Safety and disease monitoring biomarkers in Duchenne muscular dystrophy: results from a Phase II trial

Aim: Evaluate the utility of glutamate dehydrogenase (GLDH) and cardiac troponin I as safety biomarkers, and creatine kinase and muscle injury panel as muscle health biomarkers in Duchenne muscular dystrophy. Patients & methods: Data were collected during a Phase II trial of domagrozumab. Results: GLDH was a more specific biomarker for liver injury than alanine aminotransferase. Cardiac troponin I elevations were variable and not sustained, limiting its applicability as a biomarker. Muscle injury panel biomarkers were no more informative than creatine kinase as a muscle health biomarker. Conclusion: Results support the use of GLDH as a specific biomarker for liver injury in patients with Duchenne muscular dystrophy

Using electronic health records to predict costs and outcomes in stable coronary artery disease

OBJECTIVES: To use electronic health records (EHR) to predict lifetime costs and health outcomes of patients with stable coronary artery disease (stable-CAD) stratified by their risk of future cardiovascular events, and to evaluate the cost-effectiveness of treatments targeted at these populations. METHODS: The analysis was based on 94 966 patients with stable-CAD in England between 2001 and 2010, identified in four prospectively collected, linked EHR sources. Markov modelling was used to estimate lifetime costs and quality-adjusted life years (QALYs) stratified by baseline cardiovascular risk. RESULTS: For the lowest risk tenth of patients with stable-CAD, predicted discounted remaining lifetime healthcare costs and QALYs were £62 210 (95% CI £33 724 to £90 043) and 12.0 (95% CI 11.5 to 12.5) years, respectively. For the highest risk tenth of the population, the equivalent costs and QALYs were £35 549 (95% CI £31 679 to £39 615) and 2.9 (95% CI 2.6 to 3.1) years, respectively. A new treatment with a hazard reduction of 20% for myocardial infarction, stroke and cardiovascular disease death and no side-effects would be cost-effective if priced below £72 per year for the lowest risk patients and £646 per year for the highest risk patients. CONCLUSIONS: Existing EHRs may be used to estimate lifetime healthcare costs and outcomes of patients with stable-CAD. The stable-CAD model developed in this study lends itself to informing decisions about commissioning, pricing and reimbursement. At current prices, to be cost-effective some established as well as future stable-CAD treatments may require stratification by patient risk

Long-term healthcare use and costs in patients with stable coronary artery disease: a population-based cohort using linked health records (CALIBER)

AIMS: To examine long-term healthcare utilization and costs of patients with stable coronary artery disease (SCAD). METHODS AND RESULTS: Linked cohort study of 94 966 patients with SCAD in England, 1 January 2001 to 31 March 2010, identified from primary care, secondary care, disease, and death registries. Resource use and costs, and cost predictors by time and 5-year cardiovascular disease (CVD) risk profile were estimated using generalized linear models. Coronary heart disease hospitalizations were 20.5% in the first year and 66% in the year following a non-fatal (myocardial infarction, ischaemic or haemorrhagic stroke) event. Mean healthcare costs were £3133 per patient in the first year and £10 377 in the year following a non-fatal event. First-year predictors of cost included sex (mean cost £549 lower in females), SCAD diagnosis (non-ST-elevation myocardial infarction cost £656 more than stable angina), and co-morbidities (heart failure cost £657 more per patient). Compared with lower risk patients (5-year CVD risk 3.5%), those of higher risk (5-year CVD risk 44.2%) had higher 5-year costs (£23 393 vs. £9335) and lower lifetime costs (£43 020 vs. £116 888). CONCLUSION: Patients with SCAD incur substantial healthcare utilization and costs, which varies and may be predicted by 5-year CVD risk profile. Higher risk patients have higher initial but lower lifetime costs than lower risk patients as a result of shorter life expectancy. Improved cardiovascular survivorship among an ageing CVD population is likely to require stratified care in anticipation of the burgeoning demand

Salivary Testosterone and Sexual Function and Behavior in Men and Women: Findings from the Third British National Survey of Sexual Attitudes and Lifestyles (Natsal-3)

Using data from the third British National Survey of Sexual Attitudes and Lifestyles (Natsal-3) we examined associations between salivary testosterone (Sal-T) and sexual function and behavior. Single morning saliva samples were self-collected from a subsample of participants aged 18–74 years and analyzed using mass spectrometry. 1,599 men and 2,123 women were included in the analysis (40.6% of those invited to provide a sample). We adjusted for confounders in a stepwise manner: in model 1 we adjusted for age only; model 2 for age, season and relationship status, and model 3 we added BMI and self-reported health. In the fully adjusted models, among men, Sal-T was positively associated with both partnered sex (vaginal sex and concurrent partners) and masturbation. Among women, Sal-T was positively associated with masturbation, the only association with partnered sex was with ever experience of same-sex sex. We found no clear association between Sal-T and sexual function. Our study contributes toward addressing the sparsity of data outside the laboratory on the differences between men and women in the relationship between T and sexual function and behavior. To our knowledge, this is the first population study, among men and women, using a mass spectrometry Sal-T assay to do so

Urinary Levoglucosan as a Biomarker of Wood Smoke Exposure: Observations in a Mouse Model and in Children

