Long-Term Assessment of Lurasidone in Schizophrenia: Post Hoc Analysis of a 12-Month, Double Blind, Active-Controlled Trial and 6-Month Open-Label Extension Study.

INTRODUCTION: A post hoc analysis of a double-blind (DB) active control trial and an open-label extension (OLE) study was conducted to evaluate the long-term effects of lurasidone in patients with schizophrenia. METHODS: In the DB trial, patients were randomised to receive lurasidone or risperidone for 12 months. In OLE, all patients received lurasidone for an additional 6 months. Treatment-emergent adverse events (TEAEs) were evaluated. Efficacy assessments included relapse rate (DB trial only), and Positive and Negative Syndrome Scale, Clinical Global Impression-Severity scale, and Montgomery-Åsberg Depression Rating Scale. RESULTS: In the DB trial, patients with schizophrenia were randomised to lurasidone (n = 399) and risperidone (n = 190), of whom 129 and 84 continued into OLE, respectively. During the DB trial, incidence of TEAEs was similar for lurasidone (84.1%) and risperidone (84.2%). Lurasidone was associated with minimal changes in metabolic variables and prolactin levels, whereas risperidone was associated with clinically significant increases in prolactin and fasting glucose levels. The proportion of patients with metabolic syndrome was significantly lower in patients treated with lurasidone versus risperidone at the end of the DB trial (25.5% vs 40.4%; p = 0.0177). During OLE, patients switching from risperidone to lurasidone experienced a reduction in weight and prolactin levels; those continuing treatment with lurasidone experienced minimal changes in metabolic variables and prolactin. At the end of OLE, the proportion of patients with metabolic syndrome was no longer significantly different between groups (23.5% vs 31.5%; p = not significant). Efficacy outcomes were generally similar between groups during the DB trial, and were maintained during OLE. CONCLUSION: Lurasidone was generally well tolerated and effective in clinically stable schizophrenia patients over the long term. Lurasidone was also generally well tolerated and maintained effectiveness over 6 months in patients switching from risperidone. Patients switching from risperidone experienced improvements in metabolic parameters and prolactin levels. These findings confirm lurasidone's long-term effectiveness and favourable metabolic profile in patients with schizophrenia. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00641745.

A whole family-based physical activity promotion intervention: findings from the families reporting every step to health (FRESH) pilot randomised controlled trial.

INTRODUCTION: This study assessed the feasibility and acceptability of FRESH (Families Reporting Every Step to Health), a theory-based child-led family physical activity (PA) intervention delivered online. We also assessed the preliminary effectiveness of the intervention on outcomes of interest and whether pre-specified criteria were met to progress to a full-scale definitive trial. METHODS: In a three-armed randomised pilot trial, 41 families (with a 7-11-year-old index child) were allocated to a: 'family' (FAM), 'pedometer-only' (PED), or a no-treatment control (CON) arm. The FAM arm received access to the FRESH website, allowing participants to select step challenges to 'travel' to target cities around the world, log their steps, and track progress as families virtually globetrot. FAM and PED arms also received family sets of pedometers. All family members could participate in the evaluation. Physical (e.g., fitness, blood pressure), psychosocial (e.g., social support), behavioural (e.g., objectively-measured PA), and economic (e.g., expenditure for PA) data were collected at baseline, 8- and 52-weeks. RESULTS: At 8- and 52-weeks, 98 and 88% of families were retained, respectively. Most children liked participating in the study (> 90%) and thought it was fun (> 80%). Compared to the PED (45%) and CON (39%) arms, a higher percentage of children in the FAM (81%) arm reported doing more activities with their family. Adults agreed that FRESH encouraged their family do more PA and made their family more aware of the amount of PA they do. No notable between-group differences were found for childrens' minutes in moderate-to-vigorous PA. Sizeable changes of 9.4 (95%CI: 0.4, 18.4) and 15.3 (95%CI: 6.0, 24.5) minutes in moderate-to-vigorous PA was found for adults in the FAM group compared to those in the PED or CON groups, respectively. No other notable differences were found. CONCLUSION: This study demonstrates feasibility and acceptability of the FRESH intervention. All progression criteria were at least partially satisfied. However, we failed to recruit the target sample size and did not find a signal of effectiveness on PA particularly long-term or in children. Further refinements are required to progress to a full-scale trial. TRIAL REGISTRATION: This study was prospectively registered ( ISRCTN12789422 ) on 16/03/2016.

