Here are the last 20 additions to the PBrain (total entries as of now = 3670)


Short term use of oral corticosteroids and related harms among adults in the United States: Population based cohort study (3651)
Waljee AK et al BMJ 357:j1415 04-12-2017

Although the adverse effects of long-term corticosteroids are clear, relatively little is known about short-term use. In this retrospective U.S. study, researchers used a nationwide commercial insurance claims dataset to determine the incidence of three adverse effects (sepsis, venous thromboembolism, and fracture) associated with oral corticosteroid use for <30 days by >1.5 million adults (age range, 18-64; mean age, 45) continuously enrolled from 2012 through 2014.

In all, 21% of participants received at least one short-term prescription for an oral corticosteroid (median duration, 6 days; median prednisone equivalent dose, 20 mg daily). Nearly half (47%) of patients received a 6-day "dosepack" of methylprednisolone. Respiratory tract infections and disorders, spinal conditions, and allergies accounted for 56% of prescriptions. In users compared with nonusers, incidence rates for sepsis (1.8 vs. 1.0 per 1000 person-years), venous thromboembolism (VTE; 4.6 vs. 2.4), and fracture (21.4 vs. 14.3) were significantly higher regardless of age. In a self-controlled case series, risks for sepsis (incidence rate ratio, 5.3), VTE (IRR, 3.3), and fracture (IRR, 1.9) were significantly higher during the 5 to 30 days after the prescription date than the 5 to 180 days before the prescription date.

Comment: An astonishing one in five commercially insured adults received a short course of oral corticosteroid therapy during this 3-year study period. Although the absolute excess risk for sepsis, VTE, and fracture associated with short-term corticosteroid use was low, the cumulative number of affected people was not trivial; widespread use of short-term oral corticosteroids thus has substantial public health implications. Clinicians should not administer short-term oral corticosteroids for conditions in which such agents are ineffective. For conditions in which corticosteroids might provide transient symptom relief but are not essential, clinicians should think twice before prescribing these drugs.


Cost-effectiveness of common diagnostic approaches for evaluation of asymptomatic microscopic hematuria (3652)
Halpern JA et al JAMA Intern Med 04-17-2017

Asymptomatic microscopic hematuria (AMH; defined by red blood cells on urine microscopy, not dipstick testing) raises concerns about occult genitourinary cancer. In this decision analysis, investigators used standard research sources and evidence-based assumptions to assess the cost-effectiveness of detecting genitourinary cancer with each of four strategies:

Neither ultrasound alone nor voided-urine cytology were evaluated, due to their relatively poor sensitivity.

Combination renal ultrasound and cystoscopy was the most cost-effective, with an incremental cost per cancer detected of about US$53,000. Substituting CT urography for ultrasound detected only one additional cancer, at markedly higher incremental cost per cancer detected (≈$6.5 million) and greater clinical risk (e.g., radiation, contrast exposure). Analyses in high-risk patients (i.e., men, smokers, and older patients [age, ≥50]) yielded similar results, although at a lower incremental cost per cancer detected. Results were the same in multiple sensitivity analyses.

Comment: These results challenge the recommendations of some U.S. professional organizations, and confirm those of some international groups. This was not a cost-utility analysis, in which length and quality of life are taken into account. However, the stability of these results across multiple analyses suggests that renal ultrasound and cystoscopy is the preferred approach to evaluation of asymptomatic microscopic hematuria.


A Man with Pain and Swelling of the Left Calf and a Purpuric Rash (3653)
Miloslavsky et al NEJM 376:1868 05-11-2017

A very interesting and clear discussion of vasculitis. First, try to determine if it is secondary to cancer, infection (RMSF, meningococcal infection, SBE), drug use (cocaine/levamisole), other inflammatory conditions (SLR, Sjogrens). If it is a primary vasculitis, check ANCA, look for eosinophils on a CBC, look for renal/lung/sinus involvement, check for hepatitis B/C - in this case, the cause was IgA vasculitis (formerly known as Henoch-Schonlien purpura).

Full article


Management of Depression in Older Adults: A Review (3654)
Kok et al JAMA 317: 2114 05-23-2017

Observations: Depression presents with the same symptoms in older adults as it does in younger populations. In contrast to younger patients, older adults with depression more commonly have several concurrent medical disorders and cognitive impairment. Depression occurring in older patients is often undetected or inadequately treated. Antidepressants are the best-studied treatment option, but psychotherapy, exercise therapy, and electroconvulsive therapy may also be effective. Psychotherapy is recommended for patients with mild to moderate severity depression. Many older patients need the same doses of antidepressant medication that are used for younger adult patients. Although antidepressants may effectively treat depression in older adults, they tend to pose greater risk for adverse events because of multiple medical comorbidities and drug-drug interactions in case of polypharmacy. High-quality evidence does not support the use of pharmacologic treatment of depression in patients with dementia. Polypharmacy in older patients can be minimized by using the Screening Tool of Older Persons Prescriptions and Screening Tool to Alert doctors to Right Treatment (STOPP/START) criteria, a valid and reliable screening tool that enables physicians to avoid potentially inappropriate medications, undertreatment, or errors of omissions in older people. Antidepressants can be gradually tapered over a period of several weeks, but discontinuation of antidepressants may be associated with relapse or recurrence of depression, so the patient should be closely observed.

