Effect of Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Initiation on Organ Support-Free Days in Patients Hospitalized With COVID-19: A Randomized Clinical Trial.

IMPORTANCE: Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective: To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS: In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non-critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS: Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES: The primary outcome was organ support-free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS: On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support-free days among critically ill patients was 10 (-1 to 16) in the ACE inhibitor group (n = 231), 8 (-1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support-free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE: In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02735707.

Comparative effectiveness of devices for transcatheter closure of atrial septal defects: Systematic review and network meta-analysis.

Atrial septal defect is a common congenital heart disease, producing a left-to-right shunt in the atrial septum; the current preferred treatment is transcatheter device closure. The aim is to conduct a systematic review to synthesize information on the comparative effectiveness and safety of atrial septal defect closure devices. The methods used: a comprehensive search of Ovid MEDLINE®, Embase, and Cochrane Central databases was conducted. Studies comparing procedural and follow-up outcomes of atrial septal defect devices were included. Network meta-analyses were conducted to generate direct and indirect evidence for comparative effectiveness and safety outcomes between devices. The results are as follows: Twelve studies met our inclusion criteria and were compared in network meta-analyses. The meta-analyses evaluated contemporary devices: the AMPLATZER Septal Occluder; the GORE CARDIOFORM Septal Occluder; the Figulla Flexible II Occluder; the CeraFlex Septal Occluder; and the HELEX Septal Occluder. These studies represented 3998 patients. The primary safety and efficacy outcomes were device embolization and follow-up residual shunt, respectively. Secondary clinical outcomes included procedural success and major and minor complications. No differences were found between devices in terms of device embolization and secondary clinical outcomes. Follow-up residual shunt was higher with the HELEX Septal Occluder compared with the AMPLATZER Septal Occluder (odds ratio 2.92, 95% confidence interval 1.12-7.61). To conclude: although most outcomes were similar between devices, evidence was largely based on observational low-quality studies. There were inconsistencies in outcome reporting and definitions; this merits future studies, with head-to-head device comparisons and standardization of outcomes.

Coronary Artery Disease in Adults Undergoing Percutaneous Patent Foramen Ovale Closure Following Cryptogenic Stroke.

BACKGROUND: A patent foramen ovale (PFO) is found in nearly half of patients with cryptogenic stroke. Little guidance on the use or necessity of coronary angiography at the time of percutaneous PFO closure exists. We aimed to characterize the presence of coronary artery disease (CAD) in patients undergoing PFO closure following a cryptogenic stroke. METHODS: A retrospective analysis of consecutive patients who underwent concurrent percutaneous PFO closure and coronary angiography was performed. Patients were ≥40 years of age and had a preceding diagnosis of cryptogenic stroke with no known CAD. Visual analysis of coronary angiograms was performed. RESULTS: Of 180 patients, 8 (4%) had severe CAD, 15 (8%) had moderate CAD, 32 (18%) had mild CAD, and 12 (7%) had luminal irregularities. Of those with moderate-to-severe CAD, 9 (5%) had proximal disease and 9 (5%) had multivessel disease. Of those with moderate-to-severe CAD, 8 (35%) underwent further risk stratification with stress testing, 4 (17%) were medically managed, and 1 (4%) underwent concurrent angioplasty. CONCLUSIONS: Coronary angiography identified a low prevalence of CAD in patients with cryptogenic stroke undergoing PFO closure, suggesting that coronary angiography is not routinely indicated in patients undergoing PFO closure.

Routine Coronary Angiography in Adults Undergoing Percutaneous Atrial Septal Defect Closure: Implications for Practice Guidelines.

OBJECTIVES: Secundum atrial septal defect (ASD) is a common adult congenital heart lesion for which percutaneous closure offers treatment in patients with suitable anatomy. We sought to determine the outcomes of coronary angiography in a population of adults >40 years of age who were undergoing percutaneous ASD closure. METHODS: Patients >40 years of age who underwent ASD closure between 2009-2016 were included in this retrospective chart review. Coronary angiograms were reviewed by 2 independent reviewers to evaluate the presence and degree of coronary artery disease (CAD) and the resulting clinical sequelae. RESULTS: A total of 398 patients underwent ASD closure, and 300 had coronary angiography at the time of closure. Mild CAD (10%-39% vessel stenosis) was found in 33 patients (11.0%), moderate CAD (40%-69% vessel stenosis) in 23 patients (7.7%), and severe CAD (≥70% vessel stenosis) in 25 patients (8.3%). Of the 48 patients with moderate to severe CAD, 24 had proximal vessel disease and 21 had multivessel disease. Four patients (8.3%) with moderate to severe CAD subsequently underwent percutaneous interventions, 16 patients (33.3%) had medication changes, 16 patients (33.3%) had perfusion testing followed by medication changes, and 12 patients (25%) had no changes in their medical management. CONCLUSIONS: Given the prevalence of CAD in this population, routine coronary angiography at the time of ASD closure should be reserved for patients with an unfavorable cardiovascular risk profile, who have a higher likelihood of CAD. While patients with ASDs suffer from chest pain and dyspnea both before and after percutaneous closure, few have established CAD.

