Multiple sclerosis health-related quality of life utility values from the UK MS register.

Background: New interventions for multiple sclerosis (MS) commonly require a demonstration of cost-effectiveness using health-related quality of life (HRQoL) utility values. The EQ-5D is the utility measure approved for use in the UK NHS funding decision-making. There are also MS-specific utility measures - e.g., MS Impact Scale Eight Dimensions (MSIS-8D) and MSIS-8D-Patient (MSIS-8D-P). Objectives: Provide EQ-5D, MSIS-8D and MSIS-8D-P utility values from a large UK MS cohort and investigate their association with demographic/clinical characteristics. Methods: UK MS Register data from 14,385 respondents (2011 to 2019) were analysed descriptively and using multivariable linear regression, with self-report Expanded Disability Status Scale (EDSS) scores. Results: The EQ-5D and MSIS-8D were both sensitive to differences in demographic/clinical characteristics. An inconsistency found in previous studies whereby mean EQ-5D values were higher for an EDSS score of 4 rather than 3 was not observed. Similar utility values were observed between MS types at each EDSS score. Regression showed EDSS score and age were associated with utility values from all three measures. Conclusions: This study provides generic and MS-specific utility values for a large UK MS sample, with the potential for use in cost-effectiveness analyses of treatments for MS.

Comprehensive assessment of cardiovascular structure and function and disease risk in middle-aged ultra-endurance athletes.

BACKGROUND AND AIMS: Recent studies suggest that long-term endurance training may be damaging to the heart, thus increasing cardiovascular disease (CVD) risk. However, studies utilizing cardiac imaging are conflicting and lack measures of central and peripheral vascular structure and function, which are also independently predictive of CVD events. METHODS: We performed a comprehensive assessment of cardiovascular structure and function in long-term (≥ 10 years) ultra-endurance athletes (ATH, 14 M/11 F, 50 ± 1 y) and physically active controls (CON, 9 M/9 F, 49 ± 2 y). RESULTS: As expected, left ventricular mass and end-diastolic volume (echocardiography) were greater in ATH vs CON, whereas there was no difference in cardiac function at rest. Coronary artery calcium scores (computed tomography) were not statistically different between groups. There was no evidence of myocardial fibrosis (contrast magnetic resonance imaging) in any subject. Aortic stiffness (carotid-femoral pulse wave velocity) was lower in ATH vs CON (6.2 ± 0.2 vs 6.9 ± 0.2 m/s, p < 0.05), whereas carotid intima-media thickness (ultrasound) was not different between groups. Peripheral vascular endothelial function (flow-mediated vasodilation of the brachial artery) and microvascular function (peak blood velocity) in response to 5 min of forearm ischemia were not different between groups. Furthermore, there was no difference in 10-year coronary heart disease risk (ATH; 2.3 ± 0.5 vs CON; 1.6 ± 0.2%, p > 0.05). CONCLUSIONS: Our data indicate that middle-aged ultra-endurance ATH do not have marked signs of widespread cardiovascular dysfunction or elevated CHD risk compared to CON meeting physical activity guidelines.

Using the Fatigue Severity Scale to inform healthcare decision-making in multiple sclerosis: mapping to three quality-adjusted life-year measures (EQ-5D-3L, SF-6D, MSIS-8D).

BACKGROUND: Fatigue has a major influence on the quality of life of people with multiple sclerosis. The Fatigue Severity Scale is a frequently used patient-reported measure of fatigue impact, but does not generate the health state utility values required to inform cost-effectiveness analysis, limiting its applicability within decision-making contexts. The objective of this study was to use statistical mapping methods to convert Fatigue Severity Scale scores to health state utility values from three preference-based measures: the EQ-5D-3L, SF-6D and Multiple Sclerosis Impact Scale-8D. METHODS: The relationships between the measures were estimated through regression analysis using cohort data from 1056 people with multiple sclerosis in South West England. Estimation errors were assessed and predictive performance of the best models as tested in a separate sample (n = 352). RESULTS: For the EQ-5D and the Multiple Sclerosis Impact Scale-8D, the best performing models used a censored least absolute deviation specification, with Fatigue Severity Scale total score, age and gender as predictors. For the SF-6D, the best performing model used an ordinary least squares specification, with Fatigue Severity Scale total score as the only predictor. CONCLUSIONS: Here we present algorithms to convert Fatigue Severity Scales scores to health state utility values based on three preference-based measures. These values may be used to estimate quality-adjusted life-years for use in cost-effectiveness analyses and to consider the health-related quality of life of people with multiple sclerosis, thereby informing health policy decisions.

