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.

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.

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.

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).

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.

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.

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.

Inflammation and autoantibody markers identify rheumatoid arthritis patients with enhanced clinical benefit following rituximab treatment.

OBJECTIVE: Rituximab significantly improves the signs and symptoms of rheumatoid arthritis (RA) and slows the progression of joint damage. The aim of this study was to identify clinical characteristics and biomarkers that identify patients with RA in whom the clinical benefit of rituximab may be enhanced. METHODS: The study group comprised 1,008 RA patients from 2 independent randomized placebo-controlled phase III clinical trials (REFLEX [Randomized Evaluation of Long-Term Efficacy of Rituximab in Rheumatoid Arthritis] and SERENE [Study Evaluating Rituximab's Efficacy in Methotrexate Inadequate Responders]). A novel threshold selection method was used to identify baseline candidate biomarkers present in at least 20% of patients that enriched for placebo-corrected American College of Rheumatology 50% improvement (ACR50 response; a high clinical efficacy bar) at week 24 after the first course of rituximab. RESULTS: The presence of IgM rheumatoid factor (IgM-RF), IgG-RF, IgA-RF, and IgG anti-cyclic citrullinated peptide (anti-CCP) antibodies together with an elevated C-reactive protein (CRP) level were associated with enhanced placebo-corrected ACR50 response rates in the REFLEX patients with RA who had an inadequate response to anti-tumor necrosis factor therapies. These findings were independently replicated using samples from patients in SERENE who had an inadequate response to disease-modifying antirheumatic drug treatment. The combination of an elevated baseline CRP level together with an elevated level of any RF isotype and/or IgG anti-CCP antibodies was further associated with an enhanced benefit to rituximab. CONCLUSION: The presence of any RF isotype and/or IgG anti-CCP autoantibodies together with an elevated CRP level identifies a subgroup of patients with RA in whom the benefit of rituximab treatment may be enhanced. Although the clinical benefit of rituximab was greater in the biomarker-positive population compared with the biomarker-negative population, the clinical benefit of rituximab compared with placebo was also clinically meaningful in the biomarker-negative population.

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.

T cells that cannot respond to TGF-beta escape control by CD4(+)CD25(+) regulatory T cells.

CD4(+)CD25(+) regulatory T (T reg) cells play a pivotal role in control of the immune response. Transforming growth factor-beta (TGF-beta) has been shown to be required for T reg cell activity; however, precisely how it is involved in the mechanism of suppression is poorly understood. Using the T cell transfer model of colitis, we show here that CD4(+)CD45RB(high) T cells that express a dominant negative TGF-beta receptor type II (dnTbetaRII) and therefore cannot respond to TGF-beta, escape control by T reg cells in vivo. CD4(+)CD25(+) T reg cells from the thymus of dnTbetaRII mice retain the ability to inhibit colitis, suggesting that T cell responsiveness to TGF-beta is not required for the development or peripheral function of thymic-derived T reg cells. In contrast, T reg cell activity among the peripheral dnTbetaRII CD4(+)CD25(+) population is masked by the presence of colitogenic effector cells that cannot be suppressed. Finally, we show that CD4(+)CD25(+) T reg cells develop normally in the absence of TGF-beta1 and retain the ability to suppress colitis in vivo. Importantly, the function of TGF-beta1(-/-) T reg cells was abrogated by anti-TGF-beta monoclonal antibody, indicating that functional TGF-beta can be provided by a non-T reg cell source.

Enhanced protection to Mycobacterium tuberculosis infection in IL-10-deficient mice is accompanied by early and enhanced Th1 responses in the lung.

IL-10 regulates the balance of an immune response between pathogen clearance and immunopathology. We show here that Mycobacterium tuberculosis (Mtb) infection in the absence of IL-10 (IL-10(-/-) mice) results in reduced bacterial loads in the lung. This reduction was preceded by an accelerated and enhanced IFN-γ response in the lung, an increased influx of CD4(+) T cells into the lung, and enhanced production of chemokines and cytokines, including CXCL10 and IL-17, in both the lung and the serum. Neutralization of IL-17 affected neither the enhanced production of CXCL10 nor the accumulation of IFN-γ-producing T cells in the lungs, but led to reduced numbers of granulocytes in the lung and reduced bacterial loads in the spleens of Mtb-infected mice. This suggests that IL-17 may contribute to dissemination of Mtb.

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.

Presentation and survival of patients with severe acute kidney injury and multiple myeloma: a 20-year experience from a single centre.