New-onset atrial fibrillation following percutaneous closure of patent foramen ovale: a systematic review and meta-analysis.

PURPOSE: A patent foramen ovale (PFO), present in up to 25% of adults, is an embryologic remnant which allows for right to left shunting and has been implicated in cryptogenic stroke (Neill and Lin, Methodist Debakey Cardiovasc J. 13(3):152-159, 2017; Bass 2015). The current standard of care for selected patients with PFO and cryptogenic stroke is transcatheter closure, but the risk of post-closure, new-onset atrial fibrillation (AF) is unknown (Vaidya et al., Cardiovasc Diagn Ther. 8(6):739-753, 2018; Kjeld et al., Acta Radiol Open. 7(9):2058460118793922, 2018; Staubach et al., Catheter Cardiovasc Interv. 74(6):889-95, 2009). This systematic review and meta-analysis synthesized evidence on AF development post transcatheter PFO closure and predictors of AF development, and assessed existing knowledge gaps. METHODS: Randomized controlled trials and observational studies were selected according to the inclusion criteria of adults that underwent a transcatheter PFO closure without a history of AF. Studies were retrieved from electronic databases from inception until February 2019. A Freeman-Tukey arcsine transformation was performed for meta-analysis of AF incidence rate. RESULTS: From 765 studies, 45 were included in quantitative data synthesis. Study sample sizes ranged between 20 and 1887 individuals, and average patient age between 37 to 67 years across studies. The overall incidence rate was 0.013 person-years, and 0.014 person-years for the within 6 months follow-up subgroup. There was no consistency in reported predictors of AF development. CONCLUSIONS: The incidence of AF post-PFO closure was low across studies, with a high level of between-study heterogeneity. Until a concerted effort is made to improve accurate AF diagnosis, it will be difficult to gauge the association between transcatheter PFO closure and incidence of AF.

Referral and access to heart function clinics: A realist review.

RATIONALE, AIM, AND OBJECTIVES: Heart failure (HF) clinics are highly effective, yet not optimally utilized. A realist review was performed to identify contexts (eg, health system characteristics, clinic capacity, and siting) and underlying mechanisms (eg, referring provider knowledge of clinics and referral criteria, barriers in disadvantaged patients) that influence utilization (provider referral [ie, of all appropriate and no inappropriate patients] and access [ie, patient attends ≥1 visit]) of HF clinics. METHODS: Following an initial scoping search and field observation in a HF clinic, we developed an initial program theory in conjunction with our expert panel, which included patient partners. Then, a literature search of seven databases was searched from inception to December 2019, including Medline; Grey literature was also searched. Studies of any design or editorials were included; studies regarding access to cardiac rehabilitation, or a single specialist for example, were excluded. Two independent reviewers screened the abstracts, and then full-texts. Relevant data from included articles were used to refine the program theory. RESULTS: A total of 29 papers from five countries (three regions) were included. There was limited information to support or refute many elements of our initial program theory (eg, referring provider knowledge/beliefs, clinic inclusion/exclusion criteria), but refinements were made (eg, specialized care provided in each clinic, lack of patient encouragement). Lack of capacity, geography, and funding arrangements were identified as contextual factors, explaining a range of mechanistic processes, including patient clinical characteristics and social determinants of health as well as clinic characteristics that help to explain inappropriate and low use of HF clinics (outcome). CONCLUSION: Given the burden of HF and benefit of HF clinics, more research is needed to understand, and hence overcome sub-optimal use of HF clinics. In particular, an understanding from the perspective of referring providers is needed.

Association of Adverse Childhood Experiences With Cardiovascular Disease Later in Life: A Review.

