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NEJM Journal Watch

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Course Description

After hearing and assimilating this program, the listener will be better able to: ( 1 ) Increase his/her basic knowledge of important advances in medicine; ( 2 ) Identify a broad range of clinical research reported in the medical literature; ( 3 ) Synthesize research findings through one-on-one interviews with authors and editorialists; ( 4 ) Integrate new treatments reviewed in the summaries into current practice; ( 5 ) Challenge oneself with thoughtful, clinically relevant questions. Disclosure In adherence to the ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, Dr. Kumar Dharmarajan reported working under contract with the Centers for Medicare & Medicaid Services in the United States to develop and maintain performance measures. Dr. Donald Tashkin and the planning committee members reported that they had nothing to disclose. MAJOR ADVERSE CV EVENTS ARE MORE COMMON IN PATIENTS WITH CHRONIC INFLAMMATORY DISEASES Rheumatoid arthritis and severe psoriasis have been linked to an excess risk for cardiovascular disease. The data on whether psoriatic arthritis also confers an excess risk arent as robust. In a cohort study in the February Annals of the Rheumatic Diseases ( http:// dx.doi.org /10.1136/annrheumdis-2014-205675 ), researchers in the United Kingdom used a large primary care database to determine the magnitude of vascular risk in patients with chronic inflammatory diseases. Nearly 200,000 adult patients with psoriatic arthritis, psoriasis, or rheumatoid arthritis were matched with 80,000 controls who didnt have any of these conditions or use disease-modifying antirheumatic drugs. After adjusting for traditional risk factors, the risk for major adverse cardiovascular events was significantly elevated in the patients with psoriatic arthritis who werent prescribed disease-modifying antirheumatic drugs, in the patients with severe psoriasis, and in the patients with rheumatoid arthritis who were or werent prescribed disease-modifying antirheumatic drugs. An incident risk for myocardial infarction was also significantly elevated in these patients. The patients with psoriatic arthritis experienced roughly 1 additional MI per 1000 person-years, compared with controls. This study confirms that patients with rheumatoid arthritis and severe psoriasis are at an excess risk for major adverse cardiovascular events and adds patients with psoriatic arthritis to this group. Most available cardiovascular-risk calculators dont take chronic inflammatory diseases into consideration. Further studies will be needed to determine if interventions to modify known cardiovascular risk factors will change outcomes in patients with these inflammatory conditions. PATIENTS WITH RA ARE AT EXCESS RISK FOR CV COMPLICATIONS The Framingham Risk Score underestimates cardiovascular risk in young patients, women, and patients with rheumatoid arthritis. Patients with rheumatoid arthritis are more likely to develop coronary artery calcifications than are patients without the condition, but because of expense and substantial radiation exposure, the measurement of coronary artery calcification isnt a standard test to determine cardiovascular risk. In a study in the Februaryissue of Arthritis & Rheumatology ( http:// dx.doi.org /10.1002/art.38944 ), researchers enrolled 100 patients with rheumatoid arthritis who met the criteria for risk stratification using the 2013 American College of Cardiology and the American Heart Association risk calculator; the patients estimated risk for coronary artery calcification was compared with their risk category as assigned by standard risk calculators (namely, the Framingham Risk Score, the Reynolds Risk Score, and the American College of Cardiology and the American Heart Association risk score). A third of the patients had high coronary artery calcification scores (greater than 300 Agatston units). Each of the standard risk calculators was applied to this high-scoring group. The Reynolds and the Framingham scores assigned only a third of the high-calcification-score group to a high-risk category; the American College of Cardiology and the American Heart Association calculator assigned 40% of the high-calcification-score group to the high-risk group. This study shows that coronary artery calcification scoring is more likely than the currently available cardiovascular risk calculators to place patients with rheumatoid arthritis in a high-risk category. But whether calcification scores in patients with rheumatoid arthritis actually predict adverse cardiovascular events more accurately than the calculators isnt known. Plus, we dont know whether patients whose calcification scores reclassify them to higher-risk categories will benefit from more-intensive risk factor interventions than otherwise would be recommended for them. CONCOMITANT USE OF NSAIDs AND ANTITHROMBOTIC AGENTS