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. Christine Albert, Dr. Caroline Vitale, Dr. Allan Brett, and the planning committee members reported that they had nothing to disclose. GUIDELINE WATCH: POSITION STATEMENT ON FEEDINGTUBES FOR PATIENTS WITH ADVANCED DEMENTIA Declining oral intake resulting from both difficulty in eating and the loss of a desire to eat is an inevitable part of the natural progression of advanced dementia; its often addressed by inserting a feeding tube (usually, a percutaneous endoscopic gastrostomy tube). A new position statement released by the American Geriatrics Society addresses this issue. Details appear in the August Journal of the American Geriatrics Society ( http:// dx.doi.org /10.1111/jgs.12924 ). There are several key points, namely: The American Geriatrics Society doesnt recommend tube feeding for older patients with advanced dementia. Caregivers should create individualized hand-feeding approaches, and should recognize that tube feeding usually doesnt improve survival, comfort, or function in these patients. Surrogate decision-makers should understand that tube feeding is a medical therapy that requires balancing benefits and burdens. Decisions to insert feeding tubes should be consistent with the patients advance directives and previously stated (or presumed) preferences. Clinical institutions (like hospitals and nursing homes) should ensure that surrogates are fully informed before making the decision to place feeding tubes; institutions shouldnt pressure families or clinicians to institute tube feeding for convenience or to meet nutritional quality measures . Many percutaneous endoscopic gastrostomy tubes are placed when patients with dementia are hospitalized with acute illnesses; clinicians and families with no past relationships often make rushed decisions in this setting. But even in outpatient settings, in-depth deliberation about the limitations of tube feedings is often lacking. This succinct and well-written position statement can serve as a guide for clinicians who are committed to involving surrogates in fully informed decision-making regarding tube feeding. CANCER SCREENING RATES ARE TOO HIGH IN OLDER ADULTS WITH LIMITEDLIFE EXPECTANCY Many health organizations recommend against routine cancer screening in patients with short life expectancies (generally, less than 10years), but there are still inappropriately high screening rates ( www. jwatch .org /na33896 ). In a study on the website of JAMA Internal Medicine ( http:// dx.doi.org /10.1001/jamainternmed.2014.3895 ), researchers evaluated self-reported cancer screening in about 30,000 patients 65 or older who were periodically queried between 2000 and 2010. A validated instrument was used to calculate the 9-year mortality risk for each patient, and the patients were grouped from low risk (lower than 25%) to very high risk (75% or higher). The overall screening rates for prostate, breast, cervical, and colorectal cancer declined with increasing 9-year mortality risk, but recent screening was done at relatively high rates (55% for prostate cancer, 40% for breast and colorectal cancers, and 30% for cervical cancer) among the patients with the highest 9-year mortality risk. Likewise, screening rates declined with age, yet 55% of women 75 or older underwent screening for breast cancer, and 30% of the patients 85 or older were screened for colorectal cancer. Among the women with past hysterectomies for benign indications (a group for whom Pap smears arent recommended), a third of those at high 9-year mortality risk had Pap smears within the past 3years. The patients who had more education, were married, had health insurance, or had sources of medical care were more likely to be screened. Although no right rate of screening can be specified for all of the categories of patients who were evaluated, some screening rates are disturbingly high, especially in the patients for whom screening is absolutely not recommended. One major barrier to discontinuing screening based on life expectancy or older age is the difficult conversation that starts when a clinician recommends no screening, and the patient responds, What? Do you think Im too old to be screened ? WHAT IS THE POSITIVITY RATE FOR COLORECTAL CANCER SCREENING BY FIT? Patients who are considering colorectal cancer screening with fecal immunochemical testing, or FIT, might be interested in their probability of testing positive and needing subsequent colonoscopy. In a study in the August American Journal of Gastroenterology ( http:// dx.doi.org /10.1038/ajg.2014.168 ), researchers in the Netherlands invited 4500 patients between the ages of 50 and 74 to undergo FIT screening with OC-Sensor Micro; a hemoglobin concentration of 50 ng/ mL or greater was considered positive. The positivity rate was 8%. On subsequent colonoscopy, 40% of those with positive tests had either advanced adenomas or cancer. Some of the patients were rescreened at intervals averaging 2years; positivity rates were 6% on second and third screening rounds. Other recent studies of FIT screening have yielded similar findings. In a study of nearly 10,000 