Here are the last 20 additions to the PBrain (total entries as of now = 3909)


Association of cardiorespiratory fitness with long-term mortality among adults undergoing exercise treadmill testing (3890)
Mandsager K et al JAMA Netw Open 1:e183605 10-19-2018

The generally accepted inverse relation between cardiovascular fitness and adverse cardiovascular events and all-cause mortality has been challenged recently by reports that suggest a possible U-shaped dose-response association, in which extreme exercise and fitness is associated with excess mortality risk due to myocardial fibrosis, atrial fibrillation, and coronary artery calcification. This retrospective cohort study overcame the limitations of many studies in which self-reported exercise patterns were used.

Cleveland Clinic researchers identified 122,000 patients (mean age, 53) who were referred for symptom-limited exercise treadmill testing. According to peak achieved metabolic equivalents (METs; similar to maximal oxygen uptake), patients were stratified into five cardiorespiratory-fitness (CRF) groups: low, below average, above average, high, and elite. During median follow-up of 8 years, researchers noted an inverse relation between level of CRF and all-cause mortality across all performance levels and through age >70. For example, mortality hazard ratios (HRs) were 1.3 for high vs. elite CRF, 1.8 for above-average vs. elite CRF, and 1.4 for below-average vs. above-average CRF. Hazard ratios were adjusted for traditional cardiovascular risk factors.

Comment: These data are reassuring that, with regard to mortality, one can exercise safely at an "elite" level throughout life. But those who aren't interested in achieving (or able to achieve) elite levels still will derive mortality benefits when they improve their cardiorespiratory fitness.


Effect of increased daily water intake in premenopausal women with recurrent urinary tract infections: A randomized clinical trial (3891)
Hooton TM et al JAMA Intern Med 10-01-2018

Recurrent urinary tract infection (UTI) in premenopausal women causes substantial morbidity and raises concerns about antimicrobial resistance associated with repeated courses of antibiotics. To test whether additional hydration lowers risk for recurrent UTI, investigators in Bulgaria randomized 140 women with ≥3 episodes of cystitis during the past year who reported drinking <1.5 L fluid daily to receive an additional 1.5 L of water daily (water group) or no additional fluid (control group).

At 1-year follow up, mean number of cystitis episodes was 1.7 in the water group versus 3.2 in the control group and mean number of antibiotic courses was 1.9 in the water group versus 3.6 in the control group (P<0.001 for both comparisons).

Comment: This study offers rigorous proof of a simple idea that drinking more water - when preexisting intake is less than recommended - substantially lowers risk for recurrent UTI. Given that frequently recurrent UTI represents a vexing problem for affected women, it's likely that these findings can be translated into a strong recommendation to increase fluid intake. However, whether drinking more fluid can also benefit women who already have adequate intake remains unknown.


Personalized gut mucosal colonization resistance to empiric probiotics is associated with unique host and microbiome features (3892)
Zmora N et al Cell 174:1388. 09-06-2018

Despite growing evidence that the gut microbiome affects human health, knowing how to exploit that knowledge to improve health is unclear. Probiotics, which are available over the counter, are used widely to reestablish "healthy" gut flora. But do they? In two new reports, researchers examine the consequences of using probiotics.

In one report, endoscopic studies showed that bacterial flora of stool are a reasonable (although imperfect) reflection of flora at mucosal surfaces throughout the gut. Controlled studies of healthy humans pre- and postadministration of probiotics with 11 bacterial strains (or placebo) showed that, although the bacterial strains in the probiotics were shed in stool of all participants, this shedding was not a reliable indicator of strain colonization in the lower gut mucosa. Most importantly, colonization of the gut mucosa was quite different from one person to the next. Indeed, some individuals were resistant to durable colonization by probiotic bacteria, whereas others were not. And some probiotic strains were more likely to produce durable colonization than others.

In another report, use of antibiotics in healthy volunteers disrupted the gut microbiome and enhanced the colonization of probiotic bacterial strains. Use of probiotics after antibiotic treatment induced delayed and incomplete reconstitution of the preantibiotic gut microbiome, compared with spontaneous recovery without probiotics. Conversely, autologous fecal microbiome transplantation achieved prompt and complete recovery of the baseline microbiome.

Comment: These studies indicate that effects of probiotics likely will be different from one person to the next. In addition, probiotics might be ineffective and possibly counterproductive in restoring the baseline gut microbiome after it has been altered by antibiotic treatment.

Suez J et al. Post-antibiotic gut mucosal microbiome reconstitution is impaired by probiotics and improved by autologous FMT. Cell 2018 Sep 6; 174:1406.


Treatment of Lower Extremity Superficial Thrombophlebitis (3893)
Di Nisio et al JAMA 320:2367 12-11-2018

Clinical Question: Which treatments for lower extremity superficial thrombophlebitis (ST) are associated with lower rates of venous thromboembolic events (VTEs) vs placebo?

