Here are the last 20 additions to the PBrain (total entries as of now = 3635)


Implementation of lung cancer screening in the Veterans Health Administration (3616)
Kinsinger LS et al JAMA Intern Med 2017 Jan 30 01-30-2017

Based largely on results of the 2011 National Lung Screening Trial (NLST), U.S. Preventive Services Task Force (USPSTF) guidelines in 2013 recommended low-dose computed tomography (CT) screening for lung cancer in high-risk patients (NEJM JW Gen Med Feb 15 2014 and Ann Intern Med 2014; 160:330). Now, in two studies, researchers have examined the implementation of this recommendation.

In a demonstration project at eight Veterans Affairs (VA) medical centers, CT lung cancer screening was offered to 4246 high-risk patients (age range, 55 to 80; current smokers or smokers who quit <15 years previously; ≥30 pack-years of smoking; predicted life expectancy, ≥6 months), of whom 2106 underwent screening. Among those screened, 1257 had nodules, including 1184 that required tracking and 73 with suspicious nodules that required further evaluation; of those with suspicious nodules, 31 had early-stage lung cancer, yielding a false-positive rate of 97.5%. Substantially more staffing was required at each site to identify and assess patients, facilitate shared decision-making, and schedule procedures and follow-up. In the second study, investigators used national health interview data from 2010 and 2015 to identify about 36,000 patients who had undergone CT lung cancer screening and 36,000 who had been screened with chest radiography. The rate of CT screening was significantly higher in 2015 than in 2010 in never-smokers (1.2% vs. 0.8%), low-risk smokers (i.e., those who did not meet high-risk criteria as above, 2.7% vs. 1.5%), and high-risk smokers (5.8% vs. 2.9%). In absolute numbers, roughly three times as many never-smokers and low-risk smokers were screened as high-risk smokers at both time points. Rates of screening with chest radiography were similar in 2010 (2.5%) and 2015 (2.7%).

Comment: Together, these studies validate many experts' skepticism when the NLST results were released, and again after USPSTF recommendations were issued. CT lung cancer screening is staff-intensive and expensive, has relatively low acceptance among high-risk patients (about 50% in the VA study), yields a very high false-positive rate, and is difficult to restrict to high-risk patients. In addition, screening with chest radiography, which might lead to more harm than benefit, has not declined in use. From the VA data, editorialists calculate that for every 1000 patients screened, 10 will be diagnosed with potentially curable lung cancer, 5 will have incurable lung cancer, 20 will undergo one or more unnecessary invasive procedures for incidental findings, and 550 will experience anxiety and additional radiation exposure from follow-up CT.

Huo J et al. Use of CT and chest radiography for lung cancer screening before and after publication of screening guidelines: Intended and unintended uptake. JAMA Intern Med 2017 Jan 30

Redberg RF and O'Malley PG.Important questions about lung cancer screening programs when incidental findings exceed lung cancer nodules by 40 to 1. JAMA Intern Med 2017 Jan 30


Association of testosterone levels with anemia in older men: A controlled clinical trial (3617)
Roy CN et al JAMA Intern Med 02-21-2017

In three studies, researchers evaluated effects of testosterone therapy in older men. Two of these were from the Testosterone Trials (T Trials), a series of seven linked studies, in which 788 men (mean age, 72) with total testosterone levels <275 ng/dL were randomized to testosterone gel (to maintain testosterone levels of 300 to 800 ng/dL), or placebo for 1 year. Sexual and physical function outcomes were published earlier (NEJM JW Gen Med Mar 15 2016 and N Engl J Med 2016; 374:611).

In one T Trial, 16% of men had anemia (hemoglobin level, <= 12.7 g/dL); anemia was unexplained in half of these men. Increases in hemoglobin levels of at least 1.0 g/dL occurred in significantly more testosterone recipients than placebo recipients (53% vs. 17%); this effect occurred in men with and without known causes of anemia. The authors imply that low serum testosterone actually might be responsible for some cases of unexplained anemia.

In another T Trial, bone outcomes were assessed in 211 men at baseline and after treatment. Testosterone recipients had significantly greater increases than placebo recipients in several measures of bone density and strength, but the study was too small and too short in duration to assess fracture risk.

Finally, in a retrospective U.S. cohort study, researchers examined adverse cardiovascular events in about 44,000 men with total testosterone levels <300 ng/dL; about 9000 men received testosterone therapy (which increased median testosterone level from 212 ng/dL to 318 ng/dL), and 35,000 did not. During median follow-up of 3.4 years, adverse cardiovascular events occurred less often in testosterone recipients than in nonrecipients (17 vs. 24 events/1000 person-years; adjusted hazard ratio, 0.67).

Comment: These results add a few new pieces to the puzzle of whether testosterone therapy benefits hypogonadal older men. However, the two randomized trials were too small and too short for researchers to assess clinical outcomes or harmful side effects. And the cohort study - with results that differ from those of several other observational studies - was subject to confounding by unmeasured variables. In the absence of results from larger, longer trials, detailed shared decision making still is strongly recommended.

Snyder PJ et al. Effect of testosterone treatment on volumetric bone density and strength in older men with low testosterone: A controlled clinical trial. JAMA Intern Med 2017 Feb 21

Cheetham TC et al. Association of testosterone replacement with cardiovascular outcomes among men with androgen deficiency.


Effects of testosterone supplementation for 3 years on muscle performance and physical function in older men (3618)
Storer TW et al J Clin Endocrinol Metab 102:583 02-01-2017

In a recently published, industry-funded, randomized trial that involved about 300 men (mean age, 68; morning total testosterone range, 100 to 400 mg/dL), subclinical atherosclerosis was the primary endpoint. During 3 years of treatment with testosterone gel or placebo, changes in carotid intima-media thickness and coronary artery calcium were similar in the two groups (NEJM JW Gen Med Sep 15 2015 and JAMA 2015; 314:570). Now, the researchers report the following additional study outcomes on quantitative measures of muscle performance and physical function:

In general, those measurements that showed statistically significant differences between the testosterone and placebo groups reflected a 1% to 2% relative improvement with testosterone and a several-percent relative decline with placebo.

