Search

Objective: Despite the well-recognized association between pre-existing diabetes mellitus and stillbirth or perinatal mortality, there remain knowledge gaps about the strength of association across different populations. The primary objective of this systematic review and meta-analysis was to quantify the association between pre-existing diabetes and stillbirth or perinatal mortality, and secondarily, to identify risk factors predictive of stillbirth or perinatal mortality among those with pre-existing diabetes., Data Sources: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials from inception to April 2022., Methods of Study Selection: Cohort studies and randomized controlled trials in English or French that examined the association between pre-existing diabetes and stillbirth or perinatal mortality (as defined by the original authors) or identified risk factors for stillbirth and perinatal mortality in individuals with pre-existing diabetes were included. Data extraction was performed independently and in duplicate with the use of prespecified inclusion and exclusion criteria. Assessment for heterogeneity and risk of bias was performed. Meta-analyses were completed with a random-effects model., Tabulation, Integration, and Results: From 7,777 citations, 91 studies met the inclusion criteria. Pre-existing diabetes was associated with higher odds of stillbirth (37 studies; pooled odds ratio [OR] 3.74, 95% CI, 3.17-4.41, I2 =82.5%) and perinatal mortality (14 studies; pooled OR 3.22, 95% CI, 2.54-4.07, I2 =82.7%). Individuals with type 1 diabetes had lower odds of stillbirth (pooled OR 0.81, 95% CI, 0.68-0.95, I2 =0%) and perinatal mortality (pooled OR 0.73, 95% CI, 0.61-0.87, I2 =0%) compared with those with type 2 diabetes. Prenatal care and prepregnancy diabetes care were significantly associated with lower odds of stillbirth (OR 0.26, 95% CI, 0.11-0.62, I2 =87.0%) and perinatal mortality (OR 0.41, 95% CI, 0.29-0.59, I2 =0%)., Conclusion: Pre-existing diabetes confers a more than threefold increased odds of both stillbirth and perinatal mortality. Maternal type 2 diabetes was associated with a higher risk of stillbirth and perinatal mortality compared with maternal type 1 diabetes., Systematic Review Registration: PROSPERO, CRD42022303112., Competing Interests: Financial Disclosure Lois E. Donovan reports in-kind donations and reduced costs for study supplies for investigator-initiated trials from Medtronic, Dexcom, Tandem Diabetes Care, and Inter-analytics. Patricia Lemieux reports receiving honorary from Dexcom for their advisory board. Jennifer M. Yamamoto has received in-kind donations for study supplies from Abbott. The other authors did not report any potential conflicts of interest., (Copyright © 2024 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in females. Modest weight loss improves reproductive and metabolic PCOS features. While lifestyle modifications and pharmacotherapies remain first-line weight loss strategies, bariatric surgery is emerging as a potentially effective treatment. We performed a systematic review and meta-analysis of published literature to examine the impact of bariatric surgery in PCOS to inform the 2023 International PCOS Evidence-based Guidelines. Electronic databases were searched for observational studies and trials comparing pharmacologic or lifestyle treatments to bariatric surgery in women with PCOS or bariatric surgery in women with or without PCOS. Anthropometric, reproductive, hormonal, and metabolic outcomes were included and, where possible, meta-analyzed using random-effects models. Risk of bias and evidence quality were assessed. Ten studies were included involving 432 women with and 590 women without PCOS. Comparisons between bariatric surgery and pharmacologic or lifestyle treatments were only reported in one study each, and most reproductive outcomes were limited to a single study; therefore, meta-analyses could not be performed. Meta-analysis found that women with PCOS experience similar improvements in anthropometric, hormonal, and metabolic outcomes after bariatric surgery compared to those without PCOS. Existing research is limited and of low quality with high risk of bias, especially in comparison to existing PCOS treatments and with respect to reproductive outcomes including pregnancy, highlighting the need for additional studies to inform clinical recommendations., (© 2024 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Polycystic ovary syndrome (PCOS), characterized by abnormal menstrual periods, elevated androgen levels and polycystic ovary morphology on ultrasound, is the most common endocrine disorder among females. PCOS is associated with cardiovascular disease (CVD) risk factors including diabetes, obesity, metabolic syndrome, adverse pregnancy outcomes such as pre-eclampsia and psychosocial distress including depression. Previous evidence on the association between PCOS and CVD is inconclusive but the latest 2023 International Evidence-Based PCOS Guideline identifies PCOS as a risk factor for CVD. This review will discuss the relationship between PCOS and CVD along with current direction for CVD screening and prevention among individuals with PCOS.

Purpose: To examine the independent and joint relationships between cigarette smoking and alcohol consumption with survival outcomes after endometrial cancer diagnosis., Methods: Pre- and post-diagnosis smoking and drinking histories were obtained from endometrial cancer survivors diagnosed between 2002 and 2006 during in-person interviews at-diagnosis and at ~ 3 years post-diagnosis. Participants were followed until death or January 2022. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with Cox proportional hazards regression for associations with disease-free survival (DFS) and overall survival (OS)., Results: During a median 16.9 years of follow-up (IQR = 15.5-18.1 years), 152 of the 540 participants had a DFS event (recurrence: n = 73; deaths: n = 79) and 134 died overall. Most participants in this cohort were current drinkers (pre = 61.3%; post = 64.7%) while few were current cigarette smokers (pre = 12.8%; post = 11.5%). Pre-diagnosis alcohol consumption was not associated with survival, yet post-diagnosis alcohol intake ≥ 2 drinks/week was associated with worse OS compared with lifetime abstention (HR = 2.36, 95%CI = 1.00-5.54) as well as light intake (HR = 3.87, 95% CI = 1.67-8.96). Increased/consistently high alcohol intake patterns were associated with worse OS (HR = 2.91, 95% CI = 1.15-7.37) compared with patterns of decreased/ceased intake patterns after diagnosis. A harmful dose-response relationship per each additional pre-diagnosis smoking pack-year with OS was noted among ever smokers. In this cohort, smoking and alcohol individually were not associated with DFS and combined pre-diagnosis smoking and alcohol intakes were not associated with either outcome., Conclusion: Endometrial cancer survivors with higher alcohol intakes after diagnosis had poorer OS compared with women who had limited exposure. Larger studies powered to investigate the individual and joint impacts of cigarette smoking and alcohol use patterns are warranted to provide additional clarity on these modifiable prognostic factors., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

This final chapter of the Canadian Women's Heart Health Alliance "ATLAS on the Epidemiology, Diagnosis, and Management of Cardiovascular Disease in Women" presents ATLAS highlights from the perspective of current status, challenges, and opportunities in cardiovascular care for women. We conclude with 12 specific recommendations for actionable next steps to further the existing progress that has been made in addressing these knowledge gaps by tackling the remaining outstanding disparities in women's cardiovascular care, with the goal to improve outcomes for women in Canada., (© 2023 The Authors.)

