Here are the last 20 additions to the PBrain (total entries as of now = 3881)


Anticonvulsants in the treatment of low back pain and lumbar radicular pain: A systematic review and meta-analysis (3862)
Enke O et al CMAJ 190:E786 07-03-2018

A meta-analysis published last year showed gabapentinoids to be largely ineffective for chronic low back pain (NEJM JW Gen Med Oct 15 2017 and PLoS Med 2017; 14:1002369). Now, another group has published a somewhat different meta-analysis: It covers anticonvulsants generally, comprises only placebo-controlled trials, and includes trials focused on radiculopathy (in addition to low back pain).

Nine trials (859 total participants) that involved gabapentin, pregabalin, or topiramate were identified. The researchers found "moderate- to high-quality evidence that anticonvulsants are ineffective for treatment of low back pain or lumbar radicular pain." In addition, they found high-quality evidence that gabapentin and pregabalin are associated with excess risk for adverse events.

Comment: Because these trials enrolled patients with various combinations of back pain and radiculopathy, varying durations of pain, varying drug doses, and varying durations of follow-up, conclusions for any particular patient subgroup cannot be drawn with certainty. Nevertheless, we now have reasonably compelling evidence that anticonvulsants - and gabapentinoids in particular - should not be prescribed for patients with low back pain. This conclusion extends to patients with lumbosacral radiculopathy (including sciatica).


Lynch Syndrome-Associated Colorectal Cancer (3863)
Sinicrope NEJM 379:764 08-23-2018

Lynch Syndrome-Associated Colorectal Cancer:

lynch criteria

Full article


Lynch Syndrome-Associated Colorectal Cancer (3864)
Sinicrope NEJM 379:764 08-23-2018

Lynch Syndrome-Associated Colorectal Cancer:

lynch criteria

Full article


Aromatherapy versus oral ondansetron for antiemetic therapy among adult emergency department patients: A randomized controlled trial (3865)
April MD et al Ann Emerg Med 02-17-2018

Though ondansetron is viewed by many as the first-line agent for nausea in the emergency department (ED), there is evidence it doesn't work in noncancer patients (NEJM JW Emerg Med Aug 2014 and Ann Emerg Med 2014; 64:526). An alternative agent, inhaled isopropyl alcohol, has shown promise (NEJM JW Emerg Med Feb 2016 and Ann Emerg Med 2016; 68:1).

In the current trial, 120 adult ED patients with nausea or vomiting who did not require intravenous access were randomized to inhaled isopropyl alcohol plus 4 mg oral ondansetron; inhaled isopropyl alcohol plus oral placebo; or inhaled saline plus 4 mg oral ondansetron. Isopropyl alcohol was provided in the form of a standard alcohol swab. Patients received a single dose of the oral intervention but could sniff alcohol or saline swabs repeatedly. Nausea was measured on a 100-mm visual analog scale at baseline and 30 minutes.

Mean nausea scores decreased by 30 mm in the alcohol/ondansetron group, 32 mm in the alcohol/placebo group, and 9 mm in the saline/ondansetron group. Rescue antiemetic therapy was given to 28%, 25%, and 45% of each group, respectively. Differences between alcohol and saline groups were statistically significant. Patients in the inhaled alcohol groups also had better nausea control at the time of discharge and reported higher satisfaction with nausea treatment. No adverse events occurred. The mechanism of action is currently unknown.

COMMENT: It is uncommon for us to assign a rating of "Practice Changing" to a small, single-center study, but these results are truly remarkable and are consistent with prior research. For patients not obviously requiring IV therapy, we should treat nausea with repeated inhalations from an isopropyl alcohol swab instead of administering any other drug. And, although this study provides no direct evidence of benefit to patients who do require IV therapy, there would seem to be little downside to trying this simple and safe intervention in that group, too.


Association between sodium-glucose cotransporter 2 inhibitors and lower extremity amputation among patients with type 2 diabetes (3866)
Chang H-Y et al JAMA Intern Med 08-13-2018

In combined results from two studies, lower-extremity amputations (mostly toe or metatarsal level) were significantly more common with the sodium-glucose cotransporter-2 (SGLT-2) inhibitor canagliflozin (Invokana) than with placebo (6.3 vs. 3.4 amputations per 1000 patient-years; NEJM JW Gen Med Aug 1 2017 and N Engl J Med 2017; 377:644). This outcome resulted in a black box warning in the drug's prescribing information. Now, in this retrospective cohort study, researchers used a U.S. commercial drug-prescribing database to determine whether use of SGLT-2 inhibitors was associated with excess risk for amputations. Data were available for about 40,000 new users of SGLT-2 inhibitors for an average of 4 months.

