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. Eva Lonn reported receiving grant support from the Canadian Institutes of Health Research and AstraZeneca during the conduct of the study; grant support from Bayer, GlaxoSmithKline, Merck Schering, and Eli Lilly, grant support and personal fees from Amgen and Sanofi, and personal fees from Novartis, Cadila Pharmaceuticals, and Servier Canada outside of the submitted work. Dr. Daniel Murphy and the planning committee members reported that they had nothing todisclose. HOPE-3: A PRIMARY CV PREVENTION TRIAL IN PATIENTS AT INTERMEDIATERISK The Heart Outcomes Prevention Evaluation-3 (known by the acronym HOPE-3) is an international randomized trial conducted in 20 countries; China, India, Colombia, Argentina, and Canada contributed the most participants. The trial included nearly 13,000 patients (age, ≥65 for women, and ≥55 for men) without known cardiovascular disease who were considered to be at an intermediate risk by virtue of meeting at least one inclusion criterion, namely: An elevated waisthip ratio, an HDL cholesterol level less than 39 mg/ dL for men or less than 50 mg/ dL for women, current or recent smoking, prediabetes or diet-controlled diabetes, premature coronary disease in first-degree relatives, or early renal dysfunction. Most of the patients had at least two of the risk factors. Findings appear on the website of the New England Journal of Medicine ( http:// dx.doi.org /10.1056/NEJMoa1600175 , http:// dx.doi.org /10.1056/NEJMoa1600176 , and http:// dx.doi.org /10.1056/NEJMoa1600177 ). In a 22 factorial design, each patient got 10 mg/ day of rosuvastatin or placebo, plus the combination of candesartan/hydrochlorothiazide (16 mg/ 12.5mg daily) or placebo. At baseline, average LDL cholesterol level was 128 mg/ dL and average blood pressure was 138/82mmHg. During a median follow-up of nearly 6years, the key results were: Compared with placebo, rosuvastatin lowered average LDL cholesterol level by 35 mg/ dL, and the antihypertensive drugs lowered average systolic blood pressure by 6mmHg and average diastolic blood pressure by 3mmHg. The first coprimary outcome (which was cardiovascular-related death, nonfatal stroke, or nonfatal myocardial infarction) was seen significantly less often with rosuvastatin than with placebo (3.7% vs . 4.8%); absolute reductions were 0.3%, 0.4%, and 0.5% for cardiovascular-related death, MI, and stroke, respectively. Overall, candesartan/hydrochlorothiazide did not significantly lower the incidence of the first coprimary outcome compared with placebo (4.1% vs . 4.4%), but it did lower the incidence in a subgroup of patients with the highest baseline systolic blood pressure (higher than 143mmHg; 4.8% vs . 6.5%). Overall, the outcomes with rosuvastatin plus candesartan/hydrochlorothiazide were not significantly better than the outcomes with rosuvastatin alone. All-cause mortality was not lowered by active therapies compared with placebo. Neither treatment increased the risk for diabetes; there was a small excess of muscle pain with rosuvastatin and dizziness with candesartan/hydrochlorothiazide. These results are certain to further unsettle the ongoing discussion about what patients and their doctors should do about the common risk factor of mildly elevated blood pressure and runs counter to the findings of the SPRINT trial, albeit with a different population and less-aggressive treatment ( www.jwatch.org /na39551 ). Its interesting that HOPE-3 had no LDL cholesterol or blood pressure thresholds for enrollment (although patients with symptomatic hypotension were excluded). For intermediate-risk patients like those in this trial (whose 10-year risk for adverse cardiovascular events is roughly 10%), the subgroup analysis of the trials antihypertensive arm suggested potential benefit when systolic blood pressure was higher than 143mmHg. For the cholesterol-lowering arm, the 1 percentage-point difference in cardiovascular-related death, myocardial infarction, or stroke that favored rosuvastatin ( vs . placebo) means that about 100 patients were treated for 5years to benefit 1 patient. In the United States, the retail cost of rosuvastatin (trade name: Crestor) for which a generic form is not yet available is nearly US$4000 /year . Obviously, patient preferences will be important to guide these decisions ( http:// dx.doi.org /10.1056/NEJMe1603504 ). HOPE-3 was funded in part by the maker of Crestor. FIRE AND ICE: FOR AF, BOTHTREATMENTS WERE EQUIVALENT Pulmonary vein isolation is the cornerstone of the ablative management of atrial fibrillation; cryoablation is a more recent addition than radiofrequency ablation. In a study on the website of the New England Journal of Medicine ( http:// dx.doi.org /10.1056/NEJMoa1602014 ), researchers randomized nearly 800 patients with paroxysmal atrial fibrillation refractory to at least one drug to either cryoablation or radiofrequency ablation. Cryoablation had