Kidney trajectory charts improve GP management of patients with reduced kidney function: a randomised controlled vignette study.

BACKGROUND: The stages of chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR) reference ranges are currently determined without considering age. AIM: To determine whether a chart that graphs age with eGFR helps GPs make better decisions about managing patients with declining eGFR. DESIGN & SETTING: A randomised controlled vignette study among Australian GPs using a percentile chart plotting the trajectory of eGFR by age. METHOD: Three hundred and seventy-three GPs received two case studies of patients with declining renal function. They were randomised to receive the cases with the chart or without the chart, and asked a series of questions about how they would manage the cases. RESULTS: In an older female patient with stable but reduced kidney function, use of the chart was associated with GPs in the study recommending a longer follow-up period, and longer time until repeat pathology testing. In a younger male First Nations patient with normal but decreasing kidney function, use of the chart was associated with GPs in the study recommending a shorter follow-up period, shorter time to repeat pathology testing, increased management of blood pressure and lifestyle, and avoidance of nephrotoxic medications. This represents more appropriate care in both cases. CONCLUSION: Having access to a chart of percentile eGFR by age was associated with more appropriate management review periods of patients with reduced kidney function, either by greater compliance with current guidelines or greater awareness of a clinically relevant kidney problem.

Centring the health of women across the HIV research continuum.

Despite tremendous advances in HIV research, women and gender diverse people-particularly women from racial and ethnic groups under-represented in research, transgender women, and young women-remain disproportionately affected by HIV. Women and gender diverse people face unique challenges and have been under-represented in HIV research. The National Institutes of Health (NIH) is tasked to apply fundamental knowledge about the nature and behaviour of living systems to enhance health, lengthen life, and reduce disability. Rigorous exploration of-and interventions for-the individual, social, biological, structural, and environmental factors that influence HIV prevention, transmission, treatment, and cure is crucial to advance research for women, girls, and gender diverse people across the lifespan. In this Position Paper, we introduce a framework for an intersectional, equity-informed, data-driven approach to research on HIV and women and highlight selected issues for women and gender diverse people, including HIV prevention, HIV cure, ageing with HIV, substance use and misuse, violence, pregnancy, and breastfeeding or chestfeeding. This framework underlines a new HIV and Women Signature Programme from the NIH Office of AIDS Research and Office of Research on Women's Health that advances the NIH vision for women's health, in which all women receive evidence-based HIV prevention, treatment, and care across their lifespan tailored to their unique needs, circumstances, and goals. The time is now to centre the health of women, girls, and gender diverse people across the HIV research continuum.

Gender as a social and structural variable: research perspectives from the National Institutes of Health (NIH).

Gender is a social and structural variable that encompasses multiple domains, each of which influences health: gender identity and expression, gender roles and norms, gendered power relations, and gender equality and equity. As such, gender has far-reaching impacts on health. Additional research is needed to continue delineating and untangling the effects of gender from the effects of sex and other biological variables. The National Institutes of Health (NIH) vision for women's health is a world in which the influence of sex and/or gender are integrated into the health research enterprise. However, much of the NIH-supported research on gender and health has, to date, been limited to a small number of conditions (e.g., HIV, mental health, pregnancy) and locations (e.g., sub-Saharan Africa; India). Opportunities exist to support transdisciplinary knowledge transfer and interdisciplinary knowledge building by advancing health-related social science research that incorporates best practices from disciplines that have well-established methods, theories, and frameworks for examining the health impacts of gender and other social, cultural, and structural variables.

Gender encompasses multiple domains, each of which influences health: identity and expression; roles and norms; relations; and power. This commentary focuses on gender-related research at the National Institutes of Health (NIH); identifies areas of opportunity for future health research efforts on gender; and articulates a vision for the robust, transdisciplinary incorporation of gender as a social, cultural, and structural variable into the NIH research agenda. The NIH vision for women's health is a world in which the influence of sex and/or gender are integrated into the health research enterprise. However, much of the NIH-supported research on gender and health has, to date, been limited to a small number of conditions (e.g., HIV, mental health, pregnancy) and locations (e.g., sub-Saharan Africa; India). Approaching the influences of gender on health with scientific rigor is critical to advancing health research that promotes health equity.

