Acute kidney injury: an acceptable risk of treatment with renin-angiotensin system blockade in primary care?

Background: Use of renin-angiotensin system (RAS) blockade has become increasingly widespread driven by evidence-based guidance. There is concern about the role of these agents in the genesis of avoidable acute kidney injury (AKI). Objectives: To investigate the association between AKI and use of RAS blockade. Design: Multilevel hierarchical analysis of a large cohort of patients registered with UK general practitioners. Setting: Primary care practices in East and West Kent, United Kingdom. Patients: 244,715 patients from 27 practices. Measurements: Demographic, clinical, biochemical and prescription data. Methods: Analyses of data acquired between 02/3/2004 and 17/04/2012 using multilevel logistic regression to determine the relationship between AKI and use of RAS blockade; further analysed by indication for treatment with RAS blockade. Results: Sufficient serum creatinine data were available to define AKI in 63,735 patients with 208,275 blood test instances. In 95,569 instances the patient was prescribed a RAS antagonist of which 5.4% fulfilled criteria for AKI. The unadjusted odds ratio (OR) for AKI in those prescribed RAS blockade was 1.93 (1.81-2.06, 95%CI) falling to 1.11 (1.02-1.20, 95%CI) when adjusted for age, gender, co-morbidity, GFR category, proteinuria, systolic blood pressure and diuretic therapy. In patients with an evidence-based indication there was no difference in absolute risk of AKI. However, prescription of RAS blockade in the absence of indication appeared to be associated with greater risk of AKI. When analysis was repeated with AKIN2/AKIN3 as the outcome, although risk of AKI remained significant when unadjusted (OR 1.73, 95%CI 1.42-2.11, p<0.001), after full adjustment there was no increased risk (OR 0.83, 95%CI 0.63-1.09) in those taking RAS antagonists. However, when analysed by indication AKIN2/AKIN3 was significantly more likely in those prescribed RAS antagonists without indication (OR 2.04, 95%CI 1.41-2.94, p<0.001). Limitations: Observational database study. No information concerning hospitalisation. Prescribing assumptions and potential inaccurate coding. Potential survival bias; patients surviving longer will contribute more data. Conclusions: Use of RAS antagonists increased the risk of AKI, independent of common confounding variables. After correction for confounders the risk fell away and became non-significant for moderate and severe AKI. However, where there was no evidence-based indication for RAS antagonists the risk of AKI, whether mild, moderate or severe, remained greater

Categorical methods in graded ring theory

Let G be a group, R a G-graded ring and X a right G-set . We study functors between categories of modules graded by G-sets, continuing the work of [M]. As an application we obtain generalizations of Cohen-Montgomery Duality Theorems by categorical methods. Then we study when some functors introduced in [M] (which generalize some functors ocurring in [D1], [D2] and [NRV]) are separable. Finally we obtain an application to the study of the weak dimension of a group graded ring

When does NICE recommend the use of health technologies within a programme of evidence development?

This article is made available through the Brunel Open Access Publishing Fund. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Background: There is growing interest internationally in linking reimbursement decisions with recommendations for further research. In the UK, the National Institute for Health and Clinical Excellence (NICE) can issue guidance to approve the routine use of a health intervention, reject routine use or recommend use within a research programme. These latter recommendations have restricted use to ‘only in research’ (OIR) or have recommended further research alongside routine use (‘approval with research’ or AWR). However, it is not currently clear when such recommendations are likely to be made. Objectives: This study aims to identify NICE technology appraisals where OIR or AWR recommendations were made and to examine the key considerations that led to those decisions. Methods: Draft and final guidance including OIR/AWR recommendations were identified. The documents were reviewed to establish the characteristics of the technology appraisal, the cost effectiveness of the technologies, the key considerations that led to the recommendations and the types of research required. Results: In total, 29 final and 31 draft guidance documents included OIR/AWR recommendations up to January 2010. Overall, 86 % of final guidance included OIR recommendations. Of these, the majority were for technologies considered to be cost ineffective (83 %) and the majority of final guidance (66 %) specified the need for further evidence on relative effectiveness. The use of OIR/AWR recommendations is decreasing over time and they have rarely been used in appraisals conducted through the single technology appraisal process. Conclusion: NICE has used its ability to recommend technologies within research programmes, although predominantly within the multiple technology appraisal process. OIR recommendations have been most frequently issued for technologies considered cost ineffective and the most frequently cited consideration is uncertainty related to relative effectiveness. Key considerations cited for most AWR recommendations and some OIR recommendations included a need for further evidence on long-term outcomes and adverse effects of treatment.Medical Research Counci

