Quantifying disease progression in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) exhibits characteristic variability of onset and rate of disease progression, with inherent clinical heterogeneity making disease quantitation difficult. Recent advances in understanding pathogenic mechanisms linked to the development of ALS impose an increasing need to develop strategies to predict and more objectively measure disease progression. This review explores phenotypic and genetic determinants of disease progression in ALS, and examines established and evolving biomarkers that may contribute to robust measurement in longitudinal clinical studies. With targeted neuroprotective strategies on the horizon, developing efficiencies in clinical trial design may facilitate timely entry of novel treatments into the clinic. Ann Neurol 2014;76:643–657     

Estimating the Health Effects of Greenhouse Gas Mitigation Strategies: Addressing Parametric,Model, and Valuation Challenges

Background: Policy decisions regarding climate change mitigation are increasingly incorporating the beneficial and adverse health impacts of greenhouse gas emission reduction strategies. Studies of such co-benefits and co-harms involve modeling approaches requiring a range of analytic decisions that affect the model output.Objective: Our objective was to assess analytic decisions regarding model framework, structure, choice of parameters, and handling of uncertainty when modeling health co-benefits, and to make recommendations for improvements that could increase policy uptake.Methods: We describe the assumptions and analytic decisions underlying models of mitigation co-benefits, examining their effects on modeling outputs, and consider tools for quantifying uncertainty.Discussion: There is considerable variation in approaches to valuation metrics, discounting methods, uncertainty characterization and propagation, and assessment of low-probability/high-impact events. There is also variable inclusion of adverse impacts of mitigation policies, and limited extension of modeling domains to include implementation considerations. Going forward, co-benefits modeling efforts should be carried out in collaboration with policy makers; these efforts should include the full range of positive and negative impacts and critical uncertainties, as well as a range of discount rates, and should explicitly characterize uncertainty. We make recommendations to improve the rigor and consistency of modeling of health co-benefits.Conclusion: Modeling health co-benefits requires systematic consideration of the suitability of model assumptions, of what should be included and excluded from the model framework, and how uncertainty should be treated. Increased attention to these and other analytic decisions has the potential to increase the policy relevance and application of co-benefits modeling studies, potentially helping policy makers to maximize mitigation potential while simultaneously improving health.Citation: Remais JV, Hess JJ, Ebi KL, Markandya A, Balbus JM, Wilkinson P, Haines A, Chalabi Z. 2014. Estimating the health effects of greenhouse gas mitigation strategies: addressing parametric, model, and valuation challenges. Environ Health Perspect 122:447–455; http://dx.doi.org/10.1289/ehp.1306744     

Creatinine index and lean body mass are excellent predictors of long-term survival in haemodiafiltration patients.

BACKGROUND: No single measurement adequately defines protein-energy malnutrition. In the dialysis population, somatic protein mass, a useful marker of protein malnutrition, is estimated using the creatinine index (CI), lean body mass (LBM) or both, but the clinical usefulness of these indices remains uncertain. Moreover, calculating these indices requires formal creatinine kinetics or urine and dialysate collection. A simpler method to estimate the creatinine generation rate (G(Cr)) probably might widen its use. METHODS: We evaluated the usefulness of creatinine-based indices for predicting mortality in a cohort of 226 French haemodiafiltration patients using the Cox proportional hazards method. We also proposed simple yet precise formulas to calculate post-dialysis creatinine (Cr(post)) concentrations and derive creatinine generation rates (G(Cr)) from readily available measures. These formulas were developed using a large database containing more than 10 000 measured Cr(post) and G(Cr) values based on formal creatinine modelling. A single set of monthly values was used to evaluate the validity of the formulas. RESULTS: When adjusted for comorbidities, sex and Kt/V, CI and LBM/body weight (LBM/BW) were better predictors of 5 year all-cause mortality than urea-based indices [survival relative risk (RR) = 0.24, P<0.01 for CI<22 mg/kg/day; RR = 0.33, P<0.02 for LBM/BW<0.75]. When the cohort was divided according to gender, similar results were found in males, but not in females. The different formulas allowed adequate prediction of Cr(post) and G(Cr) and classification of patients with good accuracy (CI<22: sensitivity = 94%, specificity = 82%; LBW/BW<0.75: sensitivity = 89%, specificity = 90%). CONCLUSIONS: In a haemodiafiltration population, CI and LBM are excellent predictors of long-term survival. In anuric Caucasian haemodialysis patients, CI and LBM can be estimated from biochemical and anthropometric measurements without relying on formal modelling.     

Alterations of glucose levels in the blood and the anterior eye segment of rabbits exposed to ketamine-xylazine anaesthesia

In rabbits the blood glucose and consequently the aqueous humour glucose levels were increased under general anaesthesia by Ketanest-xylazine. Between 60 and 90 min of the general anaesthesia the average blood glucose levels were found to be three times and those of the aqueous humour twice the normal values. After more than 75 min of anaesthesia the glucose levels tended to be further elevated.     