Comment: In this study, testosterone supplementation resulted in statistically significant improvement for several measures of muscle performance. However, as noted by the authors, "...the magnitude of change...was small and the clinical meaningfulness of these changes remains unclear." These findings are consistent with those of the recently published "Testosterone Trials," a larger but shorter-duration study (790 patients; mean age, 72; trial duration, 1 year), in which improvement in physical function with testosterone was modest and of questionable clinical importance (NEJM JW Gen Med Mar 15 2016 and N Engl J Med 2016; 374:611).


The American Academy of Orthopaedic Surgeons appropriate use criteria for the management of patients with orthopaedic implants undergoing dental procedures (3619)
Quinn RH et al J Bone Joint Surg Am 99:161 01-18-2017

Several years ago, I presented a brief historical review of recommendations on antibiotic prophylaxis before dental procedures in patients with prosthetic joint implants (NEJM JW Gen Med May 15 2013). In 2009, the American Academy of Orthopaedic Surgeons (AAOS) essentially had endorsed routine prophylaxis for all patients with prosthetic joints, with no time limit after the date of the orthopedic procedure. However, in a 2013 guideline issued jointly by the AAOS and the American Dental Association (ADA), clinicians were advised to "consider discontinuing the practice of routinely prescribing prophylactic antibiotics for patients with hip and knee prosthetic joint implants undergoing dental procedures." The guideline indicated that no evidence justified prophylaxis and that several studies - albeit observational studies with limitations - argued against it. Nevertheless, the somewhat ambiguous wording, inviting clinicians to "consider" not prescribing antibiotics "routinely," left the door open for those who still favored prophylaxis. This resulted in confusion for dentists, dentists' reliance on orthopedists to make these decisions, and a continuing practice of widespread, indefinite provision of antibiotic prophylaxis.

The latest iteration of this controversy is a new document entitled "Appropriate Use Criteria for the Management of Patients with Orthopaedic Implants Undergoing Dental Procedures." The AAOS and ADA appointed an 11-member panel (5 orthopedists and 6 dentists) to identify criteria that might affect risk for developing infected orthopedic implants due to dental procedure-related bacteremia. Five risk criteria were chosen: invasiveness of the dental procedure, immunocompromised status, diabetes and glycemic control, previous history of prosthetic infection, and time since joint replacement.

Next, panel members generated 64 case scenarios that reflected various combinations of these putative risk factors and presented those scenarios to a separate voting panel consisting of nine dentists, three orthopedists, and two infectious disease specialists. The outcome of this process was a designation of "rarely appropriate," "may be appropriate," or "appropriate" for each scenario. For the 32 scenarios involving "dental procedures that do not result in the manipulation of gingival or periapical tissues, or perforation of the oral mucosa," antibiotics always were considered to be "rarely appropriate," regardless of presence of other risk factors. However, few visits will fall into the "no manipulation" category, because most dental visits (including cleanings) do involve manipulation of gingival tissues. For the 32 scenarios describing visits with tissue manipulation, antibiotics were deemed "rarely appropriate" when no additional risk factors were present. But when such visits involved patients with other risk factors, voting panelists concluded that antibiotic prophylaxis "is appropriate" for 8 scenarios and "may be appropriate" for 17 scenarios - despite lack of evidence that antibiotic prophylaxis before dental procedures prevents implant infections, regardless of risk factors. The AAOS has provided an online calculator that gives a patient's "appropriateness" category when the five patient-specific variables are entered.

Although most patients will fall into the "rarely appropriate" category, I suspect that this latest AAOS document - based essentially on opinions of physicians and dentists whose expertise for addressing this issue is unclear - is unlikely to change practice substantially. The term "rarely appropriate" still leaves the door open for antibiotic prophylaxis, and the authors note that these ratings are "not meant to supersede clinician expertise...or patient preference." My admittedly anecdotal impression (from speaking with a number of orthopedists and dentists during the past few weeks) is that most orthopedists will continue to recommend prophylactic antibiotics for at least several years after joint replacement surgery and that most dentists will defer to their patients' orthopedists. Notably, a 2016 consensus statement from Canada (representing orthopedists, dentists, and infectious disease specialists) recommends against prophylaxis.

Because patients with orthopedic implants and their dentists sometimes ask the primary care clinician (rather than the orthopedist) to prescribe prophylactic antibiotics, this topic is relevant to general practice. In my view, primary care clinicians are not obligated to prescribe antibiotics on behalf of orthopedists or dentists when supportive evidence is lacking and guidelines are ambiguous; hence, the orthopedist or dentist should assume responsibility for these prescribing decisions.This article and its associated tables are available in pdf form at http://journals.lww.com/ free of charge.


Diazepam is no better than placebo when added to naproxen for acute low back pain (3620)
Friedman BW et al Ann Emerg Med 01-19-2017

Benzodiazepines are centrally acting sedatives and are commonly, although inaccurately, considered to be "muscle relaxants" when prescribed for low back pain. Investigators at two urban academic emergency departments randomized 114 patients with acute nontraumatic nonradicular low back pain to receive naproxen 500 mg twice daily as needed for pain along with either placebo or diazepam 5 mg twice daily as needed.

At 1-week follow-up, improvements in pain and disability were similar in the two groups: 32% of diazepam patients and 22% of placebo patients reported moderate or severe low back pain, and scores on the Roland-Morris Disability Questionnaire improved by 11 points in both groups. Adverse events were mild and comparable in the two groups.