AFTER MI Essentially all of the patients who survive myocardial infarction get one or more antithrombotic agents for at least a year, and many MI patients get oral anticoagulants. Most nonsteroidal anti-inflammatory drugs are associated with an excess risk for both bleeding and adverse cardiovascular events, and their use is discouraged in patients with cardiovascular disease. In a retrospective study in the February24 issue of JAMA ( http:// dx.doi.org /10.1001/jama.2015.0809 ), researchers in Denmark analyzed a data registry and identified 90,000 patients with an average age of 68 who were discharged after first MIs. About a third of the patients got NSAIDs at some point during follow-up. In Denmark, prescriptions are required for all NSAIDs except low-dose ibuprofen. Nearly all of the post-MI patients got some combination of aspirin, clopidogrel, and an anticoagulant. Health outcomes were tracked for a median of 3.5years, during which time there were 18,000 deaths and 5000 major bleeding events (800 were fatal). In the study population overall, the use of NSAIDs with at least one antithrombotic drug was associated with twice as many major bleeding events as was no NSAID use; when NSAIDs were added to double and triple antithrombotic regimens, the risk was about fourfold higher. The risk was similar for all classes of NSAIDs. Fatal and nonfatal adverse cardiovascular events were about 40% more common in those using NSAIDs, driven mostly by the concomitant use of NSAIDs with aspirin or clopidogrel. The risks associated with nonsteroidal anti-inflammatory drugs were obvious with as little as 3days of use. Widespread (and some would say indiscriminant) over-the-counter NSAID use in the United States suggests that the effect on post-myocardial infarction patients who use antithrombotic therapy could be very large. Clinicians should be proactive in discouraging the use of NSAIDs in these patients. BLEEDING RISK IS ASSOCIATED INVERSELY WITH KIDNEY FUNCTION IN PATIENTS TAKING WARFARIN FOR AF The risk for bleeding during warfarin treatment is higher in patients with end-stage kidney disease than in those without kidney disease. Whether the same is true for patients with less-severe kidney disease isnt clear. In a retrospective study on the website of The BMJ ( http:// dx.doi.org /10.1136/bm j. h246 ), researchers evaluated kidney function and the risk for major bleeding (like intracranial or gastrointestinal) in more than 12,000 patients with atrial fibrillation and an average age of 77 who got first prescriptions for warfarin. The patients were stratified by baseline kidney function into six groups: The groups ranged from an estimated glomerular filtration rate of 90 mL/minute /1.73 m 2 or higher to a rate lower than 15mL /minute /1.73m 2 . During a median follow-up of 2years, 12% of the patients experienced major bleeding episodes. The risk for bleeding rose with worsening kidney function across all levels of estimated glomerular filtration rate, but this risk was attenuated after a month of warfarin therapy. For example, during the first month of warfarin treatment, the risk for major bleeding was 10 times higher in the patients with estimated glomerular filtration rates lower than 15mL /minute /1.73m 2 than in those with estimated rates of 90mL /minute /1.73m 2 or higher, whereas the risk was 2times higher after a month of starting warfarin. In this study, the risk for bleeding was inversely associated with kidney function in older patients with atrial fibrillation who were treated with warfarin. These results make sense: Worsening kidney function can result in an accumulation of uremic toxins, which can adversely affect platelet function and predispose patients to bleeding. Adding warfarin to this milieu accentuates the tendency to bleed. We dont know why the risk for bleeding was highest during the first month of warfarin treatment. One explanation might be the difficulty in achieving therapeutic, yet safe and moderate, levels of anticoagulation in patients with kidney disease. DEVICE TO NARROW THE CORONARYSINUS IS EFFECTIVE FOR REFRACTORY ANGINA Patients with refractory angina that isnt amenable to revascularization have few options. To test a new device designed to improve symptoms in patients like these, researchers conducted a phase II, randomized, sham-controlled trial of an hourglass-shaped, metal-mesh Reducer that is inserted into the coronary sinus to create a pressure gradient that theoretically redistributes blood toward ischemic myocardium. Details appear in the February5 New England Journal of Medicine ( http:// dx.doi.org /10.1056/NEJMoa1402556 ). The study involved 100 patients with Canadian Cardiovascular Society class III or IV angina despite maximal medical therapy; the patients had evidence of reversible ischemia and werent eligible for coronary revascularization. The patients were randomized to undergo either implantation of the device or a sham procedure. Improvement of 1 or more Canadian Cardiovascular