BACKGROUND: Myeloma is the second most common haematological malignancy and is a cause of severe acute kidney injury (serum creatinine >or=500 micromol/L) that has long been associated with a poor prognosis, although previous series have been small. METHODS: We have therefore documented the natural history of all 107 patients referred to a large regional renal unit over a 20-year period and investigated factors associated with survival over a long period of time using Cox regression methods. RESULTS: Three factors were found to be significantly and independently associated with survival: use of chemotherapy [hazard ratio (HR) 0.21, 95% CI: 0.08-0.46, P < 0.001], serum albumin (HR 0.49, 95% CI: 0.29-0.82, P = 0.02 for >or=35 g/L versus <35 g/L) and dialysis independence (HR 0.43, 95% CI: 0.24-0.76, P = 0.005). However, survival was not found to be better for patients presenting in the second decade compared to the first (HR 0.88, 95% CI: 0.52-1.50, P = 0.65). CONCLUSIONS: This analysis highlights the need for clinical trials of novel chemotherapy regimens in this complicated group of patients. Furthermore, whether strategies to restore or preserve dialysis-independent renal function provide additional benefit to effective chemotherapy also requires further investigation. The advent of efficacious low toxicity chemotherapy (such as thalidomide and bortezomib) and new dialysis techniques to remove free light chains may radically alter the outcome of this group of patients.

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.

A graph-theory method for pattern identification in geographical epidemiology--a preliminary application to deprivation and mortality.

BACKGROUND: Graph theoretical methods are extensively used in the field of computational chemistry to search datasets of compounds to see if they contain particular molecular sub-structures or patterns. We describe a preliminary application of a graph theoretical method, developed in computational chemistry, to geographical epidemiology in relation to testing a prior hypothesis. We tested the methodology on the hypothesis that if a socioeconomically deprived neighbourhood is situated in a wider deprived area, then that neighbourhood would experience greater adverse effects on mortality compared with a similarly deprived neighbourhood which is situated in a wider area with generally less deprivation. METHODS: We used the Trent Region Health Authority area for this study, which contained 10,665 census enumeration districts (CED). Graphs are mathematical representations of objects and their relationships and within the context of this study, nodes represented CEDs and edges were determined by whether or not CEDs were neighbours (shared a common boundary). The overall area in this study was represented by one large graph comprising all CEDs in the region, along with their adjacency information. We used mortality data from 1988-1998, CED level population estimates and the Townsend Material Deprivation Index as an indicator of neighbourhood level deprivation. We defined deprived CEDs as those in the top 20% most deprived in the Region. We then set out to classify these deprived CEDs into seven groups defined by increasing deprivation levels in the neighbouring CEDs. 506 (24.2%) of the deprived CEDs had five adjacent CEDs and we limited pattern development and searching to these CEDs. We developed seven query patterns and used the RASCAL (Rapid Similarity Calculator) program to carry out the search for each of the query patterns. This program used a maximum common subgraph isomorphism method which was modified to handle geographical data. RESULTS: Of the 506 deprived CEDs, 10 were not identified as belonging to any of the seven groups because they were adjacent to a CED with a missing deprivation category quintile, and none fell within query Group 1 (a deprived CED for which all five adjacent CEDs were affluent). Only four CEDs fell within Group 2, which was defined as having four affluent adjacent CEDs and one non-affluent adjacent CED. The numbers of CEDs in Groups 3-7 were 17, 214, 95, 81 and 85 respectively. Age and sex adjusted mortality rate ratios showed a non-significant trend towards increasing mortality risk across Groups (Chi-square = 3.26, df = 1, p = 0.07). CONCLUSION: Graph theoretical methods developed in computational chemistry may be a useful addition to the current GIS based methods available for geographical epidemiology but further developmental work is required. An important requirement will be the development of methods for specifying multiple complex search patterns. Further work is also required to examine the utility of using distance, as opposed to adjacency, to describe edges in graphs, and to examine methods for pattern specification when the nodes have multiple attributes attached to them.

Shaping the T cell repertoire to a bona fide autoantigen: lessons from autoimmune gastritis.

Murine autoimmune gastritis is one of the most well-defined organ-specific autoimmune diseases. CD4(+) T cells, which mediate the disease, recognize the highly abundant gastric H(+)/K(+) ATPase heterodimer. The H(+)/K(+) ATPase alpha subunit is also expressed in the thymus, in an aire-independent manner, whereas the H(+)/K(+) ATPase beta subunit is absent from the thymus. Analysis of both H(+)/K(+) ATPase-specific T cell receptor transgenic mice with different affinities for the gastric antigen and mice deficient in the H(+)/K(+) ATPase subunits has provided information on thymic and peripheral selection events. The H(+)/K(+) ATPase antigens play an important role in purging the repertoire of gastritogenic T cells, and recent data have suggested that this tolerance induction occurs primarily in the periphery. The gastritis system provides a powerful approach to determine the impact of peripheral antigen presentation in the target organ draining lymph node on tolerance and autoimmune disease.