Percutaneous Revascularization for Ischemic Left Ventricular Dysfunction: Cost-Effectiveness Analysis of the REVIVED-BCIS2 Trial.

BACKGROUND: Percutaneous coronary intervention (PCI) is frequently undertaken in patients with ischemic left ventricular systolic dysfunction. The REVIVED (Revascularization for Ischemic Ventricular Dysfunction)-BCIS2 (British Cardiovascular Society-2) trial concluded that PCI did not reduce the incidence of all-cause death or heart failure hospitalization; however, patients assigned to PCI reported better initial health-related quality of life than those assigned to optimal medical therapy (OMT) alone. The aim of this study was to assess the cost-effectiveness of PCI+OMT compared with OMT alone. METHODS: REVIVED-BCIS2 was a prospective, multicenter UK trial, which randomized patients with severe ischemic left ventricular systolic dysfunction to either PCI+OMT or OMT alone. Health care resource use (including planned and unplanned revascularizations, medication, device implantation, and heart failure hospitalizations) and health outcomes data (EuroQol 5-dimension 5-level questionnaire) on each patient were collected at baseline and up to 8 years post-randomization. Resource use was costed using publicly available national unit costs. Within the trial, mean total costs and quality-adjusted life-years (QALYs) were estimated from the perspective of the UK health system. Cost-effectiveness was evaluated using estimated mean costs and QALYs in both groups. Regression analysis was used to adjust for clinically relevant predictors. RESULTS: Between 2013 and 2020, 700 patients were recruited (mean age: PCI+OMT=70 years, OMT=68 years; male (%): PCI+OMT=87, OMT=88); median follow-up was 3.4 years. Over all follow-ups, patients undergoing PCI yielded similar health benefits at higher costs compared with OMT alone (PCI+OMT: 4.14 QALYs, £22 352; OMT alone: 4.16 QALYs, £15 569; difference: -0.015, £6782). For both groups, most health resource consumption occurred in the first 2 years post-randomization. Probabilistic results showed that the probability of PCI being cost-effective was 0. CONCLUSIONS: A minimal difference in total QALYs was identified between arms, and PCI+OMT was not cost-effective compared with OMT, given its additional cost. A strategy of routine PCI to treat ischemic left ventricular systolic dysfunction does not seem to be a justifiable use of health care resources in the United Kingdom. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01920048.

Carpal Tunnel Syndrome as a Test Case for Value Assessment During the Presurgical Period: The Impact of Structure and Processes of Care.

BACKGROUND: Few performance measures assess presurgical value (quality and utilization). OBJECTIVES: Using carpal tunnel syndrome (CTS) as a case study: (1) develop a model to evaluate presurgical quality and utilization and (2) identify opportunities for value improvement. RESEARCH DESIGN: A retrospective cohort study utilizing Veterans Affairs (VA) national administrative data. SUBJECTS: Patients who were evaluated in a VA primary care clinic on at least 1 occasion for CTS and received carpal tunnel release over a 7-year period. MEASURES: We modeled facility-level performance on 2 outcomes: surgical delay (marker of quality) and number of presurgical encounters (utilization) for CTS, and examined association between patient, facility, and care process variables and performance. RESULTS: Among 41,912 Veterans undergoing carpal tunnel release at 127 VA medical centers, the median facility-level predicted probability of surgical delay was 48%, with 16 (13%) facilities having significantly less delay than the median and 13 (10%) facilities having greater delay. The median facility-level predicted number of presurgical encounters was 8.8 visits, with 22 (17%) facilities having significantly fewer encounters and 22 (17%) facilities having more. Care processes had a stronger association with both outcomes than structural variables included in the models. Processes associated with the greatest deviations in predicted delay and utilization included receipt of repeat electrodiagnostic testing, use of 2 or more nonoperative treatments, and community referral outside of VA. CONCLUSIONS: Using CTS as a test case, this study demonstrates the potential to assess presurgical value and identify modifiable care processes associated with presurgical delay and utilization performance.

Percutaneous Revascularization for Ischemic Left Ventricular Dysfunction.

