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Background/aims: The authors have previously reported a short term mean 15 month follow up of nasolacrimal intubation in adults. The effectiveness of this procedure for long term (mean 78 months) control of epiphoria is assessed here. Methods: 65 eyes from 40 patients who underwent nasolacrimal intubation were followed. Mean age at intubation was 59.2 years. The mean follow up period was 6.2 years. The results were based on long term symptomatic improvement. Results: Complete long term resolution of symptoms was reported in 50.7%. A partial improvement was reported in 38.5%, and no improvement in 10.7%. A better outcome was associated with a canalicular than nasolacrimal duct obstruction. On long term follow up 16.9% required dacrocysto-rhinostomy (DCR). Conclusion: Nasolacrimal intubation, a minimally invasive procedure is successful in the long term control of epiphora. Selection of patients with canalicular duct obstruction gives higher success rates with fewer patients subsequently requiring the DCR procedure. [ABSTRACT FROM AUTHOR]

Objective(s): To evaluate if the type of abortion patients prefer differs for those with a history of intimate partner violence (IPV) compared to those without a history of IPV., Study Design: We compared choice of medication versus procedural abortion between those with a history of lifetime IPV and those without a history of IPV among patients seeking abortion at 11 weeks' gestation or less. Secondarily, we compared preferred abortion characteristics and assessed reproductive autonomy. Individuals presenting for abortion care were recruited for an anonymous, cross-sectional survey study at Planned Parenthood League of Massachusetts, Boston Health Center from September 2021 to August 2022. We required 336 subjects to detect a 20% difference in abortion method between those with a lifetime history of IPV and those without, with 80% power., Results: We enrolled 342 participants and excluded 6 with missing data. A total of seventy-one individuals (21%) reported a lifetime history of IPV. A majority of individuals with a lifetime history of IPV chose procedural abortion, although their abortion method choice did not differ significantly from individuals with no history of IPV (56.3% versus 47.2%, p=.244). Individuals with a lifetime IPV history used abortion funds more frequently than those without a history of lifetime IPV (8.5% versus 1.5%, p=.047). There was no statistical difference between individuals with and without a lifetime history of IPV regarding what individuals considered important for the type of abortion they chose or reproductive autonomy., Conclusion(s): Access to procedural abortion services and abortion funds are important to meet the abortion needs of patients with a lifetime history of IPV., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Hypertensive disorders of pregnancy (HDP) are significant drivers of maternal and neonatal morbidity and mortality. Current management strategies include early identification and initiation of risk mitigating interventions facilitated by a rules-based checklist. Advanced analytic techniques, such as machine learning, can potentially offer improved and refined predictive capabilities., Objective: To develop and internally validate a machine learning prediction model for hypertensive disorders of pregnancy (HDP) when initiating prenatal care., Study Design: We developed a prediction model using data from the prospective multisite cohort Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b) among low-risk individuals without a prior history of aspirin utilization for preeclampsia prevention. The primary outcome was the development of HDP. Random forest modeling was utilized to develop predictive models. Recursive feature elimination (RFE) was employed to create a reduced model for each outcome. Area under the curve (AUC), 95% confidence intervals (CI), and calibration curves were utilized to assess discrimination and accuracy. Sensitivity analyses were conducted to compare the sensitivity and specificity of the reduced model compared to existing risk factor-based algorithms., Results: Of 9,124 assessed low risk nulliparous individuals, 21% (n=1,927) developed HDP. The prediction model for HDP had satisfactory discrimination with an AUC of 0.73 (95% CI: 0.70, 0.75). After RFE, a parsimonious reduced model with 30 features was created with an AUC of 0.71 (95% CI: 0.68, 0.74). Variables included in the model after RFE included body mass index at the first study visit, pre-pregnancy weight, first trimester complete blood count results, and maximum systolic blood pressure at the first visit. Calibration curves for all models revealed relatively stable agreement between predicted and observed probabilities. Sensitivity analysis noted superior sensitivity (AUC 0.80 vs 0.65) and specificity (0.65 vs 0.53) of the model compared to traditional risk factor-based algorithms., Conclusion: In cohort of low-risk nulliparous pregnant individuals, a prediction model may accurately predict HDP diagnosis at the time of initiating prenatal care and aid employment of close interval monitoring and prophylactic measures earlier in pregnancy., (© 2024 The Authors.)

