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. Fernando Martinez reported receiving support from Forest, Janssen, GlaxoSmithKline, Nycomed/Takeda, Amgen, Astra Zeneca, Boehringer Ingelheim, Carden Jennings, CSA Medical, Ikaria/Bellerophon, Genentech, Merck, Novartis, Pearl, Pfizer, Roche, Sunovion, Theravance, Axon, CME Incite, the California Society for Allergy and Immunology, Annenberg, Inova Health System, Integritas, InThought, Miller Medical, the National Association for Continuing Education, Paradigm, Peer Voice, UpToDate, Haymarket Communications, St Johns Hospital, St Marys Hospital, the Western Society of Allergy and Immunology, Informa, Bioscale, Unity Biotechnology, Centocor, Gilead, Promedior, Ikaria, Kadmon, Vertex, Veracyte, the American Thoracic Society, Academic CME, Falco, MedScape, the National Association for Continuing Education, Axon Communication, Genzyme, Johnson & Johnson, Spectrum Health System, University of Texas Southwestern, and Biogen; and receiving grants from the National Institutes of Health and the National Heart, Lung, and Blood Institute. Dr. Robert Wood and the planning committee members reported that they had nothing to disclose. FASTING ISNT REQUIRED BEFORE LIPID LEVELS ARE MEASURED In an evidence-based clinical review on the website of JAMA Internal Medicine ( http:// dx.doi.org /10.1001/jamainternmed.2016.1979 ), the author identified three meta-analyses and five clinical practice guidelines that addressed whether fasting was required to accurately measure lipid levels and whether the prediction of incident cardiovascular disease events differed between fasting and nonfasting lipid levels. The reviewer came to several conclusions, namely: Nonfasting testing results in clinically insignificant changes compared with fasting results in total, high-density, and low-density lipoprotein cholesterol levels and in only modest changes in triglyceride levels. Nonfasting and fasting lipid levels are at least equally predictive for adverse cardiovascular disease events; nonfasting levels were sometimes more strongly predictive, presumably because nonfasting is the predominant metabolic condition for most patients. Clinical practice guidelines have shifted during the past 5years to endorse nonfasting testing in most routine circumstances. The recent European Atherosclerosis Society and European Federation for Laboratory Medicine guidelines recommend that, when triglyceride levels are greater than 400 mg/ dL with nonfasting testing, ordering a fasting test is appropriate ( http://eurheart j. oxfordjournals .org /content/early/2016/04/22/eurheart j. ehw152.long ). No studies directly compared the cost or convenience of nonfasting vs . fasting testing, but a study from Denmark (where nonfasting testing has been the standard since 2009) showed that only 10% of patients who underwent nonfasting testing needed repeat fasting testing. Nearly all clinicians have had the common experience of requiring patients to return for fasting lipid tests that frequently result in extra expense and inconvenience for patients and breakdowns in care for the patients who dont return. The author of this clinical review believes that nonfasting lipidlevel assessment should become routine clinical practice. LOWERING RISK FOR HEPARIN-INDUCED THROMBOCYTOPENIA Heparin-induced thrombocytopenia is a serious immunologically mediated complication of heparin therapy and, in its most severe form, is associated with thrombosis. The risk for heparin-induced thrombocytopenia is approximately 5- to 10-fold lower with low-molecular-weight heparin than with unfractionated heparin. In the April21 issue of Blood ( http:// dx.doi.org /10.1182/blood-2015-07-660001 ), researchers in Canada present the findings of a 10-year single-institution study in which they examined whether substituting low-molecular-weight heparin for unfractionated heparin would lower the risk for heparin-induced thrombocytopenia and heparin-induced thrombocytopenia with thrombosis. The annual incidence of adjudicated cases of heparin-induced thrombocytopenia decreased from about 11 to 2 per 10,000 admissions; the annual incidence of adjudicated cases of heparin-induced thrombocytopenia with thrombosis decreased from 5 to 0.4 per 10,000 admissions. Avoiding the use of unfractionated heparin reduced the average estimated annual costs of heparin-induced thrombocytopenia care by more than 80%. Although low-molecular-weight heparin is more expensive than unfractionated heparin, reducing the incidence of heparin-induced thrombocytopenia results in a substantial decrease in costs. Gradually, low-molecular-weight heparin and the novel oral anticoagulants are replacing unfractionated heparin for most anticoagulant indications. DIABETES ISNT EQUIVALENT TO PASTCORONARY HEART DISEASE AS A RISK FACTOR FOR FUTURE CHD EVENTS