Importance: Adverse childhood experiences (ACEs) are potentially harmful events that occur during childhood, spanning neglect, physical or sexual abuse, parental separation, or death, among others. At least 50% of the US adult population has experienced 1 or more ACEs before the age of 18 years, but in clinical practice, ACEs remain underrecognized. Adults who have experienced ACEs are at increased risk of developing health risk behaviors and, ultimately, cardiovascular disease (CVD). This review summarizes the evidence regarding the association of ACEs with CVD and the accompanying diagnostic and therapeutic approaches in the adult population. Observations: ACEs are commonly classified into 3 domains: abuse (psychological, physical, or sexual), household dysfunction (eg, substance use by household members, mental illness, parental separation), and neglect. These experiences elicit chronic activation of the stress response system, leading to autonomic, neuroendocrine, and inflammatory dysfunction. The subsequent development of traditional risk factors, such as diabetes, hypertension, smoking, and obesity, results in the onset of CVD and premature mortality. Adults with 4 or more ACEs compared with those with none have a more than 2-fold higher risk of developing CVD and an almost 2-fold higher risk of premature mortality. Conclusions and Relevance: Identifying methods of mitigating the health consequences of ACEs may lead to better cardiovascular outcomes. Inquiry into ACE exposure during clinical encounters and subsequent referral to psychological services when appropriate may be helpful, but strategies aimed at CVD prevention via management of ACEs in adults continue to lack adequate evidence.

Predicting the Risk of Right Ventricular Failure in Patients Undergoing Left Ventricular Assist Device Implantation: A Systematic Review.

BACKGROUND: Right ventricular failure (RVF) is a cause of major morbidity and mortality after left ventricular assist device (LVAD) implantation. It is, therefore, integral to identify patients who may benefit from biventricular support early post-LVAD implantation. Our objective was to explore the performance of risk prediction models for RVF in adult patients undergoing LVAD implantation. METHODS: A systematic search was performed on Medline, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews from inception until August 2019 for all relevant studies. Performance was assessed by discrimination (via C statistic) and calibration if reported. Study quality was assessed using the Prediction Model Risk of Bias Assessment Tool criteria. RESULTS: After reviewing 3878 citations, 25 studies were included, featuring 20 distinctly derived models. Five models were derived from large multicenter cohorts: the European Registry for Patients With Mechanical Circulatory Support, Interagency Registry for Mechanically Assisted Circulatory Support, Kormos, Pittsburgh Bayesian, and Mechanical Circulatory Support Research Network RVF models. Seventeen studies (68%) were conducted in cohorts implanted with continuous-flow LVADs exclusively. The definition of RVF as an outcome was heterogenous among models. Seven derived models (28%) were validated in at least 2 cohorts, reporting limited discrimination (C-statistic range, 0.53-0.65). Calibration was reported in only 3 studies and was variable. CONCLUSIONS: Existing RVF prediction models exhibit heterogeneous derivation and validation methodologies, varying definitions of RVF, and are mostly derived from single centers. Validation studies of these prediction models demonstrate poor-to-modest discrimination. Newer models are derived in cohorts implanted with continuous-flow LVADs exclusively and exhibit modest discrimination. Derivation of enhanced discriminatory models and their validations in multicenter cohorts is needed.

Reduced Rate of Hospital Presentations for Heart Failure During the COVID-19 Pandemic in Toronto, Canada.

Coronavirus disease 2019 (COVID-19) has resulted in public health measures and health care reconfigurations likely to have impact on chronic disease care. We aimed to assess the volume and characteristics of patients presenting to hospitals with acute decompensated heart failure (ADHF) during the 2020 COVID-19 pandemic compared with a time-matched 2019 cohort. Patients presenting to hospitals with ADHF from March 1, to April 19, 2020 and 2019 in an urban hospital were examined. Multivariable logistic-regression models were used to evaluate the difference in probability of ADHF-related hospitalization between the 2 years. During the COVID-19 pandemic, a total of 1106 emergency department (ED) visits for dyspnea or peripheral edema were recorded, compared with 800 ED visits in 2019. A decrease in ADHF-related ED visits of 43.5% (14.8%-79.4%, P = 0.002) and ADHF-related admissions of 39.3% (8.6%-78.5%, P = 0.009) was observed compared with 2019. Patients with ADHF presenting to hospitals (n = 128) were similar in age, sex, and comorbidities compared with the 2019 cohort (n = 186); however, a higher proportion had recent diagnoses of heart failure. Upon ED presentation, the relative probability of hospitalization or admission to intensive care was not statistically different. There was a trend toward higher in-hospital mortality in 2020. The decline in ADHF-related hospitalizations raises the timely question of how patients with heart failure are managing beyond the acute-care setting and reinforces the need for public education on the availability and safety of emergency services throughout the COVID-19 pandemic.

