Humans

Association of Treatment With 5α-Reductase Inhibitors and Prostate Cancer Mortality Among Older Adults

Author/s: 
Kumar, A, Nalawade, V, Riviere, P, Sarkar, RR, Parsons, JK, Murphy, JD, Rose, BS

5α-reductase inhibitors (5-ARIs) are used to treat benign prostatic enlargement, a common condition causing urinary outflow obstruction. They also reduce prostate-specific antigen (PSA) by approximately 50%. Our group has recently published that among US military veterans, 5-ARIs are associated with delays in prostate cancer (PC) diagnoses, higher grade and stage at presentation, and worse PC-specific mortality (PCSM), presumably because of misinterpreted PSA values. We hypothesized that these results are generalizable to the broader US population.

Bisphosphonates for Postmenopausal Osteoporosis

Author/s: 
Ensrud, KE, Crandall, CJ

Bisphosphonates are the first-line pharmacologic treatment for postmenopausal osteoporosis and the most commonly prescribed medication for this condition.1 Bisphosphonates, classified as antiresorptive agents, have a very high affinity for bone mineral and bind to hydroxyapatite crystals on bony surfaces, where they inhibit osteoclast-mediated bone resorption.

Pharmacologic and Nonpharmacologic Therapies in Adult Patients With Exacerbation of COPD: A Systematic Review

Author/s: 
Dobler, CC, Morrow, AS, Farah, MH, Beuschel, B, Majzoub, AM, Wilson, ME, Hasan, B, Seisa, MO, Daraz, L, Prokop, LJ, Murad, MH, Wang, Z

Objectives. To synthesize existing knowledge about the effectiveness and harms of pharmacologic and nonpharmacologic treatments for exacerbations of chronic obstructive pulmonary disease (ECOPD).

Data sources. Embase®, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, MEDLINE® Daily, MEDLINE, Cochrane Central Registrar of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus from database inception to January 2, 2019.

Review methods. We included randomized controlled trials (RCTs) that evaluated pharmacologic intervention or nonpharmacologic interventions for ECOPD. The strength of evidence (SOE) was graded for critical final health outcomes.

Results. We included 98 RCTs (13,401 patients, mean treatment duration 9.9 days, mean followup 3.7 months). Final health outcomes, including mortality, resolution of exacerbation, hospital readmissions, repeat exacerbations, and need for intubation, were infrequently evaluated and often showed no statistically significant differences between groups. Antibiotic therapy increases the clinical cure rate and reduces the clinical failure rate regardless of the severity of ECOPD (moderate SOE). There is insufficient evidence to support a particular antibiotic regimen. Oral and intravenous corticosteroids improve dyspnea and reduce the clinical failure rate (low SOE). Despite the ubiquitous use of inhaled bronchodilators in ECOPD, we found only a small number of trials that assessed lung function tests, and not final health outcomes. The evidence is insufficient to support the effect of aminophyllines, magnesium sulfate, mucolytics, inhaled corticosteroids, inhaled antibiotics, 5-lipoxygenase inhibitor, and statins on final health outcomes. Titrated oxygen reduces mortality compared with high flow oxygen (low SOE). Low SOE suggested benefit from some nonpharmacologic interventions such as chest physiotherapy using vibration/percussion/massage or breathing technique (on dyspnea), resistance training (on dyspnea and quality of life), early pulmonary rehabilitation commenced before hospital discharge during the initial most acute phase of exacerbation rather than the convalescence period (on dyspnea) and whole body vibration training (on quality of life). Vitamin D supplementation may improve quality of life (low SOE).

Conclusions. Although chronic obstructive pulmonary disease is a common condition, the evidence base for most interventions in ECOPD remains limited. Systemic antibiotics and corticosteroids are associated with improved outcomes in mild and moderate to severe ECOPD. Titrated oxygen reduces mortality. Future research is required to assess the effectiveness of several emerging nonpharmacologic and dietary treatments.

Subconcussive Football Hits May Leave a Telltale Signature of Brain Damage

Author/s: 
Sancar, F

College football players in the United States endure over 1000 head hits every season. Although many don’t produce symptoms such as dizziness or blurred vision that often accompany frank concussion, these “clinically silent” hits are associated with the same type of brain damage as concussion, according to a recent Science Advances study.