Conclusions and Relevance: Major depression in older adults is common and can be effectively treated with antidepressants and electroconvulsive therapy. Psychological therapies and exercise may also be effective for mild-moderate depression, for patients who prefer nonpharmacological treatment, or for patients who are too frail for drug treatments.

STOPP-START

Full article


Antithrombotic Therapy for Venous Thromboembolic Disease (3655)
Jain et al JAMA 317:2008 05-16-2017

Major recommendations:

Full article


Thiazide treatment in primary hyperparathyroidism - a new indication for an old medication? (3656)
Tsvetov G et al J Clin Endocrinol Metab 102 04-01-2017

A recent study suggested that primary hyperparathyroidism often is present in patients with thiazide-associated hypercalcemia and that the hypercalcemia usually is mild and nonprogressive in these cases (NEJM JW Gen Med Apr 15 2016 and J Clin Endocrinol Metab 2016; 101:1166). In this new retrospective study, researchers analyzed data on 72 patients with known primary hyperparathyroidism who had serum and urine calcium measurements both before initiation of hydrochlorothiazide (HCTZ) and during an average of 3 years of HCTZ therapy.

Mean serum calcium level was 10.7 mg/dL before HCTZ exposure and did not change significantly during HCTZ therapy. Eleven patients had pre-HCTZ serum calcium levels ≥11.5 mg/dL; after HCTZ was initiated, serum calcium levels declined in 9 of these patients and increased to >12.0 mg/dL in 2 patients. HCTZ was associated with decreases in mean urine calcium level (from 427 mg/day to 251 mg/day) and mean parathyroid hormone level (from 115 pg/day to 74 pg/dL).

Comment: This study suggests that thiazide diuretics can be given safely to patients with primary hyperparathyroidism. In fact, thiazide-induced reduction in hypercalciuria might benefit patients by lowering risk for calcium kidney stone formation. However, serum calcium levels still should be monitored periodically, because they occasionally will increase further when patients with primary hyperparathyroidism receive thiazide diuretics.


Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report: GOLD executive summary (3657)
Vogelmeier CF et al Am J Respir Crit Care Med 195:557 03-01-2017

The World Health Organization (WHO) and NIH convened the original GOLD expert panel in 1998 to make recommendations for managing COPD. Since the release of its first guidelines in 2001, GOLD has published several revisions, most recently in 2014.

Key Points:

COMMENT: Although not a lot is new in these guidelines, big "take homes" include less emphasis on inhaled steroids, shorter duration of systemic steroids for exacerbations, and more emphasis on symptoms and exacerbation history in guiding therapy choices. A 37-page "pocket guide" to the 2017 GOLD guidelines is available online.


Spiraling Out of Control (3658)
Mixter et al NEJM 376:2183 06-01-2017

A 22-year-old man presented to the emergency department on Christmas Day with a 5-day history of myalgias, cough, dyspnea, nonbilious emesis, and nonbloody diarrhea. Although he had been ill for several days, he ultimately sought treatment because of intractable vomiting. He reported feeling feverish, although he had not measured his temperature, and noted one episode of hemoptysis.

Full case report.


A Boy with Acute Fear of Choking while Swallowing (3659)
Carroll et al NEJM 376:2266 06-08-2017

A 14-year-old boy was seen in the emergency department of this hospital because of fear of choking while swallowing.

The patient had been well until 2 days before admission, when he choked while eating a piece of chicken during dinner. He became fearful of swallowing and was unable to finish the meal despite cutting his food into small pieces. The next day, he vomited after trying to eat ice cream, and his daily fluid intake decreased to only 710 ml (24 oz) of water. He reportedly needed his mother near him throughout the day and had an "irrational fear" of choking. He had not had recent fevers, rhinorrhea, cough, or sore throat. Nine days earlier, during a routine annual examination at the clinic of the patient’s primary care pediatrician, the patient's mother reported that he had had several episodes of inspiratory stridor while he was sleeping during the past few weeks; the patient was referred to an otolaryngologist, but this visit had not yet occurred. On the day of this presentation, the patient consumed only small sips of water, reported feeling hungry, and slept most of the day. His mother noted that, in addition to the inspiratory stridor during sleep, the patient had some gasping for air that was associated with deep involuntary burping. She contacted a physician at this hospital and was advised to bring the patient to the emergency department for evaluation.