NPWT in diabetic foot wounds-a systematic review and meta-analysis of observational studies.

PURPOSE: Negative-pressure wound therapy (NPWT) is an adjunct modality in diabetic foot ulcerations (DFUs). Randomized controlled trials (RCTs) have shown its advantage over standard approaches; however, data from observational studies remain scarce.We performed a systematic review of observational non-RCTs evaluating NPWT efficacy and safety in patients with DFU. METHODS: Electronic databases were searched for observational studies involving NPWT. The results of single-arm studies were presented as percentages of patients with the outcome of interest. A meta-analysis of comparative studies provided point estimates of outcomes. Continuous outcomes were reported as either weighted or standardized mean differences and dichotomous data as relative risks (RR). RESULTS: The search identified 16 relevant observational studies, 12 single-arm, and 4 comparative, reporting on a total of 18,449 patients with DFU, of whom 1882 were managed with NPWT. In the NPWT-treated patients, ulcers were larger (average size range 6.6-27.9 cm2), as compared with controls (≤3 cm2). The pooled results showed healing and major amputation in 51% and 5% of NPWT patients, respectively. The meta-analysis of comparative studies revealed lower risk of major amputation [RR = 0.23 (0.07; 0.80)] in NPWT-treated patients. The pooled results for healing rate and risk of any amputation were inconclusive due to large between-study heterogeneity. Overall, 6 deaths out of 158 patients were reported, none of them related to NPWT. Serious adverse events occurred in 6% of patients on NPWT. CONCLUSIONS: This systematic review of observational studies provided supportive evidence that NWPT is an efficient and safe adjunct treatment in the management of DFUs.

Assessing progress of the Pan American Health Organization's Policy Research for Health in member states / Evaluación del progreso de la Política sobre Investigación Sanitaria de la Organización Panamericana de la Salud en sus Estados miembros

The improvement of health in the twenty-first century is inextricably linked to research for health. In response to growing international appeal to address regional health needs, the Pan American Health Organization (PAHO) and its Member States approved the Policy on Research for Health (CD49/10) in 2009. This document represents the flagship regional policy on research for health and outlines how health systems and services in the region can be strengthened through research. It has been implemented by the two components of PAHO -the Member States and the Pan American Sanitary Bureau. The policy contained a specific directive mandating PAHO to report on its implementation, development of subsequent strategies, and action plans targeting its governing bodies. The Americas are the first World Health Organization (WHO) region to issue a regional Policy on Research for Health, which was harmonized with WHO's Strategy on Research for Health, approved in 2010. Attending to the recommendations issued by PAHO's Advisory Committee on Health Research and WHO's Advisory Committee on Health Research, the PAHO Department of Knowledge Management, Bioethics and Research set out to advance the assessment of the implementation of the Policy on Research for Health through the creation of a monitoring and evaluation Scorecard. Indicators relevant to the Policy on Research for Health objectives were mapped from the Compendium of Impact and Outcome Indicators, with new indicators created. A practical framework based on available indicator data was proposed to generate a baseline policy assessment and incorporate a means of incrementally enhancing the measurements. In this case study, we outline the iterations of the PAHO Policy on Research for Health Scorecard, as well as the lessons learned throughout the development process that may be a valuable guide for health research entities monitoring and evaluating the progress of their own policies