Reflecting on Progress in and Establishing Benchmarks for Sex and Gender Health Education.

ABSTRACT: Sex and gender influence every aspect of human health; thus, sex- and gender-related topics should be incorporated in all aspects of health education curricula. Sex and gender health education (SGHE) is the rigorous, intersectional, data-driven integration of sex and gender into all elements of health education. A multisectoral group of thought leaders has collaborated to advance SGHE since 2012. This cross-sector collaboration to advance SGHE has been successful on several fronts, primarily developing robust interprofessional SGHE programs, hosting a series of international SGHE summits, developing sex- and gender-specific resources, and broadening the collaboration beyond medical education. However, other deeply entrenched challenges have proven more difficult to address, including accurate and consistent sex and gender reporting in research publications, broadening institutional support for SGHE, and the development and implementation of evaluation plans for assessing learner outcomes and the downstream effects of SGHE on patient care. This commentary reflects on progress made in SGHE over the first decade of the current collaboration (2012-2022), articulates a vision for next steps to advance SGHE, and proposes 4 benchmarks to guide the next decade of SGHE: (1) integrate sex, gender, and intersectionality across health curricula; (2) develop sex- and gender-specific resources for health professionals; (3) improve sex and gender reporting in research publications; and (4) develop evaluation plans to assess learner and patient outcomes.

Comparison of the performance of cardiovascular risk prediction tools in rural India: the Rishi Valley Prospective Cohort Study.

AIMS: We compared the performance of cardiovascular risk prediction tools in rural India. METHODS AND RESULTS: We applied the World Health Organization Risk Score (WHO-RS) tools, Australian Risk Score (ARS), and Global risk (Globorisk) prediction tools to participants aged 40-74 years, without prior cardiovascular disease, in the Rishi Valley Prospective Cohort Study, Andhra Pradesh, India. Cardiovascular events during the 5-year follow-up period were identified by verbal autopsy (fatal events) or self-report (non-fatal events). The predictive performance of each tool was assessed by discrimination and calibration. Sensitivity and specificity of each tool for identifying high-risk individuals were assessed using a risk score cut-off of 10% alone or this 10% cut-off plus clinical risk criteria of diabetes in those aged >60 years, high blood pressure, or high cholesterol. Among 2333 participants (10 731 person-years of follow-up), 102 participants developed a cardiovascular event. The 5-year observed risk was 4.4% (95% confidence interval: 3.6-5.3). The WHO-RS tools underestimated cardiovascular risk but the ARS overestimated risk, particularly in men. Both the laboratory-based (C-statistic: 0.68 and χ2: 26.5, P = 0.003) and non-laboratory-based (C-statistic: 0.69 and χ2: 20.29, P = 0.003) Globorisk tools showed relatively good discrimination and agreement. Addition of clinical criteria to a 10% risk score cut-off improved the diagnostic accuracy of all tools. CONCLUSION: Cardiovascular risk prediction tools performed disparately in a setting of disadvantage in rural India, with the Globorisk performing best. Addition of clinical criteria to a 10% risk score cut-off aids assessment of risk of a cardiovascular event in rural India. LAY SUMMARY: In a cohort of people without prior cardiovascular disease, tools used to predict the risk of cardiovascular events varied widely in their ability to accurately predict who would develop a cardiovascular event.The Globorisk, and to a lesser extent the ARS, tools could be appropriate for this setting in rural India.Adding clinical criteria, such as sustained high blood pressure, to a cut-off of 10% risk of a cardiovascular event within 5 years could improve identification of individuals who should be monitored closely and provided with appropriate preventive medications.

Continuous Glucose Monitoring Metrics in High-Risk Pregnant Women with Type 2 Diabetes.