Bottom Line A dose of 2.5 mg of fondaparinux administered subcutaneously once daily for 45 days is associated with fewer cases of symptomatic VTE without an increase in major bleeding vs placebo. Low-molecular-weight heparin (LMWH) and nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with lower rates of ST extension or recurrence vs placebo, but data regarding symptomatic VTE remain inconclusive. Oral rivaroxaban requires further evaluation.

Full article


Lung Nodules Summary (3894)
Kney Various 12-04-2018

Incidental Pulmonary Nodules Detected on CT Images from JAMA 12/4/18 (JAMA Guidelines).

Fleischner


Radical Prostatectomy or Watchful Waiting in Prostate Cancer: 29-Year Follow-up (3895)
Bill-Axelson et al NEJM 379:2319 12-13-2018

METHODS: We randomly assigned 695 men with localized prostate cancer to watchful waiting or radical prostatectomy from October 1989 through February 1999 and collected follow-up data through 2017. Cumulative incidence and relative risks with 95% confidence intervals for death from any cause, death from prostate cancer, and metastasis were estimated in intention-to-treat and per-protocol analyses, and numbers of years of life gained were estimated. We evaluated the prognostic value of histopathological measures with a Cox proportional-hazards model.

RESULTS: By December 31, 2017, a total of 261 of the 347 men in the radical-prostatectomy group and 292 of the 348 men in the watchful-waiting group had died; 71 deaths in the radical-prostatectomy group and 110 in the watchful-waiting group were due to prostate cancer (relative risk, 0.55; 95% confidence interval [CI], 0.41 to 0.74; P<0.001; absolute difference in risk, 11.7 percentage points; 95% CI, 5.2 to 18.2). The number needed to treat to avert one death from any cause was 8.4. At 23 years, a mean of 2.9 extra years of life were gained with radical prostatectomy. Among the men who underwent radical prostatectomy, extracapsular extension was associated with a risk of death from prostate cancer that was 5 times as high as that among men without extracapsular extension, and a Gleason score higher than 7 was associated with a risk that was 10 times as high as that with a score of 6 or lower (scores range from 2 to 10, with higher scores indicating more aggressive cancer).

CONCLUSIONS: Men with clinically detected, localized prostate cancer and a long life expectancy benefited from radical prostatectomy, with a mean of 2.9 years of life gained. A high Gleason score and the presence of extracapsular extension in the radical prostatectomy specimens were highly predictive of death from prostate cancer. (Funded by the Swedish Cancer Society and others.)


Baloxavir marboxil for uncomplicated influenza in adults and adolescents (3896)
Hayden FG et al NEJM 379:913 09-06-2018

Baloxavir marboxil (Xofluza) was approved by the FDA on October 24, 2018, after expedited review, to treat acute uncomplicated influenza infection in patients 12 years of age and older. Approval was based primarily on two randomized, controlled, manufacturer-sponsored studies involving a total of 1836 patients, to whom medication was administered within 48 hours of flu symptom onset (NEJM JW Infect Dis Nov 2018 and N Engl J Med 2018; 379:913). Baloxavir was compared with placebo in one trial and with placebo or the neuraminidase inhibitor oseltamivir (given twice daily for 5 days) in the other trial. In both trials, self-reported symptom relief was earlier in the baloxavir group than in the placebo group (about 54 hours vs. 80 hours; relief with baloxavir was faster in younger than in older patients). Onset of symptom relief was similar with baloxavir versus oseltamivir. Few side effects (primarily gastrointestinal) occurred in any study group but were more common with oseltamivir than with baloxavir.

Viral load in respiratory secretions was lower at 24 hours with baloxavir than with oseltamivir or placebo, an effect that might correlate with decreased person-to-person transmission. However, even in this relatively small trial group, some mutation-based emergence of resistance to baloxavir was evident. Relative replication and transmissibility competence of the mutant viruses are unknown.

Comment: In considering the release of the first new anti-influenza drug in almost 20 years, it is worthwhile to recall that this is the hundredth anniversary of the 1918 influenza pandemic that resulted, over the subsequent 3 years, in about as many deaths as have resulted from AIDS in the 37 years it has been recognized. Previous to baloxavir, two drug classes were available for influenza treatment and prevention. The adamantanes (amantadine and rimantadine), discovered serendipitously, were effective against only type A influenza virus and acted via viral uncoating. Emergence of viral resistance during the 2005-2006 influenza season has rendered these drugs virtually useless. Inhibitors of viral neuraminidase, which facilitates separation of daughter viruses from the infected cell, are active against both types of flu viruses and can be used for prophylaxis as well as treatment. Baloxavir functions through inhibition of an endonuclease involved in viral RNA replication, so it should be effective against avian flu viruses that require this process, and there should be no cross-resistance with the other antivirals. The single-dose pill is 40 mg; two pills are suggested for those weighing >80 kg.

