Background: Anaemia is a common side-effect of cancer treatments and can lead to a reduction in quality of life. Erythropoiesis-stimulating agents (ESAs) are licensed for use in conjunction with red blood cell transfusions (RBCTs) to improve cancer treatment-induced anaemia (CIA).
Methods: the clinical effectiveness review followed principles published by NHS CRD. Randomised controlled trials (RCTs), or systematic reviews of RCTs, of ESAs (epoetin or darbepoetin) for treating people with CIA were eligible for inclusion in the review. Comparators were best supportive care (BSC), placebo, or other ESA. Anaemia- and malignancy-related outcomes, health-related quality of life (HRQoL), and adverse events (AEs) were evaluated. Where appropriate, data were pooled using meta-analysis. An empirical health economic model was developed comparing ESA treatment to no ESA treatment. The model has two components: one evaluating short-term costs and QALYs (while patients are anaemic); and one evaluating long-term QALYs. Costs and benefits were discounted at 3.5% pa. Probabilistic and univariate deterministic sensitivity analyses were performed.
Results: Twenty-three studies assessing ESAs within their licensed indication (based on start dose administered) were included. None of the RCTs were completely aligned with current EU licenses. Results suggest that there is clinical benefit from ESAs for anaemia-related outcomes. Data suggest improvement in HRQoL scores. The impact of ESAs on AEs and survival remains highly uncertain; although point estimates are lower confidence intervals are wide and not statistically significant. Base case incremental cost-effectiveness ratios (ICERs) for ESA treatment versus no ESA treatment ranged from £19,429–£35,018 per quality-adjusted life year (QALY) gained, but sensitivity and scenario analyses demonstrate considerable uncertainty in these ICERs, including the possibility of overall health disbenefit. All ICERs were sensitive to survival and cost.
Conclusions: ESAs could be cost-effective when used closer to licence but there is considerable uncertainty mainly due to unknown impacts on overall survival.

BACKGROUND: Mobility limitations in older populations have a substantial impact on health outcomes, quality of life, and social care costs. The Retirement in Action (REACT) randomised controlled trial assessed a 12-month community-based group physical activity and behaviour maintenance intervention to help prevent decline in physical functioning in older adults at increased risk of mobility limitation. We aimed to do an economic evaluation of the REACT trial to investigate whether the intervention is cost-effective. METHODS: in this health economic evaluation, we did cost-effectiveness and cost-utility analyses of the REACT programme versus standard care on the basis of resource use, primary outcome, and health-related quality-of-life data measured in the REACT trial. We also developed a decision analytic Markov model that forecasts the mobility of recipients beyond the 24-month follow-up of the trial and translated this into future costs and potential benefit to health-related quality of life using the National Health Service and Personal Social Services perspective. Participants completed questionnaire booklets at baseline, and at 6, 12, and 24 months after randomisation, which included a resource use questionnaire and the EQ-5D-5L and 36-item short-form survey (SF-36) health-related quality-of-life instruments. The cost of delivering the intervention was estimated by identifying key resources, such as REACT session leader time, time of an individual to coordinate the programme, and venue hire. EQ-5D-5L and SF-36 responses were converted to preference-based utility values, which were used to estimate quality-adjusted life-years (QALYs) over the 24-month trial follow-up using the area-under-the-curve method. We used generalised linear models to examine the effect of the REACT programme on costs and QALYs and adjust for baseline covariates. Costs and QALYs beyond 12 months were discounted at 3·5% per year. This is a pre-planned analysis of the REACT trial; the trial itself is registered with ISRCTN (ISRCTN45627165). FINDINGS: the 12-month REACT programme was estimated to cost £622 per recipient to deliver. The most substantial cost components are the REACT session leader time (£309 per participant), venue hire (£109), and the REACT coordinator time (£80). The base-case analysis of the trial-based economic evaluation showed that reductions in health and social care usage due to the REACT programme could offset the REACT delivery costs (£3943 in the intervention group vs £4043 in the control group; difference: -£103 [95% CI -£695 to £489]) with a health benefit of 0·04 QALYs (0·009-0·071; 1·354 QALYs in the intervention group vs 1·314 QALYs in the control group) within the 24-month timeframe of the trial. INTERPRETATION: the REACT programme could be considered a cost-effective approach for improving the health-related quality of life of older adults at risk of mobility limitations. FUNDING: National Institute for Health Research Public Health Research Programme.

Abstract
. Background
. Loneliness and unemployment are each detrimental to health and well-being. Recent evidence suggests a potential bidirectional relationship between loneliness and unemployment in working age individuals. As most existing research focuses on the outcomes of unemployment, this paper seeks to understand the impact of loneliness on unemployment, potential interaction with physical health, and assess bidirectionality in the working age population.
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. Methods
. This study utilised data from waves 9 (2017–19) and 10 (2018–2020) of the Understanding Society UK Household Longitudinal Study. Nearest-neighbour probit propensity score matching with at least one match was used to infer causality by mimicking randomisation. Analysis was conducted in three steps: propensity score estimation; matching; and stratification. Propensity scores were estimated controlling for age, gender, ethnicity, education, marital status, household composition, number of own children in household and region. Findings were confirmed in panel data random effect models, and heterogeneous treatment effects assessed by the matching-smoothing method.
.
. Results
. Experience of loneliness in at least one wave increased the probability of being unemployed in wave 10 by 17.5 [95%CI: 14.8, 20.2] percentage points. Subgroup analysis revealed a greater effect from sustained than transitory loneliness. Further exploratory analysis identified a positive average treatment effect, of smaller magnitude, for unemployment on loneliness suggesting bidirectionality in the relationship. The impact of loneliness on unemployment was further exacerbated by interaction with physical health.
.
. Conclusions
. This is the first study to directly consider the potentially bidirectional relationship between loneliness and unemployment through analysis of longitudinal data from a representative sample of the working age population. Findings reinforce the need for greater recognition of wider societal impacts of loneliness. Given the persisting and potentially scarring effects of both loneliness and unemployment on health and the economy, prevention of both experiences is key. Decreased loneliness could mitigate unemployment, and employment abate loneliness, which may in turn relate positively to other factors including health and quality of life. Thus, particular attention should be paid to loneliness with additional support from employers and government to improve health and well-being.
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ObjectiveTo investigate the importance of key characteristics relating to diagnostic testing for ovarian cancer and to understand how previous test experience influences priorities.DesignCase 1 best–worst scaling embedded in an online survey.SettingPrimary care diagnostic testing in England and Wales.Participants150 women with ovaries over 40 years old living in England and Wales.MethodsWe used best–worst scaling, a preference-based survey method, to elicit the relative importance of 25 characteristics relating to ovarian cancer testing following a systematic review. Responses were modelled using conditional logit regression. Subgroup analysis investigated variations based on testing history.Main outcome measuresRelative importance scores.Results‘Chance of dying from ovarian cancer’ (0.380, 95% CI 0.26 to 0.49) was the most important factor to respondents, closely followed by ‘test sensitivity’ (0.308, 95% CI 0.21 to 0.40). In contrast, ‘time away from usual activities’ (−0.244, 95% CI −0.33 to −0.15) and ‘gender of healthcare provider’ (−0.243, 95% CI −0.35 to −0.14) were least important to respondents overall. Women who had previously undergone testing placed higher importance on certain characteristics including ‘openness of healthcare providers’ and ‘chance of diagnosing another condition’ at the expense of reduced emphasis on characteristics such as ‘pain and discomfort’ and ‘time away from usual activities’.ConclusionsThe results clearly demonstrated items at the extreme, which were most and least important to women considering ovarian cancer testing. Differences in priorities by testing history demonstrate an experience effect, whereby preferences adapt over time based on evidence and experience. Acknowledging these differences helps to identify underlying barriers and facilitators for women with no test experience as well as shortcomings of current service based on women with experience.