Primary care referral for knee MRI in the United Kingdom: Association with demography and subsequent surgical intervention.

BACKGROUND: Since 2008 primary care physicians (GPs) in our region have been allowed open access to knee MRI scans. There are questions about whether this changes referral practice and if it is an effective use of resources. PURPOSE: To describe the change in demographics of patients referred for knee MRI following implementation of a new referral pathway. STUDY TYPE: Retrospective observational study. POPULATION: All primary care referrals between 2008 and 2015 for knee MRI from a population of 900,000. FIELD STRENGTH/SEQUENCE: Not applicable. ASSESSMENT: Demographic profile and number of knee MRI referrals and subsequent arthroscopies. STATISTICAL TESTS: Comparisons between urban and rural populations used the t-test. Test for normality used Shapiro-Wilks. Comparison between abnormal MRI proportions used a chi-squared test. RESULTS: There were 23,928 knee MRI referrals (10,695 from GPs) between 2000 and 2015. MRI knee referrals rose from 210 in 2008 to 2379 in 2015. The average age of the patient decreased from 46.8 (SD = 14.9) in 2008 to 41.3 (SD = 14.7) in 2015. Conversion to arthroscopy declined from 15.4% to 10.2%, but there was no significant change in abnormal scan proportion. Conversion rates showed no significant difference between rural (9.6%) and urban populations (10.5%). Referral rates were significantly higher in low socioeconomic status areas (47.3% vs. 34.6%). The median referral rate per 1000 patients was 13.8 (interquartile range = 8.4). Referral rates varied widely between practices. DATA CONCLUSION: Despite a large rise in knee MRI referrals from primary care, there has been no substantial change in the age profile, suggesting that there has been no increase in inappropriate referral of elderly patients in whom MRI is unlikely to influence management. A modest decrease in the conversion rate to arthroscopy may be reasonably offset against a decrease in secondary care referrals. Socioeconomic status of the target population must be considered when planning primary care knee MRI services. LEVEL OF EVIDENCE: 4 Technical Efficacy Stage: 6 J. Magn. Reson. Imaging 2019.

Is foreign direct investment good for health in low and middle income countries? An instrumental variable approach.

There is a scarcity of quantitative research into the effect of FDI on population health in low and middle income countries (LMICs). This paper investigates the relationship using annual panel data from 85 LMICs between 1974 and 2012. When controlling for time trends, country fixed effects, correlation between repeated observations, relevant covariates, and endogeneity via a novel instrumental variable approach, we find FDI to have a beneficial effect on overall health, proxied by life expectancy. When investigating age-specific mortality rates, we find a stronger beneficial effect of FDI on adult mortality, yet no association with either infant or child mortality. Notably, FDI effects on health remain undetected in all models which do not control for endogeneity. Exploring the effect of sector-specific FDI on health in LMICs, we provide preliminary evidence of a weak inverse association between secondary (i.e. manufacturing) sector FDI and overall life expectancy. Our results thus suggest that FDI has provided an overall benefit to population health in LMICs, particularly in adults, yet investments into the secondary sector could be harmful to health.

The relationship between international trade and non-nutritional health outcomes: A systematic review of quantitative studies.

