Providing capacity in glaucoma care using trained and accredited optometrists: A qualitative evaluation.

INTRODUCTION: The role of optometrists in glaucoma within primary and secondary care has been well described. Whilst many studies examined safety and clinical effectiveness, there is a paucity of qualitative research evaluating enablers and barriers for optometrists delivering glaucoma care. The aims of this study are to investigate qualitatively, and from a multi-stakeholder perspective whether optometric glaucoma care is accepted as an effective alternative to traditional models and what contextual factors impact upon their success. METHODS: Patients were recruited from clinics at Manchester Royal Eye Hospital and nationally via a Glaucoma UK registrant database. Optometrists, ophthalmologists, and other stakeholders involved in glaucoma services were recruited via direct contact and through an optometry educational event. Interviews and focus groups were recorded and transcribed anonymously, then analysed using the framework method and NVivo 12. RESULTS: Interviews and focus groups were conducted with 38 participants including 14 optometrists and 6 ophthalmologists (from all 4 UK nations), and 15 patients and 3 commissioners/other stakeholders. Themes emerging related to: enablers and drivers; challenges and barriers; training; laser; professional practice; the role of other health professionals; commissioning; COVID-19; and patient experience. CONCLUSION: Success in developing glaucoma services with optometrists and other health professionals is reliant on multi-stakeholder input, investment in technology and training, inter-professional respect and appropriate time and funding to set up and deliver services. The multi-stakeholder perspective affirms there is notable support for developing glaucoma services delivered by optometrists in primary and secondary care, with caveats around training, appropriate case selection and clinical responsibility.

Towards a contemporary social care 'prevention narrative' of principled complexity: An integrative literature review.

Prevention has become increasingly central in social care policy and commissioning strategies within the United Kingdom (UK). Commonly there is reliance on understandings borrowed from the sphere of public health, leaning on a prevention discourse characterised by the 'upstream and downstream' metaphor. Whilst framing both structural factors and responses to individual circumstances, the public health approach nonetheless suggests linearity in a cause and effect relationship. Social care and illness follow many trajectories and this conceptualisation of prevention may limit its effectiveness and scope in social care. Undertaken as part of a commissioned evaluation of the Social Services and Wellbeing Act (2014) Wales, a systematic integrative review was conducted to establish the key current debates within prevention work, and how prevention is conceptually framed, implemented and evaluated within the social care context. The databases Scopus, ASSIA, CINAHL and Social Care Online were initially searched in September 2019 resulting in 52 documents being incorporated for analysis. A further re-run of searches was run in March 2021, identifying a further 14 documents, thereby creating a total of 66. Predominantly, these were journal articles or research reports (n = 53), with the remainder guidance or strategy documents, briefings or process evaluations (n = 13). These were categorised by their primary theme and focus, as well as document format and research method before undergoing thematic analysis. This highlighted the continued prominence of three-tiered, linear public health narratives in the framing of prevention for social care, with prevention work often categorised and enacted with inconsistency. Common drivers for prevention activity continue to be cost reduction and reduced dependence on the care system in the future. Through exploring prevention for older people and caregivers, we argue for an approach to prevention aligning with the complexities of the social world surrounding it. Building on developments in complexity theory in social science and healthcare, we offer an alternative view of social care prevention guided by principles rooted in the everyday realities of communities, service users and caregivers.

Virtual clinics for glaucoma care - Patients' and clinicians' experiences and perceptions: a qualitative evaluation.