Cost-Related Medication Nonadherence Among Older Adults: Findings From a Nationally Representative Sample.

OBJECTIVES: To estimate the rate of and risk factors associated with cost-related medication nonadherence among older adults. DESIGN: Cross-sectional analysis of the 2017 National Health Interview Survey (NHIS). SETTING: Nationally representative health interview survey in the United States. PARTICIPANTS: Survey respondents, aged 65 years or older (n = 5701 unweighted) in the 2017 wave of the NHIS. MEASUREMENTS: Self-reported, cost-related medication nonadherence (due to cost: skip dose, reduce dose, or delay or not fill a prescription) and actions taken due to cost-related medication nonadherence (ask for lower-cost prescription, use alternative therapy, or buy medications from another country) were quantified. We used a series of multivariable logistic regression analyses to identify factors associated with cost-related medication nonadherence. We also reported analyses by chronic disease subgroups. RESULTS: In 2017, 408 (6.8%) of 5901 older adults, representative of 2.7 million older adults nationally, reported cost-related medication nonadherence. Among those with cost-related medication nonadherence, 44.2% asked a physician for lower-cost medications, 11.5% used alternative therapies, and 5.3% bought prescription drugs outside the United States to save money. Correlates independently associated with a higher likelihood of cost-related medication nonadherence included: younger age, female sex, lower socioeconomic levels (eg, low income and uninsured), mental distress, functional limitations, multimorbidities, and obesity (P < .05 for all). Similar patterns were found in subgroup analyses. CONCLUSION: Cost-related medication nonadherence among older adults is increasingly common, with several potentially modifiable risk factors identified. Interventions, such as medication therapy management, may be needed to reduce cost-related medication nonadherence in older adults. J Am Geriatr Soc 67:2463-2473, 2019.

The projected costs and benefits of a supervised injection facility in Seattle, WA, USA.

BACKGROUND: As one strategy to improve the health and survival of people who inject drugs, the King County Heroin & Opioid Addiction Task Force recommended the establishment of supervised injection facilities (SIF) where people can inject drugs in a safe and hygienic environment with clinical supervision. Analyses for other sites have found them to be cost-effective, but it is not clear whether these findings are transferable to other settings. METHODS: We utilized local estimates and other data sources deemed appropriate for our setting to implement a mathematical model that assesses the impact of a hypothetical SIF on overdose deaths, non-fatal overdose health service utilization, skin and soft tissue infections, bacterial infections, viral infections, and enrollment in medication assisted treatment (MAT). We estimated the costs and savings that would occur on an annual basis for a small-scale pilot site given current overdose rates, as well as three other scenarios of varying scale and underlying overdose rates. RESULTS: Assuming current overdose rates, a hypothetical Seattle SIF in a pilot phase is projected to annually reverse 167 overdoses and prevent 6 overdose deaths, 45 hospitalizations, 90 emergency department visits, and 92 emergency medical service deployments. Additionally, the site would facilitate the enrollment of 41 SIF clients in medication assisted treatment programs. These health benefits correspond to a monetary value of $5,156,019. The annual estimated cost of running the SIF is $1,222,332. The corresponding cost-benefit ratio suggests that the pilot SIF would generate $4.22 for every dollar spent on SIF operational costs. The pilot SIF is projected to save the healthcare system $534,453. If Seattle experienced elevated overdose rates and Seattle SIF program were scaled up, the health benefits and financial value would be considerably greater. CONCLUSION: This analysis suggests that a SIF program in Seattle would save lives and result in considerable health benefits and cost savings.