Full case report


Alzheimer Disease: Pharmacologic and Nonpharmacologic Therapies (3660)
Epperly et al AFP 95:771 06-15-2017

Alzheimer disease comprises a syndrome of progressive cognitive and functional decline. Treatments should target cognitive and functional symptoms. Cholinesterase inhibitors, memantine, and a combination of a cholinesterase inhibitor and memantine have produced statistically significant but clinically small delays in various domains of cognitive and functional decline in select patients with Alzheimer disease. Vitamin E has been shown to delay functional decline in patients with mild to moderate Alzheimer disease, especially when taken in combination with a cholinesterase inhibitor. Structured programs of physical exercise improve physical function and reduce rates of neuropsychiatric symptoms in patients with mild to severe Alzheimer disease. Cognitive stimulation programs show benefit in maintenance of cognitive function and improved self-reported quality of life in patients with mild to moderate Alzheimer disease.

The bottom line is that, though cholinesterase inhibitors are commonly prescribed (some at great cost), the benefit is on the order of 3 points on a 70 point dementia scale. Even combined therapy with memantine results in about a 3 point benefit on a 100 point scale. There is no lasting benefit - once meds are stopped, the scores between placebo and active treatment are identical. Vitamin E 2000 IU bid results in about the same benefit - 3 points on a 78 point scale over 4 years (one estimate is that this treatment reduces the decline in function by the equivalent of about 7 months. We clearly need better treatments.

Full article


Reducing CV Risk in Diabetes: ADA Update (3661)
Skolnik et al JFP 66:300 05-01-2017

Tidbits:

Full article


Effect of intra-articular triamcinolone vs saline on knee cartilage volume and pain in patients with knee osteoarthritis: A randomized clinical trial (3662)
McAlindon TE et al JAMA 317:1967 05-16-2017

Inflammation probably plays a role in osteoarthritis (OA), and some evidence suggests that this inflammation can lead to progressive cartilage loss. Corticosteroid injections have been evaluated for managing OA of the knee, and an earlier report suggested that injections every 3 months are safe (Arthritis Rheum 2003; 48:370), even though steroids have antianabolic effects on healthy cartilage.

In this 2-year, double-blind U.S. clinical trial, 140 patients (mean age, 58) with symptomatic knee OA and ultrasound-demonstrated effusion and synovitis were randomized to intra-articular injections of triamcinolone or placebo every 3 months. At 2 years, triamcinolone patients exhibited significantly greater loss in cartilage thickness (mean, 0.2 mm vs. 0.1 mm in placebo patients) and no significant difference in pain. Triamcinolone was not associated with faster progression of other osteoarthritis features, structurally or clinically.

Comment: In this study, pain relief was assessed only every 3 months, short-term pain relief was not evaluated, and patients were permitted to continue background treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). We don't know exactly what loss of cartilage volume means clinically, and short-term pain relief without radiographic changes has been demonstrated in other studies. I would not abandon intra-articular steroid injections as an option for some patients: For example, occasional injections are reasonable for patients with severe pain who cannot take NSAIDs or who don't respond to them. However, this study raises concerns about repetitive injections, and, in a 2014 study, faster rates of cartilage loss were associated with higher incidence of arthroplasties (Osteoarthritis Cartilage 2014; 22:1542).


Adverse events associated with unblinded, but not with blinded, statin therapy in the ASCOT-LLA: A randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase (3663)
Gupta A et al Lancet 05-02-2017

In randomized, blinded clinical trials, statin therapy is associated only rarely with myopathy (muscle pain or weakness plus substantially elevated creatine kinase levels; generally <0.2% of patients per year of treatment). But, in observational studies, as many as one fifth of statin users report muscle pain or weakness.

To better understand this discrepancy, researchers (funded by a manufacturer of atorvastatin) reanalyzed data from the lipid-lowering arm of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT-LLA; NEJM JW Gen Med May 15 2003 and Lancet 2003; 361:1149), in which more than 10,000 adults with hypertension were randomized to daily atorvastatin (10 mg) or placebo. The lipid arm of the trial was stopped after a mean 3.3 years of follow-up after an interim analysis showed significantly better cardiovascular outcomes with atorvastatin. All patients then were offered open-label atorvastatin (about two thirds of each group accepted), and clinical follow-up continued for a mean 2.3 additional years. In the blinded phase, muscle symptoms were reported at a similar rate in both groups (about 2% annually). However, in the unblinded phase, muscle symptoms were reported significantly more often among statin users than nonusers (1.26% vs. 1.00% annually).

Comment: In this study, selection and ascertainment bias were eliminated, because the same patients and ascertainment methodology were used in both phases. It appears to exemplify the "nocebo effect" - the subjective experience of expected adverse drug effects that occurs equally in both arms of a blinded trial but is revealed in an unblinded observational study. Editorialists urge physicians to "alert their patients to possible statin-associated side-effects without raising negative expectations."


Arthroscopic surgery for degenerative knee arthritis and meniscal tears: A clinical practice guideline (3664)
Siemieniuk RAC et al BMJ 357:j1982 05-10-2017

Many studies show that conservative therapy, including physical therapy, is not inferior to arthroscopy for patients with knee osteoarthritis (e.g., NEJM JW Gen Med Aug 1 2015 and BMJ 2015; 350:274). For this report, investigators reviewed 13 randomized, controlled trials and 12 observational studies in which arthroscopic surgery was compared with conservative management (including sham surgery) in patients with degenerative knee disease. Degenerative knee disease was defined as persistent knee pain, with or without osteoarthritis, that affects a patient's quality of life. Arthroscopic procedures were defined as debridement, partial meniscectomy, or both.