In adjusted analyses, SGLT-2 inhibitor users were significantly more likely than users of older antidiabetes drugs (sulfonylureas, metformin, and thiazolidinediones) to undergo amputations (hazard ratio, 2.1) or to develop osteomyelitis (HR, 1.44) or leg ulcers (HR, 1.3). However, absolute risks were small for each of these outcomes (≈0.5, 1, and 2 per 1000 patient-years, respectively). Risks for amputation and osteomyelitis with SGLT-2 inhibitors were not significantly higher than risks with dipeptidyl peptidase-4 (DPP-4) inhibitors or glucagon-like peptide-1 (GLP-1) agonists.

Comment: This study reinforces concern about amputation as a potential complication of using SGLT-2 inhibitors. Although excess amputation risk was much smaller in this observational study than in the canagliflozin randomized trials, this study had much shorter follow-up - and the participants were younger and healthier - than in the randomized trials. Because most SGLT-2 inhibitor users in this study were receiving canagliflozin, the relevance of these findings to other SGLT-2 inhibitors is unclear.


Long-term effects of omitting antibiotics in uncomplicated acute diverticulitis (3867)
van Dijk ST et al Am J Gastroenterol 113:1045 07-01-2018

In the U.S., patients with acute diverticulitis almost always receive antibiotic therapy. However, in two recent randomized controlled trials from Sweden and the Netherlands, antibiotics did not improve outcomes in patients with uncomplicated diverticulitis during 6 to 12 months of follow-up (Br J Surg 2012; 99:532; Br J Surg 2017; 104:52). Now, the researchers from the Dutch trial - which involved 528 patients with first episodes of relatively mild, uncomplicated diverticulitis - report 2-year follow-up results.

Diverticulitis recurred in 15% of patients in both the antibiotic and no-antibiotic groups. During follow-up, incidences of complicated diverticulitis were not significantly different between groups (3.3% and 4.8%, P=0.403); sigmoid resection incidences also were similar (5% and 9%; P=0.085).

Comment: The authors and an editorialist note several caveats about this study; for example, about 10% of patients were lost to follow-up, and the difference in sigmoid resections approached statistical significance. But two randomized trials now have suggested that antibiotic therapy might be unnecessary for acute uncomplicated diverticulitis, and an American Gastroenterological Association guideline makes a conditional recommendation that "antibiotics should be used selectively, rather than routinely, in patients with acute uncomplicated diverticulitis" (Gastroenterology 2015; 149:1944). Nevertheless, I doubt that most U.S. clinicians will withhold antibiotic therapy in the foreseeable future. However, patients with mild diverticulitis sometimes present with symptoms that are spontaneously improving by the time they're seen in primary care; in such cases, it would be reasonable to observe without antibiotic therapy when patients are not ill-appearing and are staying well hydrated.


Management of Groin Hernias in Adults - 2018 (3868)
Montgomery et al JAMA 320:1029 09-11-2018

Full article


Diagnosis and Treatment of Clostridium difficile Infection (3869)
Gupta et al JAMA 320:1031 09-11-2018

Metronidazole is no longer the initial drug of choice. Start with vancomycin or fidaxomicin.

Full article


Primary Hyperparathyroidism (3870)
Insogna NEJM 379:1050 09-13-2018

Full article


Aspirin-Exacerbated Respiratory Disease (3871)
White et al NEJM 379:1060 09-13-2018

Full article


Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents (3872)
Hayden et al NEJM 379:913 09-06-2018

BACKGROUND: Baloxavir marboxil is a selective inhibitor of influenza cap-dependent endonuclease. It has shown therapeutic activity in preclinical models of influenza A and B virus infections, including strains resistant to current antiviral agents.

METHODS: We conducted two randomized, double-blind, controlled trials involving otherwise healthy outpatients with acute uncomplicated influenza. After a dose-ranging (10 to 40 mg) placebo-controlled trial, we undertook a placebo- and oseltamivir-controlled trial of single, weight-based doses of baloxavir (40 or 80 mg) in patients 12 to 64 years of age during the 2016-2017 season. The dose of oseltamivir was 75 mg twice daily for 5 days. The primary efficacy end point was the time to alleviation of influenza symptoms in the intention-to-treat infected population.

