Here are the last 20 additions to the PBrain (total entries as of now = 3894)


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

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

Full article


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

Full article


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

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

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

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

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

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

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

Editorial


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

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

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

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


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

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

Findings of the meta-analysis included the following:

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


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

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

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

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


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

Full article


Association of thyroid hormone therapy with quality of life and thyroid-related symptoms in patients with subclinical hypothyroidism: A systematic review and meta-analysis (3882)
Feller M et al JAMA 320:1349 10-02-2018

The benefits of treating subclinical hypothyroidism (defined as elevated thyrotropin level and normal free thyroxine level) are unclear, and recent large trials have shown no value (e.g., NEJM JW Gen Med May 15 2017 and N Engl J Med 2017; 376:2534). This new meta-analysis included 21 randomized trials (2192 total patients) in which patients were treated for at least 1 month, with follow-up for at least 3 months. Various outcomes were assessed, including general quality of life, fatigue, depression, cognitive function, systolic blood pressure, and body-mass index.

Mean thyrotropin levels ranged from 4.4 to 12.8 mIU/L at baseline and from 0.5 to 3.7 mIU/L at the end of follow-up. Duration of therapy ranged from 3 to 18 months. No differences were found between the active treatment and control groups for any outcome.

Comment: We now have convincing evidence that treating patients with subclinical hypothyroidism generally is ineffective; if treatment does benefit occasional patients, we can't identify them prospectively. When clinicians treat patients with subclinical hypothyroidism who have symptoms they might associate with overt hypothyroidism, any benefit could well represent a placebo response.


Transcatheter mitral-valve repair in patients with heart failure (3883)
Stone GW et al NEJM 09-23-2018

Patients with heart failure (HF) and secondary mitral regurgitation (MR) have frequent hospitalizations and poor prognoses. Surgery, a class IIb guideline recommendation, is infrequently performed due to risk, a high recurrence rate with annuloplasty alone, and lack of demonstrated benefit. In the manufacturer-funded, randomized COAPT trial (NCT01626079), investigators compared transcatheter mitral repair with MitraClip plus guideline-directed medical therapy (GDMT) or GDMT alone in 614 patients with severe MR who were not appropriate for surgery (MR grades, 3+ or 4+; left ventricular ejection fraction, 20% to 50%; mean effective regurgitant orifice area, EROA, 0.40 cm2). Patients were included only if they had remained symptomatic despite previous GDMT, including resynchronization therapy where appropriate.

Patients were followed for up to 24 months. HF hospitalizations, the primary efficacy endpoint, were significantly fewer in the device group (36%/patient-year) than in the control group (68%/patient-year; hazard ratio, 0.53). All-cause mortality was 29% versus 46% (HR, 0.62). Device therapy also improved symptoms (New York Heart Association class) and quality of life (Kansas City Cardiomyopathy Questionnaire score) and better preserved functional capacity (6-minute walk distance). At 30 days, MR grade was reduced to ≤2+ in >90% of the device group and to 1+ in >70% of patients; at 2 years, improvement was sustained. The primary safety outcome, rate of freedom from device-related complications, was 97% at 1 year.

Comment: This is the first therapy demonstrating improved prognoses in patients with HF and severe secondary MR despite GDMT. The remarkable improvements in HF hospitalization, quality of life, and survival are due, to some extent, to deterioration in the control group and stabilization in the device group. The results contrast starkly with those of the Mitra.FR trial (JW Cardiol Oct 2018 and N Engl J Med 2018 Aug 27 [e-pub]); possible reasons include COAPT's inclusion of patients with more-severe MR, less end-stage left-ventricular function, more stable GDMT, and better MitraClip results (greater MR reduction and fewer complications). The findings will undoubtedly result in an expanded indication for MitraClip therapy and provide another option for our patients with HF and severe MR.


tatins for primary prevention of cardiovascular events and mortality in old and very old adults with and without type 2 diabetes: Retrospective cohort study (3884)
Ramos R et al BMJ 362:k3359 09-05-2018

Guidelines on cardiovascular disease (CVD) prevention classify most elders (age, ≥75) as eligible for statin therapy, because CVD risk is highly associated with age (NEJM JW Gen Med Dec 15 2013 and J Am Coll Cardiol 2014; 63:2935). However, little evidence supports statins for primary prevention in older patients. In this retrospective study, researchers in Spain used a primary care database to determine whether initiating statins for primary prevention lowers risks for atherosclerotic CVD and all-cause death in old and very old adults.