Background: Gestational Diabetes Mellitus (GDM) affects approximately 1 in 7 pregnancies globally. It is associated with short- and long-term risks for both mother and baby. Therefore, optimizing treatment to effectively treat the condition has wide-ranging beneficial effects. However, despite the known heterogeneity in GDM, treatment guidelines and approaches are generally standardized. We hypothesized that a precision medicine approach could be a tool for risk-stratification of women to streamline successful GDM management. With the relatively short timeframe available to treat GDM, commencing effective therapy earlier, with more rapid normalization of hyperglycaemia, could have benefits for both mother and fetus., Methods: We conducted two systematic reviews, to identify precision markers that may predict effective lifestyle and pharmacological interventions., Results: There was a paucity of studies examining precision lifestyle-based interventions for GDM highlighting the pressing need for further research in this area. We found a number of precision markers identified from routine clinical measures that may enable earlier identification of those requiring escalation of pharmacological therapy (to metformin, sulphonylureas or insulin). This included previous history of GDM, Body Mass Index and blood glucose concentrations at diagnosis., Conclusions: Clinical measurements at diagnosis could potentially be used as precision markers in the treatment of GDM. Whether there are other sensitive markers that could be identified using more complex individual-level data, such as omics, and if these can feasibly be implemented in clinical practice remains unknown. These will be important to consider in future studies., (© 2023. Springer Nature Limited.)

Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Utilization of anti-obesity agents is rising in reproductive-age females with some planning for future pregnancy. Lifestyle-induced weight loss has been shown to increase spontaneous conception rate, improve rates of fertility intervention complications, and decrease pregnancy comorbidities. However, the definitive role of assisting weight loss with medication prior to pregnancy remains to be established. The implications of anti-obesity agent used prior to pregnancy are explored in this narrative review, considering benefits of weight loss as well as available evidence for use and risks of anti-obesity agents prior to pregnancy., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme. All rights reserved.)

Objective: To examine the proportion of participants with poor sleep quality, evaluate the associations between sleep quality and anthropometric and cardiometabolic health markers, and evaluate the effect of high intensity interval training (HIIT) and continuous aerobic exercise training (CAET) on sleep quality in polycystic ovary syndrome (PCOS)., Design: Secondary analysis of a pilot randomized controlled trial., Patients: Women with PCOS aged 18-40 years., Measurements: The Pittsburgh Sleep Quality Index (PSQI) was measured at baseline and following a 6-month exercise intervention. A PSQI score >5 indicates poor sleep. Linear regression was used to evaluate the associations between PSQI score and anthropometric and cardiometabolic health markers, and the effect of exercise training on these associations., Results: Thirty-four participants completed the PSQI at baseline, and 29 postintervention: no-exercise control (n = 9), HIIT (n = 12) and CAET (n = 8). At baseline, 79% had poor sleep quality. Baseline PSQI score was positively correlated with body mass index, waist circumference, body weight, haemoglobin A1c and insulin resistance. Mean PSQI score changes were -0.4 (SD 1.1), -0.7 (SD 0.6) and -0.5 (SD 0.9) for control, HIIT and CAET, respectively. For HIIT participants, change in PSQI score was associated with changes in body weight (B = .27, 95% CI 0.10-0.45) and waist circumference (B = .09, 95% CI 0.02-0.17)., Conclusion: Most participants had poor sleep quality which was associated with poorer anthropometric and cardiometabolic health markers. There were no statistically significant changes in PSQI score with exercise training. With HIIT training, decreases in the sleep efficiency score were associated with reductions in body weight and waist circumference. Further studies are needed to determine the effect of exercise training on sleep quality., (© 2023 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)

Background: People with kidney failure treated with dialysis are at increased risk of SARS-CoV-2 infection, and severe COVID-19 outcomes such as hospitalization and death. Though there are well-defined sex differences in outcomes for the general population with COVID-19, we do not know whether this translates into kidney failure populations. We aimed to estimate the differences in COVID-19 symptoms and clinical outcomes between males and females treated with maintenance dialysis., Methods: In this prospective observational cohort study, we included adults treated with maintenance dialysis in Southern Alberta, Canada that tested positive for COVID-19 between March 2020 and February 2022. We examined the association between sex (dichotomized as male and female) with COVID-19 symptoms including fever, cough, malaise, shortness of breath, muscle joints/aches, nausea and/or vomiting, loss of appetite, diarrhea, headache, sore throat, and loss of smell/taste using chi-square or Fisher's exact tests. Secondary outcomes included 30-day hospitalization, ICU admission, and death., Results: Of 1,329 cohort participants, 246 (18.5%) tested positive for SARS-CoV-2 and were included in our study, including 95 females (39%). Of 207 participants with symptoms assessed, females had less frequent fever (p = 0.003), and more nausea or vomiting (p = 0.003) compared to males, after correction for multiple testing. Males exhibited no symptoms 25% of the time, compared with 10% of females (p = 0.01, not significant when corrected for multiple testing). We did not identify statistically significant differences in clinical outcomes between the sexes, though vaccinated patients had lower odds of hospitalization., Conclusions: Sex differences in COVID-19 symptoms were identified in a cohort of patients treated with maintenance dialysis, which may inform sex-specific screening strategies in dialysis units. Further work is necessary to examine mechanisms for identified sex differences., (© 2022. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Background: Adherence to nonpharmaceutical interventions for COVID-19, including physical distancing, masking, staying home while sick, and avoiding crowded indoor spaces, remains critical for limiting the spread of COVID-19., Objective: The aim of this study was to test the effectiveness of using various persuasive appeals (deontological moral frame, empathy, identifiable victim, goal proximity, and reciprocity) at improving intentions to adhere to prevention behaviors., Methods: A randomized online experiment using a representative sample of adult Canadian residents with respect to age, ethnicity, and province of residence was performed from March 3 to March 6, 2021. Participants indicated their intentions to follow public health guidelines, saw one of six flyers featuring a persuasive appeal or no appeal, and then rated their intentions a second time. Known correlates of attitudes toward public health measures were also measured., Results: Intentions to adhere to public health measures increased in all appeal conditions. The message featuring an empathy appeal resulted in a greater increase in intentions than the control (no appeal) message. Moreover, the effectiveness of persuasive appeals was moderated by baseline intentions. Deontological, empathy, identifiable victim, and reciprocity appeals improved intentions more than the control message, but only for people with lower baseline intentions to adhere to nonpharmaceutical interventions., Conclusions: Public health marketing campaigns aiming to increase adherence to COVID-19 protective behaviors could achieve modest gains by employing a range of persuasive appeals. However, to maximize impact, it is important that these campaigns be targeted to the right individuals., Trial Registration: ClinicalTrials.gov NCT05722106; https://clinicaltrials.gov/ct2/show/NCT05722106., (©Mehdi Mourali, Jamie L Benham, Raynell Lang, Madison M Fullerton, Jean-Christophe Boucher, Kirsten Cornelson, Robert J Oxoby, Cora Constantinescu, Theresa Tang, Deborah A Marshall, Jia Hu. Originally published in JMIR Human Factors (https://humanfactors.jmir.org), 13.02.2023.)