Given the known morbidity and mortality of influenza, there are reasons to be excited about the development and approval of this new anti-influenza drug. However, we have no data yet on its efficacy in severe or life-threatening influenza, or on how readily flu viruses will become resistant if the drug is widely used. The price of this drug, which appears pegged to the list price of a 10-pill regimen of oseltamivir, may prove an obstacle to ubiquitous use. Most important, annual vaccination is still the key to minimizing the morbidity and mortality of influenza.


Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia (3897)
Bhatt DL et al NEJM 11-10-2018

High triglyceride levels are associated with cardiovascular (CV) events, but triglyceride reduction has not been shown to lower risk for such events. REDUCE-IT (NCT01492361) is an international, industry-sponsored study of icosapent ethyl (a highly purified eicosapentaenoic acid ethyl ester) in patients with established CV disease or diabetes in the setting of statin therapy. A total of 8179 eligible participants (fasting triglycerides, 135-499 mg/dL; median baseline age, 64; median LDL, 75 mg/dL) were randomized to icosapent ethyl (2 g twice daily) or placebo. The primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina.

From baseline to 1 year, serum triglycerides fell by a median 18.3% (icosapent ethyl) and rose by a median 2.2% (placebo). During a median follow-up of 4.9 years, 1606 primary endpoint events occurred. Compared with placebo, icosapent ethyl resulted in a 25% relative risk reduction and a 4.8% absolute risk difference; the number needed to treat was 21. The benefit was seen across all the components of the primary endpoint, with similar effect sizes. Although adverse event rates were generally low, atrial fibrillation, peripheral edema, and serious bleeding were more common with icosapent ethyl.

Comment: For clinicians seeking to reduce residual CV risk after statin administration, these results may be practice changing. Unlike other triglyceride-lowering agents (niacin, fibrates, and other omega-3 fatty acids) that have failed to show CV benefits, high-dose icosapent ethyl appears to have impressive efficacy. These results confirm that the mechanism of lipid lowering matters and cannot be generalized, even among similar agents. More research is needed to identify the mechanism of action responsible for this observed benefit (as well as the slightly higher risk for certain adverse events). For now, I will recommend checking triglycerides for my patients at elevated cardiovascular risk and consider prescribing icosapent ethyl. More studies are needed to determine if the observed benefit extends to other omega-3 fatty acids and to lower-risk patients.


Reduced salt intake for heart failure: A systematic review (3898)
Mahtani KR et al JAMA Intern Med 11-05-2018

The idea of sodium restriction for patients with heart failure is well ingrained in teaching and practice. And yet, compliance with this recommendation is low, and the evidence underlying it is weak. To better characterize the literature addressing interventions reducing dietary salt in adults with heart failure, investigators in the U.K. conducted a systematic review, identifying nine relevant studies (2 with inpatients and 7 with outpatients) involving 479 people.

None of the studies included more than 100 participants. None had a low risk of bias across all seven domains examined. None of the studies provided sufficient data on cardiovascular mortality. Many studies were missing key information, thus precluding meta-analysis because of a lack of suitable data. The investigators concluded that they found no robust high-quality evidence as to the value of low-salt diets in patients with heart failure.

Comment: This systematic review illuminates the paucity of evidence supporting the practice of low-sodium diets for people with heart failure. In response to this study, the editorialist states appropriately, "The first step is not a call for more trials but a retreat from an unbridled and potentially harmful insistence on rigorous sodium restriction in those with symptomatic heart failure." I could not agree more.


Alirocumab and cardiovascular outcomes after acute coronary syndrome (3899)
Schwartz GG et al NEJM 11-07-2018

Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors reduce the risk for ischemic cardiovascular events in patients with stable atherosclerotic coronary artery disease and elevated atherogenic lipoproteins despite statin therapy. In the industry-sponsored, randomized, placebo-controlled, international ODYSSEY Outcomes trial (1315 sites in 57 countries; NCT01663402), researchers examined whether the FDA-approved PCSK9 inhibitor alirocumab could reduce ischemic cardiovascular events in patients on high-intensity statin therapy who had elevated atherogenic lipoproteins and a history of acute coronary syndrome (ACS; occurring >1 month but <12 months before enrollment).

Most of the 18,924 participants had an LDL ≥70 mg/dL; median time from the ACS event to randomization was 2.6 months. Median follow-up was 2.8 years. Premature discontinuation occurred in 14.2% and 15.8% of the alirocumab and placebo groups, respectively. At baseline, the mean LDL was 92 mg/dL; at 4 months after randomization, it was 40 mg/dL in the alirocumab group and 93 mg/dL in the placebo group. The composite primary endpoint (death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, or unstable angina requiring hospitalization) occurred in 9.5% of the alirocumab group versus 11.1% of the placebo group (hazard ratio, 0.85); to avoid one event, 49 patients would need to be treated for 4 years). The greatest benefit was in patients with the highest baseline LDL. Deaths were less frequent with alirocumab than placebo (3.5% vs. 4.1%; HR, 0.85). Safety events were similar in the two groups.