For many years, patients with diabetes and no known coronary heart disease were thought to have the same risk for future myocardial infarction as did patients with known coronary heart disease. Studies supporting this assertion had important limitations, and now, many are dated. The risk assessment guideline issued by the American College of Cardiology and the American Heart Association in 2013moved away from treating prevalent coronary heart disease and diabetes as risk equivalents , and defined diabetes as only one of several factors that contribute to cardiovascular risk ( www.jwatch.org /na32830 ). To quantify the effects of diabetes and current coronary heart disease on future coronary heart disease risk more precisely, researchers studied prevalent diabetes and past coronary heart disease (defined as a history of MI or revascularization) and incident coronary heart disease in roughly 2 million patients between the ages of 30 and 90 who were enrolled in a Kaiser-Permanente healthcare system between 2002 and 2011. Median follow-up was 10years. Findings appear in the April Journal of General Internal Medicine ( http:// dx.doi.org /10.1007/s11606-015-3556-3 ). Compared with the risk in patients who did not have diabetes or coronary heart disease at baseline, adjusted relative risks for future coronary heart disease events were nearly doubled in the patients with diabetes only, nearly tripled in the patients with coronary heart disease only, and nearly quadrupled in the patients with both diabetes and coronary heart disease. Similar adjusted relative risks were seen in subgroups stratified by sex and age at baseline. Among the patients with diabetes alone, the risk for coronary heart disease events increased with the duration of their diabetes; the patients with diabetes for longer than 10years at baseline had about the same coronary heart disease risk as the patients with past coronary heart disease events. This large, contemporary, long-term population study confirms and strengthens recent conclusions from smaller studies and meta-analyses that diabetes and a history of coronary heart disease are not necessarily risk equivalent for future coronary heart disease events. These findings will be particularly useful in evaluating the risk in young patients with diabetes of relatively recent onset. CANAGLIFLOZIN-ASSOCIATED DIABETIC KETOACIDOSIS The sodiumglucose cotransporter-2 inhibitor canagliflozin (trade name: Invokana) is approved by the Food and Drug Administration for use only in patients with type2 diabetes. But anecdotal reports suggest that its prescribed off-label for patients with type1 diabetes and that it can increase the risk for diabetic ketoacidosis in these patients ( www.jwatch.org /na39138 ). Now, in the Aprilissue of Diabetes Care ( http:// dx.doi.org /10.2337/dc15-1995 ), researchers describe the incidence and characteristics of diabetic ketoacidosis among 350 patients with type1 diabetes and an average age of 42; the patients were randomized to 18-week courses of either canagliflozin or placebo, added to insulin. Diabetic ketoacidosis was diagnosed in 5% of the canagliflozin patients and in none of the placebo patients. Infection, insulin pump malfunction, and a suboptimal adherence to insulin therapy were the underlying precipitants. Nearly half of the patients with diabetic ketoacidosis presented with blood glucose levels that were relatively low for diabetic ketoacidosis (lower than 250 mg/ dL). Sodiumglucose cotransporter-2 inhibitors lower blood glucose by increasing glycosuria. This mechanism could blunt the development of the severe hyperglycemia that typically develops in diabetic ketoacidosis and could lead patients in the earliest stages of diabetic ketoacidosis to mistakenly cut back on their insulin and promote clinically evident diabetic ketoacidosis. Canagliflozin (and probably all of the drugs in its class) should not be prescribed for either patients with type1 diabetes or patients with type2 diabetes who are prone to diabetic ketoacidosis. The general results of this industry-sponsored trial were reported last year ( http:// dx.doi.org /10.2337/dc15-1730 ). CAN VITAMIN D SUPPLEMENTATION PREVENT TYPE 2 DIABETES? Animal experiments and observational studies in people suggest that vitamin D deficiency might play a role in the development of diabetes. To see whether supplementation affects progression to diabetes, researchers in Norway randomized 500 adults with prediabetes (defined as impaired fasting glucose or impaired glucose tolerance) to either 20,000 IU/ week of vitamin D 3 supplementation or placebo for 5years. At baseline, the average serum 25-hydroxyvitamin D level was 24 ng/ mL; during the study, levels doubled in the treatment group and stayed the same in the placebo group. Findings appear in the Aprilissue of The Journal of Clinical Endocrinology & Metabolism ( http:// dx.doi.org /10.1210/jc.2015-4013 ). At 5years, the proportions of patients who developed type2 diabetes were similar in the vitamin D and placebo groups (40% vs . 