Probiotic supplements have been shown to improve bone health in animal models, although it remains uncertain whether these beneficial effects extend to humans. We undertook a systematic review of the literature to determine the effects of probiotic interventions on skeletal outcomes in postmenopausal women. MEDLINE, EMBASE, CENTRAL, and the Cochrane Database of Systematic Reviews were searched from inception to October 2020 for controlled trials comparing the effects of probiotic-containing supplements with placebo on bone mineral density (BMD) or bone turnover markers. Risk of bias was assessed using the Cochrane Risk of Bias 2 Tool. Of 338 records identified, six randomized, placebo-controlled trials ( n  = 632) were eligible for inclusion. All studies assessed postmenopausal women for durations of 6-12 months; three were considered to be at high risk of bias. Four studies examined Lactobacillus-containing probiotics, one assessed a proprietary blend of lactic acid bacteria, and one evaluated Bacillus subtilis . Effects of probiotic interventions on BMD were inconsistent, with the majority of studies demonstrating no benefit at the spine or hip. Probiotic effects on bone turnover markers were similarly heterogeneous. High quality studies are needed to determine whether probiotic interventions have a role in maintaining bone health in humans.

Background: There is limited information regarding the association between missed appointments and neonatal outcomes for diabetes in pregnancy., Study Methods: This retrospective live birth cohort included pregnant women with Type 1 or 2 diabetes who attended specialized clinics from 2008 to 2020. The association between at least one missed antenatal diabetes appointments and outcomes were assessed using logistic regression and reported as adjusted odds ratios (aOR) (95% confidence interval). Mediation analyses were conducted to examine if above target HbA1c mediated these relationships., Results: The cohort included 407 and 902 women with Type 1 and 2 diabetes, respectively, of whom 25.1% and 34.5% missed at least one appointment. Women with Type 1 diabetes who missed an appointment were more likely to have a caesarean section (aOR 1.95 [1.15, 3.31]) and their babies more likely to be admitted to the neonatal intensive care unit (aOR 2.25 [1.35, 3.75]). Women with Type 2 diabetes who missed an appointment were more likely to have a large-for-gestational-age infant (aOR 1.61 [1.13, 2.28]), and an extreme large-for-gestational-age infant (aOR 1.69 [1.02, 2.81]) compared with women who did not miss appointments. Above target HbA1c mediated the relationship between missed appointments and caesarean delivery in Type 1 diabetes and large-for-gestational age and extreme large-for-gestational age in Type 2 diabetes., Conclusion: In individuals with Type 1 and 2 diabetes, there are differences in neonatal outcomes between those who missed an appointment compared to those who did not. It remains unclear if missed diabetes appointments are causative or a marker of other health behaviours or risk factors leading to neonatal morbidity., (© 2022 Diabetes UK.)

Objectives: Individuals with type 2 diabetes should engage in ≥150 min of moderate- to vigorous-intensity physical activity (MVPA) weekly, but most do not meet this guideline. Understanding how social determinants correlate with physical activity in adults with type 2 diabetes may improve development and delivery of physical activity interventions. This study aimed to explore associations between objectively measured MVPA with sociodemographic characteristics in adults with type 2 diabetes., Methods: Cross-sectional data from cycles 1 through 5 of the Canadian Health Measures Survey were analyzed. Participants (N=876) 20 to 79 years of age with type 2 diabetes and ≥4 days of valid activity monitor wear were included. Proportions with 95% confidence intervals for objectively measured MVPA were compared according to sociodemographic characteristics. Ordinal logistic regression was used. Secondary outcomes included light-intensity physical activity, screen time and proportion of activity monitor wear time spent sedentary., Results: Only 15.5% of women and 26.2% of men met Diabetes Canada physical activity guidelines, and approximately 75% of activity monitor wear time was spent in a sedentary state. Higher odds of achieving low levels of physical activity were observed among women who were former or current smokers (odds ratio [OR], 4.51; p<0.001), and among men who were ≥65 years of age (OR, 2.92; p<0.001), of middle (OR, 2.20; p<0.05) and lowest (OR, 3.06; p<0.05) income tertiles and current or former smokers (OR, 3.01; p<0.05)., Conclusions: Sociodemographic factors are strongly associated with levels of MVPA in adults with type 2 diabetes. Sociodemographic information should be routinely collected by clinicians and used to inform more tailored and effective interventions for this patient population., (Copyright © 2022. Published by Elsevier Inc.)

Background: Bluetooth-enabled smartphone apps have been developed and implemented in different sites globally to help overcome capacity limitations of traditional interview-based COVID-19 contact tracing. Two apps are currently available in Canada: ABTraceTogether exclusively in Alberta and COVID Alert in nine other provinces and territories. This study aims to examine factors associated with downloading of these apps to inform targeted promotion and marketing to increase app uptake., Methods: We performed a cross-sectional survey with adult participants (≥18 years old) from an online national panel. Participants were asked if they had downloaded an app and, if applicable, reasons for not downloading. Logistic regression was used to identify sociodemographic factors and trusted information sources associated with downloading and reasons for not downloading., Results: Of the included 4,503 respondents (36% response rate), 1,394 (31%) had downloaded an app. Demographic and socioeconomic factors positively associated with app download were: 1) being female, 2) higher household income, 3) higher education level attained, and 4) more liberal political views. The odds of downloading an app were higher for participants who trusted health-related information sources, and lower for those who trusted internet searches, family and friend, or Facebook. The most cited reasons for not downloading were related to data security concerns and perceived lack of benefit from the apps., Interpretation: These findings identify sociodemographic segments with the lowest app uptake, reasons for not downloading and trusted information sources to inform targeted promotion and marketing strategies to improve uptake of apps to facilitate contact tracing., Competing Interests: The authors have declared that no competing interests exist.

Introduction: We explored associations between sociodemographic factors and public beliefs, behaviors, and information acquisition related to the coronavirus disease 2019 (COVID-19) to identify how the experiences of subpopulations in Canada may vary., Methods: We administered a national online survey through Ipsos Incorporated to adults residing in Canada. Sampling was stratified by population age, sex, and regional distributions. We used descriptive statistics to summarize responses and test for differences based on gender, age, educational attainment, and household income using chi-squared tests, followed by weighted logistic regression., Results: We collected 1996 eligible questionnaires between April 26th and May 1st, 2020. Respondents mean age was 50 years, 51% were women, 56% had a post-secondary degree, and 72% had a household income <$100,000. Our analysis found differences within the four demographic groups, with age effects most acutely evidenced. Respondents 65 years and older were more likely to perceive the pandemic as very serious, less likely to report declines in overall health, and more likely to intend to get vaccinated, compared to 18-29 year olds. Women overall were more likely to report negative outcomes than men, including stress due to the pandemic, and worsening social, mental/emotional, and spiritual health. Respondents 45 and older were more likely to seek and trust information from traditional Canadian news sources, while 18-29 year olds were more likely to seek and trust information on social media; overall, women and respondents with a post-secondary degree were more likely to access and trust online information from public health sites., Conclusion: This study found important demographic differences in how adults living in Canada perceived the COVID-19 pandemic, the impacts on their health, and their preferences for information acquisition. Our results highlight the need to consider demographic characteristics in tailoring the format and information medium to improve large scale acceptance and uptake of mitigation and containment measures., (© 2022. The Author(s).)

