Women versus men with chronic atrial fibrillation: insights from the Standard versus Atrial Fibrillation spEcific managemenT studY (SAFETY)

BACKGROUND: Gender-based clinical differences are increasingly being identified as having significant influence on the outcomes of patients with cardiovascular disease (CVD), including atrial fibrillation (AF). OBJECTIVE: To perform detailed clinical phenotyping on a cohort of hospitalised patients with chronic forms of AF to understand if gender-based differences exist in the clinical presentation, thrombo-embolic risk and therapeutic management of high risk patients hospitalised with chronic AF. METHODS: We are undertaking the Standard versus Atrial Fibrillation spEcific managemenT studY (SAFETY) - a multi-centre, randomised controlled trial of an AF-specific management intervention versus usual care. Extensive baseline profiling of recruited patients was undertaken to identify gender-specific differences for risk delineation. RESULTS: We screened 2,438 patients with AF and recruited 335 into SAFETY. Of these, 48.1% were women who were, on average, 5 years older than their male counterparts. Women and men displayed divergent antecedent profiles, with women having a higher thrombo-embolic risk but being prescribed similar treatment regimens. More women than men presented to hospital with co-morbid thyroid dysfunction, depression, renal impairment and obesity. In contrast, more men presented with coronary artery disease (CAD) and/or chronic obstructive pulmonary disease (COPD). Even when data was age-adjusted, women were more likely to live alone (odds ratio [OR] 2.33; 95% confidence interval [CI] 1.47 to 3.69), have non-tertiary education (OR 2.69; 95% CI 1.61 to 4.48) and be symptomatic (OR 1.93; 95% CI 1.06 to 3.52). CONCLUSION: Health care providers should be cognisant of gender-specific differences in an attempt to individualise and, hence, optimise the management of patients with chronic AF and reduce potential morbidity and mortality.Jocasta Ball, Melinda J. Carrington, Kathryn A. Wood, Simon Stewart (the SAFETY Investigators

Diabetes and lipid screening among patients in primary care: A cohort study

<p>Abstract</p> <p>Background</p> <p>Obesity is associated with increased cardiovascular diseases and diabetes mellitus. Guidelines call for intensified glucose and lipid screening among overweight and obese patients. Data on compliance with these guidelines are scarce. The purpose of this study was to assess rates of diabetes and lipid screening in primary care according to demographic variables and weight status.</p> <p>Methods</p> <p>Over a 3-year follow-up period, we assessed screening rates for blood glucose, triglycerides, and HDL- and LDL-cholesterol among 5025 patients in primary care. From proportional hazards models we estimated screening rates among low, moderate, high, and very-high risk patients and compared them with recommendations of the American Diabetes Association (ADA), National Cholesterol Education Program (ATP III) and U.S. Preventive Services Task Force (USPSTF).</p> <p>Results</p> <p>Mean (SD) age was 47.4 (15.6); 69% were female, 21% were non-white, and 30% of males and 25% of females were obese (BMI ≥ 30 kg/m²). For both diabetes and lipid screening, the adjusted hazard was 260–330% higher among ≥65 than <35 year-olds, 50–90% higher in persons with BMI ≥ 35 than <25 kg/m², 10–30% lower for females than males, and not lower among racial/ethnic minorities. Screening rates were at least 80% among very-high risk persons, which we defined as 55–64 years old, BMI ≥ 35 kg/m², non-white, with baseline hypertension. In contrast, high-risk persons who were younger (35–44 years old) and less obese (BMI 30–<35 kg/m²) were screened less often (43% for LDL-cholesterol among females to 83% for diabetes among males) even though ADA, ATP III and USPSTF recommend diabetes and lipid screening among them.</p> <p>Conclusion</p> <p>Patients with higher BMI or age were more likely to be screened for cardiometabolic risk factors. Women were screened at lower rates than men. Even in a highly structured medical group practice, some obese patients were under-screened for diabetes and dyslipidemia.</p

Clinical Benefit of Low Molecular Weight Heparin for ST-segment Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention with Glycoprotein IIb/IIIa Inhibitor