44%; P =0.45); the annual rates of progression to diabetes were also similar in the two groups. Plus, vitamin D supplementation did not prevent diabetes in a subgroup of 112 patients who were vitamin Ddeficient at baseline (i.e., 25-hydroxyvitamin D level <20 ng/ mL). Vitamin D supplementation did not prevent progression from prediabetes to type2 diabetes in this 5-year trial (which is the largest such trial to date); vitamin D should not be given for this purpose. Whether supplementation might alter the natural history of prediabetes or diabetes in patients with severe vitamin D deficiency remains unclear. LOWERING FRACTURE RISK IN PATIENTS WITH PRIMARY HYPERPARATHYROIDISM For patients with asymptomatic primary hyperparathyroidism, the guideline-recommended indications for parathyroidectomy include the presence of osteoporosis or vertebral fracture ( http:// dx.doi.org /10.1210/jc.2014-1413 ). But the relative effects of parathyroid surgery and bisphosphonate therapy on fracture outcomes are unclear. Using data from Kaiser Permanente Southern California, researchers identified 6300 patients with primary hyperparathyroidism and retrospectively determined the skeletal outcomes of parathyroidectomy (22% of patients), bisphosphonate therapy (22%), or observation without treatment (55%). Findings appear on the website of the Annals of Internal Medicine ( http:// dx.doi.org /10.7326/M15-1232 ). At baseline, there were substantial differences among the three groups. For example, the bisphosphonate group, compared with the surgery group, had a higher median age (71 vs . 56), a higher proportion with osteoporosis (79% and 42%), and substantially higher Charlson comorbidity scores. Baseline parameters in the observation group tended to be between those of the other two groups. At 10years, the absolute risk for hip fracture was nearly 90per 1000 patients in the bisphosphonate group, nearly 60 per 1000 in the observation group, and 20 per 1000 in the surgery group. Similarly, the risk for any fracture at 10years was highest for the bisphosphonate patients vs . the observation or the surgery patients (303, 206, and 157 per 1000 patients, respectively). After adjusting for baseline imbalances among the three groups and after stratifying for baseline bone-mineral density, parathyroidectomy was associated with a lower risk for fracture among the patients with osteopenia or osteoporosis, whereas bisphosphonates were associated with an excess fracture risk in these patients. This observational study showed a significantly lower fracture risk among primary hyperparathyroidism patients who underwent parathyroidectomy vs . observation or treatment with bisphosphonates. Given the relatively low rate of surgical complications with parathyroidectomy, the findings suggest that surgery is the preferred approach for patients with primary hyperparathyroidism and osteopenia or osteoporosis. But because the bisphosphonate patients were substantially older and less healthy than were the surgery patients at baseline, they were probably at a higher risk for fracture independent of their primary hyperparathyroidism. Although the researchers used statistical adjustments to account for these baseline differences, residual confounding still may have, at least partially, affected the findings. GUIDELINE WATCH: USPSTF AGAIN RECOMMENDS AGAINST SCREENING FOR COPD IN ASYMPTOMATIC ADULTS Back in 2008, the United States Preventive Services Task Force recommended against screening asymptomatic adults for chronic obstructive pulmonary disease ( http:// dx.doi.org /10.7326/0003-4819-148-7-200804010-00212 ). In an updated recommendation statement in the April5 issue of JAMA ( http:// dx.doi.org /10.1001/jama.2016.2638 ), the Task Force reiterates this advice based on a systematic review of studies published since the year 2000 ( http:// dx.doi.org /10.1001/jama.2016.2654 ). Key points include: Of the screening instruments studied, indirect evidence suggests that the most accurate is the COPD Diagnosis Questionnaire ( https:// www. pcrs-uk .org /validated-copd-diagnosis-questionnaire ), with a sensitivity of 90% and a specificity of 40% in a primary care population. No studies directly evaluated the benefits of screening for morbidity, mortality, or quality of life in asymptomatic patients. Of five studies in which the effects of screening on the rates of smoking cessation were evaluated, four showed no evidence of benefit. Because no treatment trials have been conducted in asymptomatic patients, its unknown whether the outcomes of drug treatment for symptomatic patients apply to asymptomatic patients. The Task Force concludes