RESULTS: In the phase 2 trial, the median time to alleviation of influenza symptoms was 23.4 to 28.2 hours shorter in the baloxavir groups than in the placebo group (P<0.05). In the phase 3 trial, the intention-to-treat infected population included 1064 patients; 84.8 to 88.1% of patients in each group had influenza A(H3N2) infection. The median time to alleviation of symptoms was 53.7 hours (95% confidence interval [CI], 49.5 to 58.5) with baloxavir, as compared with 80.2 hours (95% CI, 72.6 to 87.1) with placebo (P<0.001). The time to alleviation of symptoms was similar with baloxavir and oseltamivir. Baloxavir was associated with greater reductions in viral load 1 day after initiation of the regimen than placebo or oseltamivir. Adverse events were reported in 20.7% of baloxavir recipients, 24.6% of placebo recipients, and 24.8% of oseltamivir recipients. The emergence of polymerase acidic protein variants with I38T/M/F substitutions conferring reduced susceptibility to baloxavir occurred in 2.2% and 9.7% of baloxavir recipients in the phase 2 trial and phase 3 trial, respectively.

CONCLUSIONS: Single-dose baloxavir was without evident safety concerns, was superior to placebo in alleviating influenza symptoms, and was superior to both oseltamivir and placebo in reducing the viral load 1 day after initiation of the trial regimen in patients with uncomplicated influenza. Evidence for the development of decreased susceptibility to baloxavir after treatment was also observed.

Editorial from NEJM.


Coronary CT Angiography and 5-Year Risk of Myocardial Infarction (3873)
SCOT-HEART Investigators NEJM 379:924 09-06-2018

BACKGROUND: Although coronary computed tomographic angiography (CTA) improves diagnostic certainty in the assessment of patients with stable chest pain, its effect on 5-year clinical outcomes is unknown.

METHODS: In an open-label, multicenter, parallel-group trial, we randomly assigned 4146 patients with stable chest pain who had been referred to a cardiology clinic for evaluation to standard care plus CTA (2073 patients) or to standard care alone (2073 patients). Investigations, treatments, and clinical outcomes were assessed over 3 to 7 years of follow-up. The primary end point was death from coronary heart disease or nonfatal myocardial infarction at 5 years.

RESULTS: The median duration of follow-up was 4.8 years, which yielded 20,254 patient-years of follow-up. The 5-year rate of the primary end point was lower in the CTA group than in the standard-care group (2.3% [48 patients] vs. 3.9% [81 patients]; hazard ratio, 0.59; 95% confidence interval [CI], 0.41 to 0.84; P=0.004). Although the rates of invasive coronary angiography and coronary revascularization were higher in the CTA group than in the standard-care group in the first few months of follow-up, overall rates were similar at 5 years: invasive coronary angiography was performed in 491 patients in the CTA group and in 502 patients in the standard-care group (hazard ratio, 1.00; 95% CI, 0.88 to 1.13), and coronary revascularization was performed in 279 patients in the CTA group and in 267 in the standard-care group (hazard ratio, 1.07; 95% CI, 0.91 to 1.27). However, more preventive therapies were initiated in patients in the CTA group (odds ratio, 1.40; 95% CI, 1.19 to 1.65), as were more antianginal therapies (odds ratio, 1.27; 95% CI, 1.05 to 1.54). There were no significant between-group differences in the rates of cardiovascular or noncardiovascular deaths or deaths from any cause.

CONCLUSIONS: In this trial, the use of CTA in addition to standard care in patients with stable chest pain resulted in a significantly lower rate of death from coronary heart disease or nonfatal myocardial infarction at 5 years than standard care alone, without resulting in a significantly higher rate of coronary angiography or coronary revascularization.

Editorial


Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): A randomised, double-blind, placebo-controlled trial (3874)
Gaziano JM et al Lancet 08-26-2018

The effectiveness of aspirin for primary prevention of adverse cardiovascular (CV) events in contemporary patient populations remains unsettled. In the ARRIVE trial (funded by Bayer), 12,546 patients with no history of CV disease who were deemed to be at moderate risk were randomized to receive daily aspirin (100 mg) or placebo. Inclusion criteria were age 55 or older plus two to four risk factors for men, and age 60 or older plus three or more risk factors for women. Patients with diabetes or previous gastroduodenal ulceration or gastrointestinal bleeding were excluded. At baseline, 75% of participants were taking antihypertensive drugs, and 43% were taking statins.