Background: Metabolic dysfunction and inflammation have been associated with endometrial cancer risk; however, their influence on endometrial cancer survival is less understood., Methods: A prospective cohort study of 540 endometrial cancer cases diagnosed between 2002 and 2006 in Alberta were followed for survival outcomes to 2019. Baseline blood samples collected either pre- or post-hysterectomy were analyzed for glucose, insulin, adiponectin, leptin, tumor necrosis factor-α, interleukin-6, and C-reactive protein. Covariates were obtained during in-person interviews and via medical chart abstraction. Cox proportional hazard regression models were used to estimate multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) for the association between each biomarker and disease-free and overall survival., Results: Blood samples were collected from 520 of the 540 participants (presurgical n = 235; postsurgical n = 285). During the median follow-up of 14.3 years (range 0.4-16.5 years), there were 125 recurrences, progressions, and/or deaths with 106 overall deaths. None of the biomarkers were associated with disease-free or overall survival in multivariable-adjusted analyses. In an exploratory stratified analysis, the highest level of presurgical adiponectin, compared to the lowest level, was associated with improved disease-free (HR = 0.42, 95% CI = 0.20-0.85) and overall (HR = 0.41, 95% CI = 0.18-0.92) survival, whereas no statistically significant associations were noted for postsurgical measures of adiponectin., Conclusions: Overall, there was no evidence of an association between biomarkers of insulin resistance and inflammation with mortality outcomes in endometrial cancer survivors. Future cohort studies with serial blood samples are needed to understand the impact of changes in insulin resistance and inflammatory markers on endometrial cancer survival., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Diversity in sex and gender are important considerations in the pathogenesis, prognostication, research, and management of diabetic kidney disease (DKD). Sex and gender differences in the disease risk, disease-specific mechanisms, and outcomes in DKD may be attributed to biological differences between males and females at the cellular and tissue level, inconsistencies in the diagnostic and assessment tools used in chronic kidney disease and DKD, as well societal differences in the way men, women, and gender-diverse individuals self-manage and interact with health care systems. This review outlines key considerations related to the impact of sex on DKD, specifically elaborating on how they contribute to observed differences in disease epidemiology, pathogenesis, and treatment strategies. We also highlight the effect of gender on DKD progression and care., (Copyright © 2022. Published by Elsevier Inc.)

Aims/hypothesis: Controversy exists over whether gestational diabetes increases the risk of stillbirth. The aim of this review was to examine the association between gestational diabetes and stillbirth., Methods: We performed searches of the published literature to May 2021. Study selection and data extraction were performed in duplicate by independent reviewers. Meta-analyses of summary measures were conducted using random-effect models for cohort and case-control studies separately. The study protocol was registered in PROSPERO (registration ID CRD42020166939)., Results: From 9981 citations, 419 were identified for full-text review and 73 met inclusion criteria (n = 70,292,090). There was no significant association between gestational diabetes and stillbirth in cohort studies (pooled OR 1.04 [95% CI 0.90, 1.21]; I 2 86.1%) or in case-control studies (pooled OR 1.57 [95% CI 0.83, 2.98]; I 2 94.8%). Gestational diabetes was associated with lower odds of stillbirth among cohort studies presenting with an adjusted OR (pooled OR 0.78 [95% CI 0.68, 0.88]; I 2 42.7%). Stratified analyses by stillbirth ≥28 weeks' gestation, studies published prior to 2013 and studies identified as low quality demonstrated a significantly higher odds of stillbirth in meta-regression (p = 0.016, 0.023 and 0.005, respectively). Egger's test for all included cohort studies (p = 0.018) suggests publication bias for the main meta-analysis., Conclusions/interpretation: Given the substantial heterogeneity across studies, there are insufficient data to define the relationship between stillbirth and gestational diabetes adequately. In the main analyes, gestational diabetes was not associated with an increased risk of stillbirth. However, heterogeneity across studies means this finding should be interpreted cautiously., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: There are concerns that vaccine hesitancy may impede COVID-19 vaccine rollout and prevent the achievement of herd immunity. Vaccine hesitancy is a delay in acceptance or refusal of vaccines despite their availability., Objective: We aimed to identify which people are more and less likely to take a COVID-19 vaccine and factors associated with vaccine hesitancy to inform public health messaging., Methods: A Canadian cross-sectional survey was conducted in Canada in October and November 2020, prior to the regulatory approval of the COVID-19 vaccines. Vaccine hesitancy was measured by respondents answering the question "what would you do if a COVID-19 vaccine were available to you?" Negative binomial regression was used to identify the factors associated with vaccine hesitancy. Cluster analysis was performed to identify distinct clusters based on intention to take a COVID-19 vaccine, beliefs about COVID-19 and COVID-19 vaccines, and adherence to nonpharmaceutical interventions., Results: Of 4498 participants, 2876 (63.9%) reported COVID-19 vaccine hesitancy. Vaccine hesitancy was significantly associated with (1) younger age (18-39 years), (2) lower education, and (3) non-Liberal political leaning. Participants that reported vaccine hesitancy were less likely to believe that a COVID-19 vaccine would end the pandemic or that the benefits of a COVID-19 vaccine outweighed the risks. Individuals with vaccine hesitancy had higher prevalence of being concerned about vaccine side effects, lower prevalence of being influenced by peers or health care professionals, and lower prevalence of trust in government institutions., Conclusions: These findings can be used to inform targeted public health messaging to combat vaccine hesitancy as COVID-19 vaccine administration continues. Messaging related to preventing COVID among friends and family, highlighting the benefits, emphasizing safety and efficacy of COVID-19 vaccination, and ensuring that health care workers are knowledgeable and supported in their vaccination counselling may be effective for vaccine-hesitant populations., (©Jamie L Benham, Omid Atabati, Robert J Oxoby, Mehdi Mourali, Blake Shaffer, Hasan Sheikh, Jean-Christophe Boucher, Cora Constantinescu, Jeanna Parsons Leigh, Noah M Ivers, Scott C Ratzan, Madison M Fullerton, Theresa Tang, Braden J Manns, Deborah A Marshall, Jia Hu, Raynell Lang. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 23.12.2021.)