Key Points Patients who undergo failed conservative therapies often erroneously attribute marked improvements after surgery to the procedure itself instead of to natural improvement over time or to placebo effects.

  • In <15% of participants, arthroscopic surgery resulted in small or very small improvement in pain or function at 3 months after surgery - this benefit was not sustained at 1 year.
  • During follow-up of at least 2 years, pain and function after arthroscopy was similar to pain and function after conservative therapy.
  • The guideline panel strongly recommends against use of arthroscopy in nearly all patients who have degenerative knee disease, with or without imaging evidence of osteoarthritis, mechanical symptoms, or sudden onset of symptoms.
  • Comment: This study makes one wonder why knee arthroscopy is the most common orthopedic procedure. These recommendations reinforce that initial conservative management is best in almost all patients with knee pain.


    Effect of statin treatment vs usual care on primary cardiovascular prevention among older adults: The ALLHAT-LLT randomized clinical trial (3665)
    Han BH et al JAMA Intern Med 05-22-2017

    One quarter to one third of older adults (age, ≥75) in the U.S. take statins for primary prevention of coronary heart disease (CHD). Researchers undertook a secondary analysis of data from the lipid-lowering component of the ALLHAT trial (NEJM JW Gen Med Feb 1 2003 and JAMA 2002; 288:2998), from which they identified 2867 adults (age, ≥65; mean age, 71) who were randomized to pravastatin (40 mg daily) or usual care. Participants had stage 1 or 2 hypertension and at least one additional CHD risk factor (about 25% were smokers; 50% had type 2 diabetes) but no known CHD. About one third of usual-care patients had crossed over to statin treatment by year 6. Data were analyzed according to original randomization.

    Six-year all-cause mortality in patients who were 65 to 74 was 15.5 per 100 pravastatin participants and 14.2 per 100 usual-care participants - a nonsignificant difference. All-cause mortality among the oldest participants (age, ≥75) was 31.0 per 100 pravastatin participants and 22.7 per 100 usual-care participants (P=0.07). No differences in cardiovascular-specific mortality were found between groups.

    Comment: The lack of benefit with pravastatin for either all-cause or cardiovascular-specific mortality in older adults with CHD risk factors but without actual CHD should influence decision making about our use of statins for primary CHD prevention in older adults.


    Long term gluten consumption in adults without celiac disease and risk of coronary heart disease: Prospective cohort study (3666)
    Lebwohl B et al BMJ 357:j1892 05-02-2017

    In people with celiac disease, the gluten found in barley, rye, and wheat triggers an inflammatory response. Some studies have suggested that celiac disease might be associated with excess risk for coronary heart disease (CHD), but whether gluten intake itself is associated with CHD is unknown. Researchers evaluated associations between long-term gluten intake and risk for CHD (fatal or nonfatal myocardial infarction) among 65,000 women in the Nurses' Health Study and 45,000 men in the Health Professionals Follow-up Study without CHD or celiac disease at baseline.

    Gluten intake was estimated from food questionnaires that were completed every 4 years between 1986 and 2010. During 26 years of follow-up, participants in the lowest quintile of gluten intake had a higher CHD incidence than participants in the highest-intake quintile (352 vs. 277 events per 100,000 person-years). The association between high gluten intake and lower CHD risk persisted after adjustment for numerous potential confounders.

    Comment: Some of my patients without celiac disease are switching to gluten-free diets on the belief that it's healthy. However, this study suggests that for at least one measure of health - coronary disease - the reverse might be true: High gluten intake was associated with lower - not higher - risk for CHD. The authors note that "avoidance of dietary gluten may result in low intake of whole grains, which are associated with cardiovascular benefits."


    Triple therapy versus biologic therapy for active rheumatoid arthritis: A cost-effectiveness analysis (3667)
    Bansback N et al Ann Intern Med 05-30-2017

    The standard of care for rheumatoid arthritis (RA) patients who respond inadequately to initial methotrexate therapy is to add either an anti-tumor necrosis factor (TNF) agent (i.e., a biologic) or sulfasalazine plus hydroxychloroquine (i.e., triple therapy). Despite evidence that these strategies yield similar responses, only 2.5% of RA patients are given triple therapy with nonbiologics before a biologic.

    In this cost-effectiveness analysis, researchers used data from a randomized trial that yielded similar outcomes for these two strategies in 353 RA patients (NEJM JW Gen Med Aug 15 2013 and N Engl J Med 2013; 369:307). Biologic therapy resulted in 0.15 additional lifetime quality-adjusted life-years (QALYs), at an additional cost of about US$77,000. This cost per 0.15 additional QALYs extrapolates to an incremental cost-effectiveness ratio of about $520,000 per QALY per patient.

