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Program Written Summary NEJM Journal Watch Volume 25, Issue 13 July 1, 2014 Digital Media $24.99 Audio CD $27.99 The following is a list of articles summarized on this issue of NEJM Journal Watch Audio General Medicine. Journal Watch Audio Program Info Accreditation Info Cultural & Linguistic Competency Resources GUIDELINE WATCH: USPSTFRECOMMENDATIONSFOR HBV SCREENING Back in 2004, the United States Preventive Services Task Force recommended screening pregnant women for hepatitis B virus ( www. uspreventiveservicestaskforce .org /3rduspstf/hepbscr/hepbrs.htm and http://annals .org / article.aspx ?Articleid=744546 ) but not asymptomatic nonpregnant adolescents or adults. Since then, evidence supporting the treatment of patients with chronic hepatitis B infection has accumulated. In an updated review on the website of the Annals of Internal Medicine ( http:// dx.doi.org /10.7326/m14-1018 ), the task force finally endorses screening for hepatitis B virus in high-risk nonpregnant adolescents and adults. Based on adequate evidence that vaccination protects against the acquisition of hepatitis B virus, convincing evidence that treating hepatitis B virus-positive patients with antivirals improves intermediate outcomes (like histologic improvement), and adequate evidence that treatment improves actual health outcomes (namely, a lower risk for liver cancer), the task force now recommends hepatitis B virus screening for asymptomatic, nonpregnant adolescents and adults who havent been vaccinated and other patients in high-risk groups (including those at high risk who were vaccinated before being screened for hepatitis B). The high-risk groups include: People from regions with a high prevalence of hepatitis B virus infection, including Africa and Asia, almost all of the Middle East and Eastern Europe, Malta, Spain, much of South America and the Caribbean, some countries in Central America (like Guatemala and Honduras), natives of Alaska, and indigenous peoples in northern Canada People born in the United States who werent previously vaccinated, whose parents were born in high-prevalence regions People who are HIV-positive Injection-drug users Household contacts of people who are positive for hepatitis B virus, and Men who have sex with men The United States Preventive Services Task Force has finally endorsed screening for hepatitis B virus for high-risk nonpregnant adolescents and adults. Guidelines from other organizations, like the Centers for Disease Control and Prevention, concur with screening the groups in the task forces recommendations but also call for testing other populations like patients who get hemodialysis or cytotoxic or immunosuppressive therapy, people who have occupational or other exposure to infectious bodily fluids, patients who are positive for hepatitis C, people who have multiple sexual partners, or inmates of correctional facilities ( http:// dx.doi.org /10.7326/m14-1153 ). INFECTIONS IN TRAVELERS WHOHAVE RETURNED FROM BRAZIL Brazil will host the World Cup games this summer and, in 2016, the Summer Olympics and Paralympics; some of the hundreds of thousands of international tourists who attend these events will inevitably become ill. Most primary care providers in the United States are probably quite rusty at constructing differential diagnoses for sick patients returning from that part of the world. In a study in the May15th issue of Clinical Infectious Diseases ( http:// dx.doi.org /10.1093/cid/ciu122 ), researchers reviewed a large travel medicine database and identified presenting illnesses among more than 1500 American travelers who visited Brazil between 1997 and 2013. The most common complaints were dermatologic conditions, diarrhea, and febrile systemic illness. Among those with skin complaints, the most common diagnosis was cutaneous larva migrans, followed by insect bites, and bacterial skin and soft tissue infections. Among those with diarrhea, most of the patients got no diagnoses (infections, including giardiasis, strongyloidiasis, and schistosomiasis, were each confirmed in fewer than 10% of the cases). Among those with febrile illnesses, 40% got no diagnosis, dengue fever was diagnosed in a third, and malaria was diagnosed in 8%. These findings remind us that Brazil is a tropical country, with all of the infections that climate implies. The data probably arent relevant for sports fans who stay in the stadium, but for those who then take a ride down the Amazon and return with health problems, this lineup might be helpful. ONCE-WEEKLY THERAPY FOR SKINAND SOFT-TISSUE INFECTIONS Many skin and soft-tissue infections are caused by methicillin-resistant Staphylococcus aureus , for which current therapies are limited. In two studies in the June5th New England Journal of Medicine , the lipoglycopeptides dalbavancin (trade name: Dalvance) and oritavancin were compared with standard therapy in adults with acute bacterial skin and soft-tissue