a significantly shorter procedure duration, but a longer fluoroscopy time than did radiofrequency ablation. Procedure-related complications were seen with similar frequency in the two groups (a 1-year estimate of about 11%), but very serious complications were rare. At an average follow-up of 1.5years (after a 3-month blanking period), about a third of the patients in both groups experienced a recurrence of their atrial fibrillation. In this trial, cryoablation and radiofrequency ablation were similar in efficacy and safety. Accordingly, most providers of these procedures will find no reason to change their preferences of ablative tools and most will point to minor differences in the results that justify their choices. The overall 1-year recurrence rate of 35% indicates the difficulty of achieving a cure with ablation for atrial fibrillation. In fact, the goal of a cure might be unreasonable for this type of arrhythmia, given its variable mechanisms and clinical course. This study was sponsored by the cryoballoon manufacturer. HOW DOES TAVR FARE IN INTERMEDIATE-RISK PATIENTS? Transcatheter aortic valve replacement is a valuable alternative to surgical aortic valve replacement in high-risk patients with severe aortic stenosis ( www.jwatch.org /na37301 ). In a multicenter study on the website of the New England Journal of Medicine ( http:// dx.doi.org /10.1056/NEJMoa1514616 ), researchers randomized 2000 patients with severe aortic stenosis who were considered to be at intermediate surgical risk to either transcatheter or surgical aortic valve replacement. The patients average age was 82. At 2years, the incidences of death or disabling stroke were similar at around 20% in the two groups. The similarity between the two approaches persisted within the transthoracic-access cohort, but transcatheter valve replacement showed a statistically significant advantage over surgical valve replacement within the transfemoral-access cohort. Aortic valve areas and gradients improved to a larger extent with the transcatheter method than with the surgical method at all time points. More often, transcatheter aortic valve replacement resulted in major vascular complications and paravalvular aortic regurgitation, but was associated with lower rates of acute kidney injury, severe bleeding, and new-onset atrial fibrillation. Transcatheter aortic valve replacement was noninferior to surgical aortic valve replacement with respect to midterm outcomes in patients who had intermediate surgical risk. If the prosthetic aortic valves prove to have long-term durability, the transcatheter method will surely be a breakthrough in how older patients with symptomatic aortic stenosis are treated ( http:// dx.doi.org /10.1056/NEJMe1603473 ). This study was funded by the manufacturer of the transcatheter aortic valve replacement system. FOR ISCHEMIC CARDIOMYOPATHY, BYPASS SURGERY MIGHT BE BETTERAFTER ALL In the STICH trial, the results of which were published 5years ago ( www.jwatch.org /jw201104260000001 ), researchers randomized 1200 patients with coronary artery disease (that was amenable to coronary artery bypass grafting) and left-ventricular ejection fractions of 35% or lower to either bypass surgery plus medical therapy or medical therapy alone. None of the patients had 50% or greater left-main coronary-artery stenosis or Canadian Cardiovascular Society class III or IV angina. During a median follow-up of nearly 5years, all-cause mortality was similar in the two groups, but mortality from cardiovascular causes was slightly lower with bypass surgery. Now, in an extension study published on the website of the New England Journal of Medicine ( http:// dx.doi.org /10.1056/NEJMoa1602001 ), researchers reviewed patient outcomes during a median follow-up of 10years and found that bypass surgery significantly outperformed medical therapy alone for all-cause mortality (59% vs . 66%), all-cause mortality or hospitalization for heart failure (66% vs . 75%), and death from cardiovascular causes (41% vs . 49%). The all-cause mortality advantage of bypass surgery over medical therapy, which began to surface at about 3years, was especially evident in the patients with 3-vessel disease and those with left-ventricular ejection fractions of 28% or lower. About 20% of the patients who were initially randomized to medical therapy alone underwent bypass surgery during follow-up, but the mortality advantage of bypass surgery persisted in a per-protocol analysis. The lack of benefit for coronary artery bypass grafting in the original STICH trial somewhat surprised most cardiologists and surgeons, who had learned from the earliest landmark revascularization studies that patients with the worst left-ventricular function got the greatest benefit from surgery. These longer-term data now support the original hypothesis that bypass surgery offers a survival benefit to patients with severe coronary artery disease and left-ventricular