    Comment: This study suggests that first-line biologic therapy is not cost-effective. So why is triple therapy used in only a small proportion of RA patients? Unquestionably, biologic therapies prompt a more rapid response; also, the pill burden of triple therapy can be difficult. But aggressive marketing to patients by the pharmaceutical industry likely is a contributing factor. In this cost-conscious era, a trial of triple therapy might be warranted, but reversing the inertia of early use of biologic therapies will be difficult in the U.S.


    Levocetirizine and prednisone are not superior to levocetirizine alone for the treatment of acute urticaria: A randomized double-blind clinical trial (3668)
    Barniol C et al Ann Emerg Med 05-03-2017

    Antihistamines are the main treatment for isolated urticaria without angioedema, but some physicians also prescribe steroids.

    To determine whether combining prednisone with the nonsedating H1 blocker levocetirizine adds benefit in this setting, French investigators at two academic emergency departments conducted a double-blind, randomized, controlled trial involving 100 patients with acute urticaria of ≤24 hours duration. Patients received levocetirizine (5 mg orally per day for 5 days) plus either prednisone or placebo (40 mg orally per day for 4 days). Similar percentages of prednisone and placebo recipients achieved an itch score of zero at 2 days (62% and 76%, respectively), suffered relapses (30% and 24%), and experienced mild adverse events (12% and 14%); no serious adverse events were reported.

    Comment: When treating isolated urticaria without angioedema, use a nonsedating antihistamine or diphenhydramine (a sedating antihistamine), if tolerated, and skip the steroids.


    Treatment of low bone density or osteoporosis to prevent fractures in men and women: A clinical practice guideline update from the American College of Physicians (3669)
    Qaseem A et al Ann Intern Med 166:818 06-06-2017

    For fracture prevention, decisions on whom to treat - and for how long - are not always straightforward. This guideline updates previous ACP recommendations for managing low bone density or osteoporosis to prevent fractures. Osteoporosis is defined as having sustained a fragility fracture or having a bone-mineral density (BMD) T-score <- -2.5.

    Key Recommendations: The authors make only two "strong" recommendations (based on high- or moderate-quality evidence):

    Four other recommendations are graded as "weak" (based on low-quality evidence):

    Comment: These guideline authors looked for evidence that an intervention lowers incidence of fractures (and does not simply bring about favorable change on the surrogate endpoint of BMD). Strong evidence results in strong treatment recommendations, whereas weak or inconclusive evidence generally leads the authors to err on the side of nonintervention. In my view, the guideline is reasonably balanced - but one must read beyond the brief bulleted list of six recommendations to appreciate it.

    An editorialist who is a clinician-researcher with expertise in this area largely supports these recommendations, noting that "they provide a solid basis for informed clinical decisions about individual patients." However, he notes that treatment beyond 5 years sometimes is warranted, that BMD monitoring during therapy sometimes is useful (although he considers the recommendation against monitoring to be "generally appropriate"), and that the parathyroid hormone fragment teriparatide (Forteo) could have received more attention.


    Follow-Up of Prostatectomy versus Observation for Early Prostate Cancer (3670)
    Wilt et al NEJM 377:132 07-13-2017

    BACKGROUND: We previously found no significant differences in mortality between men who underwent surgery for localized prostate cancer and those who were treated with observation only. Uncertainty persists regarding nonfatal health outcomes and long-term mortality.

    METHODS: From November 1994 through January 2002, we randomly assigned 731 men with localized prostate cancer to radical prostatectomy or observation. We extended follow-up through August 2014 for our primary outcome, all-cause mortality, and the main secondary outcome, prostate-cancer mortality. We describe disease progression, treatments received, and patient-reported outcomes through January 2010 (original follow-up).

    RESULTS: During 19.5 years of follow-up (median, 12.7 years), death occurred in 223 of 364 men (61.3%) assigned to surgery and in 245 of 367 (66.8%) assigned to observation (absolute difference in risk, 5.5 percentage points; 95% confidence interval [CI], −1.5 to 12.4; hazard ratio, 0.84; 95% CI, 0.70 to 1.01; P=0.06). Death attributed to prostate cancer or treatment occurred in 27 men (7.4%) assigned to surgery and in 42 men (11.4%) assigned to observation (absolute difference in risk, 4.0 percentage points; 95% CI, −0.2 to 8.3; hazard ratio, 0.63; 95% CI, 0.39 to 1.02; P=0.06). Surgery may have been associated with lower all-cause mortality than observation among men with intermediate-risk disease (absolute difference, 14.5 percentage points; 95% CI, 2.8 to 25.6) but not among those with low-risk disease (absolute difference, 0.7 percentage points; 95% CI, −10.5 to 11.8) or high-risk disease (absolute difference, 2.3 percentage points; 95% CI, −11.5 to 16.1) (P=0.08 for interaction). Treatment for disease progression was less frequent with surgery than with observation (absolute difference, 26.2 percentage points; 95% CI, 19.0 to 32.9); treatment was primarily for asymptomatic, local, or biochemical (prostate-specific antigen) progression. Urinary incontinence and erectile and sexual dysfunction were each greater with surgery than with observation through 10 years. Disease-related or treatment-related limitations in activities of daily living were greater with surgery than with observation through 2 years.