INTRODUCTION: a mobile app, BlueIce, was codesigned with young people with a history of self-harm to provide them with more accessible and available evidence-based support at times of distress. A preliminary evaluation found that BlueIce was acceptable, safe and used by young people and helped to reduce self-harm. The present study is designed to assess the effectiveness and cost-effectiveness of adding BlueIce to usual Child and Adolescent Mental Health Service (CAMHS). METHODS AND ANALYSIS: This study is a single-blind, randomised controlled trial comparing usual CAMHS care with usual care plus BlueIce. A total of 138 adolescents aged 12-17 with current or a history of self-harm will be recruited through the Oxford Health National Health Service (NHS) Foundation Trust via their CAMHS clinician. The primary outcome is self-harm at 12 weeks assessed using the Risk Taking and Self-Harm Inventory for Adolescents. Secondary outcomes include mood, anxiety, hopelessness, general behaviour, sleep and impact on everyday life at 12 weeks and 6 months. Health-related quality of life and healthcare resource utilisation data will be collected at baseline, 12 weeks and 6 months. Postuse interviews at 12 weeks will determine the acceptability, safety and usability of BlueIce. ETHICS AND DISSEMINATION: the study was approved by the NHS South Central-Oxford B NHS Research Ethics Committee (19/SC/0212) and by the Health Research Authority (HRA) and Health and Care Research Wales. Findings will be disseminated in peer review open-access journals and at academic conferences. TRIAL REGISTRATION NUMBER: ISRCTN10541045.

Realist evaluation has become widespread partly because of its sensitivity to the influence of contexts on policy implementation. In many such evaluations, the range of contexts considered relevant nevertheless remains disparate and under-conceptualised. This article uses findings from a realist evaluation of English Patient Safety Collaboratives during 2015–2018 to develop a realist taxonomy of contexts, differentiating contexts according to how they affect the corresponding policy mechanism. By analysing the main context-mechanism-outcome configurations that made up the English Patient Safety Collaboratives, we derive a taxonomy of the contexts that affected implementation and outcomes. The categories of context were structural (network, hierarchy, market and organisational contexts); resource-based (actors, material, financial); motivational (receptivity, outcome headroom), and temporal (continuity, history and convergence). To the categories found in previous studies, this study adds the three temporal contexts.

Much attention has been given to how we can make consumption more responsible—better for the planet and society. However, research on the associations between consumer purchasing behavior and their psychological concern for health, the environment and ethics lacks consensus on the significance and directionality of these concerns. This study aims to examine how (relatively) important these concerns are in determining consumer purchasing behavior. Systematic searches were conducted in PubMed, EconLit, Web of Science and Scopus databases from 2000 to 2020. Results were summarized through narrative synthesis of the evidence and meta-analysis. The meta-analysis revealed a significant positive correlation between health, environmental and ethical concerns and purchasing behavior, indicating that changes in health, environmental and ethical concerns will result in a consistent shift in purchase behavior towards choices consistent with the concern. This association is susceptible to moderating factors including types of products (food, non-food and non-specific products) and country’s level of economic development. In addition, the health, environmental and ethical concerns appear to have a weaker impact on the actual purchase behavior than on purchase intention, suggesting that interventions should focus on translating these “purchasing intentions” into actual purchasing behaviors. Narrative review of the studies that were not subject to meta-analysis showed good agreement, with almost all relationships reported having the same direction as those indicated by the meta-analysis. Overall, this study suggests that there is substantial potential for marketing strategies aimed at encouraging pro-health, pro-environment and ethical purchasing behaviors.