La mejora de la salud en el siglo XXI está inextricablemente ligada a la investigación sanitaria. En respuesta a la llamada internacional creciente, de cara a abordar las necesidades sanitarias regionales, la Organización Panamericana de la Salud (OPS) y sus Estados miembros aprobaron en 2009 la Política sobre Investigación Sanitaria (CD49/10). Este documento constituye la política regional insignia sobre investigación sanitaria, y destaca cómo pueden reforzarse los sistemas y servicios sanitarios en la región a través de la investigación. Ha sido implementado por parte de los dos componentes de la OPS: los Estados miembros y la Agencia Sanitaria Panamericana. La política contenía una directiva específica, que encomendaba a la OPS la realización de un informe sobre su implementación, desarrollo y políticas subsiguientes, al igual que los planes de acción dirigidos a sus órganos directivos. El continente americano es la primera región de la Organización Mundial de la Salud (OMS) que establece una política regional sobre investigación sanitaria, armonizada con la Estrategia sobre investigación sanitaria de la OMS, aprobada en 2010. Atendiendo a las recomendaciones emitidas por el Comité Asesor sobre investigación sanitaria de la OPS y el Comité Asesor sobre investigación sanitaria de la OMS, el Departamento de Gestión del Conocimiento, Bioética e Investigación de la OPS propuso avanzar en la evaluación de la implementación de la política de investigación sanitaria a través de la creación de un cuadro de mando de supervisión y evaluación. Los indicadores relevantes de los objetivos de la política sobre investigación sanitaria fueron pareados a partir de los indicadores de Compendio del Impacto y Resultados, con los nuevos indicadores. Se propuso un marco práctico basado en los datos indicadores disponibles, para generar una evaluación de la política basal e incorporar un medio de mejorar las medidas gradualmente. En este estudio de caso destacamos las iteraciones del cuadro de mando de la política sobre investigación sanitaria de la OPS, así como las lecciones aprendidas a lo largo del proceso de desarrollo, que podrían constituir una guía valiosa para las entidades de investigación sanitaria de cara a supervisar y evaluar el progreso de sus propias políticas

Negative pressure wound therapy use in diabetic foot syndrome-from mechanisms of action to clinical practice.

BACKGROUND: Diabetes and its complications constitute a rising medical challenge. Special attention should be given to diabetic foot syndrome (DFS) due to its high rate of associated amputation and mortality. Negative pressure wound therapy (NPWT) is a frequently used supportive modality in a diabetic foot with ulcerations (DFUs). DESIGN: Here, we reviewed the current knowledge concerning the tissue and molecular mechanisms of NPWT action with an emphasis on diabetes research followed by a summary of clinical DFU studies and practice guidelines. RESULTS: Negative pressure wound therapy action results in two types of tissue deformations-macrodeformation, such as wound contraction, and microdeformation occurring at microscopic level. Both of them stimulate a wound healing cascade including tissue granulation promotion, vessel proliferation, neoangiogenesis, epithelialization and excess extracellular fluid removal. On the molecular level, NPWT results in an alteration towards more pro-angiogenic and anti-inflammatory conditions. It increases expression of several key growth factors, including vascular endothelial growth factor and fibroblast growth factor 2, while expression of inflammatory cytokinesis reduced. The NPWT application also alters the presence and function of matrix metalloproteinases. Clinical studies in DFU patients showed a superiority of NPWT over standard therapy in terms of efficacy outcomes, primarily wound healing and amputation rate, without a rise in adverse events. International guidelines point to NPWT as an important adjuvant therapy in DFU whose use is expected to increase. CONCLUSIONS: This current knowledge improves our understanding of NPWT action and its tailoring for application in diabetic patients. It may inform the development of new treatments for DFU.

Assessing progress of the Pan American Health Organization's Policy Research for Health in member states.

The improvement of health in the twenty-first century is inextricably linked to research for health. In response to growing international appeal to address regional health needs, the Pan American Health Organization (PAHO) and its Member States approved the Policy on Research for Health (CD49/10) in 2009. This document represents the flagship regional policy on research for health and outlines how health systems and services in the region can be strengthened through research. It has been implemented by the two components of PAHO -the Member States and the Pan American Sanitary Bureau. The policy contained a specific directive mandating PAHO to report on its implementation, development of subsequent strategies, and action plans targeting its governing bodies. The Americas are the first World Health Organization (WHO) region to issue a regional Policy on Research for Health, which was harmonized with WHO's Strategy on Research for Health, approved in 2010. Attending to the recommendations issued by PAHO's Advisory Committee on Health Research and WHO's Advisory Committee on Health Research, the PAHO Department of Knowledge Management, Bioethics and Research set out to advance the assessment of the implementation of the Policy on Research for Health through the creation of a monitoring and evaluation Scorecard. Indicators relevant to the Policy on Research for Health objectives were mapped from the Compendium of Impact and Outcome Indicators, with new indicators created. A practical framework based on available indicator data was proposed to generate a baseline policy assessment and incorporate a means of incrementally enhancing the measurements. In this case study, we outline the iterations of the PAHO Policy on Research for Health Scorecard, as well as the lessons learned throughout the development process that may be a valuable guide for health research entities monitoring and evaluating the progress of their own policies.