Balance Right in Multiple Sclerosis (BRiMS): a guided self-management programme to reduce falls and improve quality of life, balance and mobility in people with secondary progressive multiple sclerosis: a protocol for a feasibility randomised controlled trial.

BACKGROUND: Impaired mobility is a cardinal feature of multiple sclerosis (MS) and is rated by people with MS as their highest priority. By the secondary progressive phase, balance, mobility and physical activity levels are significantly compromised; an estimated 70% of people with secondary progressive MS fall regularly. Our ongoing research has systematically developed 'Balance Right in MS' (BRiMS), an innovative, manualised 13-week guided self-management programme tailored to the needs of people with MS, designed to improve safe mobility and minimise falls. Our eventual aim is to assess the clinical and cost effectiveness of BRiMS in people with secondary progressive MS by undertaking an appropriately statistically powered, multi-centre, assessor-blinded definitive, randomised controlled trial. This feasibility study will assess the acceptability of the intervention and test the achievability of running such a definitive trial. METHODS/DESIGN: This is a pragmatic multi-centre feasibility randomised controlled trial with blinded outcome assessment. Sixty ambulant people with secondary progressive MS who self-report two or more falls in the previous 6 months will be randomly allocated (1:1) to either the BRiMS programme plus usual care or to usual care alone. All participants will be assessed at baseline and followed up at 15 weeks and 27 weeks post-randomisation. The outcomes of this feasibility trial include:Feasibility outcomes, including trial recruitment, retention and completionAssessment of the proposed outcome measures for the anticipated definitive trial (including measures of walking, quality of life, falls, balance and activity level)Measures of adherence to the BRiMS programmeData to inform the economic evaluation in a future trialProcess evaluation (assessment of treatment fidelity and qualitative evaluation of participant and treating therapist experience). DISCUSSION: The BRiMS intervention aims to address a key concern for MS service users and providers. However, there are several uncertainties which need to be addressed prior to progressing to a full-scale trial, including acceptability of the BRiMS intervention and practicality of the trial procedures. This feasibility trial will provide important insights to resolve these uncertainties and will enable a protocol to be finalised for use in the definitive trial. TRIAL REGISTRATION: ISRCTN13587999.

Standing up in multiple sclerosis (SUMS): protocol for a multi-centre randomised controlled trial evaluating the clinical and cost effectiveness of a home-based self-management standing frame programme in people with progressive multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an incurable, unpredictable but typically progressive neurological condition. It is the most common cause of neurological disability in young adults. Within 15 years of diagnosis, approximately 50 % of affected people are unable to walk unaided, and over time an estimated 25 % depend on a wheelchair. Typically, people with such limited mobility are excluded from clinical trials. Severely impaired people with MS spend much of their day sitting, often with limited ability to change position. In response, secondary complications can occur including: muscle wasting, pain, reduced skin integrity, spasms, limb stiffness, constipation, and associated psychosocial problems such as depression and lowered self-esteem. Effective self-management strategies, which can be implemented relatively easily and cheaply within people's homes, are needed to improve or maintain mobility and reduce sedentary behaviour. However this is challenging, particularly in the latter stages of disease. Regular supported standing using standing frames is one potential option. METHODS/DESIGN: SUMS is a pragmatic multi-centre randomised controlled trial evaluating use of Oswestry standing frames with blinded outcome assessment and full economic evaluation. Participants will be randomly allocated (1:1) to either a home-based, self-management standing programme (with advice and support) along with their usual care or to usual care alone. Those in the intervention group will be asked to stand for a minimum of 30 min three times weekly over 20 weeks. Each participant will be followed-up at 20 and 36 weeks post baseline. The primary clinical outcome is motor function, assessed using the Amended Motor Club Assessment. The primary economic endpoint is quality-adjusted life years. The secondary outcomes include measures of explanatory physical impairments, key clinical outcomes, and health-related quality of life. An embedded qualitative component will explore participant's and carer's experiences of the standing programme. DISCUSSION: This is the first large scale multi-centre trial to assess the clinical and cost effectiveness of a home based standing frame programme for people who are severely impaired by MS. If demonstrated to be effective and cost-effective, we will use this evidence to develop recommendations for a health service delivery model which could be implemented across the United Kingdom. TRIAL REGISTRATION: ISRCTN69614598 DATE OF REGISTRATION: 3.2.16 (retrospectively registered).

