Protocol for a mixed-methods exploratory investigation of care following intensive care discharge: the REFLECT study

© Author(s) 2019. Re-use permitted under CC BY. Published by BMJ.INTRODUCTION: A substantial number of patients discharged from intensive care units (ICUs) subsequently die without leaving hospital. It is unclear how many of these deaths are preventable. Ward-based management following discharge from ICU is an area that patients and healthcare staff are concerned about. The primary aim of REFLECT (Recovery Following Intensive Care Treatment) is to develop an intervention plan to reduce in-hospital mortality rates in patients who have been discharged from ICU. METHODS AND ANALYSIS: REFLECT is a multicentre mixed-methods exploratory study examining ward care delivery to adult patients discharged from ICU. The study will be made up of four substudies. Medical notes of patients who were discharged from ICU and subsequently died will be examined using a retrospective case records review (RCRR) technique. Patients and their relatives will be interviewed about their post-ICU care, including relatives of patients who died in hospital following ICU discharge. Staff involved in the care of patients post-ICU discharge will be interviewed about the care of this patient group. The medical records of patients who survived their post-ICU stay will also be reviewed using the RCRR technique. The analyses of the substudies will be both descriptive and use a modified grounded theory approach to identify emerging themes. The evidence generated in these four substudies will form the basis of the intervention development, which will take place through stakeholder and clinical expert meetings. ETHICS AND DISSEMINATION: Ethical approval has been obtained through the Wales Research and Ethics Committee 4 (17/WA/0107). We aim to disseminate the findings through international conferences, international peer-reviewed journals and social media. TRIAL REGISTRATION NUMBER: ISRCTN14658054.Peer reviewedFinal Published versio

Outcomes following the surgical management of left ventricular outflow tract obstruction; A systematic review and meta-analysis

BACKGROUND: Left ventricular outflow tract obstruction (LVOTO) causes exertional symptoms in two thirds of patients with hypertrophic cardiomyopathy (HCM). Consensus guidelines recommend surgical intervention in patients with drug refractory symptoms. The primary aim of this study was to perform a systematic review and meta-analysis to determine morbidity and mortality after surgery. METHODS: Study Selection: Studies reporting outcomes following surgical intervention for symptomatic LVOTO in HCM. RESULTS: 85 studies were included in the systematic review and 35 studies in the meta-analysis. Contemporary early (30 days) mortality following septal myectomy were 1.4% (CI 0.8, 2.4) I^{2} 9.0%, p = 0.36 and 0.7% (CI 0.3, 1.2) I^{2} 70.7%, p < 0.05 respectively. Sixty-eight studies (80%) reported perioperative complications. The contemporary rate of a perioperative ventricular septal defect was 1.4% (0.8, 2.3) I^{2} 0%, p < 0.05. Late morbidities including atrial fibrillation, stroke, heart failure and transplant were reported in fewer than 22% of studies and few studies compared mortality and clinical outcomes using different surgical approaches to LVOTO. The incidence rate (IR) of reintervention with a further surgical procedure was 0.3% (CI 0.2, 0.4) I^{2} 52.5%, p < 0.05. CONCLUSIONS: Contemporary surgical management of LVOTO is associated with low operative mortality rates but further studies are needed to investigate the impact of surgical therapy on non-fatal early and late complications

A Data Trust for Industry Data Sharing

This document is an extract from the report Building a Trusted Framework for Coordinating OA Monograph Usage Data, which forms part of the Andrew W. Mellon Foundation funded project, Understanding OA Ebook Usage: Toward a Common Framework

Predicting in-hospital mortality and unanticipated admissions to the intensive care unit using routinely collected blood tests and vital signs: development and validation of a multivariable model.