Comment: A prior study by the same investigators provided good evidence that opioids and cyclobenzaprine are not beneficial in the treatment of nontraumatic nonradicular low back pain (NEJM JW Emerg Med Dec 2015 and JAMA 2015; 314:1572).We should treat low back pain with nonsteroidal anti-inflammatory medications, acetaminophen, or a combination, and specifically not opioids or benzodiazepines, and certainly not muscle relaxants.


Risk of acute kidney injury after intravenous contrast media administration (3621)
Hinson JS et al Ann Emerg Med 01-19-2017

It is an article of faith in emergency medicine and radiology that the intravenous contrast used for computed tomography (CT) may cause kidney injury. In a retrospective cohort study, investigators at a U.S. academic emergency department (ED) compared the incidence of acute kidney injury among three groups of patients: 7201 who underwent contrast-enhanced CT, 5499 who underwent unenhanced CT, and 5234 who did not undergo CT. Patients met stringent inclusion criteria, including baseline creatinine of 0.4 to 4.0 mg/dL.

Patients who underwent contrast-enhanced CT were no more likely to develop acute kidney injury than those who underwent unenhanced CT (odds ratio, 1.0) or those who did not undergo CT (OR, 1.0). After controlling for baseline characteristics by propensity-score matching, the results were the same. In addition, there were no differences among the groups in renal outcomes at 6 months.

Comment: Our understanding of contrast-induced nephropathy is largely informed by studies that predated the use of low-osmolar and iso-osmolar contrast agents, and by extrapolation from angiography, which involves higher contrast loads. In the absence of a randomized trial, a retrospective cohort study with propensity score matching provides the best evidence we can hope for in the search for a causal relationship between contrast use and nephropathy. This rigorous study suggests that modern contrast-enhanced CT techniques are not risky for the kidneys in patients with creatinine levels ≤4 mg/dL. How this finding should inform practice is difficult to answer given the varied added benefit from contrast in different situations. If contrast-enhanced CT is essential for ruling out a serious condition and no alternative test is readily available, this study should reassure emergency physicians and radiologists to proceed with the scan, even in patients with creatinine levels as high as 4 mg/dL. If a patient has an elevated creatinine after contrast-enhanced CT, a causal relationship should not be assumed, and the providers who ordered and performed the study in good faith should not be faulted.


End-of-Life Care: Managing Common Symptoms (3622)
Ross AFP 95:356 03-15-2017

Physicians should be proficient at managing symptoms as patients progress through the dying process. When possible, proactive regimens that prevent symptoms should be used, because it is generally easier to prevent than to treat an acute symptom. As swallowing function diminishes, medications are typically administered sublingually, transdermally, or via rectal suppository. Opiates are the medication of choice for the control of pain and dyspnea, which are common symptoms in the dying process. Delirium and agitation may be caused by reversible etiologies, which should be identified and treated when feasible. When medications are required, haloperidol and risperidone are effective options for delirium. Nausea and vomiting should be treated with medications targeting the etiology. Constipation may be caused by low oral intake or opiate use. Preventive regimens to avoid constipation should include a stimulant laxative with a stool softener. Oropharyngeal secretions may lead to noisy breathing, sometimes referred to as a death rattle, which is common at the end of life. Providing anticipatory guidance helps families and caregivers normalize this symptom. Anticholinergic medications can modestly help reduce these secretions. Effective symptom control in end-of-life care can allow patients to progress through the dying process in a safe, dignified, and comfortable manner.

Full article


End-of-Life Care: Managing Common Symptoms (3623)
Ross AFP 95:356 03-15-2017

Physicians should be proficient at managing symptoms as patients progress through the dying process. When possible, proactive regimens that prevent symptoms should be used, because it is generally easier to prevent than to treat an acute symptom. As swallowing function diminishes, medications are typically administered sublingually, transdermally, or via rectal suppository. Opiates are the medication of choice for the control of pain and dyspnea, which are common symptoms in the dying process. Delirium and agitation may be caused by reversible etiologies, which should be identified and treated when feasible. When medications are required, haloperidol and risperidone are effective options for delirium. Nausea and vomiting should be treated with medications targeting the etiology. Constipation may be caused by low oral intake or opiate use. Preventive regimens to avoid constipation should include a stimulant laxative with a stool softener. Oropharyngeal secretions may lead to noisy breathing, sometimes referred to as a death rattle, which is common at the end of life. Providing anticipatory guidance helps families and caregivers normalize this symptom. Anticholinergic medications can modestly help reduce these secretions. Effective symptom control in end-of-life care can allow patients to progress through the dying process in a safe, dignified, and comfortable manner.

Full article


Trial of pregabalin for acute and chronic sciatica (3624)
Mathieson S et al NEJM 376:111 03-23-2017

Gabapentin and pregabalin (Lyrica) are prescribed frequently for lumbosacral radicular pain, despite a lack of evidence that they are effective for this condition. In this randomized trial from Australia, researchers randomized 209 patients with sciatica to receive either pregabalin (titrated from 150 mg to 600 mg, depending on response and side effects) or placebo for as long as 8 weeks. At enrollment, duration of pain had been 1 week to 1 year (mean, 2 months); all patients had pain radiating below the knee and either dermatomal pain distribution, motor or sensory deficit, or diminished reflex. The primary outcome was leg pain at 8 weeks.

Improvement in the mean leg-pain score at 8 weeks actually was slightly greater in the placebo group than in the pregabalin group (decrease of 3.0 vs. 2.6 points, from a mean baseline of ≈6.1 on a 10-point scale), but the difference was not statistically significant; pain scores remained similar in the two groups at 1 year. Moreover, the groups did not differ on any secondary outcome (e.g., ratings of disability, quality of life, and global perceived effect). However, the frequency of side effects was significantly higher with pregabalin than with placebo - dizziness was most common (40% vs. 13%).