Background: Maternal weight gain during pregnancy is required for fetal development; however, excess gestational weight gain is associated with increased maternal and neonatal morbidity. We aimed to determine the proportion of Canadian women who gained excess weight during pregnancy and to identify risk factors for excess gestational weight gain., Methods: Self-reported data on maternal weight gain were collected from the 2015/16 and 2017/18 cycles of the Canadian Community Health Survey (CCHS), a cross-sectional population-based survey. We included females aged 15 to 54 years with data on height, prepregnancy weight and gestational weight gain. We defined excess gestational weight gain in terms of preconception body mass index (BMI) according to the 2009 guideline of the US Institute of Medicine. We used logistic regression to evaluate potential risk factors for excess gestational weight gain., Results: Of 1 335 615 Canadian women (weighted from approximately 9300 survey respondents), 422 043 (32%) gained excess weight during pregnancy. Women with obesity had 33% lower odds of gaining excess weight relative to women with overweight (odds ratio 0.67, 95% confidence interval 0.48-0.94). Risk factors for excess gestational weight gain were lower education level, white or Indigenous identity, smoking, mood disorder, anxiety disorder and Canadian citizenship., Interpretation: One-third of Canadian women in this survey had excess gestational weight gain during pregnancy, and women with obesity had lower odds of gaining excess weight during pregnancy relative to women with overweight. Strategies are needed to reduce the proportion of Canadian women who gain excess weight during pregnancy, regardless of preconception BMI., Competing Interests: Competing interests: None declared., (© 2021 CMA Joule Inc. or its licensors.)

Adoption of non-pharmaceutical interventions (NPIs) remains critical to curtail the spread of COVID-19. Using self-reported adherence to NPIs in Canada, assessed through a national cross-sectional survey of 4498 respondents, we aimed to identify and characterize non-adopters of NPIs, evaluating their attitudes and behaviours to understand barriers and facilitators of adoption. A cluster analysis was used to group adopters separately from non-adopters of NPIs. Associations with sociodemographic factors, attitudes towards COVID-19 and the public health response were assessed using logistic regression models comparing non-adopters to adopters. Of the 4498 respondents, 994 (22%) were clustered as non-adopters. Sociodemographic factors significantly associated with the non-adoption cluster were: (1) being male, (2) age 18-34 years, (3) Albertans, (4) lower education level and (5) higher conservative political leaning. Participants who expressed low concern for COVID-19 and distrust towards several institutions had greater odds of being non-adopters. This information characterizes individuals at greatest odds for non-adoption of NPIs to inform targeted marketing interventions., (© 2021. The Author(s).)

Purpose of Review: To review the current evidence for the use of metformin in pregnancy for women with type 2 diabetes., Recent Findings: A large, multicenter, double-blind randomized controlled trial found that women with type 2 diabetes in pregnancy treated with metformin as an adjunct to insulin therapy had less gestational weight gain, insulin requirements, caesarian sections, macrosomia, and neonatal adiposity, but more neonates were small for gestational age (SGA) compared with insulin alone. It is unclear if the higher number of SGA infants are a direct result of metformin exposure or mediated through other effects such as less gestational weight gain and improved glycemic control. Additional follow-up studies of offspring exposed to metformin in utero are required. Metformin may be a useful adjunctive treatment for women with type 2 diabetes in pregnancy to help meet glycemic targets if there are no concerns for or indications of SGA., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The rollout of COVID-19 vaccines has brought vaccine hesitancy to the forefront in managing this pandemic. COVID-19 vaccine hesitancy is fundamentally different from that of other vaccines due to the new technologies being used, rapid development, and widespread global distribution. Attitudes on vaccines are largely driven by online information, particularly information on social media. The first step toward influencing attitudes about immunization is understanding the current patterns of communication that characterize the immunization debate on social media platforms., Objective: We aimed to evaluate societal attitudes, communication trends, and barriers to COVID-19 vaccine uptake through social media content analysis to inform communication strategies promoting vaccine acceptance., Methods: Social network analysis (SNA) and unsupervised machine learning were used to characterize COVID-19 vaccine content on Twitter globally. Tweets published in English and French were collected through the Twitter application programming interface between November 19 and 26, 2020, just following the announcement of initial COVID-19 vaccine trials. SNA was used to identify social media clusters expressing mistrustful opinions on COVID-19 vaccination. Based on the SNA results, an unsupervised machine learning approach to natural language processing using a sentence-level algorithm transfer function to detect semantic textual similarity was performed in order to identify the main themes of vaccine hesitancy., Results: The tweets (n=636,516) identified that the main themes driving the vaccine hesitancy conversation were concerns of safety, efficacy, and freedom, and mistrust in institutions (either the government or multinational corporations). A main theme was the safety and efficacy of mRNA technology and side effects. The conversation around efficacy was that vaccines were unlikely to completely rid the population of COVID-19, polymerase chain reaction testing is flawed, and there is no indication of long-term T-cell immunity for COVID-19. Nearly one-third (45,628/146,191, 31.2%) of the conversations on COVID-19 vaccine hesitancy clusters expressed concerns for freedom or mistrust of institutions (either the government or multinational corporations) and nearly a quarter (34,756/146,191, 23.8%) expressed criticism toward the government's handling of the pandemic., Conclusions: Social media content analysis combined with social network analysis provides insights into the themes of the vaccination conversation on Twitter. The themes of safety, efficacy, and trust in institutions will need to be considered, as targeted outreach programs and intervention strategies are deployed on Twitter to improve the uptake of COVID-19 vaccination., Competing Interests: Conflicts of Interest: None declared., (©Jean-Christophe Boucher, Kirsten Cornelson, Jamie L Benham, Madison M Fullerton, Theresa Tang, Cora Constantinescu, Mehdi Mourali, Robert J Oxoby, Deborah A Marshall, Hadi Hemmati, Abbas Badami, Jia Hu, Raynell Lang. Originally published in JMIR Infodemiology (https://infodemiology.jmir.org), 12.08.2021.)

Objective: Exercise is recommended for polycystic ovary syndrome (PCOS), but the most effective exercise prescription is unclear. This trial compared effects of high-intensity interval training (HIIT), continuous aerobic exercise training (CAET) and no-exercise control on reproductive, anthropometric and cardiometabolic outcomes in PCOS., Design: Pilot randomized controlled trial., Participants: Previously inactive women aged 18-40 years with PCOS., Measurements: Feasibility outcomes included recruitment, retention, adherence to exercise and daily ovulation prediction kit (OPK) testing. Preliminary efficacy outcomes included reproductive, anthropometric and cardiometabolic health markers., Results: Forty-seven women were randomized to no-exercise control (n = 17), HIIT (n = 16), or CAET (n = 14). Forty (85%) participants completed the trial. Median exercise adherence was 68% (IQR 53%, 86%). Median daily OPK-testing adherence in the first half of the intervention was 87% (IQR 61%, 97%) compared with 65% (IQR 0%, 96%) in the second half. Body mass index decreased significantly in CAET compared with control (-1.0 kg/m 2 , p = .01) and HIIT (-0.9 kg/m 2 , p = .04). Mean waist circumference decreased in all groups (-7.3 cm, -6.9 cm, -4.5 cm in HIIT, CAET and control) with no significant between-group differences. Mean LDL-C was significantly reduced for HIIT compared to CAET (-0.33 mmol/L, p = .03). HDL-C increased in HIIT compared with control (0.18 mmol/L, p = .04)., Conclusions: There were feasibility challenges with adherence to daily ovulation assessment limiting the ability to analyse the effect of the exercise interventions on ovulation. CAET and HIIT were both effective at improving anthropometrics and some cardiometabolic health markers. Further studies need to determine optimal and acceptable exercise prescriptions for this population., (© 2021 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)