During median follow-up of 5 years, the incidence of the primary endpoint (CV-related death, myocardial infarction, unstable angina, stroke, or transient ischemic event) was similar in the aspirin and placebo groups (4.3% and 4.5%; P=0.6), with no significant difference in time to first event and no differences for individual components of the primary endpoint. No subgroup (according to sex, age, smoking status, body-mass index [BMI], or baseline calculated 10-year risk) clearly benefited from aspirin. Gastrointestinal bleeding occurred more frequently with aspirin than with placebo (1.0% vs. 0.5%; P=0.0007), but only a few bleeding events in each group were "severe."

Comment: This primary prevention study, conducted mainly in the U.K., Germany, and Poland, should influence practice: Aspirin did not add incremental benefit for moderate-risk, nondiabetic patients, many of whom were receiving treatment for hypertension and hyperlipidemia; results of a 2014 Japanese trial were similar (NEJM JW Gen Med Dec 15 2014 and JAMA 2014; 312:2510). Although a recent meta-analysis showed that low-dose aspirin was effective only in nonobese patients (NEJM JW Gen Med Aug 15 2018 and Lancet 2018; 392:387), this study's low dose (100 mg) showed no significant benefit in a subgroup with BMI <25 kg/m2. Finally, in a recent 7-year primary prevention trial conducted in diabetic patients, aspirin prevented one vascular event but caused one serious hemorrhage for every 100 treated patients (NEJM JW Cardiol Oct 2018 and N Engl J Med 2018 Aug 26; [e-pub]).


The ASCEND Study Collaborative Group. Effects of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med 2018 Aug 26

The utility of aspirin for the primary prevention of cardiovascular disease in patients with diabetes is not known. Diabetes confers cardiovascular risk for many people, and aspirin has the potential to reduce that risk, but some people speculate that diabetes may reduce the antiplatelet effects of aspirin.

Investigators in the ASCEND trial (which also included a trial of n-3 fatty acids, reported separately; NEJM JW Cardiol Aug 26 2018; [e-pub]) randomized 15,480 people with diabetes, but without known cardiovascular disease, to 100 mg daily of aspirin or placebo (NCT00135226). The primary efficacy outcome was the first serious vascular event (nonfatal myocardial infarction or stroke, transient ischemic attack, or death from any vascular cause), and the primary safety outcome was the first major bleeding event.

During a mean follow-up of 7.4 years, the incidence of serious vascular events was significantly lower in the aspirin group than the placebo group (8.5% vs. 9.6%; rate ratio [RR], 0.88), but the incidence of major bleeding was significantly higher (4.1% vs. 3.2%; RR, 1.29); most of the bleeding events were gastrointestinal. The efficacy difference was seen mainly in the first 5 years. The findings were consistent across subgroups. There was no significant benefit of aspirin on death from all vascular causes, and no association with cancer.

Comment: This well-done trial shows the benefit and harm of aspirin for primary prevention in patients with diabetes: For every 100 people treated with aspirin, there is about 1 vascular event averted and 1 major bleed caused. The decision about whether these people would want to take aspirin might depend on how they weigh these respective outcomes - and, perhaps, their absolute risk for these outcomes using any of the traditional risk prediction tools.


Editorial by Allan Brett, MD, in Journal Watch, 10/1/18

The scene is all too familiar in primary care practice. Aspirin is on the medication list of a new patient with well-controlled hypertension and hyperlipidemia and no history of clinically evident cardiovascular (CV) disease. You ask how he came to be taking aspirin, and he replies, "I started doing this on my own. Isn't aspirin supposed to prevent heart attacks and strokes?" Or, maybe you don't even ask - you just tacitly endorse the aspirin use. Two new studies, published in August 2018 and supported by Bayer, might help us navigate some of these cases.

In the first trial (ARRIVE; NEJM JW Gen Med Oct 1 2018 and Lancet 2018 Aug 26; [e-pub]), about 12,000 nondiabetic patients were randomized to 100 mg of aspirin or placebo daily. Enrolled men were 55 or older and had ≥2 CV risk factors; enrolled women were 60 or older and had ≥3 CV risk factors. During average follow-up of 5 years, aspirin conferred no CV benefit: The incidence of a composite endpoint that included myocardial infarction (MI) and stroke was about 4% in both groups. Gastrointestinal bleeding was slightly, but statistically significantly, more common with aspirin (1% vs. 0.5%; P=0.0007).

In the second trial (ASCEND; NEJM JW Gen Med Oct 1 2018 and N Engl J Med 2018 Aug 26; [e-pub]), 15,000 middle-aged or older diabetic patients were randomized to daily aspirin (100 mg) or placebo. During average follow-up of ≈7 years, the incidence of serious vascular events was 1 percentage point lower in the aspirin group than in the placebo group (8.5% vs. 9.6%; P=0.01), but the incidence of major bleeding events was 1 percentage point higher with aspirin (4.1% vs. 3.2%; P=0.003).

