Impact of policy support on uptake of evidence-based continuous quality improvement activities and the quality of care for Indigenous Australians: a comparative case study.

Objectives: To examine the impact of state/territory policy support on (1) uptake of evidence-based continuous quality improvement (CQI) activities and (2) quality of care for Indigenous Australians. Design: Mixed-method comparative case study methodology, drawing on quality-of-care audit data, documentary evidence of policies and strategies and the experience and insights of stakeholders involved in relevant CQI programmes. We use multilevel linear regression to analyse jurisdictional differences in quality of care. Setting: Indigenous primary healthcare services across five states/territories of Australia. Participants: 175 Indigenous primary healthcare services. Interventions: A range of national and state/territory policy and infrastructure initiatives to support CQI, including support for applied research. Primary and secondary outcome measures: (i) Trends in the consistent uptake of evidence-based CQI tools available through a research-based CQI initiative (the Audit and Best Practice in Chronic Disease programme) and (ii) quality of care (as reflected in adherence to best practice guidelines). Results: Progressive uptake of evidence-based CQI activities and steady improvements or maintenance of high-quality care occurred where there was long-term policy and infrastructure support for CQI. Where support was provided but not sustained there was a rapid rise and subsequent fall in relevant CQI activities. Conclusions: Health authorities should ensure consistent and sustained policy and infrastructure support for CQI to enable wide-scale and ongoing improvement in quality of care and, subsequently, health outcomes. It is not sufficient for improvement initiatives to rely on local service managers and clinicians, as their efforts are strongly mediated by higher system-level influences

Genome-wide association study of endometrial cancer in E2C2

Endometrial cancer (EC), a neoplasm of the uterine epithelial lining, is the most common gynecological malignancy in developed countries and the fourth most common cancer among US women. Women with a family history of EC have an increased risk for the disease, suggesting that inherited genetic factors play a role. We conducted a two-stage genome-wide association study of Type I EC. Stage 1 included 5,472 women (2,695 cases and 2,777 controls) of European ancestry from seven studies. We selected independent single-nucleotide polymorphisms (SNPs) that displayed the most significant associations with EC in Stage 1 for replication among 17,948 women (4,382 cases and 13,566 controls) in a multiethnic population (African America, Asian, Latina, Hawaiian and European ancestry), from nine studies. Although no novel variants reached genome-wide significance, we replicated previously identified associations with genetic markers near the HNF1B locus. Our findings suggest that larger studies with specific tumor classification are necessary to identify novel genetic polymorphisms associated with EC susceptibility. Electronic supplementary material The online version of this article (doi:10.1007/s00439-013-1369-1) contains supplementary material, which is available to authorized users

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

An "all teach, all learn" approach to research capacity strengthening in Indigenous primary health care continuous quality improvement

In Australia, Indigenous people experience poor access to health care and the highest rates of morbidity and mortality of any population group. Despite modest improvements in recent years, concerns remains that Indigenous people have been over-researched without corresponding health improvements. Embedding Indigenous leadership, participation, and priorities in health research is an essential strategy for meaningful change for Indigenous people. To centralize Indigenous perspectives in research processes, a transformative shift away from traditional approaches that have benefited researchers and non-Indigenous agendas is required. This shift must involve concomitant strengthening of the research capacity of Indigenous and non-Indigenous researchers and research translators-all must teach and all must learn. However, there is limited evidence about how to strengthen systems and stakeholder capacity to participate in and lead continuous quality improvement (CQI) research in Indigenous primary health care, to the benefit of Indigenous people. This paper describes the collaborative development of, and principles underpinning, a research capacity strengthening (RCS) model in a national Indigenous primary health care CQI research network. The development process identified the need to address power imbalances, cultural contexts, relationships, systems requirements and existing knowledge, skills, and experience of all parties. Taking a strengths-based perspective, we harnessed existing knowledge, skills and experiences; hence our emphasis on capacity "strengthening". New insights are provided into the complex processes of RCS within the context of CQI in Indigenous primary health care

An “All Teach, All Learn” Approach to Research Capacity Strengthening in Indigenous Primary Health Care Continuous Quality Improvement

In Australia, Indigenous people experience poor access to health care and the highest rates of morbidity and mortality of any population group. Despite modest improvements in recent years, concerns remains that Indigenous people have been over-researched without corresponding health improvements. Embedding Indigenous leadership, participation, and priorities in health research is an essential strategy for meaningful change for Indigenous people. To centralize Indigenous perspectives in research processes, a transformative shift away from traditional approaches that have benefited researchers and non-Indigenous agendas is required. This shift must involve concomitant strengthening of the research capacity of Indigenous and non-Indigenous researchers and research translators—all must teach and all must learn. However, there is limited evidence about how to strengthen systems and stakeholder capacity to participate in and lead continuous quality improvement (CQI) research in Indigenous primary health care, to the benefit of Indigenous people. This paper describes the collaborative development of, and principles underpinning, a research capacity strengthening (RCS) model in a national Indigenous primary health care CQI research network. The development process identified the need to address power imbalances, cultural contexts, relationships, systems requirements and existing knowledge, skills, and experience of all parties. Taking a strengths-based perspective, we harnessed existing knowledge, skills and experiences; hence our emphasis on capacity “strengthening”. New insights are provided into the complex processes of RCS within the context of CQI in Indigenous primary health care