Temporal Trends in Cardiovascular Hospital Discharges Following a Mass Chlorine Exposure Event in Graniteville, South Carolina

Background: On January 6, 2005, a train derailed in Graniteville, South Carolina, releasing nearly 60,000 kg of toxic chlorine gas. The disaster left nine people dead and was responsible for hundreds of hospitalizations and outpatient visits in the subsequent weeks. While chlorine gas primarily affects the respiratory tract, a growing body of evidence suggests that acute exposure may also cause vascular injury and cardiac toxicity. Here, we describe the incidence of cardiovascular hospitalizations among residents of the zip codes most affected by the chlorine gas plume, and compare the incidence of cardiovascular discharges in the years leading up to the event (2000–2004) to the incidence in the years following the event (2005–2014). Methods: De-identified hospital discharge information was collected from the South Carolina Revenue and Fiscal Affairs Office for individuals residing in the selected zip codes for the years 2000 to 2014. A quasi-experimental study design was utilized with a population-level interrupted time series model to examine hospital discharge rates for Graniteville-area residents for three cardiovascular diagnoses: hypertension (HTN), acute myocardial infarction (AMI), and coronary heart disease (CHD). We used linear regression with autoregressive error correction to compare slopes for pre- and post-spill time periods. Data from the 2000 and 2010 censuses were used to calculate rates and to provide information on potential demographic shifts over the course of the study. Results: A significant increase in hypertension-related hospital discharge rates was observed for the years following the Graniteville chlorine spill (slope 8.2, p \u3c 0.001). Concurrent changes to CHD and AMI hospital discharge rates were in the opposite direction (slopes −3.2 and −0.3, p \u3c 0.01 and 0.14, respectively). Importantly, the observed trend cannot be attributed to an aging population. Conclusions: An unusual increase in hypertension-related hospital discharge rates in the area affected by the Graniteville chlorine spill contrasts with national and state-level trends. A number of factors related to the spill may be contributing the observation: disaster-induced hypertension, healthcare services access issues, and, possibly, chlorine-induced susceptibility to vascular pathologies. Due to the limitations of our data, we cannot determine whether the individuals who visited the hospital were the ones exposed to chlorine gas, however, the finding warrants additional research. Future studies are needed to determine the etiology of the increase and whether individuals exposed to chlorine are at a heightened risk for hypertensive heart disease

Alpha-2-adrenergic receptor agonists for the prevention of delirium and cognitive decline after open heart surgery (ALPHA2PREVENT): protocol for a multicentre randomised controlled trial

INTRODUCTION: Postoperative delirium is common in older cardiac surgery patients and associated with negative short-term and long-term outcomes. The alpha-2-adrenergic receptor agonist dexmedetomidine shows promise as prophylaxis and treatment for delirium in intensive care units (ICU) and postoperative settings. Clonidine has similar pharmacological properties and can be administered both parenterally and orally. We aim to study whether repurposing of clonidine can represent a novel treatment option for delirium, and the possible effects of dexmedetomidine and clonidine on long-term cognitive trajectories, motor activity patterns and biomarkers of neuronal injury, and whether these effects are associated with frailty status. METHODS AND ANALYSIS: This five-centre, double-blind randomised controlled trial will include 900 cardiac surgery patients aged 70+ years. Participants will be randomised 1:1:1 to dexmedetomidine or clonidine or placebo. The study drug will be given as a continuous intravenous infusion from the start of cardiopulmonary bypass, at a rate of 0.4 µg/kg/hour. The infusion rate will be decreased to 0.2 µg/kg/hour postoperatively and be continued until discharge from the ICU or 24 hours postoperatively, whichever happens first.Primary end point is the 7-day cumulative incidence of postoperative delirium (Diagnostic and Statistical Manual of Mental Disorders, fifth edition). Secondary end points include the composite end point of coma, delirium or death, in addition to delirium severity and motor activity patterns, levels of circulating biomarkers of neuronal injury, cognitive function and frailty status 1 and 6 months after surgery. ETHICS AND DISSEMINATION: This trial is approved by the Regional Committee for Ethics in Medical Research in Norway (South-East Norway) and by the Norwegian Medicines Agency. Dissemination plans include publication in peer-reviewed medical journals and presentation at scientific meetings. TRIAL REGISTRATION NUMBER: NCT05029050

Variability in childhood allergy and asthma across ethnicity, language, and residency duration in El Paso, Texas: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>We evaluated the impact of migration to the USA-Mexico border city of El Paso, Texas (USA), parental language preference, and Hispanic ethnicity on childhood asthma to differentiate between its social and environmental determinants.</p> <p>Methods</p> <p>Allergy and asthma prevalence was surveyed among 9797 fourth and fifth grade children enrolled in the El Paso Independent School District. Parents completed a respiratory health questionnaire, in either English or Spanish, and a sub-sample of children received spirometry testing at their school. Here we report asthma and allergy outcomes across ethnicity and El Paso residency duration.</p> <p>Results</p> <p>Asthma and allergy prevalence increased with longer duration of El Paso residency independent of ethnicity and preferred language. Compared with immigrants who arrived in El Paso after entering first grade (18%), lifelong El Paso residents (68%) had more prevalent allergy (OR, 1.72; 95% CI, 1.32 - 2.24), prevalent asthma (OR, 1.75; 95% CI, 1.24 - 2.46), and current asthma (OR, 2.01; 95% CI, 1.37 - 2.95). Spirometric measurements (FEV₁/FVC and FEF_25-75) also declined with increasing duration of El Paso residency (0.16% and 0.35% annual reduction, respectively).</p> <p>Conclusion</p> <p>These findings suggest that a community-wide environmental exposure in El Paso, delayed pulmonary development, or increased health of immigrants may be associated with allergy and asthma development in children raised there.</p

Multi-ethnic genome-wide association study for atrial fibrillation

Atrial fibrillation (AF) affects more than 33 million individuals worldwide and has a complex heritability. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Epidemiologic Methods Lessons Learned from Environmental Public Health Disasters: Chernobyl, the World Trade Center, Bhopal, and Graniteville, South Carolina

Background: Environmental public health disasters involving hazardous contaminants may have devastating effects. While much is known about their immediate devastation, far less is known about long-term impacts of these disasters. Extensive latent and chronic long-term public health effects may occur. Careful evaluation of contaminant exposures and long-term health outcomes within the constraints imposed by limited financial resources is essential. Methods: Here, we review epidemiologic methods lessons learned from conducting long-term evaluations of four environmental public health disasters involving hazardous contaminants at Chernobyl, the World Trade Center, Bhopal, and Graniteville (South Carolina, USA). Findings: We found several lessons learned which have direct implications for the on-going disaster recovery work following the Fukushima radiation disaster or for future disasters. Interpretation: These lessons should prove useful in understanding and mitigating latent health effects that may result from the nuclear reactor accident in Japan or future environmental public health disasters