In sum, among nondiabetic patients with CV risk factors, aspirin conferred no benefit and was associated with slight harm. Among diabetic patients, the tradeoff between small probabilities of benefit and harm was a close call. Notably, a large proportion of patients in both studies were taking statins and antihypertensive drugs, and only a small proportion were current smokers. Thus, one could reasonably conclude that these studies examined the incremental benefit of aspirin, added to other standard preventive interventions.

What did the U.S. Preventive Services Task Force (USPSTF) say about primary prevention with aspirin in its 2016 guideline (NEJM JW Gastroenterol Sep 2016 and Ann Intern Med 2016; 164:836)? Based on data from 11 randomized trials published between 1989 and 2014, the USPSTF recommends low-dose aspirin for adults (age range, 50-59) whose 10-year CV risk exceeded 10% and who are not at excess risk for bleeding. For people in their 60s, the USPSTF judges the benefits and harms as too closely balanced to merit a decisive recommendation and found that evidence was inadequate to address younger or older age groups. The USPSTF recommends the American College of Cardiology (ACC) calculator for estimating baseline CV risk, and the guideline provides a table for estimating life-years gained per 10,000 people taking aspirin (stratified by age and CV risk). However, the ACC calculator's accuracy is controversial (NEJM JW Gen Med Apr 15 2015 and Ann Intern Med 2015; 162:266), and the aforementioned table incorporates decision analytic modeling that might not reflect the incremental benefit of aspirin in contemporary patients who already are addressing CV risk through pharmacologic and lifestyle measures.

At least two other sources of uncertainty merit attention. First, there is growing interest in prophylactic aspirin to prevent colorectal cancer - a projected benefit that was incorporated into the USPSTF recommendation. Aspirin did not lower rates of colorectal cancer in either ASCEND or ARRIVE, but the duration of these studies might have been too short to demonstrate lower cancer incidence. Second, a recently published meta-analysis suggested that higher-dose aspirin (e.g., ≥325 mg) might be necessary to confer CV benefit in overweight people; however, because higher-dose aspirin has been associated with higher risk for serious bleeding, tradeoffs remain uncertain (NEJM JW Gen Med Aug 15 2018 and Lancet 2018; 392:387).

Wrap-Up: In my view, the new studies should push the pendulum away from aspirin prophylaxis for primary prevention - at least in moderate-risk patients. Differences between benefits and harms are likely to be razor thin, and balancing one adverse CV event against one bleeding event is not straightforward. For example, a fatal MI is more lethal than a minimally symptomatic gastrointestinal bleed, whereas some bleeding events (e.g., severe intracranial hemorrhage) are more lethal than some ischemic CV events (e.g., transient ischemic attack). Prospectively, we can't predict which of those outcomes would apply to any given patient.

As it happens, several days after ASCEND was published, a 50-year-old man with type 2 diabetes and hyperlipidemia (treated with insulin, metformin, and atorvastatin) came in for a routine visit. Aspirin was also on his medication list, but in previous visits, I had regarded it with benign neglect. I pulled up the ASCEND paper online, we discussed the results together, and he made an informed decision to discontinue aspirin. If he had deferred the decision to me ("Dr. Brett, I'll do whatever you think is best"), I would have made the same call.


Standardizing Your Approach to Dizziness and Vertigo (3875)
Wu et al JFP 67:490 01-01-2018

Provides a nice algorithm for the work-up of "dizziness". This is a complaint that often has no clear etiology in my experience.

Full article


Consider These Exercises for Chronic Musculoskeletal Conditions (3876)
Carek et al JFP 67:535 09-01-2018

Full article


Effect of aspirin on cardiovascular events and bleeding in the healthy elderly (3877)
McNeil JJ et al NEJM 09-16-2018

In two recent primary prevention studies - one conducted in nondiabetic patients with cardiovascular risk factors and the other in type 2 diabetic patients - aspirin raised risk for serious bleeding while conferring no or minimal cardiovascular (CV) benefit (NEJM JW Gen Med Oct 1 2018 and Lancet 2018 Aug 26; [e-pub]; NEJM JW Gen Med Oct 1 2018 and N Engl J Med 2018 Aug 26; [e-pub]). Now, in a third study (ASPREE) researchers have examined preventive aspirin use in "healthy elderly" community-dwelling people in the U.S. and Australia. The main enrollment criterion was age (≥70 for whites; ≥65 for blacks and Hispanics). People with known CV disease, substantial cognitive or physical disability, or high risk for bleeding were excluded, but most participants had one or more CV risk factors.