Comment: Pregabalin does not relieve pain associated with sciatica and should not be prescribed for this purpose; presumably, the same holds true for the related drug gabapentin. This finding is not surprising: Although pregabalin has some efficacy - and is FDA-approved for use - in patients with postherpetic neuralgia or diabetic peripheral neuropathy, the pathogenesis of pain in those conditions is different from that of radicular pain.


Pharmacologic treatment of hypertension in adults aged 60 years or older to higher versus lower blood pressure targets: A clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians (3625)
Qaseem A et al Ann Intern Med 01-17-2017

This joint guideline presents evidence on benefits and harms of treating to higher versus lower systolic blood pressure (SBP) targets in older adults (age, ≥60) with hypertension. Recommendations are based on a systematic review of randomized controlled trials (for primary outcomes) and observational studies (for harms).

Key Findings:

Recommendations:

Comment: Joint National Committee (JNC) 8 guideline caused controversy by recommending a higher systolic treatment threshold for older patients than for younger patients and those with diabetes or CKD (<150 vs. <140 mm Hg; NEJM JW Gen Med Jan 15 2014 and JAMA 2014; 311:507). This guideline takes a similar approach and advises a target SBP of <150 mm Hg for older patients (age, ≥60) and suggests that we consider additional lowering of SBP for patients with previous stroke or TIA, or for those at high CV risk. The authors acknowledge the influence of the SPRINT trial in making the latter recommendation for patients at high CV risk. However, note that, in SPRINT, researchers compared SBP targets of 120 mm Hg and 140 mm Hg (although measured BPs probably were lower than typical office BPs, given the SPRINT protocol), and it excluded patients with previous stroke or diabetes (NEJM JW Gen Med Dec 15 2015 and N Engl J Med 2015; 373:2103). A recurring theme within the guideline was the need to individualize treatment goals for each patient.

Weiss J et al. Benefits and harms of intensive blood pressure treatment in adults aged 60 years or older: A systematic review and meta-analysis. Ann Intern Med 2017 Jan 17

Pignone M and Viera AJ.Blood pressure treatment targets in adults aged 60 years or older. Ann Intern Med 2017 Jan 17


Vitamin D supplementation to prevent acute respiratory tract infections: Systematic review and meta-analysis of individual participant data (3626)
Martineau AR et al BMJ356:i6583 02-15-2017

Observational evidence suggests that low blood concentrations of 25-hydroxyvitamin D are associated with susceptibility for acute respiratory tract infections. In this meta-analysis of 25 randomized, double-blind, placebo-controlled trials, researchers used individual participant data on about 11,000 children and adults to examine whether vitamin D supplementation lowered risk for acute respiratory tract infections (upper, lower, and unclassified location).

In all studies, vitamin D was administered orally: bolus doses every 1 to 3 months, weekly doses, daily doses, or a combination of bolus and daily doses. Vitamin D supplementation significantly lowered risk for acute respiratory tract infections (by 12%; adjusted odds ratio, 0.88). This protective effect was observed only in participants who received daily or weekly vitamin D and was stronger in participants whose baseline 25-hydroxyvitamin D levels were <10 ng/mL (<25 nmol/L; adjusted OR, 0.3) than in those whose baseline levels were higher (AOR, 0.75). In addition, the protective effect appeared to be limited to upper respiratory infections. Vitamin D supplementation was not associated with serious adverse events.

COMMENT: In this study, vitamin D supplementation lowered risk for acute respiratory tract infections, especially among participants with severe vitamin D deficiency (baseline 25-hydroxyvitamin D level, <10 ng/mL). Notably, the prevalence of severe vitamin D deficiency among U.S. adults has been estimated to be 6% or about 20 million people (Arch Intern Med 2009; 169:626). These results are biologically plausible - as noted by the authors, in vitro studies have shown that vitamin D and its metabolites induce antimicrobial effects.


Noninvasive treatments for acute, subacute, and chronic low back pain: A clinical practice guideline from the American College of Physicians (3627)
Qaseem A et al Ann Intern Med 02-14-2017

The ACP has developed a guideline that updates its 2007 recommendations on noninvasive approaches to treating patients with low back pain (NEJM JW Gen Med Nov 15 2007 and Ann Intern Med 2007; 147:478). Randomized trials and systematic reviews were included in the analysis. Reviewers evaluated outcomes including pain, function, health-related quality of life, work disability and return to work, global improvement, and patient satisfaction. The guideline does not include topical therapies or epidural injections.

Key Findings:

Recommendations

What's Changed: A significant change from the 2007 guideline is dropping acetaminophen and TCAs from recommended medications. The deletion of acetaminophen is based on a study in which researchers evaluated pain at 3 weeks; no improvement in pain was seen relative to placebo. However, head-to-head studies failed to demonstrate a difference in efficacy between NSAIDs and acetaminophen.

COMMENT: Most patients do not require any specific intervention for low back pain. For those who do, many available options are not very effective - most interventions had only a small benefit on pain or function. Given how little we have to offer, one can summarize these recommendations as: Do no harm (and avoid opioids).

Chou R et al. Systemic pharmacologic therapies for low back pain: A systematic review for an American College of Physicians clinical practice guideline. Ann Intern Med 2017 Feb 14

Chou R et al. Nonpharmacologic therapies for low back pain: A systematic review for an American College of Physicians clinical practice guideline. Ann Intern Med 2017 Feb 14

Atlas SJ.Management of low back pain: Getting from evidence-based recommendations to high-value care. Ann Intern Med 2017 Feb 14


Hiccups (3628)
PL 24:24 04-01-2017

Persistent hiccups are rare. May occur after surgery, or with GERD, cancer, pneumonia, or electrolyte imbalances. The standard treatment was chlorpromazine or metoclopramide. But chlorpromazine causes QT prolongation, and metoclopramide can cause tremors/movement disorders. Instead, try baclofen or gabapentin. Use for 7-10 days - if hiccups persist, change to another medication.