Objective: To describe glucose metrics in a high-risk population of women with type 2 diabetes (T2DM) in pregnancy and to explore the associations with neonatal outcomes. Research Design and Methods: Prospective observational study of 57 women. Continuous glucose monitoring (CGM) trajectories were determined from metrics collected in early and late gestation using the first and last two (mean 16 and 35) weeks of Freestyle Libre data. Logistic regression was used to examine associations of CGM metrics with neonatal hypoglycemia (glucose <2.6 mmol/L requiring intravenous dextrose) and large for gestational age (LGA) (>90th percentile for gestational age and sex). Pregnancy-specific target glucose range was 3.5-7.8 mmol/L (63-140 mg/dL). Results: Forty-one women used CGM for 15 weeks (mean age 33 years, 73% Aboriginal or Torres Strait Islander, 32% living remotely). There was limited change in average metrics from early to late pregnancy. For the subgroup with sensor use >50% (n = 29), mean time in range (TIR) increased by 9%, time above range reduced by 12%, average glucose reduced by 1 mmol/L, and time below range increased by 3%. Neonatal hypoglycemia was associated with most CGM metrics, HbA1c and CGM targets, particularly those from late pregnancy. LGA was associated with hyperglycemic metrics from early pregnancy. Each 1% increase TIR was associated with a 4%-5% reduction in risk of neonatal complications. Conclusion: In this high-risk group of women with T2DM, CGM metrics only improved during pregnancy in those with greater sensor use and were associated with LGA in early pregnancy and neonatal hypoglycemia throughout. Culturally appropriate health care strategies are critical for successful use of CGM technology.

Increasing the meaningful involvement of women in HIV cure-related research: a qualitative interview study in the United States.

BACKGROUND: Cisgender women represent over half of people living with HIV globally. However, current research efforts toward a cure for HIV focus predominantly on cisgender men. The under-representation of women in HIV cure clinical studies is particularly problematic given data suggesting that sex-dependent phenotypes limit scientific discovery. OBJECTIVE: We aimed to generate considerations to increase the meaningful involvement of women in HIV cure-related research. MATERIALS AND METHODS: We conducted in-depth interviews with biomedical researchers and community members to better understand factors that could increase the meaningful involvement of women in HIV cure clinical trials. Participants were affiliated with academia, industry, community advisory boards, and community-based organizations, and were identified using listings from the AIDS Clinical Trials Group and the Martin Delaney Collaboratories. We used conventional content analysis to analyze the qualitative data. RESULTS: We recruited 27 participants, of whom 11 were biomedical researchers and 16 were community members. Participants included 25 cisgender women, 1 transgender woman, and 1 cisgender man. Key considerations emerged, including the need to ensure that HIV cure studies reflect HIV epidemiologic trends and having accurate representation by sex and gender in HIV cure research. To increase the meaningful involvement of women, recommendations included instituting intentional enrollment goals, frequent and mandatory reporting on enrollment, and incentives for sites to enroll women. Additional themes included the need for agency and self-determination, attention to lived experiences, trauma and healing, and adequate support for women (e.g. logistical, psychosocial, mental, emotional, and physical). Participants noted that women would be willing to participate in HIV cure trials, related procedures (e.g. biopsies), and analytical treatment interruptions. They also expressed a desired for women-centered and holistic clinical trial designs that account for intersectionality. CONCLUSIONS: Our empirical inquiry extends recent calls to action to increase diversity of people involved in HIV cure research. Redressing the under-inclusion of women in HIV cure research is an urgent imperative. The entire field must mobilize and reform to achieve this goal. Meaningfully involving women across the gender spectrum in HIV cure research is needed to ensure that interventions are safe, effective, scalable, and acceptable for all people with HIV.

Association between maternal hyperglycemia in pregnancy and offspring anthropometry in early childhood: the pandora wave 1 study.

