Economy-Wide Estimates of the Implications of Climate Change: Human Health

We study the economic impacts of climate-change-induced change in human health, viz. cardiovascular and respiratory disorders, diarrhoea, malaria, dengue fever and schistosomiasis. Changes in morbidity and mortality are interpreted as changes in labour productivity and demand for health care, and used to shock the GTAP-E computable general equilibrium model, calibrated for the year 2050. GDP, welfare and investment fall (rise) in regions with net negative (positive) health impacts. Prices, production, and terms of trade show a mixed pattern. Direct cost estimates, common in climate change impact studies, underestimate the true welfare losses.Impacts of climate change, Human health, Computable general equilibrium

Fatal infantile mitochondrial encephalomyopathy, hypertrophic cardiomyopathy and optic atrophy associated with a homozygous OPA1 mutation.

BACKGROUND: Infantile-onset encephalopathy and hypertrophic cardiomyopathy caused by mitochondrial oxidative phosphorylation defects are genetically heterogeneous with defects involving both the mitochondrial and nuclear genomes. OBJECTIVE: To identify the causative genetic defect in two sisters presenting with lethal infantile encephalopathy, hypertrophic cardiomyopathy and optic atrophy. METHODS: We describe a comprehensive clinical, biochemical and molecular genetic investigation of two affected siblings from a consanguineous family. Molecular genetic analysis was done by a combined approach involving genome-wide autozygosity mapping and next-generation exome sequencing. Biochemical analysis was done by enzymatic analysis and Western blot. Evidence for mitochondrial DNA (mtDNA) instability was investigated using long-range and real-time PCR assays. Mitochondrial cristae morphology was assessed with transmission electron microscopy. RESULTS: Both affected sisters presented with a similar cluster of neurodevelopmental deficits marked by failure to thrive, generalised neuromuscular weakness and optic atrophy. The disease progression was ultimately fatal with severe encephalopathy and hypertrophic cardiomyopathy. Mitochondrial respiratory chain complex activities were globally decreased in skeletal muscle biopsies. They were found to be homozygous for a novel c.1601T>G (p.Leu534Arg) mutation in the OPA1 gene, which resulted in a marked loss of steady-state levels of the native OPA1 protein. We observed severe mtDNA depletion in DNA extracted from the patients' muscle biopsies. Mitochondrial morphology was consistent with abnormal mitochondrial membrane fusion. CONCLUSIONS: We have established, for the first time, a causal link between a pathogenic homozygous OPA1 mutation and human disease. The fatal multisystemic manifestations observed further extend the complex phenotype associated with pathogenic OPA1 mutations, in particular the previously unreported association with hypertrophic cardiomyopathy. Our findings further emphasise the vital role played by OPA1 in mitochondrial biogenesis and mtDNA maintenance

Inflammatory cytokines and atherosclerotic plaque progression. therapeutic implications

Inflammatory cytokines play a major role in atherosclerotic plaque progression. This review summarizes the rationale for personalized anti-inflammatory therapy

Developing Predictive Models for Risk of Postoperative Complications and Hemodynamic Instability in Patients Undergoing Surgery