with moderate-to-high certainty that screening for COPD in asymptomatic adults has no net benefit. The United States Preventive Services Task Force distinguishes between screening for chronic obstructive pulmonary disease in asymptomatic adults and COPD case-finding ( http:// dx.doi.org /10.1001/jama.2016.3274 ) through questionnaires or spirometry in patients with respiratory symptoms that suggest COPD (like chronic cough and dyspnea); this guideline does not apply to symptomatic patients. Notably, the Task Force did not specifically address the targeted screening of smokers only ( vs . adults generally) because it found no strong evidence applicable to either population. The only exception was the finding that giving smokers objective data about their lung function has no effect on smoking cessation. SMOKING CESSATION: COLD TURKEY vs . QUITTING GRADUALLY Most smoking cessation guidelines advise patients to set a quit date and stop smoking abruptly, rather than gradually, but data to support the superiority of abrupt quitting have been inconsistent. In a study in the May3 Annals of Internal Medicine ( http:// dx.doi.org /10.7326/M14-2805 ), researchers in the United Kingdom randomized 700 adult smokers (who smoked an average of 20 cigarettes /day ) to set a quit date and stop smoking abruptly on that date, or to set a quit date and cut back gradually for 2weeks before quitting. All of the patients got nicotine replacement therapy and behavioral support. Abstinence was confirmed by exhaled carbon monoxide measurement. At a month, half of the patients in the abrupt-cessation group were abstinent, compared with 40% of those in the gradual-cessation group; at 6months, abstinence rates were still significantly higher in the abrupt-cessation group (22% vs . 16%). At baseline, half of all of the patients said that they would have preferred a gradual cessation, and a third preferred an abrupt cessation; at a month, those whose baseline preference was to quit gradually were significantly less likely to be abstinent, regardless of allocation, than those who preferred to quit abruptly (38% vs . 52%). These findings support current smoking cessation guidelines, which advise quitting abruptly. But for patients who are unwilling to do so, cutting back gradually still might be worthwhile. These results also suggest that a willingness to quit abruptly, rather than gradually, might signal a higher level of motivation. VARENICLINE AND BUPROPION ARENTASSOCIATED WITH PSYCHIATRIC RISKS Back in 2009, the Food and Drug Administration mandated black-box warnings for the smoking cessation medications varenicline (trade name: Chantix) and bupropion (trade name: Zyban) stating that they might cause serious neuropsychiatric adverse events; the drugs manufacturers were required to evaluate this risk in a randomized controlled trial. In a study on the website of The Lancet ( http:// dx.doi.org /10.1016/ S0140-6 736(16)30272-0 ), researchers randomized more than 8000motivated adults who smoked an average of 10 or more cigarettes /day to varenicline, bupropion, a transdermal nicotine patch, or placebo for 3months (80% of the patients had made at least 1 previous attempt to quit). All of the patients got counseling and agreed to stop smoking within a week of randomization; the patients were followed for 3months after treatment ended. Half of the patients met DSM-IV-TR criteria for psychiatric disorders, but were clinically stable; patients with substance abuse or unstable psychiatric conditions were excluded. Outcomes were analyzed in separate psychiatric and nonpsychiatric cohorts. Neuropsychiatric adverse events (like moderate- or severe-intensity anxiety, depression, agitation, and hostility) during and after treatment were significantly more common in the psychiatric cohort than in the nonpsychiatric cohort (5.8% vs . 2.1%), but within each cohort, adverse event rates were similar across all four of the treatment groups. In both of the cohorts, the rates of continuous smoking abstinence at 9weeks to 12weeks were significantly higher with varenicline than bupropion or transdermal nicotine, and the latter two were significantly better than placebo. These findings should reassure clinicians that varenicline and bupropion can be used for tobacco dependence in a broad range of patients, including those with stable psychiatric disease, without undue concern about neuropsychiatric adverse events. CALORIE RESTRICTION IN NONOBESEADULTS IS ASSOCIATEDWITH IMPROVEMENTS IN MOOD, SLEEP QUALITY, AND SEXUALFUNCTION Calorie restriction extends lifespan in many animal species, including nonhuman primates, but whether it has adverse effects on mood and quality of life in people remains an open question. In a multisite study on the website of JAMA Internal Medicine ( http:// dx.doi.org /10.1001/jamainternmed.2016.1189 ), researchers in the United States randomized 200 healthy nonobese patients with an average age of 38 and an average body-mass index of 25kg/m 2 to 2years of either 25% calorie restriction or usual calorie intake on an ad libitum basis. The calorie-restriction patients got individual and group counseling throughout the study period. At 2years, average weight loss was nearly 8kg in the calorie-restriction group (which was 10% of their baseline weight) and 0.4kg in the ad libitum group. Compared with the ad libitum group, the calorie-restriction group showed significant improvements in mood, quality of life, sleep quality, and sexual drive and relationship satisfaction. Most of the measures of improvement in the calorie-restriction group correlated with percent weight loss. These findings are reassuring that calorie restriction in nonobese adults results not only in weight loss, but also in improvements in mood and quality of life. POPULATION-BASED ESTIMATES OF APPROPRIATE AND INAPPROPRIATE ANTIBIOTIC PRESCRIBING Usually research about inappropriate antibiotic prescribing focuses on specific conditions and age groups. But in a study in the May3 issue of JAMA ( http:// dx.doi.org /10.1001/jama.2016.4151 ), researchers used several national ambulatory care databases to provide overall population-based estimates that could guide government and professional mandates designed to reduce inappropriate antibiotic prescribing. The researchers evaluated the appropriateness of antibiotic use in nearly 200,000 ambulatory visits (not including urgent care centers, minute clinics, federal facilities, or long-term care facilities) in 2010 and 2011 using accepted clinical practice guidelines. If guidelines were not available (like for sinusitis), the lowest regional level of antibiotic use was used as a surrogate for appropriateness (almost certainly still an overestimate). For some conditions (like pneumonia), all antibiotic use was deemed to be appropriate. The overall annual rate of antibiotic use was 500 prescriptions per 1000 people, of which roughly two thirds of the prescriptions (350 prescriptions/1000 people) were deemed to be appropriate. The overall rate ranged from 420 prescriptions per 1000 people in the West to 550 prescriptions per 1000 people in the South. Most of the inappropriate antibiotic use was for acute respiratory conditions (111 prescriptions/1000 people every year). A 50% reduction in inappropriate antibiotic prescribing could be achieved mostly through eliminating prescriptions for acute respiratory conditions ( http:// dx.doi.org /10.1001/jama.2016.4286 ). This drop would translate to an overall annual rate of about 400 prescriptions per 1000 people, still much higher (as the researchers note) than the prescribing rate in Sweden (which is 330 prescriptions/1000 people), a country with a very low rate of antibiotic resistance. PROMISING NEW TREATMENTS FOR EBOLA VIRUS In small uncontrolled studies, a cocktail of three different monoclonal antibodies known as Z-Mapp benefited patients with Ebola virus disease, but Z-Mapp is expensive and slow to produce. In a study in the March18 issue of Science ( http:// dx.doi.org /10.1126/science.aad5224 ), international researchers report that they have isolated a single monoclonal antibody (from a long-term survivor of Ebola virus disease) that neutralizes, in vitro, many different strains of Ebola virus that have emerged during the past 40years. Subsequent in vivo studies in monkeys showed that the antibody had a powerful protective effect even when administered 5days after exposure to the virus. In another study, this one published in the March17 issue of Nature ( http:// dx.doi.org /10.1038/nature17180 ), international researchers report that a small molecule called GS-5734 greatly inhibits in vitro replication of Ebola virus. Subsequent studies in monkeys showed that the molecule, when given intravenously once /day for 12 consecutive days, protected the monkeys from lethal doses of the virus even when treatment was started as long as 3days after exposure. Even more interesting, the molecule also has potent activity against other filoviruses (like Marburg virus) and against arenaviruses and coronaviruses (like severe acute respiratory syndrome and Middle East Respiratory Syndrome viruses). GS-5734 is inexpensive and relatively easy to produce in large quantities. The worlds response to the recent outbreak of Ebola virus disease that devastated parts of West Africa was slow and poorly coordinated. But todays technology (combined with commercial incentives) has led to promising new treatments emerging with remarkable speed. DUPILUMAB MIGHT HELP PATIENTSWITH SEVEREUNCONTROLLED ASTHMA Recently, the antiinterleukin-4monoclonal antibody dupilumab improved symptoms in patients with nasal polyposis ( www.jwatch.org /na40366 ). Now, in