Acute Kidney Injury in COVID-19: secondary analysis of prospective data from the EthICAL study

Statistical Analysis Plan – This secondary analysis of the EthICAL study will focus on the incidence, risk factors and outcomes associated with AKI within COVID-19 patients admitted to five acute hospitals in East London. We will also examine follow-up data to investigate what proportion of COVID-19 patients who developed an AKI never recovered their renal function and progressed to chronic kidney disease (CKD)

Comorbid disease and ethnicity in emergency hospital admissions in east London

Statistical Analysis Plan – This aim of this comparative study is to determine in a cohort of non-COVID emergency hospital admissions within the same representative population in east London, whether there is a difference in outcomes in patients of different ethnicities. It will test the hypothesis that patients of Black, Asian and other ethnicities have poorer outcomes defined using mortality and length of stay. Data generated has the potential to influence and shape relevant policy and practice to improve health outcomes in BAME communities

Biochemical estimation of muscle mass and unbiased assessment of kidney function using serum creatinine and cystatin-C: A prognostic validation study within UK Biobank

Statistical Analysis Plan – A proposal for the biochemical estimation of muscle mass and the unbiased assessment of kidney function using serum creatinine and cystatin-C: A prognostic validation study within UK Biobank

Subclinical cardiopulmonary dysfunction in stage 3 chronic kidney disease.

OBJECTIVE: Reduced exercise capacity is well documented in end-stage chronic kidney disease (CKD), preceded by changes in cardiac morphology in CKD stage 3. However, it is unknown whether subclinical cardiopulmonary dysfunction occurs in CKD stage 3 independently of heart failure. METHODS: Prospective observational cross-sectional study of exercise capacity assessed by cardiopulmonary exercise testing in 993 preoperative patients. Primary outcome was peak oxygen consumption (VO2peak). Anaerobic threshold (AT), oxygen pulse and exercise-evoked measures of autonomic function were analysed, controlling for CKD stage 3, age, gender, diabetes mellitus and hypertension. RESULTS: CKD stage 3 was present in 93/993 (9.97%) patients. Diabetes mellitus (RR 2.49 (95% CI 1.59 to 3.89); p<0.001), and hypertension (RR 3.20 (95% CI 2.04 to 5.03); p<0.001)) were more common in CKD stage 3. Cardiac failure (RR 0.83 (95% CI 0.30 to 2.24); p=0.70) and ischaemic heart disease (RR 1.40 (95% CI 0.97 to 2.02); p=0.09) were not more common in CKD stage 3. Patients with CKD stage 3 had lower predicted VO2peak (mean difference: 6% (95% CI 1% to 11%); p=0.02), lower peak heart rate (mean difference:9 bpm (95% CI 3 to 14); p=0.03)), lower AT (mean difference: 1.1 mL/min/kg (95% CI 0.4 to 1.7); p<0.001) and impaired heart rate recovery (mean difference: 4 bpm (95% CI 1 to 7); p<0.001)). CONCLUSIONS: Subclinical cardiopulmonary dysfunction in CKD stage 3 is common. This study suggests that maladaptive cardiovascular/autonomic dysfunction may be established in CKD stage 3, preceding pathophysiology reported in end-stage CKD

Sustainable Health Care Systems: An International Study

In many countries, the operation of the healthcare system is an important political issue and any changes to healthcare provision are often fiercely resisted by many stakeholders and can prove difficult to implement. Such changes to the organization and/or financing of healthcare may be necessitated by factors such as the continuing increase in service demands, the development of new medical science advances and the impact of financial and economic austerity across the globe. This paper considers how well the existing healthcare systems in eleven countries and across several continents are coping with various challenges, and looks at potential best practices. The general conclusion is that many such healthcare systems are unsustainable in the longer term and are in urgent need of reform

Socioeconomic deprivation and surgical outcomes: ISOS and VISION-UK sub-study (Statistical Analysis Plan)

In this paper, we aim to determine if socioeconomic deprivation in England is associated with outcomes after surgery: mortality, in-hospital complications at 30 days, and hospital length of stay. We will also identify clinical factors associated with social deprivation and assess whether adjustment for these factors modify the effect of socioeconomic deprivation on outcomes for a range of surgical categories

Perioperative blood transfusion is associated with a gene transcription profile characteristic of immunosuppression: a prospective cohort study