BACKGROUND: Whether revascularization by percutaneous coronary intervention (PCI) can improve event-free survival and left ventricular function in patients with severe ischemic left ventricular systolic dysfunction, as compared with optimal medical therapy (i.e., individually adjusted pharmacologic and device therapy for heart failure) alone, is unknown. METHODS: We randomly assigned patients with a left ventricular ejection fraction of 35% or less, extensive coronary artery disease amenable to PCI, and demonstrable myocardial viability to a strategy of either PCI plus optimal medical therapy (PCI group) or optimal medical therapy alone (optimal-medical-therapy group). The primary composite outcome was death from any cause or hospitalization for heart failure. Major secondary outcomes were left ventricular ejection fraction at 6 and 12 months and quality-of-life scores. RESULTS: A total of 700 patients underwent randomization - 347 were assigned to the PCI group and 353 to the optimal-medical-therapy group. Over a median of 41 months, a primary-outcome event occurred in 129 patients (37.2%) in the PCI group and in 134 patients (38.0%) in the optimal-medical-therapy group (hazard ratio, 0.99; 95% confidence interval [CI], 0.78 to 1.27; P = 0.96). The left ventricular ejection fraction was similar in the two groups at 6 months (mean difference, -1.6 percentage points; 95% CI, -3.7 to 0.5) and at 12 months (mean difference, 0.9 percentage points; 95% CI, -1.7 to 3.4). Quality-of-life scores at 6 and 12 months appeared to favor the PCI group, but the difference had diminished at 24 months. CONCLUSIONS: Among patients with severe ischemic left ventricular systolic dysfunction who received optimal medical therapy, revascularization by PCI did not result in a lower incidence of death from any cause or hospitalization for heart failure. (Funded by the National Institute for Health and Care Research Health Technology Assessment Program; REVIVED-BCIS2 ClinicalTrials.gov number, NCT01920048.).

Inequities in Health Care Services Caused by the Adoption of Digital Health Technologies: Scoping Review.

BACKGROUND: Digital health technologies (ie, the integration of digital technology and health information) aim to increase the efficiency of health care delivery; they are rapidly adapting to health care contexts to provide improved medical services for citizens. However, contrary to expectations, their rapid adoption appears to have led to health inequities, with differences in health conditions or inequality in the distribution of health care resources among different populations. OBJECTIVE: This scoping review aims to identify and describe the inequities of health care services brought about by the adoption of digital health technologies. The factors influencing such inequities, as well as the corresponding countermeasures to ensure health equity among different groups of citizens, were also studied. METHODS: Primary studies and literature, including articles and reviews, published in English between 1990 and 2020 were retrieved using appropriate search strategies across the following three electronic databases: Clarivate Analytics' Web of Science, PubMed, and Scopus. Data management was performed by two authors (RY and WZ) using Thomson Endnote (Clarivate Analytics, Inc), by systematically screening and identifying eligible articles for this study. Any conflicts of opinion were resolved through discussions with the corresponding author. A qualitative descriptive synthesis was performed to determine the outcomes of this scoping review. RESULTS: A total of 2325 studies were collected during the search process, of which 41 (1.76%) papers were identified for further analysis. The quantity of literature increased until 2016, with a peak in 2020. The United States, the United Kingdom, and Norway ranked among the top 3 countries for publication output. Health inequities caused by the adoption of digital health technologies in health care services can be reflected in the following two dimensions: the inability of citizens to obtain and adopt technology and the different disease outcomes found among citizens under technical intervention measures. The factors that influenced inequities included age, race, region, economy, and education level, together with health conditions and eHealth literacy. Finally, action can be taken to alleviate inequities in the future by government agencies and medical institutions (eg, establishing national health insurance), digital health technology providers (eg, designing high-quality tools), and health care service recipients (eg, developing skills to access digital technologies). CONCLUSIONS: The application of digital health technologies in health care services has caused inequities to some extent. However, existing research has certain limitations. The findings provide a comprehensive starting point for future research, allowing for further investigation into how digital health technologies may influence the unequal distribution of health care services. The interaction between individual subjective factors as well as social support and influencing factors should be included in future studies. Specifically, access to and availability of digital health technologies for socially disadvantaged groups should be of paramount importance.

The Impact of Community Care Referral on Time to Surgery for Veterans With Carpal Tunnel Syndrome.