AIM: The National Early Warning System (NEWS) is based on vital signs; the Laboratory Decision Tree Early Warning Score (LDT-EWS) on laboratory test results. We aimed to develop and validate a new EWS (the LDTEWS:NEWS risk index) by combining the two and evaluating the discrimination of the primary outcome of unanticipated intensive care unit (ICU) admission or in-hospital mortality, within 24 hours. METHODS: We studied emergency medical admissions, aged 16 years or over, admitted to Oxford University Hospitals (OUH) and Portsmouth Hospitals (PH). Each admission had vital signs and laboratory tests measured within their hospital stay. We combined LDT-EWS and NEWS values using a linear time-decay weighting function imposed on the most recent blood tests. The LDTEWS:NEWS risk index was developed using data from 5 years of admissions to PH, and validated on a year of data from both PH and OUH. We tested the risk index's ability to discriminate the primary outcome using the c-statistic. RESULTS: The development cohort contained 97,933 admissions (median age = 73 years) of which 4,723 (4.8%) resulted in in-hospital death and 1,078 (1.1%) in unanticipated ICU admission. We validated the risk index using data from PH (n = 21,028) and OUH (n = 16,383). The risk index showed a higher discrimination in the validation sets (c-statistic value (95% CI)) (PH, 0.901 (0.898-0.905); OUH, 0.916 (0.911-0.921)), than NEWS alone (PH, 0.877 (0.873-0.882); OUH, 0.898 (0.893-0.904)). CONCLUSIONS: The LDTEWS:NEWS risk index increases the ability to identify patients at risk of deterioration, compared to NEWS alone

Evaluation of a training program for device operators in the Australian Government's Point of Care Testing in General Practice Trial: issues and implications for rural and remote practices

From September 2005 to February 2007 the Australian Government funded the Point of Care Testing (PoCT) in General Practice Trial, a multi-centre, cluster randomised controlled trial to determine the safety, clinical effectiveness, cost-effectiveness and satisfaction of PoCT in General Practice. In total, 53 practices (23 control and 30 intervention) based in urban, rural or remote locations across three states (South Australia [SA], New South Wales [NSW] and Victoria [VIC]) participated in the Trial. Control practices had pathology testing performed by their local laboratory, while intervention practices conducted pathology testing by PoCT. In total, 4968 patients (1958 control and 3010 intervention) participated in the Trial. The point-of-care (PoC) tests performed by intervention practices were: haemoglobin A1c (HbA1c) and urine albumin:creatinine ratio (ACR) on patients with diabetes, total cholesterol, triglyceride and high density lipoprotein (HDL) cholesterol on patients with hyperlipidaemia, and international normalised ratio (INR) on patients on anticoagulant therapy. Three PoCT devices measured these tests: the Siemens DCA 2000 (Siemens HealthCare Diagnostics, Melbourne, VIC, Australia) for HbA1c and urine ACR; Point of Care Diagnostics Cholestech LDX analyser (Point of Care Diagnostics; Sydney, NSW, Australia) for lipids; and the Roche CoaguChek S (Roche Diagnostics; Sydney, NSW, Australia) for INR. Point-of-care testing in the General Practice Trial was underpinned by a quality management framework which included an on-going training and competency program for PoCT device operators. This article describes the design, implementation and results of the training and competency program

Gridded and direct Epoch of Reionisation bispectrum estimates using the Murchison Widefield Array

We apply two methods to estimate the 21~cm bispectrum from data taken within the Epoch of Reionisation (EoR) project of the Murchison Widefield Array (MWA). Using data acquired with the Phase II compact array allows a direct bispectrum estimate to be undertaken on the multiple redundantly-spaced triangles of antenna tiles, as well as an estimate based on data gridded to the $uv$-plane. The direct and gridded bispectrum estimators are applied to 21 hours of high-band (167--197~MHz; $z$=6.2--7.5) data from the 2016 and 2017 observing seasons. Analytic predictions for the bispectrum bias and variance for point source foregrounds are derived. We compare the output of these approaches, the foreground contribution to the signal, and future prospects for measuring the bispectra with redundant and non-redundant arrays. We find that some triangle configurations yield bispectrum estimates that are consistent with the expected noise level after 10 hours, while equilateral configurations are strongly foreground-dominated. Careful choice of triangle configurations may be made to reduce foreground bias that hinders power spectrum estimators, and the 21~cm bispectrum may be accessible in less time than the 21~cm power spectrum for some wave modes, with detections in hundreds of hours.Comment: 19 pages, 10 figures, accepted for publication in PAS