. Background
. Tools based on diagnostic prediction models are available to help general practitioners diagnose cancer. It is unclear whether or not tools expedite diagnosis or affect patient quality of life and/or survival.
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.
. Objectives
. The objectives were to evaluate the evidence on the validation, clinical effectiveness, cost-effectiveness, and availability and use of cancer diagnostic tools in primary care.
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.
. Methods
. Two systematic reviews were conducted to examine the clinical effectiveness (review 1) and the development, validation and accuracy (review 2) of diagnostic prediction models for aiding general practitioners in cancer diagnosis. Bibliographic searches were conducted on MEDLINE, MEDLINE In-Process, EMBASE, Cochrane Library and Web of Science) in May 2017, with updated searches conducted in November 2018. A decision-analytic model explored the tools’ clinical effectiveness and cost-effectiveness in colorectal cancer. The model compared patient outcomes and costs between strategies that included the use of the tools and those that did not, using the NHS perspective. We surveyed 4600 general practitioners in randomly selected UK practices to determine the proportions of general practices and general practitioners with access to, and using, cancer decision support tools. Association between access to these tools and practice-level cancer diagnostic indicators was explored.
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.
. Results
. Systematic review 1 – five studies, of different design and quality, reporting on three diagnostic tools, were included. We found no evidence that using the tools was associated with better outcomes. Systematic review 2 – 43 studies were included, reporting on prediction models, in various stages of development, for 14 cancer sites (including multiple cancers). Most studies relate to QCancer® (ClinRisk Ltd, Leeds, UK) and risk assessment tools.
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.
. Decision model
. In the absence of studies reporting their clinical outcomes, QCancer and risk assessment tools were evaluated against faecal immunochemical testing. A linked data approach was used, which translates diagnostic accuracy into time to diagnosis and treatment, and stage at diagnosis. Given the current lack of evidence, the model showed that the cost-effectiveness of diagnostic tools in colorectal cancer relies on demonstrating patient survival benefits. Sensitivity of faecal immunochemical testing and specificity of QCancer and risk assessment tools in a low-risk population were the key uncertain parameters.
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. Survey
. Practitioner- and practice-level response rates were 10.3% (476/4600) and 23.3% (227/975), respectively. Cancer decision support tools were available in 83 out of 227 practices (36.6%, 95% confidence interval 30.3% to 43.1%), and were likely to be used in 38 out of 227 practices (16.7%, 95% confidence interval 12.1% to 22.2%). The mean 2-week-wait referral rate did not differ between practices that do and practices that do not have access to QCancer or risk assessment tools (mean difference of 1.8 referrals per 100,000 referrals, 95% confidence interval –6.7 to 10.3 referrals per 100,000 referrals).
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. Limitations
. There is little good-quality evidence on the clinical effectiveness and cost-effectiveness of diagnostic tools. Many diagnostic prediction models are limited by a lack of external validation. There are limited data on current UK practice and clinical outcomes of diagnostic strategies, and there is no evidence on the quality-of-life outcomes of diagnostic results. The survey was limited by low response rates.
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. Conclusion
. The evidence base on the tools is limited. Research on how general practitioners interact with the tools may help to identify barriers to implementation and uptake, and the potential for clinical effectiveness.
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. Future work
. Continued model validation is recommended, especially for risk assessment tools. Assessment of the tools’ impact on time to diagnosis and treatment, stage at diagnosis, and health outcomes is also recommended, as is further work to understand how tools are used in general practitioner consultations.
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. Study registration
. This study is registered as PROSPERO CRD42017068373 and CRD42017068375.
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. Funding
. This project was funded by the National Institute for Health Research (NIHR) Health Technology programme and will be published in full in Health Technology Assessment; Vol. 24, No. 66. See the NIHR Journals Library website for further project information.
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BACKGROUND: Neonatal sepsis is a major cause of mortality worldwide, with most deaths occurring in low-income countries. The World Health Organisation (WHO) '5 Moments for Hand Hygiene' poster has been used to reduce hospital-acquired infections, but there is no similar tool to prevent community-acquired newborn infections in low-resource settings. This assessment, part of the BabyGel Pilot study, evaluated the acceptability of the 'Newborn Moments for Hand Hygiene in the Home' poster. This was an educational tool which aimed to remind mothers in rural Uganda to clean their hands to prevent neonatal infection. METHODS: the BabyGel pilot was a cluster randomised trial that assessed the post-partum use of alcohol-based hand rub (ABHR) to prevent neonatal infections in Mbale, Uganda. Fifty-five women in 5 village clusters received the ABHR and used it from birth to 3 months postnatally, with use guided by the new poster. Following the study, 5 focus group discussions (FGDs) were conducted consisting of 6-8 purposively sampled participants from intervention villages. FGDs were audio-recorded, transcribed then translated into English. Transcripts were inductively coded using ATLAS.ti® and qualitatively analysed using thematic content analysis. RESULTS: Most mothers reported that they understood the message in the poster ("The picture shows me you must use these drugs to keep your baby healthy") and that they could adhere to the moments from the poster. Some participants used the information from the poster to encourage other caregivers to use the ABHR ("after explaining to them, they liked it"). Other potential moments for hand hygiene were introduced by participants, such as after tending to domestic animals and gardening. CONCLUSION: the poster was well-received, and participants reported compliance with the moments for hand hygiene (although the full body wipe of the baby has since been removed). The poster will be adapted into a sticker format on the ABHR bottle. More focus could be put into an education tool for other caregivers who wish to hold the baby. Overall, the study demonstrated the acceptability of an adapted version of the WHO Moments for Hand Hygiene poster in the introduction of an intervention in the community. TRIAL REGISTRATION: ISRCTN67852437 , registered 02/03/2015. TRIAL FUNDING: Medical Research Council/ Wellcome Trust/ DfID (Global Health Trials Scheme).

BACKGROUND: Alcohol-based hand rub (ABHR) is widely used in both health and social facilities to prevent infection, but it is not known whether supplying it for regular perinatal use can prevent newborn sepsis in African rural homes. Our study piloted a cluster randomised trial of providing ABHR to postpartum mothers to prevent neonatal infection-related morbidity in the communities. METHODS: We conducted a pilot parallel cluster randomised controlled trial across ten villages (clusters) in rural Eastern Uganda. Pregnant women of over 34 weeks' gestation were recruited over a period of 3 months. Both clusters received the standard of care of antenatal health education, Maama Kit, and clinic appointments. In addition, women in the intervention villages received ABHR, instructions on ABHR use, a poster on the 'three moments of hand hygiene', and training. We followed up each mother-baby pair for 3 months after birth and measured rates of consent, recruitment, and follow-up (our target rate was more than 80%). Other measures included ABHR use (the acceptable use was more than four times a day) and its mode of distribution (village health workers (VHWs) or pharmacy), acceptability of study protocol and electronic data capture, and the use of WHO Integrated Management of Childhood Illness (IMCI) tool to screen for newborn infection. RESULTS: We selected 36% (10/28) of villages for randomisation to either intervention or control. Over 12 weeks, 176 pregnant women were screened and 58.5% (103/176) were eligible. All, 100% (103/103), eligible women gave consent and were enrolled into the trial (55 intervention and 48 control). After birth, 94.5% (52/55) of mothers in the intervention and 100% (48/48) of mothers in the control villages were followed up within 72 h. Most, 90.9% (50/55), of the mothers in the intervention villages (96.2% of live births) and 95.8% (46/48) of mothers in the control villages (95.9% of live births) were followed up at 3 months. In intervention villages, the average hand rub use was 6.6 times per day. VHWs accounted for all ABHR stock, compared to the pharmacy that could not account for 5 l of ABHR. The screening tool was positive for infection among a third of babies, i.e. 29.2% (14/48) in the intervention villages versus 31.4% (16/51) in the control villages.VHWs completed the first four questions of IMCI screening tool with ease and accuracy. There were no adverse reactions with the ABHR. CONCLUSION: it is feasible to conduct a cluster-randomised controlled trial (cRCT) of the provision of ABHR to postpartum mothers to prevent neonatal infection-related morbidity in the community in resource-poor settings. Our results indicate that home recruitment promotes excellent follow-up and retention of participants in community trials. The intervention was safe. This pilot study informed the substantial changes necessary in the larger cRCT, including a change in the primary outcome to a composite outcome considering multiple methods of infection detection. A large BabyGel cluster randomised controlled trial is now required. TRIAL REGISTRATION: ISRCTN67852437, registered March 02, 2015. TRIAL FUNDING: Medical Research Council/WellcomeTrust/DfID (Global Health Trials Scheme).