Cost-effectiveness of ocriplasmin for the treatment of vitreomacular traction and macular hole

Background: If left untreated, vitreomacular traction (VMT) will infrequently improve through spontaneous resolution of vitreomacular adhesion (VMA), and patients remain at risk of further deterioration in vision. The mainstay of treatment for VMT is vitrectomy, an invasive procedure that carries the risk of rare but serious complications and further vision loss. As such, a ‘watch and wait’ approach is often adopted before this surgical intervention is performed. Ocriplasmin (microplasmin) is a potential alternative treatment for patients with symptomatic VMA/VMT that may remove the requirement for vitrectomy. Objective: The purpose of this study was to evaluate the cost-effectiveness of ocriplasmin for the treatment of VMT in comparison to standard of care. Study design: A cohort-based computer simulation model was developed, capturing three mutually exclusive subgroups: 1) VMT without epiretinal membrane (ERM) or full thickness macular hole (FTMH), 2) VMT with ERM but no FTMH, and 3) VMT with FTMH. Transition probabilities between health states, utilities, and resource utilisation were estimated based on clinical trial results, the literature, and expert opinion. The cost per quality-adjusted life year (QALY) gained was estimated over a lifetime, using UK unit costs and utilities associated with visual acuity, adverse events, metamorphopsia, and surgical interventions. Setting: Analyses were conducted from a UK payer perspective. Population: Transition probabilities for the model were primarily estimated from patient-level data from the combined Phase 3 MIVI-TRUST trials in patients with symptomatic VMA/VMT, including when associated with a FTMH ≤400 µm. Intervention: Ocriplasmin (microplasmin) is a one-time intravitreal injection designed specifically to release the abnormal traction between the macula and the vitreous and thereby treat VMT, as well as macular hole with persistent vitreous attachment. Main outcome measure: The main outcome measure of the economic evaluation was cost per QALY. Results: In all subgroups, ocriplasmin management generated more QALYs: 1) VMT without ERM or FTMH (0.105, (0.036, 0.191)); 2) VMT with ERM but no FTMH (0.041, (0.011, 0.131)); and 3) VMT with FTMH (0.053, (−0.002, 0.113)). The initial treatment costs were partially offset by later savings and net costs were estimated at £1,901 (£1,325, £2,474), £2,491 (£1,067, £2,511), and £1,912 (£1,233, £2,506), respectively. Costs per QALY were estimated at £18,056 (£8,241, £64,874), £61,059 (£8,269, £168,664), and £36,250 (−£144,788, £290,338), respectively. Short-term efficacy parameters were found to be key drivers of results. Conclusion: Ocriplasmin is most cost-effective in VMT patients without either ERM or FTMH

National Certification Programme for Cardiovascular Rehabilitation – aiming to improve practice

Cardiovascular disease (CVD) continues to be a leading cause of mortality and morbidity in the United Kingdom.1 It is also a leading contributor to health inequalities; reducing excess deaths from coronary heart disease in the most deprived fifth of areas would have the greatest impact on the life expectancy gap in England.2 Cardiovascular rehabilitation (CR) is a multifaceted secondary prevention programme which aims to improve outcomes for people with CVD, with strong evidence of clinical and cost-effectiveness,3 and is recommended by the National Institute for Health and Care Excellence (NICE).4,5 The evidence-based service standards for delivery6,7 include centre or home-based options (equally effective8), by a multidisciplinary team supported by community services (such as smoking cessation). The British Association for Cardiovascular Prevention and Rehabilitation (BACPR) recommends that a CR programme should be based on seven components which have health behaviour change and education at their core (Figure 1). Quality assurance of CR delivery is monitored, assessed and findings published, annually, by the British Heart Foundation–funded National Audit of Cardiac Rehabilitation (NACR) based at the University of York. The NACR collects both programme and patient-level data from a majority of CR programmes across most of the United Kingdom (with the exception of Scotland). To ensure data security and quality, NACR data are hosted by NHS Digital