Characteristics of Case Management in Primary Care Associated With Positive Outcomes for Frequent Users of Health Care: A Systematic Review

Author/s: 
Hudon, C, Chouinard, MC, Pluye, P, El Sherif, R, Bush, PL, Rihoux, B, Poitras, ME, Lambert, M, Zomahoun, HTV, Legare, F

PURPOSE:

Case management (CM) interventions are effective for frequent users of health care services, but little is known about which intervention characteristics lead to positive outcomes. We sought to identify characteristics of CM that yield positive outcomes among frequent users with chronic disease in primary care.

METHODS:

For this systematic review of both quantitative and qualitative studies, we searched MEDLINE, CINAHL, Embase, and PsycINFO (1996 to September 2017) and included articles meeting the following criteria: (1)population: adult frequent users with chronic disease, (2)intervention: CM in a primary care setting with a postintervention evaluation, and (3)primary outcomes: integration of services, health care system use, cost, and patient outcome measures. Independent reviewers screened abstracts, read full texts, appraised methodologic quality (Mixed Methods Appraisal Tool), and extracted data from the included studies. Sufficient and necessary CM intervention characteristics were identified using configurational comparative methods.

RESULTS:

Of the 10,687 records retrieved, 20 studies were included; 17 quantitative, 2 qualitative, and 1 mixed methods study. Analyses revealed that it is necessary to identify patients most likely to benefit from a CM intervention for CM to produce positive outcomes. High-intensity intervention or the presence of a multidisciplinary/interorganizational care plan was also associated with positive outcomes.

CONCLUSIONS:

Policy makers and clinicians should focus on their case-finding processes because this is the essential characteristic of CM effectiveness. In addition, value should be placed on high-intensity CM interventions and developing care plans with multiple types of care providers to help improve patient outcomes.

Clinical Approach to Lactose Intolerance

Author/s: 
Micic, D, Rao, VL, Rubin, DT

Lactose intolerance refers to the clinical syndrome in which symptoms of bloating, flatulence, abdominal discomfort, and diarrhea arise following the consumption of lactose-containing foods. Lactose malabsorption results from congenital lactase deficiency, secondary lactose intolerance, and, most commonly, from acquired primary lactase deficiency, a highly prevalent condition affecting 65% to 74% of the worldwide population, with wide regional and ethnic variations. Symptoms arising from lactose malabsorption result from fluid shifts into the intestinal lumen driven by an osmotic gradient and subsequent fermentation of lactose by bacteria residing in the gastrointestinal tract. In this article we review the development of clinical lactose intolerance, diagnostic testing, and treatment of individuals presenting with symptoms of lactose intolerance.

Changes in nut consumption influence long-term weight change in US men and women

Author/s: 
X, Li, Y, Guasch-Ferre, M, Willett, WC, Drouin-Chartier, JP, Bhupathiraju, SN, Tobias, DK

Background Nut consumption has increased in the US but little evidence exists on the association between changes in nut consumption and weight change. We aimed to evaluate the association between changes in total consumption of nuts and intakes of different nuts (including peanuts) and long-term weight change, in three independent cohort studies.

Methods and findings Data collected in three prospective, longitudinal cohorts among health professionals in the US were analysed. We included 27 521 men (Health Professionals Follow-up Study, 1986 to 2010), 61 680 women (Nurses’ Health Study, 1986 to 2010), and 55 684 younger women (Nurses’ Health Study II, 1991 to 2011) who were free of chronic disease at baseline in the analyses. We investigated the association between changes in nut consumption over 4-year intervals and concurrent weight change over 20–24 years of follow-up using multivariate linear models with an unstructured correlation matrix to account for within-individual repeated measures. 21 322 individuals attained a body mass index classification of obesity (BMI ≥30 kg/m2) at the end of follow-up.