INTRODUCTION Blood transfusion in the perioperative period has frequently been associated with an excess of nosocomial infections. Whilst transfused whole blood induces specific host immune alteration that may predispose to nosocomial infections, the immunomodulating properties associated with leukodepleted blood remain incompletely understood. In this study, we explore the hypothesis that the transfusion of leukodepleted allogeneic blood during or following major gastrointestinal surgery is associated with an immunosuppressed phenotype, which may in turn predispose to postoperative infectious complications. METHODS Patients aged over 45 years undergoing scheduled inpatient major gastrointestinal surgery were recruited. Gene expression profiles of specific inflammatory genes were assayed from blood collected preoperatively, at 24 and at 48 hours after surgery. Genes were selected based on their ability to represent specific immune pathways. Gene expression was quantified using quantitative real-time polymerase chain reaction (qRT-PCR) to measure messenger RNA (mRNA) levels. Postoperative infections were documented using predefined criteria. RESULTS One hundred and nineteen patients were recruited. Fifteen (13%) patients required blood transfusion within 24 hours of surgery, 44 (37%) patients developed infections and 3 (2%) patients died prior to discharge. Patients receiving a blood transfusion were more likely to develop postoperative infections (P =0.02) and to have lower tumour necrosis factor alpha (TNFα), interleukin (IL)-12, IL-23 and RAR-related orphan receptor gamma T (RORγt) gene expression in the postoperative period (P <0.05). The TNFα/IL-10 mRNA ratio at 24 hours (P =0.0006) and at 48 hours (P =0.01) was lower in patients receiving a blood transfusion over this period. Multivariable analysis confirmed that these observations were independent of the severity of the surgical insult. CONCLUSIONS An association between an immunosuppressive pattern of gene expression and blood transfusion following major elective gastrointestinal surgery is described. This gene expression profile includes a reduction in the activity of innate immunity and T helper cell type 1 (Th1) and T helper cell type 17 (Th17) pathways in those patients receiving a blood transfusion. Blood transfusion was also associated with an excess of infectious complications in this cohort. A mechanistic link is suggested but not proven

Meeting the Escalating Demands for Health and Social Care Services of Elderly Populations in Developing Countries: a Strategic Perspective

Population ageing is a phenomenon affecting developed and developing countries alike and represents a major global challenge. This paper is concerned with the impact of ageing populations, in developing countries, on the future provision of health and social care services to the growing elderly population. As well as reviewing previous research and available data, the paper presents the findings of a series of qualitative interviews with policy makers and clinicians in a small number of developing countries in various parts of the world. The paper argues that developing countries cannot expect to see major increases in financial resources available to health and social care for the foreseeable future. Thus, the key issue is establishing how best the available public funding for delivering health and social care services to the elderly can best be used to maximize public value at a time when public services around the world face ongoing austerity measures. The paper focuses on a number of key strategic themes to achieve this which are as follows: the strengthening of public health infrastructure and capabilities; the reconfiguration of existing health systems; a stronger focus on elderly medicine as a distinct specialty; a strengthened role for mobile healthcare, particularly in rural areas; the development of models of generic health and social care assistants; the promotion of community based social care; the utilization of appropriate public/ private health care partnerships

Changes in gene expression following trauma are related to the age of transfused packed red blood cells

BACKGROUND Transfusion of packed red blood cells (PRBCs) is associated with an increased incidence of nosocomial infections and an increased risk of death. The duration of storage before transfusion may influence these outcomes. Here, we explore the association between the age of transfused PRBCs and specific patterns of inflammatory gene expression in severely injured trauma patients. METHODS Severely injured trauma patients requiring intensive care unit treatment and receiving transfusion of PRBCs within 24 hours of the injury were recruited. Blood samples were obtained within 2 hours of the trauma, at 24 hours, and at 72 hours. Messenger RNA was extracted from whole blood, and gene expression was quantified using quantitative polymerase chain reaction. The median age of the units of PRBCs transfused to each patient was recorded. The primary outcome measure was the change in candidate gene expression over the initial 72 hours. RESULTS Sixty-four patients were studied. Fifty-three patients (83%) were male, and the median age was 40.5 years (interquartile range [IQR], 31-59). Median Injury Severity Score (ISS) was 31.5 (IQR, 23-43), and 55 patients (86%) experienced a blunt injury. Forty-one patients (64%) developed a nosocomial infection, and 15 patients (23%) died before hospital discharge. Each patient received a median of 5 U of PRBCs (IQR, 4-9.8 U) during the first 24 hours of hospital admission. The median age of the units of PRBCs transfused in each patient was 20 days (IQR, 17-22 days). Older blood was associated with greater decreases in interleukin 12 (IL-12), IL-23, and RORγt (all p's < 0.05) gene expression over the initial 24 hours, greater decreases in IL-12 gene expression over 72 hours, and a rise in transforming growth factor β gene expression over the first 72 hours. A multivariate analysis confirmed the independence of these associations. CONCLUSION Increasing the duration of storage of PRBCs before transfusion is associated with a pattern of gene expression consistent with more severe immunosuppression. LEVEL OF EVIDENCE Epidemiologic study, level III