Home-based Circuit Training and Community Walking for Intermittent Claudication

Background: Supervised exercise training is recommended for people with peripheral artery disease (PAD), yet it remains underutilized. Home-based exercise programs (HBEPs) are a potential alternative. The aim of this study was to assess the feasibility of conducting a full scale trial of a 12-week HBEP for people living with symptomatic PAD. Methods: In a randomized feasibility trial, patients with intermittent claudication were allocated to either an HBEP or a nonexercise control. The HBEP group was given a Fitbit to use during a 12-week exercise program comprising of personalized step goals and a resistance-based circuit to be undertaken at home twice weekly. The primary outcome was feasibility, assessed via eligibility, recruitment, attrition, tolerability, and adherence. Acceptability was assessed via semistructured interviews. Secondary analysis was undertaken to determine the feasibility of collecting clinical outcome data. Results: 188 people were screened, 133 were eligible (70.7%), 30 were recruited (22.6%) and one withdrew (3.33%). Mean adherence to the daily step goal was 53.5% (range ¼ 29.8e 90.5%), and 58.6% of prescribed circuits were completed of which 56.4% were at the desired intensity. Six adverse events were recorded, 3 of which were related to study involvement. No significant differences were observed in exploratory outcomes. Small clinically important differences were seen in walking speed and pain-free treadmill walking distance which should be confirmed or refuted in a larger trial. Conclusions: The HBEP was feasible and well tolerated, with successful recruitment and minimal attrition. The intervention was acceptable, with walking seen as more enjoyable than circuit exercise. The WALKSTRONG program may be suitable for those who will not, or cannot, take part in supervised exercise outside of the home

Cost-effectiveness of High-Intensity Interval Training (HIIT) vs Moderate Intensity Steady-State (MISS) Training in UK Cardiac Rehabilitation

Objective: To perform a cost-effectiveness analysis of high-intensity interval training (HIIT) compared with moderate intensity steady-state (MISS) training in people with coronary artery disease (CAD) attending cardiac rehabilitation (CR). Design: Secondary cost-effectiveness analysis of a prospective, assessor-blind, parallel group, multi-center RCT. Setting: Six outpatient National Health Service cardiac rehabilitation centers in England and Wales, UK. Participants: 382 participants with CAD (N=382). Interventions: Participants were randomized to twice-weekly usual care (n=195) or HIIT (n=187) for 8 weeks. Usual care was moderate intensity continuous exercise (60%-80% maximum capacity, MISS), while HIIT consisted of 10 × 1-minute intervals of vigorous exercise (>85% maximum capacity) interspersed with 1-minute periods of recovery. Main Outcome Measures: We conducted a cost-effectiveness analysis of the HIIT or MISS UK trial. Health related quality of life was measured with the EQ-5D-5L to estimate quality-adjusted life years (QALYs). Costs were estimated with health service resource use and intervention delivery costs. Cost-utility analysis measured the incremental cost-effectiveness ratio (ICER). Bootstrapping assessed the probability of HIIT being cost-effective according to the UK National Institute for Health and Care Excellence (NICE) threshold value (£20,000 per QALY). Missing data were imputed. Uncertainty was estimated using probabilistic sensitivity analysis. Assumptions were tested using univariate/1-way sensitivity analysis. Results: 124 (HIIT, n=59; MISS, n=65) participants completed questionnaires at baseline, 8 weeks, and 12 months. Mean combined health care use and delivery cost was £676 per participant for HIIT, and £653 for MISS. QALY changes were 0.003 and -0.013, respectively. For complete cases, the ICER was £1448 per QALY for HIIT compared with MISS. At a willingness-to-pay threshold of £20,000 per QALY, the probability of HIIT being cost-effective was 96% (95% CI, 0.90 to 0.95). Conclusion: For people with CAD attending CR, HIIT was cost-effective compared with MISS. These findings are important to policy makers, commissioners, and service providers across the health care sector

The Science of Sungrazers, Sunskirters, and Other Near-Sun Comets

This review addresses our current understanding of comets that venture close to the Sun, and are hence exposed to much more extreme conditions than comets that are typically studied from Earth. The extreme solar heating and plasma environments that these objects encounter change many aspects of their behaviour, thus yielding valuable information on both the comets themselves that complements other data we have on primitive solar system bodies, as well as on the near-solar environment which they traverse. We propose clear definitions for these comets: We use the term near-Sun comets to encompass all objects that pass sunward of the perihelion distance of planet Mercury (0.307 AU). Sunskirters are defined as objects that pass within 33 solar radii of the Sun’s centre, equal to half of Mercury’s perihelion distance, and the commonly-used phrase sungrazers to be objects that reach perihelion within 3.45 solar radii, i.e. the fluid Roche limit. Finally, comets with orbits that intersect the solar photosphere are termed sundivers. We summarize past studies of these objects, as well as the instruments and facilities used to study them, including space-based platforms that have led to a recent revolution in the quantity and quality of relevant observations. Relevant comet populations are described, including the Kreutz, Marsden, Kracht, and Meyer groups, near-Sun asteroids, and a brief discussion of their origins. The importance of light curves and the clues they provide on cometary composition are emphasized, together with what information has been gleaned about nucleus parameters, including the sizes and masses of objects and their families, and their tensile strengths. The physical processes occurring at these objects are considered in some detail, including the disruption of nuclei, sublimation, and ionisation, and we consider the mass, momentum, and energy loss of comets in the corona and those that venture to lower altitudes. The different components of comae and tails are described, including dust, neutral and ionised gases, their chemical reactions, and their contributions to the near-Sun environment. Comet-solar wind interactions are discussed, including the use of comets as probes of solar wind and coronal conditions in their vicinities. We address the relevance of work on comets near the Sun to similar objects orbiting other stars, and conclude with a discussion of future directions for the field and the planned ground- and space-based facilities that will allow us to address those science topics

Genetic Diversity and Protective Efficacy of the RTS,S/AS01 Malaria Vaccine.