Perioperative mortality rates in low-income and middle-income countries: a systematic review and meta-analysis.

INTRODUCTION: The Lancet Commission on Global Surgery proposed the perioperative mortality rate (POMR) as one of the six key indicators of the strength of a country's surgical system. Despite its widespread use in high-income settings, few studies have described procedure-specific POMR across low-income and middle-income countries (LMICs). We aimed to estimate POMR across a wide range of surgical procedures in LMICs. We also describe how POMR is defined and reported in the LMIC literature to provide recommendations for future monitoring in resource-constrained settings. METHODS: We did a systematic review of studies from LMICs published from 2009 to 2014 reporting POMR for any surgical procedure. We extracted select variables in duplicate from each included study and pooled estimates of POMR by type of procedure using random-effects meta-analysis of proportions and the Freeman-Tukey double arcsine transformation to stabilise variances. RESULTS: We included 985 studies conducted across 83 LMICs, covering 191 types of surgical procedures performed on 1 020 869 patients. Pooled POMR ranged from less than 0.1% for appendectomy, cholecystectomy and caesarean delivery to 20%-27% for typhoid intestinal perforation, intracranial haemorrhage and operative head injury. We found no consistent associations between procedure-specific POMR and Human Development Index (HDI) or income-group apart from emergency peripartum hysterectomy POMR, which appeared higher in low-income countries. Inpatient mortality was the most commonly used definition, though only 46.2% of studies explicitly defined the time frame during which deaths accrued. CONCLUSIONS: Efforts to improve access to surgical care in LMICs should be accompanied by investment in improving the quality and safety of care. To improve the usefulness of POMR as a safety benchmark, standard reporting items should be included with any POMR estimate. Choosing a basket of procedures for which POMR is tracked may offer institutions and countries the standardisation required to meaningfully compare surgical outcomes across contexts and improve population health outcomes.

Comparative Efficacy of Angiotensin II Antagonists in Essential Hypertension: Systematic Review and Network Meta-Analysis of Randomised Controlled Trials.

BACKGROUND: Evidence on the long-term clinical benefits of individual members of angiotensin II receptor blockers is limited given the lack of head-to-head studies. We conducted a network meta-analysis to determine the comparative efficacy of different members within this drug class with respect to outcomes of (i) blood pressure reduction (at 24 and 52 weeks) and (ii) prevention of cardiovascular disease (>104 weeks). METHODS: A systematic literature review was conducted - Protocol registration: (PROSPERO - CRD42014007067) - to identify relevant literature from the following databases: Cochrane Library, PubMed, Medline and EMBASE; searched from inception to July 2016. Randomised controlled trials (RCTs) were included if they reported long-term effectiveness relating to blood pressure, mortality, myocardial infarction or stroke. Eligible studies included those with placebo or specific active-treatment comparators (either another angiotensin II receptor blockers or hydrochlorothiazide). A Bayesian random-effects network model was used to combine direct within-trial comparisons between treatment groups with indirect evidence from other trials. RESULTS: Thirty-six studies were identified, representing 28 unique trials. Blood pressure reduction, based on 12 studies (n=807) with fixed dosing regimen, was found to be similar amongst members of the angiotensin receptor blocker drug class at both 24 and 52 weeks. A network meta-analysis of five studies (n=16,716) with a treat-to-target approach found that prevention of all-cause mortality, stroke and myocardial infarction was similar across the angiotensin-receptor blockers therapies initiated. CONCLUSIONS: Current evidence is insufficient to show differences in any members within the angiotensin II receptor blocker drug class with respect to blood pressuring lowering effects or a reduction in cardiovascular diseases.

Adult Congenital Heart Disease Intervention: The Canadian Landscape.