BACKGROUND: In-utero hyperglycemia exposure influences later cardiometabolic risk, although few studies include women with pre-existing type 2 diabetes (T2D) or assess maternal body mass index (BMI) as a potential confounder. OBJECTIVE: To explore the association of maternal T2D and gestational diabetes mellitus (GDM) with childhood anthropometry, and the influence of maternal BMI on these associations. METHODS: The PANDORA cohort comprises women (n = 1138) and children (n = 1163). Women with GDM and T2D were recruited from a hyperglycemia in pregnancy register, and women with normoglycemia from the community. Wave 1 follow-up included 423 children, aged 1.5-5 years (median follow-up age 2.5 years). Multivariable linear regression assessed associations between maternal antenatal variables, including BMI and glycemic status, with offspring anthropometry (weight, height, BMI, skinfold thicknesses, waist, arm and head circumferences). RESULTS: Greater maternal antenatal BMI was associated with increased anthropometric measures in offspring independent of maternal glycemic status. After adjustment, including for maternal BMI, children exposed to maternal GDM had lower mean weight (-0.54 kg, 95% CI: -0.99, -0.11), BMI (-0.55 kg/m2, 95% CI: -0.91, -0.20), head (-0.52 cm, 95% CI: -0.88, -0.16) and mid-upper arm (-0.32 cm, 95% CI: -0.63, -0.01) circumferences, and greater mean suprailiac skinfold (0.78 mm, 95% CI: 0.13, 1.43), compared to children exposed to normoglycemia. Adjustment for maternal BMI strengthened the negative association between GDM and child weight, BMI and circumferences. Children exposed to maternal T2D had smaller mean head circumference (-0.82 cm, 95% CI: -1.33, -0.31) than children exposed to normoglycemia. Maternal T2D was no longer associated with greater child mean skinfolds (p = 0.14) or waist circumference (p = 0.18) after adjustment for maternal BMI. CONCLUSIONS: Children exposed to GDM had greater suprailiac skinfold thickness than unexposed children, despite having lower mean weight, BMI and mid-upper arm circumference, and both GDM and T2D were associated with smaller mean head circumference. Future research should assess whether childhood anthropometric differences influence lifetime cardiometabolic and neurodevelopmental risk.

Pharmacogenetic interactions of efavirenz or rifampin and isoniazid with levonorgestrel emergency contraception during treatment of HIV or tuberculosis.

OBJECTIVE: In AIDS Clinical Trials Group study A5375, a pharmacokinetic trial of levonorgestrel emergency contraception, double-dose levonorgestrel (3 mg, versus standard dose 1.5 mg) offset the induction effects of efavirenz or rifampin on plasma levonorgestrel exposure over 8 h post-dose (AUC 0-8h ). We characterized the pharmacogenetics of these interactions. METHODS: Cisgender women receiving efavirenz- or dolutegravir-based HIV therapy, or on isoniazid-rifampin for tuberculosis, were followed after a single oral dose of levonorgestrel. Linear regression models, adjusted for BMI and age, characterized associations of CYP2B6 and NAT2 genotypes (which affect plasma efavirenz and isoniazid exposure, respectively) with levonorgestrel pharmacokinetic parameters. RESULTS: Of 118 evaluable participants, 17 received efavirenz/levonorgestrel 1.5 mg, 35 efavirenz/levonorgestrel 3 mg, 34 isoniazid-rifampin/levonorgestrel 3 mg, and 32 (control group) dolutegravir/levonorgestrel 1.5 mg. There were 73 Black and 33 Asian participants. Regardless of genotype, women on efavirenz and isoniazid-rifampin had higher levonorgestrel clearance. In the efavirenz/levonorgestrel 3 mg group, CYP2B6 normal/intermediate metabolizers had levonorgestrel AUC 0-8h values similar to controls, while CYP2B6 poor metabolizers had AUC 0-8h values of 40% lower than controls. In the isoniazid-rifampin group, NAT2 rapid/intermediate acetylators had levonorgestrel AUC 0-8h values similar to controls, while NAT2 slow acetylators had AUC 0-8h values 36% higher than controls. CONCLUSION: CYP2B6 poor metabolizer genotypes exacerbate the efavirenz-levonorgestrel interaction, likely by increased CYP3A induction with higher efavirenz exposure, making the interaction more difficult to overcome. NAT2 slow acetylator genotypes attenuate the rifampin-levonorgestrel interaction, likely by increased CYP3A inhibition with higher isoniazid exposure.