    CONCLUSIONS: After nearly 20 years of follow-up among men with localized prostate cancer, surgery was not associated with significantly lower all-cause or prostate-cancer mortality than observation. Surgery was associated with a higher frequency of adverse events than observation but a lower frequency of treatment for disease progression, mostly for asymptomatic, local, or biochemical progression.

    Full article

    These results are a little difficult to put in a 15 second summary. I think it is easiest to show the charts on page 137 with confidence intervals - and that death from prostate cancer (where the rubber meets the road) is less likely with surgery, For those with Gleason <= 7, death from prostate cancer occurred in about 8% with observation vs 5% with surgery. For those with PSA < 10, the death from prostate cancer occurred in about 10% with observation vs 7% with surgery.


    Here are the last 10 additions to the PBrain by date


    Follow-Up of Prostatectomy versus Observation for Early Prostate Cancer (3670)
    Wilt et al NEJM 377:132 07-13-2017

    BACKGROUND: We previously found no significant differences in mortality between men who underwent surgery for localized prostate cancer and those who were treated with observation only. Uncertainty persists regarding nonfatal health outcomes and long-term mortality.

    METHODS: From November 1994 through January 2002, we randomly assigned 731 men with localized prostate cancer to radical prostatectomy or observation. We extended follow-up through August 2014 for our primary outcome, all-cause mortality, and the main secondary outcome, prostate-cancer mortality. We describe disease progression, treatments received, and patient-reported outcomes through January 2010 (original follow-up).

    RESULTS: During 19.5 years of follow-up (median, 12.7 years), death occurred in 223 of 364 men (61.3%) assigned to surgery and in 245 of 367 (66.8%) assigned to observation (absolute difference in risk, 5.5 percentage points; 95% confidence interval [CI], −1.5 to 12.4; hazard ratio, 0.84; 95% CI, 0.70 to 1.01; P=0.06). Death attributed to prostate cancer or treatment occurred in 27 men (7.4%) assigned to surgery and in 42 men (11.4%) assigned to observation (absolute difference in risk, 4.0 percentage points; 95% CI, −0.2 to 8.3; hazard ratio, 0.63; 95% CI, 0.39 to 1.02; P=0.06). Surgery may have been associated with lower all-cause mortality than observation among men with intermediate-risk disease (absolute difference, 14.5 percentage points; 95% CI, 2.8 to 25.6) but not among those with low-risk disease (absolute difference, 0.7 percentage points; 95% CI, −10.5 to 11.8) or high-risk disease (absolute difference, 2.3 percentage points; 95% CI, −11.5 to 16.1) (P=0.08 for interaction). Treatment for disease progression was less frequent with surgery than with observation (absolute difference, 26.2 percentage points; 95% CI, 19.0 to 32.9); treatment was primarily for asymptomatic, local, or biochemical (prostate-specific antigen) progression. Urinary incontinence and erectile and sexual dysfunction were each greater with surgery than with observation through 10 years. Disease-related or treatment-related limitations in activities of daily living were greater with surgery than with observation through 2 years.

    CONCLUSIONS: After nearly 20 years of follow-up among men with localized prostate cancer, surgery was not associated with significantly lower all-cause or prostate-cancer mortality than observation. Surgery was associated with a higher frequency of adverse events than observation but a lower frequency of treatment for disease progression, mostly for asymptomatic, local, or biochemical progression.

    Full article

    These results are a little difficult to put in a 15 second summary. I think it is easiest to show the charts on page 137 with confidence intervals - and that death from prostate cancer (where the rubber meets the road) is less likely with surgery, For those with Gleason <= 7, death from prostate cancer occurred in about 8% with observation vs 5% with surgery. For those with PSA < 10, the death from prostate cancer occurred in about 10% with observation vs 7% with surgery.


    Alzheimer Disease: Pharmacologic and Nonpharmacologic Therapies (3660)
    Epperly et al AFP 95:771 06-15-2017

    Alzheimer disease comprises a syndrome of progressive cognitive and functional decline. Treatments should target cognitive and functional symptoms. Cholinesterase inhibitors, memantine, and a combination of a cholinesterase inhibitor and memantine have produced statistically significant but clinically small delays in various domains of cognitive and functional decline in select patients with Alzheimer disease. Vitamin E has been shown to delay functional decline in patients with mild to moderate Alzheimer disease, especially when taken in combination with a cholinesterase inhibitor. Structured programs of physical exercise improve physical function and reduce rates of neuropsychiatric symptoms in patients with mild to severe Alzheimer disease. Cognitive stimulation programs show benefit in maintenance of cognitive function and improved self-reported quality of life in patients with mild to moderate Alzheimer disease.