dysfunction, thereby offsetting the early operative risk ( http:// dx.doi.org /10.1056/NEJMe1603615 ). GASTROPROTECTION WITH OMEPRAZOLE IN DUALANTIPLATELETTHERAPY: DOESASPIRIN DOSE MATTER? In the COGENT study from 2010, patients who were taking aspirin plus clopidogrel (in most cases after coronary stenting) were randomized to either the proton-pump inhibitor omeprazole or placebo. Omeprazole protected against gastrointestinal bleeding without affecting adverse cardiovascular event rates ( www.jwatch.org /jw201010280000004 ). In a post hoc analysis of COGENT data, researchers examined whether omeprazole was effective and safe regardless of aspirin dose; 2500 patients got low-dose aspirin (up to 100 mg/ day) and 1300 patients got high-dose aspirin (more than 100 mg/ day). Median follow-up was about 4months. Details appear in the April1 Journal of the American College of Cardiology ( http:// dx.doi.org /10.1016/ j. jacc.2015.12.068 ). High-dose and low-dose aspirin were associated with similar rates of adverse GI events (about 2%) and adverse cardiovascular events (about 5%). The omeprazole patients had lower rates of adverse GI events than the placebo patients among both high-dose aspirin users (0.9% vs . 2.6%) and low-dose users (1.2% vs . 3.1%). Among both groups of aspirin users, the rates of adverse cardiovascular events were similar in the omeprazole and the placebo patients. This analysis suggests that in patients who take clopidogrel plus aspirin, proton-pump inhibitor therapy prevents adverse gastrointestinal events regardless of aspirin dose. Aspirin dosing in this trial was at the providers discretion and was quite variable, with approximately a third of the patients getting high-dose aspirin. Clinicians should keep in mind that the specific antiplatelet drug being used can also influence aspirin dose. For example, lower aspirin doses are recommended when ticagrelor is used. At the time NEJM Journal Watch reviewed this paper, its publisher stated that it was not in final form and that subsequent changes might be made. OLDER U.S. ADULTS ARE USING MORE PRESCRIPTION MEDICATIONS AND DIETARY SUPPLEMENTS Recently, it was shown that prescription drug use and the prevalence of polypharmacy among older patients in the United States rose significantly between 1999 and 2012 ( www.jwatch.org /NA39516 ). In a study in the Aprilissue of JAMA Internal Medicine ( http:// dx.doi.org /10.1001/jamainternmed.2015.8581 ), researchers added to those findings by evaluating the use of over-the-counter drugs, prescription medications, and dietary supplements among 2400 older adults in 2005 and 2006 and in 2200 older adults in 2011 and 2012. The average age in both of the groups was 71. Between the two survey periods, the percentage of patients who used prescription drugs rose slightly, from 84% to 88%; OTC medication use declined from 44% to 38%, whereas dietary supplement use increased from 52% to 64%. The concurrent use of 5 or more prescription drugs increased from 31% to 36%; the concurrent use of 5 or more prescription or OTC drugs or supplements rose from 53% to 67%. Based on standard criteria to identify potentially major drugdrug interactions, the risk for these interactions was about 8% in the earlier cohort and 15% in the later cohort. These results serve as a reminder to clinicians to ask about over-the-counter medication and dietary supplement use, especially among patients who take multiple prescribed medications. ANOTHER INTERVENTION TO ENHANCESAFE DRUG PRESCRIBING Increasingly, researchers are examining ways to improve the quality and the safety of drug prescribing. In a study in the March17 New England Journal of Medicine ( http:// dx.doi.org /10.1056/NEJMsa1508955 ), researchers in Scotland assigned 30 primary care practices to implement three interventions to reduce the high-risk prescribing of nonsteroidal anti-inflammatory drugs and antiplatelet drugs; those interventions were: 1.A 1-hour educational program plus written materials 2.Financial incentives for performing chart reviews (about US$900 per clinician) 3.Alerts on high-risk prescriptions in patients electronic health records Specifically, these interventions were aimed at promoting the use of gastroprotective drugs when NSAIDS or aspirin were prescribed to patients at high risk for gastrointestinal bleeding, and lowering NSAID prescribing to patients with chronic renal disease or heart failure. Compared with a preintervention baseline, the rate of high-risk prescribing significantly declined during the yearlong intervention period from 3.7% to 2.2% for 30,000 patients with risk factors for adverse outcomes from NSAIDs and antiplatelet drugs; this effect lasted for a year after the intervention period. The combined intervention was also associated with significantly fewer hospitalizations for both gastrointestinal complications (4 fewer per 10,000 patient-years) and acute kidney injury (24 fewer per 10,000 patient-years). This