patients in North America (using OC FIT-CHEK; a hemoglobin concentration greater than 100 ng/ mL was considered positive), 7% had positive findings ( www. jwatch .org /na33982 ). In a study of nearly 9000 patients in Spain (using OC-Sensor; a hemoglobin concentration of 75 ng/ mL or greater was considered positive), 7.5% of the patients tested positive ( www. jwatch .org /jw201203150000001 ). The positivity rate of fecal immunochemical testing will depend on which assay is used, the hemoglobin concentration considered to be positive, characteristics of the screened population, and whether a patient has been screened before. But these studies suggest that clinicians might reasonably quote a positivity rate of roughly 7% to 8% when they discuss initial FIT screening with their patients. This means that roughly 1 of every 12 to 14 patients screened by fecal immunochemical testing will need to undergo colonoscopy. A FOURTH RANDOMIZED, CONTROLLEDTRIAL OF FLEXIBLESIGMOIDOSCOPY SCREENING Trials from the United Kingdom, Italy, and the United States have shown that flexible sigmoidoscopy lowers the incidence of distal colorectal cancer and colorectal cancer-related mortality. In a study in the August13th issue of JAMA ( http:// dx.doi.org /10.1001/jama.2014.8266 ), researchers in Norway randomized 100,000 asymptomatic patients between the ages of 50 and 64 to no screening, flexible sigmoidoscopy, or flexible sigmoidoscopy plus guaiac-based fecal occult blood testing. Based on intent to screen analyses, the incidence of colorectal cancer (during a median follow-up of 11years) was 20% lower overall 30% in men and 10% in women in the screening groups. The incidence of distal cancer was 24% lower and the incidence of proximal cancer wasnt significantly lower. The incidence of colorectal cancer was 30% lower in the sigmoidoscopy-only group, but not significantly lower in the sigmoidoscopy-plus-fecal occult blood testing group. Mortality associated with colorectal cancer was 30% lower overall in the screening groups and was 40% lower in men (there was no mortality benefit seen in women). Mortality was 40% lower with sigmoidoscopy plus fecal occult blood testing and 16% lower (which wasnt significant) with sigmoidoscopy alone. The lower overall incidences of colorectal cancer in this study are similar to those reported in past trials of screening. But this study featured several methodological design improvements, namely the inclusion of a 50-to-54year old age group, the use of a population-based sample ( vs . volunteers), and minimal contamination of the control arm with screening procedures. The apparent benefit of fecal occult blood testing wasnt consistent between the incidence and the mortality calculations. For various reasons, the United States isnt likely to return to flexible sigmoidoscopy for screening. The lack of benefit in the proximal colon emphasizes the need for colonoscopists to be well trained in lesion detection, achieve high-quality right colon bowel preparation, and perform detailed inspection of the proximal colon. NEW FOLLOW-UP DATA FROM THE EUROPEAN PSA SCREENING STUDY The controversy surrounding the use of prostate-specific antigen measurement as a screening tool for prostate cancer has been fueled by conflicting results in two large randomized trials: A study from the United States ( www. jwatch .org /jw200903180000001 and www. jwatch .org /jw201202020000002 ) that showed no advantage for screening after 11 and 13years of follow-up, and a study from Europe ( www. jwatch .org /jw200903180000001 and www. jwatch .org /jw201203140000001 ) that showed modest reductions in prostate cancerrelated mortality associated with screening after 9 and 11years of follow-up. Both of the trial groups continue to follow their patients in view of the long latency period of prostate cancer. On the website of The Lancet ( http:// dx.doi.org /10.1016/S0140-6736(14)60525-0 ), the European group now has reported 13-year follow-up data. In this trial, more than 160,000 men in eight countries were randomized either to PSA screening every 2 to 4years with further evaluation if PSA level exceeded 3 ng/ mL or to no intervention. These new data again show a small but statistically significant advantage for screening, with 1 prostate cancerrelated death averted for every 800 men invited for screening and for every 30 men in whom prostate cancer was diagnosed. (After 9years of follow-up, preventing 1 death had required 1400 men invited for screening and 50 cases detected.) The relative risk for death from prostate cancer was 0.8 in the screened group, which was the same as the finding in the 11-year report. All-cause mortality was similar in the two groups. Although the number needed to screen and the number needed to treat to prevent one death from prostate cancer have improved somewhat with a longer follow-up of this European trial cohort, this report didnt address the substantial harms that can result from overdiagnosis (which happens in about 40% of positive screens) and consequent overtreatment ( http:// dx.doi.org /10.1016/S0140-6736(14)61008-4 ). The researchers acknowledge the need for