PURPOSE: to assess health-related quality of life (HRQoL) and its associated factors among people living with HIV/AIDS (PLWHA) in Rio de Janeiro, Brazil. METHODS: a cross-sectional study including PLWHA receiving usual HIV-care at Instituto Nacional de Infectologia Evandro Chagas (INI/Fiocruz) was conducted between 2014 and 2016 in Rio de Janeiro, Brazil. The EQ-5D-3L assessed HRQoL; PHQ-2 and ASSIST were used for screening depression and substance use, respectively. Clinical variables were obtained from the INI/Fiocruz cohort database, and structured questions evaluated intimate partner violence, sexual abstinence and relationship status. Data were analysed using multivariable Tobit regression model. RESULTS: a total of 1480 PLWHA were included: 64.7% were male at birth (38.4% men who have sex with men [MSM], 24.3% heterosexual men and 2% transgender women [TGW]); median age was 43.1 years, and 95.8% were receiving antiretroviral therapy. The median EQ-5D-3L utility score was 0.801. Results showed that the following factors: MSM and women; older age; lower educational level; no engagement in a relationship; depression screening positive; polysubstance use; and, detectable viral load were independently associated with worse HRQoL. CONCLUSIONS: PLWHA under care at INI/Fiocruz presented good HRQoL. Polysubstance use, depression and lower educational level were among the factors negatively associated with HRQoL. This was the first time that the EQ-5D-3L utility scores were calculated for a considerable number of PLWHA in Brazil, which is a fundamental piece of information for future cost-effectiveness analysis.

BACKGROUND: Due to their immature immune system, neonates are at high risk of infection. This vulnerability when combined with limited resources and health education in developing countries can lead to sepsis, resulting in high global neonatal mortality rates. Many of these deaths are preventable. The BabyGel pilot trial tested the feasibility of conducting the main randomised trial, with the provision of alcohol handgel to postpartum mothers for prevention of neonatal infective morbidity in the rural community. This secondary analysis sought to evaluate the methods of detecting infections in babies up to 3 months of age. METHODS: the pilot two-arm cluster randomised controlled trial took place in 10 villages around Mbale, Eastern Uganda. Women were eligible and recruited antenatally if their gestation was ≥ 34 weeks. All infants of mothers participating in the BabyGel pilot trial were followed up for the first 3 months of life. Evidence for infant infection was collected using five different methods: clinician diagnosed infection, microbiologically confirmed infection, maternally reported infection, a positive infection screen using the World Health Organization (WHO) Integrated Management of Childhood Illness (IMCI) screening criteria, and reported antibiotic use identified during home and clinic visits. These methods were assessed quantitatively regarding the detection rates of suspected infections and qualitatively by exploring the challenges collecting data in the rural community setting. RESULTS: a total of 103 eligible women participated in the BabyGel pilot trial, with 1 woman delivering twins. of the 99 mother-infant pairs who consented to participate in the study, 55 infants were identified with infection in total. Maternal report of illness provided the highest estimate, with mothers reporting suspected illness for 45 infants (81.8% of the total suspected infections identified). The WHO IMCI screening criteria identified 30 infants with suspected infection (54.5%), and evidence for antibiotic use was established in 22 infants (40%). Finally, clinician-diagnosed infection identified 19 cases (34.5%), which were also microbiologically confirmed in 5 cases (9.1%). Data collection in the rural setting was hindered by poor communication between mothers and the research team, limited staff awareness of the study in health centres resulting in reduced safeguarding of clinical notes, and widespread use of antibiotics prior to notification and clinical review. Furthermore, identification of suspected infection may not have been limited to severe infections, with ambiguity and no official clinical diagnosis being given to those identified solely by maternal report of infection. CONCLUSIONS: a high rate of suspected infection was identified spanning the five sources of data collection, but no ideal method was found for detection of community neonatal infection. Although maternal self-reports of infant infection provided the highest detection rate, data collection via each source was limited and may have identified minor rather than major infections. Future studies could utilise the IMCI screening tool to detect severe community infection leading to referral for clinical confirmation. This should be combined with weekly contact with mothers to detect maternally suspected illness. Obtaining more details of the symptoms and timescale will improve the accuracy when detecting the total burden of suspected disease, and advising participants to retain medication packaging and prescriptions will improve identification of antibiotic use. TRIAL REGISTRATION: Babygel pilot trial - trial registration: ISCRCTN 67852437. Registered 02/03/2015.

BACKGROUND: the REtirement in ACTion (REACT) study is a multi-centre, pragmatic, two-arm, parallel-group randomised controlled trial (RCT) with an internal pilot phase. It aims to test the effectiveness and cost-effectiveness of a community, group-based physical activity intervention for reducing, or reversing, the progression of functional limitations in older people who are at high risk of mobility-related disability. METHODS/DESIGN: a sample of 768 sedentary, community-dwelling, older people aged 65 years and over with functional limitations, but who are still ambulatory (scores between 4 and 9 out of 12 in the Short Physical Performance Battery test (SPPB)) will be randomised to receive either the REACT intervention, delivered over a period of 12 months by trained facilitators, or a minimal control intervention. The REACT study incorporates comprehensive process and economic evaluation and a nested sub-study which will test the hypothesis that the REACT intervention will slow the rate of brain atrophy and of decline in cognitive function assessed using magnetic resonance imaging (MRI). Outcome data will be collected at baseline, 6, 12 and 24 months for the main study, with MRI sub-study data collected at baseline, 6 and 12 months. The primary outcome analysis (SPPB score at 24 months) will be undertaken blinded to group allocation. Primary comparative analyses will be on an intention-to-treat (ITT) basis with due emphasis placed on confidence intervals. DISCUSSION: REACT represents the first large-scale, pragmatic, community-based trial in the UK to target the non-disabled but high-risk segment of the older population with an intervention to reduce mobility-related disability. A programme that can successfully engage this population in sufficient activity to improve strength, aerobic capacity, coordination and balance would have a major impact on sustaining health and independence. REACT is also the first study of its kind to conduct a full economic and comprehensive process evaluation alongside the RCT. If effective and cost-effective, the REACT intervention has strong potential to be implemented widely in the UK and elsewhere. TRIAL REGISTRATION: ISRCTN, ID: ISRCTN45627165. Retrospectively registered on 13 June 2016. Trial sponsor: University of Bath. Protocol Version 1.5.