BACKGROUND: The role of glaucoma virtual clinics has developed to help meet demand for capacity within busy glaucoma services. There is limited research of patient and clinician experiences and perceptions of these clinics and the aim of this study is to provide further information to help improve patient experience and guide service delivery. METHODS: A mixed methods research design was employed comprising of a patient satisfaction survey, and patient and clinician interviews. Consultant ophthalmologists were recruited from throughout the UK, and patients and data gathering clinical staff recruited from the Manchester Royal Eye Hospital and Bristol Eye Hospital. RESULTS: We received a total of 148 patient satisfaction questionnaires with an overall response rate of 55.4%. Most respondents were diagnosed with primary open angle glaucoma (33.9%) at Manchester and glaucoma suspect status at Bristol (50.6%). Patients had high levels of confidence in the person conducting the tests (94.8% Manchester, 98.8% Bristol), and most were likely to recommend the service to family or friends (94.8% Manchester, 92.6% Bristol). We interviewed 10 consultant ophthalmologists, 10 data gathering staff and 20 patients. A number of key themes emerged from the transcribed interviews including: patient experience, clinician perception of patient experience, service delivery, staffing and staff experience, and patient safety. CONCLUSIONS: Glaucoma virtual clinics can be acceptable to both clinicians and patients, including those with a varied complexity of glaucoma and glaucoma-related disease. Dissatisfaction seemed to relate to poor communication or processes and systems within the service rather than complexity of disease.

Normalisation process theory and the implementation of a new glaucoma clinical pathway in hospital eye services: Perspectives of doctors, nurses and optometrists.

BACKGROUND: Normalisation process theory reports the importance of contextual integration in successfully embedding novel interventions, with recent propositions detailing the role that 'plasticity' of intervention components and 'elasticity' of an intended setting contribute. We report on the introduction of a clinical pathway assessing patient non-responsiveness to treatment for glaucoma and ocular hypertension. The aim of this study was to assess the feasibility of implementing the Cardiff Model of Glaucoma Care into hospital eye services, identifying any issues of acceptability for staff through the filter of normalisation process theory. METHODS: A prospective observational study was undertaken in four hospital eye services. This incorporated detailed qualitative semi-structured interviews with staff (n = 8) to gather their perceptions on the intervention's usefulness and practicality. In addition, observational field notes of patient and staff consultations (n = 88) were collected, as well as broader organisational observations from within the research sites (n = 52). Data collection and analysis was informed by the normalisation process theory framework. RESULTS: Staff reported the pathway led to beneficial knowledge on managing patient treatment, but the model was sometimes perceived as overly prescriptive. This perception varied significantly based on the composition of clinics in relation to staff experience, staff availability and pre-existing clinical structures. The most commonly recounted barrier came in contextually integrating into sites where wider administrative systems were inflexible to intervention components. CONCLUSIONS: Flexibility will be the key determinant of whether the clinical pathway can progress to wider implementation. Addressing the complexity and variation associated with practice between clinics required a remodelling of the pathway to maintain its central benefits but enhance its plasticity. Our study therefore helps to confirm propositions developed in relation to normalisation process theory, contextual integration, intervention plasticity, and setting elasticity. This enables the transferability of findings to healthcare settings other than ophthalmology, where any novel intervention is implemented.

Evaluation of training, patient and practitioner perspectives on community-based monitoring of patients with stable age-related macular degeneration compared to hospital-based care: The FENETRE study report no. 1.

PURPOSE: Describe the development, delivery, acceptability and evaluation of a modular training programme for community-based, non-medical practitioners monitoring patients with quiescent neovascular age related macular degeneration (QnAMD). Also, report on a qualitative process evaluation conducted during the pilot phase of a randomised control trial (the FENETRE Study) exploring patient and practitioner acceptability of community-based QnAMD care relative to hospital-based care. METHODS: Learning outcomes from The College of Optometrists' Medical Retina higher qualifications and the Royal College of Ophthalmologists' Common Clinical Competency Framework were used to develop a competency framework for QnAMD care. Training was delivered online, comprising six asynchronous lectures followed by two synchronous case-based discussion webinars, with an accredited assessment of 24 case vignettes. An anonymous evaluation survey was conducted with the first two FENETRE cohorts (n = 38). Separately, we undertook a qualitative process evaluation, sampling purposively in four hospitals and five community-based practices, interviewing nine patients and eight practitioners. RESULTS: Survey responses (n = 26) showed community optometrists were very satisfied (n = 12; 46%) or satisfied (n = 14; 54%) with the training; feedback reflected by qualitative process evaluation data. Overall, optometrists also felt either confident (n = 15; 58%) or very confident (n = 8; 31%) in conducting AMD monitoring appointments following training, a finding also corroborated by interview data from optometrists participating in the initial pilot phase roll-out. Optometrists identified patient convenience and alleviating pressures in hospital care as the primary reasons for acceptability of community pathways. Data from patients entering community practices suggested they largely found this at least as safe and convenient as hospital care, although some patients randomised to hospital care perceived that as safer. CONCLUSION: This pilot study has shown the development and implementation of a collaborative community monitoring model is feasible, with satisfaction from community optometrists for training and accreditation, and broad acceptance for the pathway by both patients and practitioners.