Patients undergoing high-risk surgeries are often at higher risk of developing hemodynamic instability during surgery resulting in poor postoperative outcomes. This is usually associated with significantly increased postoperative morbidity and mortality, which therefore makes the early identification of these critical events and those patients at risk of postoperative complications crucial. With these motivations in mind, we first created a large deidentified research dataset of surgical case medical records from University of California, Irvine Medical Center (UCIMC) matched with physiological waveforms as well as intermittent vital sign values, lab values, and ventilator settings. To our knowledge, such a dataset does not currently exist for the intraoperative environment. We hope that creating a such a dataset will allow for advances in machine learning for intraoperative care. Using medical data from UCLA, we have developed deep neural network models to classify the risks of postoperative mortality, acute kidney injury, and reintubation utilizing readily available intraoperative information. Our risk scores were compared to currently commonly used risk indices ASA and Surgical Apgar as well as logistic regression. While the deep neural network models performed better than the risk scores and logistic regression, clinicians require additional information to assess what led to increased risk of complications. To address this, we also assessed the use of generalized additive neural networks (GANNs) to create a graphical look at how different features contributed to the risk of in hospital mortality. Finally, we were also interested in predicting critical intraoperative events to allow for time for the clinician to avoid such events. We focused on intraoperative hypotension as it is easier to define and has been shown to lead to increased risk of acute kidney injury, stroke, and myocardial injury. For the hypotension prediction models, we looked at the arterial pressure waveform and EMR data as inputs. Overall, these aims address a gap in current clinical decision guidance and support to reduce adverse events during surgery as well complications after

The burden of severe cases of Influenza disease: The Friuli Venezia Giulia Region experience

IIntroduction. Influenza is a matter of serious concern for clinicians, in both outpatient and in-hospital settings. Worldwide, the 2017-18 epidemic proved to be the most severe since 2003-04. We report a real-world experience regarding the management of patients with influenza admitted to a large teaching hospital in the Friuli Venezia Giulia region during the 2017-2018 influenza season. We also provide a practical guide for the management of hospitalized influenza patients. Methods. A retrospective observational analysis was conducted among all influenza patients requiring admission to our center during the 2017-18 season. Results. Overall, 29 patients were admitted to the University Hospital of Udine during the 2017-18 season with a diagnosis of influenza. B virus was responsible for the majority of cases. More than 65.5% of the subjects presented with a complication. We estimated that 41.4% of the patients admitted were affected by a \u201csevere form\u201d. All these cases required admission to the Intensive Care Unit, with 27.6% and 10.3% needing Orotracheal Intubation and Extracorporeal Membrane Oxygenation, respectively. The fatality rate was 24.1%. Notably, only 9 subjects in our cohort had been vaccinated. Based on the experience acquired during the past season, we propose a practical guide to the management of influenza cases in everyday hospital practice. Conclusion. The cornerstones of the management of all hospitalized influenza patients are the rapid identification and treatment of severe forms. Timely and strict adherence to contact and respiratory precautions are also fundamental to reducing the risk of intra-hospital outbreaks. Despite improvements in antiviral therapies and supportive measures, influenza-related morbidity and mortality remain high. In our opinion, a universal vaccination program is the only safe and effective method of filling the gap

Risk adjusted mortality rates : Do they differ if bases on administrative data (hospital standardised mortality ratio) versus a physiological predictive model (APACHE IV ®)?

Background: The measurement of, and reporting on clinical outcomes, is an integral part of clinical governance but no consensus has been reached about which measures to use and the validity thereof. Objective: To compare an administrative predictive model (Hospital Standardised Mortality Ratio [HSMR]) with a physiological predictive model (APACHE ®IV) to determine the correlation in the predicted risk adjusted mortality rates. To determine whether stratifying the patients into low (80%) risk bands will lead to more accurate comparisons. Design: Prospective cohort study Setting: 63 critical care units in 34 private acute care facilities across South Africa Methods: Both HSMR and APACHE ®IV are calculated routinely in all participating facilities and the research study will use the data generated. An additional audit process will be implemented to determine and ensure the integrity of the data. Ethics: The healthcare facilities have standard processes in place to ensure confidentiality and the statistician analysing the data is employed by the healthcare group and bound to a confidentiality agreement. Ethics approval has also been obtained by the University of Cape Town ethic committee before the approval of the research proposal

Endothelial Dysfunction: Associations with Exposure to Ambient Fine Particles in Diabetic Individuals

