Assessing the clinical and cost-effectiveness of inpatient mental health rehabilitation services provided by the NHS and independent sector (ACER): protocol

Background: Mental health rehabilitation services provide specialist treatment to people with particularly severe and complex problems. In 2018, the Care Quality Commission reported that over half the 4,400 mental health inpatient rehabilitation beds in England were provided by the independent sector. They raised concerns that the length of stay and cost of independent sector care was double that of the NHS and that their services tended to be provided much further from people’s homes. However, there has been no research comparing the two sectors and we therefore do not know if these concerns are justified. The ACER Study (Assessing the Clinical and cost-Effectiveness of inpatient mental health Rehabilitation services provided by the NHS and independent sector) is a national programme of research in England, funded from 2021 to 2026, that aims to investigate differences in inpatient mental health rehabilitation provided by the NHS and independent sector in terms of: patient characteristics; service quality; patient, carer and staff experiences; clinical and cost effectiveness. Methods: ACER comprises a:1) detailed survey of NHS and independent sector inpatient mental health rehabilitation services across England; 2) qualitative investigation of patient, family, staff and commissioners’ experiences of the two sectors; 3) cohort study comparing clinical outcomes in the two sectors over 18 months; 4) comprehensive national comparison of inpatient service use in the two sectors, using instrumental variable analysis of routinely collected healthcare data over 18 months; 5) health economic evaluation of the relative cost-effectiveness of the two sectors. In Components 3 and 4, our primary outcome is ‘successful rehabilitation’ defined as a) being discharged from the inpatient rehabilitation unit without readmission and b) inpatient service use over the 18 months. Discussion: The ACER study will deliver the first empirical comparison of the clinical and cost-effectiveness of NHS and independent sector inpatient mental health rehabilitation services. Trial registration: ISRCTN17381762 retrospectively registered

"Environmental risk factors associated with juvenile idiopathic arthritis associated uveitis:a systematic review of the literature"

BACKGROUND: Juvenile idiopathic arthritis associated uveitis (JIA-U) is the most common extra-articular manifestation of juvenile idiopathic arthritis (JIA) and carries considerable risk to vision. The aim of this systematic review was to synthesise evidence of environmental risk factors for JIA-U and identify risk factors which may be modifiable or used to stratify JIA patients. METHODS: This systematic review was carried out in accordance with PRISMA guidelines. Four online databases - Cumulative Index of Nursing and Allied Health Literature, Web of Science, MEDLINE and Embase - were searched from database inception to 12th August 2020. Identified studies were screened by two independent reviewers against pre-defined inclusion and exclusion criteria. Data was extracted from all primary studies meeting inclusion criteria and independently checked. RESULTS: We identified three studies from 895 unique records which met the inclusion criteria, each examining a different environmental risk factor. This systematic review includes 973, predominantly female, participants with JIA across these three studies. The use of allergy medication or documentation of “allergy”/“allergic” in the medical records was associated with an increased risk of JIA-U in all models presented. Vitamin D sufficiency was associated with reduced risk of JIA-U. There was insufficient evidence to support an association between seasonality and JIA-U. CONCLUSIONS: This review identifies a potential role for allergy and vitamin D in JIA-U. It also illustrates the paucity of data regarding environmental risk factors for JIA-U and highlights the need for further research to both identify additional risk factors and replicate existing findings

Cost-effectiveness of peer-supported self-management for people discharged from a mental health crisis team: methodological challenges and recommendations

Background Mental health acute crisis episodes are associated with high inpatient costs. Self-management interventions may reduce readmission by enabling individuals to manage their condition. Delivery of such interventions by Peer Support Workers (PSWs) may be cost-effective. CORE, a randomized control trial of a PSW self-management intervention compared to usual care, found a significant reduction in admissions to acute mental healthcare for participants receiving the intervention. This paper aims to evaluate the cost-effectiveness of the intervention over 12 months from a mental health service perspective. Analysis methods of increasing complexity were used to account for data missingness and distribution. Methods Participants were recruited from six crisis resolution teams in England from 12 March 2014 to 3 July 2015 (trial registration ISRCTN: 01027104). Resource use was collected from patient records at baseline and 12 months. The EQ-5D-3L was collected at baseline and 4 and 18 months, and linear interpolation was used to calculate 12-month values for quality-adjusted life-years (QALYs). The primary analysis of adjusted mean incremental costs and QALYs for complete cases are calculated separately using OLS regression. Secondly, a complete-case non-parametric two-stage bootstrap (TSB) was performed. The impacts of missing data and skewed cost data were explored using multiple imputation using chained equations and general linear models, respectively. Results Four hundred and forty-one participants were recruited to CORE; 221 randomized to the PSW intervention and 220 to usual care plus workbook. The probability that the PSW intervention was cost-effective compared with the workbook plus usual care control at 12 months varied with the method used, and ranged from 57% to 96% at a cost-effectiveness threshold of £20,000 per QALY gained. Discussion There was a minimum 57% chance that the intervention was cost-effective compared to the control using 12-month costs and QALYs. The probability varied by 40% when methods were employed to account for the relationship between costs and QALYs, but which restricted the sample to those who provided both complete cost and utility data. Caution should therefore be applied when selecting methods for the evaluation of healthcare interventions that aim to increase precision but may introduce bias if missing data are heavily unbalanced between costs and outcomes