Association Between Radiation Therapy, Surgery, or Observation for Localized Prostate Cancer and Patient-Reported Outcomes After 3 Years (3629)
Barocas et al JAMA 317:1126 03-21-2017

Design, Setting, and Participants: Prospective, population-based, cohort study involving 2550 men (≤80 years) diagnosed in 2011-2012 with clinical stage cT1-2, localized prostate cancer, with prostate-specific antigen levels less than 50 ng/mL, and enrolled within 6 months of diagnosis.

Exposures: Treatment with radical prostatectomy, EBRT, or active surveillance was ascertained within 1 year of diagnosis.

Main Outcomes and Measures: Patient-reported function on the 26-item Expanded Prostate Cancer Index Composite (EPIC) 36 months after enrollment. Higher domain scores (range, 0-100) indicate better function. Minimum clinically important difference was defined as 10 to 12 points for sexual function, 6 for urinary incontinence, 5 for urinary irritative symptoms, 5 for bowel function, and 4 for hormonal function.

Results: The cohort included 2550 men (mean age, 63.8 years; 74% white, 55% had intermediate- or high-risk disease), of whom 1523 (59.7%) underwent radical prostatectomy, 598 (23.5%) EBRT, and 429 (16.8%) active surveillance. Men in the EBRT group were older (mean age, 68.1 years vs 61.5 years, P < .001) and had worse baseline sexual function (mean score, 52.3 vs 65.2, P < .001) than men in the radical prostatectomy group. At 3 years, the adjusted mean sexual domain score for radical prostatectomy decreased more than for EBRT (mean difference, −11.9 points; 95% CI, −15.1 to −8.7). The decline in sexual domain scores between EBRT and active surveillance was not clinically significant (−4.3 points; 95% CI, −9.2 to 0.7). Radical prostatectomy was associated with worse urinary incontinence than EBRT (−18.0 points; 95% CI, −20.5 to −15.4) and active surveillance (−12.7 points; 95% CI, −16.0 to −9.3) but was associated with better urinary irritative symptoms than active surveillance (5.2 points; 95% CI, 3.2 to 7.2). No clinically significant differences for bowel or hormone function were noted beyond 12 months. No differences in health-related quality of life or disease-specific survival (3 deaths) were noted (99.7%-100%).

Conclusions and Relevance: In this cohort of men with localized prostate cancer, radical prostatectomy was associated with a greater decrease in sexual function and urinary incontinence than either EBRT or active surveillance after 3 years and was associated with fewer urinary irritative symptoms than active surveillance; however, no meaningful differences existed in either bowel or hormonal function beyond 12 months or in in other domains of health-related quality-of-life measures. These findings may facilitate counseling regarding the comparative harms of contemporary treatments for prostate cancer.

Full article that includes some helpful graphs that can visually show patients the outcomes for each option.


Bariatric Surgery Summary (3630)
Kney Various 04-21-2017

Zinc supplements: If level is < 60 (normal 60-130 mcg/dl) - supplement with 1-2 mg/kg of elemental zinc. One common form is zinc sulfate 220 mg - containing 50 mg of elemental zinc.


Holter-electrocardiogram- ischaemic stroke (Find-AFRANDOMISED): An open-label randomised controlled trial (3631)
Wachter R et al Lancet Neurol 16:282 04-01-2017

Recent studies have found that in patients with stroke of unknown cause (cryptogenic stroke), extended poststroke monitoring detects intermitted atrial fibrillation (AF) in 5% to 20%. In this manufacturer-funded study, investigators from Germany randomized 400 patients (aged >60) to 10-day Holter monitor recordings at three time points following ischemic stroke (baseline, 3 months, and 6 months) or to standard monitoring (≥24-hour Holter or telemetry monitoring). Patients with severe, ipsilateral carotid or intracranial stenosis or prior AF diagnosis were excluded. The primary endpoint was detection of AF or atrial flutter lasting 30 seconds or longer.

At 6 months, 14% of patients in the extended-monitoring group had AF detected, significantly more than the 5% in the standard group (number needed to screen, 11). The median time from study enrollment to detection of AF was similar in both groups (33 days vs. 36 days). Among 25 patients with AF detected by prolonged monitoring, 18 were noted in the first Holter recording period, 6 in the second period, and 1 in the third. All patients with AF detection were offered oral anticoagulation.

Comment: These findings add to the literature showing that screening for AF in older patients with stroke of no obvious atherosclerotic cause is worthwhile. The 14% detection rate is clinically significant, even with an older technique (Holter-ECG recordings). Whether extremely brief (<1 minute) episodes of AF require anticoagulation is still being studied. Nonetheless, clinicians should consider extended monitoring for AF in cryptogenic stroke, especially in older patients and patients with risk factors for AF such as prior congestive heart failure or left atrial enlargement.


Association between dietary factors and mortality from heart disease, stroke, and type 2 diabetes in the United States (3632)
Micha R et al JAMA 317:912 03-07-2017

Dietary factors affect risk for cardiometabolic diseases (e.g., heart disease, stroke, and type 2 diabetes), but the specific factors involved and their individual effects on risk are unclear. In this study, investigators used various sources of data to quantify the effect of suboptimal diet on cardiometabolic disease-related mortality in the U.S. in 2012. They identified 10 specific dietary factors (e.g., fruits, vegetables, whole grains, sodium, nuts and seeds, processed meats) that were associated strongly with cardiometabolic disease and estimated the absolute number and proportion of cardiometabolic disease-related deaths associated with suboptimal intake of each food.

On multivariate analysis, overall suboptimal intake of the 10 dietary factors accounted for 45.4% of 702,308 cardiometabolic disease-related deaths in 2012; the largest contributors to these deaths were high sodium intake (9.5%), low consumption of nuts and seeds (8.5%), and high intake of processed meats (8.2%). Between 2002 and 2012, cardiometabolic disease-related mortality fell by 25%, with the greatest effects coming from improved intakes of polyunsaturated fats and nuts and seeds and lower intake of sugar-sweetened beverages.