Markets throughout the world have been reducing barriers to international trade and investment in recent years. The resulting increases in levels of international trade and investment have subsequently generated research interest into the potential population health impact. We present a systematic review of quantitative studies investigating the relationship between international trade, foreign direct investment and non-nutritional health outcomes. Articles were systematically collected from the SCOPUS, PubMed, EconLit and Web of Science databases. Due to the heterogeneous nature of the evidence considered, the 16 included articles were subdivided into individual level data analyses, selected country analyses and international panel analyses. Articles were then quality assessed using a tool developed as part of the project. Nine of the studies were assessed to be high quality, six as medium quality, and one as low quality. The evidence from the quantitative literature suggests that overall, there appears to be a beneficial association between international trade and population health. There was also evidence of the importance of foreign direct investment, yet a lack of research considering the direction of causality. Taken together, quantitative research into the relationship between trade and non-nutritional health indicates trade to be beneficial, yet this body of research is still in its infancy. Future quantitative studies based on this foundation will provide a stronger basis on which to inform relevant national and international institutions about the health consequences of trade policies.

Improving access to high-quality primary care for socioeconomically disadvantaged older people in rural areas: a mixed method study protocol.

INTRODUCTION: The UK has an ageing population, especially in rural areas, where deprivation is high among older people. Previous research has identified this group as at high risk of poor access to healthcare. The aim of this study is to generate a theory of how socioeconomically disadvantaged older people from rural areas access primary care, to develop an intervention based on this theory and test it in a feasibility trial. METHODS AND ANALYSIS: On the basis of the MRC Framework for Developing and Evaluating Complex Interventions, three methods will be used to generate the theory. First, a realist review will elucidate the patient pathway based on existing literature. Second, an analysis of the English Longitudinal Study of Ageing will be completed using structural equation modelling. Third, 15 semistructured interviews will be undertaken with patients and four focus groups with health professionals. A triangulation protocol will be used to allow each of these methods to inform and be informed by each other, and to integrate data into one overall realist theory. Based on this theory, an intervention will be developed in discussion with stakeholders to ensure that the intervention is feasible and practical. The intervention will be tested within a feasibility trial, the design of which will depend on the intervention. Lessons from the feasibility trial will be used to refine the intervention and gather the information needed for a definitive trial. ETHICS AND DISSEMINATION: Ethics approval from the regional ethics committee has been granted for the focus groups with health professionals and interviews with patients. Ethics approval will be sought for the feasibility trial after the intervention has been designed. Findings will be disseminated to the key stakeholders involved in intervention development, to researchers, clinicians and health planners through peer-reviewed journal articles and conference publications, and locally through a dissemination event.

Children's sedentary behaviour: descriptive epidemiology and associations with objectively-measured sedentary time.

BACKGROUND: Little is known regarding the patterning and socio-demographic distribution of multiple sedentary behaviours in children. The aims of this study were to: 1) describe the leisure-time sedentary behaviour of 9-10 year old British children, and 2) establish associations with objectively-measured sedentary time. METHODS: Cross-sectional analysis in the SPEEDY study (Sport, Physical activity and Eating behaviour: Environmental Determinants in Young people) (N=1513, 44.3% boys). Twelve leisure-time sedentary behaviours were assessed by questionnaire. Objectively-measured leisure-time sedentary time (Actigraph GT1M, <100 counts/minute) was assessed over 7 days. Differences by sex and socioeconomic status (SES) in self-reported sedentary behaviours were tested using Kruskal-Wallis tests. The association between objectively-measured sedentary time and the separate sedentary behaviours (continuous (minutes) and categorised into 'none' 'low' or 'high' participation) was assessed using multi-level linear regression. RESULTS: Sex differences were observed for time spent in most sedentary behaviours (all p ≤ 0.02), except computer use. Girls spent more time in combined non-screen sedentary behaviour (median, interquartile range: girls: 770.0 minutes, 390.0-1230.0; boys: 725.0, 365.0 - 1182.5; p = 0.003), whereas boys spent more time in screen-based behaviours (girls: 540.0, 273.0 - 1050.0; boys: 885.0, 502.5 - 1665.0; p < 0.001). Time spent in five non-screen behaviours differed by SES, with higher values in those of higher SES (all p ≤ 0.001). Regression analyses with continuous exposures indicated that reading (ß = 0.1, p < 0.001) and watching television (ß = 0.04, p < 0.01) were positively associated with objectively-measured sedentary time, whilst playing board games (ß = -0.12, p < 0.05) was negatively associated. Analysed in categorical form, sitting and talking (vs. none: 'low' ß = 26.1,ns; 'high' 30.9, p < 0.05), playing video games (vs. none: 'low' ß = 49.1, p < 0.01; 'high' 60.2, p < 0.01) and watching television (vs. lowest tertile: middle ß = 22.2,ns; highest ß = 31.9, p < 0.05) were positively associated with objectively-measured sedentary time whereas talking on the phone (vs. none: 'low' ß = -38.5, p < 0.01; 'high' -60.2, p < 0.01) and using a computer/internet (vs. none: 'low' ß = -30.7, p < 0.05; 'high' -4.2,ns) were negatively associated. CONCLUSIONS: Boys and girls and children of different socioeconomic backgrounds engage in different leisure-time sedentary behaviours. Whilst a number of behaviours may be predictive of total sedentary time, collectively they explain little overall variance. Future studies should consider a wide range of sedentary behaviours and incorporate objective measures to quantify sedentary time where possible.