“Attending to History” in Major System Change in Healthcare in England: Specialist Cancer Surgery Service Reconfiguration

BACKGROUND: The reconfiguration of specialist hospital services, with service provision concentrated in a reduced number of sites, is one example of major system change (MSC) for which there is evidence of improved patient outcomes. This paper explores the reconfiguration of specialist oesophago-gastric (OG) cancer surgery services in a large urban area of England (Greater Manchester, GM), with a focus on the role of history in this change process and how reconfiguration was achieved after previous failed attempts. METHODS: This study draws on qualitative research from a mixed-methods evaluation of the reconfiguration of specialist cancer surgery services in GM. Forty-six interviews with relevant stakeholders were carried out, along with ~160 hours of observations at meetings and the acquisition of ~300 pertinent documents. Thematic analysis using deductive and inductive approaches was undertaken, guided by a framework of 'simple rules' for MSC. RESULTS: Through an awareness of, and attention to, history, leaders developed a change process which took into account previous unsuccessful reconfiguration attempts, enabling them to reduce the impact of potentially challenging issues. Interviewees described attending to issues involving competition between provider sites, change leadership, engagement with stakeholders, and the need for a process of change resilient to challenge. CONCLUSION: Recognition of, and response to, history, using a range of perspectives, enabled this reconfiguration. Particularly important was the way in which history influenced and informed other aspects of the change process and the influence of stakeholder power. This study provides further learning about MSC and the need for a range of perspectives to enable understanding. It shows how learning from history can be used to enable successful change

METRIC-EF: magnetic resonance enterography to predict disabling disease in newly diagnosed Crohn's disease-protocol for a multicentre, non-randomised, single-arm, prospective study

INTRODUCTION: Crohn's disease (CD) is characterised by discontinuous, relapsing enteric inflammation. Instituting advanced therapies at an early stage to suppress inflammation aims to prevent future complications such as stricturing or penetrating disease, and subsequent surgical resection. Therapeutics are effective but associated with certain side-effects and relatively expensive. There is therefore an urgent need for robust methods to predict which newly diagnosed patients will develop disabling disease, to identify patients who are most likely to benefit from early, advanced therapies. We aim to determine if magnetic resonance enterography (MRE) features at diagnosis improve prediction of disabling CD within 5 years of diagnosis. METHODS AND ANALYSIS: We describe the protocol for a multicentre, non-randomised, single-arm, prospective study of adult patients with newly diagnosed CD. We will use patients already recruited to the METRIC study and extend their clinical follow-up, as well as a separate group of newly diagnosed patients who were not part of the METRIC trial (MRE within 3 months of diagnosis), to ensure an adequate sample size. Follow-up will extend for at least 4 years. The primary outcome is to evaluate the comparative predictive ability of prognostic models incorporating MRE severity scores (Magnetic resonance Enterography Global Score (MEGS), simplified MAgnetic Resonance Index of Activity (sMaRIA) and Lémann Index) versus models using standard characteristics alone to predict disabling CD (modified Beaugerie definition) within 5 years of new diagnosis. ETHICS AND DISSEMINATION: This study protocol achieved National Health Service Research Ethics Committee (NHS REC), London-Hampstead Research Ethics Committee approval (IRAS 217422). Our findings will be disseminated via conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: ISRCTN76899103

Expert panel process to optimise the design of a randomised controlled trial in chronic rhinosinusitis (the MACRO programme).

BACKGROUND: MACRO (Defining best Management for Adults with Chronic RhinOsinusitis) is an NIHR-funded programme of work designed to establish best practice for adults with chronic rhinosinusitis (CRS). The 7-year programme comprises three consecutive workstreams, designed to explore NHS care pathways through analysis of primary and secondary data sources, and to undertake a randomised controlled trial to evaluate a longer-term course of macrolide antibiotics and endoscopic sinus surgery for patients with CRS. A number of outstanding elements still required clarification at the funding stage. This paper reports an expert panel review process designed to agree and finalise the MACRO trial design, ensuring relevance to patients and clinicians whilst maximising trial recruitment and retention. METHODS: An expert panel, consisting of the MACRO Programme Management Group, independent advisors, and patient contributors, was convened to review current evidence and the mixed-method data collected as part of the programme, and reach agreement on MACRO trial design. Specifically, agreement was sought for selection of macrolide antibiotic, use of orally administered steroids, inclusion of CRS phenotypes (with/without nasal polyps), and overall trial design. RESULTS: A 12-week course of clarithromycin was agreed as the main trial comparator due to its increasing use as a first- and second-line treatment for patients with CRS, and the perceived need to establish its role in CRS management. Orally administered steroids will be used as a rescue medication during the trial, rather than routinely either pre or post trial randomisation, to limit any potential effects on surgical outcomes and better reflect current UK prescribing habits. Both CRS phenotypes will be included in a single trial to ensure that the MACRO trial is both pragmatic and generalisable to primary care. A modified, three-arm trial design was agreed after intense discussions and further exploratory work. Inclusion criteria were amended to ensure that the patients recruited would be considered eligible for the treatment offered in the trial due to having already received appropriate medical therapy as deemed suitable by their ENT surgeon. A proposed 6-week run-in period prior to randomisation was removed due to the new criteria prior to randomisation. CONCLUSION: The expert panel review process resulted in agreement on key elements and an optimal design for the MACRO trial, considered most likely to be successful in terms of both recruitment potential and ability to establish best management of patients with CRS