COMMENT: These data - which provide guidance on dietary modifications that are likely to have the largest effects - have value for public health professionals who plan population-based initiatives and for clinicians who advise individual patients.


Pioglitazone and risk for bone fracture: Safety data from a randomized clinical trial (3633)
Viscoli CM et al J Clin Endocrinol Metab 102:91 03-01-2017

In a recently published, placebo-controlled, randomized trial that involved nearly 4000 insulin-resistant (but not frankly diabetic) patients with recent stroke or transient ischemic attack, pioglitazone lowered risk for cardiovascular events (NEJM JW Gen Med Apr 1 2016 and N Engl J Med 2016; 374:1371). However, fracture incidence was significantly higher in pioglitazone recipients than in placebo recipients - an adverse effect noted in other studies.

In this report, the trial's investigators provide additional detail on fractures:

COMMENT:Fractures are an adverse effect of pioglitazone that should be considered when the drug is prescribed; other common adverse effects are weight gain and edema. Pioglitazone increases sensitivity to insulin by binding to PPAR-γ receptors, which are found in adipose tissue, muscle, and liver. But these receptors also are found in bone - which might explain the excess fracture risk.


Association of suicidality and depression with 5&#945;-reductase inhibitors (3634)
Welk B et al JAMA Intern Med 03-20-2017

Postmarketing surveillance has raised concerns that 5α-reductase inhibitors might increase risk for depression and suicide; the biologic plausibility of this association is supported by evidence that these drugs affect neuropeptides, testosterone, and other neurotransmitters. In this retrospective Canadian study, researchers identified about 93,000 older men (mean age, 75) who started new prescriptions for finasteride or dutasteride between 2003 and 2013; these men were matched by age, history of depression or suicidal thoughts, and other demographic and clinical variables with an equal number of men without such prescriptions. Data also were collected on suicide, new-onset depression, and self-harm (e.g., hospitalization or emergency department visits for suicide attempts) during continuous medication use plus 12 months after stopping.

At median follow-up of about 18 months, suicide rates were similar in both groups. Risk for self-harm was modestly but significantly elevated with active treatment compared with placebo (71 vs. 53 events per 100,000 person-years), as was risk for incident depression (767 vs. 530 events per 100,000 person-years). After 18 months, risk for self-harm faded and was no longer significant; risk for depression also faded but remained significant.

COMMENT: Retrospective cohort studies are messy, given the potential for unidentified confounders, and the differences in risk in this study are small, albeit statistically significant. These results might encourage clinicians to counsel patients about potential risks to mental health, but they're unlikely to discourage patients from using 5α-reductase inhibitors.


Determining when to stop prostate specific antigen monitoring after radical prostatectomy: The role of ultrasensitive prostate specific antigen (3635)
Matsumoto K et al J Urol 197:655 03-01-2017

In patients who have undergone radical prostatectomy for localized prostate cancer, periodic monitoring of prostate-specific antigen (PSA) levels is recommended to screen for "biochemical recurrence" - a rise in PSA that might predict clinically evident recurrence. In this Japanese study, researchers sought to determine when postprostatectomy PSA monitoring can be stopped.

Nearly 600 patients who underwent radical prostatectomy were followed an average of 10 years; patients had PSA testing (using an ultrasensitive assay) every 3 to 6 months during the first 3 postprostatectomy years and annually thereafter. Among 187 patients with undetectable PSA (<0.01 ng/mL) at 3 years, only 2 patients had later biochemical recurrence (defined as PSA elevation to >0.2 ng/mL). Among 162 patients with undetectable PSA at 5 years, none had later biochemical recurrence.

COMMENT: This study suggests that if the PSA level, measured by an ultrasensitive assay, remains undetectable 3 to 5 years after radical prostatectomy, probability of biochemical recurrence is extremely low, and PSA monitoring could reasonably be stopped. The authors also remind us that biochemical recurrence is a surrogate marker: It doesn't necessarily predict clinically evident progression of prostate cancer during the patient's lifetime.


Here are the last 10 additions to the PBrain by date


Risk of venous thromboembolism and myocardial infarction associated with factor V Leiden and prothrombin mutations and blood type (2877)
Sode BF et al CMAJ 2013 Mar 19; 185:E229 03-19-3013

Genetic conditions associated with venous and arterial thrombosis include relatively rare disorders such as dyslipidemia and hyperhomocystinemia. However, recent reports suggest that ABO blood group (non-O) is also an important risk factor. To examine associations among ABO blood groups, inherited thrombophilias (factor V Leiden [FVL] and prothrombin G20210A), and venous and arterial thrombotic events, investigators analyzed data from 60,000 persons in the Danish general population who were enrolled in two independent studies.

Venous thromboembolism (VTE) was identified in 3.5% of the study cohort, and was significantly associated with non-O blood group, FVL R506Q mutation, and prothrombin G20210A mutation. Combining non-O blood type with either FVL R506Q or prothrombin G20210A increased the adjusted hazard ratio for VTE from 1.4 for non-O blood type alone to 3.1 for non-O blood type with FVL heterozygosity and to 2.2 for non-O blood type with prothrombin G20210A heterozygosity. The population-attributable risk for VTE was 20% for non-O blood type, 10% for FVL R506Q, and 1% for prothrombin G20210A. Myocardial infarction was present in 4.1% of study participants but was not associated with non-O blood group or FVL R506Q; its association with prothrombin 20210 was of borderline significance (HR, 1.3; 95% confidence interval, 1.0-1.7; P=0.04).