Society classes at 6months was seen in significantly more implanted patients than in controls. Periprocedural myocardial infarction happened in one implantation patient. Other adverse events were similar in the two groups. This novel device seems to improve angina, quality of life, and possibly exercise duration in patients with refractory angina that isnt amenable to revascularization. The study was small, and follow-up was only 6months. But if the findings can be reproduced in more patients and are durable, the device could represent a breakthrough for patients with no other options. This study was manufacturer-sponsored. READMISSION OR DEATH IS COMMONAFTER HOSPITALIZATION FOR HEARTFAILURE, MI, OR PNEUMONIA Among elders, the risks for readmission and death are high during the month after hospital discharge. But we dont know the risks associated with specific conditions and the extent to which these risks change over time. In a retrospective study on the website of The BMJ ( http:// dx.doi.org /10.1136/bm j. h411 ), researchers determined the risks for hospital readmissions and death during a year after hospitalization from 2008 to 2010 for heart failure, acute myocardial infarction, or pneumonia in more than 3million Medicare beneficiaries 65 or older. The 28 million Medicare beneficiaries in the general population served as controls. Within a year of discharge, hospital readmissions happened after two thirds of the hospitalizations for heart failure, half of the hospitalizations for MI, and 60% of the hospitalizations for pneumonia. A third of the heart failure patients, a quarter of the MI patients, and a third of the pneumonia patients died during the year after their hospitalizations. The risks for readmission were highest during the first several weeks after discharge and then declined. Even so, the relative risks for hospital admission and death during the 3months after hospitalization for elders with these diagnoses were 6 to 11 times greater than for elders in the general population. This large study shows that, among elders, the risks for readmission and death are high after hospitalization for heart failure, acute myocardial infarction, and pneumonia. Although these risks decline over time, they remain elevated compared with nonaffected elders. The researchers reasonably recommend that patients should be monitored carefully well beyond the first month after hospital discharge and that clinicians should provide follow-up care that is timely, longitudinal, and comprehensive and should confirm that advance directives have been completed. ADJUNCTIVE STEROIDS FOR SEVERECAP: NOT YET, AND NOT FOR ALL Adjunctive steroids may provide potential benefit in the treatment of community-acquired pneumonia ( www.jwatch.org /na36895 ). In a study in the February17 issue of JAMA ( http:// dx.doi.org /10.1001/jama.2015.88 ), researchers in Spain randomized 120 adults with severe community-acquired pneumonia and high inflammatory responses (a C-reactive protein level greater than 150 mg/ L) to either 0.5 mg/ kg of intravenous methylprednisolone or placebo every 12hours for 5days; 90 of the patients were in intensive care units. Exclusion criteria included severe immunosuppression, nosocomial pneumonia, uncontrolled diabetes, H1N1 infection, and past treatment with steroids. The primary endpoint was treatment failure a composite that included clinical outcomes (like shock, mechanical ventilation, or death) and radiographic progression. A specific microbiologic diagnosis (most commonly Streptococcus pneumoniae ) was made in 40% of the cases. The steroid patients were significantly less likely than were the placebo patients to experience treatment failure or to show radiographic progression. In-hospital mortality, causes of death, and the incidence of adverse events were similar in the two groups. In this relatively small study of patients with severe community-acquired pneumonia and elevated inflammatory responses, steroid treatment was associated with fewer treatment failures. An editorialist observes ( http:// dx.doi.org /10.1001/jama.2015.115 ) that the trial participants represented only a small proportion of patients with community-acquired pneumonia and that a larger study is needed to confirm that less radiographic progression is associated with lower mortality. He also notes that the response to steroids might vary by the etiology of community-acquired pneumonia. IS GIANT CELL ARTERITIS A ZOSTERSYNDROME? Giant cell arteritis is a vasculopathy of the external carotid and ophthalmic arteries; its etiology isnt known. To examine a possible association of giant cell arteritis with varicella-zoster virus, an international coalition of researchers collected 80 temporal artery biopsy specimens that were positive for giant cell arteritis. Details appear on the website of Neurology ( http:// dx.doi.org /10.1212/WNL.0000000000001409 ). The researchers found varicella-zoster virus antigen in three quarters of the pathologically