Comparing biparametric to multiparametric MRI in the diagnosis of clinically significant prostate cancer in biopsy-naive men (PRIME): a prospective, international, multicentre, non-inferiority within-patient, diagnostic yield trial protocol

INTRODUCTION: Prostate MRI is a well-established tool for the diagnostic work-up for men with suspected prostate cancer (PCa). Current recommendations advocate the use of multiparametric MRI (mpMRI), which is composed of three sequences: T2-weighted sequence (T2W), diffusion-weighted sequence (DWI) and dynamic contrast-enhanced sequence (DCE). Prior studies suggest that a biparametric MRI (bpMRI) approach, omitting the DCE sequences, may not compromise clinically significant cancer detection, though there are limitations to these studies, and it is not known how this may affect treatment eligibility. A bpMRI approach will reduce scanning time, may be more cost-effective and, at a population level, will allow more men to gain access to an MRI than an mpMRI approach. METHODS: Prostate Imaging Using MRI±Contrast Enhancement (PRIME) is a prospective, international, multicentre, within-patient diagnostic yield trial assessing whether bpMRI is non-inferior to mpMRI in the diagnosis of clinically significant PCa. Patients will undergo the full mpMRI scan. Radiologists will be blinded to the DCE and will initially report the MRI using only the bpMRI (T2W and DWI) sequences. They will then be unblinded to the DCE sequence and will then re-report the MRI using the mpMRI sequences (T2W, DWI and DCE). Men with suspicious lesions on either bpMRI or mpMRI will undergo prostate biopsy. The main inclusion criteria are men with suspected PCa, with a serum PSA of ≤20 ng/mL and without prior prostate biopsy. The primary outcome is the proportion of men with clinically significant PCa detected (Gleason score ≥3+4 or Gleason grade group ≥2). A sample size of at least 500 patients is required. Key secondary outcomes include the proportion of clinically insignificant PCa detected and treatment decision. ETHICS AND DISSEMINATION: Ethical approval was obtained from the National Research Ethics Committee West Midlands, Nottingham (21/WM/0091). Results of this trial will be disseminated through peer-reviewed publications. Participants and relevant patient support groups will be informed about the results of the trial

Risk of mortality and cardiovascular events following macrolide prescription in chronic rhinosinusitis patients: a cohort study using linked primary care electronic health records

Background: Macrolide antibiotics have demonstrated important anti-inflammatory and immunomodulatory properties in chronic rhinosinusitis (CRS) patients. However, reports of increased risks of cardiovascular events have led to safety concerns. We investigated the risk of all-cause and cardiac death, and cardiovascular outcomes, associated with macrolide use. Methodology: Observational cohort (1997-2016) using linked data from the Clinical Practice Research Datalink, Hospital Episodes Statistics, and the Office for National Statistics. Patients aged 16-80 years with CRS prescribed a macrolide antibiotic or penicillin were included, comparing prescriptions for macrolide antibiotics to penicillin. Outcomes were all-cause mortality, cardiac death, myocardial infarction, stroke, diagnosis of peripheral vascular disease, and cardiac arrhythmia. Results: Analysis included 320,798 prescriptions received by 66,331 patients. There were 3,251 deaths, 815 due to cardiovascular causes, 925 incident myocardial infarctions, 859 strokes, 637 diagnoses of peripheral vascular disease, and 1,436 cardiac arrhythmias. A non-statistically significant trend towards increased risk of myocardial infarction during the first 30 days following macrolide prescription was observed (fully adjusted hazard ratio 1.60, 95% confidence interval: 0.95, 2.68, p=0.08). No statistically significant short- or long-term risks were observed for macrolide prescription. No significant risks were identified for clarithromycin in particular. Conclusions: Although not statistically significant, our best estimates suggest an increased short-term risk of myocardial infarction in patients with CRS following macrolide prescription, supporting previous observational evidence. However, confounding by indication remains a possible explanation for this apparent increased risk. We found no evidence of longer term increased risks

How Can I Drink Safely?; Perception Versus the Reality of Alcohol Consumption

This article investigates differences between perception and actual consumption of alcohol in young adults within the UK, suggesting that inaccurate information in the public domain may hamper those seeking to drink safely plus the development of moderate drinking cultures. Results confirm that inaccurate information may be preventing the development of safe drinking behaviours among certain groups. In addition, they indicate that some groups choose to ignore safe consumption limits in particular circumstances. Results indicate that many government strategies aimed at reducing unsafe drinking behaviour are inaccurately targeted; changing male public consumption behaviour may trigger changes in female behaviour