Comment: A striking finding of this study is that the population-attributable risk for venous thromboembolism is higher in persons with non-O blood groups (20%) than in those with obesity (16%) or smoking (6%). The mechanism underlying this larger risk is unknown; less rapid clearance of certain procoagulants (factor VIII, von Willebrand factor) in persons with a non-O blood group is a possibility. Whatever the cause, blood type should be considered when evaluating a person's risk for VTE. - David Green, MD, PhD


Diabetic Ketoacidosis: Evaluation and Treatment (2869)
Westerberg AFP 87:337 03-01-3013

Diabetic ketoacidosis is characterized by a serum glucose level greater than 250 mg per dL, a pH less than 7.3, a serum bicarbonate level less than 18 mEq per L, an elevated serum ketone level, and dehydration. Insulin deficiency is the main precipitating factor. Diabetic ketoacidosis can occur in persons of all ages, with 14 percent of cases occurring in persons older than 70 years, 23 percent in persons 51 to 70 years of age, 27 percent in persons 30 to 50 years of age, and 36 percent in persons younger than 30 years. The case fatality rate is 1 to 5 percent. About one-third of all cases are in persons without a history of diabetes mellitus. Common symptoms include polyuria with polydipsia (98 percent), weight loss (81 percent), fatigue (62 percent), dyspnea (57 percent), vomiting (46 percent), preceding febrile illness (40 percent), abdominal pain (32 percent), and polyphagia (23 percent). Measurement of A1C, blood urea nitrogen, creatinine, serum glucose, electrolytes, pH, and serum ketones; complete blood count; urinalysis; electrocardiography; and calculation of anion gap and osmolar gap can differentiate diabetic ketoacidosis from hyperosmolar hyperglycemic state, gastroenteritis, starvation ketosis, and other metabolic syndromes, and can assist in diagnosing comorbid conditions. Appropriate treatment includes administering intravenous fluids and insulin, and monitoring glucose and electrolyte levels. Cerebral edema is a rare but severe complication that occurs predominantly in children. Physicians should recognize the signs of diabetic ketoacidosis for prompt diagnosis, and identify early symptoms to prevent it. Patient education should include information on how to adjust insulin during times of illness and how to monitor glucose and ketone levels, as well as information on the importance of medication compliance.

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Motivational Interviewing (2386)
JFP JFP 59:216 04-01-2020

Motivational Interviewing Tool Kit


Bariatric Surgery Summary (3630)
Kney Various 04-21-2017

Zinc supplements: If level is < 60 (normal 60-130 mcg/dl) - supplement with 1-2 mg/kg of elemental zinc. One common form is zinc sulfate 220 mg - containing 50 mg of elemental zinc.


Hiccups (3628)
PL 24:24 04-01-2017

Persistent hiccups are rare. May occur after surgery, or with GERD, cancer, pneumonia, or electrolyte imbalances. The standard treatment was chlorpromazine or metoclopramide. But chlorpromazine causes QT prolongation, and metoclopramide can cause tremors/movement disorders. Instead, try baclofen or gabapentin. Use for 7-10 days - if hiccups persist, change to another medication.


Holter-electrocardiogram- ischaemic stroke (Find-AFRANDOMISED): An open-label randomised controlled trial (3631)
Wachter R et al Lancet Neurol 16:282 04-01-2017

Recent studies have found that in patients with stroke of unknown cause (cryptogenic stroke), extended poststroke monitoring detects intermitted atrial fibrillation (AF) in 5% to 20%. In this manufacturer-funded study, investigators from Germany randomized 400 patients (aged >60) to 10-day Holter monitor recordings at three time points following ischemic stroke (baseline, 3 months, and 6 months) or to standard monitoring (≥24-hour Holter or telemetry monitoring). Patients with severe, ipsilateral carotid or intracranial stenosis or prior AF diagnosis were excluded. The primary endpoint was detection of AF or atrial flutter lasting 30 seconds or longer.

At 6 months, 14% of patients in the extended-monitoring group had AF detected, significantly more than the 5% in the standard group (number needed to screen, 11). The median time from study enrollment to detection of AF was similar in both groups (33 days vs. 36 days). Among 25 patients with AF detected by prolonged monitoring, 18 were noted in the first Holter recording period, 6 in the second period, and 1 in the third. All patients with AF detection were offered oral anticoagulation.

Comment: These findings add to the literature showing that screening for AF in older patients with stroke of no obvious atherosclerotic cause is worthwhile. The 14% detection rate is clinically significant, even with an older technique (Holter-ECG recordings). Whether extremely brief (<1 minute) episodes of AF require anticoagulation is still being studied. Nonetheless, clinicians should consider extended monitoring for AF in cryptogenic stroke, especially in older patients and patients with risk factors for AF such as prior congestive heart failure or left atrial enlargement.


Trial of pregabalin for acute and chronic sciatica (3624)
Mathieson S et al NEJM 376:111 03-23-2017

Gabapentin and pregabalin (Lyrica) are prescribed frequently for lumbosacral radicular pain, despite a lack of evidence that they are effective for this condition. In this randomized trial from Australia, researchers randomized 209 patients with sciatica to receive either pregabalin (titrated from 150 mg to 600 mg, depending on response and side effects) or placebo for as long as 8 weeks. At enrollment, duration of pain had been 1 week to 1 year (mean, 2 months); all patients had pain radiating below the knee and either dermatomal pain distribution, motor or sensory deficit, or diminished reflex. The primary outcome was leg pain at 8 weeks.

Improvement in the mean leg-pain score at 8 weeks actually was slightly greater in the placebo group than in the pregabalin group (decrease of 3.0 vs. 2.6 points, from a mean baseline of ≈6.1 on a 10-point scale), but the difference was not statistically significant; pain scores remained similar in the two groups at 1 year. Moreover, the groups did not differ on any secondary outcome (e.g., ratings of disability, quality of life, and global perceived effect). However, the frequency of side effects was significantly higher with pregabalin than with placebo - dizziness was most common (40% vs. 13%).