infections. Dalbavancin has just been approved by the Food and Drug Administration; a ruling on oritavancin is expected soon. In the first study ( http:// dx.doi.org /10.1056/nejmoa1310480 ), researchers compared dalbavancin (1dose intravenously on days 1 and 8) with vancomycin (1 dose intravenously every 12hours, with an option to switch to oral linezolid after 3 or more days, for a total of 10 to 14days). Early clinical response (indicating treatment success, which was the primary end point) was seen in about 80% of the patients in each group. Adverse events were more common in the vancomycin/linezolid group. In the second study ( http:// dx.doi.org /10.1056/nejmoa1310422 ), researchers compared oritavancin (1 dose intravenously on day 1) with vancomycin (administered intravenously twice /day for 7 to 10days). Based on a prespecified noninferiority margin of 10 percentage points, oritavancin was noninferior to vancomycin on all three efficacy end points. The rates of serious adverse events were similar in the two groups; the proportion of patients who discontinued the study drug due to side effects was lower in the oritavancin group. The adoption of drugs with long plasma half-lives, like dalbavancin and oritavancin, could dramatically change the outpatient management of skin and soft-tissue infections ( http:// dx.doi.org /10.1056/nejme1405078 ). Depending on the pricing of these drugs, cost savings could be sizable. For example, indwelling venous catheters could potentially be avoided a change that could also improve treatment safety. And heres a final note: These two studies were manufacturer-sponsored. WHEN DOES OUTPATIENT THERAPY FAIL FOR CELLULITIS? In the United States, more than 3% of all emergency department visits are for skin infections, and about four out of five of these infections are cellulitis rather than abscesses. Most of the patients with cellulitis are treated as outpatients, but past research suggests that treatment isnt often successful. In a study in the Mayissue of Academic Emergency Medicine ( http:// dx.doi.org /10.1111/acem.12371 ), researchers in Canada looked for predictors of treatment failure in patients with cellulitis who had gotten outpatient treatment at two academic emergency departments. Full follow-up was available for 500 patients; therapy failed in 20% (they needed different antibiotics or hospital admission). Predictors of treatment failure were a temperature greater than 38°C at triage, chronic leg ulcers, chronic edema or lymphedema, past cellulitis in the same area, and cellulitis at a wound site. The researchers found no obvious connection between initial antibiotic choice and treatment success or failure. That chronic and recurrent conditions would be more difficult to cure makes sense, and these findings on the predictors of outpatient antibiotic therapy failure in patients with cellulitis support the common-sense wisdom of ensuring good follow-up for these patients. Plus, regardless of chronicity and etiology, adjunctive measures (like compression, immobilization, elevation, and nonsteroidal anti-inflammatory medication) might be helpful in speeding resolution. KEEP USING MACROLIDES FOR COMMUNITY-ACQUIRED PNEUMONIA The Infectious Diseases Society of America and the American Thoracic Society recommend treating patients with community-acquired pneumonia with either a fluoroquinolone or the combination of a β-lactam and a macrolide ( http:// dx.doi.org /10.1086/511159 ). Unfortunately, theres conflicting evidence regarding an association between an excess risk for cardiovascular-related mortality and the use of azithromycin ( www. jwatch .org /jw201305010000001 and www. jwatch .org /jw201205220000001 ), but none of this research focused specifically on patients with community-acquired pneumonia. In a retrospective study in the June4th issue of JAMA ( http:// dx.doi.org /10.1001/jama.2014.4304 ), researchers examined data on more than 60,000 patients from the Veterans Affairs System who were hospitalized with pneumonia. The patients average age was 78; nearly all were men; and most had multiple comorbidities. Based on propensity-score analysis, 90-day mortality was lower in the patients who got azithromycin than in the patients who didnt, although the incidence of myocardial infarction was higher in the azithromycin patients. There was no difference between the two closely matched groups in the rates of arrhythmia or heart failure. The number needed to treat for a lower 90-day mortality risk was 20, whereas the number needed to harm (that is to say, myocardial infarction) was 140. Although this wasnt a randomized, controlled trial, this large, population-based cohort analysis supports the continued use of azithromycin as a first-line agent (in conjunction with a β-lactam) for patients hospitalized with community-acquired pneumonia. The researchers speculate that the beneficial effects of azithromycin might reflect not only its antimicrobial, but also its