combination of interventions to improve drug prescribing was effective. But nonsteroidal anti-inflammatory drugs and antiplatelet drugs represent just a fraction of the many potential targets for higher-quality prescribing (others might include the overprescribing of antibiotics, sedatives, and opioids), and payers are unlikely to provide financial incentives for each of these possible targets. Plus, the increasing burden of electronic health records inbox notifications might lead to clinicians overlooking important clinical warnings. WHAT HAPPENS AFTER PEOPLE UNDERGO DIRECT-TO-CONSUMER GENOMIC TESTING? We now can learn about our DNA through direct-to-consumer personal genomic testing. In a study on the website of the Annals of Internal Medicine ( http:// dx.doi.org /10.7326/M15-0995 ), researchers evaluated the perceptions of 1000 people who underwent testing through either 23andMe or Pathway Genomics. The study participants were recruited online and completed baseline surveys and follow-up surveys at 6months. A greater proportion of the respondents had family incomes lower than US$40,000 /year than US$200,000 /year or higher (16% vs. 12%). Sixty percent of the respondents planned to discuss the results with their primary care providers, but at 6months, two thirds had not shared their results with any clinician. Among those who hadnt discussed the results with any clinician, 9% had concerns about the results becoming a part of their medical record and 40% still planned on discussing the results. Among those who shared their results with their primary care clinicians, a third were very satisfied with the discussions, nearly half were somewhat satisfied, and 18% were not at all satisfied. Whether its coronary calcium scoring, C-reactive protein measurement, or genomic testing, we have entered into an era where access to information and testing is widely available. Potentially, this access has positive effects, including promoting the active engagement of patients with the healthcare system. What remains uncertain is whether this type of genetic information can be translated into improved health outcomes ( http:// dx.doi.org /10.7326/M16-0257 ). UNTANGLING THE OBESITY PARADOX The term obesity paradox was coined after studies found that mortality was lower among middle-aged and older people who are overweight or mildly obese, compared with those who are of normal weight. To clarify the contributions of body-mass index and adiposity to all-cause mortality, researchers in Canada examined data from a study of bone density in 50,000 women with an average age of 63 and 5000 men with an average age of 65; dual-energy x-ray absorptiometry scans were used to estimate percent body fat. The average follow-up was nearly 7years in women and nearly 5years in men. Findings appear on the website of the Annals of Internal Medicine ( http:// dx.doi.org /10.7326/M15-1181 ). The patients were divided into five groups based on increasing body-mass index and DEXA-derived percent adiposity, with the middle group serving as the reference. In fully adjusted models where body-mass index and adiposity were examined together, lower body-mass index (25 kg/m 2 or lower in women and 24 kg/m 2 or lower in men) was associated with a higher risk for all-cause death in both women and men, whereas a higher BMI ( 28 kg/m 2 or higher) was not, but a high body-fat percentage was associated with higher mortality. In this observational study of mostly white women, higher adiposity was associated with higher mortality after adjusting for body-mass index, and lower body-mass index was associated with higher mortality after adjusting for adiposity. This finding indicates that BMI might not be a reliable measure of adiposity as it relates to adverse health outcomes, and it might help explain the obesity paradox seen in some studies. EFFECT OF A MASS-PARTICIPATION MOBILE TECHNOLOGYBASED EXERCISE PROGRAM Mobile lifestyle-modification programs in which pedometers and web-based communications are used to encourage physical activity have been effective in relatively small studies in workplace settings and populations in high-income countries. In a study on the website of the Journal of the American College of Cardiology ( http:// dx.doi.org /10.1016/ j. jacc.2016.03.472 ), researchers in Australia evaluated the real-world effectiveness of a mobile technologybased health program called Stepathlon in 70,000 people in mostly low- and middle-income countries; 90% of the participants were in India; the other 10% were distributed across 60 other countries (including Singapore, the United States, and China). The program was conducted as a 100-day global event during each of 3 consecutive years. The participants were organized into workplace-based teams, were issued pedometers, and were challenged to boost their daily steps and physical activity. The pedometer data were uploaded to an interactive website that provided personalized analyses