BACKGROUND: The RTS,S/AS01 vaccine targets the circumsporozoite protein of Plasmodium falciparum and has partial protective efficacy against clinical and severe malaria disease in infants and children. We investigated whether the vaccine efficacy was specific to certain parasite genotypes at the circumsporozoite protein locus. METHODS: We used polymerase chain reaction-based next-generation sequencing of DNA extracted from samples from 4985 participants to survey circumsporozoite protein polymorphisms. We evaluated the effect that polymorphic positions and haplotypic regions within the circumsporozoite protein had on vaccine efficacy against first episodes of clinical malaria within 1 year after vaccination. RESULTS: In the per-protocol group of 4577 RTS,S/AS01-vaccinated participants and 2335 control-vaccinated participants who were 5 to 17 months of age, the 1-year cumulative vaccine efficacy was 50.3% (95% confidence interval [CI], 34.6 to 62.3) against clinical malaria in which parasites matched the vaccine in the entire circumsporozoite protein C-terminal (139 infections), as compared with 33.4% (95% CI, 29.3 to 37.2) against mismatched malaria (1951 infections) (P=0.04 for differential vaccine efficacy). The vaccine efficacy based on the hazard ratio was 62.7% (95% CI, 51.6 to 71.3) against matched infections versus 54.2% (95% CI, 49.9 to 58.1) against mismatched infections (P=0.06). In the group of infants 6 to 12 weeks of age, there was no evidence of differential allele-specific vaccine efficacy. CONCLUSIONS: These results suggest that among children 5 to 17 months of age, the RTS,S vaccine has greater activity against malaria parasites with the matched circumsporozoite protein allele than against mismatched malaria. The overall vaccine efficacy in this age category will depend on the proportion of matched alleles in the local parasite population; in this trial, less than 10% of parasites had matched alleles. (Funded by the National Institutes of Health and others.)

Alberta Diabetes and Physical Activity Trial (ADAPT): A randomized theory-based efficacy trial for adults with type 2 diabetes - rationale, design, recruitment, evaluation, and dissemination

Background: The primary aim of this study was to compare the efficacy of three physical activity (PA) behavioural intervention strategies in a sample of adults with type 2 diabetes. Method/Design: Participants (N = 287) were randomly assigned to one of three groups consisting of the following intervention strategies: (1) standard printed PA educational materials provided by the Canadian Diabetes Association [i.e., Group 1/control group)]; (2) standard printed PA educational materials as in Group 1, pedometers, a log book and printed PA information matched to individuals' PA stage of readiness provided every 3 months (i.e., Group 2); and (3) PA telephone counseling protocol matched to PA stage of readiness and tailored to personal characteristics, in addition to the materials provided in Groups 1 and 2 (i.e., Group 3). PA behaviour measured by the Godin Leisure Time Exercise Questionnaire and related social-cognitive measures were assessed at baseline, 3, 6, 9, 12 and 18-months (i.e., 6-month follow-up). Clinical (biomarkers) and health-related quality of life assessments were conducted at baseline, 12-months, and 18-months. Linear Mixed Model (LMM) analyses will be used to examine time-dependent changes from baseline across study time points for Groups 2 and 3 relative to Group 1. Discussion: ADAPT will determine whether tailored but low-cost interventions can lead to sustainable increases in PA behaviours. The results may have implications for practitioners in designing and implementing theory-based physical activity promotion programs for this population

The 5-Choice Continuous Performance Test: Evidence for a Translational Test of Vigilance for Mice

Attentional dysfunction is related to functional disability in patients with neuropsychiatric disorders such as schizophrenia, bipolar disorder, and Alzheimer's disease. Indeed, sustained attention/vigilance is among the leading targets for new medications designed to improve cognition in schizophrenia. Although vigilance is assessed frequently using the continuous performance test (CPT) in humans, few tests specifically assess vigilance in rodents.We describe the 5-choice CPT (5C-CPT), an elaboration of the 5-choice serial reaction (5CSR) task that includes non-signal trials, thus mimicking task parameters of human CPTs that use signal and non-signal events to assess vigilance. The performances of C57BL/6J and DBA/2J mice were assessed in the 5C-CPT to determine whether this task could differentiate between strains. C57BL/6J mice were also trained in the 5CSR task and a simple reaction-time (RT) task involving only one choice (1CRT task). We hypothesized that: 1) C57BL/6J performance would be superior to DBA/2J mice in the 5C-CPT as measured by the sensitivity index measure from signal detection theory; 2) a vigilance decrement would be observed in both strains; and 3) RTs would increase across tasks with increased attentional load (1CRT task<5CSR task<5C-CPT).C57BL/6J mice exhibited superior SI levels compared to DBA/2J mice, but with no difference in accuracy. A vigilance decrement was observed in both strains, which was more pronounced in DBA/2J mice and unaffected by response bias. Finally, we observed increased RTs with increased attentional load, such that 1CRT task<5CSR task<5C-CPT, consistent with human performance in simple RT, choice RT, and CPT tasks. Thus we have demonstrated construct validity for the 5C-CPT as a measure of vigilance that is analogous to human CPT studies