further quantification of harms and their reduction and conclude that the time for population-based screening hasnt yet arrived. This report shouldnt change the recent recommendation by the United States Preventive Services Task Force against screening ( www. jwatch .org /jw201206070000001 ). A HIGH-POTENCY FLU VACCINEIMPROVES PROTECTION IN OLDERADULTS Although standard influenza vaccination is moderately helpful in protecting elders from seasonal influenza, the ongoing burden of disease in this age group mandates something better. Back in 2009, a high-dose inactivated vaccine preparation that contained four times the standard amount of antigen ( www. jwatch .org /jw200908110000002 ) was licensed for use in patients 65 or older on the basis of its safety and promising immunogenicity, with the caveat that clinical benefits had yet to be shown. Now, in a study in the August14th New England Journal of Medicine ( http:// dx.doi.org /10.1056/NEJMoa1315727 ), researchers have provided those data for flu seasons ranging from 2011 to 2013 in 30,000 patients with an average age of 73; most of the patients had at least 1 chronic medical condition and none were seriously ill. The patients were enrolled from 130 centers in the United States and Canada. Flu-like illnesses were diagnosed in similar percentages of those who got standard-dose vaccinations and those who got high-dose vaccinations. But polymerase chain reaction or culture-confirmed influenza was significantly less common in the high-dose group. Hospitalization rates were also similar in the two groups, but the rates of pneumonia after respiratory illness were somewhat lower in the high-dose group; no patient died from the flu. Slightly fewer side effects were associated with high-dose vaccination, but two high-dose patients had vaccination-related neurological sequelae (namely, cranial nerve palsy and acute encephalomyelitis), which were complications not seen with standard dosing. This trial confirms that a high-potency influenza vaccine confers somewhat more protection than a standard vaccine in older patients: The researchers estimate that it increased the protection rate from 50% to 60%. Unanswered questions include the high-dose preparations performance during flu seasons with different matches of vaccine to circulating virus (the match during the flu seasons studied wasnt so good) and its performance in sicker patients who are more vulnerable to the complications associated with the flu. This study was manufacturer-supported. DIARRHEA IN OUTPATIENTS C.difficile IS MORE COMMON THAN WE THOUGHT Clostridium difficile infection is a well-recognized cause of nosocomial diarrhea, but its also present in the community. To characterize C. difficile infection among outpatients with diarrhea, researchers tested for C.difficile toxin, regardless of whether that test had been requested, on all unformed stool samples submitted by general practitioners to three laboratories in the Netherlands during 16months. Details appear on the website of Clinical Microbiology and Infection ( http:// dx.doi.org /10.1111/1469-0691.12758 ). C. difficile infection was detected generally as the sole pathogen in 1.5% of the nearly 13,000 samples analyzed; Salmonella species were found in 1.6%. Diarrheal symptoms had started in the community in more than 90% of the patients with C. difficile infection. Forty percent hadnt gotten antibiotics or been hospitalized before their episodes of C. difficile infection; 14% had no underlying diseases, past hospitalizations, or medication use. The general practitioners had requested C. difficile toxin testing on 7% of the submitted specimens, allowing for a detection rate of 40% of the cases of C. difficile infection. If clinicians had followed current Dutch recommendations to order toxin testing for all patients with diarrhea and recent hospitalization or antibiotic treatment, 18% of all of the samples would have been tested, allowing for the identification of 60% of C. difficile infection cases. This study suggests that many episodes of C. difficile infection in the outpatient setting remain undiagnosed, partly because clinicians dont recognize patients risk factors, but also because many patients with C. difficile infection lack typical risk factors. With an increasing incidence of C. difficile infection in the community, this important diagnosis should be considered more frequently. At the time that NEJM Journal Watch reviewed this paper, its publisher noted that it wasnt in its final form and that subsequent changes might be made. STEROID INJECTION AND PHYSICAL THERAPY ARE EQUALLY EFFECTIVE FOR SHOULDER IMPINGEMENT SYNDROME Shoulder impingement syndrome encompasses several conditions that cause shoulder pain, including rotator cuff tendinitis and subacromial bursitis. Conservative treatments include corticosteroid injections and physical therapy. To compare the effectiveness of these interventions, researchers at a United States Army medical center randomized 100 patients between the ages of 18 and 65 with shoulder pain secondary to impingement syndrome either to 40-mg subacromial injections of triamcinolone