confirmed biopsy specimens, compared with 8% of healthy-control specimens that is a significant difference. Varicella-zoster virus antigen was located most commonly within so-called skip areas , and giant cell vasculitis was adjacent to these areas. Varicella-zoster virus DNA was detected by polymerase chain reaction in 40% of the testable specimens that were positive for giant cell arteritis and varicella-zoster virus antigen. The discovery that at least some cases of giant cell arteritis might be due to varicella-zoster virus could have substantial clinical implications. One concern in diagnosing giant cell arteritis is a negative result if a skiparea (meaning an area without vasculitis) is biopsied. If varicella-zoster virus testing is confirmed to have high sensitivity and specificity in the setting of high clinical suspicion, a negative biopsy that is varicella-zoster virus antigenpositive could provide the needed evidence to treat giant cell arteritis. Whether treatment with antivirals is effective for varicella-zoster virus-associated giant cell arteritis will need to be studied. The researchers make a strong case that the virus should be considered to be the etiology of the vasculopathy, instead of an aberrant reactivation of latent virus due to inflammation. But a definitive cause and effect association cant be discerned from this study; that will require confirmation studies. MONITORING SYPHILIS DURING PREGNANCY Clinicians consider a patient with syphilis to be adequately treated when the nontreponemal titers fall fourfold or more within 6months to 2years, depending on the stage of disease and the patients HIV status. But this standard was derived from studies in nonpregnant adults. It isnt clear how (or if) this standard should apply to pregnant women, in whom the overriding concern is preventing congenital syphilis in the neonate. In a retrospective study in the March1 issue of Clinical Infectious Diseases ( http:// dx.doi.org /10.1093/cid/ciu920 ), researchers at a single hospital in Texas reviewed the serology of 170 pregnant women in whom syphilis was diagnosed at 18weeks gestation or later and who were treated before delivery with regimens approved by the Centers for Disease Control and Prevention. The patients were seen between 1981 and 2011. Half of the women had early disease (primary, secondary, or early latent). Only one was HIV positive. Titers declined after treatment along typical patterns: The titers in the patients with primary and secondary disease fell more rapidly than in those with later-stage disease, and older age predicted a relatively slow titer response. Although only 40% of the women achieved fourfold decreases in titer by delivery, the 30 cases of congenital syphilis were divided equally between the neonates of faster and slower responders. None of the women needed retreatment for presumed treatment failure. This cohort is the largest to date in which the response to syphilis treatment during pregnancy was examined, and the results generally confirm that the response to treatment in pregnant women echoes that seen elsewhere. The researchers conclude that patterns in maternal titer after treatment are probably less important in predicting the likelihood of congenital syphilis than is the time from treatment to delivery, which is a risk factor that has been established in past studies. EARLY PEANUT INTRODUCTIONLOWERS RISK FOR PEANUT ALLERGY During the past 10years, the prevalence of childhood peanut allergy has reached 3% in some Western countries. Back in 2000, the American Academy of Pediatrics recommended that children at high risk for the allergy should avoid peanut consumption until the age of 3. Then, in 2008, these recommendations were withdrawn due to a lack of evidence. Now, in a study in the February26 New England Journal of Medicine ( http:// dx.doi.org /10.1056/NEJMoa1414850 ), researchers in the United Kingdom examined whether an early introduction of peanut products can prevent peanut allergy. They randomized 640 high-risk babies (between the ages of 4 months and 11months at enrollment) with severe atopic dermatitis or egg allergy either to consume 2 g of peanut protein 3times /week or to avoid peanuts until the age of 5. The children were also stratified into two cohorts: Those with negative skin-prick results and those with wheal sizes of 1 mm to 4mm. Babies with skin-prick wheals larger than 4mm and those who reacted to an oral peanut challenge were excluded. At the age of 5, all of the children underwent another peanut challenge. Among the children with negative skin-prick tests at baseline, the prevalence of peanut allergy was significantly lower in the peanut-consumption group than in the peanut-avoidance group. Likewise, among the patients with initial positive skin-prick tests, but no reaction to peanut challenges, the prevalence was also significantly lower in the intervention group. Early peanut ingestion resulted in remarkably fewer incident peanut allergies