Participants were 47,000 elders (age, ≥75) without clinically recognized atherosclerotic CVD. Of these, 16% started statins. Median follow-up was 7.7 years. After multivariable adjustment, statins did not lower risks for atherosclerotic CVD and all-cause death among participants without diabetes. Among participants with type 2 diabetes who were 75 to 84, statins significantly lowered risks for atherosclerotic CVD (from 29 to 24 events/1000 person-years) and all-cause death (from 55 to 42 deaths/1000 person-years); among participants with type 2 diabetes who were 85 or older, statins did not lower risks for CVD and all-cause death.

Comment: In this study (which is subject to confounding), statin therapy for primary prevention did not lower risks for atherosclerotic CVD and all-cause death in older adults, except for those with type 2 diabetes who were 75 to 84. Notably, an Australian placebo-controlled randomized trial of statins for primary prevention of atherosclerotic CVD in people older than 70 will be completed in 2022. In the meantime, statin therapy for primary prevention in older people should be individualized.


Diclofenac use and cardiovascular risks: Series of nationwide cohort studies (3885)
Schmidt M et al BMJ 362:k3426 09-04-2018

Diclofenac is a commonly prescribed traditional nonsteroidal anti-inflammatory drug (NSAID) that targets mainly cyclooxygenase (COX)-2, similar to celecoxib and rofecoxib, which have been associated with excess cardiovascular (CV) risk. Indeed, evidence suggests that diclofenac also is associated with excess CV risk (NEJM JW Gen Med Sep 15 2018 and Ann Rheum Dis 2018; 77:1137). In this study, Danish researchers used a national propensity-matched patient registry to compare rates of major adverse CV events (i.e., a composite of cardiac-related death, myocardial infarction [MI], ischemic stroke, heart failure, and atrial fibrillation) after initiation of diclofenac, other NSAIDs, or acetaminophen.

Within 30 days of drug initiation, major adverse CV events occurred among 0.11% of diclofenac initiators, 0.08% of ibuprofen initiators, and 0.07% of naproxen initiators. In one propensity-adjusted comparison, major adverse CV events occurred among 0.16% of diclofenac initiators versus 0.13% of acetaminophen initiators; in another such comparison, adverse events occurred in 0.11% of diclofenac initiators versus 0.07% of those who did not initiate any drug. Compared with ibuprofen, acetaminophen, or naproxen, diclofenac conferred 20% to 30% higher adjusted relative risks for major adverse CV events; diclofenac initiators had 50% higher relative risk than did noninitiators. Risks remained elevated when data were stratified by age and sex. Risk for gastrointestinal (GI) bleeding at 30 days among diclofenac initiators was 4.5 times higher than risk in noninitiators, 2.5 times higher than that in ibuprofen and acetaminophen initiators, and similar to risk in naproxen initiators.

Comment: In this study, initiating diclofenac was associated with excess short-term CV and GI bleeding risks compared with initiating other NSAIDs or acetaminophen (or with no use of any drug). Given these risks, the authors conclude "there is little justification to initiate diclofenac treatment before other traditional NSAIDs."


