Can different primary care databases produce comparable estimates of burden of disease: results of a study exploring venous leg ulceration

Background. Primary care databases from the UK have been widely used to produce evidence on the epidemiology and health service usage of a wide range of conditions. To date there have been few evaluations of the comparability of estimates between different sources of these data. Aim. To estimate the comparability of two widely used primary care databases, the Health Improvement Network Database (THIN) and the General Practice Research Database (GPRD) using venous leg ulceration as an exemplar condition. Design of study. Cross prospective cohort comparison. Setting. GPRD and the THIN databases using data from 1998 to 2006. Method. A data set was extracted from both databases containing all cases of persons aged 20 years or greater with a database diagnosis of venous leg ulceration recorded in the databases for the period 1998–2006. Annual rates of incidence and prevalence of venous leg ulceration were calculated within each database and standardized to the European standard population and compared using standardized rate ratios. Results. Comparable estimates of venous leg ulcer incidence from the GPRD and THIN databases could be obtained using data from 2000 to 2006 and of prevalence using data from 2001 to 2006. Conclusions. Recent data collected by these two databases are more likely to produce comparable results of the burden venous leg ulceration. These results require confirmation in other disease areas to enable researchers to have confidence in the comparability of findings from these two widely used primary care research resources

What promotes or prevents greater use of appropriate compression in people with venous leg ulcers? A qualitative interview study with nurses in the north of England using the Theoretical Domains Framework

OBJECTIVES: To investigate factors that promote and prevent the use of compression therapy in people with venous leg ulcers. DESIGN: Qualitative interview study with nurses using the Theoretical Domains Framework (TDF). SETTING: Three National Health Service Trusts in England. PARTICIPANTS: Purposive sample of 15 nurses delivering wound care. RESULTS: Nurses described factors which made provision of compression therapy challenging. Organisational barriers (TDF domains environmental context and resources/knowledge, skills/behavioural regulation) included heavy/increasing caseloads; lack of knowledge/skills and the provision of training; and prescribing issues (variations in bandaging systems/whether nurses could prescribe). Absence of specialist leg ulcer services to refer patients into was perceived as a barrier to providing optimal care by some community-based nurses. Compression use was perceived to be facilitated by clinics for timely initial assessment; continuity of staff and good liaison between vascular/leg ulcer clinics and community teams; clear local policies and care pathways; and opportunities for training such as ‘shadowing’ in vascular/leg ulcer clinics. Patient engagement barriers (TDF domains goals/beliefs about consequences) focused on getting patients ‘on board’ with compression, and supporting them in using it. Clear explanations were seen as key in promoting compression use. CONCLUSIONS: Rising workload pressures present significant challenges to enhancing leg ulcer services. There may be opportunities to develop facilitated approaches to enable community nursing teams to make changes to practice, enhancing quality of patient care. The majority of venous leg ulcers could be managed in the community without referral to specialist community services if issues relating to workloads/skills/training are addressed. Barriers to promoting compression use could also be targeted, for example, through the development of clear patient information leaflets. While the patient engagement barriers may be easier/quicker to address than organisational barriers, unless organisational barriers are addressed it seems unlikely that all people who would benefit from compression therapy will receive it

Compression hosiery to avoid post-thrombotic syndrome (CHAPS) protocol for a randomised controlled trial (ISRCTN73041168)

Introduction: Up to 50% of patients develop post-thrombotic syndrome (PTS) after an above knee deep vein thrombosis (DVT). The aim of the study was to determine the effect of graduated compression stockings in preventing PTS after DVT. Methods and analysis: Pragmatic, UK multicentre randomised trial in adults with first above knee DVT. The standard of care arm is anticoagulation. The intervention arm will receive anticoagulation plus stockings (European class II, 23–32 mm Hg compression) worn for a median of 18 months. The primary endpoint is PTS using the Villalta score. Analysis of this will be through a time to event approach and cumulative incidence at median 6, 12 and 18 months. An ongoing process evaluation will examine factors contributing to adherence to stockings to understand if and how the behavioural interventions were effective. Ethics and dissemination: UK research ethics committee approval (reference 19/LO/1585). Dissemination though the charity Thrombosis UK, the Imperial College London website, peer-reviewed publications and international conferences. Trial registration number: ISRCTN registration number 73041168

The effect of a patient centred care bundle intervention on pressure ulcer incidence (INTACT): a cluster randomised trial