in sensitized and unsensitized children. Although it isnt known if this extrapolates to other foods, clinicians should no longer recommend avoidance of allergenic foods in babies. An editorialist recommends ( http:// dx.doi.org /10.1056/NEJMe1500186 ) skin-prick testing of all high-risk babies and, in those with negative skin tests or challenges, regular consumption of peanuts until the age of 5. This might be logistically difficult, but the benefits could be tremendous. ROFLUMILAST SHOWS SOME BENEFITAS AN ADD-ON THERAPY FOR COPD PATIENTS WITH FREQUENTEXACERBATIONS The drug roflumilast (trade name: Daliresp) is a selective phosphodiesterase-4 inhibitor; it reduces the frequency of exacerbations in patients who have chronic obstructive pulmonary disease with severe airflow limitation (defined as a forced expiratory volume in 1 second of 50% or less of predicted). We dont know whether it offers additional benefit in patients who are getting optimal doses of long-acting β-agonists, inhaled corticosteroids, and long-acting muscarinic antagonists. In a study on the website of The Lancet ( http:// dx.doi.org /10.1016/ S0140- 6736(14)62410-7 ), researchers randomized nearly 2000 patients with COPD and severe airflow obstruction to either 500 μg/day of oral roflumilast or placebo and then followed them for a year. All of the patients had experienced more than 2exacerbations during the past year and continued their fixed dose combination of a long-acting β-agonist and an inhaled corticosteroid (70% of the patients were taking a long-acting muscarinic antagonist as well). The incidences of moderate-to-severe exacerbations that needed to be treated with systemic corticosteroids were 0.8 per patient-year in the roflumilast group and 0.9 per patient-year in the placebo group that is a difference of borderline statistical significance. In the roflumilast patients, the researchers also noted significantly fewer exacerbations that needed hospitalization and a roughly 50 cc increase from baseline FEV 1 . The roflumilast group had roughly 5% more episodes of diarrhea, weight loss, and nausea than did the placebo group. GOLD guidelines ( www. goldcopd .com ) currently recommend adding inhaled corticosteroids to long-acting bronchodilators in patients with severe chronic obstructive pulmonary disease and frequent exacerbations; the guidelines do offer roflumilast as an alternative add-on for patients with frequent exacerbations who are already getting a long-acting muscarinic antagonist or a combination of a long-acting β-agonist and inhaled corticosteroid. Although the benefit of roflumilast was only borderline statistically significant, it might provide some additional benefit, possibly through an anti-inflammatory mechanism ( http:// dx.doi.org /10.1016/ S0140- 6736(15)60212-4 ), for patients who continue to have exacerbations while getting optimal inhaled therapy. But the known gastrointestinal side effects of roflumilast should be considered in the decision. This study was industry-funded. A HEALTHFUL DIET IS ASSOCIATED WITH LOWER RISK FOR COPD Smoking is the main cause of chronic obstructive pulmonary disease, but as many as a third of the patients with COPD have never smoked. Might other modifiable behaviors, like diet, affect the risk for COPD? To explore this issue, researchers examined the association between diet quality and the risk for COPD in 120,000 health professionals (70,000 women and 50,000 men) who completed food frequency questionnaires between 1984 and 2000. The patients diets were scored using the Alternate Healthy Eating Index 2010: Higher scores signify healthier diets (that is to say, a higher intake of whole grains, polyunsaturated fats, nuts, and long-chain ω-3 fats and lower intakes of red or processed meats, refined grains, and sugar-sweetened drinks). Details appear on the website of The BMJ ( http:// dx.doi.org /10.1136/bm j. h286 ). During the study, 700 women and 170 men were diagnosed with COPD. The incidence of newly diagnosed COPD was inversely associated with healthy-eating scores. After adjusting for multiple variables, including smoking, the risk for developing COPD was a third lower among the patients with the highest vs . the lowest eating scores. The results were similar in subanalyses of former and current smokers. In this study, a healthful diet was associated with a lower risk for chronic obstructive pulmonary disease. These results are consistent with those of past studies in which diets rich in antioxidants were associated with better lung function and lower COPD-related mortality. Although this association between diet and lung function isnt necessarily intuitive, it is biologically plausible. The researchers note that the lungs exist in a high-oxygen environment and might be susceptible to dietary exposures, both toxic and protective. VARENICLINE FACILITATES SMOKING CESSATION IN SMOKERS WHO ARE UNABLE TO STOP ABRUPTLY Most smoking-cessation guidelines recommend abrupt cessation, rather than