Chronic Conditions and Behavioural Change Approaches to Medication Adherence: Rethinking Clinical Guidance and Recommendations.

Patient adherence to medication is an ongoing concern for clinicians, obfuscating treatment efficacy and resulting in wastage of medicine, reduced clinical benefit, and increased mortality. Despite this, procedural guidance on how clinicians should best engage patients regarding their medicine-taking is limited in the United Kingdom. Adherence for chronic conditions is notably complex, requiring clear education, communication, and behavioural shifts to initiate and sustain daily regimens successfully. This article explores current clinician guidance on assuring patient adherence to medication within the National Health Service, comparing it to that provided for healthcare workers in the field of behavioural change. Outlining the inertia of the former and the progress of the latter, we consider what steps should be taken to address this deficit, including greater focus on patient concerns, as well as knowledge translation for healthcare professionals in future adherence research. Current United Kingdom clinical guidance for assuring patient adherence is largely outdated based on inconclusive evidence for best practice. However, efforts to encourage behavioural change in the public health setting demonstrate evidence-based success. Integrating knowledge generated around adherence behaviour and the practical application of adherence and behavioural change research, as well as funding for longer-term studies with a focus on clinical outcomes, may help to solidify the NICE guidance on adherence and further progress the field. This would require close involvement from patient groups and networks informing ethical aspects of study design and clinical implementation.

Acceptability, adherence and economic analyses of a new clinical pathway for the identification of non-responders to glaucoma eye drops: a prospective observational study.

BACKGROUND/AIMS: Assess whether a new clinical pathway for glaucoma was acceptable to patients and healthcare professionals and whether it provided useful clinical information on non-responsiveness and non-adherence to the treatment of elevated intraocular pressure with latanoprost eye drops. METHODS: A single arm non-randomised prospective observational study incorporating new glaucoma/ocular hypertension patients. To assess issues of acceptability, qualitative observation and interviews were conducted with patients and healthcare professionals. To determine clinical responsiveness, intraocular pressures were measured before and 4 hours after a clinician-instilled eye drop over two distinct appointments. Adherence data were collected using a Medicine Event Monitoring System. Economic analyses compared the costs between novel and standard care pathways. RESULTS: Of 72 patients approached, 53 entered the study (74.3%) and 50 completed all procedures (94.3%). Intraocular pressure was reduced more than 15% in 83 out of 92 study eyes by final visit (90.2%). The non-response rate was 5.1% once the effect of low adherence was minimised. For the 1376 drop instillation days under observation, eye drops were instilled as prescribed on 1004 days (73.0%), over-instilled on 137 days (9.9%) and not instilled on 235 days (17.1%). The Cardiff Model of Glaucoma Care involved negligible cost, although acceptance for healthcare professionals showed variation. CONCLUSIONS: The Cardiff Model of Glaucoma Care offers novel clinical and adherence insights at marginal costs while acceptable to patients. Healthcare professionals felt that 4 hour and 4 week follow-up appointments could cause administrative problems. A streamlined version of the pathway has therefore been developed to facilitate clinical adoption. TRIAL REGISTRATION NUMBER: ISRCTNID:ISRCTN75888393.