About 19,000 people (median age, 74) were randomized to receive aspirin (100 mg) or placebo daily. During median follow-up of 4.7 years, the following outcomes (published in three separate papers) were noted:

Comment: This trial further strengthens the case against use of aspirin for primary CV prevention. Unlike participants in previous studies, participants in this one were selected solely based on older age, and the primary endpoint included functional outcomes that are important to most patients - freedom from cognitive and physical disability. The reason for excess cancer mortality in aspirin recipients is unclear, but gastrointestinal cancers were particularly represented among the excess.

McNeil JJ et al. Effect of aspirin on cardiovascular events and bleeding in the healthy elderly. N Engl J Med 2018 Sep 16

McNeil JJ et al. Effect of aspirin on disability-free survival in the healthy elderly. N Engl J Med 2018 Sep 16

McNeil JJ et al. Effect of aspirin on all-cause mortality in the healthy elderly. N Engl J Med 2018 Sep 16


Effectiveness of lumbar facet joint blocks and predictive value before radiofrequency denervation: The Facet Treatment Study (FACTS), a randomized, controlled clinical trial (3878)
Cohen SP et al Anesthesiology 129:517 09-01-2018

For patients with chronic low back pain, lumbar facet blocks sometimes are used diagnostically (to predict response to a more definitive procedure, radiofrequency denervation) and sometimes are used therapeutically. Two types of lumbar facet blocks are injections of local anesthetic and steroid into facet joints (intra-articular injection) and injections into the area of the nerves supplying facet joints (medial branch block).

In this complicated study, 229 patients with chronic low back pain, but without spinal stenosis or neurological findings, were randomized to receive intra-articular facet injections or medial branch blocks (both with bupivacaine plus steroid) or saline placebo. Patients in either active-treatment group were significantly more likely to experience immediate pain relief than were placebo recipients (≈55% vs. 30%); however, at 1 month, improvement in pain was minimal in all three groups. At that point, patients in active-treatment groups who had experienced immediate response to injection underwent radiofrequency denervation; all placebo recipients also were offered radiofrequency denervation. Three months later, patients who underwent radiofrequency ablation because they were immediate responders to facet or medial branch injections were twice as likely as placebo recipients to report significant pain relief (≈50% vs. 25%).

Comment: This study suggests that facet joint or medial branch injections have some diagnostic value as predictors of short-term response to radiofrequency denervation, but they have little therapeutic value themselves. Note, however, that the overall effectiveness of radiofrequency denervation was challenged recently: In a randomized trial, this procedure had no value when added to an exercise program (NEJM JW Gen Med Aug 15 2017 and JAMA 2017; 318:68).


Association of use of omega-3 polyunsaturated fatty acids with changes in severity of anxiety symptoms: A systematic review and meta-analysis (3879)
Su K-P et al JAMA Netw Open 1:e182327 09-14-2018

Dietary supplements containing ω-3 polyunsaturated fatty acids (PUFAs) - both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) - are purported to alleviate anxiety symptoms. In this meta-analysis, researchers identified 19 randomized trials (16 placebo controlled; 2240 total patients; mean patient age, 42) in which benefits of ω-3 PUFA supplements (mean dosage, ≈1600 mg/day) were evaluated in a wide array of anxiety diagnoses and conditions.

Findings of the meta-analysis included the following:

Comment: These findings give clinicians some guidance when patients ask whether ω-3 PUFA supplements are useful for diagnosed anxiety. However, this benefit is modest, and other proposed benefits, particularly for preventing cardiovascular disease, are unproven.


Association of mortality and acute aortic events with ascending aortic aneurysm: A systematic review and meta-analysis (3880)
Guo MH et al AMA Netw Open 1:e181281 08-24-2018

The official guideline of the American College of Cardiology and American Heart Association (NEJM JW Cardiol Jun 2014 and J Am Coll Cardiol 2014; 63:2438) recommends ascending aortic aneurysm (AsAA) repair at a diameter of 55 mm for appropriate surgical candidates. However, expert opinion and the belief of many surgeons is that repair at a diameter as small as 45 mm is reasonable because of declining surgical mortality. To assess the natural history of these aneurysms, researchers conducted a meta-analysis of 20 observational studies of small AsAAs (total of 8800 patients; mean age, 58; 76% men; mean AsAA diameter, 43 mm). Studies were eliminated if they included patients with descending aortic or combined aneurysms, genetic-related aneurysms, replaced bicuspid aortic valves, or patient age <16.