anti-inflammatory properties. RISK FACTORS FOR SHINGLES Age is an important risk factor for herpes zoster; experts at the Centers for Disease Control and Prevention recommend a single dose of shingles vaccine for patients 60 or older ( www. cdc .gov /vaccines/vpd-vac/shingles/hcp-vaccination.htm#recommendations ). But whether younger patients, especially those with chronic medical conditions, might benefit from vaccination isnt clear. In a case-control study on the website of the British Medical Journal ( http:// dx.doi.org /10.1136/bm j. g2911 ), researchers in the United Kingdom quantified the effects of potential risk factors for herpes zoster among 150,000 adults diagnosed with the condition between 2000 and 2011 and among 600,000 controls who were matched by age, sex, and practice with the case patients. The median age at the diagnosis of zoster was 62; nearly half of the zoster cases happened before the age of 60. Adjusted for multiple variables (including treatments), the medical conditions associated with an excess risk for shingles were HIV infection, lymphoma, myeloma, leukemia, lupus, inflammatory bowel disease, type1 diabetes, rheumatoid arthritis, chronic obstructive pulmonary disease, depression, asthma, and chronic kidney disease. A higher risk was also seen among the patients with past hematopoietic stem cell transplant and those who took oral or inhaled corticosteroids. The relative effects of these risk factors decreased with increasing age. This study had several important findings: Nearly half of cases of shingles are diagnosed before the age of 60; there are many risk factors for shingles; and, in general, the relative effects of these risk factors are larger for younger patients. But we dont know how effective shingles vaccination is in younger patients with 1 or more of these risk factors, and some of these risk factors are contraindications to vaccination (for example, the vaccine isnt recommended for immunocompromised patients, including those taking immunosuppressive drugs ( www. cdc .gov /mmwr/preview/mmwrhtml/rr5705a1.htm ). HIGH RATE OF ANTIBIOTICPRESCRIBING FOR ACUTEBRONCHITIS STILL! During the past 15years, national education programs have focused on eliminating the inappropriate use of antibiotics generally, and expensive, broad-spectrum antibiotics specifically. To see whether these programs have had any effect, researchers used data from two national surveys of ambulatory care in physicians offices and hospital outpatient facilities to evaluate antibiotic prescribing in more than 3000 visits by adults for acute bronchitis a diagnosis for which guidelines explicitly advise against antibiotic therapy in patients without chronic lung disease. Visits that resulted in hospitalization or were associated with chronic pulmonary disease, immunodeficiency, cancer, or other serious conditions were excluded. Details appear in the May21st issue of JAMA ( http:// dx.doi.org /10.1001/jama.2013.286141 ). Between 1996 and 2010, the overall rate of antibiotic prescribing was 70%, with little variation by the patients age, sex, race, or insurance status, or by region or population density (meaning rural or urban); prescribing rates were similar in primary care and emergency department settings, and prescribing increased in both of these settings (significantly so in emergency departments). The prescribing of extended macrolides increased from 25 to 40% during the 15-year study. Other antibiotics most commonly, broad-spectrum antibiotics were prescribed at a third of the visits. The researchers bemoan the apparent lack of effect of 15years of practice guideline dissemination, evidence-based exhortations, and educational efforts on antibiotic prescribing for adults with acute bronchitis, although its possible that the prescribing rate might have been even higher by now without these measures. Clinician education, of whatever sort, apparently isnt the key factor. PRIMARY CNS VASCULITIS: OFTEN IN THE DIFFERENTIAL, BUT RARELY CONFIRMED The onset of focal neurological symptoms, headaches, and seizures generates a broad differential diagnosis, and primary central nervous system vasculitis is often invoked. In a cohort study in the Mayissue of Arthritis and Rheumatology ( http:// dx.doi.org /10.1002/art.38340 ), researchers at 20 hospitals in France present their findings on 50 patients in whom primary CNS vasculitis was diagnosed between 1996 and 2012 and for whom other potential diagnoses were excluded. Diagnoses were confirmed by brain biopsy or neuroimaging using either conventional cerebral angiography or magnetic resonance angiography. At the time of diagnosis, about half of the patients had new-onset headaches that preceded by a few days or months or were associated with other neurological symptoms (like focal deficits, speech disorders, and seizures); overall, 80% of the patients had focal neurological deficits, and a third had seizures. C-reactive protein levels were abnormal in a quarter of the