JACC: Cardiovascular Interventions ( http:// dx.doi.org /10.1016/ j.jcin.2015.07.022 ), researchers in Canada and Spain describe hospital readmission rates after transcatheter aortic valve replacement. Among 700 patients discharged from the hospital after the procedure, 15% were readmitted within a month, and another 12% were readmitted between 1 and 3months. Cardiac causes accounted for 40% of the readmissions and noncardiac causes accounted for 60%. In yet another study, this one published in the December17, 2015 New England Journal of Medicine ( http:// dx.doi.org /10.1056/NEJMoa1500893 ), researchers in Germany and France reviewed experiences with transcatheter aortic valve replacement since the procedure became available in Germany. Between 2007 and 2013, the number of surgical aortic valve replacements declined slightly (from about 8600 to 7000), whereas the number of transcatheter aortic valve replacements increased dramatically (from about 150 to 9000). During this 7-year period, in-hospital mortality decreased from 13% to 5% in the transcatheter patients, and the periprocedural stroke rate decreased from 4% to 3%. In the surgical patients, in-hospital mortality decreased from 4% to 2%, and the stroke rate decreased from 2% to 1%. These findings provide useful information for counseling patients; although the rates of periprocedural mortality and stroke seem to be decreasing over time, the still-substantial rates of death, complications, and hospital readmissions reflect the high-risk clinical characteristics of the patients who undergo transcatheter aortic valve replacement. TARGETING A POTENT NEW RISK FACTOR FOR ATHEROSCLEROSIS VIA THE GUT MICROBIOME Back in 2013, researchers reported on a potent new risk factor for atherosclerosis, namely, trimethylamine- N -oxide ( www.jwatch.org /na31263 ). Gut microbes metabolize nutrients in food, particularly choline and L-carnitine, and produce trimethylamine, which is transformed by a liver enzyme into trimethylamine- N -oxide. Circulating trimethylamine- N -oxide levels in people correlate with atherosclerosis burden. The production of trimethylamine- N -oxide can be reduced by inhibiting the liver enzyme that produces it, but this causes adverse effects particularly hepatic inflammation. To avoid this adverse effect, researchers at Cleveland Clinic sought to lower trimethylamine- N -oxide levels by inhibiting the bacterial production of trimethylamine. Details appear in the December17, 2015 issue of Cell ( http:// dx.doi.org /10.1016/ j. cell.2015.11.055 ). The researchers identified a small molecule, called 3,3-dimethyl-1-butanol, that inhibits trimethylamine production. When this molecule was added to the drinking water of mice with diet-induced or genetic atherosclerosis, it dramatically lowered circulating trimethylamine- N -oxide levels, and it also prevented macrophage foam cell formation in atherosclerotic plaques and the progression of those plaques. There seemed to be no adverse effects in the mice. In mice, a simple treatment lowered the circulating levels of a potent, newly recognized risk factor for atherosclerosis namely, trimethylamine- N -oxide and slowed atherosclerosis itself. The treatment targets the gut microbiome, which plays a major role in raising the levels of the metabolite. Whether this approach will have value in people remains to be seen. ANOTHER TRIAL OF TAMSULOSIN FOR PATIENTS WITH URETERAL STONES The efficacy of α-blockers (like tamsulosin) to facilitate the passage of ureteral stones is unclear. In a 2014 meta-analysis (of mostly small studies), tamsulosin shortened the time to stone passage, but study quality was not highly rated ( http:// dx.doi.org /10.1002/14651858.CD008509.pub2 ). In a subsequent large trial from 2015, tamsulosin was not better than placebo, but stone passage wasnt confirmed by imaging ( www.jwatch.org /na38016 ). Now, in a double-blind study in the Januaryissue of the Annals of Emergency Medicine ( http:// dx.doi.org /10.1016/ j. annemergmed.2015.06.001 ), researchers at five emergency departments in Australia randomized 400 adults with computed tomographyconfirmed distal ureteral stones to either 0.4 mg/ day of tamsulosin or placebo for a month. Stone size was smaller than 5mm in three quarters of the patients and 5mm to 10mm in the rest; patients were excluded if stone size exceeded 10mm. In the patients with smaller stones, stone passage (confirmed by the absence of stone on CT at a month) was seen with equal frequency (at around 90%) in the two groups. In contrast, stones measuring 5mm to 10mm passed significantly more often with tamsulosin than with placebo. The median time to stone passage was a week with tamsulosin and 11days with placebo; this endpoint was not reported separately for small and large stones. At a month, 13 patients (5 in the tamsulosin group and 8 in the placebo group) had undergone urologic intervention. Pain scores were similar in the two groups throughout follow-up. In this study, tamsulosin increased the probability that 5- to 10-mm distal ureteral stones would be passed. The clinical importance of