BACKGROUND: The US Department of Veterans Affairs (VA) enacted policies offering Veterans care in the community, aiming to improve access challenges. However, the impact of receipt of community care on wait times for Veterans receiving surgical care is poorly understood. OBJECTIVES: To compare wait times for surgery for Veterans with carpal tunnel syndrome who receive VA care plus community care (mixed care) and those who receive care solely within the VA (VA-only). RESEARCH DESIGN: Retrospective cohort study. SUBJECTS: Veterans undergoing carpal tunnel release (CTR) between January 1, 2010 and December 31, 2016. MEASURES: Our primary outcome was time from primary care physician (PCP) referral to CTR. RESULTS: Of the 29,242 Veterans undergoing CTR, 23,330 (79.8%) received VA-only care and 5912 (20.1%) received mixed care. Veterans receiving mixed care had significantly longer time from PCP referral to CTR (median mixed care: 378 days; median VA-only care: 176 days, P<0.001). After controlling for patient and facility covariates, mixed care was associated with a 37% increased time from PCP referral to CTR (adjusted hazard ratio, 0.63; 95% confidence interval, 0.61-0.65). Each additional service provided in the community was associated with a 23% increase in time to surgery (adjusted hazard ratio, 0.77; 95% confidence interval, 0.76-0.78). CONCLUSIONS: VA-only care was associated with a shorter time to surgery compared with mixed care. Moreover, there were additional delays for each service received in the community. With likely increases in Veterans seeking community care, strategies must be used to identify and mitigate sources of delay through the spectrum of care between referral and definitive treatment.

Preoperative intravenous iron to treat anaemia before major abdominal surgery (PREVENTT): a randomised, double-blind, controlled trial.

BACKGROUND: Preoperative anaemia affects a high proportion of patients undergoing major elective surgery and is associated with poor outcomes. We aimed to test the hypothesis that intravenous iron given to anaemic patients before major open elective abdominal surgery would correct anaemia, reduce the need for blood transfusions, and improve patient outcomes. METHODS: In a double-blind, parallel-group randomised trial, we recruited adult participants identified with anaemia at preoperative hospital visits before elective major open abdominal surgery at 46 UK tertiary care centres. Anaemia was defined as haemoglobin less than 130 g/L for men and 120 g/L for women. We randomly allocated participants (1:1) via a secure web-based service to receive intravenous iron or placebo 10-42 days before surgery. Intravenous iron was administered as a single 1000 mg dose of ferric carboxymaltose in 100 mL normal saline, and placebo was 100 mL normal saline, both given as an infusion over 15 min. Unblinded study personnel prepared and administered the study drug; participants and other clinical and research staff were blinded to treatment allocation. Coprimary endpoints were risk of the composite outcome of blood transfusion or death, and number of blood transfusions from randomisation to 30 days postoperatively. The primary analysis included all randomly assigned patients with data available for the primary endpoints; safety analysis included all randomly assigned patients according to the treatment received. This study is registered, ISRCTN67322816, and is closed to new participants. FINDINGS: Of 487 participants randomly assigned to placebo (n=243) or intravenous iron (n=244) between Jan 6, 2014, and Sept 28, 2018, complete data for the primary endpoints were available for 474 (97%) individuals. Death or blood transfusion occurred in 67 (28%) of the 237 patients in the placebo group and 69 (29%) of the 237 patients in the intravenous iron group (risk ratio 1·03, 95% CI 0·78-1·37; p=0·84). There were 111 blood transfusions in the placebo group and 105 in the intravenous iron group (rate ratio 0·98, 95% CI 0·68-1·43; p=0·93). There were no significant differences between the two groups for any of the prespecified safety endpoints. INTERPRETATION: Preoperative intravenous iron was not superior to placebo to reduce need for blood transfusion when administered to patients with anaemia 10-42 days before elective major abdominal surgery. FUNDING: UK National Institute of Health Research Health Technology Assessment Program.

Evaluation of resource utilization efficiency in obstetrics and gynecology units in China: A three-stage data envelopment analysis of the Shanxi province.