The efficacy of low molecular weight heparin (LMWH) with low dose unfractionated heparin (UFH) during percutaneous coronary intervention (PCI) with or without glycoprotein (Gp) IIb/IIIa inhibitor compared to UFH with or without Gp IIb/IIIa inhibitor has not been elucidated. Between October 2005 and July 2007, 2,535 patients with ST elevation acute myocardial infarction (STEMI) undergoing PCI in the Korean Acute Myocardial Infarction Registry (KAMIR) were assigned to either of two groups: a group with Gp IIb/IIIa inhibitor (n=476) or a group without Gp IIb/IIIa inhibitor (n=2,059). These groups were further subdivided according to the use of LMWH with low dose UFH (n=219) or UFH alone (n=257). The primary end points were cardiac death or myocardial infarction during the 30 days after the registration. The primary end point occurred in 4.1% (9/219) of patients managed with LMWH during PCI and Gp IIb/IIIa inhibitor and 10.8% (28/257) of patients managed with UFH and Gp IIb/IIIa inhibitor (odds ratio [OR], 0.290; 95% confidence interval [CI], 0.132-0.634; P=0.006). Thrombolysis In Myocardial Infarction (TIMI) with major bleeding was observed in LMHW and UFH with Gp IIb/IIIa inhibitor (1/219 [0.5%] vs 1/257 [0.4%], P=1.00). For patients with STEMI managed with a primary PCI and Gp IIb/IIIa inhibitor, LMWH is more beneficial than UFH

The Women's international study of long-duration oestrogen after menopause (WISDOM): a randomised controlled trial

BACKGROUND: At the time of feasibility work and final design of the trial there was no randomised control trial evidence for the long-term risks and benefits of hormone replacement therapy. Observational studies had suggested that long term use of estrogen was likely to be associated, amongst other things, with reduced risks of osteoporosis and ischaemic heart disease and increased risks of breast and endometrial cancer. Concomitant use of progestogens had been shown to protect against endometrial cancer, but there were few data showing how progestogen might affect estrogen actions on other conditions. Disease specific risks from observational studies suggested that, overall, long-term HRT was likely to be beneficial. Several studies showed that mortality from all causes was lower in HRT users than in non-users. Some secondary cardiovascular prevention trials were ongoing but evidence was also required for a range of outcomes in healthy women. The WISDOM trial was designed to compare combined estrogen and progestogen versus placebo, and estrogen alone versus combined estrogen and progestogen. During the development of WISDOM the Women's Health Initiative trial was designed, funded and started in the US. DESIGN: Randomised, placebo, controlled, trial. METHODS: The trial was set in general practices in the UK (384), Australia (94), and New Zealand (24). In these practices 284175 women aged 50–69 years were registered with 226282 potentially eligible. We sought to randomise 22300 postmenopausal women aged 50 – 69 and treat for ten years. The interventions were: conjugated equine estrogens, 0.625 mg orally daily; conjugated equine estrogens plus medroxyprogesterone acetate 2.5/5.0 mg orally daily; matched placebo. Primary outcome measures were: major cardiovascular disease, osteoporotic fractures, breast cancer and dementia. Secondary outcomes were: other cancers, all cause death, venous thromboembolism and cerebro-vascular disease. RESULTS: The trial was prematurely closed during recruitment following publication of early results from the Women's Health Initiative. At the time of closure, 56583 had been screened, 8980 entered run-in, and 5694 (26% of target of 22,300) randomised. Those women randomised had received a mean of one year of therapy, mean age was 62.8 years and total follow-up time was 6491 person years. DISCUSSION: The WISDOM experience leads to some simple messages. The larger a trial is the more simple it needs to be to ensure cost effective and timely delivery. When a trial is very costly and beyond the resources of one country, funders and investigators should make every effort to develop international collaboration with joint funding

A systematic review of clinical trials of pharmacological interventions for acute ischaemic stroke (1955-2008) that were completed, but not published in full