Health, agricultural, and economic effects of adoption of healthy diet recommendations

Transition to diets that are high in saturated fat and sugar has caused a global public health concern, as the pattern of food consumption is a major modifiable risk factor for chronic non-communicable diseases. Although agri-food systems are intimately associated with this transition, agriculture and health sectors are largely disconnected in their priorities, policy, and analysis, with neither side considering the complex inter-relation between agri-trade, patterns of food consumption, health, and development. We show the importance of connection of these perspectives through estimation of the eff ect of adopting a healthy diet on population health, agricultural production, trade, the economy, and livelihoods,with a computable general equilibrium approach. On the basis of case-studies from the UK and Brazil, we suggest that benefits of a healthy diet policy will vary substantially between different populations, not only because of population dietary intake but also because of agricultural production, trade, and other economic factors.     

Periodontopathic bacteria and herpesviruses in chronic periodontitis

Periodontal disease involves complex interactions of microorganisms and host defenses. This work investigated the associations between putative bacterial pathogens, herpesviruses and chronic periodontitis. Subgingival samples were collected from 40 periodontally healthy individuals and from 40 patients with chronic periodontitis with probing depths of ≤3 mm or ≥6 mm. Multiplex and nested polymerase chain reactions were used to identify bacterial pathogens and herpesviruses. Porphyromonas gingivalis, Tannerella forsythia, Epstein–Barr virus (EBV) type 1, cytomegalovirus (CMV), Aggregatibacter actinomycetemcomitans and EBV type 2 were detected in, respectively, 95, 75, 72.5, 50, 12.5 and 10% of sites with probing depths ≥6 mm. P. gingivalis, T. forsythia, EBV‐1 and CMV were statistically associated with probing depths ≥6 mm. A. actinomycetemcomitans and EBV‐2 showed no association with periodontitis sites, and no significant associations were found for any of the test infectious agents and probing depths ≤3 mm. Our results confirm an association between P. gingivalis, T. forsythia, EBV‐1 and CMV, and chronic periodontitis. These infectious agents may play an important synergistic role in the pathogenesis of chronic periodontitis.     

Current and future climate- and air pollution-mediated impacts on human health

Background

We describe a project to quantify the burden of heat and ozone on mortality in the UK, both for the present-day and under future emission scenarios.

Methods

Mortality burdens attributable to heat and ozone exposure are estimated by combination of climate-chemistry modelling and epidemiological risk assessment. Weather forecasting models (WRF) are used to simulate the driving meteorology for the EMEP4UK chemistry transport model at 5 km by 5 km horizontal resolution across the UK; the coupled WRF-EMEP4UK model is used to simulate daily surface temperature and ozone concentrations for the years 2003, 2005 and 2006, and for future emission scenarios. The outputs of these models are combined with evidence on the ozone-mortality and heat-mortality relationships derived from epidemiological analyses (time series regressions) of daily mortality in 15 UK conurbations, 1993-2003, to quantify present-day health burdens.

Results

During the August 2003 heatwave period, elevated ozone concentrations > 200 μg m^-3 were measured at sites in London and elsewhere. This and other ozone photochemical episodes cause breaches of the UK air quality objective for ozone. Simulations performed with WRF-EMEP4UK reproduce the August 2003 heatwave temperatures and ozone concentrations. There remains day-to-day variability in the high ozone concentrations during the heatwave period, which on some days may be explained by ozone import from the European continent.Preliminary calculations using extended time series of spatially-resolved WRF-EMEP4UK model output suggest that in the summers (May to September) of 2003, 2005 & 2006 over 6000 deaths were attributable to ozone and around 5000 to heat in England and Wales. The regional variation in these deaths appears greater for heat-related than for ozone-related burdens.Changes in UK health burdens due to a range of future emission scenarios will be quantified. These future emissions scenarios span a range of possible futures from assuming current air quality legislation is fully implemented, to a more optimistic case with maximum feasible reductions, through to a more pessimistic case with continued strong economic growth and minimal implementation of air quality legislation.

Conclusion

Elevated surface ozone concentrations during the 2003 heatwave period led to exceedences of the current UK air quality objective standards. A coupled climate-chemistry model is able to reproduce these temperature and ozone extremes. By combining model simulations of surface temperature and ozone with ozone-heat-mortality relationships derived from an epidemiological regression model, we estimate present-day and future health burdens across the UK. Future air quality legislation may need to consider the risk of increases in future heatwaves.

     

An ultrasound speckle tracking (two-dimensional strain) analysis of myocardial deformation in professional soccer players compared with healthy subjects and hypertrophic cardiomyopathy

Deformation analysis using 2-dimensional strain echocardiography can detect early systolic function abnormalities in patients with left ventricular hypertrophy. This study was designed to characterize global and regional myocardial deformation using 2-dimensional strain in professional soccer players (PSPs) compared with control subjects and patients with hypertrophic cardiomyopathy (HC). Twenty nine PSPs, 26 patients with HC, and 17 controls were investigated at rest using transthoracic echocardiography with 2-dimensional strain analysis. Radial and transverse strains were significantly higher in PSPs compared with controls, whereas longitudinal strain was lower. Compared with patients with HC, athletes had higher values for transverse, radial, and circumferential strains. In pathologic hypertrophic segments, longitudinal strain was lower in patients with HC than in PSPs. In conclusion, 2-dimensional strain can identify specific patterns of myocardial deformation in PSPs, controls, and patients with HC. It has the potential to become a routinely used method for the differentiation of athlete's heart and HC.