and tools, and other data were collected from Web-based questionnaires that were completed by the participants. All of the participants got encouraging e-mails every day. The program costs (which were between US$50US$60 per participant) were borne by employers. Complete baseline and post-participation data were available for a little more than half of the participants. Among those who finished the program, walking time increased by an average of 3500 steps /day , exercise frequency rose by an average of 0.9days /week , and sitting time fell by an average of 0.7hours /day ; average weight loss was 1.5kg. Adherence in this study was relatively good, compared with most lifestyle modification studies, and the results were impressive, especially for a middle- and lower-income study population. This type of program could be recommended for many community and workplace populations. At the time NEJM Journal Watch reviewed this paper, its publisher noted that it was an accepted manuscript and that subsequent changes might be made. TOO MANY NOTIFICATIONS IN ELECTRONIC HEALTH RECORDS? The burden of inbox notifications in electronic health records is one reason many clinicians have lovehate relationships with their electronic health records systems. In a study in the Aprilissue of JAMA Internal Medicine ( http:// dx.doi.org /10.1001/jamainternmed.2016.0209 ), researchers tabulated the number of electronic health records notifications received by 50 primary care physicians and 50 specialists at three large practices in Texas during 125 workdays in 2015. The electronic health records systems used were Epic and General Electric Centricity. On average, each primary care physician got 80 notifications per full workday; the specialists averaged 30 notifications /day . Twenty percent of the notifications to primary care physicians were test results. Extrapolating from other research in which clinicians spent an average of nearly a minute per processed message, the researchers estimate that the primary care physicians in this study averaged more than an hour /day processing electronic health records notifications. Clinicians and health systems need help in managing the burden of electronic notifications, but the best way to accomplish this task is unclear. As the volume of notifications rises, clinicians will surely experience alert fatigue and overlook or mishandle some notifications with potentially serious consequences. This isnt a totally new problem: Sometimes, oral or printed notifications were overlooked or mishandled in the pre-electronic era, too. BOTH MINDFULNESS-BASED STRESSREDUCTION AND CBT ARE USEFUL FOR LOW BACK PAIN Often, the recommendations for nonpharmacological approaches to managing low back pain focus on cognitive behavioral therapy; the benefits of mindfulness-based stress reduction are less clear. In a study in the March22 and 29 issue of JAMA ( http:// dx.doi.org /10.1001/jama.2016.2323 ), researchers randomized 340 patients with an average age of 49 and with moderate-to-severe back pain for 3months or longer (the average duration of the pain was 7years) to cognitive behavioral therapy (education about pain, emotion, sleep, and dysfunctional thoughts), to mindfulness-based stress reduction (including body awareness and meditation) or to usual care. Both of the interventions were delivered in eight weekly 2-hour sessions. About half of each intervention group attended at least six sessions. At 6months, there were clinically meaningful improvements in functional limitation in about 60% of the patients in each of the intervention groups, compared with 45% of the patients in the usual-care group thats a significant difference. Clinically meaningful improvement in the so-called bothersomeness of pain was seen in about 45% of each intervention group vs . 30% of the usual-care group thats also a significant difference. The results were similar at a year. These results on the effects of mindfulness-based stress reduction and cognitive behavioral therapy on chronic low back pain are impressive, especially given the relatively poor adherence to both interventions. As has been mentioned in other discussions of pain management, access for primary care patients and clinicians to nonpharmacological approaches is limited ( http:// dx.doi.org /10.1001/jama.2016.2437 ), but if these interventions are available, clinicians should encourage their use. VITAMIN D SUPPLEMENTATION DOESNT PREVENT COLDS IN ADULTASTHMA PATIENTS Vitamin D deficiency has been linked to asthma and to susceptibility for acute respiratory tract infections, but vitamin D supplementation has yielded inconsistent benefit. In a study published 2years ago, 400 adult patients with mild-to-moderate asthma and serum 25-hydroxyvitamin D levels lower than 30 ng/ mL were randomized to either placebo or vitamin D 3 (cholecalciferol) the initial dose was 100,000 IU, then 4000 IU/ day for 7months while inhaled corticosteroids were