Our data suggest a U-shaped pattern for ICD efficacy in the low-EF population, with pronounced benefit in intermediate-risk patients and attenuated efficacy in lower- and higher-risk subsets.

Objective The NLRP3 inflammasome plays key roles in inflammation and autoimmunity, and puriner-gic receptor P2X7 has been proposed to be upstream of NLRP3 activation. The aim of the present study, using murine models, was to investigate whether the P2X7/ NLRP3 inflammasome pathway contributes to the pathogenesis of lupus nephritis (LN). Methods MRL/lpr mice were treated with the selective P2X7 antagonist brilliant blue G (BBG) for 8 weeks. Following treatment, the severity of renal lesions, production of anti-double-stranded DNA (anti-dsDNA) antibodies, rate of survival, activation of the NLRP3/ ASC/caspase 1 inflammasome pathway, and ratio of Thl7 cells to Treg cells were evaluated. P2X7-targeted small interfering RNA (siRNA) was also used for in vivo intervention. Similar evaluations were carried out in NZM2328 mice, a model of LN in which the disease was accelerated by administration of adenovirus-expressing interferon-α (AdIFNα). Results Significant up-regulation of P2X7/NLRP3 inflammasome signaling molecules was detected in the kidneys of MLR/lpr mice as compared with normal control mice. Blockade of P2X7 activation by BBG suppressed NLRP3/ASC/caspase 1 assembly and the subsequent release of interleukin-1β (IL-1β), resulting in a significant reduction in the severity of nephritis and circulating anti-dsDNA antibodies. The lifespan of the treated mice was significantly prolonged. BBG treatment reduced the serum levels of IL-1β and IL-17 and the Thl7:Treg cell ratio. Similar results were obtained by specific siRNA silencing of P2X7 in vivo. The effectiveness of BBG treatment in modulating LN was confirmed in NZM2328 mice with AdIFNα-accelerated disease. Conclusion Activation of the P2X7 signaling pathway accelerates murine LN by activating the NLRP3/ASC/caspase 1 inflammasome, resulting in increased IL-1β production and enhanced Thl7 cell polarization. Thus, targeting of the P2X7/NLRP3 pathway should be considered as a novel therapeutic strategy in patients with lupus.

Poor adherence to recommended preventive asthma medications is common, leading to preventable morbidity. We developed the School-Based Telemedicine Enhanced Asthma Management (SB-TEAM) program to build on school-based supervised therapy programs by incorporating telemedicine at school to overcome barriers to preventive asthma care. OBJECTIVE To evaluate the effect of the SB-TEAM program on asthma morbidity among urban children with persistent asthma. DESIGN, SETTING, AND PARTICIPANTS In this randomized clinical trial, children with persistent asthma aged 3 to 10 years in the Rochester City School District in Rochester, New York, were stratified by preventive medication use at baseline and randomly assigned to the SB-TEAM program or enhanced usual care for 1 school year. Participants were enrolled at the beginning of the school year (2012-2016), and outcomes were assessed through the end of the school year. Data were analyzed between May 2017 and November 2017 using multivariable modified intention-to-treat analyses. INTERVENTIONS Supervised administration of preventive asthma medication at school as well as 3 school-based telemedicine visits to ensure appropriate assessment, preventive medication prescription, and follow-up care. The school site component of the telemedicine visit was completed by telemedicine assistants, who obtained history and examination data. These data were stored in a secure virtual waiting room and then viewed by the primary care clinician, who completed the assessment and communicated with caregivers via videoconference or telephone. Preventive medication prescriptions were sent to pharmacies that deliver to schools for supervised daily administration. MAIN OUTCOMES AND MEASURES The primary outcome was the mean number of symptom-free days per 2 weeks, assessed by bimonthly blinded interviews. RESULTS Of the 400 enrolled children, 247 (61.8%) were male and 230 (57.5%) were African American, and the mean (SD) age was 7.8 (1.7) years. Demographic characteristics and asthma severity in the 2 groups were similar at baseline. Among children in the SB-TEAM group, 196 (98.0%) had 1 or more telemedicine visits, and 165 (82.5%) received supervised therapy through school. We found that children in the SB-TEAM group had more symptom-free days per 2 weeks postintervention compared with children in the enhanced usual care group (11.6 vs 10.97; difference, 0.69; 95% CI, 0.15-1.22; P = .01), with the largest difference observed at the final follow-up (difference, 0.85; 95% CI, 0.10-1.59). In addition, children in the SB-TEAM group were less likely to have an emergency department visit or hospitalization for asthma (7% vs 15%; odds ratio, 0.52; 95% CI, 0.32-0.84). CONCLUSIONS AND RELEVANCE The SB-TEAM intervention significantly improved symptoms and reduced health care utilization among urban children with persistent asthma. This program could serve as a model for sustainable asthma care among school-aged children. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01650844

The log transformation has been widely used in biomedical research to deal with the skewed data. However, in the medical publications, we have found many misuses and misinterpretations of analysis based on log-transformed data. In this paper, we list some common scenarios of misuse and misinterpretation of log transformation in biomedical applications. We also provide both theoretical and practical justifications to support our viewpoints.

To evaluate the impact of the School-Based Asthma Therapy trial on asthma symptoms among urban children with persistent asthma.Design: Randomized trial, with children stratified by smoke exposure in the home and randomized to a schoolbased care group or a usual care control group.