Individual, socio-cultural and environmental predictors of uptake and maintenance of active commuting in children: longitudinal results from the SPEEDY study.

BACKGROUND: Active commuting is prospectively associated with physical activity in children. Few longitudinal studies have assessed predictors of change in commuting mode. PURPOSE: To investigate the individual, socio-cultural and environmental predictors of uptake and maintenance of active commuting in 10-year-old children. METHODS: Children were recruited in 2007 and followed-up 12 months later. Children self-reported usual travel mode to school. 31 child, parent, socio-cultural and physical environment characteristics were assessed via self-reported and objective methods. Associations with uptake and maintenance of active travel were studied using multi-level multiple logistic regression models in 2012. RESULTS: Of the 912 children (59.1% girls, mean ± SD baseline age 10.2 ± 0.3 yrs) with complete data, 15% changed their travel mode. Those children who lived less than 1 km from school were more likely to take up (OR: 4.73, 95% CI: 1.97, 11.32, p = 0.001) and maintain active commuting (OR: 2.80 95% CI: 0.98, 7.96, p = 0.02). Children whose parents reported it was inconvenient to use the car for school travel were also more likely to take up (OR: 2.04, 95% CI: 1.08, 3.85, p = 0.027) and maintain their active commuting (OR: 5.43 95% CI: 1.95, 15.13, p = 0.001). Lower socio-economic status and higher road safety were also associated with uptake. CONCLUSIONS: Findings from this longitudinal study suggest that reducing the convenience of the car and improving the convenience of active modes as well as improving the safety of routes to school may promote uptake and maintenance of active commuting and the effectiveness of these interventions should be evaluated.

Predictors of change differ for moderate and vigorous intensity physical activity and for weekdays and weekends: a longitudinal analysis.

BACKGROUND: Predictors of physical activity (PA) change are rarely investigated separately for different PA intensities and for weekdays/weekends. We investigated whether individual-level predictors of one-year change in objectively-measured physical activity differ for moderate PA (MPA) and vigorous PA (VPA) and for weekends and weekdays. METHODS: Accelerometer-assessed PA (mins) was obtained at baseline and +1 year (n = 875, 41.5% male, Mean ± SD baseline age: 9.8 ± 0.4 years-old). Potential predictors (n = 38) were assessed at baseline from psychological (e.g., self-efficacy), socio-cultural (e.g., parent support) and environmental domains (e.g., land use). Associations between predictors and change in MPA (2000-3999 counts/minute (cpm)) and VPA (≥4000 cpm) separately for weekdays and weekends were studied using multi-level linear regression. Analyses were adjusted for school clustering, sex and baseline PA. RESULTS: Weekend PA declined (MPA decline 4.6 ± 21.8 mins/day; VPA decline: 2.1 ± 20.1 mins/day; both p < 0.001) whereas weekday PA did not significantly change. Higher baseline PA and being a girl were associated with greater PA declines in all four outcomes; remaining predictors differed for MPA and VPA and/or weekdays and weekends. Family logistic support was associated with less of a decline in weekend MPA (CI 95%) 0.15 (0.05, 0.25) and VPA 0.19 (0.09, 0.29), and peer support with less of a decline in weekday MPA 0.18 (0.02, 0.34) and VPA 0.22 (0.06, 0.38). CONCLUSIONS: Results highlight the relevance of investigating predictors of PA change separately for different PA intensities and for weekdays/weekends. In addition to continued focus on school PA promotion, more effort to target interventions during weekends, such as in the family and community appears important. Encouraging peer support to increase weekday PA and targeting parent support for weekend PA may be health promotion priorities.