tapered. The time to first asthma treatment failure and the incidence of exacerbations were similar in the two groups ( www.jwatch.org /na34705 ). Now, in a prospectively planned, secondary analysis published in the March15 American Journal of Respiratory and Critical Care Medicine ( http:// dx.doi.org /10.1164/rccm.201506-1169OC ), the researchers evaluated whether vitamin D 3 supplementation lowers the incidence and severity of colds. The average 25-hydroxyvitamin D level in the vitamin D 3 group, after treatment, was 42 ng/ mL. Half of the patients experienced at least one self-reported cold; there was no difference between the two groups in the number of colds or in the primary endpoint of the severity of symptoms of a cold (measured by validated questionnaires). Among black patients, those who got vitamin D 3 were significantly more likely than were those who got placebo to experience cold symptoms. Vitamin D supplementation seems to be a cure waiting for a disease. Although some studies suggest that vitamin D 3 supplementation benefits children, it shows no benefit for preventing asthma exacerbations or cold symptoms in adults with mild-to-moderate asthma. On the contrary, the researchers speculate that supplementation might have made some otherwise asymptomatic colds symptomatic by reconstituting the inflammatory response. PROLONGED THERAPY FOR PERSISTENT LYME DISEASE SYMPTOMS Whether prolonged treatment lessens the persistent symptoms of Lyme disease is controversial. To resolve this issue, researchers in the Netherlands conducted a multicenter trial that involved nearly 300 patients with Lyme disease and persistent musculoskeletal pain, arthritis, arthralgia, neuralgia, sensory disturbances, dysesthesia, neuropsychological disorders, or cognitive disorders, with or without persistent fatigue; the median duration of symptoms was longer than 2years. Findings appear in the March31 New England Journal of Medicine ( http:// dx.doi.org /10.1056/NEJMoa1505425 ). The patients got initial intravenous ceftriaxone for 2weeks, followed by randomization to one of three oral regimens: Namely, doxycycline, clarithromycin plus hydroxychloroquine, or placebo for 3months. On standardized questionnaires, health-related quality-of-life and fatigue scores were similar among the treatment groups, as was the rate of treatment discontinuation. There were four serious adverse events, none of which was drug-related. This important study showed that longer-term therapy did not benefit patients with Lyme disease who had symptoms that had been present for months to years following their diagnosis ( http:// dx.doi.org /10.1056/NEJMe1502350 ). KIDNEY TRANSPLANTS FROM HLA-INCOMPATIBLE LIVE DONORS Some patients who are awaiting kidney transplantation have anti-human leukocyte antigen (HLA) antibodies. Although these patients can undergo desensitization and transplantation with kidneys from incompatible live donors, these transplants have poorer outcomes than those from compatible live donors. Even so, a transplant from an incompatible live donor might be preferable to remaining on a waiting list. In a multicenter study in the March10 New England Journal of Medicine ( http:// dx.doi.org /10.1056/NEJMoa1508380 ), researchers in the United States examined outcomes among 1000 adults who underwent transplantation with kidneys from HLA-incompatible live donors. Controls were patients who were on a waiting list for compatible deceased donors, but were otherwise similar to the transplanted patients. The 1-year survival rate in the patients with transplants from HLA-incompatible live donors was 95%; 5-year survival was 86%; and 8-year survival was 77%. The survival rates were significantly lower (90%, 59%, and 44%, respectively) among the controls who stayed on the waiting list and never got transplants. Among the wait-listed controls who either stayed on the waiting list or subsequently got compatible deceased-donor kidneys, survival rates were 94% at 1year, 74% at 5years, and 63% at 8years. These survival rates were lower than those with incompatible live donor kidneys. This study shows that the patients who get kidney transplants from HLA-incompatible live donors have extended survival compared with the patients who await transplantation from deceased donors. Because more than 20 centers were involved, the results are probably generalizable ( http:// dx.doi.org /10.1056/NEJMe1601379 ). NATURAL HISTORY OF INCIDENTAL SMALL PANCREATIC CYSTS Frequently, incidental pancreatic cysts are identified when patients undergo abdominal imaging, but malignant transformation is uncommon ( www.jwatch.org /na32639 ). Guidelines vary on recommendations for managing small asymptomatic pancreatic cysts without high-risk features. For example, the American Gastroenterological Association recommends follow-up magnetic resonance imaging at 1, 3, and 5years ( www.jwatch.org /na37714 ), whereas the American College of Radiology recommends