Once considered a childhood disease, the number of adults living with congenital heart disease (CHD) has now exceeded the number of pediatric patients. The landscape of percutaneous intervention for adult congenital heart disease (ACHD) has evolved over the past decade and has yet to be characterized in Canada. The aim of this study was to begin to understand the current infrastructure underlying ACHD interventions in Canada and to characterize the type and number of interventions being carried out across the country. A cross-sectional national survey was distributed by e-mail to all cardiac catheterization laboratory directors in 2015. All Canadian laboratories involved in ACHD interventions responded, encompassing 19 institutions spanning 69 cardiac catheterization laboratories. A total of 1451 percutaneous interventions were recorded. Nationwide, the most common simple ACHD interventions were for atrial septal defect and patent foramen ovale closures. The most common ACHD interventions of increased complexity were for coarctation stenting and transcatheter pulmonary valve implantation. There was a marked clustering of procedures in Ontario, Québec, British Columbia, and Alberta in keeping with Canada's population-density distribution. A total of 23 ACHD operators were identified, half of whom had ACHD-specific fellowship training. These data can be used as a starting point to inform the present state of affairs in the area and lay the groundwork for further work to assess resource allocation and human resource planning for the care of patients with ACHD in Canada.

Understanding academic clinicians' intent to treat pediatric obesity.

AIM: To examine the extent to which the theory of planned behavior (TPB) predicts academic clinicians' intent to treat pediatric obesity. METHODS: A multi-disciplinary panel iteratively devised a Likert scale survey based on the constructs of the TPB applied to a set of pediatric obesity themes. A cross-sectional electronic survey was then administered to academic clinicians at tertiary care centers across Canada from January to April 2012. Descriptive statistics were used to summarize demographic and item agreement data. A hierarchical linear regression analysis controlling for demographic variables was conducted to examine the extent to which the TPB subscales predicted intent to treat pediatric obesity. RESULTS: A total of 198 physicians, surgeons, and allied health professionals across Canada (British Columbia, Alberta, Manitoba, Saskatchewan, Nova Scotia, Ontario and Quebec) completed the survey. On step 1, demographic factors accounted for 7.4% of the variance in intent scores. Together in step 2, demographic variables and TPB subscales predicted 56.9% of the variance in a measure of the intent to treat pediatric obesity. Perceived behavioral control, that is, confidence in one's ability to manage pediatric obesity, and subjective norms, congruent with one's context of practice, were the most significant predictors of the intent to treat pediatric obesity. Attitudes and barriers did not predict the intent to treat pediatric obesity in this context. CONCLUSION: Enhancing self-confidence in the ability to treat pediatric obesity and the existence of supportive treatment environments are important to increase clinician's intent to treat pediatric obesity.

Cardiovascular and cerebrovascular outcomes of long-term angiotensin receptor blockade: meta-analyses of trials in essential hypertension.

Angiotensin receptor blockers (ARBs) are widely used in managing essential hypertension, with considerable evidence available on their short-term efficacy in lowering blood pressure (BP). However, there currently exists limited "pooled" data examining the long-term efficacy of ARB treatment in controlling BP or mitigating cardiovascular and cerebrovascular events. The purpose of this study was to conduct a systematic review and meta-analysis assessing the long-term effects of ARBs as a class on BP control, myocardial infarction, hospitalization for heart failure, cerebrovascular events (ie, stroke), cardiovascular mortality, and all-cause mortality. MEDLINE, EMBASE, PubMed, and the Cochrane Library databases were searched from inception to March 2015. Two evaluators independently reviewed studies for eligibility. Randomized controlled hypertension trials were included if they reported on ARB efficacy in either BP control (relative to placebo for periods ≥ 6 months) or cardiovascular/cerebrovascular outcomes (relative to non-ARB antihypertensive therapies for periods ≥ 24 months). Studies were pooled with a random-effects model using weighted mean differences (WMDs) and relative risks for continuous and dichotomous outcomes, respectively. A total of 11 articles were included in the narrative synthesis, representing seven unique trials (16,864 participants). Six ARB agents were studied: candesartan, eprosartan, irbesartan, olmesartan, losartan (each represented by one trial arm), and telmisartan (represented by two arms). ARB therapy significantly reduced mean systolic BP (WMD: -4.86; 95% CI: -6.19, -3.53 mm Hg) and diastolic BP (WMD: -2.75; 95% CI: -3.65, -1.86 mm Hg] compared to placebo. The risk of stroke was reduced by 21% in the ARB group compared with alternative antihypertensives (risk ratio: 0.79; 95% CI: 0.66, 0.96). ARBs did not, however, produce statistically significant reductions in the risk of myocardial infarction, heart failure hospitalization, or mortality. Our findings suggest that ARBs, as a class, are more effective than placebo therapy in long-term BP lowering in patients with essential hypertension. Long-term ARB treatment may also confer enhanced protection against stroke but not other cardiovascular outcomes relative to placebo.