Background: Workers supporting adults with intellectual disabilities (ID) experience significant stress in their essential role during COVID-19 due to the high risk of their clients contracting COVID-19 and having adverse outcomes. The purpose of the current study was to describe the attitudes of workers towards COVID-19 vaccination prior to vaccination rollout, with a view to informing strategies to promote vaccine uptake within this high-risk sector., Methods: An online survey was sent via email to workers supporting adults with ID in Ontario, Canada, between January 21 and February 3, 2021 by agency leadership and union representatives., Results: Three thousand and three hundred and seventy-one workers, representing approximately 11.2% of Ontario workers supporting adults with ID completed an online survey. Most reported that they were very likely (62%) or likely (20%) to get a COVID-19 vaccine (vaccination intent) although 18% reported they were less likely to do so (vaccination nonintent). Workers with vaccination nonintent were younger and were more likely to endorse the beliefs that (1) it will not benefit them or those around them, (2) it was not part of their job, (3) rapid development confers uncertainties and risks, and (4) they were scared of potential vaccine side effects., Conclusions: There is need to address common misconceptions among workers supporting adults with ID to help activate them as vaccine advocates in the communities they serve. Partnered efforts between workers, unions and agency leadership with public health experts to address concerns are required., (© 2021 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.)

Background: Public support of public health measures including physical distancing, masking, staying home while sick, avoiding crowded indoor spaces and contact tracing/exposure notification applications remains critical for reducing spread of COVID-19. The aim of our work was to understand current behaviours and attitudes towards public health measures as well as barriers individuals face in following public health measures. We also sought to identify attitudes persons have regarding a COVID-19 vaccine and reasons why they may not accept a vaccine., Methods: A cross-sectional online survey was conducted in August 2020, in Alberta, Canada in persons 18 years and older. This survey evaluated current behaviours, barriers and attitudes towards public health measures and a COVID-19 vaccine. Cluster analysis was used to identify key patterns that summarize data variations among observations., Results: Of the 60 total respondents, the majority of persons were always or often physically distancing (73%), masking (65%) and staying home while sick (67%). Bars/pubs/lounges or nightclubs were visited rarely or never by 63% of respondents. Persons identified staying home while sick to provide the highest benefit (83%) in reducing spread of COVID-19. There were a large proportion of persons who had not downloaded or used a contact tracing/exposure notification app (77%) and who would not receive a COVID-19 vaccine when available (20%) or were unsure (12%). Reporting health authorities as most trusted sources of health information was associated with greater percentage of potential uptake of vaccine but not related to contact tracing app download and use. Individuals with lower concern of getting and spreading COVID-19 showed the least uptake of public health measures except for avoiding public places such as bars. Lower concern regarding COVID-19 was also associated with more negative responses to taking a potential COVID-19 vaccine., Conclusion: These results suggest informational frames and themes focusing on individual risks, highlighting concern for COVID-19 and targeting improving trust for health authorities may be most effective in increasing public health measures. With the ultimate goal of preventing spread of COVID-19, understanding persons' attitudes towards both public health measures and a COVID-19 vaccine remains critical to addressing barriers and implementing targeted interventions and messaging to improve uptake.

Background: Effective and efficient participant recruitment is a key determinant of the success of a research program. Previously reported recruitment strategies have displayed variable success rates in studies on women with polycystic ovary syndrome (PCOS)., Objective: This study aimed to evaluate the effectiveness and cost per participant of the recruitment strategies that we used in a prospective randomized controlled trial to examine the effects of exercise training among inactive women with PCOS, who are aged 18-40 years., Methods: The 4 recruitment methods we used were as follows: (1) referral by health care providers or by word of mouth, (2) media (eg, local newspaper stories and radio interviews), (3) Facebook advertisements, and (4) unpaid advertisements including posters and websites. The proportions of potential, eligible, and enrolled participants recruited with each method were determined and compared using tests of proportion. The time investment and cost per participant enrolled were calculated for each recruitment strategy., Results: Of 200 potential participants screened, 98 (49%) were recruited from unpaid advertisements (posters and websites), 70 (35%) from Facebook advertisements, 16 (8%) by referral, and 16 (8%) from traditional media (newspaper and radio). Every potential participant was recruited from separate means (ie, no participant was approached through more than one recruitment method). A total of 109 (54.5%) women were deemed eligible for participation in the trial, and 60 (30.0%) were enrolled. The proportion of potential participants who completed the trial was higher for those recruited from traditional media than from Facebook advertisements (n=7/16, 44% vs n=13/70, 19%, respectively; P=.03) or unpaid advertisements (n=7/16, 44% vs n=13/98, 13%, respectively; P=.002). The cost per participant was Can $18.21 (US $14.46) for Facebook advertisements and Can $43.88 (US $34.85) for unpaid advertisements. There were no direct trial costs for referrals or traditional media., Conclusions: For this trial, each method was important for recruiting inactive women with PCOS because no participant reported learning about the trial through more than one method. Unpaid advertisements and Facebook advertisements helped recruit the largest number of participants in the trial, the former resulting in a higher cost per participant than the latter., Trial Registration: ClinicalTrials.gov NCT03362918; https://clinicaltrials.gov/ct2/show/NCT03362918., (©Jamie L Benham, Jane E Booth, Christine M Friedenreich, Doreen M Rabi, Ronald J Sigal. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 30.03.2021.)