acetonide (up to 3 injections, given at least a month apart, during a yearlong follow-up) or to physical therapy (twice /week during 3weeks) plus home exercises. (The physical therapy intervention is described in detail in BMJOpen [ http:// dx.doi.org /10.1136/bmjopen-2011-000137 ]. ) Details appear in the August5th Annals of Internal Medicine ( http:// dx.doi.org /10.7326/M13-2199 ). At a month, average pain and disability scores in both of the groups were significantly improved and that improvement was sustained for a year; neither treatment was better than the other at 1, 3, 6, or 12months. During the follow-up, the physical-therapy patients made fewer shoulder painrelated visits to their primary care providers and had fewer additional treatments or procedures. Other than transient pain from the steroid injections, there were no side effects in either group. In this study, corticosteroid injection and physical therapy yielded similar and significant improvements in pain and disability related to shoulder impingement syndrome. The lack of a minimally treated control group is a limitation of this study; many patients improve simply by avoiding those repetitive motions that aggravate pain while keeping the shoulder otherwise active. Patient preference and insurance coverage should determine which intervention to select. This study was funded by a company that makes physical therapy equipment. ANTERIOR KNEE PAIN OFTEN IS A SIGN OF PATELLOFEMORALOSTEOARTHRITIS Knee osteoarthritis can present in the patellofemoral joint, the medial or lateral component of the tibiofemoral joint, or both. Much research has been focused on the tibiofemoral joint, but its been shown that patellofemoral joint arthritis is as common as is tibiofemoral joint arthritis. Differentiating between the two is important, because treatment options are different. Traditionally, patellofemoral joint arthritis is diagnosed based on the presence of anterior knee pain, knee effusion, and quadriceps/vastus atrophy. To see whether the self-reported location of knee pain and exacerbators of knee pain discriminated among the patients with isolated patellofemoral joint damage, isolated tibiofemoral joint damage, or no damage, researchers questioned 400 patients with magnetic resonance imaging-confirmed patellofemoral joint damage, tibiofemoral joint damage, or neither. Their findings appear in the August Journal of Rheumatology ( http:// dx.doi.org /10.3899/jrheum.131555 ). No particular answer to any question accurately distinguished between the patients with and without patellofemoral joint damage. For example, isolated anterior knee pain in combination with moderate pain on stairs had a high specificity (97%) for identifying patellofemoral joint damage, but the sensitivity was only 9% (meaning that only 1 out of every 11 patients with patellofemoral joint damage reported this combination). In contrast, the absence of at least moderate pain in any knee location while walking on level ground was very sensitive for patellofemoral joint damage (93%), but the specificity was only 13% (so most of the patients without patellofemoral joint damage also had this finding). The diagnosis of patellofemoral joint damage should be considered in patients with anterior knee pain who have maximal pain on stairs or in those whose pain is absent when walking on level ground; unfortunately, these symptoms arent accurate enough to neatly separate tibiofemoral joint damage from other causes of knee pain. Still, using these questions during the initial investigation might be useful, because most patients wont initially undergo magnetic resonance imaging, and the patients with these symptoms will be helped by physical therapy to strengthen the quadriceps/vastus, even if the main lesion turns out to be in the tibiofemoral joint. BISPHOSPHONATE-RELATED OSTEONECROSIS OF THE JAW, REVISITED Bisphosphonate-related osteonecrosis of the jaw consists of exposed necrotic bone that lasts for weeks or months; it can happen spontaneously or after invasive dental procedures. The condition was initially noted after high-dose intravenous bisphosphonate treatment for malignant conditions, but its been suggested that jaw osteonecrosis can develop in users of oral bisphosphonates for osteoporosis ( www. jwatch .org /jw200804080000001 ). Areport in the August Journal of Clinical Endocrinology and Metabolism ( http:// dx.doi.org /10.1210/jc.2013-4119 ) adds to the evidence. Among 7300 patients in Taiwan who were taking oral alendronate, 0.6% were diagnosed with osteonecrosis of the jaw an average of 4years after starting the drug. The cases were verified by a manual review of radiographic, operative, and pathology reports. In contrast, in a control group of nearly 2000 patients who were treated for osteoporosis with raloxifene (which isnt a bisphosphonate), only 1 patient developed jaw osteonecrosis. After adjusting for potentially confounding factors, the incidence of jaw osteonecrosis was sevenfold higher with alendronate than with raloxifene. The risk factors for developing jaw osteonecrosis among the users of alendronate included diabetes, rheumatoid