    The bottom line is that, though cholinesterase inhibitors are commonly prescribed (some at great cost), the benefit is on the order of 3 points on a 70 point dementia scale. Even combined therapy with memantine results in about a 3 point benefit on a 100 point scale. There is no lasting benefit - once meds are stopped, the scores between placebo and active treatment are identical. Vitamin E 2000 IU bid results in about the same benefit - 3 points on a 78 point scale over 4 years (one estimate is that this treatment reduces the decline in function by the equivalent of about 7 months. We clearly need better treatments.

    Full article


    A Boy with Acute Fear of Choking while Swallowing (3659)
    Carroll et al NEJM 376:2266 06-08-2017

    A 14-year-old boy was seen in the emergency department of this hospital because of fear of choking while swallowing.

    The patient had been well until 2 days before admission, when he choked while eating a piece of chicken during dinner. He became fearful of swallowing and was unable to finish the meal despite cutting his food into small pieces. The next day, he vomited after trying to eat ice cream, and his daily fluid intake decreased to only 710 ml (24 oz) of water. He reportedly needed his mother near him throughout the day and had an "irrational fear" of choking. He had not had recent fevers, rhinorrhea, cough, or sore throat. Nine days earlier, during a routine annual examination at the clinic of the patient’s primary care pediatrician, the patient's mother reported that he had had several episodes of inspiratory stridor while he was sleeping during the past few weeks; the patient was referred to an otolaryngologist, but this visit had not yet occurred. On the day of this presentation, the patient consumed only small sips of water, reported feeling hungry, and slept most of the day. His mother noted that, in addition to the inspiratory stridor during sleep, the patient had some gasping for air that was associated with deep involuntary burping. She contacted a physician at this hospital and was advised to bring the patient to the emergency department for evaluation.

    Full case report


    Treatment of low bone density or osteoporosis to prevent fractures in men and women: A clinical practice guideline update from the American College of Physicians (3669)
    Qaseem A et al Ann Intern Med 166:818 06-06-2017

    For fracture prevention, decisions on whom to treat - and for how long - are not always straightforward. This guideline updates previous ACP recommendations for managing low bone density or osteoporosis to prevent fractures. Osteoporosis is defined as having sustained a fragility fracture or having a bone-mineral density (BMD) T-score <- -2.5.

    Key Recommendations: The authors make only two "strong" recommendations (based on high- or moderate-quality evidence):

    Four other recommendations are graded as "weak" (based on low-quality evidence):

    Comment: These guideline authors looked for evidence that an intervention lowers incidence of fractures (and does not simply bring about favorable change on the surrogate endpoint of BMD). Strong evidence results in strong treatment recommendations, whereas weak or inconclusive evidence generally leads the authors to err on the side of nonintervention. In my view, the guideline is reasonably balanced - but one must read beyond the brief bulleted list of six recommendations to appreciate it.

    An editorialist who is a clinician-researcher with expertise in this area largely supports these recommendations, noting that "they provide a solid basis for informed clinical decisions about individual patients." However, he notes that treatment beyond 5 years sometimes is warranted, that BMD monitoring during therapy sometimes is useful (although he considers the recommendation against monitoring to be "generally appropriate"), and that the parathyroid hormone fragment teriparatide (Forteo) could have received more attention.


    Spiraling Out of Control (3658)
    Mixter et al NEJM 376:2183 06-01-2017

    A 22-year-old man presented to the emergency department on Christmas Day with a 5-day history of myalgias, cough, dyspnea, nonbilious emesis, and nonbloody diarrhea. Although he had been ill for several days, he ultimately sought treatment because of intractable vomiting. He reported feeling feverish, although he had not measured his temperature, and noted one episode of hemoptysis.

    Full case report.


    Triple therapy versus biologic therapy for active rheumatoid arthritis: A cost-effectiveness analysis (3667)
    Bansback N et al Ann Intern Med 05-30-2017

    The standard of care for rheumatoid arthritis (RA) patients who respond inadequately to initial methotrexate therapy is to add either an anti-tumor necrosis factor (TNF) agent (i.e., a biologic) or sulfasalazine plus hydroxychloroquine (i.e., triple therapy). Despite evidence that these strategies yield similar responses, only 2.5% of RA patients are given triple therapy with nonbiologics before a biologic.

    In this cost-effectiveness analysis, researchers used data from a randomized trial that yielded similar outcomes for these two strategies in 353 RA patients (NEJM JW Gen Med Aug 15 2013 and N Engl J Med 2013; 369:307). Biologic therapy resulted in 0.15 additional lifetime quality-adjusted life-years (QALYs), at an additional cost of about US$77,000. This cost per 0.15 additional QALYs extrapolates to an incremental cost-effectiveness ratio of about $520,000 per QALY per patient.

    Comment: This study suggests that first-line biologic therapy is not cost-effective. So why is triple therapy used in only a small proportion of RA patients? Unquestionably, biologic therapies prompt a more rapid response; also, the pill burden of triple therapy can be difficult. But aggressive marketing to patients by the pharmaceutical industry likely is a contributing factor. In this cost-conscious era, a trial of triple therapy might be warranted, but reversing the inertia of early use of biologic therapies will be difficult in the U.S.