Multiple sclerosis: relapses, resource use, and costs.

BACKGROUND: Relapses can have a major impact on the lives of people with multiple sclerosis (MS), and yet relapse-related healthcare costs have received little attention. This has limited cost-effectiveness analyses of treatments for MS and hampered decision-making regarding the funding of MS healthcare services. OBJECTIVE: To describe health/social care resource use and costs according to the frequency, severity, and endurance of MS relapses. METHODS: Data from the prospective, longitudinal UK South West Impact of Multiple Sclerosis cohort were used. A total of 11,800 questionnaires from 1441 people with MS were available, including data on relapses, contacts with health/social care professionals, and other MS-related resource use. RESULTS: The mean (SD) 6-monthly MS-related health/social care cost for individuals who reported a relapse was £519 (£949), compared to £229 (£366) for those who had not did report a relapse. Care costs varied widely dependent on the characteristics of the relapse. The mean (SD) cost when a relapse was not treated with steroids was £381 (£780), whilst the equivalent cost was £3579 (£1727) when a relapse resulted in hospitalization. CONCLUSIONS: The impact of relapses on health and social care resources and costs differs according to their frequency, length, and severity. The data provided here can be used in cost-effectiveness analyses and to inform decision-making regarding healthcare provision for people with this condition.

Clinical effectiveness and cost-effectiveness of the Rehabilitation Enablement in Chronic Heart Failure (REACH-HF) facilitated self-care rehabilitation intervention in heart failure patients and caregivers: rationale and protocol for a multicentre randomised controlled trial.

INTRODUCTION: The Rehabilitation EnAblement in CHronic Heart Failure (REACH-HF) trial is part of a research programme designed to develop and evaluate a health professional facilitated, home-based, self-help rehabilitation intervention to improve self-care and health-related quality of life in people with heart failure and their caregivers. The trial will assess the clinical effectiveness and cost-effectiveness of the REACH-HF intervention in patients with systolic heart failure and impact on the outcomes of their caregivers. METHODS AND ANALYSIS: A parallel two group randomised controlled trial with 1:1 individual allocation to the REACH-HF intervention plus usual care (intervention group) or usual care alone (control group) in 216 patients with systolic heart failure (ejection fraction <45%) and their caregivers. The intervention comprises a self-help manual delivered by specially trained facilitators over a 12-week period. The primary outcome measure is patients' disease-specific health-related quality of life measured using the Minnesota Living with Heart Failure questionnaire at 12 months' follow-up. Secondary outcomes include survival and heart failure related hospitalisation, blood biomarkers, psychological well-being, exercise capacity, physical activity, other measures of quality of life, patient safety and the quality of life, psychological well-being and perceived burden of caregivers at 4, 6 and 12 months' follow-up. A process evaluation will assess fidelity of intervention delivery and explore potential mediators and moderators of changes in health-related quality of life in intervention and control group patients. Qualitative studies will describe patient and caregiver experiences of the intervention. An economic evaluation will estimate the cost-effectiveness of the REACH-HF intervention plus usual care versus usual care alone in patients with systolic heart failure. ETHICS AND DISSEMINATION: The study is approved by the North West-Lancaster Research Ethics Committee (ref 14/NW/1351). Findings will be disseminated via journals and presentations to publicise the research to clinicians, commissioners and service users. TRIAL REGISTRATION NUMBER: ISRCTN86234930; Pre-results.

Results from the IQ-CSRC prospective study support replacement of the thorough QT study by QT assessment in the early clinical phase.

