Carvedilol for children and adolescents with heart failure: a randomized controlled trial

Context  Although -blockers improve symptoms and survival in adults with heart failure, little is known about these medications in children and adolescents. Objective  To prospectively evaluate the effects of carvedilol in children and adolescents with symptomatic systemic ventricular systolic dysfunction. Design, Setting, and Participants  A multicenter, randomized, double-blind, placebo-controlled study of 161 children and adolescents with symptomatic systolic heart failure from 26 US centers. In addition to treatment with conventional heart failure medications, patients were assigned to receive placebo or carvedilol. Enrollment began in June 2000 and the last dose was given in May 2005 (each patient received medication for 8 months). Interventions  Patients were randomized in a 1:1:1 ratio to twice-daily dosing with placebo, low-dose carvedilol (0.2 mg/kg per dose if weight <62.5 kg or 12.5 mg per dose if weight 62.5 kg), or high-dose carvedilol (0.4 mg/kg per dose if weight <62.5 kg or 25 mg per dose if weight 62.5 kg) and were stratified according to whether each patient's systemic ventricle was a left ventricle or not. Main Outcome Measures  The primary outcome was a composite measure of heart failure outcomes in patients receiving carvedilol (low- and high-dose combined) vs placebo. Secondary efficacy variables included individual components of this composite, echocardiographic measures, and plasma b-type natriuretic peptide levels. Results  There was no statistically significant difference between groups for the composite end point based on the percentage of patients who improved, worsened, or were unchanged. Among 54 patients assigned to placebo, 30 improved (56%), 16 worsened (30%), and 8 were unchanged (15%); among 103 patients assigned to carvedilol, 58 improved (56%), 25 worsened (24%), and 20 were unchanged (19%). The rates of worsening were lower than expected. The odds ratio for worsened outcome for patients in the combined carvedilol group vs the placebo group was 0.79 (95% CI, 0.36-1.59; P = .47). A prespecified subgroup analysis noted significant interaction between treatment and ventricular morphology (P = .02), indicating a possible differential effect of treatment between patients with a systemic left ventricle (beneficial trend) and those whose systemic ventricle was not a left ventricle (nonbeneficial trend). Conclusions  These preliminary results suggest that carvedilol does not significantly improve clinical heart failure outcomes in children and adolescents with symptomatic systolic heart failure. However, given the lower than expected event rates, the trial may have been underpowered. There may be a differential effect of carvedilol in children and adolescents based on ventricular morphology. Trial Registration  clinicaltrials.gov Identifier: NCT00052026      

Does this adult patient have septic arthritis?

Mary E. Margaretten, MD; Jeffrey Kohlwes, MD, MPH; Dan Moore, PhD; Stephen Bent, MD

JAMA. 2007;297:1478-1488.

Context  In patients who present with an acutely painful and swollen joint, prompt identification and treatment of septic arthritis can substantially reduce morbidity and mortality.

Objective  To review the accuracy and precision of the clinical evaluation for the diagnosis of nongonococcal bacterial arthritis.

Data Sources  Structured PubMed and EMBASE searches (1966 through January 2007), limited to human, English-language articles and using the following Medical Subject Headings terms: arthritis, infectious, physical examination, medical history taking, diagnostic tests, and sensitivity and specificity.

Study Selection  Studies were included if they contained original data on the accuracy or precision of historical items, physical examination, serum, or synovial fluid laboratory data for diagnosing septic arthritis.

Data Extraction  Three authors independently abstracted data from the included studies.

Data Synthesis  Fourteen studies involving 6242 patients, of whom 653 met the gold standard for the diagnosis of septic arthritis, satisfied all inclusion criteria. Two studies examined risk factors and found that age, diabetes mellitus, rheumatoid arthritis, joint surgery, hip or knee prosthesis, skin infection, and human immunodeficiency virus type 1 infection significantly increase the probability of septic arthritis. Joint pain (sensitivity, 85%; 95% confidence interval [CI], 78%-90%), a history of joint swelling (sensitivity, 78%; 95% CI, 71%-85%), and fever (sensitivity, 57%; 95% CI, 52%-62%) are the only findings that occur in more than 50% of patients. Sweats (sensitivity, 27%; 95% CI, 20%-34%) and rigors (sensitivity, 19%; 95% CI, 15%-24%) are less common findings in septic arthritis. Of all laboratory findings readily available to the clinician, the 2 most powerful were the synovial fluid white blood cell (WBC) count and percentage of polymorphonuclear cells from arthrocentesis. The summary likelihood ratio (LR) increased as the synovial fluid WBC count increased (for counts <25 000/µL: LR, 0.32; 95% CI, 0.23-0.43; for counts 25 000/µL: LR, 2.9; 95% CI, 2.5-3.4; for counts >50 000/µL: LR, 7.7; 95% CI, 5.7-11.0; and for counts >100 000/µL: LR, 28.0; 95% CI, 12.0-66.0). On the same synovial fluid sample, a polymorphonuclear cell count of at least 90% suggests septic arthritis with an LR of 3.4 (95% CI, 2.8-4.2), while a polymorphonuclear cell count of less than 90% lowers the likelihood (LR, 0.34; 95% CI, 0.25-0.47).