gradual reduction, despite the inability of many smokers to even contemplate such an approach. To see whether gradual reduction with varenicline (trade name: Chantix) might be more effective for some smokers, researchers randomized 1500 smokers who werent willing or werent able to stop abruptly to varenicline (titrated to 1mg twice /day ) or placebo for 6months. The patients got standard cessation counseling and were encouraged to reduce consumption by at least three quarters by 2months, with the goal of eventual cessation. Smokers with a wide range of medical, psychiatric, and substance abuse diagnoses were excluded. Findings appear in the February17 issue of JAMA ( http:// dx.doi.org /10.1001/jama.2015.280 ). The overall study completion rate was about 70%. In the first 2months of treatment, a quarter of the intervention patients vs . 15% of the controls had reduced their smoking by at least three quarters. After 6months of treatment, the patients were followed for another 7 nontreatment months; at a year, the continuous abstinence rate was about 30% in the varenicline group vs . 10% in the placebo group (the number needed to treat was 6). The varenicline patients were 2 to 3 times more likely than were the placebo patients to experience nausea, constipation, abdominal pain, insomnia, or strange dreams. The success of complete cessation at a year, in the varenicline group, was similar to that in other studies of motivated quitters, presumably because the gradual reduction that preceded cessation helped these smokers. Even if patients arent able to quit completely, clinicians often want to help them at least reduce consumption, and varenicline might facilitate that goal. ASSOCIATION BETWEEN MODERATE ALCOHOL CONSUMPTION AND MORTALITY BENEFITS: DWINDLINGEVIDENCE? A J-shaped association between alcohol consumption and all-cause mortality has been shown, which suggests that moderate drinkers live longer than nondrinkers and heavy drinkers. But in some studies, former heavy drinkers (who have poorer health than never drinkers) were categorized as nondrinkers, so the J-shaped association might reflect confounding rather than a biological mechanism. In a study on the website of The BMJ ( http:// dx.doi.org /10.1136/bm j. h384 ), researchers in the United Kingdom reevaluated the link between alcohol consumption and all-cause mortality in 50,000 adults who participated in a health survey. Analyses were stratified by sex and age group (patients between 50 and 64 and patients 65 or older) and adjusted for multiple potential confounders like body-mass index and smoking. Compared with nondrinkers (a category that included former drinkers), alcohol consumption at levels ranging from less than 1 unit /month to up to 20 units /week (a standard drink contains between 1 and 2 units of alcohol) was significantly associated with lower all-cause mortality in both age and sex groups. But compared with never drinkers (excluding former drinkers), the mortality benefits were significant only among men between the ages of 50 and 64 who consumed 15 to 20 units /week or between 0.1 and 1.5 units on the heaviest drinking day and among women 65 or older who consumed up to 10units /week . The J-shaped association between alcohol consumption and all-cause mortality might be attributable in part to including former drinkers in the referent group and a lack of adjustment for confounders. In this study, when never drinkers were used as the referent group and the results were adjusted for numerous confounders, moderate alcohol consumption was significantly associated with mortality benefits only in younger men and in older women. These results call into question the widely held assumption that moderate alcohol consumption confers health benefits in most adults. INTENSIFYING TREATMENT IN PATIENTS WITH STAGE1HYPERTENSION We dont know whether treating patients with stage 1 systolic hypertension (those with a systolic blood pressure between 140 and 159mmHg) improves health outcomes. We also dont know the optimal time intervals between measuring elevated blood pressure, a dose escalation of or adding antihypertensive medications, and follow-up blood pressure measurement. In a study on the website of TheBMJ ( http:// dx.doi.org /10.1136/bm j. h158 ), researchers used a primary care research database from the United Kingdom to determine the optimal systolic blood pressure goal above which medication intensification (meaning, increasing the dose of current antihypertensive medication or adding a new medication) is helpful; they also looked at the associations between delays in medication intensification and adverse cardiovascular events or death. During a median follow-up of about 3years, 11% of 90,000 patients with hypertension experienced acute adverse cardiovascular events or died. After adjusting for multiple variables, the risk for this composite outcome was similar among the patients who got treatment intensification at a systolic blood pressure threshold