this finding depends on whether tamsulosin lowered the overall need for invasive urologic interventions (both during and after the month-long follow-up), but unfortunately, that outcome was not reported. So, the ultimate clinical benefit remains speculative. THREE COMMON APPROACHES TO SMOKING CESSATION ARE ROUGHLYEQUAL IN EFFICACY Its been shown that varenicline (trade name: Chantix) and nicotine replacement combination therapy (meaning nicotine patches plus nicotine lozenges) are more effective than nicotine replacement monotherapy, but the two superior approaches have not been directly compared. Until now. In a study in the January26 issue of JAMA ( http:// dx.doi.org /10.1001/jama.2015.19284 ), researchers randomized 1100 smokers to one of three open-label 3-month interventions, namely: Varenicline alone (starting at 0.5 mg/ day and titrated up to 1mg twice /day ) 21-mg nicotine patches, tapered to 7-mg patches by 2months Nicotine patches as above, plus five 2-mg or 4-mg lozenges every day (depending on smoking history) All of the regimens were adjusted as needed for side effects, and all of the patients got weekly counseling sessions. The average age of the patients was 48; the average number of cigarettes they smoked every day was 17; and their average smoking duration was about 30years. Adherence rates were about 45% for all of the interventions at 2months. In intent-to-treat analyses, quit rates (evaluated by self-report and confirmed by exhaled carbon monoxide) were similar for all three of the interventions and were about 35% at a month, 30% at 3months, 25% at 6months, and 20% at a year. The overall frequency of side effects was similar across the groups, but insomnia, somnolence, and nausea were most common with varenicline, and itching and rash were most common with nicotine. All pharmacotherapeutic approaches to smoking cessation seem to be similarly effective when combined with structured support and follow-up. Resources: 1-800-QUIT NOW and www. smokefree .gov E-CIGARETTE USE IS ASSOCIATED WITH RESPIRATORY SYMPTOMS IN ADOLESCENTS The health effects of electronic cigarettes are not yet clear. In a study in the Januaryissue of JAMA Pediatrics ( http:// dx.doi.org /10.1001/jamapediatrics.2015.3024 ), researchers in Hong Kong investigated the respiratory effects of e-cigarettes in 45,000 adolescents with an average age of 15 who completed anonymous in-school surveys on tobacco and e-cigarette use. The students were classified into four tobacco groups, namely: Never-smokers, experimental smokers (once or a few times), ex-smokers, or current smokers. The students also indicated whether they had used e-cigarettes in the past month and whether they had respiratory symptoms (like cough or phlegm) for 3 or more consecutive months in the past year. In analyses adjusted for sex, age, perceived family affluence, secondhand smoke exposure, and school clustering, never-smokers, ever-smokers, and ex-smokers who used e-cigarettes were significantly more likely to report respiratory symptoms than were none-cigarette users in the same tobacco-smoking categories. E-cigarette use was not significantly associated with the presence of respiratory symptoms among current or experimental smokers. Although the data are self-reported, these results provide credible evidence that e-cigarette use negatively affects the respiratory tract in adolescents. Lending further credence to the results, the effect seems to be most noticeable among those whose airways are not already irritated by cigarette smoke. These study findings support the recommendations of the World Health Organization to regulate the use of e-cigarettes. HOW COMMON IS ASTHMA IN PATIENTS WITH COPD? Back in the 1960s, experts proposed the Dutch Hypothesis, which stated that: 1.Asthma and chronic obstructive pulmonary disease are different expressions of the same disease that has been shaped by environmental influences 2.That asthma predisposes patients to COPD later in life This theory was countered by the British Hypothesis, which claimed that asthma and COPD are separate disease processes. Then, in 2015, an international panel defined asthmaCOPD overlap syndrome as, persistent airflow limitation with several features usually associated with asthma and several usually associated with COPD . Knowledge about asthmaCOPD overlap syndrome is limited, because, typically, clinical trials exclude patients with features of both diseases. Asthma is characterized by TH 2 lymphocyteinduced airway inflammation with mast cell activation and eosinophilic infiltration, whereas COPD is characterized by CD8 + lymphocyteinduced inflammation with neutrophil and macrophage infiltration. Often, asthma starts in childhood and is associated with atopy, whereas COPD typically starts after the age of 40 and is associated with cigarette smoking. The hallmarks of asthma include airway hyperreactivity and reversible obstruction, but some asthmatics develop irreversible obstruction due to airway remodeling. Likewise, certain patients with COPD showed marked reversibility with bronchodilators. Some phenotypes of asthma