Comment: Pregabalin does not relieve pain associated with sciatica and should not be prescribed for this purpose; presumably, the same holds true for the related drug gabapentin. This finding is not surprising: Although pregabalin has some efficacy - and is FDA-approved for use - in patients with postherpetic neuralgia or diabetic peripheral neuropathy, the pathogenesis of pain in those conditions is different from that of radicular pain.


Association Between Radiation Therapy, Surgery, or Observation for Localized Prostate Cancer and Patient-Reported Outcomes After 3 Years (3629)
Barocas et al JAMA 317:1126 03-21-2017

Design, Setting, and Participants: Prospective, population-based, cohort study involving 2550 men (≤80 years) diagnosed in 2011-2012 with clinical stage cT1-2, localized prostate cancer, with prostate-specific antigen levels less than 50 ng/mL, and enrolled within 6 months of diagnosis.

Exposures: Treatment with radical prostatectomy, EBRT, or active surveillance was ascertained within 1 year of diagnosis.

Main Outcomes and Measures: Patient-reported function on the 26-item Expanded Prostate Cancer Index Composite (EPIC) 36 months after enrollment. Higher domain scores (range, 0-100) indicate better function. Minimum clinically important difference was defined as 10 to 12 points for sexual function, 6 for urinary incontinence, 5 for urinary irritative symptoms, 5 for bowel function, and 4 for hormonal function.

Results: The cohort included 2550 men (mean age, 63.8 years; 74% white, 55% had intermediate- or high-risk disease), of whom 1523 (59.7%) underwent radical prostatectomy, 598 (23.5%) EBRT, and 429 (16.8%) active surveillance. Men in the EBRT group were older (mean age, 68.1 years vs 61.5 years, P < .001) and had worse baseline sexual function (mean score, 52.3 vs 65.2, P < .001) than men in the radical prostatectomy group. At 3 years, the adjusted mean sexual domain score for radical prostatectomy decreased more than for EBRT (mean difference, −11.9 points; 95% CI, −15.1 to −8.7). The decline in sexual domain scores between EBRT and active surveillance was not clinically significant (−4.3 points; 95% CI, −9.2 to 0.7). Radical prostatectomy was associated with worse urinary incontinence than EBRT (−18.0 points; 95% CI, −20.5 to −15.4) and active surveillance (−12.7 points; 95% CI, −16.0 to −9.3) but was associated with better urinary irritative symptoms than active surveillance (5.2 points; 95% CI, 3.2 to 7.2). No clinically significant differences for bowel or hormone function were noted beyond 12 months. No differences in health-related quality of life or disease-specific survival (3 deaths) were noted (99.7%-100%).

Conclusions and Relevance: In this cohort of men with localized prostate cancer, radical prostatectomy was associated with a greater decrease in sexual function and urinary incontinence than either EBRT or active surveillance after 3 years and was associated with fewer urinary irritative symptoms than active surveillance; however, no meaningful differences existed in either bowel or hormonal function beyond 12 months or in in other domains of health-related quality-of-life measures. These findings may facilitate counseling regarding the comparative harms of contemporary treatments for prostate cancer.

Full article that includes some helpful graphs that can visually show patients the outcomes for each option.


Association of suicidality and depression with 5&#945;-reductase inhibitors (3634)
Welk B et al JAMA Intern Med 03-20-2017

Postmarketing surveillance has raised concerns that 5α-reductase inhibitors might increase risk for depression and suicide; the biologic plausibility of this association is supported by evidence that these drugs affect neuropeptides, testosterone, and other neurotransmitters. In this retrospective Canadian study, researchers identified about 93,000 older men (mean age, 75) who started new prescriptions for finasteride or dutasteride between 2003 and 2013; these men were matched by age, history of depression or suicidal thoughts, and other demographic and clinical variables with an equal number of men without such prescriptions. Data also were collected on suicide, new-onset depression, and self-harm (e.g., hospitalization or emergency department visits for suicide attempts) during continuous medication use plus 12 months after stopping.

At median follow-up of about 18 months, suicide rates were similar in both groups. Risk for self-harm was modestly but significantly elevated with active treatment compared with placebo (71 vs. 53 events per 100,000 person-years), as was risk for incident depression (767 vs. 530 events per 100,000 person-years). After 18 months, risk for self-harm faded and was no longer significant; risk for depression also faded but remained significant.

COMMENT: Retrospective cohort studies are messy, given the potential for unidentified confounders, and the differences in risk in this study are small, albeit statistically significant. These results might encourage clinicians to counsel patients about potential risks to mental health, but they're unlikely to discourage patients from using 5α-reductase inhibitors.


End-of-Life Care: Managing Common Symptoms (3622)
Ross AFP 95:356 03-15-2017

Physicians should be proficient at managing symptoms as patients progress through the dying process. When possible, proactive regimens that prevent symptoms should be used, because it is generally easier to prevent than to treat an acute symptom. As swallowing function diminishes, medications are typically administered sublingually, transdermally, or via rectal suppository. Opiates are the medication of choice for the control of pain and dyspnea, which are common symptoms in the dying process. Delirium and agitation may be caused by reversible etiologies, which should be identified and treated when feasible. When medications are required, haloperidol and risperidone are effective options for delirium. Nausea and vomiting should be treated with medications targeting the etiology. Constipation may be caused by low oral intake or opiate use. Preventive regimens to avoid constipation should include a stimulant laxative with a stool softener. Oropharyngeal secretions may lead to noisy breathing, sometimes referred to as a death rattle, which is common at the end of life. Providing anticipatory guidance helps families and caregivers normalize this symptom. Anticholinergic medications can modestly help reduce these secretions. Effective symptom control in end-of-life care can allow patients to progress through the dying process in a safe, dignified, and comfortable manner.

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