a study on the website of The Lancet ( http:// dx.doi.org /10.1016/ S0140-6736(16)30307-5 ), researchers randomized nearly 800 adults with uncontrolled asthma despite treatment with inhaled steroids plus long-acting β-agonists to add-on therapy with either subcutaneous dupilumab or placebo for 6months. Dupilumab is not approved by the Food and Drug Administration. Treatment every 2weeks was significantly associated with a 12% improvement in forced expiratory volume, 70% fewer severe exacerbations, and improved quality-of-life scores, compared with placebo. Plus, asthma-control and quality-of-life scores favored treatment every 2weeks rather than every 4weeks. Dose-related injection-site reactions were more common with dupilumab, and elevations in blood eosinophil counts were seen in patients with higher baseline eosinophil levels; one patient was treated with systemic steroids for hypereosinophilia. When added to inhaled corticosteroid and long-acting β-agonist therapy, dupilumab confers clinically significant improvements in lung function and symptoms and fewer exacerbations in patients with severe uncontrolled asthma. It represents a potential third class of monoclonal antibody for asthma (others are the IgE inhibitor omalizumab [trade name: Xolair] and the interleukin-5 antagonists mepolizumab [trade name: Nucala] and reslizumab [trade name: Cinqair]). But the risk for hypereosinophilic syndrome is worrisome. HOUSE DUST MITE SUBLINGUAL IMMUNOTHERAPY PREVENTS SOME ASTHMA EXACERBATIONS House dust mites are the most important allergic trigger for asthma and perennial allergic rhinitis. Subcutaneous immunotherapy improves allergic rhinitis and allergic asthma and has a disease-modifying effect, but it comes with multiple injections and the risk for systemic allergic reactions. Dust mite sublingual immunotherapy consists of a tablet or a liquid, administered every day, and held under the tongue; it improves the symptoms of allergic rhinitis and often results in lower required doses of inhaled corticosteroids in patients with asthma, but it has not been shown to prevent exacerbations of asthma. In a multicenter study in the April26 issue of JAMA ( http:// dx.doi.org /10.1001/jama.2016.3964 ), researchers in Europe randomized more than 800 patients with a dust mite allergy as well as uncontrolled asthma, despite treatment with inhaled corticosteroids, to lower or higher doses of sublingual immunotherapy or to placebo. During 6months of treatment plus the reduction and discontinuation of inhaled corticosteroids, moderate or severe exacerbations were seen significantly less commonly with sublingual immunotherapy than with placebo (25% vs . 32%). There was no difference in patient-reported asthma control or quality of life. Plus, there were no serious adverse events, but more sublingual immunotherapy patients than placebo patients reported oral symptoms, like oral pruritus (17% vs . 3%). Although its not yet approved by the Food and Drug Administration, sublingual house dust mite immunotherapy is a viable option for asthma patients with allergic symptoms that are not controlled with inhaled corticosteroids ( http:// dx.doi.org /10.1001/jama.2016.4078 ). The overall improvement was modest, but the therapy was safe and well tolerated, except for oral irritation. This study was industry-funded. FLUOROQUINOLONES AND RETINALDETACHMENT: THEPENDULUM SWINGS AGAIN There are conflicting data on the association between fluoroquinolone antibiotics and retinal detachment; the two most prominent studies one positive and one negative were published a few years ago ( www.jwatch.org /id201204110000004 and www.jwatch.org /na33046 ). Now, in a study in the Aprilissue of JAMA Ophthalmology ( http:// dx.doi.org /10.1001/jamaophthalmol.2015.6205 ), researchers in France evaluated nationwide healthcare databases and identified nearly 30,000 eligible patients who underwent retinal-detachment surgery during a recent 3-year period. Using a case-crossover design, the researchers compared oral fluoroquinolone use during the 10days before retinal surgery with use during a control period (which was 2months to 6months before retinal surgery). Current exposure to fluoroquinolones was associated with a significantly higher risk for retinal detachment (adjusted odds ratio, 1.5); the only individual fluoroquinolone associated with this risk was levofloxacin (AOR, 2.1). In this study, current fluoroquinolone use was associated with a moderately increased relative risk for retinal detachment. But the absolute risk although not estimated in this report would be extremely low: Only about 1 per 1000 retinal-detachment patients had current fluoroquinolone exposure (compared with control-period exposure), and the researchers note that about 5million fluoroquinolone prescriptions are dispensed in France every year. Although