Unlabelled: User engagement with remote blood pressure monitoring during pregnancy is critical to optimize the associated benefits of blood pressure control and early detection of hypertensive disorders of pregnancy. In our study population of pregnant individuals, we found that connected blood pressure cuffs, which automatically sync measures to a monitoring platform or health record, increase engagement (2.13 [95% CI 1.36-3.35] times more measures per day) with remote blood pressure monitoring compared to unconnected cuffs that require manual entry of measures., (© Mia Charifson, Timothy Wen, Bonnie Zell, Priyanka Vaidya, Cynthia I Rios, C Funsho Fagbohun, Isabel Fulcher. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org).)

Background: Continuous glucose monitoring has facilitated the evaluation of dynamic changes in glucose throughout the day and their effect on fetal growth abnormalities in pregnancy. However, studies of multiple continuous glucose monitoring metrics combined and their association with other adverse pregnancy outcomes are limited., Objective: This study aimed to (1) use machine learning techniques to identify discrete glucose profiles based on weekly continuous glucose monitoring metrics in pregnant individuals with pregestational diabetes mellitus and (2) investigate their association with adverse pregnancy outcomes., Study Design: This study analyzed data from a retrospective cohort study of pregnant patients with type 1 or 2 diabetes mellitus who used Dexcom G6 continuous glucose monitoring and delivered a nonanomalous, singleton pregnancy at a tertiary center between 2019 and 2023. Continuous glucose monitoring data were collapsed into 39 weekly glycemic measures related to centrality, spread, excursions, and circadian cycle patterns. Principal component analysis and k-means clustering were used to identify 4 discrete groups, and patients were assigned to the group that best represented their continuous glucose monitoring patterns during pregnancy. Finally, the association between glucose profile groups and outcomes (preterm birth, cesarean delivery, preeclampsia, large-for-gestational-age neonate, neonatal hypoglycemia, and neonatal intensive care unit admission) was estimated using multivariate logistic regression adjusted for diabetes mellitus type, maternal age, insurance, continuous glucose monitoring use before pregnancy, and parity., Results: Of 177 included patients, 90 (50.8%) had type 1 diabetes mellitus, and 85 (48.3%) had type 2 diabetes mellitus. This study identified 4 glucose profiles: (1) well controlled; (2) suboptimally controlled with high variability, fasting hypoglycemia, and daytime hyperglycemia; (3) suboptimally controlled with minimal circadian variation; and (4) poorly controlled with peak hyperglycemia overnight. Compared with the well-controlled profile, the suboptimally controlled profile with high variability had higher odds of a large-for-gestational-age neonate (adjusted odds ratio, 3.34; 95% confidence interval, 1.15-9.89). The suboptimally controlled with minimal circadian variation profile had higher odds of preterm birth (adjusted odds ratio, 2.59; 95% confidence interval, 1.10-6.24), cesarean delivery (adjusted odds ratio, 2.76; 95% confidence interval, 1.09-7.46), and neonatal intensive care unit admission (adjusted odds ratio, 4.08; 95% confidence interval, 1.58-11.40). The poorly controlled profile with peak hyperglycemia overnight had higher odds of preeclampsia (adjusted odds ratio, 2.54; 95% confidence interval, 1.02-6.52), large-for-gestational-age neonate (adjusted odds ratio, 3.72; 95% confidence interval, 1.37-10.4), neonatal hypoglycemia (adjusted odds ratio, 3.53; 95% confidence interval, 1.37-9.71), and neonatal intensive care unit admission (adjusted odds ratio, 3.15; 95% confidence interval, 1.20-9.09)., Conclusion: Discrete glucose profiles of pregnant individuals with pregestational diabetes mellitus were identified through joint consideration of multiple continuous glucose monitoring metrics. Prolonged exposure to maternal hyperglycemia may be associated with a higher risk of adverse pregnancy outcomes than suboptimal glycemic control characterized by high glucose variability and intermittent hyperglycemia., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Although community health worker (CHW) programs focus on improving access to healthcare, some individuals may not receive the intended quality or quantity of an intervention. The objective of this research was to examine if certain populations of pregnant women differentially experience the implementation of a community health worker-led maternal health intervention in Zanzibar., Methods: We included pregnant women enrolled in the Safer Deliveries (Uzazi Salama) program, which operated in 10 of 11 districts in Zanzibar, Tanzania between January 1, 2017, and June 19, 2019 (N = 33,914). The outcomes of interest were receipt of the entire postpartum intervention (three CHW visits) and time to first postpartum CHW visit (days). Visits by CHWs were done at the women's home, however, a telehealth option existed for women who were unable to be reached in-person. We conducted statistical tests to investigate the bivariate associations between our outcomes and each demographic and health characteristic. We used multivariate logistic regression to estimate the relationships between covariates and the outcomes and multivariate linear regression to estimate the association between covariates and the average time until first postpartum visit., Results: Higher parity (OR = 0.85; P = 0.014; 95%CI: 0.75-0.97), unknown or unreported HIV status (OR = 0.64; p < 0.001; 95%CI: 0.53-0.78), and receipt of phone consultations (OR = 0.77; p < 0.001; 95%CI: 0.69-0.87) were associated with a lower odds of receiving all postpartum visits. Similarly, women with an unknown or unreported HIV status (estimated mean difference of 1.81 days; p < 0.001; 95%CI: 1.03-2.59) and those who received a phone consultation (estimated mean difference of 0.83 days; p < 0.001; 95%CI: 0.43-1.23), on average, experienced delays to first visit. In addition, current delivery at a referral hospital was associated with lower odds of receiving a postpartum visit and longer time to first visit compared to delivery at home, cottage hospital, PHCU + , or district hospital. Women from all other districts received their first visit earlier than women from Kaskazini B. There were no differences in the odds of receiving the entire postpartum intervention by sociodemographic variables, including age, education, and poverty assessment indicators., Conclusion: The results indicate no differences in intervention contact across wealth and education levels, suggesting that the program is effectively reaching women regardless of SES. However, women with other characteristics (e.g., higher parity, unknown or unreported HIV status) had lower odds of receiving the complete intervention. Overall, this work generates knowledge on existing disparities in intervention coverage and enables future programs to develop approaches to achieve equity in health care utilization and outcomes., (© 2024. The Author(s).)

Objectives: To describe human chorionic gonadotropin (hCG) trends for patients with a pregnancy of unknown location (PUL) presenting for medication abortion by management strategy and outcome., Study Design: This retrospective cohort study included patients presenting for medication abortion with a PUL at ≤42 days gestation managed with either (1) immediate mifepristone with serial hCG follow-up (same-day-start) or (2) hCG testing every 48 to 72 hours ± ultrasonography to confirm pregnancy location followed by treatment (delay-for-diagnosis). The primary outcome was percent hCG change over time between presentation and diagnosis, summarized using a multivariate regression model., Results: Of the 55 same-day-start patients, none were treated for ectopic. The eight who eventually required suction curettage had median hCG percent changes (interquartile range) on days 3, 4, and 5 of +57% (-14 to 127; n = 2), +292% (226-353; n = 4), and +392% (n = 1), while the 41 successful medication abortions had declines of -64% (n = 1), -65% (-75 to -27; n = 17), and -77% (-85 to -68; n = 13). Of the 380 delay-for-diagnosis patients, the 30 ectopic pregnancies had day 3, 4, and 5 changes of +38% (-17 to 56; n = 14), +50% (17-71; n = 7), and +115% (87-177; n = 4). None of the ectopic pregnancies declined ≥50% by days 3 to 5. The hCG trend for ectopic pregnancies differed from successful medication abortions (p < 0.01), but not medication abortions with retained intrauterine pregnancies (p = 0.41)., Conclusions: Serum hCG trends can help differentiate ectopic pregnancy from successful medication abortion, but cannot distinguish between ectopic and retained intrauterine pregnancy., Implications: Serial serum hCG testing is effective for confirming successful medication abortion and identifying patients requiring further follow-up among patients undergoing medication abortion for an undesired PUL., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The COVID-19 pandemic has disrupted health services worldwide, which may have led to increased mortality and secondary disease outbreaks. Disruptions vary by patient population, geographic area, and service. While many reasons have been put forward to explain disruptions, few studies have empirically investigated their causes., Objective: We quantify disruptions to outpatient services, facility-based deliveries, and family planning in seven low- and middle-income countries during the COVID-19 pandemic and quantify relationships between disruptions and the intensity of national pandemic responses., Methods: We leveraged routine data from 104 Partners In Health-supported facilities from January 2016 to December 2021. We first quantified COVID-19-related disruptions in each country by month using negative binomial time series models. We then modelled the relationship between disruptions and the intensity of national pandemic responses, as measured by the stringency index from the Oxford COVID-19 Government Response Tracker., Results: For all the studied countries, we observed at least one month with a significant decline in outpatient visits during the COVID-19 pandemic. We also observed significant cumulative drops in outpatient visits across all months in Lesotho, Liberia, Malawi, Rwanda, and Sierra Leone. A significant cumulative decrease in facility-based deliveries was observed in Haiti, Lesotho, Mexico, and Sierra Leone. No country had significant cumulative drops in family planning visits. For a 10-unit increase in the average monthly stringency index, the proportion deviation in monthly facility outpatient visits compared to expected fell by 3.9% (95% CI: -5.1%, -1.6%). No relationship between stringency of pandemic responses and utilisation was observed for facility-based deliveries or family planning., Conclusions: Context-specific strategies show the ability of health systems to sustain essential health services during the pandemic. The link between pandemic responses and healthcare utilisation can inform purposeful strategies to ensure communities have access to care and provide lessons for promoting the utilisation of health services elsewhere.