Structural Sexism and Cancer Care: The Effects on the Patient and Oncologist.

Despite progress toward equity within our broad social context, the domains of gender as a social, cultural, and structural variable continue to exert influence on the delivery of oncology care. Although there have been vast advances in our understanding of the biological underpinnings of cancer and significant improvements in clinical care, disparities in cancer care for all women-including cisgender, transgender, and gender diverse women-persist. Similarly, despite inclusion within the oncology physician workforce, women and gender minorities, particularly those with additional identities under-represented in medicine, still face structural barriers to clinical and academic productivity and career success. In this article, we define and discuss how structural sexism influences both the equitable care of patients with cancer and the oncology workforce and explore the overlapping challenges in both realms. Solutions toward creating environments where patients with cancer of any gender receive optimal care and all physicians can thrive are put forward.

Public Priorities in Women's Health: Analysis of Request for Information Published to Inform "Advancing NIH Research on the Health of Women: A 2021 Conference".

Objectives: To assist with planning a congressionally requested conference on women's health research, the National Institutes of Health (NIH) Office of Research on Women's Health (ORWH) invited comments to characterize public concerns related to any or all of the specified public health issues: maternal morbidity and mortality (MMM); stagnant rates of cervical cancer survival; and the growing incidence of chronic debilitating conditions in women (CDCW). This analysis summarizes public priorities in women's health research. Materials and Methods: All comments received in response to a request for information were open coded and a master list of keywords was created, and comments were categorized. Comments addressing CDCW were categorized using a conceptual framework developed by the NIH. Results: Two hundred forty-seven comments were coded and analyzed. One hundred four comments (42%) addressed MMM; 182 comments (73%) discussed CDCW; and 27 comments (10%) addressed cervical cancer. Comments focused on CDCW most frequently addressed female-specific conditions (83%). The 10 most frequently identified keywords in order of frequency from the manual coding were as follows: (1) MMM, (2) racial disparities, (3) access to care, (4) provider training, (5) mental health, (6) Black or African American women, (7) screening, (8) quality of care, (9) time to diagnosis, and (10) social determinants of health. Conclusions: Comments demonstrate a broad range of concerns related to the health of women, including MMM, CDCW, and cervical cancer. A wide array of commenters included patients, advocacy groups, and academic and professional organizations originating from geographically diverse locations. These comments reflect a strong desire from the public to prioritize research on the health of women.

Chronic conditions in women: the development of a National Institutes of health framework.

Rising rates of chronic conditions were cited as one of the key public health concerns in the Fiscal Year (FY) 2021 U.S. Senate and House of Representatives appropriations bills, where a review of current National Institutes of Health (NIH) portfolios relevant to research on women's health was requested. Chronic conditions were last defined by the US Department of Health and Human Services (HHS) in 2010. However, existing definitions of chronic conditions do not incorporate sex or gender considerations. Sex and gender influence health, yet significant knowledge gaps exist in the evidence-base for prevention, diagnosis, and treatment of chronic diseases amongst women. The presentation, prevalence, and long-term effects of chronic conditions and multimorbidity differs in women from men. A clinical framework was developed to adequately assess the NIH investment in research related to chronic conditions in women. The public health needs and NIH investment related to conditions included in the framework were measured. By available measures, research within the NIH has not mapped to the burden of chronic conditions among women. Clinical research questions and endpoints centered around women can be developed and implemented; clinical trials networks with expanded or extended eligibility criteria can be created; and data science could be used to extrapolate the effects of overlapping or multiple morbidities on the health of women. Aligning NIH research priorities to address the specific needs of women with chronic diseases is critical to addressing women's health needs from a life course perspective.