During mean follow-up of 3.6 years, the annualized growth rate was 0.61 mm. Annualized mortality was 1.99%, and incidence of the composite outcome (i.e., all-cause mortality, aortic dissection, and aortic rupture) was 2.16%. About 14% of patients underwent elective repair during a median 4.2 years.

Comment: Once patients know they have aneurysms, they often feel an inexorable push toward repair given the sometimes catastrophic consequences of rupture. However, these results can inform decision making about elective AsAA repair: Annualized rates of both growth and complications are low for AsAAs smaller than 50 mm in diameter. We have no good answer to this dilemma, but patients should be aware of the arguments for both surgery and watchful waiting.


Management of Chronic Wounds - 2018 (3881)
Jones et al JAMA 320:1481 10-09-2018

Full article


Here are the last 10 additions to the PBrain by date


Management of Chronic Wounds - 2018 (3881)
Jones et al JAMA 320:1481 10-09-2018

Full article


Effect of aspirin on cardiovascular events and bleeding in the healthy elderly (3877)
McNeil JJ et al NEJM 09-16-2018

In two recent primary prevention studies - one conducted in nondiabetic patients with cardiovascular risk factors and the other in type 2 diabetic patients - aspirin raised risk for serious bleeding while conferring no or minimal cardiovascular (CV) benefit (NEJM JW Gen Med Oct 1 2018 and Lancet 2018 Aug 26; [e-pub]; NEJM JW Gen Med Oct 1 2018 and N Engl J Med 2018 Aug 26; [e-pub]). Now, in a third study (ASPREE) researchers have examined preventive aspirin use in "healthy elderly" community-dwelling people in the U.S. and Australia. The main enrollment criterion was age (≥70 for whites; ≥65 for blacks and Hispanics). People with known CV disease, substantial cognitive or physical disability, or high risk for bleeding were excluded, but most participants had one or more CV risk factors.

About 19,000 people (median age, 74) were randomized to receive aspirin (100 mg) or placebo daily. During median follow-up of 4.7 years, the following outcomes (published in three separate papers) were noted:

Comment: This trial further strengthens the case against use of aspirin for primary CV prevention. Unlike participants in previous studies, participants in this one were selected solely based on older age, and the primary endpoint included functional outcomes that are important to most patients - freedom from cognitive and physical disability. The reason for excess cancer mortality in aspirin recipients is unclear, but gastrointestinal cancers were particularly represented among the excess.

McNeil JJ et al. Effect of aspirin on cardiovascular events and bleeding in the healthy elderly. N Engl J Med 2018 Sep 16

McNeil JJ et al. Effect of aspirin on disability-free survival in the healthy elderly. N Engl J Med 2018 Sep 16

McNeil JJ et al. Effect of aspirin on all-cause mortality in the healthy elderly. N Engl J Med 2018 Sep 16


Association of use of omega-3 polyunsaturated fatty acids with changes in severity of anxiety symptoms: A systematic review and meta-analysis (3879)
Su K-P et al JAMA Netw Open 1:e182327 09-14-2018

Dietary supplements containing ω-3 polyunsaturated fatty acids (PUFAs) - both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) - are purported to alleviate anxiety symptoms. In this meta-analysis, researchers identified 19 randomized trials (16 placebo controlled; 2240 total patients; mean patient age, 42) in which benefits of ω-3 PUFA supplements (mean dosage, ≈1600 mg/day) were evaluated in a wide array of anxiety diagnoses and conditions.

Findings of the meta-analysis included the following:

Comment: These findings give clinicians some guidance when patients ask whether ω-3 PUFA supplements are useful for diagnosed anxiety. However, this benefit is modest, and other proposed benefits, particularly for preventing cardiovascular disease, are unproven.


Primary Hyperparathyroidism (3870)
Insogna NEJM 379:1050 09-13-2018

Full article


Aspirin-Exacerbated Respiratory Disease (3871)
White et al NEJM 379:1060 09-13-2018

Full article


Management of Groin Hernias in Adults - 2018 (3868)
Montgomery et al JAMA 320:1029 09-11-2018

Full article


Diagnosis and Treatment of Clostridium difficile Infection (3869)
Gupta et al JAMA 320:1031 09-11-2018

Metronidazole is no longer the initial drug of choice. Start with vancomycin or fidaxomicin.