BACKGROUND: Poor participant understanding of research information can be a problem in community interventional studies with rural African women, whose levels of illiteracy are high. This study aimed to improve the informed consent process for women living in rural eastern Uganda. We assessed the impact of alternative consent models on participants' understanding of clinical trial information and their contribution to the informed consent process in rural Uganda. METHODS: the study applied a parallel mixed-methods design for a prospective comparative cohort, nested within a pilot study on the community distribution of an alcohol-based hand rub to prevent neonatal sepsis (BabyGel pilot trial). Women of at least 34 weeks' pregnancy, suitable for inclusion in the BabyGel pilot trial, were recruited into this study from their homes in 13 villages in Mbale District. As part of the informed consent process, information about the trial was presented using one of three consent methods: standard researcher-read information, a slide show using illustrated text on a flip chart or a video showing the patient information being read as if by a newsreader in either English or the local language. In addition, all women received the patient information sheet in their preferred language. Each information-giving method was used in recruitment for 1 week. Two days after recruitment, women's understanding of the clinical trial was evaluated using the modified Quality of Informed Consent (QuIC) tool. They were also shown the other two methods and their preference assessed using a 5-point Likert scale. Semi-structured interviews were administered to each participant. The interviews were audio-recorded, transcribed and translated verbatim, and thematically analysed. RESULTS: a total of 30 pregnant women in their homes participated in this study. Their recall of the trial information within the planned 48 h was assessed for the majority (90%, 27/30). For all three consent models, women demonstrated a high understanding of the study. There was no statistically significant difference between the slide-show message (mean 4.7; standard deviation, SD 0.47; range 4-5), video message (mean 4.9; SD 0.33; range 4-5) and standard method (mean 4.5; SD 0.53; range 4-5; all one-way ANOVA, p = 0.190). The slide-show message resulted in the most objective understanding of question items with the highest average QuIC score of 100 points. For women who had been recruited using any of the three models, the slide show was the most popular method, with a mean score for all items of not less than 4.2 (mean 4.8; SD 0.6; range 4-5). Most women (63%, 19/30) preferred the slide-show message, compared with 17% (5/30) and 20% (6/30) for the standard and video messages, respectively. The reasons given included the benefits of having pictures to aid understanding and the logical progression of the information. CONCLUSION: Our results from this small study suggest that slide-show messages may be an effective and popular alternative way of presenting trial information to women in rural Uganda, many of whom have little or no literacy. TRIAL REGISTRATION: ISRCTN, ISRCTN67852437. Registered on 18 March 2018.

Purpose: There appears to be an association between poor oral hygiene and increased risk of aspiration pneumonia – a leading cause of mortality post-stroke. We aim to synthesise what is known about oral care after stroke, identify knowledge gaps and outline priorities for research that will provide evidence to inform best practice. Methods: a narrative review from a multidisciplinary perspective, drawing on evidence from systematic reviews, literature, expert and lay opinion to scrutinise current practice in oral care after a stroke and seek consensus on research priorities. Findings: Oral care tends to be of poor quality and delegated to the least qualified members of the caring team. Nursing staff often work in a pressured environment where other aspects of clinical care take priority. Guidelines that exist are based on weak evidence and lack detail about how best to provide oral care. Discussion: Oral health after a stroke is important from a social as well as physical health perspective, yet tends to be neglected. Multidisciplinary research is needed to improve understanding of the complexities associated with delivering good oral care for stroke patients. Also to provide the evidence for practice that will improve wellbeing and may reduce risk of aspiration pneumonia and other serious sequelae. Conclusion: Although there is evidence of an association, there is only weak evidence about whether improving oral care reduces risk of pneumonia or mortality after a stroke. Clinically relevant, feasible, cost-effective, evidence-based oral care interventions to improve patient outcomes in stroke care are urgently needed.

BACKGROUND: in bipolar spectrum disorder, some individuals experience ongoing, frequent fluctuations in mood outside of affective episodes. There are currently no evidence-based psychological interventions designed to address this. This feasibility study is a phase II evaluation of a dialectical behavioural therapy-informed approach (Therapy for Inter-episode mood Variability in Bipolar [ThrIVe-B]). It seeks to examine the feasibility and acceptability of a future definitive trial evaluating the clinical and cost effectiveness of the ThrIVe-B programme. METHODS/DESIGN: Patients will be randomised 1:1 to either treatment as usual only (control arm) or the ThrIVe-B intervention plus treatment as usual (intervention arm). Follow-up points will be at 3, 6, 9 and 15 months after baseline, with 9 months as the primary end point for the candidate primary outcome measures. We aim to recruit 48 individuals meeting diagnostic criteria for a bipolar spectrum disorder and reporting frequent mood swings outside of acute episodes, through primary and secondary care services and self-referral. To evaluate feasibility and acceptability, we will examine recruitment and retention rates, completion rates for study measures and feedback from participants on their experience of study participation and therapy. DISCUSSION: Proceeding to a definitive trial will be indicated if the following criteria are met: (1) trial participation does not lead to serious negative consequences for our participants; (2) any serious concerns about the acceptability and feasibility of the trial procedures can be rectified prior to a definitive trial; (3) follow-up data at 9 months are available for at least 60% of participants; (4) at least 60% of patients in the ThrIVe-B arm complete treatment. TRIAL REGISTRATION: ISRCTN, ISRCTN54234300. Registered on 20 July 2017.

Objectives to assess whether it is feasible to quantify acute change in temporal lobe volume and total oedema volumes in herpes simplex virus (HSV) encephalitis as a preliminary to a trial of corticosteroid therapy. Methods the study analysed serially acquired magnetic resonance images (MRI), of patients with acute HSV encephalitis who had neuroimaging repeated within four weeks of the first scan. We performed volumetric measurements of the left and right temporal lobes and of cerebral oedema visible on T2 weighted Fluid Attenuated Inversion Recovery (FLAIR) images using stereology in conjunction with point counting. Results Temporal lobe volumes increased on average by 1.6% (standard deviation (SD 11%) in five patients who had not received corticosteroid therapy and decreased in two patients who had received corticosteroids by 8.5%. FLAIR hyperintensity volumes increased by 9% in patients not receiving treatment with corticosteroids and decreased by 29% in the two patients that had received corticosteroids. Conclusions This study has shown it is feasible to quantify acute change in temporal lobe and total oedema volumes in HSV encephalitis and suggests a potential resolution of swelling in response to corticosteroid therapy. These techniques could be used as part of a randomized control trial to investigate the efficacy of corticosteroids for treating HSV encephalitis in conjunction with assessing clinical outcomes and could be of potential value in helping to predict the clinical outcomes of patients with HSV encephalitis.

Background: Lack of viral load monitoring of ART is known to be associated with slower switch from a failing regimen and thereby higher prevalence of MDR HIV-1. Many countries have continued to use thymidine analogue drugs despite recommendations to use tenofovir in combination with a cytosine analogue and NNRTI as firstline ART. The effect of accumulated thymidine analogue mutations (TAMs) on phenotypic resistance over time has been poorly characterized in the African setting. Patients and methods: a retrospective analysis of individuals with ongoing viral failure between weeks 48 and 96 in the NORA (Nevirapine OR Abacavir) study was conducted. We analysed 36 genotype pairs from weeks 48 and 96 of first-line ART (14 treated with zidovudine/lamivudine/nevirapine and 22 treated with zidovudine/lamivudine/abacavir). Phenotypic drug resistance was assessed using the Antivirogram assay (v. 2.5.01, Janssen Diagnostics). Results: at 96 weeks, extensive TAMs (≥ 3 mutations) were present in 50% and 73% of nevirapine- and abacavirtreated patients, respectively. The mean (SE) number of TAMs accumulating between week 48 and week 96 was 1.50 (0.37) in nevirapine-treated participants and 1.82 (0.26) in abacavir-treated participants. Overall, zidovudine susceptibility of viruses was reduced between week 48 [geometric mean fold change (FC) 1.3] and week 96 (3.4, P=0.01). There was a small reduction in tenofovir susceptibility (FC 0.7 and 1.0, respectively, P=0.18). Conclusions: Ongoing viral failure with zidovudine-containing first-line ART is associated with rapidly increasing drug resistance that could be mitigated with effective viral load monitoring.