Alcohol consumption and risk of dementia: 23 year follow-up of Whitehall II cohort study (3886)
Sabia S et al BMJ 362:k2927 08-01-2018

Prior studies suggest a J- or U-shaped relation between alcohol consumption and incident dementia, with moderate alcohol consumption associated with lowest dementia risk. However, these studies were methodologically flawed (e.g., assessed late-life, rather than lifetime, alcohol consumption). In this long-term, prospective, U.K. cohort study, researchers assessed the association between alcohol consumption and risk for dementia among 9100 middle-aged people (age range, 35-55 at study inception) without dementia. Midlife alcohol consumption was based on the mean of three assessments.

After mean follow-up of 23 years, 397 participants had developed dementia. After adjustment for multiple variables, abstinence at midlife was associated with significantly higher risk for dementia than was alcohol consumption of 1 to 14 units weekly. However, among participants who consumed >14 units weekly at midlife, each 7-unit increase in consumption was associated with a significant 18% increase in relative risk for dementia. The researchers also assessed longer-term patterns of alcohol intake beyond midlife: Compared with long-term consumption of 1 to 14 units weekly, significantly higher risks for dementia were observed for long-term abstinence (67% higher), decreasing consumption (50% higher), and long-term consumption of >14 units weekly (36% higher).

Comment: These results - which still could reflect confounding, despite extensive adjustments for sociodemographic and clinical variables - showed that abstaining from alcohol or consuming >14 units weekly was associated with higher risk for dementia, compared with moderate alcohol consumption. These results don't suggest that clinicians should recommend alcohol consumption to abstainers for preventing dementia. Rather, clinicians should advise patients who drink alcohol not to consume >14 units weekly.


Alcohol Use and Burden for 195 Countries and Territories, 1990-2016: A Systematic Analysis for the Global Burden of Disease Study, 2016 (3887)
GBD 2016 Alcohol Collaborators Lancet 392:1015 09-22-2018

Epidemiologic research conducted in developed nations has shown that moderate alcohol consumption - 1 to 2 drinks daily in men, and 1 drink daily in women - confers overall health benefits. In these studies, one drink generally is defined as consumption of 10 g of pure ethyl alcohol.

In the Global Burden of Diseases study, data were collected from developed and developing nations. Researchers report that all-cause and cancer-related mortality increase linearly with alcohol use, with no protective effect from moderate consumption. However, an apparent protective effect of moderate alcohol intake against ischemic heart disease was noted.

Comment: Some media coverage of this research claimed that the study disproved past advice on the health benefits of moderate alcohol intake. In my opinion, that is not the case. Past advice was predicated on moderate alcohol consumption's protective effect against vascular diseases, the chief causes of death in developed nations, and the results of this new study are consistent with that. The causes of death in developing nations are different: For example, in this study, tuberculosis (TB) was the major cause of death in young adults - showing the influence of mortality data from developing nations on the overall data set - and alcohol probably raises risk for TB reactivation. For our patients in developed nations, except for those with personal or family histories of breast (and possibly other) cancers, the vascular benefit of moderate alcohol intake still appears to offset potential harms.


Association between antibiotic prescribing for respiratory tract infections and patient satisfaction in direct-to-consumer telemedicine (3888)
Martinez KA et al Ann Intern Med 10-01-2018

Doctors might suspect that at least some patients gauge the quality of their medical care by the quantity of pharmaceuticals prescribed: The more drugs they receive, the happier they are. Researchers investigated this impression by analyzing telemedicine encounters from a single platform serving patients around the U.S. During a 3.5-year period, 8437 televisits were made for respiratory tract infections that usually are caused by viruses in adults; 66% of visits ended in antibiotic prescriptions, 15% in nonantibiotic prescriptions, and 18% in no prescriptions. Most patients were young adults (age range, 30-49); most of the 85 doctors were U.S.-trained family medicine specialists. All encounters included patient satisfaction ratings.

Top satisfaction scores were given by 72% of patients who received no prescription, by 86% of those who received nonantibiotic prescriptions, and by 91% of those who received antibiotic prescriptions. Physicians' satisfaction ratings correlated strongly with antibiotic prescribing rates: Few physicians with low antibiotic prescribing rates achieved high satisfaction scores, whereas almost all those who scored above the 90th percentile in satisfaction prescribed antibiotics more than 75% of the time.