have a neutrophilic-predominant inflammatory response and tend to be harder to treat, whereas some COPD patients have eosinophilia and exacerbations that are more responsive to inhaled corticosteroids. In an ongoing cohort study in the Januaryissue of Chest ( http:// dx.doi.org /10.1378/chest.15-1055 ), researchers in Spain sought to characterize asthmaCOPD overlap syndrome in 800 patients with COPD; 15% met the criteria for asthmaCOPD overlap syndrome (1 major criterion [history of asthma or 15%/400mL bronchodilator response] or 2minor criteria [IgE >100 IU, history of atopy, blood eosinophils >5%, or a 12%/200mL bronchodilator response on 2 separate occasions]). At baseline, most of the patients had mild-to-moderate disease, and two thirds were treated with inhaled corticosteroids. At a year, survival in the asthmaCOPD overlap syndrome subgroup was 95% vs . 87% in the subgroup without the syndrome. Other outcomes were similar in the two groups. These researchers used easily obtainable information to classify about 15% of chronic obstructive pulmonary disease patients as having asthmaCOPD overlap syndrome. This percentage agrees with that found in other studies, but in those trials, patients with the syndrome had worse outcomes (possibly attributable to more severe disease at baseline and less use of inhaled corticosteroids). Its not yet known how best to manage patients with asthma-COPD overlap syndrome, but for now, a reasonable approach might be to treat these patients early with inhaled corticosteroids plus long-acting bronchodilators and treat COPD patients without the syndrome with long-acting bronchodilators and only add inhaled corticosteroids for those who still experience exacerbations. MENOPAUSE IS ASSOCIATED WITH EXCESS RISK FOR NEW-ONSETASTHMA Asthma is more prevalent in boys than in girls, but this tendency reverses in adulthood. Menopause is a systemic inflammatory state that predisposes women to cardiovascular disease and might have similar effects on pulmonary disease. In a study in the Januaryissue of The Journal of Allergy and Clinical Immunology ( http:// dx.doi.org /10.1016/ j. jaci.2015.08.019 ), researchers followed 2300 premenopausal women from Europe who were older than 44 and were free from asthma at baseline. After 12years, 20% of the women were still premenopausal, 10% were transitional, 60% were early postmenopausal, and 10% were late postmenopausal. In analyses adjusted for age and other potentially confounding variables, the women who were in transition, early postmenopause, and late postmenopause were significantly more likely to have developed asthma than were the women who were still premenopausal. The proportion of women with new diagnoses of asthma ranged from 3% in the premenopausal group to 7% in those who were late menopausal. New-onset asthma in older adults is more common in women and is usually nonatopic and more resistant to treatment than earlier-onset asthma. As women enter menopause, clinicians should routinely ask about respiratory symptoms and get spirometry in patients with cough, wheezing, and dyspnea. LOWER OXYGEN SATURATION GOALS ARE SAFE IN MECHANICALLY VENTILATED PATIENTS The optimal oxygenation goal for patients who are getting invasive mechanical ventilation remains unclear. Usually, clinicians target the resolution of hypoxemia and pay little attention to weaning levels of oxygen once 100% saturation has been achieved. But harms caused by hyperoxia, including effects on cardiac function and lung parenchyma, are of concern. To evaluate the safety of a lower oxygenation target, researchers randomized 100 patients who were getting invasive mechanical ventilation to either a conservative strategy (a peripheral oxygen saturation between 88% and 92%) or a liberal strategy (a peripheral oxygen saturation of greater than 95%) for the duration of ventilator support. Positive end expiratory pressure levels were determined by treating clinicians who were not blinded to the intervention. Three quarters of the patients had medical diagnoses. The average fraction of inspired oxygen at randomization was 0.44. Findings appear in the January1 American Journal of Respiratory and Critical Care Medicine ( http:// dx.doi.org /10.1164/rccm.201505-1019OC ). There were no differences between the two groups in organ dysfunction or mortality. Average saturation in the conservative arm was 93% ( vs . 