Comment: The evidence for the benefit of PCSK9 inhibitors is growing stronger. The findings here are not unexpected but raise the question of whether more patients should be treated with these medications. Certainly, patients should know about the PCSK9 inhibitors as an option for secondary prevention if they meet the inclusion criteria of the published trials.


Rivaroxaban (Xarelto) plus Aspirin for Secondary Prevention of Cardiovascular Events (3900)
Med Ltr Med Ltr 60:196 12-03-2018

In one large randomized controlled trial, a low dose of the direct oral anticoagulant rivaroxaban (Xarelto) taken twice daily in addition to low-dose aspirin once daily was more effective than aspirin alone in preventing major cardiovascular events in patients with stable atherosclerotic vascular disease, but the combination caused significantly more major bleeding, mostly in the GI tract. Whether the benefits outweigh the drawbacks of taking two daily doses of an expensive second drug that is more likely to cause bleeding and to interact with other drugs is debatable.

Full article


Diagnosis and Management of NAFLD (3901)
Paul et al JAMA 320:2474 12-18-2018

Full article


Drugs for Cough (3902)
Med Ltr Med Ltr 60:206 12-17-2018

Full article


Migraine Headache Prophylaxis (3903)
Hein et al AFP 99:17 01-01-2019

Migraines impose significant health and financial burdens. Approximately 38% of patients with episodic migraines would benefit from preventive therapy, but less than 13% take prophylactic medications. Preventive medication therapy reduces migraine frequency, severity, and headache-related distress. Preventive therapy may also improve quality of life and prevent the progression to chronic migraines. Some indications for preventive therapy include four or more headaches a month, eight or more headache days a month, debilitating headaches, and medication-overuse headaches. Identifying and managing environmental, dietary, and behavioral triggers are useful strategies for preventing migraines. First-line medications established as effective based on clinical evidence include divalproex, topiramate, metoprolol, propranolol, and timolol. Medications such as amitriptyline, venlafaxine, atenolol, and nadolol are probably effective but should be second-line therapy. There is limited evidence for nebivolol, bisoprolol, pindolol, carbamazepine, gabapentin, fluoxetine, nicardipine, verapamil, nimodipine, nifedipine, lisinopril, and candesartan. Acebutolol, oxcarbazepine, lamotrigine, and telmisartan are ineffective. Newer agents target calcitonin gene-related peptide pain transmission in the migraine pain pathway and have recently received approval from the U.S. Food and Drug Administration; however, more studies of long-term effectiveness and adverse effects are needed. The complementary treatments petasites, feverfew, magnesium, and riboflavin are probably effective. Nonpharmacologic therapies such as relaxation training, thermal biofeedback combined with relaxation training, electromyographic feedback, and cognitive behavior therapy also have good evidence to support their use in migraine prevention.

Full article


Urine Drug Tests: Ordering and Interpretation (3904)
Kale AFP 99:33 01-01-2019

Urine drug testing is an essential component of monitoring patients who are receiving long-term opioid therapy, and it has been suggested for patients receiving long-term benzodiazepine or stimulant therapy. Family physicians should be familiar with the characteristics and capabilities of screening and confirmatory drug tests. Immunoassays are used for initial screening and can give false-positive and false-negative results. All results are considered presumptive until confirmatory testing is performed. False-positive results have significant implications for a patient's pain treatment plan, and false-negative results can be a missed opportunity to detect misuse. Urine drug testing is an essential component of monitoring patients who are receiving long-term opioid therapy, and it has been suggested for patients receiving long-term benzodiazepine or stimulant therapy. Family physicians should be familiar with the characteristics and capabilities of screening and confirmatory drug tests. Immunoassays are qualitative tests used for initial screening of urine samples. They can give false-positive and false-negative results, so all results are considered presumptive until confirmatory testing is performed. Immunoassays for opioids may not detect commonly prescribed semisynthetic and synthetic opioids such as methadone and fentanyl; similarly, immunoassays for benzodiazepines may not detect alprazolam or clonazepam. Immunoassays can cross-react with other medications and give false-positive results, which have important implications for a patient's pain treatment plan. False-negative results can cause missed opportunities to detect misuse. Urine samples can be adulterated with other substances to mask positive results on urine drug testing. Family physicians must be familiar with these substances, the methods to detect them, and their effects on urine drug testing.