Average weight gain across the three cohorts was 0.32 kg each year. Increases in nut consumption, per 0.5 servings/day (14 g), was significantly associated with less weight gain per 4-year interval (p<0.01 for all): −0.19 kg (95% CI -0.21 to -0.17) for total consumption of nuts, -0.37 kg (95% CI -0.45 to -0.30) for walnuts, -0.36 kg (95% CI -0.40 to -0.31) for other tree nuts, and -0.15 kg (95% CI -0.19 to -0.11) for peanuts.

Increasing intakes of nuts, walnuts, and other tree nuts by 0.5 servings/day was associated with a lower risk of obesity. The multivariable adjusted RR for total nuts, walnuts, and other tree nuts was 0.97 (95% CI 0.96 to 0.99, p=0.0036), 0.85 (95% CI 0.81 to 0.89, p=0.0002), and 0.89 (95% CI 0.87 to 0.91, p<0.0001), respectively. Increasing nut consumption was also associated with a lower risk of gaining ≥2 kg or ≥5 kg (RR 0.89–0.98, p<0.01 for all).

In substitution analyses, substituting 0.5 servings/day of nuts for red meat, processed meat, French fries, desserts, or potato, chips (crisps) was associated with less weight gain (p<0.05 for all).

Our cohorts were largely composed of Caucasian health professionals with relatively higher socioeconomic status; thus the results may not be generalisable to other populations.

Conclusion Increasing daily consumption of nuts is associated with less long-term weight gain and a lower risk of obesity in adults. Replacing 0.5 servings/day of less healthful foods with nuts may be a simple strategy to help prevent gradual long-term weight gain and obesity.

Keywords 

Step-Up Therapy in Black Children and Adults with Poorly Controlled Asthma

Author/s: 
Wechsler, ME, Szefler, SJ, Ortega, VE, Pongracic, JA, Chinchili, V, Lima, JJ, Krishnan, JA, Kunselman, SJ, Mauger, D, Bleecker, ER, Bacharier, LB, Beigelman, A, Benson, M, Blake, KV, Cabana, MD, Cardet, JC, Castro, M, Chmiel, JF, Covar, R, Denlinger, L, DiMango, E, Fitzpatrick, AM, Gentile, D, Grossman, N, Holguin, F, Jackson, DJ, Kumar, H, Kraft, M, LaForce, CF, Lang, J, Lazarus, SC, Lemanske, RF Jr, Long, D, Lugogo, N, Martinez, F, Meyers, DA, Moore, WC, Moy, J, Naureckas, E, Olin, JT, Peters, SP, Phipatanakul, W, Que, L, Raissy, H, Robison, RG, Ross, K, Sheehan, W, Smith, LJ, Solway, J, Sorkness, CA, Sullivan-Vedder, L, Wenzel, S, Israel, E, NHLBI AsthmaNet

BACKGROUND:

Morbidity from asthma is disproportionately higher among black patients than among white patients, and black patients constitute the minority of participants in trials informing treatment. Data indicate that patients with inadequately controlled asthma benefit more from addition of a long-acting beta-agonist (LABA) than from increased glucocorticoids; however, these data may not be informative for treatment in black patients.

METHODS:

We conducted two prospective, randomized, double-blind trials: one involving children and the other involving adolescents and adults. In both trials, the patients had at least one grandparent who identified as black and had asthma that was inadequately controlled with low-dose inhaled glucocorticoids. We compared combinations of therapy, which included the addition of a LABA (salmeterol) to an inhaled glucocorticoid (fluticasone propionate), a step-up to double to quintuple the dose of fluticasone, or both. The treatments were compared with the use of a composite measure that evaluated asthma exacerbations, asthma-control days, and lung function; data were stratified according to genotypic African ancestry.

RESULTS:

When quintupling the dose of fluticasone (to 250 μg twice a day) was compared with adding salmeterol (50 μg twice a day) and doubling the fluticasone (to 100 μg twice a day), a superior response occurred in 46% of the children with quintupling the fluticasone and in 46% of the children with doubling the fluticasone and adding salmeterol (P = 0.99). In contrast, more adolescents and adults had a superior response to added salmeterol than to an increase in fluticasone (salmeterol-low-dose fluticasone vs. medium-dose fluticasone, 49% vs. 28% [P = 0.003]; salmeterol-medium-dose fluticasone vs. high-dose fluticasone, 49% vs. 31% [P = 0.02]). Neither the degree of African ancestry nor baseline biomarkers predicted a superior response to specific treatments. The increased dose of inhaled glucocorticoids was associated with a decrease in the ratio of urinary cortisol to creatinine in children younger than 8 years of age.