Objective: To evaluate the effect of levothyroxine therapy on pregnancy outcomes compared with placebo or no treatment in women without overt hypothyroidism with presence of thyroid peroxidase antibodies (TPOAb) and/or thyroglobulin antibodies (TgAb)., Design: Systematic review and meta-analysis of randomised controlled trials STUDY ELIGIBILITY CRITERIA: Prespecified criteria for inclusion were: randomised trials of levothyroxine versus control (placebo or no treatment) among women with positive TPOAb or TgAb who were pregnant or considering conception., Data Sources: Ovid MEDLINE, EMBASE, CINAHL, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials were searched from 1980 to 5 November 2020., Outcome Measures: Prespecified data elements were extracted and where appropriate, meta-analyses were conducted. Main outcomes include pregnancy achieved, miscarriage, preterm delivery and live birth., Risk of Bias Assessment: Cochrane Risk of Bias Tool for Quality Assessment of Randomised Controlled Trials., Results: From 3023 citations, 79 citations were identified for full-text review. Of these, six trials (total of 2263 women) were included for qualitative and quantitative analyses. Risk of bias was deemed low for only one trial. There was no significant difference in the relative risk (RR) of pregnancy achieved (RR 1.03; 95% CI 0.93 to 1.13), miscarriage (RR 0.93; 95% CI 0.76 to 1.14), preterm delivery (RR 0.66; 95% CI 0.39 to 1.10) or live births (RR 1.01; 95% CI 0.89 to 1.16) in thyroid autoimmune women treated with levothyroxine compared with controls. Sensitivity analyses of preterm birth identified study quality and timing of levothyroxine initiation as sources of heterogeneity., Conclusions: Among pregnant women or women planning conception, with thyroid autoimmunity, there is a lack of evidence of benefit for levothyroxine use (moderate to high Grading of Recommendations, Assessment, Development and Evaluations). Recommendations to use levothyroxine in this setting need to be reconsidered., Prospero Registration Number: CRD42019130459., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Public health measures to reduce COVID-19 transmission include masking in public places, physical distancing, staying home when ill, avoiding high-risk locations, using a contact tracing app, and being willing to take a COVID-19 vaccine. However, adoption of these measures varies greatly. We aimed to improve health messaging to increase adherence to public health behaviours to reduce COVID-19 transmission by: 1) determining attitudes towards public health measures and current behaviours; 2) identifying barriers to following public health measures; and, 3) identifying public health communication strategies. We recruited participants from a random panel of 3000 phone numbers across Alberta to fill a predetermined quota: age (18-29; 30-59; 60+ years), geographic location (urban; rural), and whether they had school-age children. Two researchers coded and themed all transcripts. We performed content analysis and in-depth thematic analysis. Nine focus groups were conducted with 2-8 participants/group in August-September, 2020. Several themes were identified: 1) importance of public health measures; 2) compliance with public health measures; 3) critiques of public health messaging; and 4) suggestions for improving public health messaging. Physical distancing and masking were seen as more important than using a contact tracing app. There were mixed views around willingness to take COVID-19 vaccine. Current public health messaging was perceived as conflicting. Participants felt that consistent messaging and using social media to reach younger people would be helpful. In conclusion, these findings provide insights that can be used to inform targeted (e.g., by age, current behaviour) public health communications to encourage behaviors that reduce COVID-19 transmission., Competing Interests: The authors have declared that no competing interests exist.

Objective: Clinical trials suggest that SGLT2 inhibitors reduce the risk of cardiovascular mortality in patients with type 2 diabetes, however the mechanism is unclear. Our objective was to test the hypothesis that blood pressure reduction is one potential mechanism underlying the observed improvements in cardiovascular outcomes with SGLT2 inhibitors., Methods: We searched MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (inception-June 2019) for randomized controlled trials that reported the effect of SGLT2 inhibitors compared with placebo on cardiovascular outcomes in adults with type 2 diabetes. Two reviewers independently extracted data and assessed study quality. Random effects meta-analyses, stratified meta-analyses and meta-regressions were conducted to evaluate the association between blood pressure reduction in SGLT2 inhibitor treated patients and cardiovascular outcomes., Results: Of 11,232 articles identified, 40 articles (n = 54,279 participants) were included. The relative risk of cardiovascular mortality was reduced by 18% with the use of SGLT2 inhibitors compared with placebo (RR 0.82; 95%CI 0.74, 0.91, I 2  = 0.0%). Meta-regression analysis revealed no detectable difference in cardiovascular mortality (RR 0.93; 95%CI 0.88, 1.13, p = 0.483), 3-point major adverse cardiovascular events (p = 0.839) or congestive heart failure hospitalizations (p = 0.844) with change in mean systolic blood pressure., Conclusions: Cardiovascular events are reduced in participants with type 2 diabetes treated with SGLT2 inhibitors compared with placebo. There was no significant relationship between the risk of developing adverse cardiovascular events and blood pressure reduction with SGLT2 inhibitors. There is insufficient evidence to suggest that blood pressure reduction is a significant contributor to the cardiovascular benefits observed., Competing Interests: There is no conflict of interest., (© 2021 The Authors.)

Setting: As of June 10, 2020, 37 people experiencing homelessness or unstable housing in Calgary, Alberta, had developed lab-confirmed COVID-19. Spread occurred despite standard outbreak controls at affected shelter and supportive housing sites. Among these 37 cases, drink sharing was frequently identified as a modifiable mode of possible transmission. We collaborated with emergency shelters, a supportive housing site, and street and encampment outreach groups, using mixed service delivery by health staff, non-profits, and peers with lived experience with homelessness., Intervention: To empower individuals to decrease COVID-19 transmission using a harm reduction approach, we provided disposable paper cups to service providers for distribution to clients. Service providers tracked the number of cups distributed. To assess effectiveness, we interviewed staff and peers who distributed the cups., Outcomes: Cup distribution was highest among populations with higher rates of alcohol use, and the intervention was well received by people who drink alcohol regularly, providing unique opportunities to promote COVID-19 awareness and safer drinking practices. Providers to these populations reported enthusiastic client engagement and repeat requests for cups for safer drinking. Intervention usefulness was limited in contexts with low alcohol consumption and in the absence of paired COVID-19 education. Provider reports suggest appropriate disposal of these cups after use., Implications: Disposable cups are a novel, rapidly implementable, low-cost harm reduction tool to empower people experiencing homelessness to reduce the risk of COVID-19 transmission due to drink sharing, ideally as part of a larger harm reduction and community education strategy.

Objectives: Randomized, controlled trials have shown that exercise interventions reduce the incidence of type 2 diabetes in people with impaired glucose tolerance, and improve glycemic control, body composition and cardiorespiratory fitness in people with type 2 diabetes. We undertook the present systematic review to determine the extent to which participants in structured exercise trials continue to be physically active after the end of the interventions., Methods: We systematically searched MEDLINE, EMBASE, CINAHL, SPORTDiscus and Cochrane Central Register of Controlled Trials for randomized, controlled trials that reported objective or self-reported physical activity levels in people with type 2 diabetes or prediabetes a minimum of 3 months after the end of a structured exercise intervention. This systematic review was registered on PROSPERO (PROSPERO CRD42018089468)., Results: Of 14,649 articles retrieved, 5 randomized, controlled trials (including 549 participants) were included in this systematic review. One study revealed significant improvements in self-reported physical activity levels in the intervention group compared with the control group 1, 3 and 5 years after baseline assessments, and decreased waist circumference, weight and body mass index at 1 year, but not 3 or 5 years. The 4 remaining studies did not find between-group differences at follow-up timepoints between 6 months and 3 years., Conclusions: Future research should report physical activity levels at follow up to determine whether participation in a structured exercise intervention results in sustained increased physical activity levels. In addition, interventions should be evaluated for their effectiveness in improving adherence to long-term physical activity., (Copyright © 2020 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Introduction: The Diabetes Aerobic and Resistance Exercise trial found that aerobic training and resistance training alone each reduced hemoglobin A1c (HbA1c) compared with nonexercising controls, and combined aerobic and resistance training caused greater HbA1c reduction than either training type alone. Our objective was to determine whether a dose-response relationship existed between frequency of exercise training and HbA1c change, and whether this varied by exercise modality or participant characteristics., Methods: Post hoc analysis of data from 185 Diabetes Aerobic and Resistance Exercise trial participants with type 2 diabetes randomized to aerobic, resistance or combined training thrice weekly. Dose-response relationships between adherence (percent of prescribed training sessions completed) and HbA1c change were assessed with linear regression., Results: Median overall adherence was 84.9% (interquartile range, 74.4%-93.6%). Higher exercise adherence was associated with greater HbA1c reduction; a 20% increase in adherence (e.g., an additional two sessions per month) was associated with a 0.15% (2 mmol·mol) decrease in HbA1c (β = -0.0076, R = -0.170, P = 0.021). Significant dose-response relationships were identified for aerobic (β = -0.0142, R = -0.313, P = 0.016) and combined training (β = -0.0109, R = -0.259, P = 0.041), but not resistance training (β = 0.0068, R = 0.153, P = 0.233). Dose-response relationships in all training groups combined were significant in subgroups younger than 55 yr (β = -0.0113, R = -0.286, P = 0.005), males (β = -0.0123, R = -0.234, P = 0.010), and baseline HbA1c ≥7.5% (58 mmol·mol) (β = -0.013, R = -0.263, P = 0.011)., Conclusions: There was a dose-response relationship between adherence to prescribed exercise and HbA1c reduction suggesting that glycemic control is improved more in individuals with type 2 diabetes with a higher training volume. Dose-response relationships existed for aerobic and combined training but not resistance training. These findings support aerobic and combined exercise prescriptions outlined in clinical practice guidelines.