The QT effects of five "QT-positive" and one negative drug were tested to evaluate whether exposure-response analysis can detect QT effects in a small study with healthy subjects. Each drug was given to nine subjects (six for placebo) in two dose levels; positive drugs were chosen to cause 10 to 12 ms and 15 to 20 ms QTcF prolongation. The slope of the concentration/ΔQTc effect was significantly positive for ondansetron, quinine, dolasetron, moxifloxacin, and dofetilide. For the lower dose, an effect above 10 ms could not be excluded, i.e., the upper bound of the confidence interval for the predicted mean ΔΔQTcF effect was above 10 ms. For the negative drug, levocetirizine, a ΔΔQTcF effect above 10 ms was excluded at 6-fold the therapeutic dose. The study provides evidence that robust QT assessment in early-phase clinical studies can replace the thorough QT study.

A survey of training in pediatric flexible bronchoscopy.

OBJECTIVE: There is currently no evidence-based method for defining competency in pediatric flexible bronchoscopy (FB). Based on expert opinion, guidelines using numbers of procedures have been published in defining competency for pediatric FB. The purpose of this study was to formally survey the opinion of USA pediatric pulmonology training directors about the assessment of competency and training experiences in pediatric FB in their programs. METHODS: An Internet-based Survey Monkey™ of the Pediatric Pulmonary Training Directors Association (PEPTDA) was administered 10/12/10 through 11/1/10 with a supplemental survey 6/1/11-6/30/11. RESULTS: This survey of US pediatric pulmonology training directors about competency and training in pediatric FB showed that a majority (86%) felt there was a minimum threshold of procedures for developing competency that could be defined, with a median of 50 and an average of 56.4 (SD = 33.0). The actual number of FBs performed by fellows during their 3-year fellowship averaged 89.4 (SD = 45.3) with a range of 10-200. The survey also revealed a variety of teaching techniques used for FB, including simulation technology. Finally many differences were reported in skill assessment, locations for performance of FB, and the range of underlying indications and patient populations. The apprenticeship model is the predominant method of learning FB in the surveyed programs. CONCLUSIONS: A majority of US pediatric pulmonology training directors felt that a minimum number of procedures could be defined for developing competency in pediatric FB. There was variability in the numbers of procedures performed, training techniques and assessment, and application of FB. This survey represents an initial step in assessing training and defining competency in pediatric FB.

Should money follow the patient: Financial implication for being the National Centre for the Treatment and Management of Pelvic and Acetabular Fractures in Ireland.

BACKGROUND: Pelvic and acetabular fractures are complex injuries requiring specialist treatment. Our institution is the National Centre for Treatment and Management of these injuries. AIM: To audit all referrals to our institution over a 6-month period and calculate the cost incurred by being the national referral centre. METHODS: Retrospective review of database, and subsequent allocation of Casemix points to assess total cost of treatment for each patient referred to our institution. RESULTS: 103 patients referred with pelvic or acetabular fracture for operative management. The furthest referral distance was 181miles. Over-all, the length of stay was 15.4 days. The average inclusive cost for a referral to our unit for operative management was €16,302. CONCLUSION: Pelvic and acetabular fractures are complex injuries that require specialist referral unit management. However for these units to remain sustainable money needs to "follow the patient".

The use of multiple sclerosis condition-specific measures to inform health policy decision-making: mapping from the MSWS-12 to the EQ-5D.

BACKGROUND: Walking impairment has a major influence on the quality of life of people with multiple sclerosis (MS). The Multiple Sclerosis Walking Scale (MSWS-12) assesses the impact of MS on walking ability from the patient's perspective, but in its current form, is not amenable for use in many policy decision-making settings. OBJECTIVES: Statistical 'mapping' methods were used to convert MSWS-12 scores to EQ-5D health state values. METHODS: The relationship between the measures was estimated using cohort data from people with MS in South West England. Regression analyses were conducted, estimation errors assessed, and predictive performance of the best models tested using longitudinal data. RESULTS: Model performance was in line with that of other mapping studies, with the best-performing models being an ordinary least squares (OLS) model using MSWS-12 item scores, and an OLS model using the total MSWS-12 score and its squared term. CONCLUSIONS: A process has been described whereby data from a patient-reported outcome measure (MSWS-12) can be converted to (EQ-5D) health state values. These values may be used to consider the health-related quality of life of people with MS, to estimate quality adjusted life-years for use in effectiveness and cost-effectiveness analyses, and to inform health policy decisions.