Background: Few low-income countries have virological monitoring widely available. We estimated the virological durability of first-line antiretroviral therapy (ART) after five years of follow-up among adult Ugandan and Zimbabwean patients in the DART study, in which virological assays were conducted retrospectively. Methods: DART compared clinically driven monitoring with/without routine CD4 measurement. Annual plasma viral load was measured on 1,762 patients. Analytical weights were calculated based on the inverse probability of sampling. Time to virological failure, defined as the first viral load measurement ≥200 copies/mL after 48 weeks of ART, was analysed using Kaplan-Meier plots and Cox regression models. Results: Overall, 65% of DART trial patients were female. Patients initiated first-line ART at a median (interquartile range; IQR) age of 37 (32-42) and with a median CD4 cell count of 86 (32-140). After 240 weeks of ART, patients initiating dual-class nucleoside reverse-transcriptase inhibitor (NRTI) -non-nucleoside reverse-transcriptase (NNRTI) regimens containing nevirapine + zidovudine + lamivudine had a lower incidence of virological failure than patients on triple-NRTI regimens containing tenofovir + zidovudine + lamivudine (21% vs 40%; hazard ratio (HR) =0.48, 95% CI:0.38-0.62; p < 0.0001). In multivariate analyses, female patients (HR = 0.79, 95% CI: 0.65-0.95; p = 0.02), older patients (HR = 0.73 per 10 years, 95% CI: 0.64-0.84; p < 0.0001) and patients with a higher pre-ART CD4 cell count (HR = 0.64 per 100 cells/mm3, 95% CI: 0.54-0.75; p < 0.0001) had a lower incidence of virological failure after adjusting for adherence to ART. No difference in failure rate between the two randomised monitoring strategies was observed (p= 0.25). Conclusions: the long-term durability of virological suppression on dual-class NRTI-NNRTI first-line ART without virological monitoring is remarkable and is enabled by high-quality clinical management and a consistent drug supply. To achieve higher rates of virological suppression viral-load-informed differentiated care may be required. Trial Registration: Prospectively registered on 18/10/2000 as ISRCTN13968779.

OBJECTIVE: Investigators within many disciplines are using measures of well-being, but it is not always clear what they are measuring, or which instruments may best meet their objectives. The aims of this review were to: systematically identify well-being instruments, explore the variety of well-being dimensions within instruments and describe how the production of instruments has developed over time. DESIGN: Systematic searches, thematic analysis and narrative synthesis were undertaken. DATA SOURCES: MEDLINE, EMBASE, EconLit, PsycINFO, Cochrane Library and CINAHL from 1993 to 2014 complemented by web searches and expert consultations through 2015. ELIGIBILITY CRITERIA: Instruments were selected for review if they were designed for adults (≥18â€
years old), generic (ie, non-disease or context specific) and available in an English version. RESULTS: a total of 99 measures of well-being were included, and 196 dimensions of well-being were identified within them. Dimensions clustered around 6 key thematic domains: mental well-being, social well-being, physical well-being, spiritual well-being, activities and functioning, and personal circumstances. Authors were rarely explicit about how existing theories had influenced the design of their tools; however, the 2 most referenced theories were Diener's model of subjective well-being and the WHO definition of health. The period between 1990 and 1999 produced the greatest number of newly developed well-being instruments (n=27). An illustration of the dimensions identified and the instruments that measure them is provided within a thematic framework of well-being. CONCLUSIONS: This review provides researchers with an organised toolkit of instruments, dimensions and an accompanying glossary. The striking variability between instruments supports the need to pay close attention to what is being assessed under the umbrella of 'well-being' measurement.

© 2016. Introduction: Chemotherapy-induced diarrhea (CID) diminishes physical performance, raises anxiety and depression levels, and increases healthcare resource utilization. Objective: to understand the impact that CID has on health-related quality of life (HRQoL) and on healthcare resource utilization. Methods: Systematic searches were conducted in MEDLINE, EMBASE, DARE, and the NHS EED databases. Results: a total of 22 articles were retrieved for full review (n = 17, HRQoL; n = 5 healthcare resource utilization). Only 2 studies had assessed HRQoL in patients experiencing CID, while cost studies demonstrated that CID episodes are unnecessarily expensive and can be avoided if diagnosed and treated early. Conclusions: Better management of CID has the potential to reduce overall economic burden and improve patients' HRQoL. Available evidence also relays the need to conduct larger studies that assess HRQoL and consider cost beyond direct medical costs in order to understand the full impact of CID on HRQoL and healthcare resource utilization.

BACKGROUND: Viral encephalitis is a devastating condition for which delayed treatment is associated with increased morbidity and mortality. Clinical audits indicate substantial scope for improved detection and treatment. Improvement strategies should ideally be tailored according to identified needs and barriers to change. The aim of the study is to evaluate the effectiveness and cost-effectiveness of a tailored intervention to improve the secondary care management of suspected encephalitis. METHODS/DESIGN: the study is a two-arm cluster randomised controlled trial with allocation by postgraduate deanery. Participants were identified from 24 hospitals nested within 12 postgraduate deaneries in the United Kingdom (UK). We developed a multifaceted intervention package including core and flexible components with embedded behaviour change techniques selected on the basis of identified needs and barriers to change. The primary outcome will be a composite of the proportion of patients with suspected encephalitis receiving timely and appropriate diagnostic lumbar puncture within 12 h of hospital admission and aciclovir treatment within 6 h. We will gather outcome data pre-intervention and up to 12 months post-intervention from patient records. Statistical analysis at the cluster level will be blind to allocation. An economic evaluation will estimate intervention cost-effectiveness from the health service perspective. TRIAL REGISTRATION: Controlled Trials: ISRCTN06886935.

BACKGROUND: Quality-adjusted life-years (QALYs) have been used since the 1980s as a standard health outcome measure for conducting cost-utility analyses, which are often inadequately labeled as 'cost-effectiveness analyses'. This synthetic outcome, which combines the quantity of life lived with its quality expressed as a preference score, is currently recommended as reference case by some health technology assessment (HTA) agencies. While critics of the QALY approach have expressed concerns about equity and ethical issues, surprisingly, very few have tested the basic methodological assumptions supporting the QALY equation so as to establish its scientific validity. OBJECTIVES: the main objective of the ECHOUTCOME European project was to test the validity of the underlying assumptions of the QALY outcome and its relevance in health decision making. METHODS: an experiment has been conducted with 1,361 subjects from Belgium, France, Italy, and the UK. The subjects were asked to express their preferences regarding various hypothetical health states derived from combining different health states with time durations in order to compare observed utility values of the couples (health state, time) and calculated utility values using the QALY formula. RESULTS: Observed and calculated utility values of the couples (health state, time) were significantly different, confirming that preferences expressed by the respondents were not consistent with the QALY theoretical assumptions. CONCLUSIONS: This European study contributes to establishing that the QALY multiplicative model is an invalid measure. This explains why costs/QALY estimates may vary greatly, leading to inconsistent recommendations relevant to providing access to innovative medicines and health technologies. HTA agencies should consider other more robust methodological approaches to guide reimbursement decisions.