Aims/hypothesis: We performed a systematic review and meta-analysis to determine whether exposure to maternal pre-existing diabetes in pregnancy is associated with neurocognitive or behavioural outcomes in offspring., Methods: We searched MEDLINE, EMBASE, PsychINFO, the Cochrane Database of Systematic Reviews and Scopus for studies that examined any neurocognitive or behavioural outcomes in offspring of mothers with pre-existing diabetes in pregnancy in accordance with a published protocol (PROSPERO CRD42018109038). Title and abstract review, full-text review and data extraction were performed independently and in duplicate. Risk of bias was assessed using the Newcastle-Ottawa scale. Meta-analyses of summary measures were performed using random-effects models., Results: Nineteen articles including at least 18,681 exposed and 2,856,688 control participants were identified for inclusion. Exposure to maternal pre-existing diabetes in pregnancy was associated with a lower pooled intelligence quotient in the offspring (pooled weighted mean difference -3.07 [95% CI -4.59, -1.55]; I 2  = 0%) and an increased risk of autism spectrum disorders (effect estimate 1.98 [95% CI 1.46, 2.68]; I 2  = 0%). There was also an increased risk of attention deficit/hyperactivity disorder (pooled HR 1.36 [95% CI 1.19, 1.55]; I 2  = 0%), though this was based on only two studies. Although most studies were found to be high quality in terms of participant selection, in many studies, comparability of cohorts and adequacy of follow-up were sources of bias., Conclusions/interpretation: There is evidence to suggest that in utero exposure to maternal pre-existing diabetes is associated with some adverse neurocognitive and behavioural outcomes. It remains unclear what the role of perinatal factors is and the degree to which other environmental factors contribute to these findings.

Objective: To determine in women with subclinical hypothyroidism diagnosed in pregnancy whether levothyroxine treatment compared with control, impacts important obstetrical or childhood outcomes (specifically IQ) in randomised controlled trials., Design: Systematic review and meta-analysis., Study Eligibility Criteria: Randomised trials which met all the following were included: (1) reported original data of women with subclinical hypothyroidism diagnosed in pregnancy (by any prespecified study definition); (2) randomised to either levothyroxine or control (placebo or no treatment); (3) reported obstetrical outcomes and/or childhood neurodevelopmental outcomes and (4) published from 1980 to January 2018 in either English or French language., Data Sources: Medline, EMBASE, CINAHL, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov., Outcome Measures: Obstetrical, neonatal and childhood outcomes including: miscarriage, gestational hypertension, pre-eclampsia, preterm delivery, mode of delivery, neonatal intensive care unit admission, birth weight, gestational age at delivery, childhood IQ and neurodevelopmental scores. Risk of bias assessment Cochrane Risk of Bias Tool (Modified) for Quality Assessment of Randomised Controlled Trials RESULTS: Three trials of low to unclear risk of bias with 1837 participants were included. Two studies were meta-analysed for maternal and neonatal outcomes and two studies for childhood IQ. No statistically significant differences were found for any clinical outcomes with levothyroxine therapy compared with control., Limitations: Only three trials were identified for inclusion., Conclusions: This review, based on three randomised trials in women with subclinical hypothyroidism diagnosed in pregnancy, found no evidence of benefit of levothyroxine therapy on obstetrical, neonatal, childhood IQ or neurodevelopmental outcomes. Current trial evidence does not support the treatment of subclinical hypothyroidism diagnosed in pregnancy., Prospero Registration Number: CRD4201707980., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Preliminary evidence suggests exercise in polycystic ovary syndrome (PCOS) may improve reproductive and cardiometabolic parameters. Our primary aim was to determine the impact of exercise training on reproductive health in women with PCOS. Our secondary aim was to determine the effect of exercise training on cardiometabolic indices. A systematic review of published literature was conducted using MEDLINE and EMBASE based on a pre-published protocol (PROSPERO CRD42017065324). The search was not limited by year. Randomized controlled trials, non-randomized controlled trials and uncontrolled trials that evaluated an exercise intervention in women with PCOS and reported reproductive outcomes were included. Reproductive outcomes were analysed semi-quantitatively and a meta-analysis was conducted for reported cardiometabolic outcomes. Of 517 screened abstracts, 14 studies involving 617 women with PCOS were included: seven randomized controlled trials, one non-randomized controlled trial and six uncontrolled trials. There were insufficient published data to describe the effect of exercise interventions on ovulation quantitatively, but semi-quantitative analysis suggested that exercise interventions may improve menstrual regularity, pregnancy and ovulation rates. Our meta-analysis found that exercise improved lipid profiles and decreased waist circumference, systolic blood pressure and fasting insulin. The impact of exercise interventions on reproductive function remains unclear. However, our meta-analysis suggests that exercise interventions may improve cardiometabolic profiles in women with PCOS., (© 2018 World Obesity Federation.)

Unilateral primary aldosteronism (PA) is often treated with adrenalectomy, but hypertension resolution rates are variable. A valid estimate of the postoperative normotension rate is necessary to inform the utility of PA testing and treatment. The authors searched MEDLINE In-Process & Other Non-Indexed Citations, Embase, and Cochrane Central Register of Controlled Trials. Prospective adult cohort studies with surgically treated PA that reported resolution of hypertension without the aid of medications were included. Among 2620 abstracts identified by the search, 25 studies in the systematic review with data on 1685 patients were investigated. The pooled proportion of normotension following adrenalectomy was 52% (95% confidence interval, 0.44-0.60). Meta-regression demonstrated a significant negative association between length of follow-up and proportion of normotension, with normotension dropping by 6.7% per year of follow-up (coefficient -0.006; 95% confidence interval, -0.01 to 0.002). Overall, approximately half of the patients experienced hypertension resolution, although this outcome may not be durable in all patients., (©2016 Wiley Periodicals, Inc.)