The clinical effectiveness and cost-effectiveness of exercise referral schemes: a systematic review and economic evaluation.

BACKGROUND: Exercise referral schemes (ERS) aim to identify inactive adults in the primary-care setting. The GP or health-care professional then refers the patient to a third-party service, with this service taking responsibility for prescribing and monitoring an exercise programme tailored to the needs of the individual. OBJECTIVE: To assess the clinical effectiveness and cost-effectiveness of ERS for people with a diagnosed medical condition known to benefit from physical activity (PA). The scope of this report was broadened to consider individuals without a diagnosed condition who are sedentary. DATA SOURCES: MEDLINE; EMBASE; PsycINFO; The Cochrane Library, ISI Web of Science; SPORTDiscus and ongoing trial registries were searched (from 1990 to October 2009) and included study references were checked. METHODS: Systematic reviews: the effectiveness of ERS, predictors of ERS uptake and adherence, and the cost-effectiveness of ERS; and the development of a decision-analytic economic model to assess cost-effectiveness of ERS. RESULTS: Seven randomised controlled trials (UK, n = 5; non-UK, n = 2) met the effectiveness inclusion criteria, five comparing ERS with usual care, two compared ERS with an alternative PA intervention, and one to an ERS plus a self-determination theory (SDT) intervention. In intention-to-treat analysis, compared with usual care, there was weak evidence of an increase in the number of ERS participants who achieved a self-reported 90-150 minutes of at least moderate-intensity PA per week at 6-12 months' follow-up [pooled relative risk (RR) 1.11, 95% confidence interval 0.99 to 1.25]. There was no consistent evidence of a difference between ERS and usual care in the duration of moderate/vigorous intensity and total PA or other outcomes, for example physical fitness, serum lipids, health-related quality of life (HRQoL). There was no between-group difference in outcomes between ERS and alternative PA interventions or ERS plus a SDT intervention. None of the included trials separately reported outcomes in individuals with medical diagnoses. Fourteen observational studies and five randomised controlled trials provided a numerical assessment of ERS uptake and adherence (UK, n = 16; non-UK, n = 3). Women and older people were more likely to take up ERS but women, when compared with men, were less likely to adhere. The four previous economic evaluations identified suggest ERS to be a cost-effective intervention. Indicative incremental cost per quality-adjusted life-year (QALY) estimates for ERS for various scenarios were based on a de novo model-based economic evaluation. Compared with usual care, the mean incremental cost for ERS was £169 and the mean incremental QALY was 0.008, with the base-case incremental cost-effectiveness ratio at £20,876 per QALY in sedentary people without a medical condition and a cost per QALY of £14,618 in sedentary obese individuals, £12,834 in sedentary hypertensive patients, and £8414 for sedentary individuals with depression. Estimates of cost-effectiveness were highly sensitive to plausible variations in the RR for change in PA and cost of ERS. LIMITATIONS: We found very limited evidence of the effectiveness of ERS. The estimates of the cost-effectiveness of ERS are based on a simple analytical framework. The economic evaluation reports small differences in costs and effects, and findings highlight the wide range of uncertainty associated with the estimates of effectiveness and the impact of effectiveness on HRQoL. No data were identified as part of the effectiveness review to allow for adjustment of the effect of ERS in different populations. CONCLUSIONS: There remains considerable uncertainty as to the effectiveness of ERS for increasing activity, fitness or health indicators or whether they are an efficient use of resources in sedentary people without a medical diagnosis. We failed to identify any trial-based evidence of the effectiveness of ERS in those with a medical diagnosis. Future work should include randomised controlled trials assessing the cinical effectiveness and cost-effectivenesss of ERS in disease groups that may benefit from PA. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Effect of exercise referral schemes in primary care on physical activity and improving health outcomes: systematic review and meta-analysis.