Glaucoma, dementia, and the "precipice of care": transitions between states of medication adherence.

PURPOSE: "She wouldn't remember. Even when I go through, and she's decided to go to bed, I'll say I'll come and do her drops. If I didn't say that, they wouldn't be done." Dementia is widely considered as a key factor in whether patients take their medication as prescribed. However, few studies have examined the effect of dementia on medication management strategies for glaucoma including how patient and carer needs impact adherence and long-term prognosis. We report findings from a qualitative grounded theory study incorporating the views of patients, carers, and healthcare professionals. METHODS: Eighty-three semistructured interviews were conducted with 35 patients, 22 lay carers, and nine healthcare professionals across sites in Wales and Scotland. These explored understanding of eye drop regimens, barriers, and facilitators to drop administration, as well as attitudes toward glaucoma, dementia, and other comorbidities. RESULTS: Using Pound's synthesis of adherence behavior, we identified categories of active and passive acceptance of medicines, alongside modification or rejection of eye drop regimens. In relation to dementia, participants highlighted transitions between such categories, with a shift from active to passive acceptance commonly reported. This loss of self-medicating capability was referred to as the precipice of care, where entwinement of multiple conditions (eg, heart disease, glaucoma, and dementia) and sociocultural influences (eg, living alone) contributed to accelerated health declines. That said, numerous factors mitigated this, with a key role being the lay carer. Spouses and family members often acted as the monitor of eye drops for patients, seeking intervention when any behavioral changes influenced their administration. CONCLUSION: Though dementia was associated with progression toward the precipice of care, factors such as communication with healthcare professionals appeared to affect patient adherence. Recommendations for healthcare practice include better recording of dementia diagnoses and integrating eye drops into preexisting routines.

Corrigendum: The RA-MAP Consortium: a working model for academia-industry collaboration.

This corrects the article DOI: 10.1038/nrrheum.2017.200.

Injury resulting from targeted violence: An emergency department perspective.

BACKGROUND: Hate crimes - those perpetrated because of perceived difference, including disability, race, religion, sexual orientation or transgender status - have not been studied at the point of the victim's hospital emergency department (ED) use. AIM: To investigate the frequency, levels of physical harm and circumstances of targeted violence in those seeking treatment at EDs in three UK cities. METHOD: In a multimethods study, face-to-face semi-structured interviews were conducted with 124 adult ED attenders with violent injuries. Victim and perpetrator socio-demographics were recorded. Patient narratives about perceived motives and circumstances were transcribed, uploaded onto NVivo for thematic analysis. RESULTS: Nearly a fifth (23, 18.5%) of the injured patients considered themselves to have been attacked by others motivated by hostility or prejudice to their 'difference' (targeted violence). Thematic analyses suggested these prejudices were to appearance (7 cases), racial tension (5 cases), territorial association (3 cases) and race, religious or sexual orientation (8 cases). According to victims, alcohol intoxication was particularly relevant in targeted violence (estimated reported frequency 90% and 56% for targeted and non-targeted violence, respectively). CONCLUSIONS: Our findings support a broader concept of hate victimisation and suggest that emergency room violence surveys could act as a community tension sensor and early warning system in this regard. Tackling alcohol misuse seems as important in this as in other forms of violence perpetration. Copyright © 2017 John Wiley & Sons, Ltd.

The RA-MAP Consortium: a working model for academia-industry collaboration.

Collaboration can be challenging; nevertheless, the emerging successes of large, multi-partner, multi-national cooperatives and research networks in the biomedical sector have sustained the appetite of academics and industry partners for developing and fostering new research consortia. This model has percolated down to national funding agencies across the globe, leading to funding for projects that aim to realise the true potential of genomic medicine in the 21st century and to reap the rewards of 'big data'. In this Perspectives article, the experiences of the RA-MAP consortium, a group of more than 140 individuals affiliated with 21 academic and industry organizations that are focused on making genomic medicine in rheumatoid arthritis a reality are described. The challenges of multi-partner collaboration in the UK are highlighted and wide-ranging solutions are offered that might benefit large research consortia around the world.