Family and home influences on children's after-school and weekend physical activity.

BACKGROUND: Family- and home-related factors have been shown to be associated with children's physical activity (PA), but may be time-dependent. Here we investigate whether family- and home-related correlates of children's PA are different for the after-school period on weekdays than for the weekend. METHODS: Data on 21 family- and home-related variables and objectively measured PA (Actigraph GT1M) were available from 1608 Year 5 children (9-10 years old) from 92 schools in Norfolk participating in the SPEEDY (Sport, Physical activity and Eating behaviour: Environmental Determinants in Young people) study. Multi-level multiple linear regression was used to quantify cross-sectional associations between the family/home variables and average min per day of moderate-to-vigorous PA (MVPA, ≥2000 counts/min) after school on weekdays and at the weekend. Models were additionally adjusted for age, sex, BMI z-score and registered accelerometer wear time. RESULTS: After-school MVPA was associated with parent education (ß: -1.1; 95% CI -2.0 to -0.2), being allowed to play out in the neighbourhood (ß: 1.3; 0.7-1.8), restrictions on walking/cycling to friends' houses (ß: -1.1; -1.6 to -0.7), restrictions on sedentary behaviour (ß: -0.3; -0.5 to -0.02) and family social support (ß: 1.0; 0.7-1.3). Weekend MVPA was associated with number of siblings (ß: 2.6; 0.5-4.8), family encouragement (ß: 1.1; 0.2-2.0) and family social support (ß: 1.5; 0.5-2.5). CONCLUSION: Family social support is positively associated with children's out-of-school PA both at weekdays and in weekends. However, rules and restrictions appear to be important only on weekdays. The results of this study merit consideration when identifying appropriate timing of PA-promotion strategies.

School-level correlates of physical activity intensity in 10-year-old children.

PURPOSE: Little is known about school environmental factors that promote or inhibit activity, especially from studies using objective measures in large representative samples. We therefore aimed to study associations between activity intensities and physical and social school environmental factors. METHODS: A population-based sample of 1 908 British children (SPEEDY study), mean age 10.3 years (Standard deviation [SD]: 0.3), recruited from 92 schools across Norfolk, UK, with valid activity data (assessed with Actigraph accelerometers). Outcome measures were school-based (8 am-4 pm on weekdays) time (in minutes) spent in sedentary (<100 counts/min), moderate (2 000-3 999 counts/min) and vigorous (≥4 000 counts/min) activity. A total of 40 school physical and social environmental factors were assessed. Multivariable multilevel linear regression analyses adjusted for children's sex and body mass index were conducted; interactions with sex were investigated. RESULTS: Availability of a 'Park and Stride' scheme was negatively associated with sedentary minutes (-7.74; 95% CI: -14.8; -0.70). Minutes of moderate activity were associated with the availability of a lollypop person (1.33, 95% CI: 0.35; 2.62) and objectively-assessed walking provision (1.70, 95% CI: 0.85; 2.56). The number of sports facilities of at least medium quality (0.47, 95% CI: 0.16; 0.79), not having a policy on physical activity (-2.28, 95% CI: -3.62; -0.95), and, in boys only, provision of pedestrian training (1.89; 95% CI: 0.77; 3.01) were associated with minutes of vigorous activity. CONCLUSIONS: Only a small number of school-level factors were associated with children's objectively-measured physical activity intensity, giving few pointers for potential future intervention efforts. Further research should focus on using objective measures to elucidate what factors may explain the school-level variance in activity levels.