Full article


Cholesterol Management: 2018 Update (3905)
Grundy et al J Am Coll Cardiol 11-10-2018

Background and Objective: The 2013 ACC/AHA prevention guidelines shifted away from LDL targets and recommended moderate- or high-intensity statin therapy for patients based on risk profiles. The 2018 updated guideline reestablishes LDL goals, incorporates new evidence on nonstatin therapies, and addresses concerns about ASCVD risk overestimation for primary prevention.

Key Recommendations:

Comment: In many respects, the 2018 guideline supports the way most of us practice by considering risk-enhancing patient factors not in ASCVD risk equations to guide shared decision-making. The guideline also endorses the importance of achieving LDL targets for high-risk groups and provides a stepwise approach to adding nonstatin therapies. CAC testing can be considered for uncertain treatment decisions. It is reasonable to withhold drug therapy when CAC scores are 0 and to provide drug therapy when scores are ≥100. Scores between 1 and 99 are less useful for refining risk.


Effects of a low carbohydrate diet on energy expenditure during weight loss maintenance: Randomized trial (3906)
Ebbeling CB et al BMJ 363:k4583 11-14-2018

Many people who lose weight intentionally struggle to maintain their lower weight. In the carbohydrate-insulin model of obesity, a high glycemic load increases the blood insulin-to-glucagon ratio, which results in increased hunger, lower energy expenditure, and weight gain. To test this model, researchers examined the effects on total-energy (kcal/day) expenditure of three diets with different carbohydrate-to-fat ratios.

Researchers randomized 164 adults (body-mass index, ≥25 kg/m2) to high-, moderate-, or low-carbohydrate diets (60%, 40%, and 20% carbohydrates, respectively) with inverse proportions of fat (20%, 40%, and 60% fats, respectively). Diets had a fixed amount of protein (20%), and total energy intakes to maintain weight loss. After 20 weeks, intent-to-treat analysis showed higher total energy expenditure in the moderate- and low-carbohydrate groups (mean, 91 kcal/day and 209 kcal/day, respectively). The effect of the low-carb diet on improving total energy expenditure was even greater in the subgroup of people whose pre-weight loss insulin levels were in the highest tertile. Blood levels of ghrelin and leptin, hormones that promote weight gain, were significantly lower in the low-carb group.

Comment: In this trial, lower carbohydrate and higher fat intake, with stable protein and energy intake, resulted in higher energy expenditure during weight-loss maintenance. These results support the carbohydrate-insulin model and should be helpful when counseling patients who have lost weight intentionally and are struggling to keep it off.


Brain glial activation in fibromyalgia - A multi-site positron emission tomography investigation (3907)
Albrecht DS et al Brain Behav Immun 75:72 01-01-2019

A disorder, known as fibromyalgia, characterized by fatigue and pain, has long frustrated clinicians because conventional diagnostic testing reveals little evidence of objective pathology. In a new study from Boston and Stockholm, researchers used positron emission tomography (PET) to assess neuroinflammation in the brains of fibromyalgia patients.

The teams conducted PET scans in 31 fibromyalgia patients and 27 age- and sex-matched healthy controls. In fibromyalgia patients, the scans revealed widespread activation of glial cells (antigen-presenting cells) in the cortex, particularly in the frontal and parietal lobes. This glial activation was not seen in controls. Moreover, the degree of glial activation correlated with reported intensity of patients' fatigue: the greater the neuroinflammation, the greater the fatigue (although not the pain).

Comment: Previous research has shown elevated levels of proinflammatory cytokines in the cerebrospinal fluid of patients with fibromyalgia. Interestingly, PET also has identified neuroinflammation in patients with a clinically similar condition, chronic fatigue syndrome. The current study provides direct evidence of neuroinflammation and suggests that neuroinflammation is a target for therapy. Indeed, one agent - low-dose naltrexone - reduced glial activation in the brain and improved symptoms in small controlled studies of fibromyalgia patients. The current study indicates that smoldering and potentially treatable neuroinflammation is present in the brains of patients with fibromyalgia.


Decolonization to Reduce Postdischarge Infection Risk among MRSA Carriers (3908)
Huang et al NEJM 380:638 02-14-2019

METHODS: We conducted a multicenter, randomized, controlled trial of postdischarge hygiene education, as compared with education plus decolonization, in patients colonized with MRSA (carriers). Decolonization involved chlorhexidine mouthwash, baths or showers with chlorhexidine, and nasal mupirocin for 5 days twice per month for 6 months. Participants were followed for 1 year. The primary outcome was MRSA infection as defined according to Centers for Disease Control and Prevention (CDC) criteria. Secondary outcomes included MRSA infection determined on the basis of clinical judgment, infection from any cause, and infection-related hospitalization. All analyses were performed with the use of proportional-hazards models in the per-protocol population (all participants who underwent randomization, met the inclusion criteria, and survived beyond the recruitment hospitalization) and as-treated population (participants stratified according to adherence).