In China, health care resources for expectant mothers and children are still not utilized to full efficiency, with health requirements still not being met. The purpose of this study is to critically examine the efficiency of gynecology and obstetrics hospital (OB/GYN) units in Shanxi province of China, with the overarching objective of exploring methods for improving their efficiency. We employ the three-stage data envelopment analysis (DEA) model to measure the efficiency of 134 OB/GYN units in Shanxi. The results show that the technical efficiency and scale efficiency scores of the sample units were low (0.48 and 0.54, respectively). The efficiency of the OB/GYN units varies by region, city, and county and by type of unit. We conclude that the main reason for the low efficiency of OB/GYN units in Shanxi province lies in the unreasonable scale. The government should, therefore, allocate health resources more reasonably, improving the efficiency of different regions, cities, and counties, as well as different types of OB/GYN units.

Protein structure prediction using multiple deep neural networks in the 13th Critical Assessment of Protein Structure Prediction (CASP13).

We describe AlphaFold, the protein structure prediction system that was entered by the group A7D in CASP13. Submissions were made by three free-modeling (FM) methods which combine the predictions of three neural networks. All three systems were guided by predictions of distances between pairs of residues produced by a neural network. Two systems assembled fragments produced by a generative neural network, one using scores from a network trained to regress GDT_TS. The third system shows that simple gradient descent on a properly constructed potential is able to perform on par with more expensive traditional search techniques and without requiring domain segmentation. In the CASP13 FM assessors' ranking by summed z-scores, this system scored highest with 68.3 vs 48.2 for the next closest group (an average GDT_TS of 61.4). The system produced high-accuracy structures (with GDT_TS scores of 70 or higher) for 11 out of 43 FM domains. Despite not explicitly using template information, the results in the template category were comparable to the best performing template-based methods.

Trial of personalised care after treatment-Prostate cancer: A randomised feasibility trial of a nurse-led psycho-educational intervention.

OBJECTIVE: The present parallel randomised control trial evaluated the feasibility of a nurse-led psycho-educational intervention aimed at improving the self-management of prostate cancer survivors. METHODS: We identified 305 eligible patients from a district general hospital, diagnosed 9-48 months previously, who completed radical treatment, or were monitored clinically (ineligible for treatment). Ninety-five patients were recruited by blinded selection and randomised to Intervention (N = 48) and Control (N = 47) groups. Participant allocation was revealed to patients and researchers after recruitment was completed. For 36 weeks, participants received augmented usual care (Control) or augmented usual care and additional nurse support (Intervention) provided in two community hospitals and a university clinic, or by telephone. RESULTS: Data from 91 participants (Intervention, N = 45; Control, N = 46) were analysed. All feasibility metrics met predefined targets: recruitment rate (31.15%; 95% CI: 25.95%-36.35%), attrition rate (9.47%; 95% CI: 3.58%-15.36%) and outcome measures completion rates (77%-92%). Forty-five patients received the intervention, with no adverse events. The Extended Prostate Cancer Index Composite can inform the minimum sample size for a future effectiveness trial. The net intervention cost was £317 per patient. CONCLUSIONS: The results supported the feasibility and acceptability of the intervention, suggesting that it should be evaluated in a fully powered trial to assess its effectiveness and cost-effectiveness.

Evaluating the cost-effectiveness of percutaneous closure of a patent foramen ovale versus medical management in patients with a cryptogenic stroke: from the UK payer perspective.

AIMS: Percutaneous closure of a patent foramen ovale (PFO) is known to lower the risk of recurrent stroke in patients with a cryptogenic stroke. However, the economic implications of transcatheter PFO closure are less well known. From a UK payer perspective, a detailed economic appraisal of PFO closure was performed for prevention of recurrent ischemic stroke in patients with a PFO who had experienced a cryptogenic stroke. MATERIALS AND METHODS: A Markov cohort model was constructed using a 5-year time-horizon with a patient mean age of 45.2 years, reflecting the characteristics reported in the REDUCE trial. Transition probabilities, clinical inputs, costs, and utility values were ascertained from published and national costing sources. Total costs, incremental costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios were calculated, utilizing a discount rate of 3.5%. A range of univariate and probabilistic sensitivity analyses were also performed. RESULTS: When applying a willingness-to-pay (WTP) threshold of £20,000/QALY in accordance with NICE guidelines, PFO closure compared with antiplatelet therapy alone showed a beneficial cost/QALY of £18,584, attained at 4 years. Applying discount rates of 0% and 6% had a negligible effect on the base-case model findings. PFO closure demonstrated a 76.9% probability of being cost-effective at a WTP threshold of £20,000/QALY at a 5-year time-horizon. LIMITATIONS: This model focused specifically on UK stroke patients and typically enrolled young (mean age <65 years old) patients. Hence, caution should be taken when comparing data vs non-UK populations, and it remains unclear how older patients might have affected cost-effectiveness findings, as the risk of paradoxical embolism can persist as patients age. CONCLUSION: Percutaneous closure of a PFO is cost-effective compared with antiplatelet therapy alone, underlining the economic benefits potentially afforded by this treatment in selected patients.