Background: Hospital-acquired pressure ulcers are a serious patient safety concern, associated with poor patient outcomes and high healthcare costs. They are also viewed as an indicator of nursing care quality. Objective: To evaluate the effectiveness of a pressure ulcer prevention care bundle in preventing hospital-acquired pressure ulcers among at risk patients. Design: Pragmatic cluster randomised trial. Setting: Eight tertiary referral hospitals with >200 beds each in three Australian states. Participants: 1600 patients (200/hospital) were recruited. Patients were eligible if they were: ≥18 years old; at risk of pressure ulcer because of limited mobility; expected to stay in hospital ≥48 h and able to read English. Methods: Hospitals (clusters) were stratified in two groups by recent pressure ulcer rates and randomised within strata to either a pressure ulcer prevention care bundle or standard care. The care bundle was theoretically and empirically based on patient participation and clinical practice guidelines. It was multi-component, with three messages for patients’ participation in pressure ulcer prevention care: keep moving; look after your skin; and eat a healthy diet. Training aids for patients included a DVD, brochure and poster. Nurses in intervention hospitals were trained in partnering with patients in their pressure ulcer prevention care. The statistician, recruiters, and outcome assessors were blinded to group allocation and interventionists blinded to the study hypotheses, tested at both the cluster and patient level. The primary outcome, incidence of hospital-acquired pressure ulcers, which applied to both the cluster and individual participant level, was measured by daily skin inspection. Results: Four clusters were randomised to each group and 799 patients per group analysed. The intraclass correlation coefficient was 0.035. After adjusting for clustering and pre-specified covariates (age, pressure ulcer present at baseline, body mass index, reason for admission, residence and number of comorbidities on admission), the hazard ratio for new pressure ulcers developed (pressure ulcer prevention care bundle relative to standard care) was 0.58 (95% CI: 0.25, 1.33; p = 0.198). No adverse events or harms were reported. Conclusions: Although the pressure ulcer prevention care bundle was associated with a large reduction in the hazard of ulceration, there was a high degree of uncertainty around this estimate and the difference was not statistically significant. Possible explanations for this non-significant finding include that the pressure ulcer prevention care bundle was effective but the sample size too small to detect this

INTroducing A Care bundle To prevent pressure injury (INTACT) in at-risk patients: A protocol for a cluster randomised trial

Background Pressure injuries are a significant clinical and economic issue, affecting both patients and the health care system. Many pressure injuries in hospitals are facility acquired, and are largely preventable. Despite growing evidence and directives for pressure injury prevention, implementation of preventative strategies is suboptimal, and pressure injuries remain a serious problem in hospitals. Objectives This study will test the effectiveness and cost-effectiveness of a patient-centred pressure injury prevention care bundle on the development of hospital acquired pressure injury in at-risk patients. Design This is a multi-site, parallel group cluster randomised trial. The hospital is the unit of randomisation. Methods Adult medical and surgical patients admitted to the study wards of eight hospitals who are (a) deemed to be at risk of pressure injury (i.e. have reduced mobility), (b) expected to stay in hospital for ≥48 h, (c) admitted to hospital in the past 36 h; and (d) able to provide informed consent will be eligible to participate. Consenting patients will receive either the pressure injury prevention care bundle or standard care. The care bundle contains three main messages: (1) keep moving; (2) look after your skin; and (3) eat a healthy diet. Nurses will receive education about the intervention. Patients will exit the study upon development of a pressure injury, hospital discharge or 28 days, whichever comes first; transfer to another hospital or transfer to critical care and mechanically ventilated. The primary outcome is incidence of hospital acquired pressure injury. Secondary outcomes are pressure injury stage, patient participation in care and health care costs. A health economic sub-study and a process evaluation will be undertaken alongside the trial. Data will be analysed at the cluster (hospital) and patient level. Estimates of hospital acquired pressure injury incidence in each group, group differences and 95% confidence interval and p values will be reported. Discussion To our knowledge, this is the first trial of an intervention to incorporate a number of pressure injury prevention strategies into a care bundle focusing on patient participation and nurse–patient partnership. The results of this study will provide important information on the effectiveness and cost-effectiveness of this intervention in preventing pressure injuries in at-risk patients. If the results confirm the utility of the developed care bundle, it could have a significant impact on clinical practice worldwide

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

Pressure ulcers

Unrelieved pressure or friction of the skin, particularly over bony prominences, can lead to pressure ulcers, which affect up to a third of people in hospitals or community care, and a fifth of nursing-home residents. Pressure ulcers are more likely in people with reduced mobility and poor skin condition, such as older people or those with vascular disease