RESULTS: In the per-protocol population, MRSA infection occurred in 98 of 1063 participants (9.2%) in the education group and in 67 of 1058 (6.3%) in the decolonization group; 84.8% of the MRSA infections led to hospitalization. Infection from any cause occurred in 23.7% of the participants in the education group and 19.6% of those in the decolonization group; 85.8% of the infections led to hospitalization. The hazard of MRSA infection was significantly lower in the decolonization group than in the education group (hazard ratio, 0.70; 95% confidence interval [CI], 0.52 to 0.96; P=0.03; number needed to treat to prevent one infection, 30; 95% CI, 18 to 230); this lower hazard led to a lower risk of hospitalization due to MRSA infection (hazard ratio, 0.71; 95% CI, 0.51 to 0.99). The decolonization group had lower likelihoods of clinically judged infection from any cause (hazard ratio, 0.83; 95% CI, 0.70 to 0.99) and infection-related hospitalization (hazard ratio, 0.76; 95% CI, 0.62 to 0.93); treatment effects for secondary outcomes should be interpreted with caution owing to a lack of prespecified adjustment for multiple comparisons. In as-treated analyses, participants in the decolonization group who adhered fully to the regimen had 44% fewer MRSA infections than the education group (hazard ratio, 0.56; 95% CI, 0.36 to 0.86) and had 40% fewer infections from any cause (hazard ratio, 0.60; 95% CI, 0.46 to 0.78). Side effects (all mild) occurred in 4.2% of the participants.

CONCLUSIONS: Postdischarge MRSA decolonization with chlorhexidine and mupirocin led to a 30% lower risk of MRSA infection than education alone.


Qbrexza - A Glycopyrronium Cloth for Axillary Hyperhidrosis (3909)
Med Ltr Med Ltr 61:10 01-28-2019

DOSAGE, ADMINISTRATION, AND COST: Qbrexza is supplied in cartons of 30 pouches, each containing one single-use cloth premoistened with a 2.4% glycopyrronium solution. One cloth should be wiped across clean, dry, unbroken skin in the underarm area once every 24 hours; the same cloth can be used for both underarms. Patients should be instructed to avoid contact of glycopyrronium with the eyes and to wash their hands immediately after application. In the ATMOS trials, patients were permitted to use a nonmedicated deodorant after applying glycopyrronium. A 30-day supply of Qbrexza cloths costs $550.

CONCLUSION: Once-daily use of topical glycopyrronium 2.4% cloths (Qbrexza) reduced sweat production modestly in patients with primary axillary hyperhidrosis. The cloths are expensive and data on their long-term efficacy and safety are lacking. Aluminum-containing over-the-counter and prescription antiperspirants should be tried first. How topical glycopyrronium compares to oral anticholinergic drugs remains to be determined. Underarm injections of onabotulinumtoxinA (Botox) may be painful, but they are probably more cost-effective than Qbrexza.


Here are the last 10 additions to the PBrain by date


Decolonization to Reduce Postdischarge Infection Risk among MRSA Carriers (3908)
Huang et al NEJM 380:638 02-14-2019

METHODS: We conducted a multicenter, randomized, controlled trial of postdischarge hygiene education, as compared with education plus decolonization, in patients colonized with MRSA (carriers). Decolonization involved chlorhexidine mouthwash, baths or showers with chlorhexidine, and nasal mupirocin for 5 days twice per month for 6 months. Participants were followed for 1 year. The primary outcome was MRSA infection as defined according to Centers for Disease Control and Prevention (CDC) criteria. Secondary outcomes included MRSA infection determined on the basis of clinical judgment, infection from any cause, and infection-related hospitalization. All analyses were performed with the use of proportional-hazards models in the per-protocol population (all participants who underwent randomization, met the inclusion criteria, and survived beyond the recruitment hospitalization) and as-treated population (participants stratified according to adherence).

RESULTS: In the per-protocol population, MRSA infection occurred in 98 of 1063 participants (9.2%) in the education group and in 67 of 1058 (6.3%) in the decolonization group; 84.8% of the MRSA infections led to hospitalization. Infection from any cause occurred in 23.7% of the participants in the education group and 19.6% of those in the decolonization group; 85.8% of the infections led to hospitalization. The hazard of MRSA infection was significantly lower in the decolonization group than in the education group (hazard ratio, 0.70; 95% confidence interval [CI], 0.52 to 0.96; P=0.03; number needed to treat to prevent one infection, 30; 95% CI, 18 to 230); this lower hazard led to a lower risk of hospitalization due to MRSA infection (hazard ratio, 0.71; 95% CI, 0.51 to 0.99). The decolonization group had lower likelihoods of clinically judged infection from any cause (hazard ratio, 0.83; 95% CI, 0.70 to 0.99) and infection-related hospitalization (hazard ratio, 0.76; 95% CI, 0.62 to 0.93); treatment effects for secondary outcomes should be interpreted with caution owing to a lack of prespecified adjustment for multiple comparisons. In as-treated analyses, participants in the decolonization group who adhered fully to the regimen had 44% fewer MRSA infections than the education group (hazard ratio, 0.56; 95% CI, 0.36 to 0.86) and had 40% fewer infections from any cause (hazard ratio, 0.60; 95% CI, 0.46 to 0.78). Side effects (all mild) occurred in 4.2% of the participants.