Rationale and design of: A Randomized tRial of Expedited transfer to a cardiac arrest center for non-ST elevation out-of-hospital cardiac arrest: The ARREST randomized controlled trial.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is a global public health issue. There is wide variation in both regional and inter-hospital survival rates from OHCA and overall survival remains poor at 7%. Regionalization of care into cardiac arrest centers (CAC) improves outcomes following cardiac arrest from ST elevation myocardial infarction (STEMI) through concentration of services and greater provider experience. The International Liaison Committee on Resuscitation (ILCOR) recommends delivery of all post-arrest patients to a CAC, but that randomized controlled trials are necessary in patients without ST elevation (STE). METHODS/DESIGN: Following completion of a pilot randomized trial to assess safety and feasibility of conducting a large-scale randomized controlled trial in patients following OHCA of presumed cardiac cause without STE, we present the rationale and design of A Randomized tRial of Expedited transfer to a cardiac arrest center for non-ST elevation OHCA (ARREST). In total 860 patients will be enrolled and randomized (1:1) to expedited transfer to CAC (24/7 access to interventional cardiology facilities, cooling and goal-directed therapies) or to the current standard of care, which comprises delivery to the nearest emergency department. Primary outcome is 30-day all-cause mortality and secondary outcomes are 30-day and 3-month neurological status and 3, 6 and 12-month mortality. Patients will be followed up for one year after enrolment. CONCLUSION: Post-arrest care is time-critical, requires a multi-disciplinary approach and may be more optimally delivered in centers with greater provider experience. This trial would help to demonstrate if regionalization of post-arrest care to CACs reduces mortality in patients without STE, which could dramatically reshape emergency care provision.

A Human Mixture Risk Assessment for Neurodevelopmental Toxicity Associated with Polybrominated Diphenyl Ethers Used as Flame Retardants.

BACKGROUND: The European Food Safety Authority recently concluded that the exposure of small children (1-3 y old) to brominated diphenyl ether (BDE)-99 may exceed acceptable levels defined in relation to neurodevelopmental toxicity in rodents. The flame retardant BDE-209 may release BDE-99 and other lower brominated BDEs through biotic and abiotic degradation, and all age groups are exposed not only to BDE-209 and -99 but also to a cocktail of BDE congeners with evidence of neurodevelopmental toxicity. The possible risks from combined exposures to these substances have not been evaluated. OBJECTIVES: We performed a congener-specific mixture risk assessment (MRA) of human exposure to combinations of BDE-209 and other BDEs based on estimated exposures via diet and dust intake and on measured levels in biologic samples. METHODS: We employed the Hazard Index (HI) method by using BDE congener-specific reference doses for neurodevelopmental toxicity. RESULTS: Our HI analysis suggests that combined exposures to polybrominated diphenyl ethers (PBDEs) may exceed acceptable levels in breastfeeding infants (0-3 mo old) and in small children (1-3 y old), even for moderate (vs. high) exposure scenarios. Our estimates also suggest that acceptable levels of combined PBDEs may be exceeded in adults whose diets are high in fish. Small children had the highest combined exposures, with some estimated body burdens that were similar to body burdens associated with developmental neurotoxicity in rodents. CONCLUSIONS: Our estimates corroborate reports from several recent epidemiological studies of associations between PBDE exposures and neurobehavioral outcomes, and they support the inclusion of BDE-209 in the persistent organic pollutant (POP) convention as well as the need for strategies to reduce exposures to PBDE mixtures, including maximum residue limits for PBDEs in food and measures for limiting the release of PBDEs from consumer waste. https://doi.org/10.1289/EHP826.

Survey of vaccination knowledge and acceptance among adults admitted to an urban emergency department.