Risk of kidney disease following a pregnancy complicated by diabetes: a longitudinal, population-based data-linkage study among Aboriginal women in the Northern Territory, Australia.

AIMS/HYPOTHESIS: The aim of this work was to investigate the risk of developing chronic kidney disease (CKD) or end-stage kidney disease (ESKD) following a pregnancy complicated by gestational diabetes mellitus (GDM) or pre-existing diabetes among Aboriginal women in the Northern Territory (NT), Australia. METHODS: We undertook a longitudinal study of linked healthcare datasets. All Aboriginal women who gave birth between 2000 and 2016 were eligible for inclusion. Diabetes status in the index pregnancy was as recorded in the NT Perinatal Data Collection. Outcomes included any stage of CKD and ESKD as defined by ICD-10 coding in the NT Hospital Inpatient Activity dataset between 2000 and 2018. Risk was compared using Cox proportional hazards regression. RESULTS: Among 10,508 Aboriginal women, the mean age was 23.1 (SD 6.1) years; 731 (7.0%) had GDM and 239 (2.3%) had pre-existing diabetes in pregnancy. Median follow-up was 12.1 years. Compared with women with no diabetes during pregnancy, women with GDM had increased risk of CKD (9.2% vs 2.2%, adjusted HR 5.2 [95% CI 3.9, 7.1]) and ESKD (2.4% vs 0.4%, adjusted HR 10.8 [95% CI 5.6, 20.8]). Among women with pre-existing diabetes in pregnancy, 29.1% developed CKD (adjusted HR 10.9 [95% CI 7.7, 15.4]) and 9.9% developed ESKD (adjusted HR 28.0 [95% CI 13.4, 58.6]). CONCLUSIONS/INTERPRETATION: Aboriginal women in the NT with GDM or pre-existing diabetes during pregnancy are at high risk of developing CKD and ESKD. Pregnancy presents an important opportunity to identify kidney disease risk. Strategies to prevent kidney disease and address the social determinants of health are needed.

Pharmacokinetics of dose-adjusted levonorgestrel emergency contraception combined with efavirenz-based antiretroviral therapy or rifampicin-containing tuberculosis regimens.

OBJECTIVES: To determine if double-dose levonorgestrel emergency contraception (EC) in combination with efavirenz or rifampicin, 2 drugs known to decrease levonorgestrel exposure, resulted in similar pharmacokinetics compared to standard-dose levonorgestrel EC without drug-drug interactions. STUDY DESIGN: We conducted a phase 2, open-label, multicenter, partially randomized, 4 parallel group trial in pre-menopausal females ≥16 years old without an indication for EC and not on hormonal contraception. Participants on dolutegravir-based antiretroviral therapy (ART) received levonorgestrel 1.5 mg (control group); those on rifampicin-containing tuberculosis therapy received levonorgestrel 3 mg; those on efavirenz-based ART were randomized 1:2 to levonorgestrel 1.5 mg or 3 mg. Plasma was collected through 48 hours post-dose to assess levonorgestrel pharmacokinetics. Area under the concentration-time curve (AUC) over 8 hours was the primary outcome. Levonorgestrel pharmacokinetic parameters were compared between groups using geometric mean ratios (GMR) with 90% confidence intervals. RESULTS: The median (Q1, Q3) age for all participants (n = 118) was 34 (27, 41) years and BMI was 23.2 (20, 26.3) kg/m2. Participants receiving levonorgestrel 1.5mg plus efavirenz (n = 17) had 50% lower AUC0-8h compared to the control group (n = 32) [0.50 (0.40, 0.62)]. Participants receiving levonorgestrel 3 mg had a similar AUC0-8h when receiving either efavirenz (n = 35) [0.99 (0.81, 1.20)] or rifampicin (n = 34) [1.16 (0.99, 1.36)] compared to control. Levonorgestrel 3 mg resulted in similar or higher maximum concentration with either efavirenz [1.17 (0.96, 1.41)] or rifampicin [1.27 (1.09, 1.49)] compared to the control group. CONCLUSIONS: Doubling the dose of levonorgestrel EC successfully increased levonorgestrel exposure over the first 8 hours in participants receiving either efavirenz-based ART or rifampicin-containing tuberculosis therapy. IMPLICATIONS: Adjusting levonorgestrel emergency contraception from 1.5 mg to 3 mg improves levonorgestrel pharmacokinetic exposure in participants receiving either efavirenz-based antiretroviral regimens or rifampicin-containing tuberculosis therapy. These data support guideline recommendations to double the dose of levonorgestrel emergency contraception in persons on medications that decrease levonorgestrel exposure by inducing levonorgestrel metabolism.