Clinical Drug Development Using Dynamic Biomarkers to Enable Personalized Health Care in COPD.

Despite massive investments in the development of novel treatments for heterogeneous diseases such as COPD, the resources spent have only benefited a fraction of the population treated. Personalized health care to guide selection of a suitable patient population already in the clinical development of new compounds could offer a solution. This review discusses past successes and failures in drug development and biomarker research in COPD, describes research in COPD phenotypes and the required characteristics of a suitable biomarker for identifying patients at higher risk of progression, and examines the role of extracellular matrix proteins found to be upregulated in COPD. Novel biomarkers of connective tissue remodeling that may provide added value for a personalized approach by detecting subgroups of patients with active disease suitable for pharmacologic intervention are discussed.

Transient systemic inflammation does not alter the induction of tolerance to gastric autoantigens by migratory dendritic cells.

It has been proposed that activation of dendritic cells (DCs) presenting self-antigens during inflammation may lead to activation of autoreactive T cells and the development of autoimmunity. To test this hypothesis, we examined the presentation of the autoantigen recognized in autoimmune gastritis, gastric H(+)/K(+) ATPase, which is naturally expressed in the stomach and is constitutively presented in the stomach-draining lymph nodes. Systemic administration to mice of the TLR9 agonist CpG DNA, agonist anti-CD40 Ab, or TLR4 agonist LPS all failed to abrogate the process of peripheral clonal deletion of H(+)/K(+) ATPase-specific CD4 T cells or promote the development of autoimmune gastritis. We demonstrated that migratory DCs from the stomach-draining lymph nodes are the only DC subset capable of constitutively presenting the endogenous gastric H(+)/K(+) ATPase autoantigen in its normal physiological context. Analysis of costimulatory molecules indicated that, relative to resident DCs, migratory DCs displayed a partially activated phenotype in the steady state. Furthermore, migratory DCs were refractory to stimulation by transient exposure to TLR agonists, as they failed to upregulate costimulatory molecules, secrete significant amounts of inflammatory cytokines, or induce differentiation of effector T cells. Together, these data show that transient systemic inflammation failed to break tolerance to the gastric autoantigen, as migratory DCs presenting the gastric autoantigen remain tolerogenic under such conditions, demonstrating the robust nature of peripheral tolerance.

Bayesian hierarchical modelling of noisy spatial rates on a modestly large and discontinuous irregular lattice.

We present Bayesian hierarchical spatial model development motivated from a recent analysis of noisy small area response rate data, named the Booster data. The Booster data are postcode-level aggregates from a recent mail-out recruitment for a physical exercise intervention in deprived urban neighbourhoods in Sheffield, UK. Bayesian hierarchical Bernoulli-binomial spatial mixture zero-inflated Binomial models were developed for modelling overdispersion and for separation of systematic and random variations in the noisy and mostly low crude response rates. We present methods that enabled us to explore the underlying spatial rate variation, clustering of low or high response rate areas and neighbourhood characteristics that were associated with variations and patterns of invitation mail-outs, zero-response and response rates. Three spatial prior formulations, the intrinsic conditional autoregressive or (iCAR), the Besag-York-Mollié (BYM) and the modified BYM models, were explored for their performance on modelling sparse data on a modestly large and discontinuous irregular lattice. An in-depth Bayesian analysis of the Booster data is presented, with the resulting posterior estimation and inference implemented via Markov chain Monte Carlo simulation in WinBUGS. With increasing availability of spatial data referenced at fine spatial scales such as the postcode, the sparse-data situation and the Bayesian models and methods discussed herein should have considerable relevance to small area disease and health mapping and to spatial regression.