BACKGROUND: Adult vaccination rates in the United States have fallen below national target levels and may be exacerbated by lack of access to a primary care physician. We assessed patient knowledge of and attitudes towards vaccines in an urban emergency department population and analyzed the feasibility of using this setting as a vaccine delivery site from a patient perspective. METHODS: In-person interviewers administered surveys to 250 adult patients presenting to the Detroit Receiving Hospital emergency department in Detroit, Michigan. Respondents were asked about vaccination status, preferences, and willingness to accept vaccination reminders via text messaging. Odds ratios and 95% Wald confidence intervals assessing differences between vaccinated and non-vaccinated individuals were generated with univariate logistic regression. RESULTS: Vaccinated adults were more likely to have a primary care provider than non-vaccinated adults (OR 1.94, 95% CI: 1.09-3.45). Non-vaccinated adults were significantly more likely to have unvaccinated adult relatives (OR8.64, 95% CI: 4.10-18.22). Nearly all respondents used a cell phone, and 75.8% of unvaccinated adults were willing to receive text messages reminders about vaccines. CONCLUSIONS: Although less likely to have a primary care access point than vaccinated participants, non-vaccinated respondents reported interest in receiving vaccinations. Emergency departments could serve as vaccination hubs for patients and unvaccinated accompanying family members. Text message reminders offer a potential source of additional vaccine prompts and education.

Hydrogen sulphide and phosphine interactions with human skin in vitro.

Accidental or intentional releases of toxic gases can have significant public health consequences and emergency resource demands. Management of exposed individuals during hazardous material incidents should be risk and evidence based, but there are knowledge gaps in relation to dermal absorption of gases and management advice for potentially exposed individuals. Using a modified Organization for Economic Co-operation and Development (OECD) in vitro toxicology protocol with human donor skin, this article reports on two common and odorous chemicals, hydrogen sulphide and phosphine. Results show that undamaged human skin provides a good barrier to hydrogen sulphide (up to 800 ppm) and phosphine (up to 1000 ppm) penetration for up to 30 min exposures, with little variability in the presence of clothing or in elevated temperature and humidity conditions. A practical guideline template for skin decontamination has been developed, and implications of the research for first responders are outlined.

Should the scope of human mixture risk assessment span legislative/regulatory silos for chemicals?

Current chemicals regulation operates almost exclusively on a chemical-by-chemical basis, however there is concern that this approach may not be sufficiently protective if two or more chemicals have the same toxic effect. Humans are indisputably exposed to more than one chemical at a time, for example to the multiple chemicals found in food, air and drinking water, and in household and consumer products, and in cosmetics. Assessment of cumulative risk to human health and/or the environment from multiple chemicals and routes can be done in a mixture risk assessment (MRA). Whilst there is a broad consensus on the basic science of mixture toxicology, the path to regulatory implementation of MRA within chemical risk assessment is less clear. In this discussion piece we pose an open question: should the scope of human MRA cross legislative remits or 'silos'? We define silos as, for instance, legislation that defines risk assessment practice for a subset of chemicals, usually on the basis of substance/product, media or process orientation. Currently any form of legal mandate for human MRA in the EU is limited to only a few pieces of legislation. We describe two lines of evidence, illustrated with selected examples, that are particularly pertinent to this question: 1) evidence that mixture effects have been shown for chemicals regulated in different silos and 2) evidence that humans are co-exposed to chemicals from different silos. We substantiate the position that, because there is no reason why chemicals allocated to specific regulatory silos would have non-overlapping risk profiles, then there is also no reason to expect that MRA limited only to chemicals within one silo can fully capture the risk that may be present to human consumers. Finally, we discuss possible options for implementation of MRA and we hope to prompt wider discussion of this issue.

Examining the feasibility of mixture risk assessment: A case study using a tiered approach with data of 67 pesticides from the Joint FAO/WHO Meeting on Pesticide Residues (JMPR).