<p>Abstract</p> <p>Background</p> <p>We assessed the prevalence, and potential impact of, trials of pharmacological agents for acute stroke that were completed but not published in full. Failure to publish trial data is to be deprecated as it sets aside the altruism of participants' consent to be exposed to the risks of experimental interventions, potentially biases the assessment of the effects of therapies, and may lead to premature discontinuation of research into promising treatments.</p> <p>Methods</p> <p>We searched the Cochrane Stroke Group's Specialised Register of Trials in June 2008 for completed trials of pharmacological interventions for acute ischaemic stroke, and searched MEDLINE and EMBASE (January 2007 - March 2009) for references to recent full publications. We assessed trial completion status from trial reports, online trials registers and correspondence with experts.</p> <p>Results</p> <p>We identified 940 trials. Of these, 125 (19.6%, 95% confidence interval 16.5-22.6) were completed but not published in full by the point prevalence date. They included 16,058 participants (16 trials had over 300 participants each) and tested 89 different interventions. Twenty-two trials with a total of 4,251 participants reported the number of deaths. In these trials, 636/4251 (15.0%) died.</p> <p>Conclusions</p> <p>Our data suggest that, at the point prevalence date, a substantial body of evidence that was of relevance both to clinical practice in acute stroke and future research in the field was not published in full. Over 16,000 patients had given informed consent and were exposed to the risks of therapy. Responsibility for non-publication lies with investigators, but pharmaceutical companies, research ethics committees, journals and governments can all encourage the timely publication of trial data.</p

Early warning systems and rapid response to the deteriorating patient in hospital: A systematic realist review.

AIM: To determine the Rapid Response System programme theory and investigate how the mechanisms of implementation and the characteristics of context combine to enable or constrain the implementation of Rapid Response Systems and the achievement of desired outcomes. BACKGROUND: Rapid Response Systems have been implemented internationally to improve the recognition and management of patient deterioration, reduce the need for cardiopulmonary resuscitation and improve patient outcomes. DESIGN: Realist review. DATA SOURCES: We searched DARE, CENTRAL, NHSEED, MEDLINE, Medline In Process, EMBASE, CINAHL, PubMed, Scopus, The Web of Science and PychInfo databases from 1997 - 2017 in addition to purposively searching the grey literature looking for articles supporting, refuting or explaining Rapid Response System programme theories. REVIEW METHODS: Included studies were critically appraised and graded using the Critical Appraisal Skills Programme tool. Data extraction and synthesis investigated the Rapid Response System theoretical propositions against the empirical evidence to refine Rapid Response System programme theories. RESULTS: The review found that the Rapid Response System programme theory achieved desired outcomes when there were sufficient skills mix of experienced staff, EWS protocols were used flexibly alongside clinical judgement and staff had access to ongoing, multiprofessional, competency-based education. However, ward cultures, hierarchical referral systems, workload and staffing resources had a negative impact on the implementation of the Rapid Response System. CONCLUSION: To improve the recognition and management of patient deterioration, policymakers need to address those cultural, educational and organizational factors that have an impact on the successful implementation of Rapid Response Systems in practice

The Surveillance After Extremity Tumor Surgery (SAFETY) trial: protocol for a pilot study to determine the feasibility of a multi-centre randomised controlled trial.

IntroductionFollowing the treatment of patients with soft tissue sarcomas (STS) that are not metastatic at presentation, the high risk for local and systemic disease recurrence necessitates post-treatment surveillance. Systemic recurrence is most often detected in the lungs. The most appropriate surveillance frequency and modality remain unknown and, as such, clinical practice is highly varied. We plan to assess the feasibility of conducting a multi-centre randomised controlled trial (RCT) that will evaluate the effect on overall 5-year survival of two different surveillance frequencies and imaging modalities in patients with STS who undergo surgical excision with curative intent.Methods and analysisThe Surveillance After Extremity Tumor Surgery trial will be a multi-centre 2×2 factorial RCT. Patients with non-metastatic primary Grade II or III STS treated with excision will be allocated to one of four treatment arms1: chest radiograph (CXR) every 3 months for 2 years2; CXR every 6 months for 2 years3; chest CT every 3 months for 2 years or4 chest CT every 6 months for 2 years. The primary outcome of the pilot study is the feasibility of a definitive RCT based on a combination of feasibility endpoints. Secondary outcomes for the pilot study include the primary outcome of the definitive trial (overall survival), patient-reported outcomes on anxiety, satisfaction and quality of life, local recurrence-free survival, metastasis-free survival, treatment-related complications and net healthcare costs related to surveillance.Ethics and disseminationThis trial received provisional ethics approval from the McMaster/Hamilton Health Sciences Research Ethics Board on 7 August 2019 (Project number 7562). Final ethics approval will be obtained prior to commencing patient recruitment. Once feasibility has been established and the definitive protocol is finalised, the study will transition to the definitive study.Trial registrationNCT03944798; Pre-results