A randomised controlled trial and cost-effectiveness evaluation of 'booster' interventions to sustain increases in physical activity in middle-aged adults in deprived urban neighbourhoods.

BACKGROUND: More evidence is needed on the potential role of 'booster' interventions in the maintenance of increases in physical activity levels after a brief intervention in relatively sedentary populations. OBJECTIVES: To determine whether objectively measured physical activity, 6 months after a brief intervention, is increased in those receiving physical activity 'booster' consultations delivered in a motivational interviewing (MI) style, either face to face or by telephone. DESIGN: Three-arm, parallel-group, pragmatic, superiority randomised controlled trial with nested qualitative research fidelity and geographical information systems and health economic substudies. Treatment allocation was carried out using a web-based simple randomisation procedure with equal allocation probabilities. Principal investigators and study statisticians were blinded to treatment allocation until after the final analysis only. SETTING: Deprived areas of Sheffield, UK. PARTICIPANTS: Previously sedentary people, aged 40-64 years, living in deprived areas of Sheffield, UK, who had increased their physical activity levels after receiving a brief intervention. INTERVENTIONS: Participants were randomised to the control group (no further intervention) or to two sessions of MI, either face to face ('full booster') or by telephone ('mini booster'). Sessions were delivered 1 and 2 months post-randomisation. MAIN OUTCOME MEASURES: The primary outcome was total energy expenditure (TEE) per day in kcal from 7-day accelerometry, measured using an Actiheart device (CamNtech Ltd, Cambridge, UK). Independent evaluation of practitioner competence was carried out using the Motivational Interviewing Treatment Integrity assessment. An estimate of the per-participant intervention costs, resource use data collected by questionnaire and health-related quality of life data were analysed to produce a range of economic models from a short-term NHS perspective. An additional series of models were developed that used TEE values to estimate the long-term cost-effectiveness. RESULTS: In total, 282 people were randomised (control = 96; mini booster = 92, full booster = 94) of whom 160 had a minimum of 4 out of 7 days' accelerometry data at 3 months (control = 61, mini booster = 47, full booster = 52). The mean difference in TEE per day between baseline and 3 months favoured the control arm over the combined booster arm but this was not statistically significant (-39 kcal, 95% confidence interval -173 to 95, p = 0.57). The autonomy-enabled MI communication style was generally acceptable, although some participants wanted a more paternalistic approach and most expressed enthusiasm for monitoring and feedback components of the intervention and research. Full boosters were more popular than mini boosters. Practitioners achieved and maintained a consistent level of MI competence. Walking distance to the nearest municipal green space or leisure facilities was not associated with physical activity levels. Two alternative modelling approaches both suggested that neither intervention was likely to be cost-effective. CONCLUSIONS: Although some individuals do find a community-based, brief MI 'booster' intervention supportive, the low levels of recruitment and retention and the lack of impact on objectively measured physical activity levels in those with adequate outcome data suggest that it is unlikely to represent a clinically effective or cost-effective intervention for the maintenance of recently acquired physical activity increases in deprived middle-aged urban populations. Future research with middle-aged and relatively deprived populations should explore interventions to promote physical activity that require less proactive engagement from individuals, including environmental interventions. STUDY REGISTRATION: Current Controlled Trials ISRCTN56495859, ClinicalTrials.gov NCT00836459. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 13. See the NIHR Journals Library website for further project information.

Vitamin A supplementation every 6 months with retinol in 1 million pre-school children in north India: DEVTA, a cluster-randomised trial.