Changes in children's physical activity over 12 months: longitudinal results from the SPEEDY study.

OBJECTIVE: We measured physical activity changes among 10-year-old British children over 12 months and assessed biological and demographic determinants. METHODS: Physical activity was measured with accelerometers (counts per minute) over ≥3 days at baseline and 1 year later in a prospective study of 844 children (41.6% male; mean±SD baseline age: 10.2±0.3 years) from 92 schools. Meeting physical activity recommendations was defined as ≥60 minutes/day at ≥2000 counts per minute. Biological (height, weight, and fat percentage) and demographic factors (gender, rural/urban home location, and socioeconomic status) were assessed at baseline. Associations between physical activity changes and multiple factors were studied. RESULTS: Physical activity decreased over 1 year (baseline: 665.7±209.8 counts per minute; follow-up: 623.2±179.2 counts per minute; P<.001), with 70.4% of children meeting physical activity recommendations at the baseline evaluation and 65.8% at the follow-up evaluation (P<.001). The decrease occurred mainly on weekends (-47.2±395.8 counts per minute; P=.002), with no significant change on weekdays (8.0±201.6 counts per minute; P=.20). Girls (P<.001), participants with greater body fat percentage (P=.001), and participants of higher socioeconomic status (P=.008) were more likely to exhibit physical activity decreases. CONCLUSIONS: Physical activity decreased over 1 year among children in primary school, predominantly during the weekend. Because these children were relatively active at baseline, prevention of physical activity decreases in childhood, particularly among girls and on weekends, may be a suitable health promotion target.

A critical review of approaches to aquatic environmental assessment.

As demands on aquatic resources increase, there is a growing need to monitor and assess their condition. This paper reviews a variety of aquatic environmental assessments, at local, national, international and global scales and finds confusion in the terminology used to describe assessments. In particular the terms 'ecosystem' and 'integrated' are often misused resulting in lack of clarity. Therefore, definitions of some assessment terminology are suggested, consolidating existing proposals and simplifying future applications. A conclusion from the review is that a new classification system is required. The categorisation system proposed builds on preliminary work of the International Council for the Exploration of the Sea (ICES). Assessment classification is based on the environmental components considered, methodologies and nature of the linkages between components, and the inclusion or exclusion of socio-economic factors. The assessment terminology and categorisation system provided could in future simplify the way that assessments are defined and used to inform development of management strategies.

DOE/NETL's phase II mercury control technology field testing program: preliminary economic analysis of activated carbon injection.

Based on results of field testing conducted by the U.S. Department of Energy's National Energy Technology Laboratory (DOE/NETL), this article provides preliminary costs for mercury control via conventional activated carbon injection (ACI), brominated ACI, and conventional ACI coupled with the application of a sorbent enhancement additive (SEA) to coal prior to combustion. The economic analyses are reported on a plant-specific basis in terms of the cost required to achieve low (50%), mid (70%), and high (90%) levels of mercury removal "above and beyond" the baseline mercury removal achieved by existing emission control equipment. In other words, the levels of mercury control are directly attributable to ACI. Mercury control costs via ACI have been amortized on a current dollar basis. Using a 20-year book life, levelized costs for the incremental increase in cost of electricity (COE), expressed in mills per kilowatt-hour (mills/kWh), and the incremental cost of mercury control, expressed in dollars per pound of mercury removed ($/lb Hg removed), have been calculated for each level of ACI mercury control. For this analysis, the increase in COE varied from 0.14 mills/kWh to 3.92 mills/kWh. Meanwhile, the incremental cost of mercury control ranged from $3810/lb Hg removed to $166000/lb Hg removed.