between 130 and 150mmHg. But the risk was progressively higher for the patients who got treatment intensification at thresholds above 150mmHg. A longer time to medication intensification (longer than 1.4months) was also associated with a progressively higher risk for the composite outcome. Finally, the patients with a time to follow-up longer than 2.7months after intensification had a higher risk for the composite outcome. The associations were similar for these factors and all-cause mortality. In this study, intensifying the treatment of systolic blood pressure in patients with measurements higher than 150mmHg, a time to treatment intensification longer than 1.4months, and a time to follow-up longer than 2.7months after treatment intensification were associated with excess risks for adverse cardiovascular events and death. These results provide practical guidance on treatment and follow-up of patients with systolic hypertension. LOWERING BP IN PATIENTS WITH TYPE2 DIABETES IS ASSOCIATEDWITH LOWER 10-YEAR MORTALITY Generally, the idea that lowering blood pressure in patients with type2 diabetes will prevent cardiovascular-related mortality is accepted by clinicians. In a meta-analysis in the February10 issue of JAMA ( http:// dx.doi.org /10.1001/jama.2014.18574 ), researchers combined 40 high-quality clinical trials (including more than 100,000 patients) to evaluate the magnitude of that benefit, to identify subgroups most likely to benefit, and to assess the effects of various classes of antihypertensive drugs. Among their findings are that: A 10-mm Hg reduction in systolic blood pressure was associated with an up to 30% reduction in the relative risk for all-cause mortality, adverse cardiovascular events, albuminuria, retinopathy, and stroke. The absolute risk reduction from a 10-mm Hg drop in systolic blood pressure was about 2 to 4 events per 1000 patient-years for most conditions, except for albuminuria (in this case, it was 9 cases per 1000patient-years). When stratified by baseline blood pressure, only the patients with systolic pressures of 140mmHg or higher benefited from blood pressure lowering for all-cause mortality, adverse cardiovascular events, and heart failure. All classes of antihypertensives conferred similar benefits, except for preventing heart failure: Diuretics and angiotensin IIreceptor blockers showed a specific benefit for lowering the risk for heart failure; in contrast, calcium-channel blockers, compared with all other classes of medication, were associated with a higher risk for heart failure. These results provide more-precise guidance for clinicians who are managing patients with type2 diabetes, with a particular focus on the patients with high baseline systolic blood pressure. It also provides precise estimates of the absolute benefits of blood pressure lowering. PARTICIPATING IN WALKING GROUPSIS ASSOCIATED WITH WIDE-RANGINGHEALTH BENEFITS Regular brisk walking (that is to say, walking at a pace of 3 to 5 miles /hour ) is a convenient form of exercise. Evidence suggests that joining a walking group is not only a cost-effective way to increase physical activity, but that it also improves adherence to walking. To evaluate the health benefits of outdoor group walking, researchers conducted a meta-analysis of 40 studies from 14 countries involving 1800 participants with an average age of 54 (three quarters were women) and 70,000hours of participant walking time. The time spent walking ranged from 20minutes /week to nearly 8hours /week , and the studies ranged in duration from 3weeks to a year. Average adherence was 75%. Findings appear on the website of the British Journal of Sports Medicine ( http:// dx.doi.org /10.1136/bjsports-2014-094157 ). During the intervention, the participants in the walking groups showed significant improvements in systolic blood pressure, diastolic blood pressure, resting heart rate, percent body fat, body-mass index, total cholesterol, depression scores, maximum volume of oxygen consumption, 6-minute walk time, and quality of life for physical functioning. There were no adverse effects. This meta-analysis shows that participating in outdoor walking groups has many physiological and psychological health benefits. A vexing challenge for patients is how to start and sustain an exercise program. Joining a walking group is easy, convenient, and safe, and its associated with high participant adherence (presumably because of the social and supportive aspects of group walking). ROUTINE OT DOESNT BENEFIT STROKE VICTIMS LIVING IN CARE HOMES Occupational therapy benefits victims of stroke who are able to return to their homes, but whether it benefits stroke victims who are institutionalized isnt clear. In a study on the website of The BMJ ( http:// dx.doi.org /10.1136/bm j. h468 ), researchers in the United Kingdom randomized 230 care homes (with more than 10 beds each) either to usual care (that was the control group) or to an intervention program consisting of 3months of