A new human chromogranin A (CgA) immunoradiometric assay involving monoclonal antibodies raised against the unprocessed central domain (145-245)

Chromogranin A (CgA), a major protein of chromaffin granules, has been described as a potential marker for neuroendocrine tumours. Because of an extensive proteolysis which leads to a large heterogeneity of circulating fragments, its presence in blood has been assessed in most cases either by competitive immunoassays or with polyclonal antibodies. In the present study, 24 monoclonal antibodies were raised against native or recombinant human CgA. Their mapping with proteolytic peptides showed that they defined eight distinct epitopic groups which spanned two-thirds of the C-terminal part of human CgA. All monoclonal antibodies were tested by pair and compared with a reference radioimmunoassay (RIA) involving CGS06, one of the monoclonal antibodies against the 198–245 sequence. It appears that CgA C-terminal end seems to be highly affected by proteolysis and the association of C-terminal and median-part monoclonal antibodies is inadequate for total CgA assessment. Our new immunoradiometric assay involves two monoclonal antibodies, whose contiguous epitopes lie within the median 145–245 sequence. This assay allows a sensitive detection of total human CgA and correlates well with RIA because dibasic cleavage sites present in the central domain do not seem to be affected by degradation. It has been proved to be efficient in measuring CgA levels in patients with neuroendocrine tumours. © 1999 Cancer Research Campaig

Rehabilitation following rotator cuff repair: A systematic review

Background: The aim of this systematic review was to evaluate the effectiveness of rehabilitation programmes following surgical repair of the rotator cuff with emphasis upon length of immobilisation and timing of introduction of load. Methods: An electronic search of CENTRAL, MEDLINE and PEDro was undertaken to August 2014 and supplemented by hand searching. Randomised controlled trials were included, quality appraised using the PEDro scale and synthesised via meta-analysis or narrative synthesis, based upon levels of evidence, where appropriate. Results: Twelve studies were included. There is strong evidence that early initiation of rehabilitation does not adversely affect clinical outcome but there is a marginally higher, statistically non-significant, incidence of tendon re-tear (OR 1.3; 95% CI 0.72 to 2.2). There is strong evidence that initiation of functional loading early in the rehabilitation programme does not adversely affect clinical outcome. Discussion: Concern about early initiation of rehabilitation and introduction of gradual functional load does not appear warranted but this should be considered in a context of potential for Type II error. There is further need to evaluate approaches that foster early initiation of rehabilitation and gradual introduction of functional load as well as considering key outcomes such as return to work

An Integrative -omics Approach to Identify Functional Sub-Networks in Human Colorectal Cancer

Emerging evidence indicates that gene products implicated in human cancers often cluster together in “hot spots” in protein-protein interaction (PPI) networks. Additionally, small sub-networks within PPI networks that demonstrate synergistic differential expression with respect to tumorigenic phenotypes were recently shown to be more accurate classifiers of disease progression when compared to single targets identified by traditional approaches. However, many of these studies rely exclusively on mRNA expression data, a useful but limited measure of cellular activity. Proteomic profiling experiments provide information at the post-translational level, yet they generally screen only a limited fraction of the proteome. Here, we demonstrate that integration of these complementary data sources with a “proteomics-first” approach can enhance the discovery of candidate sub-networks in cancer that are well-suited for mechanistic validation in disease. We propose that small changes in the mRNA expression of multiple genes in the neighborhood of a protein-hub can be synergistically associated with significant changes in the activity of that protein and its network neighbors. Further, we hypothesize that proteomic targets with significant fold change between phenotype and control may be used to “seed” a search for small PPI sub-networks that are functionally associated with these targets. To test this hypothesis, we select proteomic targets having significant expression changes in human colorectal cancer (CRC) from two independent 2-D gel-based screens. Then, we use random walk based models of network crosstalk and develop novel reference models to identify sub-networks that are statistically significant in terms of their functional association with these proteomic targets. Subsequently, using an information-theoretic measure, we evaluate synergistic changes in the activity of identified sub-networks based on genome-wide screens of mRNA expression in CRC. Cross-classification experiments to predict disease class show excellent performance using only a few sub-networks, underwriting the strength of the proposed approach in discovering relevant and reproducible sub-networks