patients. Of 50 patients who underwent lumbar puncture, findings were abnormal in two thirds. Fifty patients were treated with steroids, 40 were treated with cyclophosphamide, and 2 patients, 1 of whom had relapsed after being treated with cyclophosphamide and steroids, got rituximab (trade name: Rituxan). After a median follow-up of 3years, 3 patients had died, 30 had responded to initial treatment, and 14 had experienced 1 or more relapses. Seizures at diagnosis and meningeal gadolinium enhancements on magnetic resonance imaging were associated with a higher risk for relapse. Central nervous system vasculitis is quite rare, but when the cause of a CNS presentation remains uncertain after an initial evaluation, brain biopsy or cerebral angiography might be helpful. Nearly all of the patients in this study were treated with steroids and cyclophosphamide. Although this disease is more often discussed than diagnosed, when its recognized and treated, mortality islow. ERADICATING H. pylori LOWERS RISK FOR GASTRIC CANCER IN ASYMPTOMATIC ADULTS Patients who are positive for Helicobacter pylori are more likely to develop gastric cancer than are patients without the infection. In a meta-analysis on the website of the British Medical Journal ( http:// dx.doi.org /10.1136/bm j. g3174 ), researchers systematically reviewed six randomized trials with durations ranging from 4 to 15years (5 were conducted in Asia) to see whether screening for and eradicating H. pylori in healthy asymptomatic patients 17 or older lowers the risk for gastric cancer. In pooled analyses of 6500 patients, the incidence of gastric cancer was 1.6% among those who got eradication therapy and 2.4% among those who got placebo or no treatment. The researchers calculated the number needed to treat by applying the findings of this meta-analysis to global data from 2008 on gastric cancer incidence; assuming the benefit of eradication therapy is lifelong, they estimate that numbers needed to treat were 20 for adults in Asia, 125 for adults in the United Kingdom, and 200 for adults in the United States. Based on data from three of the trials, mortality from gastric cancer was 1.1% among those who got eradication therapy and 1.6% among those who got placebo. Eradication therapy didnt lower all-cause mortality. In this study, screening for and eradicating Helicobacter pylori in healthy, asymptomatic Asian adults significantly lowered the risk for and death from gastric cancer. We need trials in other populations to more widely establish whether the benefits of screening and eradication outweigh the potential harms. Notably, H. pylori infection is also linked to mucosa-associated lymphoma of the stomach, and eradication therapy induces remission in most cases. IS COLORECTAL CANCERSCREENING INDICATED IN PREVIOUSLYUNSCREENED ELDERS? The United States Preventive Services Task Force advises against colorectal cancer screening in patients older than 85; for unscreened patients who are between 75 and 85, decisions to screen should be guided by the individuals health status and competing risks ( www. jwatch .org /jw200810280000003 ). But few data are available to guide clinicians on screening previously unscreened older patients. Until now. Using modeling, researchers evaluated to what age screening should be considered in unscreened patients between the ages of 76 and 90 who are at an average risk for colorectal cancer. Strategies included one-time colonoscopy, sigmoidoscopy, or fecal immunochemical testing (known by the acronym FIT). The findings of their analysis appear in the June3rd Annals of Internal Medicine ( http:// dx.doi.org /10.7326/m13-2263 ). Compared with no screening, colorectal cancer screening at the age of 80 prevented 4 (with a 1-time FIT test) to 11 (with 1-time colonoscopy) colorectal cancer-related deaths for every 1000 patients screened. As the age at screening increased, the number of colorectal cancer-related deaths prevented and the number of quality-adjusted life-years gained decreased. When US$100,000/quality-adjusted life-year was used as a cutoff, colorectal cancer screening was cost-effective in unscreened elders without comorbid conditions until the age of 83 (with colonoscopy), 84 (with sigmoidoscopy), and 86 (with FIT). In elders with severe comorbid conditions, colonoscopy was cost-effective until the age of 77; sigmoidoscopy was cost-effective until the age of 78, and FIT was cost-effective until the age of 80. Close to a quarter of patients older than 75 have never undergone colorectal cancer screening. Although clinicians shouldnt base decisions solely on simulation models, this study suggests that one-time screening for colorectal cancer in patients older than 75 is cost-effective (at a threshold of $100,000/quality-adjusted life-year) and probably should be considered in elders without comorbid conditions. PROMISING NEW DRUGS FOR IDIOPATHIC PULMONARY FIBROSIS Generally, the therapeutic options for idiopathic pulmonary fibrosis are