In a randomized comparison of nevirapine or abacavir with zidovudine plus lamivudine, routine viral load monitoring was not performed, yet 27% of individuals with viral failure at week 48 experienced resuppression by week 96 without switching. This supports World Health Organization recommendations that suspected viral failure should trigger adherence counseling and repeat measurement before a treatment switch is considered.

© 2016. Introduction: Cancer anorexia-cachexia syndrome (CACS) negatively impacts patients' quality of life (QoL) and increases the burden on healthcare resources. Objectives: to review published CACS data regarding health-related QOL (HRQoL) and its economic impact on the healthcare system. Methods: Searches were conducted in MEDLINE, EMBASE, DARE, and NHS EED databases. Results: a total of 458 HRQoL and 189 healthcare resources utilisation abstracts were screened, and 42 and 2 full-text articles were included, respectively.The EORTC QLQ-C30 and FAACT instruments were most favoured for assessing HRQOL but none of the current tools cover all domains affected by CACS. Economic estimates for managing CACS are scarce, with studies lacking a breakdown of healthcare resource utilisation items. Conclusions: HRQoL instruments that can better assess and incorporate all the domains affected by CACS are required. Rigorous assessment of costs and benefits of treatment are needed to understand the magnitude of the impact of CACS.

BACKGROUND: the evidence on determinants of individuals' choices for anti-malarial drug treatments is scarce. This study sought to measure the strength of preference for adult antimalarial drug treatment attributes of heads of urban, rural and peri-urban households in a resource-limited malaria-endemic area of sub-Saharan Africa. METHODS: Discrete choice experiments were conducted with 508 heads of household interviewed face-to-face for a household population survey of health-seeking behavior in Zomba District, Malawi. The interviews were held in Chichewa and the choice experiment questions were presented with cartoon aids. The anti-malarial drug attributes included in the stated preference experiment were: speed of fever resolution, side effects (pruritus) risk, protection (duration of prophylactic effect), price, duration of treatment course and recommendation by a health professional. Sixteen treatment profiles from a fractional factorial design by orthogonal array were paired into choice scenarios, and scenarios were randomly assigned to participants so that each participant was presented with a series of eight pairwise choice scenarios. Respondents had the option to state indifference between the two profiles or decline to choose. Data were analysed in a mixed logit model, with normally distributed coefficients for all six attributes. RESULTS: the sex ratio was balanced in urban areas, whereas 63% of participants in rural areas were male. The proportion of individuals with no education was considerably higher in the rural group (25%) than in the urban (5%) and peri-urban (6%) groups. All attributes investigated had the expected influence, and traded-off in most respondents' choices. There were heterogeneous effects of price, pruritus risk, treatment recommendation by a professional, and duration of prophylaxis across respondents, only partly explained by their differences in education, household per capita expenditure, sex and age. Individuals' demand elasticity (simulated median, inter-quartile range) was highest (most responsive) to speed of symptom resolution (0.88, 0.80-0.89) and pruritus risk (0.25, 0.08-0.62). CONCLUSIONS: Most adult antimalarial users are willing to use treatments without recommendation from health professional, and may be influenced by price. Future studies should investigate the magnitude of differences in price and treatment attribute sensitivity between adult anti-malarial drug users in rural, peri-urban and urban areas in order to determine optimal price subsidies.

OBJECTIVE: Several countries in sub-Saharan Africa have implemented policies to remove or reduce user fees. Our aim was to identify criteria guiding such decisions among national policy entrepreneurs, those who link up problem definition, solution development and political processes. METHODS: We administered a best-worst scaling (BWS) experiment to 89 policy entrepreneurs, asking them to identify the most and the least important criteria on a series of predefined sets. Sets were compiled using a Balance Incomplete Block Design which generated random combinations of all 11 criteria included in the experiment. In turn, those had emerged from a prior set of focus group discussions organized among policy entrepreneurs. Ordered logit models were used to investigate the value of single criteria as well as heterogeneity of preferences. RESULTS: Political commitment was identified as the most important criterion guiding policy decisions on user fee abolition or reduction to the overall sample, but particularly so for more experienced respondents aged over 50 years. International pressure and donor money were identified as least important while equity and institutional capacity were deemed of relatively little importance. Respondents more involved in advising on policy than on formulating policy rated economic issues such as financial sustainability and cost-effectiveness as less important. CONCLUSIONS: it is feasible to apply BWS experiments in low-income countries, although whether the technique can be adjusted to elicit preferences among non-literate respondents in these settings is unclear.

BACKGROUND: over 133,000 children present to hospitals with Acute Encephalitis Syndrome (AES) annually in Asia. Japanese encephalitis (JE) accounts for approximately one-quarter of cases; in most cases no pathogen is identified and management is supportive. Although JE is known to result in neurological impairment, few studies have examined the wider impact of JE and AES on patients and their families. METHODOLOGY/PRINCIPAL FINDINGS: Children (aged 1 month-14 years) with AES were assessed 5-12 months after discharge from two Nepali hospitals. Assessment included clinical examination, the Liverpool Outcome Score (LOS) - a validated assessment of function following encephalitis, questionnaires about the child's social participation since discharge, and out-of-pocket costs to the family. Children were classified as JE or 'other AES' based on anti-JE virus antibody titres during acute illness. Contact was made with the families of 76% (73/96) of AES children. Six children had died and one declined participation. 48% (32/66) reported functional impairment at follow-up, most frequently affecting behaviour, language or limb use. Impairment was more frequent in JE compared to 'other AES' cases (68% [13/19] versus 40% [19/47]; p = 0.06). 49% (26/53) had improvement in LOS between discharge and follow-up. The median out-of-pocket cost to families, including medical bills, medication and lost earnings was US$ 1151 (10 times their median monthly income) for children with severe/moderate impairment and $524 (4.6 times their income) for those with mild/no impairment (P = 0.007). Acute admission accounted for 74% of costs. Social participation was limited in 21% of children (n = 14). CONCLUSIONS/SIGNIFICANCE: Prolonged functional impairment was common following AES. Economic impact to families was substantial. Encouragingly, almost half the children improved after discharge and most reported sustained social participation. This study highlights a need for long-term medical support following AES. Rationalisation of initial expensive hospital treatments may be warranted, especially since only supportive treatment is available.