only a single follow-up MRI at 1year, after which surveillance can stop if the cyst hasnt changed ( http:// dx.doi.org /10.1016/ j. jacr.2010.06.013 ). In a single-center retrospective study in the Marchissue of Radiology ( http:// dx.doi.org /10.1148/radiol.2015140972 ), researchers reviewed imaging in 260 patients with asymptomatic incidental small pancreatic cysts (between 5mm and 20mm in diameter) who had 2 or more MRIs at least 6months apart. The median number of MRIs was three per patient; the average time between the first and the last MRI was 3years (range, 0.5-11years). Cysts increased in size in a quarter of the patients. After 1year of initial stability, delayed growth of a cyst was seen in 11% of the patients; after 2years of stability, cyst growth was seen in 6% of the patients; and after 3years of stability, cyst growth was seen in 1.5% of the patients. During an average clinical follow-up of 5years, one patient died from a pancreatic cancer that arose in a site distant from her cyst. A second patient, whose cyst enlarged and developed high-risk characteristics during 6years, had surgery that revealed intraductal papillary mucinous neoplasm with high-grade dysplasia. Given that some pancreatic cysts exhibit delayed growth after a period of stability, the researchers suggest that MRI surveillance should continue beyond 1year. But they acknowledge that the clinical benefit of prolonged surveillance is unclear, and that a patients age and comorbidities should influence decisions on whether (and how long) to continue surveillance. RISKS FOR SECOND CANCERS AFTER PROSTATE RADIOTHERAPY The risk for second cancers in patients who get therapeutic radiation for Hodgkin lymphoma, breast cancer, and testicular cancer is well recognized. But whether an excess risk is also present in the patients who get radiotherapy for prostate cancer is unclear. In a meta-analysis on the website of The BMJ ( http:// dx.doi.org /10.1136/bm j. i851 ), researchers systematically reviewed 20 studies that involved patients with prostate cancer who got radiotherapy (mostly conformal external beam radiotherapy) vs . surgery or vs . no radiotherapy. The primary outcome was the development of secondary bladder, colorectal, lung, or hematologic cancer. Compared with the patients who were unexposed to radiotherapy, those who got radiotherapy had excess risks for secondary bladder cancer (hazard ratio, 1.67), colorectal cancer (HR, 1.79), and rectal cancer (HR, 1.79), but not lung or hematologic malignancies. The incidences of second cancers ranged from 0.1% to 4% for bladder cancer, 0.3% to 4% for colon cancer, and 0.3% to 1% for rectal cancer. The risks for second cancers were much higher with external beam radiotherapy than with brachytherapy. As noted by editorialists ( http:// dx.doi.org /10.1136/bm j. i1073 ), clinicians and patients must decide whether the increase in relative risk for a second cancer should influence the choice of curative-intent local therapy, especially for younger patients. They also point out that these results support the use of modern external beam radiotherapy, which is administered with much tighter treatment volumes. HAS THE AFFORDABLE CARE ACT AFFECTED HOSPITAL READMISSIONS? Back in 2010, the Affordable Care Act began to apply financial penalties to hospitals for higher than expected 30-day hospital readmission rates for targeted clinical conditions (namely, acute myocardial infarction, heart failure, and pneumonia). In a study on the website of the New England Journal of Medicine ( http:// dx.doi.org /10.1056/NEJMsa1513024 ), researchers evaluated more than 50 million hospital stays in 3400 hospitals in the United States and their associated 30-day hospital readmission rates; the researchers used an interrupted time series design and Centers for Medicare & Medicaid Services data from 2007 through 2015. Annual readmission rates declined throughout the study period, but a significantly faster decline in hospital readmission rates began in 2010 for conditions that were both targeted and not targeted by the Affordable Care Act. The rates of readmissions declined more rapidly for the targeted conditions than for the nontargeted ones, and the rates of hospital-observation admissions (observation-unit stays and observation readmissions) were not affected by the implementation of the Affordable Care Act. The passage and implementation of the Affordable Care Act, with its incentives and financial readmission penalties, likely had an overarching effect on the rates of all hospital readmissions in the United States and readmissions for targeted conditions were probably affected most of all. In all likelihood, the laws effects will be realized further in the years to come, as other clinical conditions (namely, total hip or knee replacement and chronic obstructive pulmonary disease) were designated as targeted conditions in 2015.
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