BACKGROUND: In north India, vitamin A deficiency (retinol <0·70 µmol/L) is common in pre-school children and 2-3% die at ages 1·0-6·0 years. We aimed to assess whether periodic vitamin A supplementation could reduce this mortality. METHODS: Participants in this cluster-randomised trial were pre-school children in the defined catchment areas of 8338 state-staffed village child-care centres (under-5 population 1 million) in 72 administrative blocks. Groups of four neighbouring blocks (clusters) were cluster-randomly allocated in Oxford, UK, between 6-monthly vitamin A (retinol capsule of 200,000 IU retinyl acetate in oil, to be cut and dripped into the child's mouth every 6 months), albendazole (400 mg tablet every 6 months), both, or neither (open control). Analyses of retinol effects are by block (36 vs 36 clusters). The study spanned 5 calendar years, with 11 6-monthly mass-treatment days for all children then aged 6-72 months. Annually, one centre per block was randomly selected and visited by a study team 1-5 months after any trial vitamin A to sample blood (for retinol assay, technically reliable only after mid-study), examine eyes, and interview caregivers. Separately, all 8338 centres were visited every 6 months to monitor pre-school deaths (100,000 visits, 25,000 deaths at ages 1·0-6·0 years [the primary outcome]). This trial is registered at ClinicalTrials.gov, NCT00222547. FINDINGS: Estimated compliance with 6-monthly retinol supplements was 86%. Among 2581 versus 2584 children surveyed during the second half of the study, mean plasma retinol was one-sixth higher (0·72 [SE 0·01] vs 0·62 [0·01] µmol/L, increase 0·10 [SE 0·01] µmol/L) and the prevalence of severe deficiency was halved (retinol <0·35 µmol/L 6%vs 13%, decrease 7% [SE 1%]), as was that of Bitot's spots (1·4%vs 3·5%, decrease 2·1% [SE 0·7%]). Comparing the 36 retinol-allocated versus 36 control blocks in analyses of the primary outcome, deaths per child-care centre at ages 1·0-6·0 years during the 5-year study were 3·01 retinol versus 3·15 control (absolute reduction 0·14 [SE 0·11], mortality ratio 0·96, 95% CI 0·89-1·03, p=0·22), suggesting absolute risks of death between ages 1·0 and 6·0 years of approximately 2·5% retinol versus 2·6% control. No specific cause of death was significantly affected. INTERPRETATION: DEVTA contradicts the expectation from other trials that vitamin A supplementation would reduce child mortality by 20-30%, but cannot rule out some more modest effect. Meta-analysis of DEVTA plus eight previous randomised trials of supplementation (in various different populations) yielded a weighted average mortality reduction of 11% (95% CI 5-16, p=0·00015), reliably contradicting the hypothesis of no effect. FUNDING: UK Medical Research Council, USAID, World Bank (vitamin A donated by Roche).

Population deworming every 6 months with albendazole in 1 million pre-school children in North India: DEVTA, a cluster-randomised trial.