Conclusions  Clinical findings identify patients with peripheral, monoarticular arthritis who might have septic arthritis. However, the synovial WBC and percentage of polymorphonuclear cells from arthrocentesis are required to assess the likelihood of septic arthritis before the Gram stain and culture test results are known.

     

Using a Decision Support Algorithm for Referrals to Post-Acute Care

Objectives

Although hospital clinicians strive to effectively refer patients who require post-acute care (PAC), their discharge planning processes often vary greatly, and typically are not evidence-based.

A Case-Crossover Analysis of Indoor Heat Exposure on Mortality and Hospitalizations among the Elderly in Houston,Texas

Background: Despite the substantial role indoor exposure has played in heat wave–related mortality, few epidemiological studies have examined the health effects of exposure to indoor heat. As a result, knowledge gaps regarding indoor heat–health thresholds, vulnerability, and adaptive capacity persist.Objective: We evaluated the role of indoor heat exposure on mortality and morbidity among the elderly (≥65 years of age) in Houston, Texas.Methods: Mortality and emergency hospital admission data were obtained through the Texas Department of State Health Services. Summer indoor heat exposure was modeled at the U.S. Census block group (CBG) level using building energy models, outdoor weather data, and building characteristic data. Indoor heat–health associations were examined using time-stratified case-crossover models, controlling for temporal trends and meteorology, and matching on CBG of residence, year, month, and weekday of the adverse health event. Separate models were fitted for three indoor exposure metrics, for individual lag days 0–6, and for 3-d moving averages (lag 0–2). Effect measure modification was explored via stratification on individual- and area-level vulnerability factors.Results: We estimated positive associations between short-term changes in indoor heat exposure and cause-specific mortality and morbidity [e.g., circulatory deaths, odds ratio per 5°C increase=1.16 (95% CI: 1.03, 1.30)]. Associations were generally positive for earlier lag periods and weaker across later lag periods. Stratified analyses suggest stronger associations between indoor heat and emergency hospital admissions among African Americans compared with Whites.Discussion: Findings suggest excess mortality among certain elderly populations in Houston who are likely exposed to high indoor heat. We developed a novel methodology to estimate indoor heat exposure that can be adapted to other U.S. locations. In locations with high air conditioning prevalence, simplified modeling approaches may adequately account for indoor heat exposure in vulnerable neighborhoods. Accounting for indoor heat exposure may improve the estimation of the total impact of heat on health. https://doi.org/10.1289/EHP6340     

Integrating gene expression profiling into NCCN high-risk cutaneous squamous cell carcinoma management recommendations: impact on patient management

Abstract

Objective: To integrate gene expression profiling into the management of high-risk cutaneous squamous cell carcinoma (cSCC) within the National Comprehensive Cancer Network (NCCN) guidelines to improve risk-aligned management recommendations.

Methods: A cohort of 300 NCCN-defined high-risk cSCC patients, along with the American Joint Committee on Cancer (AJCC) T stage, Brigham and Women’s Hospital (BWH) T stage, and known patient outcomes were analyzed. Risk classifications using a validated 40-gene expression profile (40-GEP) test and T stage were applied to NCCN patient management guidelines. Risk-directed patient management recommendations within the NCCN guidelines framework were aligned based on risk for metastasis.

Results: Of the 300 NCCN high-risk cSCC patients, 159 (53.0%) were 40-GEP Class 1 and AJCC T1-T2, and 173 (57.7%) were Class 1 and BWH T1-2a, indicating low risk for metastasis and, thereby, suggesting low management intensity. The 40-GEP integration suggested high intensity management for only 24 (8.0%) patients (all Class 2B), and moderate intensity management for the remainder of the cohort.

Conclusions: The 40-GEP test can be integrated within existing NCCN guideline recommendations for managing cSCC patients to help refine risk-directed management decisions. Integration of the 40-GEP test would allow >50% of this NCCN-defined high-risk cohort to be managed with the lowest intensity recommendations within the broad NCCN guidelines. High intensity management was deemed risk-appropriate for a small subpopulation (8.0%). This study demonstrates that the 40-GEP test, in combination with T stage, has clinical utility to impact patient management decisions in NCCN high-risk cSCC for improving risk-aligned management within the NCCN guidelines framework.     

Prevention and treatment of pressure ulcers/injuries: The protocol for the second update of the international Clinical Practice Guideline 2019

Aim

The European Pressure Ulcer Advisory Panel, the Pan Pacific Pressure Injury Alliance, and the National Pressure Ulcer Advisory Panel are updating the ‘Prevention and Treatment of Pressure Ulcers: Clinical Practice Guideline’ (CPG) in 2019. The aim of this contribution is to summarize and to discuss the guideline development protocol for the 2019 update.