An Intervention for Pulmonary Rehabilitators to Develop a Social Identity for Patients Attending Exercise Rehabilitation: A Feasibility and Pilot Randomised Control Trial Protocol

Background: Chronic obstructive pulmonary disease (COPD) is a degenerative condition that can impair health related quality of life (HRQoL). A number of self-management interventions, employing a variety of behavioural change techniques (BCTs), have been adopted to improve HRQoL for COPD patients. However, a lack of attention has been given to group management interventions with an emphasis on incorporating BCTs into rehabilitators practice. This study aims to pilot and feasibly explore a social identity group- management intervention, delivered by COPD rehabilitation staff to patients attending exercise pulmonary rehabilitation. Doing so will help inform the plausibility of the intervention before conducting a full trial to evaluate its effectiveness to improve HRQoL. Methods: This is a two center, randomized cross-over controlled trial. Two pulmonary rehabilitation centres based in the UK will be randomly allocated to two treatment arms (standard care and intervention). Outcome measurements relating to HRQoL and social identity will be completed pre and post exercise rehabilitation. Focus group interviews will be conducted at the end of exercise rehabilitation to capture participants’ contextualised experiences of the intervention. COPD rehabilitators will undertake semi-structured interviews at the end of the trial to garner their holistic perspectives of intervention fidelity and implementation. Discussion: This is the first study to adopt a social identity approach to develop a rehabilitator-led, group management intervention for COPD patients attending exercise pulmonary rehabilitation. The results of this study will provide evidence for the feasibility and sample size requirements to inform a larger study, which can ascertain the intervention’s effectiveness for improving HRQoL for COPD patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02288039. Date 31st October 2014

Impact of community-based chronic obstructive pulmonary disease service, a multidisciplinary intervention in an area of high deprivation: A longitudinal matched controlled study

Objective: To examine the effects of a consultant-led, community-based chronic obstructive pulmonary disease (COPD) service, based in a highly deprived area on emergency hospital admissions. Design: A longitudinal matched controlled study using difference-in-differences analysis to compare the change in outcomes in the intervention population to a matched comparison population, five years before and after implementation. Setting: A deprived district in the North West of England between 2005 and 2016. Intervention: A community-based, consultant-led COPD service providing diagnostics, treatment and rehabilitation from 2011–2016. Main outcome measures: Emergency hospital admissions, length of stay per emergency admission, and emergency re-admissions for COPD. Results: The intervention was associated with 24 fewer emergency COPD admissions per 100,000 population per year (95%CI -10.6 to 58.8, p=0.17) in the post-intervention period, relative to the control group. There were significantly fewer emergency admissions in populations with medium levels of deprivation (64 per 100,000 per year; 95%CI 1.8 to 126.9) and amongst men (60 per 100,000 per year; 95%CI 12.3 to 107.3). Conclusion: We found limited evidence that the service reduced emergency hospital admissions, after an initial decline the effect was not sustained. The service, however, may have been more effective in some subgroups

Adult-type granulosa cell tumor of the ovary : a FOXL2-centric disease

Adult-type granulosa cell tumors (aGCTs) account for 90% of malignant ovarian sex cord-stromal tumors and 2-5% of all ovarian cancers. These tumors are usually diagnosed at an early stage and are treated with surgery. However, one-third of patients relapse between 4 and 8 years after initial diagnosis, and there are currently no effective treatments other than surgery for these relapsed patients. As the majority of aGCTs (>95%) harbor a somatic mutation in FOXL2 (c.C402G; p.C134W), the aim of this study was to identify genetic mutations besides FOXL2 C402G in aGCTs that could explain the clinical diversity of this disease. Whole-genome sequencing of 10 aGCTs and their matched normal blood was performed to identify somatic mutations. From this analysis, a custom amplicon-based panel was designed to sequence 39 genes of interest in a validation cohort of 83 aGCTs collected internationally. KMT2D inactivating mutations were present in 10 of 93 aGCTs (10.8%), and the frequency of these mutations was similar between primary and recurrent aGCTs. Inactivating mutations, including a splice site mutation in candidate tumor suppressor WNK2 and nonsense mutations in PIK3R1 and NLRC5, were identified at a low frequency in our cohort. Missense mutations were identified in cell cycle-related genes TP53, CDKN2D, and CDK1. From these data, we conclude that aGCTs are comparatively a homogeneous group of tumors that arise from a limited set of genetic events and are characterized by the FOXL2 C402G mutation. Secondary mutations occur in a subset of patients but do not explain the diverse clinical behavior of this disease. As the FOXL2 C402G mutation remains the main driver of this disease, progress in the development of therapeutics for aGCT would likely come from understanding the functional consequences of the FOXL2 C402G mutation.Peer reviewe

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability