Cardiology professionals' views of social robots in augmenting heart failure patient care.

Aims: Social robots are arriving to the modern healthcare system. Whether patients with heart failure, a prevalent chronic disease with high health and human costs would derive benefit from a social robot intervention has not been investigated empirically. Diverse healthcare provider's perspectives are needed to develop an acceptable and feasible social robot intervention to be adopted for the clinical benefit of patients with heart failure. Using a qualitative research design, this study investigated healthcare providers' perspectives of social robot use in heart failure patient care. Methods and results: Interdisciplinary healthcare providers from a tertiary care cardiac hospital completed a structured individual interview and a supplemental questionnaire. The framework method was used to analyse the qualitative data. Respondents (n = 22; saturation was reached with this sample; 77% female; 52% physicians) were open to using social robots to augment their practice, particularly with collecting pertinent data and providing patient and family education and self-management prompts, but with limited responsibility for direct patient care. Prior to implementation, providers required robust evidence of: value-added beyond current remote patient monitoring devices, patient and healthcare provider partnerships, streamlined integration into existing practice, and capability of supporting precision medicine goals. Respondents were concerned that social robots did not address and masked broader systemic issues of healthcare access and equity. Conclusion: The adoption of social robots is a viable option to assist in the care of patients with heart failure, albeit in a restricted capacity. The results inform the development of a social robotic intervention for patients with heart failure, including improving social robot efficiencies and increasing their uptake, while protecting patients' and providers' best interest.

Personalized care of patients with heart failure: are we ready for a REWOLUTION? Insights from two international surveys on healthcare professionals' needs and patients' perceptions.

AIMS: Guidelines for the management of heart failure (HF) are evolving, and increasing emphasis is placed on patient-centred care. As part of the REWOLUTION HF (REal WOrLd EdUcaTION in HF) programme, we conducted two international surveys aimed at assessing healthcare professionals' (HCPs) educational needs and patients' perspectives on the care of HF. METHODS AND RESULTS: Anonymous online questionnaires co-developed by HF experts and patients assessed HCPs' educational needs (520 respondents, mostly cardiologists, in 67 countries) and patients' perceptions on HF impact and management (98 respondents in 18 countries). Among HCPs, 62.7% prioritized rapid initiation of all guideline-mandated medications over up-titration of some medications, and 87.7% always or frequently discussed treatment goals with patients. There was good agreement between HCPs and patients on key treatment goals, except for a greater emphasis on reducing hospitalizations among HCPs. The most frequently cited barriers to the provision of guideline-recommended pharmacological therapy were treatment side effects/intolerance, complex treatment regimens, low blood pressure, cost/reimbursement issues, and low estimated glomerular filtration rate. Most patients (81.6%) reported no difficulties taking medications as prescribed, although 21.4% felt they were taking too many pills. Patients wanted more information about HF and its consequences, prognosis, and treatments (70.4%, 74.5% and 76.6%, respectively). Cardiologists were the preferred source of information about HF, followed by general practitioners and HF nurses. CONCLUSIONS: These surveys provide valuable insights into HCPs' needs about personalized care for patients with HF, as well as patients' perceptions, expectations and preferences. These findings will be helpful to develop patient-centred, needs-driven quality improvement programmes.

Epidemiology of COVID-19 and Its Cardiac and Neurologic Complications Among Chinese and South Asians in Ontario: Waves 1, 2, and 3.

Background: Although we had previously reported the cardiac and neurologic outcomes of Chinese and South Asian Ontarians in wave 1 of COVID-19, data on subsequent waves of COVID-19 remain unexamined. This is an extension study of this cohort in waves 2 and 3. Methods: We identified adult Ontarians with a positive COVID-19 polymerase chain reaction test from January 1, 2020 to June 30, 2021, and they were classified as being Chinese or South Asian using a validated surname algorithm; we compared their outcomes of mortality, and cardiac and neurologic complications with those of the general population using multivariable logistic regression models. Results: Compared to the general population (n = 439,977), the Chinese population (n = 15,208) was older (mean age 44.2 vs 40.6 years, P < 0.001) and the South Asian population (n = 46,333) was younger (39.2 years, P < 0.001). The Chinese population had a higher 30-day mortality (odds ratio [OR] 1.44; 95% confidence interval [CI] 1.28-1.61) and more hospitalization or emergency department visits (OR, 1.14; 95% CI, 1.09-1.28), with a trend toward a higher incidence of cardiac complications (OR, 1.03; 95% CI, 0.87-1.12) and neurologic complications (OR, 1.23; 95% CI, 0.96-1.58). South Asians had a lower 30-day mortality (OR, 0.88; 95% CI, 0.78-0.98) but a higher incidence of hospitalization or emergency department visits (OR, 1.17; 95% CI, 1.14-1.20) with a trend toward a lower incidence of cardiac complications (OR, 0.76; 95% CI, 0.67-0.87) and neurologic complications (OR, 0.89; 95% CI, 0.73-1.09). There was also a significant difference in these outcomes between wave 1, 2 and 3, with a greater mortality in all groups in waves 2 and 3. Conclusions: Ethnicity continues to be an important determinant of mortality, cardiac and neurologic outcomes, and healthcare use among patients with COVID-19, requiring further studies to understand factors driving these differences.

Contexte: Nous avons déjà présenté les issues cliniques cardiaques et neurologiques chez les Ontariens de descendance chinoise ou sud-asiatique pour la première vague de la pandémie de COVID-19, mais les données au sujet des vagues ultérieures n'avaient pas encore été analysées. Nous présentons ici une prolongation de cette étude de cohortes pour la seconde et la troisième vague de COVID-19. Méthodologie: Notre analyse porte sur des adultes ontariens ayant obtenu un résultat positif à un test de COVID-19 par réaction en chaîne de la polymérase entre le 1er janvier 2020 et le 30 juin 2021. Un algorithme validé pour l'analyse des noms de famille a été utilisé pour isoler les sujets de descendance chinoise ou sud-asiatique, et leur taux de mortalité de même que les complications cardiaques et neurologiques ont été comparés à ceux de la population générale à l'aide de modèles de régression logistique multivariée. Résultats: En comparaison de la population générale (n = 439 977), les personnes de descendance chinoise (n = 15 208) se sont révélées plus âgées (âge moyen de 44,2 ans contre 40,6 ans, P < 0,001), tandis que les personnes de descendance sud-asiatique (n = 46 333) étaient plus jeunes (39,2 ans, P < 0,001). Dans la population de descendance chinoise, le taux de mortalité après 30 jours était plus élevé (rapport de cotes [RC] de 1,44; intervalle de confiance [IC] à 95 % de 1,28 à 1,61), et davantage d'hospitalisations ou de consultations aux urgences sont survenues (RC de 1,14; IC à 95 % de 1,09 à 1,28). L'incidence de complications cardiaques (RC de 1,03; IC à 95 % de 0,87 à 1,12) et de complications neurologiques (RC de 1,23; IC à 95 % de 0,96 à 1,58) avait également tendance à être plus élevée. Chez les personnes de descendance sud-asiatique, le taux de mortalité après 30 jours était plus faible (RC de 0,88; IC à 95 % de 0,78 à 0,98), mais l'incidence d'hospitalisations ou de consultations aux urgences était plus élevée (RC de 1,17; IC à 95 % de 1,14 à 1,20). Elles présentaient également une tendance vers une plus faible incidence de complications cardiaques (RC de 0,76; IC à 95 % de 0,67 à 0,87) et de complications neurologiques (RC de 0,89; IC à 95 % de 0,73 à 1,09). Des différences significatives ont également été observées pour ces paramètres entre les vagues 1, 2 et 3 de la maladie, et le taux de mortalité était plus élevé pour tous les groupes des vagues 2 et 3. Conclusions: L'origine ethnique demeure un déterminant important de la mortalité, des issues cliniques cardiaques et neurologiques ainsi que de l'utilisation des ressources en santé chez les patients atteints de la COVID-19. D'autres études sont toutefois nécessaires pour mieux comprendre les facteurs qui expliquent ces différences.

Derivation and External Validation of a Clinical Model to Predict Heart Failure Onset in Patients With Incident Diabetes.

OBJECTIVE: Heart failure (HF) often develops in patients with diabetes and is recognized for its role in increased cardiovascular morbidity and mortality in this population. Most existing models predict risk in patients with prevalent rather than incident diabetes and fail to account for sex differences in HF risk factors. We derived sex-specific models in Ontario, Canada to predict HF at diabetes onset and externally validated these models in the U.K. RESEARCH DESIGN AND METHODS: Retrospective cohort study using international population-based data. Our derivation cohort comprised all Ontario residents aged ≥18 years who were diagnosed with diabetes between 2009 and 2018. Our validation cohort comprised U.K. patients aged ≥35 years who were diagnosed with diabetes between 2007 and 2017. Primary outcome was incident HF. Sex-stratified multivariable Fine and Gray subdistribution hazard models were constructed, with death as a competing event. RESULTS: A total of 348,027 Ontarians (45% women) and 54,483 U.K. residents (45% women) were included. At 1, 5, and 9 years, respectively, in the external validation cohort, the C-statistics were 0.81 (95% CI 0.79-0.84), 0.79 (0.77-0.80), and 0.78 (0.76-0.79) for the female-specific model; and 0.78 (0.75-0.80), 0.77 (0.76-0.79), and 0.77 (0.75-0.79) for the male-specific model. The models were well-calibrated. Age, rurality, hypertension duration, hemoglobin, HbA1c, and cardiovascular diseases were common predictors in both sexes. Additionally, mood disorder and alcoholism (heavy drinker) were female-specific predictors, while income and liver disease were male-specific predictors. CONCLUSIONS: Our findings highlight the importance of developing sex-specific models and represent an important step toward personalized lifestyle and pharmacologic prevention of future HF development.

Trends in glucose testing among individuals without diabetes in Ontario between 2010 and 2017: a population-based cohort study.

BACKGROUND: Early identification of people with diabetes or prediabetes enables greater opportunities for glycemic control and management strategies to prevent related complications. To identify gaps in screening for these conditions, we examined population trends in receipt of timely glucose testing overall and in specific clinical subgroups. METHODS: Using linked administrative databases, we conducted a retrospective cohort study of people aged 40 years and older without diabetes at baseline. Our primary outcome was up-to-date glucose testing, defined as having received testing at least once in the 3 years before each index year from 2010 to 2017, using linked administrative databases of people residing in Ontario, Canada. We calculated rates of up-to-date testing by age group, sex, ethnicity (South Asian, Chinese, general population) and comorbidities (hypertension, hyperlipidemia, cardiovascular disease). RESULTS: Over the 8-year study period, up-to-date glucose testing rates were stable at 67% for men and 77% for women (both relative risk 1.00 per year; 95% confidence interval 1.00-1.00). Testing rates were significantly lower in men than in women (all age groups p < 0.001) and lower in younger than older age groups (except those aged ≥ 80 yr). South Asian people had the highest testing rates, although among people aged 70 years or older, testing was highest in the general population (p < 0.001). Among people with hypertension, hyperlipidemia and cardiovascular disease, annual testing rates were also stable, but only 58% overall among people with hypertension. INTERPRETATION: We found lower glucose testing rates in younger men and people with hypertension. Our findings reinforce the need for initiatives to increase awareness of glycemic testing.

COVID-19 and its Cardiac and Neurological Complications among Ontario Visible Minorities.

BACKGROUND: Due to lack of data on the epidemiology, cardiac, and neurological complications among Ontario visible minorities (Chinese and South Asians) affected by coronavirus disease (COVID-19), this population-based retrospective study was undertaken to study them systematically. METHODS: From January 1, 2020 to September 30, 2020 using the last name algorithm to identify Ontario Chinese and South Asians who were tested positive by PCR for COVID-19, their demographics, cardiac, and neurological complications including hospitalization and emergency visit rates were analyzed compared to the general population. RESULTS: Chinese (N = 1,186) with COVID-19 were found to be older (mean age 50.7 years) compared to the general population (N = 42,547) (mean age 47.6 years) (p < 0.001), while South Asians (N = 3,459) were younger (age of 42.1 years) (p < 0.001). The 30-day crude rate for cardiac complications among Chinese was 169/10,000 (p = 0.069), while for South Asians, it was 64/10,000 (p = 0.008) and, for the general population, it was 112/10,000. For neurological complications, the 30-day crude rate for Chinese was 160/10,000 (p < 0.001); South Asians was 40/10,000 (p = 0.526), and general population was 48/10,000. The 30-day all-cause mortality rate was significantly higher for Chinese at 8.1% vs 5.0% for the general population (p < 0.001), while it was lower in South Asians at 2.1% (p < 0.001). CONCLUSIONS: Chinese and South Asians in Ontario affected by COVID-19 during the first wave of the pandemic were found to have a significant difference in their demographics, cardiac, and neurological outcomes.

Features of Inflammatory Heart Reactions Following mRNA COVID-19 Vaccination at a Global Level.

Myocarditis and pericarditis may constitute adverse reactions of mRNA coronavirus disease 2019 (COVID-19) vaccines. This study aimed to document these reactions and to assess the association with patient sex and age. This is as an observational retrospective study using a case-non-case design (also called disproportionality study) on inflammatory heart reactions reported with mRNA COVID-19 vaccines within the World Health Organization (WHO) global safety database (VigiBase), up to June 30, 2021. Results are expressed using reporting odds ratios (RORs) and their 95% confidence interval (95% CI). Of 716,576 reports related to mRNA COVID-19 vaccines, 2,277 were cases of inflammatory heart reactions, including 1241 (55%) myocarditis and 851 (37%) pericarditis. The main age group was 18-29 years (704, 31%), and mostly male patients (1,555, 68%). Pericarditis onset was delayed compared with myocarditis with a median time to onset of 8 (3-21) vs. 3 (2-6) days, respectively (P = 0.001). Regarding myocarditis, an important disproportionate reporting was observed in adolescents (ROR, 22.3, 95% CI 19.2-25.9) and in 18-29 years old (ROR, 6.6, 95% CI 5.9-7.5) compared with older patients, as well as in male patients (ROR, 9.4, 95% CI 8.3-10.6). Reporting rate of myocarditis was increased in young adults and adolescents. Inflammatory heart reactions may rarely occur shortly following mRNA COVID-19 vaccination. Although an important disproportionate reporting of myocarditis was observed among adolescents and young adults, particularly in male patients, reporting rates support a very rare risk, that does not seem to compromise the largely positive benefit-risk balance of these vaccines. Furthermore, this study confirmed the value of disproportionality analyses for estimation of relative risks among subgroups of patients.

Multiple omics study identifies an interspecies conserved driver for nonalcoholic steatohepatitis.

Lipotoxicity is a recognized pathological trigger and accelerator of nonalcoholic steatohepatitis (NASH). However, the molecular basis of lipotoxicity-induced NASH remains elusive. Here, we systematically mapped the changes in hepatic transcriptomic landscapes in response to lipotoxic insults across multiple species. Conserved and robust activation of the arachidonic acid pathway, in particular the arachidonate 12-lipoxygenase (ALOX12) gene, was closely correlated with NASH severity in humans, macaques with spontaneously developed NASH, as well as swine and mouse dietary NASH models. Using gain- and loss-of-function studies, we found that ALOX12 markedly exacerbated NASH in both mice and Bama pig models. ALOX12 was shown to induce NASH by directly targeting acetyl-CoA carboxylase 1 (ACC1) via a lysosomal degradation mechanism. Overall, our findings reveal a key molecular driver of NASH pathogenesis and suggest that ALOX12-ACC1 interaction may be a therapeutic target in NASH.

A small molecule targeting ALOX12-ACC1 ameliorates nonalcoholic steatohepatitis in mice and macaques.

Nonalcoholic steatohepatitis (NASH) is a progressive liver disease and has become a leading indication for liver transplantation in the United States. The development of effective therapies for NASH is a major unmet need. Here, we identified a small molecule, IMA-1, that can treat NASH by interrupting the arachidonate 12-lipoxygenase (ALOX12)­acetyl-CoA carboxylase 1 (ACC1) interaction. IMA-1 markedly blocked diet-induced NASH progression in both male mice and Cynomolgus macaque therapeutic models. The anti-NASH efficacy of IMA-1 was comparable to ACC inhibitor in both species. Protein docking simulations and following functional experiments suggested that the anti-NASH effects of IMA-1 were largely dependent on its direct binding to a pocket in ALOX12 proximal to its ACC1-interacting surface instead of inhibiting ALOX12 lipoxygenase activity. IMA-1 treatment did not elicit hyperlipidemia, a known side effect of direct inhibition of ACC enzymatic activity, in both mice and macaques. These findings provide proof of concept across multiple species for the use of small molecule­based therapies for NASH.

The Pathophysiologic Role of Gelsolin in Chronic Kidney Disease: Focus on Podocytes.

Chronic kidney disease (CKD) is normally related to proteinuria, a common finding in a compromised glomerular filtration barrier (GFB). GFB is a structure composed of glomerular endothelial cells, the basement membrane, and the podocytes. CKD with podocyte damage may be associated with actin cytoskeleton reorganization, resulting in podocyte effacement. Gelsolin plays a critical role in several diseases, including cardiovascular diseases and cancer. Our current study aimed to determine the connection between gelsolin and podocyte, and thus the mechanism underlying podocyte injury in CKD. Experiments were carried out on Drosophila to demonstrate whether gelsolin had a physiological role in maintaining podocyte. Furthermore, the survival rate of gelsolin-knocked down Drosophila larvae was extensively reduced after AgNO3 exposure. Secondly, the in vitro podocytes treated with puromycin aminonucleoside (PAN) enhanced the gelsolin protein expression, as well as small GTPase RhoA and Rac1, which also regulated actin dynamic expression incrementally with the PAN concentrations. Thirdly, we further demonstrated in vivo that GSN was highly expressed inside the glomeruli with mitochondrial dysfunction in a CKD mouse model. Our findings suggest that an excess of gelsolin may contribute to podocytes damage in glomeruli.

Pharmacological inhibition of arachidonate 12-lipoxygenase ameliorates myocardial ischemia-reperfusion injury in multiple species.

Myocardial ischemia-reperfusion (MIR) injury is a major cause of adverse outcomes of revascularization after myocardial infarction. To identify the fundamental regulator of reperfusion injury, we performed metabolomics profiling in plasma of individuals before and after revascularization and identified a marked accumulation of arachidonate 12-lipoxygenase (ALOX12)-dependent 12-HETE following revascularization. The potent induction of 12-HETE proceeded by reperfusion was conserved in post-MIR in mice, pigs, and monkeys. While genetic inhibition of Alox12 protected mouse hearts from reperfusion injury and remodeling, Alox12 overexpression exacerbated MIR injury. Remarkably, pharmacological inhibition of ALOX12 significantly reduced cardiac injury in mice, pigs, and monkeys. Unexpectedly, ALOX12 promotes cardiomyocyte injury beyond its enzymatic activity and production of 12-HETE but also by its suppression of AMPK activity via a direct interaction with its upstream kinase TAK1. Taken together, our study demonstrates that ALOX12 is a novel AMPK upstream regulator in the post-MIR heart and that it represents a conserved therapeutic target for the treatment of myocardial reperfusion injury.

Patient- and Physician-Level Factors Associated With Adherence to C-CHANGE Recommendations in Primary Care Settings in Ontario.

BACKGROUND: We previously found large variation among family physicians in adherence to the Canadian Cardiovascular Harmonization of National Guidelines Endeavour (C-CHANGE). We assessed the role of patient- and physician-level factors in the variation in adherence to recommendations for managing cardiovascular disease risk factors. METHODS: We conducted a retrospective study using multilevel logistic regression analyses with the Electronic Medical Record Administrative data Linked Database (EMRALD) housed at ICES in Ontario. Five quality indicators based on C-CHANGE guidelines were modelled. Effects of clustering and between-group variation, patient-level (sociodemographics, comorbidities) and physician-level characteristics (demographic and practice information) were assessed to determine odds ratios of receiving C-CHANGE recommended care. RESULTS: In all, 324 Ontario physicians practicing in 41 clinics who provided care to 227,999 adult patients were studied. We found significant variation in quality indicators, with 15% to 39% of the total variation attributable to nonpatient factors. The largest variation was in performing 2-hour plasma glucose testing in prediabetic patients. Patient-level factors most frequently associated with recommendation adherence included sex, age, and multi-comorbidities. Women were more likely than men to have their body mass index measured, and their blood pressure controlled, but less likely to receive antiplatelet medications and liver-enzyme testing if overweight or obese. CONCLUSIONS: The majority of variations in adherence were attributable to patient attributes, but a substantial proportion of unexplained variation was due to differences among physicians and clinics. This finding may signal suboptimal processes or structures and warrant further investigation to improve the quality of primary care management of cardiovascular disease in Ontario.

CONTEXTE: Nous avions déjà constaté que l'observance des recommandations canadiennes en matière de prévention et de gestion des maladies cardiovasculaires de l'initiative C-CHANGE ( C anadian C ardiovascular H armonization of N ational G uidelines E ndeavour) varie beaucoup d'un médecin de famille à l'autre. Nous avons évalué l'effet de caractéristiques des patients et des médecins sur l'observance de ces recommandations pour la gestion des facteurs de risque de maladies cardiovasculaires. MÉTHODOLOGIE: Nous avons mené une étude rétrospective reposant sur des analyses de régression logistique multiniveaux au sein de la base de données liée aux dossiers médicaux électroniques EMRALD ( E lectronic M edical R ecord A dministrative data L inked D atabase) qui se trouve à l'ICES, en Ontario. Nous avons modélisé cinq indicateurs de la qualité en nous basant sur les recommandations de l'initiative C-CHANGE. Nous avons évalué les effets de regroupement, de la variation entre les groupes, des caractéristiques des patients (données sociodémographiques, maladies concomitantes), des caractéristiques des médecins (données démographiques et renseignements sur la pratique) afin de déterminer les risques relatifs approchés associés aux soins conformes aux recommandations de l'initiative C-CHANGE. RÉSULTATS: L'étude a porté sur un total de 324 médecins ontariens pratiquant dans 41 cliniques et ayant prodigué des soins à 227 999 adultes. Nous avons observé une variation significative entre les indicateurs de qualité, et de 15 % à 39 % de la variation totale était attribuable aux caractéristiques non reliées aux patients. La variation la plus importante concernait le test d'hyperglycémie provoquée (2 heures) chez les patients prédiabétiques. Les caractéristiques des patients qui étaient le plus souvent associées à l'observance des recommandations étaient le sexe, l'âge et la présence de multiples maladies concomitantes. L'indice de masse corporelle et la pression artérielle étaient plus souvent mesurés chez les femmes que chez les hommes, mais les femmes étaient moins susceptibles de recevoir un traitement antiplaquettaire ou de subir une analyse des enzymes hépatiques si elles étaient en surpoids ou obèses. CONCLUSIONS: La plus grande partie des variations dans l'observance des recommandations était liée aux caractéristiques des patients, mais une proportion importante de variations injustifiées était associée aux différences entre les médecins et entre les cliniques. Ces observations pourraient indiquer la présence de processus ou de structures sous-optimales et méritent une analyse approfondie qui permettra d'améliorer la qualité de la prise en charge des maladies cardiovasculaires par les médecins de soins primaires en Ontario.

Sex-specific temporal trends in ambulatory heart failure incidence, mortality and hospitalisation in Ontario, Canada from 1994 to 2013: a population-based cohort study.

OBJECTIVES: To examine the temporal trends in mortality and heart failure (HF) hospitalisation in ambulatory patients following a new diagnosis of HF. DESIGN: Retrospective cohort study SETTING: Outpatient PARTICIPANTS: Ontario residents who were diagnosed with HF in an outpatient setting between 1994 and 2013. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was all-cause mortality within 1 year of diagnosis and the secondary outcome was HF hospitalisation within 1 year. Risks of mortality and hospitalisation were calculated using the Kaplan-Meier method and the relative hazard of death was assessed using multivariable Cox proportional hazard models. RESULTS: A total of 352 329 patients were studied (50% female). During the study period, there was a greater decline in age standardised 1-year mortality rates (AMR) in men (33%) than in women (19%). Specifically, female AMR at 1 year was 10.4% (95% CI 9.1% to 12.0%) in 1994 and 8.5% (95% CI 7.5% to 9.5%) in 2013, and male AMR at 1 year was 12.3% (95% CI 11.1% to 13.7%) in 1994 and 8.3% (95% CI 7.5% to 9.1%) in 2013. Conversely, age standardised HF hospitalisation rates declined in men (11.4% (95% CI 10.1% to 12.9%) in 1994 and 9.1% (95% CI 8.2% to 10.1%) in 2013) but remained unchanged in women (9.7% (95% CI 8.3% to 11.3%) in 1994 and 9.8% (95% CI 8.6% to 11.0%) in 2013). CONCLUSION: Among patients with HF over a 20-year period, there was a greater improvement in the prognosis of men compared with women. Further research should focus on the determinants of this disparity and ways to reduce this gap in outcomes.