arthritis, older age, and taking alendronate for longer than 3years. The possibility that oral bisphosphonate therapy might cause osteonecrosis of the jaw got quite a bit of attention about 5years ago; more recently, the literature has focused on atypical femur fractures after the long-term use of oral bisphosphonates ( www. jwatch .org /jw201112290000009 ). This new study provides additional support for jaw osteonecrosis as a likely albeit an uncommon side effect of oral bisphosphonate therapy. EVEN MODERATE ALCOHOL INTAKE IS ASSOCIATED WITH AF We know that consuming large quantities of alcohol is linked to an excess risk for atrial fibrillation, but what about more moderate intake? To answer that question, researchers in Sweden conducted a prospective cohort study and then performed a meta-analysis that included their study and six others. Details appear in the July22nd Journal of the American College of Cardiology ( http:// dx.doi.org /10.1016/ j. jacc.2014.03.048 ). In the researchers study, compared with the patients who had less than 1 drink /week , the risk for atrial fibrillation among the patients whose weekly alcohol intakes were 1to 6 drinks was 1.01; for 7 to 14 drinks /week , the risk was 1.07; for 15 to 21 drinks, it was 1.14; and for more than 21drinks /week , the relative risk for atrial fibrillation was 1.4. The results were similar even when binge drinkers (defined as those who consumed 5 or more drinks on a single occasion) were excluded. In the meta-analysis (including more than 12,000 cases of atrial fibrillation), the relative risk associated with alcohol intakes of 1 drink /day was 1.08; of 3 drinks /day was 1.26; and of 5 drinks /day was 1.47, compared with nondrinking. This large meta-analysis not only confirms the association between the risk for atrial fibrillation and high alcohol consumption, it also suggests that even moderate alcohol intake is associated with a significantly higher risk. Plus, the strong dose-response effect seen in this study suggests causality, although not all of the mechanisms by which alcohol begets atrial fibrillation are known. The elevated risk for atrial fibrillation associated with small to moderate amounts of alcohol should be balanced against the lower risk for ischemic heart disease thats also associated with mild to moderate alcohol intake ( http:// dx.doi.org /10.1016/ j. jacc.2014.04.038 ). SODIUM INTAKE, POTASSIUM INTAKE, BP, AND CV EVENTS Theres real controversy regarding the associations among sodium intake, blood pressure, and adverse cardiovascular events. In an observational study in the August14th New England Journal of Medicine , researchers explored this issue in 100,000 patients from a mix of 18 high- and low-income countries. Using fasting urinary sodium and potassium measurements, the researchers estimated daily sodium and potassium excretion which is a surrogate for intake. The key blood pressure findings ( http:// dx.doi.org /10.1056/NEJMoa1311989 ) were: A higher daily sodium excretion was associated with significantly higher systolic and diastolic blood pressure; this association was limited to the patients whose sodium excretion exceeded 3 g /day . A higher daily potassium excretion was associated with significantly lower systolic blood pressure it was an inverse association. The average blood pressure measurement of the patients with the highest sodium excretion and the lowest potassium excretion was 12/5mmHg higher than that of the patients with the lowest sodium and the highest potassium excretion. The associations among sodium, potassium, and blood pressure were stronger among the patients with hypertension than among those without it. The key findings for a primary composite outcome (namely, death or a major adverse cardiovascular event http:// dx.doi.org /10.1056/NEJMoa1311889 ) during an average follow-up of nearly 4years were: A sodium excretion of greater than 7 g /day was associated with an excess risk for the primary outcome compared with a sodium excretion between 4 and 6 g /day . A sodium excretion of less than 3 g /day was also associated with an excess risk for the primary outcome, so the highest and the lowest sodium intakes were both associated with adverse clinical outcomes (this was a classic U-shaped association). Adjusting for blood pressure attenuated the association between the primary outcome and high sodium excretion (but not low sodium excretion), which suggests that blood pressure partly mediated the high-sodium finding. Low potassium excretion was associated with an excess risk for the primary outcome. For some observers, these findings might suggest that a low-sodium, high-potassium diet will substantially lower blood pressure and promote favorable clinical outcomes, but this studys observational nature precludes strong inferences about causality or the effects of dietary intervention. The U-shaped association between sodium excretion and adverse clinical outcomes has been noted in past studies and could represent reverse causality if higher-risk patients are more likely to restrict sodium intake. On the other hand, the researchers speculate that excessive sodium restriction