Comment: It's hard to generalize from this study to ordinary medical care: Presumably patients and doctors were strangers, had no physical contact, and visits were quite brief (mean, 7 minutes). Still, this study lends credence to the theory that many patients expect something tangible from a medical visit. It also suggests that some physicians need to master the essential art of persuading patients they don't need unnecessary drugs (a conversation doubtless even more difficult to pull off during a tele-encounter than in the office).


Strategies for Caring for the Well Cancer Survivor (3889)
Arnold et al JFP 67:624 10-01-2018

Provides a nice summary of what we should be doing and how often in cancer survivors. For FU after radical prostatectomy, DRE are not needed so long as PSA is undetectable.

Full article


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


Here are the last 10 additions to the PBrain by date


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


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.


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

Full article


Association of thyroid hormone therapy with quality of life and thyroid-related symptoms in patients with subclinical hypothyroidism: A systematic review and meta-analysis (3882)
Feller M et al JAMA 320:1349 10-02-2018

The benefits of treating subclinical hypothyroidism (defined as elevated thyrotropin level and normal free thyroxine level) are unclear, and recent large trials have shown no value (e.g., NEJM JW Gen Med May 15 2017 and N Engl J Med 2017; 376:2534). This new meta-analysis included 21 randomized trials (2192 total patients) in which patients were treated for at least 1 month, with follow-up for at least 3 months. Various outcomes were assessed, including general quality of life, fatigue, depression, cognitive function, systolic blood pressure, and body-mass index.

Mean thyrotropin levels ranged from 4.4 to 12.8 mIU/L at baseline and from 0.5 to 3.7 mIU/L at the end of follow-up. Duration of therapy ranged from 3 to 18 months. No differences were found between the active treatment and control groups for any outcome.

Comment: We now have convincing evidence that treating patients with subclinical hypothyroidism generally is ineffective; if treatment does benefit occasional patients, we can't identify them prospectively. When clinicians treat patients with subclinical hypothyroidism who have symptoms they might associate with overt hypothyroidism, any benefit could well represent a placebo response.


Association between antibiotic prescribing for respiratory tract infections and patient satisfaction in direct-to-consumer telemedicine (3888)
Martinez KA et al Ann Intern Med 10-01-2018

Doctors might suspect that at least some patients gauge the quality of their medical care by the quantity of pharmaceuticals prescribed: The more drugs they receive, the happier they are. Researchers investigated this impression by analyzing telemedicine encounters from a single platform serving patients around the U.S. During a 3.5-year period, 8437 televisits were made for respiratory tract infections that usually are caused by viruses in adults; 66% of visits ended in antibiotic prescriptions, 15% in nonantibiotic prescriptions, and 18% in no prescriptions. Most patients were young adults (age range, 30-49); most of the 85 doctors were U.S.-trained family medicine specialists. All encounters included patient satisfaction ratings.

Top satisfaction scores were given by 72% of patients who received no prescription, by 86% of those who received nonantibiotic prescriptions, and by 91% of those who received antibiotic prescriptions. Physicians' satisfaction ratings correlated strongly with antibiotic prescribing rates: Few physicians with low antibiotic prescribing rates achieved high satisfaction scores, whereas almost all those who scored above the 90th percentile in satisfaction prescribed antibiotics more than 75% of the time.

Comment: It's hard to generalize from this study to ordinary medical care: Presumably patients and doctors were strangers, had no physical contact, and visits were quite brief (mean, 7 minutes). Still, this study lends credence to the theory that many patients expect something tangible from a medical visit. It also suggests that some physicians need to master the essential art of persuading patients they don't need unnecessary drugs (a conversation doubtless even more difficult to pull off during a tele-encounter than in the office).