a causal association remains uncertain, this potential complication serves as yet another reminder to prescribe quinolone antibiotics only for valid clinical indications. STEM CELL TREATMENTS FOR DAMAGED CORNEAS AND CONGENITALCATARACTS Stem cell biology is starting to become stem cell medicine. In the March17 issue of Nature , two studies show advances in ophthalmologic medicine that take advantage of stem cell technology. Human induced pluripotent stem cells ( www.jwatch.org /jw200808260000003 ) can be chemically coaxed to becomea primitive eye. In the first study ( http:// dx.doi.org /10.1038/nature17000 ), researchers in Japan took cornea-like cells from such primitive eyes and grew them into sheets that resembled corneas. These corneas restored the vision of rabbits that had a blinding corneal stem cell deficiency. In the second study ( http:// dx.doi.org /10.1038/nature17181 ), researchers discovered that the lens capsule contains lens stem cells, which can be chemically coaxed to form a lens. They developed a minimally invasive surgical technique that removes a cataractous lens without damaging the lens stem cells that remain in the capsule. They then showed that this surgical technique allows monkeys and rabbits to grow new lenses. The researchers employed this technique in 12 human children with congenital cataracts, and the children grew their own cataract-free lenses in the 3months following surgery, without complications. Usually, the century-old technique of corneal transplantation works, although it can be complicated by inflammation and rejection. Although using corneal sheets grown from a persons own induced pluripotent stem cells will likely not enter clinical practice any time soon, this research opens the door for eventual implementation. In contrast, implanting synthetic lenses for congenital cataracts in children is much less successful than using synthetic lenses in adults in large part, because a young childs eye keeps growing. The remarkable technique of encouraging a childs eye to regrow its own cataract-free lens might enter clinical practice relatively soon ( http:// dx.doi.org /10.1038/nature17305 ). EXCELLENT FIT PERFORMANCE IN A LARGE ORGANIZED SCREENINGPROGRAM Kaiser Permanente operates the largest organized colorectal cancer screening program in the United States, in which eligible patients (between the ages of 50 and 75) are mailed annual fecal immunochemical tests (FITs) with instructions for test completion and return. In a retrospective study in the April5 Annals of Internal Medicine ( http:// dx.doi.org /10.7326/M15-0983 ), researchers analyzed the performance of FIT in this population during 4 consecutive years and found that: Among nearly 700,000 invited patients, nearly half returned FITs in the first year. Among those who stayed eligible for screening after round-one testing, participation was about 80% in years 2, 3, and 4. FIT was positive in 5% of the screened patients in the first year and was positive in 4% in the subsequent years. Among the patients with positive FITs, 80% underwent colonoscopy within a year. The positive predictive value for any adenoma was 56% in men and 42% in women and was 11% for advanced adenomas. Colorectal cancer was detected in roughly 3% of the screened patients. The estimated sensitivity of FIT for colorectal cancer, based on follow-up of all of the patients who returned first year FITs, was about 80% in the subsequent years. These results show excellent performance of fecal immunochemical tests during four rounds of screening for colorectal cancer in an organized program in the United States. A program like this one requires a substantial investment, but the Kaiser project is the largest screening program of its type and can serve as a model for other healthcare plans across the country. DAILY USE OF CHECKLISTS DIDNT CHANGE ICU OUTCOMES Checklists have become incorporated into a myriad of clinical settings since it was shown, seven years ago, that theres decreased morbidity and mortality with their use in the operating room ( www.jwatch.org /jw200902030000003 ). Many intensive care units have adopted checklists as part of daily interdisciplinary rounds as a means to address quality metrics, whether checklists make a difference is unclear. In a study in the April12 issue of JAMA ( http:// dx.doi.org /10.1001/jama.2016.3463 ), researchers in Brazil randomized 118 ICUs to either routine care or the implementation of interdisciplinary rounds with quality-improvement checklists (the average duration of the intervention was 5months). Metrics on the checklist included venous thromboembolism prophylaxis, removal of unnecessary central venous or urinary catheters, optimization of nutrition, appropriate analgesia and sedation, assessment for readiness for extubation, appropriate antibiotic use and the