could promote harm by activating the renin-angiotensin-aldosterone system in vulnerable patients. ARE FASTING LIPID DETERMINATIONS REALLY NECESSARY? Current guidelines on treating patients with high cholesterol levels to prevent adverse cardiovascular events support risk stratification of patients on the basis of fasting lipid panels ( www. jwatch .org /na32828 ). But does a fasting lipid determination allow better prognostication of all-cause and cardiovascular-related mortality than do nonfasting results? To answer this question, researchers used data from the National Health and Nutrition Survey and National Death Index on 16,000 middle-aged patients who were followed for 14years. Propensity score matching was used to create fasting and nonfasting cohorts with similar characteristics. Fasting was defined as not eating for 8 or more hours before drawing blood. Findings appear in the August12th issue of Circulation ( http:// dx.doi.org /10.1161/CIRCULATIONAHA.114.010001 ). For the primary outcome of all-cause mortality, fasting vs . nonfasting LDL cholesterol determinations (estimated via the Friedewald equation) yielded similar prognostic values. The results were also similar for the secondary outcome of cardiovascular-related mortality. In this analysis, nonfasting and fasting LDL cholesterol determinations yielded similar prognostic information, leading the researchers to call for a reevaluation of existing guidelines and practices. These researchers didnt evaluate the effect of fasting on the prognostic value of triglyceride measurements, but an editorialist points out ( http:// dx.doi.org /10.1161/CIRCULATIONAHA.114.011512 ) that we lack good evidence that lowering triglyceride levels apart from lowering LDL cholesterol levels prevents adverse cardiovascular events. Clearly, nonfasting lipid determinations are logistically attractive, although we probably need more data before the recommendation to obtain fasting lipid determinations is changed. DRUGS THAT RAISE HDL CHOLESTEROL LEVELS DONT CHANGE ALL-CAUSE MORTALITY OR PREVENT FATALCARDIAC-RELATED EVENTS HDL cholesterol levels are inversely associated with cardiovascular risks. In a meta-analysis on the website of the British Medical Journal ( http:// dx.doi.org /10.1136/bm j. g4379 ), researchers reviewed 40 randomized, controlled trials (that included 117,000 patients) to see whether drugs that raise HDL cholesterol levels lower the risk for adverse cardiovascular outcomes. All of the drugs namely, niacin, fibrates, and cholesteryl ester transfer protein inhibitors significantly raised HDL cholesterol levels. But across all of the trials, none of the drugs lowered all-cause mortality, coronary heart diseaserelated mortality, or the risk for stroke, compared with control treatments (mostly placebo). In statin-naive patients, the risk for nonfatal myocardial infarction was significantly lower among those who took niacin or fibrates, and niacin was associated with a lower risk for stroke. None of the drugs lowered the risk for adverse cardiovascular outcomes in the patients who were taking statins. Although niacin, fibrates, and cholesteryl ester transfer protein inhibitors significantly raised HDL cholesterol levels, none of these drugs lowered the risk for all-cause death, death from coronary heart disease, or stroke. Notably, cholesteryl ester transfer protein inhibitors arent available for clinical use. Do niacin and fibrates have roles in selected patients? Probably not for niacin: Its been shown that niacin isnt effective in patients with vascular disease who are taking statins ( www. jwatch .org /na35071 ). In contrast, evidence from subgroups embedded in larger randomized trials suggests that fibrates might lower the risk for adverse cardiovascular outcomes in statin-treated patients with both high triglyceride and low HDL cholesterol levels ( http:// dx.doi.org /10.1016/ j. atherosclerosis.2011.04.020 ). It seems that a trial devoted to low-HDL, high-triglyceride patients would be appropriate. GUIDELINE WATCH: SCREENING ASYMPTOMATIC PATIENTSFOR CAROTID ARTERY STENOSIS Mortality from stroke has significantly decreased during the past 50years; better blood pressure control is thought to be the most important factor in this decline. Although carotid artery stenosis is a risk factor for stroke, its the cause in only a small proportion of cases. On the website of the Annals of Internal Medicine ( http:// dx.doi.org /10.7326/M14-1333 ), the United States Preventive Services Task Force has updated its recommendation statement from 2007 ( www. jwatch .org /jw200801150000001 ) on screening asymptomatic adults for carotid artery stenosis. There are several key points, namely: Auscultation for carotid bruits has limited value to detect carotid artery stenosis. Carotid ultrasound has a high sensitivity and specificity for detecting carotid artery stenosis of 50% or greater, but when the prevalence is low (1% or lower), ultrasound yields a high number of false positives. Carotid artery angioplasty or stenting hasnt been compared head-to-head with optimal medical therapy. In the trials conducted at elite surgical