The way in which mixture risk assessment (MRA) should be included in chemical risk assessment is a current topic of debate. We used data from 67 recent pesticide evaluations to build a case study using Hazard Index calculations to form risk estimates in a tiered MRA approach in line with a Framework proposed by WHO/IPCS. The case study is used to illustrate the approach and to add detail to the existing Framework, and includes many more chemicals than previous case studies. A low-tier MRA identified risk as being greater than acceptable, but refining risk estimates in higher tiers was not possible due to data requirements not being readily met. Our analysis identifies data requirements, which typically expand dramatically in higher tiers, as being the likely cause for an MRA to fail in many realistic cases. This forms a major obstacle to routine implementation of MRA and shows the need for systematic generation and collection of toxicological data. In low tiers, hazard quotient inspection identifies chemicals that contribute most to the HI value and thus require attention if further refinement is needed. Implementing MRA requires consensus on issues such as scope setting, criteria for performing refinement, and decision criteria for actions.

A pilot randomised controlled trial of personalised care after treatment for prostate cancer (TOPCAT-P): nurse-led holistic-needs assessment and individualised psychoeducational intervention: study protocol.

INTRODUCTION: Prostate cancer is common and the incidence is increasing, but more men are living longer after diagnosis, and die with their disease rather than of it. Nonetheless, specific and substantial physical, sexual, emotional and mental health problems often lead to a poor quality of life. Urology services increasingly struggle to cope with the demands of follow-up care, and primary care is likely to play the central role in long-term follow-up. The present phase II trial will evaluate the feasibility and acceptability of a nurse-led, person-centred psychoeducational intervention, delivered in community or primary care settings. METHODS AND ANALYSIS: Prostate cancer survivors diagnosed in the past 9-48 months and currently biochemically stable will be identified from hospital records by their treating clinician. Eligible men would have either completed radical treatment, or would be followed up with prostate specific antigen monitoring and symptom reporting. We will recruit 120 patients who will be randomised to receive either an augmented form of usual care, or an additional nurse-led intervention for a period of 36 weeks. Following the health policy in Wales, the intervention is offered by a key worker, is promoting prudent healthcare and is using a holistic needs assessment. Outcome measures will assess physical symptoms, psychological well-being, confidence in managing own health and quality of life. Healthcare service use will be measured over 36 weeks. Feedback interviews with patients and clinicians will further inform the acceptability of the intervention. Recruitment, attrition, questionnaire completion rates and outcome measures variability will be assessed, and results will inform the design of a future phase III trial and accompanying economic evaluation. ETHICS AND DISSEMINATION: Ethics approval was granted by Bangor University and North Wales REC (13/WA/0291). Results will be reported in peer-reviewed publications, at scientific conferences, and directly through national cancer and primary care networks. TRIAL REGISTRATION NUMBER: ISRCTN 34516019.

Results of a pilot randomised controlled trial to measure the clinical and cost effectiveness of peer support in increasing hope and quality of life in mental health patients discharged from hospital in the UK.

BACKGROUND: Mental health patients can feel anxious about losing the support of staff and patients when discharged from hospital and often discontinue treatment, experience relapse and readmission to hospital, and sometimes attempt suicide. The benefits of peer support in mental health services have been identified in a number of studies with some suggesting clinical and economic gains in patients being discharged. METHODS: This pilot randomised controlled trial with economic evaluation aimed to explore whether peer support in addition to usual aftercare for patients during the transition from hospital to home would increase hope, reduce loneliness, improve quality of life and show cost effectiveness compared with patients receiving usual aftercare only, with follow-up at one and three-months post-discharge. RESULTS: A total of 46 service users were recruited to the study; 23 receiving peer support and 23 in the care-as-usual arm. While this pilot trial found no statistically significant benefits for peer support on the primary or secondary outcome measures, there is an indication that hope may be further increased in those in receipt of peer support. The total cost per case for the peer support arm of the study was £2154 compared to £1922 for the control arm. The mean difference between costs was minimal and not statistically significant. However, further analyses demonstrated that peer support has a reasonably high probability of being more cost effective for a modest positive change in the measure of hopelessness. Challenges faced in recruitment and follow-up are explored alongside limitations in the delivery of peer support. CONCLUSIONS: The findings suggest there is merit in conducting further research on peer support in the transition from hospital to home consideration should be applied to the nature of the patient population to whom support is offered; the length and frequency of support provided; and the contact between peer supporters and mental health staff. There is no conclusive evidence to support the cost effectiveness of providing peer support, but neither was it proven a costly intervention to deliver. The findings support an argument for a larger scale trial of peer support as an adjunct to existing services. TRIAL REGISTRATION: Current Controlled Trials ISRCTN74852771.