    Management of Depression in Older Adults: A Review (3654)
    Kok et al JAMA 317: 2114 05-23-2017

    Observations: Depression presents with the same symptoms in older adults as it does in younger populations. In contrast to younger patients, older adults with depression more commonly have several concurrent medical disorders and cognitive impairment. Depression occurring in older patients is often undetected or inadequately treated. Antidepressants are the best-studied treatment option, but psychotherapy, exercise therapy, and electroconvulsive therapy may also be effective. Psychotherapy is recommended for patients with mild to moderate severity depression. Many older patients need the same doses of antidepressant medication that are used for younger adult patients. Although antidepressants may effectively treat depression in older adults, they tend to pose greater risk for adverse events because of multiple medical comorbidities and drug-drug interactions in case of polypharmacy. High-quality evidence does not support the use of pharmacologic treatment of depression in patients with dementia. Polypharmacy in older patients can be minimized by using the Screening Tool of Older Persons Prescriptions and Screening Tool to Alert doctors to Right Treatment (STOPP/START) criteria, a valid and reliable screening tool that enables physicians to avoid potentially inappropriate medications, undertreatment, or errors of omissions in older people. Antidepressants can be gradually tapered over a period of several weeks, but discontinuation of antidepressants may be associated with relapse or recurrence of depression, so the patient should be closely observed.

    Conclusions and Relevance: Major depression in older adults is common and can be effectively treated with antidepressants and electroconvulsive therapy. Psychological therapies and exercise may also be effective for mild-moderate depression, for patients who prefer nonpharmacological treatment, or for patients who are too frail for drug treatments.

    STOPP-START

    Full article


    Effect of statin treatment vs usual care on primary cardiovascular prevention among older adults: The ALLHAT-LLT randomized clinical trial (3665)
    Han BH et al JAMA Intern Med 05-22-2017

    One quarter to one third of older adults (age, ≥75) in the U.S. take statins for primary prevention of coronary heart disease (CHD). Researchers undertook a secondary analysis of data from the lipid-lowering component of the ALLHAT trial (NEJM JW Gen Med Feb 1 2003 and JAMA 2002; 288:2998), from which they identified 2867 adults (age, ≥65; mean age, 71) who were randomized to pravastatin (40 mg daily) or usual care. Participants had stage 1 or 2 hypertension and at least one additional CHD risk factor (about 25% were smokers; 50% had type 2 diabetes) but no known CHD. About one third of usual-care patients had crossed over to statin treatment by year 6. Data were analyzed according to original randomization.

    Six-year all-cause mortality in patients who were 65 to 74 was 15.5 per 100 pravastatin participants and 14.2 per 100 usual-care participants - a nonsignificant difference. All-cause mortality among the oldest participants (age, ≥75) was 31.0 per 100 pravastatin participants and 22.7 per 100 usual-care participants (P=0.07). No differences in cardiovascular-specific mortality were found between groups.

    Comment: The lack of benefit with pravastatin for either all-cause or cardiovascular-specific mortality in older adults with CHD risk factors but without actual CHD should influence decision making about our use of statins for primary CHD prevention in older adults.


    Antithrombotic Therapy for Venous Thromboembolic Disease (3655)
    Jain et al JAMA 317:2008 05-16-2017

    Major recommendations:

    Full article


    Effect of intra-articular triamcinolone vs saline on knee cartilage volume and pain in patients with knee osteoarthritis: A randomized clinical trial (3662)
    McAlindon TE et al JAMA 317:1967 05-16-2017

    Inflammation probably plays a role in osteoarthritis (OA), and some evidence suggests that this inflammation can lead to progressive cartilage loss. Corticosteroid injections have been evaluated for managing OA of the knee, and an earlier report suggested that injections every 3 months are safe (Arthritis Rheum 2003; 48:370), even though steroids have antianabolic effects on healthy cartilage.

    In this 2-year, double-blind U.S. clinical trial, 140 patients (mean age, 58) with symptomatic knee OA and ultrasound-demonstrated effusion and synovitis were randomized to intra-articular injections of triamcinolone or placebo every 3 months. At 2 years, triamcinolone patients exhibited significantly greater loss in cartilage thickness (mean, 0.2 mm vs. 0.1 mm in placebo patients) and no significant difference in pain. Triamcinolone was not associated with faster progression of other osteoarthritis features, structurally or clinically.

    Comment: In this study, pain relief was assessed only every 3 months, short-term pain relief was not evaluated, and patients were permitted to continue background treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). We don't know exactly what loss of cartilage volume means clinically, and short-term pain relief without radiographic changes has been demonstrated in other studies. I would not abandon intra-articular steroid injections as an option for some patients: For example, occasional injections are reasonable for patients with severe pain who cannot take NSAIDs or who don't respond to them. However, this study raises concerns about repetitive injections, and, in a 2014 study, faster rates of cartilage loss were associated with higher incidence of arthroplasties (Osteoarthritis Cartilage 2014; 22:1542).