Full article


Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents (3872)
Hayden et al NEJM 379:913 09-06-2018

BACKGROUND: Baloxavir marboxil is a selective inhibitor of influenza cap-dependent endonuclease. It has shown therapeutic activity in preclinical models of influenza A and B virus infections, including strains resistant to current antiviral agents.

METHODS: We conducted two randomized, double-blind, controlled trials involving otherwise healthy outpatients with acute uncomplicated influenza. After a dose-ranging (10 to 40 mg) placebo-controlled trial, we undertook a placebo- and oseltamivir-controlled trial of single, weight-based doses of baloxavir (40 or 80 mg) in patients 12 to 64 years of age during the 2016-2017 season. The dose of oseltamivir was 75 mg twice daily for 5 days. The primary efficacy end point was the time to alleviation of influenza symptoms in the intention-to-treat infected population.

RESULTS: In the phase 2 trial, the median time to alleviation of influenza symptoms was 23.4 to 28.2 hours shorter in the baloxavir groups than in the placebo group (P<0.05). In the phase 3 trial, the intention-to-treat infected population included 1064 patients; 84.8 to 88.1% of patients in each group had influenza A(H3N2) infection. The median time to alleviation of symptoms was 53.7 hours (95% confidence interval [CI], 49.5 to 58.5) with baloxavir, as compared with 80.2 hours (95% CI, 72.6 to 87.1) with placebo (P<0.001). The time to alleviation of symptoms was similar with baloxavir and oseltamivir. Baloxavir was associated with greater reductions in viral load 1 day after initiation of the regimen than placebo or oseltamivir. Adverse events were reported in 20.7% of baloxavir recipients, 24.6% of placebo recipients, and 24.8% of oseltamivir recipients. The emergence of polymerase acidic protein variants with I38T/M/F substitutions conferring reduced susceptibility to baloxavir occurred in 2.2% and 9.7% of baloxavir recipients in the phase 2 trial and phase 3 trial, respectively.

CONCLUSIONS: Single-dose baloxavir was without evident safety concerns, was superior to placebo in alleviating influenza symptoms, and was superior to both oseltamivir and placebo in reducing the viral load 1 day after initiation of the trial regimen in patients with uncomplicated influenza. Evidence for the development of decreased susceptibility to baloxavir after treatment was also observed.

Editorial from NEJM.


Coronary CT Angiography and 5-Year Risk of Myocardial Infarction (3873)
SCOT-HEART Investigators NEJM 379:924 09-06-2018

BACKGROUND: Although coronary computed tomographic angiography (CTA) improves diagnostic certainty in the assessment of patients with stable chest pain, its effect on 5-year clinical outcomes is unknown.

METHODS: In an open-label, multicenter, parallel-group trial, we randomly assigned 4146 patients with stable chest pain who had been referred to a cardiology clinic for evaluation to standard care plus CTA (2073 patients) or to standard care alone (2073 patients). Investigations, treatments, and clinical outcomes were assessed over 3 to 7 years of follow-up. The primary end point was death from coronary heart disease or nonfatal myocardial infarction at 5 years.

RESULTS: The median duration of follow-up was 4.8 years, which yielded 20,254 patient-years of follow-up. The 5-year rate of the primary end point was lower in the CTA group than in the standard-care group (2.3% [48 patients] vs. 3.9% [81 patients]; hazard ratio, 0.59; 95% confidence interval [CI], 0.41 to 0.84; P=0.004). Although the rates of invasive coronary angiography and coronary revascularization were higher in the CTA group than in the standard-care group in the first few months of follow-up, overall rates were similar at 5 years: invasive coronary angiography was performed in 491 patients in the CTA group and in 502 patients in the standard-care group (hazard ratio, 1.00; 95% CI, 0.88 to 1.13), and coronary revascularization was performed in 279 patients in the CTA group and in 267 in the standard-care group (hazard ratio, 1.07; 95% CI, 0.91 to 1.27). However, more preventive therapies were initiated in patients in the CTA group (odds ratio, 1.40; 95% CI, 1.19 to 1.65), as were more antianginal therapies (odds ratio, 1.27; 95% CI, 1.05 to 1.54). There were no significant between-group differences in the rates of cardiovascular or noncardiovascular deaths or deaths from any cause.

CONCLUSIONS: In this trial, the use of CTA in addition to standard care in patients with stable chest pain resulted in a significantly lower rate of death from coronary heart disease or nonfatal myocardial infarction at 5 years than standard care alone, without resulting in a significantly higher rate of coronary angiography or coronary revascularization.

Editorial


Consider These Exercises for Chronic Musculoskeletal Conditions (3876)
Carek et al JFP 67:535 09-01-2018

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