centers, carotid endarterectomy in the patients with asymptomatic carotid artery stenosis lowered the absolute incidence of a combined endpoint (which was all strokes plus perioperative death) by approximately 4% during 3 to 4years of follow-up. The magnitude of the benefit is expected to be lower with contemporary optimal medical therapy, and the net benefit depends on whether patients survive the perioperative period and live for 5 or more years. The Task Force concludes with moderate certainty that the harms of screening asymptomatic patients for carotid artery stenosis outweigh the benefits. The United States Preventive Services Task Forces recommendation against screening for carotid artery stenosis focuses on the general adult population . Several other organizations (like the Society for Vascular Surgery http:// dx.doi.org /10.1016/ j. jvs.2011.07.031 ) suggest screening in patients with vascular risk factors or known disease in other vascular beds. But in the systematic review ( http:// dx.doi.org /10.7326/M14-0530 ) that accompanies the Task Forces current guideline, the researchers note that there are no risk-stratification tools that reliably select the patients who are most likely to have asymptomatic carotid artery stenosis or the patients with asymptomatic stenosis who are most likely to derive net benefit from endarterectomy. SMOKING CESSATION INTERVENTION IS EFFECTIVE WITH POSTHOSPITAL DISCHARGE FOLLOW-UP Interventions for smoking cessation in hospitalized patients can be particularly effective, because the consequences of smoking are usually more apparent to the patients who are admitted for smoking-related issues. But its been suggested that these interventions are effective only with longer-term outpatient follow-up, which can be expensive. Plus, medications for smoking-cessation arent often covered by insurance. In a study in the August20th issue of JAMA ( http:// dx.doi.org /10.1001/jama.2014.9237 ), researchers randomized 400 hospitalized adult smokers either to a postdischarge treatment program or to usual care (which was access to a telephone quit line and discharge recommendations for a smoking-cessation medication). Patients were excluded if they were admitted to an obstetrical or psychiatric unit or had substance abuse problems, cognitive impairment, or language difficulties. The intervention patients got five interactive voice response telephone calls during the subsequent 3months, during which they got encouragement, quit advice, medication refills, and problem-solving approaches; they could also request a call-back from a trained counselor. Smoking-cessation medications, chosen by the patient and an inpatient counselor, were provided at no cost for the entire 3months. Smoking cessation at 6months postdischarge, measured by saliva cotinine analysis, was nearly 30% in the intervention group and 15% in the control group thats a significant difference. Nine patients would need to be treated for one to benefit. These results on smoking cessation which are encouraging and suggest that this intervention could be considered for clinical use likely depend on both the availability of free medication and the innovative approach to counseling and support. Whats most important here is a seamless linkage in care between the hospital and outpatient follow-up, which is often lacking. HUGE STUDY ELUCIDATES GENETICS OF SCHIZOPHRENIA In the mid-20th century, some psychiatrists viewed schizophrenia as a result of psychological assaults that could be revealed through (if not corrected by) psychoanalysis. But in the modern age, researchers have found that schizophrenia is highly heritable, implying that genetics are involved. The era of gene mapping and gene sequencing generated many studies of schizophrenia. Unfortunately, the small size of some of the studies, and the immaturity of bioinformatics, led to many putative genetic links of dubious validity. In a genome-wide association study in the July24th issue of Nature ( http:// dx.doi.org /10.1038/nature13595 ), researchers processed the genotypes of nearly 40,000 patients with schizophrenia and 113,000 controls and identified 100 genetic loci linked to schizophrenia (80 of these loci havent been reported in the past). The loci predominantly involve genes expressed in the brain, most of which involve dopamine or glutamatergic neurotransmission. Intriguingly, some of the loci are also involved in the acquired immune response (including some in the major histocompatibility complex). The huge size of this landmark study and the researchers use of contemporary statistical techniques lend validity to these findings. Many new potential therapeutic targets have now been identified. This study supports the hypothesis that the biology of schizophrenia involves changes in neurotransmission that are affected by the acquired immune response. Plus, it suggests that environmental agents might trigger the disease in genetically vulnerable people ( http:// dx.doi.org /10.1038/nature13645 ). GUIDELINE WATCH: DIAGNOSING OBSTRUCTIVE SLEEPAPNEA Despite the relatively high prevalence of obstructive sleep apnea, experts still disagree on the