BACKGROUND: In north India many pre-school children are underweight, many have intestinal worms, and 2-3% die at ages 1·0-6·0 years. We used the state-wide Integrated Child Development Service (ICDS) infrastructure to help to assess any effects of regular deworming on mortality. METHODS: Participants in this cluster-randomised study were children in catchment areas of 8338 ICDS-staffed village child-care centres (under-5 population 1 million) in 72 administrative blocks. Groups of four neighbouring blocks were cluster-randomly allocated in Oxford between 6-monthly vitamin A (retinol capsule of 200,000 IU retinyl acetate in oil, to be cut and dripped into the child's mouth every 6 months), albendazole (400 mg tablet every 6 months), both, or neither (open control). Analyses of albendazole effects are by block (36 vs 36 clusters). The study spanned 5 calendar years, with 11 6-monthly mass-treatment days for all children then aged 6-72 months. Annually, one centre per block was randomly selected and visited by a study team 1-5 months after any trial deworming to sample faeces (for presence of worm eggs, reliably assessed only after mid-study), weigh children, and interview caregivers. Separately, all 8338 centres were visited every 6 months to monitor pre-school deaths (100,000 visits, 25,000 deaths at age 1·0-6·0 years [the primary outcome]). This trial is registered at ClinicalTrials.gov, NCT00222547. FINDINGS: Estimated compliance with 6-monthly albendazole was 86%. Among 2589 versus 2576 children surveyed during the second half of the study, nematode egg prevalence was 16% versus 36%, and most infection was light. After at least 2 years of treatment, weight at ages 3·0-6·0 years (standardised to age 4·0 years, 50% male) was 12·72 kg albendazole versus 12·68 kg control (difference 0·04 kg, 95% CI -0·14 to 0·21, p=0·66). Comparing the 36 albendazole-allocated versus 36 control blocks in analyses of the primary outcome, deaths per child-care centre at ages 1·0-6·0 years during the 5-year study were 3·00 (SE 0·07) albendazole versus 3·16 (SE 0·09) control, difference 0·16 (SE 0·11, mortality ratio 0·95, 95% CI 0·89 to 1·02, p=0·16), suggesting absolute risks of dying between ages 1·0 and 6·0 years of roughly 2·5% albendazole versus 2·6% control. No specific cause of death was significantly affected. INTERPRETATION: Existing ICDS village staff can be organised to deliver simple pre-school interventions sustainably for many years at low cost, but regular deworming had little effect on mortality in this lightly infected pre-school population. FUNDING: UK Medical Research Council, USAID, World Bank (albendazole donated by GlaxoSmithKline).

Risk, governance and the experience of care.

Drawing on perspectives from the governmentality literature and the sociology of risk, this article explores the strategies, tools and mechanisms for managing risk in acute hospital trusts in the United Kingdom. The article uses qualitative material from an ethnographic study of four acute hospital trusts undertaken between 2008 and 2010 focusing on the provision of dignified care for older people. Extracts from ethnographic material show how the organisational mechanisms that seek to manage risk shape the ways in which staff interact with and care for patients. The article bridges the gap between the sociological analysis of policy priorities, management strategy and the organisational cultures of the NHS, and the everyday interactions of care provision. In bringing together this ethnographic material with sociological debates on the regulation of healthcare, the article highlights the specific ways in which forms of governance shape how staff care for their patients challenging the possibility of providing dignified care for older people.

Effect of baseline rheumatoid factor and anticitrullinated peptide antibody serotype on rituximab clinical response: a meta-analysis.

BACKGROUND: Studies examining the relationship between serological status (rheumatoid factor and/or anticitrullinated antibody) and rituximab treatment outcome in rheumatoid arthritis (RA) have been hampered by limited numbers of seronegative patients. OBJECTIVE: To carry out a meta-analysis of trials from the rituximab RA clinical programme to investigate this relationship further. METHODS: This was a meta-analysis of four placebo-controlled, phase II or III clinical trials. The efficacy end point in all analyses was change from baseline in Disease Activity Score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) at 24 weeks. Assay of serotype and missing data imputation methods were consistent across all studies. RESULTS: The population analysed comprised 2177 patients (rituximab, n=1416; placebo, n=761). Demographics and baseline disease characteristics were well balanced. When a fixed-effects meta-analysis approach was used, the overall-effect model indicated evidence of additional treatment benefit with rituximab in seropositive patients: reduction in DAS28-ESR at week 24 was on average 0.35 units (95% CI 0.12 to 0.84; n=1394) greater than in seronegative patients; this effect was not seen in placebo patients. Heterogeneity indices indicated significant uncertainty in the overall-effect model (Q=8.8, I=0.77; p=0.03 (χ(2) test)). Baseline Health Assessment Questionnaire score, pain visual analogue scale, swollen joint counts of 28 joints and race were significant contributors to this heterogeneity, with additional analysis indicating that these effects may predominate in early RA (methotrexate-naïve) populations. A dominant effect was seen in patients for whom one or more tumour necrosis factor inhibitors had failed. CONCLUSION: Although the difference was modest, the overall-effect model indicates that seropositive patients respond better to rituximab than seronegative patients.