CONCLUSIONS: Postdischarge MRSA decolonization with chlorhexidine and mupirocin led to a 30% lower risk of MRSA infection than education alone.


Qbrexza - A Glycopyrronium Cloth for Axillary Hyperhidrosis (3909)
Med Ltr Med Ltr 61:10 01-28-2019

DOSAGE, ADMINISTRATION, AND COST: Qbrexza is supplied in cartons of 30 pouches, each containing one single-use cloth premoistened with a 2.4% glycopyrronium solution. One cloth should be wiped across clean, dry, unbroken skin in the underarm area once every 24 hours; the same cloth can be used for both underarms. Patients should be instructed to avoid contact of glycopyrronium with the eyes and to wash their hands immediately after application. In the ATMOS trials, patients were permitted to use a nonmedicated deodorant after applying glycopyrronium. A 30-day supply of Qbrexza cloths costs $550.

CONCLUSION: Once-daily use of topical glycopyrronium 2.4% cloths (Qbrexza) reduced sweat production modestly in patients with primary axillary hyperhidrosis. The cloths are expensive and data on their long-term efficacy and safety are lacking. Aluminum-containing over-the-counter and prescription antiperspirants should be tried first. How topical glycopyrronium compares to oral anticholinergic drugs remains to be determined. Underarm injections of onabotulinumtoxinA (Botox) may be painful, but they are probably more cost-effective than Qbrexza.


Migraine Headache Prophylaxis (3903)
Hein et al AFP 99:17 01-01-2019

Migraines impose significant health and financial burdens. Approximately 38% of patients with episodic migraines would benefit from preventive therapy, but less than 13% take prophylactic medications. Preventive medication therapy reduces migraine frequency, severity, and headache-related distress. Preventive therapy may also improve quality of life and prevent the progression to chronic migraines. Some indications for preventive therapy include four or more headaches a month, eight or more headache days a month, debilitating headaches, and medication-overuse headaches. Identifying and managing environmental, dietary, and behavioral triggers are useful strategies for preventing migraines. First-line medications established as effective based on clinical evidence include divalproex, topiramate, metoprolol, propranolol, and timolol. Medications such as amitriptyline, venlafaxine, atenolol, and nadolol are probably effective but should be second-line therapy. There is limited evidence for nebivolol, bisoprolol, pindolol, carbamazepine, gabapentin, fluoxetine, nicardipine, verapamil, nimodipine, nifedipine, lisinopril, and candesartan. Acebutolol, oxcarbazepine, lamotrigine, and telmisartan are ineffective. Newer agents target calcitonin gene-related peptide pain transmission in the migraine pain pathway and have recently received approval from the U.S. Food and Drug Administration; however, more studies of long-term effectiveness and adverse effects are needed. The complementary treatments petasites, feverfew, magnesium, and riboflavin are probably effective. Nonpharmacologic therapies such as relaxation training, thermal biofeedback combined with relaxation training, electromyographic feedback, and cognitive behavior therapy also have good evidence to support their use in migraine prevention.

Full article


Urine Drug Tests: Ordering and Interpretation (3904)
Kale AFP 99:33 01-01-2019

Urine drug testing is an essential component of monitoring patients who are receiving long-term opioid therapy, and it has been suggested for patients receiving long-term benzodiazepine or stimulant therapy. Family physicians should be familiar with the characteristics and capabilities of screening and confirmatory drug tests. Immunoassays are used for initial screening and can give false-positive and false-negative results. All results are considered presumptive until confirmatory testing is performed. False-positive results have significant implications for a patient's pain treatment plan, and false-negative results can be a missed opportunity to detect misuse. Urine drug testing is an essential component of monitoring patients who are receiving long-term opioid therapy, and it has been suggested for patients receiving long-term benzodiazepine or stimulant therapy. Family physicians should be familiar with the characteristics and capabilities of screening and confirmatory drug tests. Immunoassays are qualitative tests used for initial screening of urine samples. They can give false-positive and false-negative results, so all results are considered presumptive until confirmatory testing is performed. Immunoassays for opioids may not detect commonly prescribed semisynthetic and synthetic opioids such as methadone and fentanyl; similarly, immunoassays for benzodiazepines may not detect alprazolam or clonazepam. Immunoassays can cross-react with other medications and give false-positive results, which have important implications for a patient's pain treatment plan. False-negative results can cause missed opportunities to detect misuse. Urine samples can be adulterated with other substances to mask positive results on urine drug testing. Family physicians must be familiar with these substances, the methods to detect them, and their effects on urine drug testing.