detection of sepsis, and the use of appropriate tidal volumes for acute respiratory distress syndrome. Average in-hospital mortality, ICU length of stay, nosocomial infection rate, and the duration of mechanical ventilation were all similar in the two groups. The intervention ICUs exhibited better (although not dramatically better) adherence to the guidelines in the four care domains with poor baseline measures, namely: Low tidal volumes, appropriate light sedation, and removal of central venous and urinary catheters. Many institutions use checklists in their intensive care units, and despite these findings, that may not change. In this study, many of the metrics were ones in which the ICUs were already performing well. Quality-improvement efforts should target local areas for improvement, and local strategies are needed to change culture. Although laudable in scope, the diffuse approach of this study made a finding of no difference very likely. EFFECTIVENESS OF PHARMACIST-LED CHRONIC DISEASE MANAGEMENT vs . USUAL CARE Direct care by clinical pharmacists of patients with chronic diseases is increasingly common and, to a growing extent, is supported by state and federal licensing laws and insurance reimbursement. In a systematic review on the website of the Annals of Internal Medicine ( http:// dx.doi.org /10.7326/M15-3058 ), researchers analyzed 60 studies to compare the outcomes of pharmacist-led chronic disease management with those of usual care in more than 30,000 community-dwelling patients. (The median duration of the studies was about a year and most were performed in primary care settings.) The patients had one or more chronic conditions (like cardiovascular disease, diabetes, and hypertension), and the pharmacists were responsible for at least one of several components of chronic-disease management (like medication monitoring, medication review, patient education and support, and independent prescribing). Major findings of the study were: Patients were more likely to attain laboratory or physiological goals (like lower blood pressure or lipid levels, and glycemic control) with pharmacist-led care than with usual care. Resource use (like office visits, emergency department visits, and hospitalizations) was similar with pharmacist-led and usual care. Medication adherence was similar, although the evidence was rated as low-strength. The reporting of outcomes was limited, and few of the studies addressed actual clinical events. Patient satisfaction results were mixed, but the evidence was poor. The reporting of harms was too limited to evaluate. These results suggest that pharmacist-led chronic disease management is probably no worse than usual care, but the evidence is weak for drawing conclusions, and little is known about the benefits for actual clinical outcomes. Whether pharmacist-led care might replace, or serve as an adjunct to, usual care is unclear. EXPANDED MEDICAID COVERAGE IS ASSOCIATED WITH GREATER HEALTHCARE UTILIZATION Back in 2012, the United States Supreme Court ruled that individual states could decide whether to expand Medicaid under the Affordable Care Act. When the law took effect in 2014, 26 states and the District of Columbia expanded their Medicaid programs. But the effects of Medicaid expansion on access to care, healthcare utilization, and health outcomes are largely unknown. Until now. In a study on the website of the Annals of Internal Medicine ( http:// dx.doi.org /10.7326/M15-2234 ), researchers analyzed self-reported data from more than 40,000 low-income patients younger than 65 who were interviewed for an ongoing, government-conducted health survey between 2010 and 2014. In a comparison of changes that happened after the implementation of the Affordable Care Act, respondents in the states that expanded Medicaid coverage (compared with those in the states that did not) were significantly more likely to acquire Medicaid coverage (10.5% difference), report that their health insurance was better than in the past year (7.1% difference), visit a general physician (6.6%), be hospitalized overnight (2.4%), and get new diagnoses of diabetes (5.2%) or high cholesterol (5.7%). After the implementation of the Affordable Care Act, fewer respondents in the expansion states than in the nonexpansion states were uninsured (7.4% difference in coverage rates). Access to care and self-reported health or mental health status were similar in the expansion and the nonexpansion states. Although limited by its nonrandomized design, reliance on self-reported data, and brief period of follow-up after the implementation of the Affordable Care Act, this large quasi-experimental study provides new evidence that Medicaid expansion promotes the utilization of health services and diagnoses of important chronic conditions.
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