occupational therapy, delivered by occupational therapists, that involved patient-centered goal setting, the education of care home staff, and adaptations to the environment. Athousand residents with an average age of 83 (two thirds were women) who had experienced strokes or transient ischemic attacks (including the residents with language and cognitive impairments) were involved. Five occupational therapy visits per resident happened in the intervention homes. The primary outcome was a change at 3months in the Barthel index of activities of daily living ( www. strokecenter .org /wp-content/uploads/2011/08/barthel.pdf ), which is a reliable disability scale for stroke victims. Secondary outcomes were Barthel index scores at 6and 12months and changes in a mobility index, a geriatric depression scale, and a quality-of-life questionnaire. No primary or secondary outcome was significantly better in the intervention group. In this trial, routine occupational therapy to maintain or improve functional activity didnt benefit stroke victims living in care homes. These results suggest that occupational therapy should be prescribed to stroke victims who are the most likely to benefit. For stroke victims who arent likely to benefit from occupational therapy, maximizing their dignity, comfort, and safety and establishing goals of care should be emphasized. ASSOCIATION BETWEEN NEWLYDIAGNOSED CANCER AND STROKE RISK Its been suggested that patients with cancer are at an elevated risk for stroke. To explore this association further, researchers linked data from the Surveillance, Epidemiology, and End Results cancer registry to Medicare data. Each of more than 300,000 patients 66 or older with newly diagnosed breast, colorectal, lung, pancreatic, or prostate cancer was matched by age, sex, race, a history of hypertension or atrial fibrillation, and Charlson comorbidity index with a control patient without cancer. Findings appear in the February Annals of Neurology ( http:// dx.doi.org /10.1002/ana.24325 ). At 3months, the cumulative incidence of ischemic and hemorrhagic stroke was significantly higher in the patients with cancer than in the controls for those with lung, pancreatic, colorectal, and breast cancers; there was no excess incidence of stroke for patients with prostate cancer. The relative increases in the risk for stroke among cancer patients gradually decreased after 3months. Patients with certain types of newly diagnosed cancer seem to be at an elevated risk for stroke. Possible mechanisms discussed by the researchers include direct effects of cancer hypercoagulability, embolization of thrombi from cancer-associated nonbacterial thrombotic endocarditis, paradoxical embolism from cancer-associated venous thrombosis, cancer-associated coagulopathy (which might precipitate hemorrhagic stroke), and the complications of cancer treatments. One potential confounding factor might be a misdiagnosis of brain metastasis or seizures as stroke in patients with focal neurological deficits, but this error probably isnt common, given that most patients undergo imaging of the brain. INCIDENCE AND OUTCOMES OF PORTAL VEIN THROMBOSIS IN CIRRHOSIS Routine screening for hepatocellular carcinoma in patients with cirrhosis results in the identification of incidental portal vein thrombosis in as many as a quarter of patients. Risk factors for portal vein thrombosis in this population and its consequences arent clear. In an ancillary study of a randomized trial, researchers evaluated the cumulative incidence of portal vein thrombosis in 1200 patients with cirrhosis (a Child-Pugh class A or B). Clinical data were collected during routine follow-up visits, and factor V Leiden and prothrombin gene mutations were evaluated using stored sera. The development of portal vein thrombosis was confirmed with dynamic imaging. Thrombi considered to be related to liver cancer were excluded. Findings appear in the Februaryissue of Hepatology ( http:// dx.doi.org /10.1002/hep.27546 ). Average follow-up was 4years. At 1year, the cumulative incidence of portal vein thrombosis was 5%; at 3years, it was 8%; and at 5years, it was 11%. Most portal vein thrombosis was partial and nonocclusive. In multivariate analysis, the risk factors for portal vein thrombosis were baseline esophageal varices and prothrombin time, but not prothrombotic mutations or liver disease progression. Plus, once portal vein thrombosis developed, it wasnt independently associated with disease progression. This large, prospective study is one of the few that provide a longitudinal evaluation of the development of portal vein thrombosis. Its findings show that portal vein thrombosis isnt a direct consequence of the progression of liver disease and that developing portal vein thrombosis doesnt directly affect liver disease progression.

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Learning Format 6 Hours
Self-Study

Credit Type(s)
Rheumatology Infectious Diseases Pediatrics Cardiology Neurology