97% for the liberal arm), and more arterial blood gases were drawn. These two findings suggest some clinician discomfort with targeting lower oxygen saturation levels. Patients in the conservative group were more likely to have episodes of severe desaturation, although these events were rare in both of the groups. This study reassures clinicians that a lower oxygen saturation target is not harmful. Whether this practice confers benefit is unclear, but these results should allow researchers to comfortably conduct larger randomized, controlled trials with lower oxygen saturation goals. BRONCHOSCOPY IS REASONABLY GOOD FOR DIAGNOSING PERIPHERALLUNG LESIONS The diagnostic evaluation of peripheral lung nodules is challenging. To evaluate the yields of different bronchoscopy techniques, researchers in the United States used a multicenter national registry to study 600 patients who had undergone bronchoscopy with transbronchial biopsy for peripheral nodules or masses. The lung periphery was defined as the segmental bronchus or beyond, such that the lesion required transbronchial biopsy rather than endobronchial biopsy . Findings appear in the January1 American Journal of Respiratory and Critical Care Medicine ( http:// dx.doi.org /10.1164/rccm.201507-1332OC ). Bronchoscopy was diagnostic in roughly half of the lesions, with primary lung cancer being the most common finding. Transbronchial biopsy was diagnostic in 40% of the patients, although it was rarely the only test with a diagnostic yield. Transbronchial needle aspiration was diagnostic in nearly half of the 100 patients in whom it was performed. Transbronchial brush and bronchoalveolar lavage added small incremental gains to the diagnostic results. There was significant variability among the centers in the use of, and physician experience with, radial endobronchial ultrasound and electromagnetic navigation. Surprisingly, the use of these advanced guidance modalities resulted in lower diagnostic yields, possibly because they were used for more challenging lesions. Complications, including pneumothorax, were seen in only 2% of the patients. In this study of clinical effectiveness, bronchoscopy was a safe diagnostic strategy with at least a moderate yield for peripheral lesions. The best results came from the combined use of multiple diagnostic approaches (like transbronchial biopsy, bronchoalveolar lavage, and transbronchial needle aspiration). The lack of benefit from adjunctive interventions (like endobronchial ultrasound and electromagnetic navigation) probably reflects some selection bias, but it should reassure clinicians that referrals need not be limited to centers with these advanced capabilities. PREVALENCE OF NONRECOMMENDED SCREENING FOR PROSTATE AND BREAST CANCER VARIES ACROSS STATES In the United States, the high rates of cancer screening in an aging population raise concern that screening is increasingly being done in patients with a life expectancy of less than 10years. In a study on the website of JAMA Oncology ( http:// dx.doi.org /10.1001/jamaoncol.2015.5871 ), researchers used a national health behavior survey to identify 150,000 patients 65 or older; more than half of the patients had gotten either prostate-specific antigen testing or mammograms in the past year. Elders with histories of breast or prostate cancer were excluded. About a third of the screened patients had predicted life spans of less than 10years. The state-based rates for nonrecommended PSA testing varied from 12% (in Hawaii) to nearly 30% (in Georgia) and, for nonrecommended mammograms, from 9% (in Colorado) to 18% (in North Dakota). The combined rates for both of the nonrecommended tests ranged from 12% (in Colorado) to 20% (in Georgia). The high correlation of nonrecommended screening for prostate and breast cancer suggests that factors that cause these high rates in some states might be worthy of further study and mitigation. As patients age and become ill, clinicians need to have difficult conversations about the guideline-recommended cessation of preventive services. SECOND CANCERS IN SURVIVORS OF HODGKIN LYMPHOMA Late complications of treatment for Hodgkin lymphoma can include other cancers. To evaluate the long-term risk for second cancers in survivors of Hodgkin lymphoma, researchers in the Netherlands analyzed data from more than 3000 patients (40% of whom were women) in three population-based registries. The patients had gotten initial treatment for Hodgkin lymphoma from 1965 to 2000 and had survived for at least 5years (the median age at diagnosis was 29). The risk of these patients was compared with that in the general population for 1965 to 1976, 1977 to 1988, and 1989 to 2000. Details appear in the December24, 2015 New England Journal of Medicine ( http:// dx.doi.org /10.1056/NEJMoa1505949 ). Thirty percent of the patients with Hodgkin lymphoma had gotten radiation therapy, 12% had gotten chemotherapy, and 60% had gotten combination therapy. The most recent treatment period was associated with smaller radiation target volumes, more anthracycline-based regimens, and fewer alkylator-based regimens than the early treatment periods. During a median follow-up of 19years, 1100 second cancers were diagnosed in 900 survivors of Hodgkin lymphoma (thats almost five times the risk seen in the general population); a few patients developed third or fourth cancers. Breast cancer accounted for the greatest absolute excess risk for second cancers; this risk was lower among the women treated with procarbazine, but procarbazine users had a higher risk for gastrointestinal cancer. Compared with the general population, survivors of Hodgkin lymphoma had 10-fold higher relative risks for thyroid cancer, soft-tissue sarcomas, mesothelioma, and non-Hodgkin lymphoma, and 5- to 10-fold higher risks for