Pancreatitis and post-pancreatitis diabetes in Central Australia.

BACKGROUND: Pancreatitis and diabetes are common among Aboriginal people of Central Australia. The contribution of pancreatitis to the development of post-pancreatitis diabetes mellitus (PPDM) is not known. AIMS: To describe among Aboriginal and non-Aboriginal people living in Central Australia, (i) the prevalence and aetiology of acute (AP) and chronic pancreatitis (CP), and (ii) diagnosis of new onset diabetes after pancreatitis. METHODS: Retrospective medical record review of patients ≥15 years admitted to hospitals in the Central Australia Health Service between 2009 and 2018 with pancreatitis. Prevalence as a proportion of the resident population and aetiology of AP and CP were determined. Diagnosis of new onset diabetes after admission with pancreatitis was assessed. RESULTS: Of the 638 patients assessed, 73% were Aboriginal and 48% female. The annual prevalence in 2009 and 2018 for AP was 171 and 203 per 100 000 persons, and for CP was 206 and 114 per 100 000 persons respectively. Rates were high in Aboriginal people. Alcohol aetiology was most common in Aboriginal people (66%) and biliary aetiology in non-Aboriginal people (37%). A diagnosis of diabetes after pancreatitis was detected in 125 (29%) of 438 patients who did not have a diabetes diagnosis previously recorded, and 20 of the 22 tested for diabetes-associated antibodies were negative, fitting criteria for PPDM. CONCLUSION: Prevalence of AP and CP in Central Australia was higher in Aboriginal than non-Aboriginal people. Few patients with diabetes recorded after pancreatitis had appropriate PPDM diagnostic testing. Interdisciplinary education on the diagnosis of PPDM is required.

Postpartum uptake of diabetes screening tests in women with gestational diabetes: The PANDORA study.

AIMS: To determine rates and predictors of postpartum diabetes screening among Aboriginal and/or Torres Strait Islander and non-Indigenous women with gestational diabetes mellitus (GDM). METHODS: PANDORA is a prospective longitudinal cohort of women recruited in pregnancy. Postpartum diabetes screening rates at 12 weeks (75-g oral glucose tolerance test (OGTT)) and 6, 12 and 18 months (OGTT, glycated haemoglobin [HbA1C ] or fasting plasma glucose) were assessed for women with GDM (n = 712). Associations between antenatal factors and screening with any test (OGTT, HbA1C , fasting plasma glucose) by 6 months postpartum were examined using Cox proportional hazards regression. RESULTS: Postpartum screening rates with an OGTT by 12 weeks and 6 months postpartum were lower among Aboriginal and/or Torres Strait Islander women than non-Indigenous women (18% vs. 30% at 12 weeks, and 23% vs. 37% at 6 months, p < 0.001). Aboriginal and/or Torres Strait Islander women were more likely to have completed a 6-month HbA1C compared to non-Indigenous women (16% vs. 2%, p < 0.001). Screening by 6 months postpartum with any test was 41% for Aboriginal and/or Torres Strait Islander women and 45% for non-Indigenous women (p = 0.304). Characteristics associated with higher screening rates with any test by 6 months postpartum included, insulin use in pregnancy, first pregnancy, not smoking and lower BMI. CONCLUSIONS: Given very high rates of type 2 diabetes among Aboriginal and Torres Strait Islander women, early postpartum screening with the most feasible test should be prioritised to detect prediabetes and diabetes for intervention.

Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses.

BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min-1·1.73 m-2, with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min-1·1.73 m-2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.

Association between hyperglycaemia in pregnancy and growth of offspring in early childhood: The PANDORA study.

BACKGROUND: Few studies have assessed whether children exposed to in utero hyperglycaemia experience different growth trajectories compared to unexposed children. OBJECTIVES: To assess association of type 2 diabetes (T2D) and gestational diabetes mellitus (GDM) with early childhood weight, length/height and body mass index (BMI) trajectories, and with timing and magnitude of peak BMI in infancy. METHODS: PANDORA is a birth cohort recruited from an Australian hyperglycaemia in pregnancy register, and women with normoglycaemia recruited from the community. Offspring growth measures were obtained from health records over a median follow-up of 3.0 years (interquartile range 1.9-4.0). This analysis included children born to Aboriginal mothers with in utero normoglycaemia (n = 95), GDM (n = 228) or T2D (n = 131). Growth trajectories (weight, length/height and BMI) were estimated using linear mixed models with cubic spline functions of child age. RESULTS: After adjustment for maternal factors (age, BMI, parity, smoking, and socioeconomic measures) and child factors (age, gestational age at birth, and sex), children born to mothers with T2D or GDM had lower weight, length/height and BMI trajectories in infancy than children born to mothers with normoglycaemia, but similar weight and BMI by completion of follow-up. Children exposed to T2D had lower mean peak BMI 17.6 kg/m2 (95% confidence interval [CI] 17.3-18.0) than children exposed to normoglycaemia (18.6 kg/m2 [18.1-18.9]) (p = 0.001). CONCLUSIONS: Maternal hyperglycaemia was associated with differences in early childhood growth trajectories after adjustment for maternal BMI. Exploration of associations between in utero hyperglycaemia exposure and growth trajectories into later childhood is required.

Prevalence and incidence of diabetes among Aboriginal people in remote communities of the Northern Territory, Australia: a retrospective, longitudinal data-linkage study.

OBJECTIVES: To assess the prevalence and incidence of diabetes among Aboriginal peoples in remote communities of the Northern Territory (NT), Australia. DESIGN: Retrospective cohort analysis of linked clinical and administrative data sets from 1 July 2012 to 30 June 2019. SETTING: Remote health centres using the NT Government Primary Care Information System (51 out of a total of 84 remote health centres in the NT). PARTICIPANTS: All Aboriginal clients residing in remote communities serviced by these health centres (N=21 267). PRIMARY OUTCOME MEASURES: Diabetes diagnoses were established using hospital and primary care coding, biochemistry and prescription data. RESULTS: Diabetes prevalence across all ages increased from 14.4% (95% CI: 13.9% to 14.9%) to 17.0% (95% CI: 16.5% to 17.5%) over 7 years. Among adults (≥20 years), the 2018/2019 diabetes prevalence was 28.6% (95% CI: 27.8% to 29.4%), being higher in Central Australia (39.5%, 95% CI: 37.8% to 41.1%) compared with the Top End region (24.2%, 95% CI: 23.3% to 25.1%, p<0.001). Between 2016/2017 and 2018/2019, diabetes incidence across all ages was 7.9 per 1000 person-years (95% CI: 7.3 to 8.7 per 1000 person-years). The adult incidence of diabetes was 12.6 per 1000 person-years (95% CI: 11.5 to 13.8 per 1000 person-years). CONCLUSIONS: The burden of diabetes in the remote Aboriginal population of the NT is among the highest in the world. Strengthened systems of care and public health prevention strategies, developed in partnership with Aboriginal communities, are needed.