OBJECTIVE: To assess the impact of exercise referral schemes on physical activity and health outcomes. Design Systematic review and meta-analysis. DATA SOURCES: Medline, Embase, PsycINFO, Cochrane Library, ISI Web of Science, SPORTDiscus, and ongoing trial registries up to October 2009. We also checked study references. Study selection Design: randomised controlled trials or non-randomised controlled (cluster or individual) studies published in peer review journals. POPULATION: sedentary individuals with or without medical diagnosis. Exercise referral schemes defined as: clear referrals by primary care professionals to third party service providers to increase physical activity or exercise, physical activity or exercise programmes tailored to individuals, and initial assessment and monitoring throughout programmes. Comparators: usual care, no intervention, or alternative exercise referral schemes. RESULTS: Eight randomised controlled trials met the inclusion criteria, comparing exercise referral schemes with usual care (six trials), alternative physical activity intervention (two), and an exercise referral scheme plus a self determination theory intervention (one). Compared with usual care, follow-up data for exercise referral schemes showed an increased number of participants who achieved 90-150 minutes of physical activity of at least moderate intensity per week (pooled relative risk 1.16, 95% confidence intervals 1.03 to 1.30) and a reduced level of depression (pooled standardised mean difference -0.82, -1.28 to -0.35). Evidence of a between group difference in physical activity of moderate or vigorous intensity or in other health outcomes was inconsistent at follow-up. We did not find any difference in outcomes between exercise referral schemes and the other two comparator groups. None of the included trials separately reported outcomes in individuals with specific medical diagnoses. Substantial heterogeneity in the quality and nature of the exercise referral schemes across studies might have contributed to the inconsistency in outcome findings. Conclusions Considerable uncertainty remains as to the effectiveness of exercise referral schemes for increasing physical activity, fitness, or health indicators, or whether they are an efficient use of resources for sedentary people with or without a medical diagnosis.

The effect of inclement weather on trauma orthopaedic workload.

BACKGROUND: Climate change models predict increasing frequency of extreme weather. One of the challenges hospitals face is how to make sure they have adequate staffing at various times of the year. AIMS: The aim of this study was to examine the effect of this severe inclement weather on hospital admissions, operative workload and cost in the Irish setting. We hypothesised that there is a direct relationship between cold weather and workload in a regional orthopaedic trauma unit. METHODS: Trauma orthopaedic workload in a regional trauma unit was examined over 2 months between December 2009 and January 2010. This corresponded with a period of severe inclement weather. RESULTS: We identified a direct correlation between the drop in temperature and increase in workload, with a corresponding increase in demand on resources. CONCLUSIONS: Significant cost savings could be made if these injuries were prevented. While the information contained in this study is important in the context of resource planning and staffing of hospital trauma units, it also highlights the vulnerability of the Irish population to wintery weather.

Outreach and Support in South London (OASIS). Outcomes of non-attenders to a service for people at high risk of psychosis: the case for a more assertive approach to assessment.

BACKGROUND: International agreement dictates that clients must be help-seeking before any assessment or intervention can be implemented by an 'at-risk service'. Little is known about individuals who decline input. This study aimed to define the size of the unengaged population of an 'at-risk service', to compare this group to those who did engage in terms of sociodemographic and clinical features and to assess the clinical outcomes of those who did not engage with the service. METHOD: Groups were compared using data collected routinely as part of the service's clinical protocol. Data on service use and psychopathology since referral to Outreach and Support in South London (OASIS) were collected indirectly from clients' general practitioners (GPs) and by screening electronic patient notes held by the local Mental Health Trust. RESULTS: Over one-fifth (n=91, 21.2%) of those referred did not attend or engage with the service. Approximately half of this group subsequently received a diagnosis of mental illness. A diagnosis of psychosis was given to 22.6%. Nearly 70% presented to other mental health services. There were no demographic differences, except that those who engaged with the service were more likely to be employed. CONCLUSIONS: Over one-fifth of those referred to services for people at high risk of psychosis do not attend or engage. However, many of this group require mental health care, and a substantial proportion has, or will later develop, psychosis. A more assertive approach to assessing individuals who are at high risk of psychosis but fail to engage may be indicated.

Trials and tribulations of an African-led research and capacity development programme: the case for EDCTP investments.