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Brain glial activation in fibromyalgia - A multi-site positron emission tomography investigation (3907)
Albrecht DS et al Brain Behav Immun 75:72 01-01-2019

A disorder, known as fibromyalgia, characterized by fatigue and pain, has long frustrated clinicians because conventional diagnostic testing reveals little evidence of objective pathology. In a new study from Boston and Stockholm, researchers used positron emission tomography (PET) to assess neuroinflammation in the brains of fibromyalgia patients.

The teams conducted PET scans in 31 fibromyalgia patients and 27 age- and sex-matched healthy controls. In fibromyalgia patients, the scans revealed widespread activation of glial cells (antigen-presenting cells) in the cortex, particularly in the frontal and parietal lobes. This glial activation was not seen in controls. Moreover, the degree of glial activation correlated with reported intensity of patients' fatigue: the greater the neuroinflammation, the greater the fatigue (although not the pain).

Comment: Previous research has shown elevated levels of proinflammatory cytokines in the cerebrospinal fluid of patients with fibromyalgia. Interestingly, PET also has identified neuroinflammation in patients with a clinically similar condition, chronic fatigue syndrome. The current study provides direct evidence of neuroinflammation and suggests that neuroinflammation is a target for therapy. Indeed, one agent - low-dose naltrexone - reduced glial activation in the brain and improved symptoms in small controlled studies of fibromyalgia patients. The current study indicates that smoldering and potentially treatable neuroinflammation is present in the brains of patients with fibromyalgia.


Diagnosis and Management of NAFLD (3901)
Paul et al JAMA 320:2474 12-18-2018

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Drugs for Cough (3902)
Med Ltr Med Ltr 60:206 12-17-2018

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Radical Prostatectomy or Watchful Waiting in Prostate Cancer: 29-Year Follow-up (3895)
Bill-Axelson et al NEJM 379:2319 12-13-2018

METHODS: We randomly assigned 695 men with localized prostate cancer to watchful waiting or radical prostatectomy from October 1989 through February 1999 and collected follow-up data through 2017. Cumulative incidence and relative risks with 95% confidence intervals for death from any cause, death from prostate cancer, and metastasis were estimated in intention-to-treat and per-protocol analyses, and numbers of years of life gained were estimated. We evaluated the prognostic value of histopathological measures with a Cox proportional-hazards model.

RESULTS: By December 31, 2017, a total of 261 of the 347 men in the radical-prostatectomy group and 292 of the 348 men in the watchful-waiting group had died; 71 deaths in the radical-prostatectomy group and 110 in the watchful-waiting group were due to prostate cancer (relative risk, 0.55; 95% confidence interval [CI], 0.41 to 0.74; P<0.001; absolute difference in risk, 11.7 percentage points; 95% CI, 5.2 to 18.2). The number needed to treat to avert one death from any cause was 8.4. At 23 years, a mean of 2.9 extra years of life were gained with radical prostatectomy. Among the men who underwent radical prostatectomy, extracapsular extension was associated with a risk of death from prostate cancer that was 5 times as high as that among men without extracapsular extension, and a Gleason score higher than 7 was associated with a risk that was 10 times as high as that with a score of 6 or lower (scores range from 2 to 10, with higher scores indicating more aggressive cancer).

CONCLUSIONS: Men with clinically detected, localized prostate cancer and a long life expectancy benefited from radical prostatectomy, with a mean of 2.9 years of life gained. A high Gleason score and the presence of extracapsular extension in the radical prostatectomy specimens were highly predictive of death from prostate cancer. (Funded by the Swedish Cancer Society and others.)


Treatment of Lower Extremity Superficial Thrombophlebitis (3893)
Di Nisio et al JAMA 320:2367 12-11-2018

Clinical Question: Which treatments for lower extremity superficial thrombophlebitis (ST) are associated with lower rates of venous thromboembolic events (VTEs) vs placebo?

Bottom Line A dose of 2.5 mg of fondaparinux administered subcutaneously once daily for 45 days is associated with fewer cases of symptomatic VTE without an increase in major bleeding vs placebo. Low-molecular-weight heparin (LMWH) and nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with lower rates of ST extension or recurrence vs placebo, but data regarding symptomatic VTE remain inconclusive. Oral rivaroxaban requires further evaluation.

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Lung Nodules Summary (3894)
Kney Various 12-04-2018

Incidental Pulmonary Nodules Detected on CT Images from JAMA 12/4/18 (JAMA Guidelines).

Fleischner


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