limited and unsatisfactory. Three reports in the May29th New England Journal of Medicine address treatments for the condition. Pirfenidone is thought to exert antifibrotic effects by inhibiting growth factors. After two past trials suggested benefit ( http:// dx.doi.org /10.1016/s0140-6736(11)60405-4 ), the drug was approved for use in many countries but not in the United States. Now, in a third industry-supported trial ( http:// dx.doi.org /10.1056/nejmoa1402582 ), researchers randomized 560 patients with idiopathic pulmonary fibrosis to either pirfenidone or placebo for a year. The proportion of patients whose forced vital capacity decreased by 10 percentage points or who died was significantly lower with pirfenidone than with placebo. In a prespecified pooling of data from all three pirfenidone trials, all-cause mortality was also significantly lower with pirfenidone. Nintedanib also inhibits growth factors that promote fibrosis. Industry-supported researchers have conducted two new trials; they randomized 1100 patients to either nintedanib or placebo and have published the results together ( http:// dx.doi.org /10.1056/nejmoa1402584 ). Compared with placebo, nintedanib blunted the decline in forced vital capacity by an average of about 110mL at a year. Trends toward improved symptoms and fewer exacerbations didnt reach statistical significance. Nintedanib isnt approved by the Food and Drug Administration. Acetylcysteine has been proposed as a treatment for idiopathic pulmonary fibrosis because of its antioxidant properties. A randomized trial in which a three-drug regimen (prednisone, azathioprine, and acetylcysteine) was compared with acetylcysteine alone or with placebo was interrupted in 2011, when excess mortality was observed in the combination arm ( http:// dx.doi.org /10.1056/nejmoa1113354 ). Now, the researchers present findings for the acetylcysteine- vs .-placebo comparison, which involved 260 patients ( http:// dx.doi.org /10.1056/nejmoa1401739 ). At a year, decline in forced vital capacity and clinical endpoints werent significantly different in the acetylcysteine and placebo groups. The results in patients with idiopathic pulmonary fibrosis for both pirfenidone and nintedanib are considered to be a major breakthrough by the editorialist ( http:// dx.doi.org /10.1056/nejme1403448 ). But the studies only lasted a year, their enrollment was limited to patients with forced vital capacity greater than 50% of predicted, and positive outcomes were seen mainly in pulmonary function testing (and not in symptoms). Finally, the latest acetylcysteine trial suggests that it has no role in idiopathic pulmonary fibrosis treatment. STATINS ARENT THE ANSWER FOR PATIENTS WITH COPD OR ARDS In observational studies, statin therapy has been associated with better outcomes in patients with various diseases, including chronic obstructive pulmonary disease and acute respiratory distress syndrome. Researchers conducted two randomized, placebo-controlled trials to more rigorously test the potential benefit of statin therapy for these disorders. Their findings appear in the June5th New England Journal of Medicine . In the first study ( http:// dx.doi.org /10.1056/nejmoa1403086 ), treatment with simvastatin didnt decrease the frequency of exacerbations, increase the time to first exacerbation, or improve lung function or quality of life in 900 patients with chronic obstructive pulmonary disease. In the second study ( h ttp:// dx.doi.org /10.1056/nejmoa1401520 ), treatment with rosuvastatin (trade name: Crestor) had no effect on in-hospital mortality, the time to liberation from a ventilator, or intensive care unit length of stay in patients with acute respiratory distress syndrome. This study was stopped early for futility after 750 patients were enrolled. The statin patients were more likely to develop hepatic and renal insufficiency than were the patients who didnt take the drug. In an accompanying editorial ( http:// dx.doi.org /10.1056/nejme1405032 ), it was noted that these two negative studies on the effects of statins in patients with chronic lung disorders reaffirm that changing practice based on observational studies can be risky. We need randomized, controlled trials to test hypotheses generated by observed associations. VITAMIN D SUPPLEMENTATION DOES LITTLE TO IMPROVE ASTHMA CONTROL In patients with asthma, lower serum levels of 25-hydroxyvitamin D have been associated with more-frequent exacerbations, airway hyper-responsiveness, and decreased lung function. Theoretically, low vitamin D levels could exacerbate pro-inflammatory states and reduce corticosteroid responsiveness. To see whether vitamin D supplementation improves responsiveness to corticosteroid therapy, researchers randomized 400 patients with asthma, an average age of 40, and 25-hydroxyvitamin D levels lower than 30 ng/ mL to either placebo or high-dose oral vitamin D 3 supplementation (at an initial dose of 100,000IU, followed by 4000 IU/ day) for 7months. All of the patients got 320 μg/day of the inhaled corticosteroid ciclesonide. During the study period, the ciclesonide dose was tapered in the patients whose asthma was controlled. Findings appear in the May28th issue of JAMA ( http:// dx.doi.org /10.1001/jama.2014.5052 ). At 7months, 80% of the patients had achieved vitamin D levels of 30 ng/ mL or higher. Overall, there were no differences between the supplementation and placebo groups in the primary outcome of asthma treatment failure (for example, a decline in lung function or the increased use of rescue medications). Plus, there were no clinically meaningful differences between the two groups in various secondary outcomes. This is yet another study that shows that, although low vitamin D levels are associated with many diseases, supplementation doesnt meaningfully affect clinical outcomes. Clinicians shouldnt check vitamin D levels or supplement vitamin D in the hope of improving the control of asthma. IS THROMBOPROPHYLAXIS WARRANTED AFTER LOWER-LEG FRACTURES? Is thromboprophylaxis warranted in patients with lower-leg fractures? To determine the incidence of symptomatic venous thromboembolism in these patients, researchers in Canada prospectively followed 1200 patients with nonoperatively treated fractures of the tibia, fibula, or ankle, and operatively or conservatively treated fractures of the patella or foot; 80% of the patients wore casts or splints for an average of 40days. Pharmacologic or mechanical thromboprophylaxis wasnt allowed during the study. Findings appear in the May21st Journal of Bone & Joint Surgery ( http:// dx.doi.org /10.2106/jbjs.m.00236 ). During 3months of follow-up, the incidence of symptomatic venous thromboembolism was only 0.6%: Five patients developed deep vein thrombosis (2 proximal and 3 calf-vein), and two patients developed pulmonary embolism (none was fatal). This observational study suggests that symptomatic venous thromboembolism happens so rarely after lower-limb fractures that thromboembolism prophylaxis isnt warranted. You might wonder why patients with surgically treated tibial, fibular, or ankle fractures were excluded: The researchers had enrolled these patients in a randomized trial of dalteparin (trade name: Fragmin) vs . placebo (D-KAF trial www. clinicaltrials .gov /ct2/show/study/nct00187408 ), and the incidence of symptomatic venous thromboembolism was so low that prophylaxis conferred no benefit ( www. bjjprocs.boneandjoint .org .uk/content/92-B/SUPP_I/7.3 ). TENUOUS RELATION BETWEEN ROTATOR CUFF TEARS AND PAIN By some estimates, full-thickness rotator cuff tears happen in at least 10% of older patients. Many of them are asymptomatic; among those who are symptomatic, we dont know whether pain severity is associated with any anatomic characteristics of rotator cuff tears. In a study in the May21st Journal of Bone & Joint Surgery ( http:// dx.doi.org /10.2106/jbjs.l.01304 ), researchers addressed this question in 400 patients with symptomatic, atraumatic full-thickness tears documented by magnetic resonance imaging. Most of the tears involved the supraspinatus tendon. MRI measures of the presumed severity of the tear (for example, the degree of retraction, humeral head migration, and supraspinatus atrophy) didnt correlate with pain severity, as recorded on visual-analog pain scales. In contrast, the number of medical comorbidities and lower education level modestly correlated with higher pain scores. In this study, severity of pain wasnt related to the imaging characteristics of full-thickness rotator cuff tears. This finding implies albeit indirectly that MRI characteristics might not be a useful way to select patients for whom surgical repair will relieve pain. The researchers note that indications for surgical repair of chronic, atraumatic rotator cuff tears are not clearly defined , and they conclude that clinicians shouldnt assume that an atraumatic rotator cuff tear is responsible for a patients shoulder pain. NEW ORAL ANTICOAGULANTSIN OLDER ADULTS Clinicians might be concerned about the relative safety of the newer oral anticoagulants (namely, dabigatran [trade name: Pradaxa], rivaroxaban [trade name: Xarelto], and apixaban [trade name: Eliquis]) in older patients. In a meta-analysis in the May Journal of the American Geriatrics Society ( http:// dx.doi.org /10.1111/jgs.12799 ), researchers identified 10 randomized trials in which the outcomes for these three agents were presented according to age subgroups; the analysis focused on 25,000 patients 75 or older. These trials involved patients with atrial fibrillation, acute venous thromboembolism, extended treatment to prevent recurrent venous thromboembolism, and prophylaxis in patients who were medically ill. Comparators were warfarin, aspirin, enoxaparin, and placebo (placebo was used only in 2 extended venous thromboembolism prevention trials). For older patients, the rates of major bleeding or clinically relevant bleeding were virtually