The development and implementation of a new hospital performance measure to assess hospital contributions to community health and equity.

OBJECTIVE: To develop and implement a measure of how US hospitals contribute to community health with a focus on equity. DATA SOURCES: Primary data from public comments and hospital surveys and secondary data from the IBM Watson Top 100 Hospitals program collected in the United States in 2020 and 2021. STUDY DESIGN: A thematic analysis of public comments on the proposed measure was conducted using an iterative grounded approach for theme identification. A cross-sectional survey of 207 hospitals was conducted to assess self-attestation to 28 community health best practice standards in the revised measure. An analysis of hospital rankings before and after inclusion of the new measure was performed. DATA COLLECTION/EXTRACTION METHODS: Public comment on the proposed measure was collected via an online survey, email, and virtual meetings in 2020. The survey of hospitals was conducted online by IBM in 2021. The analysis of hospital ranking compared the 2020 and 2021 IBM Watson Top 100 Hospitals program results. PRINCIPAL FINDINGS: More than 650 discrete comments from 83 stakeholders were received and analyzed during measure development. Key themes identified in thematic analysis included equity, fairness, and community priorities. Hospitals that responded to a cross-sectional survey reported meeting on average 76% of applicable best practice standards. Least met standards included providing emergent buprenorphine treatment for opioid use disorder (53%), supporting an evidence-based home visiting program (53%), and establishing a returning citizens employment program (27%). Thirty-seven hospitals shifted position in the 100 Top Hospital rankings after the inclusion of the new measure. CONCLUSIONS: There is broad interest in measuring hospital contributions to community health with a focus on equity. Many highly ranked hospitals report meeting best practice standards, but significant gaps remain. Improving measurement to incentivize greater hospital contributions to community health and equity is an important priority.

Cx43 hemichannels contribute to astrocyte-mediated toxicity in sporadic and familial ALS.

Connexin 43 (Cx43) gap junctions and hemichannels mediate astrocyte intercellular communication in the central nervous system under normal conditions and contribute to astrocyte-mediated neurotoxicity in amyotrophic lateral sclerosis (ALS). Here, we show that astrocyte-specific knockout of Cx43 in a mouse model of ALS slows disease progression both spatially and temporally, provides motor neuron (MN) protection, and improves survival. In addition, Cx43 expression is up-regulated in human postmortem tissue and cerebrospinal fluid from ALS patients. Using human induced pluripotent stem cell­derived astrocytes (hiPSC-A) from both familial and sporadic ALS, we establish that Cx43 is up-regulated and that Cx43-hemichannels are enriched at the astrocyte membrane. We also demonstrate that the pharmacological blockade of Cx43-hemichannels in ALS astrocytes using GAP 19, a mimetic peptide blocker, and tonabersat, a clinically tested small molecule, provides neuroprotection of hiPSC-MN and reduces ALS astrocyte-mediated neuronal hyperexcitability. Extending the in vitro application of tonabersat with chronic administration to SOD1G93A mice results in MN protection with a reduction in reactive astrocytosis and microgliosis. Taking these data together, our studies identify Cx43 hemichannels as conduits of astrocyte-mediated disease progression and a pharmacological target for disease-modifying ALS therapies.

Classroom Temperatures and Asthma-Related School-Based Health Care Utilization: An Exploratory Study.

OBJECTIVE: Schools with aging infrastructure may expose students to extreme temperatures. Extreme outdoor temperatures have previously been linked to more asthma-related health care utilization. Explore the relationship between classroom temperatures and school-based health care visits for asthma in an urban school building with an outdated heating and cooling system. METHODS: Participants were students in grades K-8 who received health care from a school-based health center (SBHC) (n = 647) or school nurse (n = 1244) in 2 co-located urban public schools between 2016 and 2018. The probability of an asthma visit to the SBHC or school nurse was modeled as a function of indoor temperature exposure using generalized estimating equations with covariates accounting for grade, sex, outdoor temperature, days at risk of asthma visit, nonasthma visits, month, and year fixed effects. RESULTS: Classroom temperatures ranged from 48.0˚F to 100.6°F. Higher mean grade-level indoor temperatures from a baseline of approximately 70˚F to 76˚F were associated with increased rates of asthma-related visits to the SBHC or school nurse on same day of exposure. Model-generated estimates suggest that an increase of 10˚F in indoor temperature relative to a baseline of 75˚F was associated with a 53% increase in the rate of asthma-related SBHC visits. CONCLUSIONS: Elevated classroom temperatures may be associated with more school-based health care utilization for asthma. Low-income and students from racial and ethnic minority groups have disproportionately higher rates of asthma and are also more likely to attend schools with poor infrastructure. The potential benefits of school infrastructure investments for student health, health care costs, and health equity merit further investigation.

A 4-year old presenting with fever and achiness.

In children under the age of 5 who have abnormalities in history, physical examination, and laboratory studies indicating multi-system disease, uncovering the correct diagnosis is challenging. Here, we report the course of a 4-year-old girl who presented with a change in behavior, fever, arthralgia, arthritis, and hematuria following three recent hospitalizations for pneumonia and impetigo. Serologic findings were suggestive of a rheumatologic etiology and a renal biopsy was consistent with Membranous Lupus Nephritis Class V which helped secure the diagnosis of pediatric systemic lupus erythematosus. We review the clinical features and diagnostic criteria of early-onset systemic lupus erythematosus and discuss diagnostic considerations and prognosis.

Global Regulatory Agencies and Data Transparency.

Egilman et al. review the current data sharing practices of three global regulatory agencies - Health Canada, the European Medicines Agency and the Food and Drug Agency. While there has been progress towards increasing transparency over the past decade, progress has been slow.

Caenorhabditis elegans establishes germline versus soma by balancing inherited histone methylation.

Formation of a zygote is coupled with extensive epigenetic reprogramming to enable appropriate inheritance of histone methylation and prevent developmental delays. In Caenorhabditis elegans, this reprogramming is mediated by the H3K4me2 demethylase SPR-5 and the H3K9 methyltransferase, MET-2. In contrast, the H3K36 methyltransferase MES-4 maintains H3K36me2/3 at germline genes between generations to facilitate re-establishment of the germline. To determine whether the MES-4 germline inheritance pathway antagonizes spr-5; met-2 reprogramming, we examined the interaction between these two pathways. We found that the developmental delay of spr-5; met-2 mutant progeny is associated with ectopic H3K36me3 and the ectopic expression of MES-4-targeted germline genes in somatic tissues. Furthermore, the developmental delay is dependent upon MES-4 and the H3K4 methyltransferase, SET-2. We propose that MES-4 prevents crucial germline genes from being repressed by antagonizing maternal spr-5; met-2 reprogramming. Thus, the balance of inherited histone modifications is necessary to distinguish germline versus soma and prevent developmental delay.This article has an associated 'The people behind the papers' interview.