esophageal, gastrointestinal, pancreatic, and lung cancers and for leukemia. The excess second-cancer risk increased over time and lasted beyond 35years, especially among the patients treated for Hodgkin lymphoma at relatively young ages. This study did not confirm that modern techniques of volume- and dose-limiting radiation lower the risk for second cancers. Using risk-adapted regimens to avoid radiation and alkylating agents, whenever possible, remains a priority. Thorough education and screening of long-term Hodgkin lymphoma survivors is crucial for the prevention and the early diagnosis of second cancers and of cardiovascular complications ( http:// dx.doi.org /10.1056/NEJMe1511947 ). LONG-TERM OUTCOMES AFTER CARDIOTOXIC CANCER THERAPY IN CHILDREN What are the long-term consequences of having gotten cardiotoxic therapy for childhood cancer? To answer that question, researchers enrolled 1800 patients 18 or older who had gotten anthracycline chemotherapy or cardiac-directed radiation for childhood cancer at least 10years earlier. Most of the patients had gotten treatment for leukemia or lymphoma, and the median time since diagnosis was 20years. All of the patients underwent evaluations that included history and physical, electrocardiography, and echocardiography. Findings appear in the January19 Annals of Internal Medicine ( http:// dx.doi.org /10.7326/M15-0424 ) and include: The prevalence of cardiomyopathy was 7% (cardiomyopathy was defined as a left ventricular ejection fraction of lower than 50%). The prevalence of coronary artery disease was 4% (coronary artery disease was defined as a history of myocardial infarction, wall motion abnormality on echocardiography, or ischemia on ECG). The prevalence of valvular disease was 30% (valvular disease was defined as regurgitation or stenosis). The prevalence of conduction/rhythm disorders was 4%. Although second cancers remain a major cause of concern ( www.jwatch.org /na40022 ), the late effects of cardiotoxic therapy are an important cause of long-term morbidity and mortality. At a median age of 30, more than a third of childhood cancer survivors exhibited evidence of decreased systolic function or functional valvular disease, a finding expected in a much older cohort. This study highlights the need to follow the 2013 Childrens Oncology Group Long-Term Follow-Up Guidelines ( www. survivorshipguidelines .org /pdf/ LTFUGuidelines_40.pdf ) when caring for survivors of childhood cancer. ADOLESCENTS PRESCRIBED TERATOGENIC MEDICATIONS INFREQUENTLY RECEIVE CONTRACEPTION Less than half of the women who get teratogenic medications prescribed by internists or family physicians receive contraceptives. To determine the prevalence in a pediatric setting, researchers at an academic medical center retrospectively reviewed electronic medical records for 1700 girls with an average age of 16 who were prescribed drugs labeled pregnancy category risk D or X at hospital discharge or outpatient visits between 2008 and 2012. For each of 4000 encounters, the researchers searched records for keywords (like abstinence, birth control, condoms, and sexually active) and prescriptions or referrals for contraception. The encounters that contained one or more of the key terms were classified as having appropriate documentation. Findings appear in the Januaryissue of Pediatrics ( http:// dx.doi.org /10.1542/peds.2015-1454 ). Topiramate, methotrexate, diazepam, isotretinoin, and enalapril were the most commonly prescribed teratogens. Counseling or prescription/referral for contraceptives was documented in 30% of the encounters. An age of 16 or older, a later year of the visit, Medicaid or no insurance, and the presence of a formal federal surveillance program for the teratogen (like iPledge) were all associated with a greater likelihood of contraceptive provision. Compared with whites, blacks and girls of other races were significantly less likely to get contraceptive care. Even if some adolescents were not at risk for pregnancy (meaning those who are not sexually active) or if some contraceptive provision was not captured, the low rate of contraceptive care is worrisome. Given that teratogens were prescribed, documenting sexual and contraceptive history at each visit is essential. That nonwhite patients were less likely to get these essential services is also troubling. These results indicate the unmet potential of electronic medical records: When a prescription is entered for a teratogenic medication, a prompt should automatically appear that requires documentation of sexual activity and contraceptive status before the order can be completed. Correction In the January1, 2016 (Volume 27, Number 1) packet insert Table of Contents of NEJM Journal Watch Audio General Medicine , the title: GENERAL MEDICINE 2014: YEAR IN REVIEW cites the incorrect year. The correct title is: GENERAL MEDICINE 2015: YEAR IN REVIEW We apologize for the error.

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Learning Format 6 Hours
Self-Study

Credit Type(s)
Internal Medicine Emergency Medicine Pediatrics Cardiology Critical Care Infectious Diseases