identical in the new-anticoagulant and conventional-treatment groups; this finding held true for the studies in which the new agents were compared with warfarin. The incidences of stroke (in the atrial fibrillation trials) and recurrent venous thromboembolism or death (in the venous thromboembolism trials) were significantly lower with the new agents than with the comparators. These efficacy and safety findings for older patients applied to each of the three individual agents. This analysis provides reassurance that the balance of efficacy and safety of dabigatran, rivaroxaban, and apixaban extends to older patients. Prescribing information for the new drugs specifies dose reductions (or contraindications) for patients with reduced renal function, but the manufacturers dont mandate adjustments in drug dose based on advanced age alone. STRUCTURED PHYSICAL ACTIVITYPRESERVES MOBILITYIN FRAIL OLDER ADULTS In elderly patients, the ability to walk independently is associated with lower morbidity and mortality. But studies of structured physical activity programs to preserve mobility in near-frail elders are scarce. In a multisite study on the website of JAMA ( http:// dx.doi.org /10.1001/jama.2014.5616 ), researchers randomized 1600 sedentary patients with an average age of 79 (two thirds were women) who had functional limitations, but were able to independently walk 400 m under 15minutes either to a physical-activity intervention or to an education control group. The intervention involved two supervised exercise sessions /week as well as home-based activity three to four times /week and included walking (with the goal of walking 150minutes /week ) and strength training. The control group attended regular education sessions that focused on health topics, but didnt address physical activity. During an average follow-up of 2.6years, the average duration of physical activity per week was significantly higher in the intervention group than in the control group. A loss of mobility (that is to say, not being able to walk 400m within 15minutes) happened in 30% of the intervention group vs . 36% of the control group. Serious adverse events were reported by similar numbers of patients in the two groups. The estimated cost of the intervention was about US$5000 per participant. In this study, structured physical activity prevented the loss of mobility in some near-frail elderly patients, but at a high cost. The number of elders who needed to participate in the program for 1 to benefit was about 20, at a cost of US$100,000. Still, the cost of becoming nonambulatory is also high. ICU TO INPATIENT HOSPICE IT CAN WORK In the United States, 10% to 20% of the patients admitted to an intensive care unit will die in the ICU. Many critical care teams have partnered with palliative care providers to deliver optimal end-of-life care in the ICU. But transitioning critically ill patients from the ICU to hospice care is relatively rare. In a retrospective study in the Mayissue of Critical Care Medicine ( http:// dx.doi.org /10.1097/ccm.0000000000000120 ), researchers examined a program in which patients were transferred from an ICU to an inpatient hospice unit in two academic medical centers within the same healthcare system. During 6months, 170 patients were transferred from the ICU to the inpatient hospice unit; 100 missed opportunities for transfer were also identified. The patients who werent transferred were less likely to have gotten palliative care consultations and more likely to have needed mechanical ventilation or vasopressors, although inpatient hospice unit admission criteria didnt exclude these interventions. An estimated 600 ICU days mightve been avoided if all of the opportunities for transfer were realized. Collaboration between palliative care and critical care providers has yielded progressively nuanced end-of-life care in the intensive care unit. Transition to inpatient hospice care might confer added benefit, because hospice provides resources that are rarely available in an ICU, including prolonged bereavement support for families. Although we need to examine the long-term effect of ICU-to-hospice transfers, theyre clearly feasible and might improve patient and family care, as well as lower hospital costs. A SCREEN TO PREDICT VIOLENCEIN MILITARY VETERANS Predicting violence in people is challenging and important, particularly in returning military veterans. Federally funded researchers developed the violence screening and assessment of needs instrument (known colloquially as VIO-SCAN) and applied it in two samples of post-9/11 veterans. Their findings appear on the website of the American Journal of Psychiatry ( http:// dx.doi.org /10.1176/appi.ajp.2014.13101316 ). The tests five yes-or-no questions address financial instability, combat experience (witnessing serious injury or death), alcohol misuse, a history of lifetime noncombat violence or arrest for crime, and probable post-traumatic stress disorder plus past-week