Strategies for Caring for the Well Cancer Survivor (3889)
Arnold et al JFP 67:624 10-01-2018

Provides a nice summary of what we should be doing and how often in cancer survivors. For FU after radical prostatectomy, DRE are not needed so long as PSA is undetectable.

Full article


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.


Transcatheter mitral-valve repair in patients with heart failure (3883)
Stone GW et al NEJM 09-23-2018

Patients with heart failure (HF) and secondary mitral regurgitation (MR) have frequent hospitalizations and poor prognoses. Surgery, a class IIb guideline recommendation, is infrequently performed due to risk, a high recurrence rate with annuloplasty alone, and lack of demonstrated benefit. In the manufacturer-funded, randomized COAPT trial (NCT01626079), investigators compared transcatheter mitral repair with MitraClip plus guideline-directed medical therapy (GDMT) or GDMT alone in 614 patients with severe MR who were not appropriate for surgery (MR grades, 3+ or 4+; left ventricular ejection fraction, 20% to 50%; mean effective regurgitant orifice area, EROA, 0.40 cm2). Patients were included only if they had remained symptomatic despite previous GDMT, including resynchronization therapy where appropriate.

Patients were followed for up to 24 months. HF hospitalizations, the primary efficacy endpoint, were significantly fewer in the device group (36%/patient-year) than in the control group (68%/patient-year; hazard ratio, 0.53). All-cause mortality was 29% versus 46% (HR, 0.62). Device therapy also improved symptoms (New York Heart Association class) and quality of life (Kansas City Cardiomyopathy Questionnaire score) and better preserved functional capacity (6-minute walk distance). At 30 days, MR grade was reduced to ≤2+ in >90% of the device group and to 1+ in >70% of patients; at 2 years, improvement was sustained. The primary safety outcome, rate of freedom from device-related complications, was 97% at 1 year.

Comment: This is the first therapy demonstrating improved prognoses in patients with HF and severe secondary MR despite GDMT. The remarkable improvements in HF hospitalization, quality of life, and survival are due, to some extent, to deterioration in the control group and stabilization in the device group. The results contrast starkly with those of the Mitra.FR trial (JW Cardiol Oct 2018 and N Engl J Med 2018 Aug 27 [e-pub]); possible reasons include COAPT's inclusion of patients with more-severe MR, less end-stage left-ventricular function, more stable GDMT, and better MitraClip results (greater MR reduction and fewer complications). The findings will undoubtedly result in an expanded indication for MitraClip therapy and provide another option for our patients with HF and severe MR.


Alcohol Use and Burden for 195 Countries and Territories, 1990-2016: A Systematic Analysis for the Global Burden of Disease Study, 2016 (3887)
GBD 2016 Alcohol Collaborators Lancet 392:1015 09-22-2018

Epidemiologic research conducted in developed nations has shown that moderate alcohol consumption - 1 to 2 drinks daily in men, and 1 drink daily in women - confers overall health benefits. In these studies, one drink generally is defined as consumption of 10 g of pure ethyl alcohol.

In the Global Burden of Diseases study, data were collected from developed and developing nations. Researchers report that all-cause and cancer-related mortality increase linearly with alcohol use, with no protective effect from moderate consumption. However, an apparent protective effect of moderate alcohol intake against ischemic heart disease was noted.

Comment: Some media coverage of this research claimed that the study disproved past advice on the health benefits of moderate alcohol intake. In my opinion, that is not the case. Past advice was predicated on moderate alcohol consumption's protective effect against vascular diseases, the chief causes of death in developed nations, and the results of this new study are consistent with that. The causes of death in developing nations are different: For example, in this study, tuberculosis (TB) was the major cause of death in young adults - showing the influence of mortality data from developing nations on the overall data set - and alcohol probably raises risk for TB reactivation. For our patients in developed nations, except for those with personal or family histories of breast (and possibly other) cancers, the vascular benefit of moderate alcohol intake still appears to offset potential harms.