Antiretroviral therapy (ART) improves the quality of life of people living with HIV/AIDS. However, adherence remains a challenge. A total of eight focus group discussions (FGD) were conducted with participants from a randomised controlled trial that monitored strategies for managing ART in African adults: Development of Antiretroviral Therapy. All FGD participants had received ART for at least one year. Perceived benefits of ART were key motivators for adherence. These benefits included improved physical health, restored self-esteem, acceptance in the community and hope for a longer and healthier life and reduced fear of HIV/AIDS-related death. Barriers to adherence included a high pill burden, ART side effects and socio-economic constraints, including lack of food and safe water for taking the pills. Visible ART side effects and involvement in an exclusively HIV/AIDS clinic could expose their HIV status, thus exacerbating stigma. Gender and socio-economic differences were found in the variety of strategies employed to ensure adherence. ART was perceived as improving the overall quality of life of recipients; however, it is crucial for ART programmes to be gender and socio-economic cognizant in order to enhance adherence to a lifelong therapy.

As antiretroviral treatment (ART) for HIV/AIDS is scaled up globally, information on per-person costs is critical to improve efficiency in service delivery and to maximize coverage and health impact. The objective of this study was to review studies on unit costs for delivery of adult and paediatric ART per patient-year, and prevention of mother-to-child transmission (PMTCT) interventions per mother-infant pair screened or treated, in low- and middle-income countries. A systematic review was conducted of English, French and Spanish publications from 2001 to 2009, reporting empirical costing that accounted for at least antiretroviral (ARV) medicines, laboratory testing and personnel. Expenditures were analysed by country-income level and cost component. All costs were standardized to $US, year 2009 values. Several sensitivity analyses were conducted. Analyses covered 29 eligible, comprehensive, costing studies. In the base case, in low-income countries (LIC), median ART cost per patient-year was $US792 (mean: 839, range: 682-1089); for lower-middle-income countries (LMIC), the median was $US932 (mean: 1246, range: 156-3904); and, for upper-middle-income countries (UMIC), the median was $US1454 (mean: 2783, range: 1230-5667). ARV drugs were the largest component of overall ART costs in all settings (64%, 50% and 47% in LIC, LMIC and UMIC, respectively). of 26 ART studies, 14 reported the drug regimes used, and only one study explicitly reported second-line treatment costs. The second cost driver was laboratory cost in LIC and LMIC (14% and 20%), and personnel costs in UMIC (26%). Two ART studies specified the types of laboratory tests costed, and three studies specifically included above facility-level personnel costs. Three studies reported detailed PMTCT costs, and three studies reported on paediatric ART. There is a paucity of data on the full unit costs for delivery of ART and PMTCT, particularly for LIC and middle-income countries. Heterogeneity in activities costed, and insufficient detail regarding components included in the costing, hampers standardization of unit cost measures. Evaluation of programme-level unit costs would benefit from international guidance on standardized costing methods, and expenditure categories and definitions. Future work should help elucidate the sources of the large variations in delivery unit costs across settings with similar income and epidemiological characteristics.

In 1975, the World Health Assembly recommended that blood for transfusion should come from voluntary, non-remunerated donors; yet, in Africa, 75-80% of blood for transfusion still comes from hospital-based replacement donors. Although comprehensive economic data are scarce, evidence indicates that blood from voluntary donors recruited and screened at centralized transfusion centres, costs four to eight times as much as blood from a hospital-based, replacement donor system. Donor recruitment, quality assurance systems and distribution mechanisms in the centralized system are major reasons for the cost difference. There are concerns about the sustainability of centralized voluntary donor systems and their compatibility with the levels of health care that exist in many poor countries yet burdening patients' families with the responsibility of finding replacement blood donors will exacerbate poverty and reduce the safety of the blood supply. There are measures that can be introduced into hospital-based systems to improve safe blood supply in Africa but their effectiveness in different contexts needs to be evaluated.

AIMS: to evaluate the characteristics of manual haemoglobin methods in use in Malawi and provide evidence for the Ministry of Health in Malawi to enable them to choose a suitable method for district hospitals. METHODS: Criteria on accuracy, clinical usefulness, user friendliness, speed, training time, and economic costs were determined by local health professionals and used to compare six different manual haemoglobin methods. These were introduced sequentially into use in a district hospital in Malawi alongside the reference method. RESULTS: HemoCue was the optimal method based on most of the outcome measures but was also the most expensive (0.75 US dollars/test). DHT meter and Jenway colorimeter were the second choice because they were cheaper (0.20-0.35 US dollars/test), but they were not as accurate or user friendly as HemoCue. CONCLUSIONS: the process for choosing appropriate laboratory methods is complex and very little guidance is available for health managers in poorer countries. This paper describes the development and testing of a practical model for gathering evidence about test efficiency that could be adapted for use in other resource poor settings.

A high burden of malaria, tuberculosis, and HIV infection contributes to national and individual poverty. We have reviewed a broad range of evidence detailing factors at individual, household, and community levels that influence vulnerability to malaria, tuberculosis, and HIV infection and used this evidence to identify strategies that could improve resilience to these diseases. This first part of the review explores the concept of vulnerability to infectious diseases and examines how age, sex, and genetics can influence the biological response to malaria, tuberculosis, and HIV infection. We highlight factors that influence processes such as poverty, livelihoods, gender discrepancies, and knowledge acquisition and provide examples of how approaches to altering these processes may have a simultaneous effect on all three diseases.

A study of unit costs and cost components of two malaria-control strategies (house spraying and bednet impregnation with residual insecticides) was undertaken in 11 malaria-endemic states (departamentos) of Colombia, using data provided by control staff on self-administered questionnaires. The accuracy of the data was verified by personal visits, telephone conversations and complementary information from 10 other states. Allthe financial-cost components of the malaria-control operations carried out in the previous 6 months and the results of the control operations themselves (including the numbers of houses sprayed and numbers of bednets impregnated/day) were recorded. The information was stratified according to whether the target communities were 'near' or 'far away' from an operational base, the far-away communities being those that needed overnight stays by the control staff. The main variables analysed were unit costs/house treated, and annual cost/person protected. The results show that house spraying was generally more expensive for the health services than bednet impregnation. This is particularly the case in 'nearby' communities, where most of those at-risk live. In such communities, spraying one house was 7.2 times more expensive than impregnating one bednet. Even if only those sleeping under an impregnated net were assumed to be protected, the unit costs/person protected in a 'nearby' community were twice as high for house spraying than for bednet impregnation. In 'nearby' communities, where technicians could return to the operational base each evening, insecticides made up 80% of the total spraying costs and 42% of the costs of bednet impregnation. In 'far-away' communities, however, salaries and 'per diems' were the most important cost components, representing, respectively, 23% and 22% of the costs of spraying, and 34% plus 27% of the costs of impregnation. Insecticide wastage and non-use of discounts on insecticide prices (available through the national Ministry of Health) increased the overall costs considerably. The multiple uses of these cost calculations for district health managers are presented.