irritability or angry outbursts. Severe violence was defined as using a knife or gun against someone, threatening to use a lethal weapon, assaulting someone, or raping someone. Among 1100 veterans who completed self-reports and had 1-year follow-up, the predicted probability for severe violence during follow-up ranged from 0.03 (for a VIO-SCAN score of 0) to 0.5 (for a score of 5). Among 200 veterans with in-depth evaluations (including interviews, self-reports, and the reports of collateral informants), the predicted 1-year probability of severe violence was around 0.4 for a score of 5. In both of the samples, VIO-SCAN scores were linearly related to the risk for subsequent violence. Screening instruments cant predict violence in people and arent comprehensive evaluations. Still, they might help identify high-risk people who merit more investigation and intervention. How the scores of the violence screening and assessment of needs test might predict subsequent suicidality merits inquiry as well. GUIDELINE WATCH: SCREENINGFOR SUICIDE RISK Back in 2010, suicide was the 10th leading cause of death in the United States and among the top five leading causes of death in people between the ages of 10 and 54. In its review in 2004, the United States Preventive Services Task Force concluded that the evidence wasnt sufficient to make a recommendation for or against screening for suicide risk ( http://annals .org / article.aspx ?Articleid=717459 ). The task force has now updated its analysis. Details appear in the May20th Annals of Internal Medicine ( http:// dx.doi.org /10.7326/m14-0589 ). The key points of the new analysis are: Nearly 40% of adults visited their primary care clinician within a month of committing suicide. In terms of risk factors: The highest suicide rates are among young native American and Alaskan natives between the ages of 19 and 24 and among non-Hispanic whites older than 75. Post-traumatic stress disorder, substance abuse, and depression raise the risk. Important social factors include adverse childhood events; unemployment; social isolation; a family history of suicide; and the discrimination associated with being gay, lesbian, bisexual, or transgender. Traumatic brain injury or post-traumatic stress disorder associated with military service and recent release from military service are also associated with an increased risk. In terms of screening tests: The sensitivity and the specificity of various instruments to identify the risk for suicide varied widely. In terms of interventions: In patients who are at risk for suicide, cognitive behavioral therapy and group therapy are often effective. No direct evidence showed that screening for suicide risk among adolescents and adults in primary care settings improved health outcomes, and the evidence about potential harms wasnt sufficient either. It seems that little evidentiary progress has been made during the past 10years, leading the United States Preventive Services Task Force to again conclude that the current evidence warrants no recommendation for screening for suicide risk. HEALTHCARE REFORM IN MASSACHUSETTS IS ASSOCIATEDWITH DROPS IN MORTALITY Back in 2006, Massachusetts expanded Medicaid, provided subsidies for private insurance, and created an individual mandate as part of statewide healthcare reform. Access to care, self-reported physical and mental health, the use of preventive services, and functional status have all improved in the ensuing years. In a study in the May6th Annals of Internal Medicine ( http:// dx.doi.org /10.7326/m13-2275 ), researchers evaluated whether healthcare reform in Massachusetts has lowered early mortality. They used propensity scores and a model that was adjusted for multiple factors including age, sex, race, income, and employment status to evaluate mortality within Massachusetts vs . that of non-reform states for 5years before and 4years after Massachusetts healthcare reform. Nearly 300,000 Massachusetts adults gained insurance coverage in 2006. All-cause mortality in Massachusetts and in the control population was similar before the implementation of healthcare reform. After 2006, adjusted all-cause mortality in Massachusetts decreased by 3% relative to the control population (the absolute decrease was 8 per 100,000 adults). The relative decrease in deaths that could be prevented by direct healthcare interventions (like stroke, cancer, and infections) was almost 5%. This study showed that health insurance coverage expansion in Massachusetts was associated with a significant relative reduction in mortality. Although the study design limits the evaluation of cause and effect, its remarkable that we see reductions in mortality just 4years after reform. Longer follow-up might show even larger gains.

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Learning Format 6 Hours
Self-Study

Credit Type(s)
Geriatrics Psychiatry Critical Care Infectious Diseases Rheumatology Emergency Medicine Internal Medicine