BACKGROUND: Exposure to fine airborne particulate matter [<= 2.5 mu m in aerodynamic diameter (PM2.5)] has been associated with cardiovascular and hematologic effects, especially in older people with cardiovascular disease. Some epidemiologic studies suggest that adults with diabetes also may be a particularly susceptible population. OBJECTIVES: The purpose of this study was to analyze the short-term effects of ambient PM2.5 on markers of endothelial function in diabetic volunteers.METHODS: We conducted a prospective panel study in 22 people with type 2 diabetes mellitus in Chapel Hill, North Carolina (USA), from November 2004 to December 2005. We acquired daily measurements of PM2.5 and meteorologic data at central monitoring sites. On 4 consecutive days, we measured endothelial function by brachial artery ultrasound in all participants and by pulsewave measurements in a subgroup. Data were analyzed using additive mixed models with a random participant effect and adjusted for season, day of the week, and meteorology. RESULTS: Flow-mediated dilatation decreased in association with PM2.5 during the first 24 hr, whereas small-artery elasticity index decreased with a delay of 1 and 3 days. These PM2.5-associated decrements in endothelial function were greater among participants with a high body mass index, high glycosylated hemoglobin Ale, low adiponectin, or the null polymorphism of glutathione S-transferase M1. However, high levels of myeloperoxidase on the examination day led to strongest effects on endothelial dysfunction. CONCLUSIONS: These data demonstrate that PM2.5 exposure may cause immediate endothelial dysfunction. Clinical characteristics associated with insulin resistance were associated with enhanced effects of PM on endothelial function. In addition, participants with greater oxidative potential seem to be more susceptible

Association between air pollution and ventricular arrhythmias in high-risk patients (ARIA study): a multicentre longitudinal study

Summary Background Although the effects of air pollution on mortality have been clearly shown in many epidemiological and observational studies, the pro-arrhythmic effects remain unknown. We aimed to assess the short-term effects of air pollution on ventricular arrhythmias in a population of high-risk patients with implantable cardioverter-defibrillators (ICDs) or cardiac resynchronisation therapy defibrillators (ICD-CRT). Methods In this prospective multicentre study, we assessed 281 patients (median age 71 years) across nine centres in the Veneto region of Italy. Episodes of ventricular tachycardia and ventricular fibrillation that were recorded by the diagnostic device were considered in this analysis. Concentrations of particulate matter of less than 10 μm (PM 10 ) and less than 2·5 μm (PM 2·5 ) in aerodynamic diameter, carbon monoxide, nitrogen dioxide, sulphur dioxide, and ozone were obtained daily from monitoring stations, and the 24 h median value was considered. Each patient was associated with exposure data from the monitoring station that was closest to their residence. Patients were followed up for 1 year and then scheduled to have a closing visit, within 1 more year. This study is registered with ClinicalTrials.gov, number NCT01723761. Findings Participants were enrolled from April 1, 2011, to Sept 30, 2012, and follow-ups (completed on April 5, 2014) ranged from 637 to 1177 days (median 652 days). The incidence of episodes of ventricular tachycardia and ventricular fibrillation correlated significantly with PM 2·5 (p 10 . An analysis of ventricular fibrillation episodes alone showed a significant increase in risk of higher PM 2·5 (p=0·002) and PM 10 values (p=0·0057). None of the gaseous pollutants were significantly linked to the occurrence of ventricular tachycardia or ventricular fibrillation. In a subgroup analysis of patients with or without a previous myocardial infarction, only the first showed a significant association between particulate matter and episodes of ventricular tachycardia or ventricular fibrillation. Interpretation Particulate matter has acute pro-arrhythmic effects in a population of high-risk patients, which increase on exposure to fine particles and in patients who have experienced a previous myocardial infarction. The time sequence of the arrhythmic events suggests there is an underlying neurally mediated mechanism. From a clinical point of view, the results of our study should encourage physicians to also consider environmental risk when addressing the prevention of arrhythmic events, particularly in patients with coronary heart disease, advising them to avoid exposure to high levels of fine particulate matter. Funding There was no funding source for this study