CONCLUSIONS:

In contrast to black adolescents and adults, almost half the black children with poorly controlled asthma had a superior response to an increase in the dose of an inhaled glucocorticoid and almost half had a superior response to the addition of a LABA. (Funded by the National Heart, Lung, and Blood Institute; BARD ClinicalTrials.gov number, NCT01967173.).

Testing of a Tool for Prostate Cancer Screening Discussions in Primary Care

Author/s: 
Misra-Hebert, AD, Hom, G, Klein, EA, Bauman, JA, Gupta, N, Ji, X, Stephenson, AJ, Jones, JS, Kattan, Kattan, MW

The link to the study is available here: https://www.ncbi.nlm.nih.gov/pubmed/30003062

BACKGROUND:

As prostate cancer (PCa) screening decisions often occur in outpatient primary care, a brief tool to help the PCa screening conversation in busy clinic settings is needed.

METHODS:

A previously created 9-item tool to aid PCa screening discussions was tested in five diverse primary care clinics. Fifteen providers were recruited to use the tool for 4 weeks, and the tool was revised based upon feedback. The providers then used the tool with a convenience sample of patients during routine clinic visits. Pre- and post-visit surveys were administered to assess patients' knowledge of the option to be screened for PCa and of specific factors to consider in the decision. McNemar's and Stuart-Maxwell tests were used to compare pre-and post-survey responses.

RESULTS:

14 of 15 providers completed feedback surveys and had positive responses to the tool. All 15 providers then tested the tool on 95 men aged 40-69 at the five clinics with 2-10 patients each. The proportion of patients who strongly agreed that they had the option to choose to screen for PCa increased from 57 to 72% (p = 0.018) from the pre- to post-survey, that there are factors in the personal or family history that may affect PCa risk from 34 to 47% (p = 0.012), and that their opinions about possible side effects of treatment for PCa should be considered in the decision from 47 to 61% (p = 0.009).

CONCLUSION:

A brief conversation tool for the PCa screening discussion was well received in busy primary-care settings and improved patients' knowledge about the screening decision.

Visual Acuity Assessment and Vision Screening Using a Novel Smartphone Application

Author/s: 
Zhao, L, Stinnett, SS, Prakalapakom, SG

OBJECTIVES:

To evaluate a smartphone-based application's (Peek Acuity) ability to assess visual acuity and screen for ocular conditions in children, we compared visual acuity assessment between Peek Acuity and the pediatric ophthalmology examination and evaluated Peek Acuity's ability to identify children with referable ocular conditions.

STUDY DESIGN:

We prospectively recruited 111 children age 3-17 years, presenting to a pediatric ophthalmology clinic, who could follow instructions. Monocular visual acuity assessments by Peek Acuity and standard clinical methods were performed in randomized order. We compared visual acuity assessments between methods using intraclass correlation coefficient (ICC) and evaluated Peek Acuity's ability to identify children with referable ocular conditions.

RESULTS:

ICC comparing visual acuity assessed between methods was 0.88 (95% CI 0.83-0.92) for first and 0.85 (95% CI 0.78-0.89) for second eyes examined. ICC among 3 to 5-year-olds (preschool-age children) was 0.88 (95% CI 0.77-0.94) for first and 0.45 (95% CI 0.13-0.68) for second eyes examined. Peek Acuity had a sensitivity of 83%-86% for decreased vision and 69%-83% for referable ocular disease. Sensitivity was highest among 3 to 5-year-olds with decreased vision, 93%-100%.

CONCLUSIONS:

Overall, Peek Acuity visual acuity assessment correlated well with visual acuity assessed by standard clinical methods, though preschool-age children appeared more susceptible to examination fatigue. Peek Acuity performed adequately as a screening tool and had the greatest sensitivity among those with decreased vision and preschool-age children.

TRIAL REGISTRATION:

ClinicalTrials.gov: NCT03212222.

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