We describe the initiation and establishment of The University of Zambia - University College London Medical School (UNZA-UCLMS) Research and Training Project, an entirely African scientist-led, south-north partnership. In its 16 year existence, the project, by successfully obtaining competitive grant funding, has transformed itself into one of Africa's most productive African-led R&D programmes with training and visible research outputs. The project serves as a role model and now networks R&D and training activities with six southern African (10 institutions) and six European countries. This project case study illustrates that deep commitment is essential for success and that the factors which facilitate success in R&D in Africa need to be evaluated. The long-term prospects for sustaining the UNZA-UCLMS Project appear bright and are dependent on several factors: the ability to retain trained African scientists; obtaining continued competitive or donor grant funding support; and serious investment by the African governments involved. The recent 255 million Euros EDCTP investment in sub-Saharan Africa through south-north partnerships is expected to enhance existing African-led R&D programmes. African governments and scientists must rise to the challenge.

Bevacizumab, sorafenib tosylate, sunitinib and temsirolimus for renal cell carcinoma: a systematic review and economic evaluation.

OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of bevacizumab, combined with interferon (IFN), sorafenib tosylate, sunitinib and temsirolimus in the treatment of people with advanced and/or metastatic renal cell carcinoma (RCC). DATA SOURCES: Electronic databases, including MEDLINE, EMBASE and the Cochrane Library, were searched up to September/October 2007 (and again in February 2008). REVIEW METHODS: Systematic reviews and randomised clinical trials comparing any of the interventions with any of the comparators in participants with advanced and/or metastatic RCC were included, also phase II studies and conference abstracts if there was sufficient detail to adequately assess quality. Results were synthesised narratively and a decision-analytic Markov-type model was developed to simulate disease progression and estimate the cost-effectiveness of the interventions under consideration. RESULTS: A total of 888 titles and abstracts were retrieved in the clinical effectiveness review, including reports of eight clinical trials. Treatment with bevacizumab plus IFN or sunitinib had clinically relevant and statistically significant advantages over treatment with IFN alone, in terms of progression-free survival and tumour response, doubling median progression-free survival from approximately 5 months to 10 months. Temsirolimus had similar advantages over treatment with IFN in terms of progression-free and overall survival, increasing median overall survival from 7.3 to 10.9 months [hazard ratio (HR) 0.73; 95% confidence interval (CI) 0.58 to 0.92)], as did sorafenib in comparison with best supportive care in terms of overall survival, progression-free survival and tumour response, with a doubling of progression-free survival (HR 0.51; 95% CI 0.43 to 0.60). However, the last was associated with an increased frequency of hypertension and hand-foot skin reaction compared with placebo. No fully published economic evaluations of any of the interventions could be located. However, estimates from the PenTAG model suggested that none of the interventions would be considered cost-effective at a willingness-to-pay threshold of 30,000 pounds per quality-adjusted life-year (QALY). Estimates of cost per QALY ranged from 71,462 pounds for sunitinib to 171,301 pounds for bevacizumab plus IFN. Although there are many similarities in the methodology and structural assumptions employed by PenTAG and the manufacturers of the interventions, in all cases the cost-effectiveness estimates from the PenTAG model were higher than those presented in the manufacturers' submissions. Cost-effectiveness estimates were particularly sensitive to variations in the estimates of treatment effectiveness, drug pricing (including dose intensity data), and health-state utility input parameters. CONCLUSIONS: Treatment with bevacizumab plus IFN and sunitinib has clinically relevant and statistically significant advantages over treatment with IFN alone in patients with metastatic RCC. In people with three of six risk factors for poor prognosis, temsirolimus had clinically relevant advantages over treatment with IFN, and sorafenib tosylate was superior to best supportive care as second-line therapy. The frequency of adverse events associated with bevacizumab plus IFN, sunitinib and temsirolimus was comparable with that seen with IFN, although the adverse event profile is different. Treatment with sorafenib was associated with a significantly increased frequency of hypertension and hand-foot syndrome. Estimates from the PenTAG model suggested that none of the interventions would be considered cost-effective at a willingness-to-pay threshold of 30,000 pounds per QALY.