optimal approach to its diagnosis. The American College of Physicians has issued a new guideline on diagnosing obstructive sleep apnea. Details appear in the August5th Annals of Internal Medicine ( http:// dx.doi.org /10.7326/M12-3187 ). For diagnosing obstructive sleep apnea, polysomnography is the gold standard, but it must be performed in a sleep lab and its costly. An alternative is a portable monitor, but the portable monitors that are currently available dont measure all of the relevant parameters: Some arent able to distinguish between central and obstructive apneas. The evidence wasnt sufficient to determine whether questionnaires are an effective screening tool. Medicare and Medicaid reimburse for obstructive sleep apnea treatment if a patients apnea-hypopnea index is 15 or more events per hour or is 5 or more events per hour in the patients with daytime somnolence, fatigue, or cardiovascular comorbid conditions like ischemic heart disease, stroke, or hypertension. High-quality evidence shows an association between apnea-hypopnea index scores of more than 30 events per hour and excess all-cause mortality. Low-quality evidence suggests an association between higher apnea-hypopnea index scores and incident diabetes. Several trials showed that continuous positive airway pressure lowers blood pressure in patients with obstructive sleep apnea who have daytime sleepiness. A randomized trial showed that CPAP failed to prevent excess mortality or adverse coronary events in patients with obstructive sleep apnea who didnt have daytime sleepiness. A sleep study is recommended for patients with unexplained daytime sleepiness. Polysomnography is recommended for diagnostic testing. A portable sleep monitor can be used if polysomnography isnt available. Given the limited quality of available evidence, this guideline provides clinicians with weak recommendations only. But the American College of Physicians does suggest focusing clinical attention on patients with suspected obstructive sleep apnea who also have daytime sleepiness, and it recommends formal polysomnography instead of portable monitors for diagnostic testing. TRANSFUSIONS PREVENT INFARCT RECURRENCE IN SICKLE CELL ANEMIA Regular blood transfusions decrease the prevalence of strokes in children with sickle cell anemia, but whether they prevent the recurrence of strokes or silent cerebral infarcts isnt clear. To examine this issue, researchers at multiple centers randomized 200 children with an average age of 10 and hemoglobin SS or Sβ0 thalassemia either to observation or to monthly transfusions to maintain hemoglobin concentration above 9 g/dL and hemoglobinS concentration at 30% or lower. The children had 1 or more infarct-like lesions on magnetic resonance imaging. Findings appear in the August21st New England Journal of Medicine ( http:// dx.doi.org /10.1056/NEJMoa1401731 ). After a median of 3years, infarct recurrence (as determined by neuroimaging or clinical evidence of neurologic injury) was less common in the transfusion group than in the observation group. Plus, the rates of pain crises, acute chest syndrome, priapism, and avascular necrosis of the hip were significantly lower in the transfusion group than in the observation group. Transfusion reactions were seen in 17% of the patients; most were allergic or febrile nonhemolytic reactions. Nine alloantibodies developed in four of the patients, for an alloimmunization rate of 0.278 per 100 units of red cells. This study confirms the beneficial effects of transfusion therapy for sickle cell disease. But implementing this treatment requires the availability of blood matched for the minor blood groups most commonly associated with antibody formation in sickle cell disease, close monitoring for iron overload and other complications of transfusion, and highly motivated patients and families with adequate financial resources. Unfortunately, these considerations limit transfusion therapy to children at the highest risk for cerebrovascular events. SOCIAL INTEGRATION AFFECTS SUICIDE RATES AMONG MIDDLE-AGEDMEN Suicide is a substantial public health issue. To evaluate the association between social integration and suicide-related mortality, researchers used data from the Health Professionals Follow-Up Study, which is a prospective cohort study of more than 30,000 male health professionals in the United States (at the time of study enrollment in 1986, the patients ranged in age from 40 to 75). Social integration was measured using a 7-item questionnaire. Findings appear in the July15th Annals of Internal Medicine ( http:// dx.doi.org /10.7326/M13-1291 ). During more than 20years of follow-up, there were 150 suicides. The risk for suicide decreased with increasing levels of social integration. Being married, having a large social network, and religious service attendance each had a significant protective effect against suicide. In this study, increasing social integration was associated with a decreasing risk for suicide. These findings reinforce the need to study suicide from both individual and societal perspectives.
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