BACKGROUND: Biomass smoke is an important source of particulate matter (PM), and much remains to be discovered with respect to the human health effects associated with this specific PM source. Exposure to biomass smoke can occur in one of two main categories: short-term exposures consist of periodic, seasonal exposures typified by communities near forest fires or intentional agricultural burning, and long-term exposures are chronic and typified by the use of biomass materials for cooking or heating. Levoglucosan (LG), a sugar anhydride released by combustion of cellulose-containing materials, is an attractive candidate as a biomarker of wood smoke exposure. OBJECTIVES: In the present study, Balb/c mice and children were assessed for LG in urine to determine its feasibility as a biomarker. METHODS: We performed urinary detection of LG by gas chromatography/mass spectrometry after intranasal instillations of LG or concentrated PM (mice) or biomass exposure (mice or humans). RESULTS: After instillation, we recovered most of the LG within the first 4 hr. Experiments using glucose instillation proved the specificity of our system, and instillation of concentrated PM from wood smoke, ambient air, and diesel exhaust supported a connection between wood smoke and LG. In addition, LG was detected in the urine of mice exposed to wood smoke. Finally, a pilot human study proved our ability to detect LG in urine of children. CONCLUSIONS: These results demonstrate that LG in the lungs is detectable in the urine of both mice and humans and that it is a good candidate as a biomarker of exposure to biomass smoke

Why do Particle Clouds Generate Electric Charges?

Grains in desert sandstorms spontaneously generate strong electrical charges; likewise volcanic dust plumes produce spectacular lightning displays. Charged particle clouds also cause devastating explosions in food, drug and coal processing industries. Despite the wide-ranging importance of granular charging in both nature and industry, even the simplest aspects of its causes remain elusive, because it is difficult to understand how inert grains in contact with little more than other inert grains can generate the large charges observed. Here, we present a simple yet predictive explanation for the charging of granular materials in collisional flows. We argue from very basic considerations that charge transfer can be expected in collisions of identical dielectric grains in the presence of an electric field, and we confirm the model's predictions using discrete-element simulations and a tabletop granular experiment

Salience-based selection: attentional capture by distractors less salient than the target

Current accounts of attentional capture predict the most salient stimulus to be invariably selected first. However, existing salience and visual search models assume noise in the map computation or selection process. Consequently, they predict the first selection to be stochastically dependent on salience, implying that attention could even be captured first by the second most salient (instead of the most salient) stimulus in the field. Yet, capture by less salient distractors has not been reported and salience-based selection accounts claim that the distractor has to be more salient in order to capture attention. We tested this prediction using an empirical and modeling approach of the visual search distractor paradigm. For the empirical part, we manipulated salience of target and distractor parametrically and measured reaction time interference when a distractor was present compared to absent. Reaction time interference was strongly correlated with distractor salience relative to the target. Moreover, even distractors less salient than the target captured attention, as measured by reaction time interference and oculomotor capture. In the modeling part, we simulated first selection in the distractor paradigm using behavioral measures of salience and considering the time course of selection including noise. We were able to replicate the result pattern we obtained in the empirical part. We conclude that each salience value follows a specific selection time distribution and attentional capture occurs when the selection time distributions of target and distractor overlap. Hence, selection is stochastic in nature and attentional capture occurs with a certain probability depending on relative salience

Clinicopathological Profile and Surgical Treatment of Abdominal Tuberculosis: A Single Centre Experience in Northwestern Tanzania.

Abdominal tuberculosis continues to be a major public health problem worldwide and poses diagnostic and therapeutic challenges to general surgeons practicing in resource-limited countries. This study was conducted to describe the clinicopathological profile and outcome of surgical treatment of abdominal tuberculosis in our setting and compare with what is described in literature. A prospective descriptive study of patients who presented with abdominal tuberculosis was conducted at Bugando Medical Centre (BMC) in northwestern Tanzania from January 2006 to February 2012. Ethical approval to conduct the study was obtained from relevant authorities. Statistical data analysis was performed using SPSS version 17.0. Out of 256 patients enrolled in the study, males outnumbered females. The median age was 28 years (range = 16-68 years). The majority of patients (77.3%) had primary abdominal tuberculosis. A total of 127 (49.6%) patients presented with intestinal obstruction, 106 (41.4%) with peritonitis, 17 (6.6%) with abdominal masses and 6 (2.3%) patients with multiple fistulae in ano. Forty-eight (18.8%) patients were HIV positive. A total of 212 (82.8%) patients underwent surgical treatment for abdominal tuberculosis. Bands /adhesions (58.5%) were the most common operative findings. Ileo-caecal region was the most common bowel involved in 122 (57.5%) patients. Release of adhesions and bands was the most frequent surgical procedure performed in 58.5% of cases. Complication and mortality rates were 29.7% and 18.8% respectively. The overall median length of hospital stay was 32 days and was significantly longer in patients with complications (p < 0.001). Advanced age (age ≥ 65 years), co-morbid illness, late presentation, HIV positivity and CD4+ count < 200 cells/μl were statistically significantly associated with mortality (p < 0.0001). The follow up of patients were generally poor as only 37.5% of patients were available for follow up at twelve months after discharge. Abdominal tuberculosis constitutes a major public health problem in our environment and presents a diagnostic challenge requiring a high index of clinical suspicion. Early diagnosis, early anti-tuberculous therapy and surgical treatment of the associated complications are essential for survival