Background: While high-quality primary health care services can meet 80%-90% of health needs over a person's lifetime, this potential is severely hindered in many low-resource countries by a constrained health care system. There is a growing consensus that effectively designed, resourced, and managed community health worker programs are a critical component of a well-functioning primary health system, and digital technology is recognized as an important enabler of health systems transformation., Objective: In this implementation report, we describe the design and rollout of Zanzibar's national, digitally enabled community health program-Jamii ni Afya., Methods: Since 2010, D-tree International has partnered with the Ministry of Health Zanzibar to pilot and generate evidence for a digitally enabled community health program, which was formally adopted and scaled nationally by the government in 2018. Community health workers use a mobile app that guides service delivery and data collection for home-based health services, resulting in comprehensive service delivery, access to real-time data, efficient management of resources, and continuous quality improvement., Results: The Zanzibar government has documented increases in the delivery of health facilities among pregnant women and reductions in stunting among children younger than 5 years since the community health program has scaled. Key success factors included starting with the health challenge and local context rather than the technology, usage of data for decision-making, and extensive collaboration with local and global partners and funders. Lessons learned include the significant time it takes to scale and institutionalize a digital health systems innovation due to the time to generate evidence, change opinions, and build capacity., Conclusions: Jamii ni Afya represents one of the world's first examples of a nationally scaled digitally enabled community health program. This implementation report outlines key successes and lessons learned, which may have applicability to other governments and partners working to sustainably strengthen primary health systems., (©Erica Layer, Salim Slim, Issa Mussa, Abdul-Wahid Al-Mafazy, Giulia V R Besana, Mwinyi Msellem, Isabel Fulcher, Heiko Hornung, Riccardo Lampariello. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 09.10.2023.)

Introduction: The COVID-19 pandemic has caused disruptions in access to routine healthcare services worldwide, with a particularly high impact on chronic care patients and low and middle-income countries. In this study, we used routinely collected electronic medical records data to assess the impact of the COVID-19 pandemic on access to cancer care at the Butaro Cancer Center of Excellence (BCCOE) in rural Rwanda., Methods: We conducted a retrospective time-series study among all Rwandan patients who received cancer care at the BCCOE between 1 January 2016 and 31 July 2021. The primary outcomes of interest included a comparison of the number of patients who were predicted based on time-series models of pre-COVID-19 trends versus the actual number of patients who presented during the COVID-19 period (between March 2020 and July 2021) across four key indicators: the number of new patients, number of scheduled appointments, number of clinical visits attended and the proportion of scheduled appointments completed on time., Results: In total, 8970 patients (7140 patients enrolled before COVID-19 and 1830 patients enrolled during COVID-19) were included in this study. During the COVID-19 period, enrolment of new patients dropped by 21.7% (95% prediction interval (PI): -31.3%, -11.7%) compared with the pre-COVID-19 period. Similarly, the number of clinical visits was 25.0% (95% PI: -31.1%, -19.1%) lower than expected and the proportion of scheduled visits completed on time was 27.9% (95% PI: -39.8%, -14.1%) lower than expected. However, the number of scheduled visits did not deviate significantly from expected., Conclusion: Although scheduling procedures for visits continued as expected, our findings reveal that the COVID-19 pandemic interrupted patients' ability to access cancer care and attend scheduled appointments at the BCCOE. This interruption in care suggests delayed diagnosis and loss to follow-up, potentially resulting in a higher rate of negative health outcomes among cancer patients in Rwanda., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Maternal and neonatal mortality remain elevated in low and middle income countries, and progress is slower than needed to achieve the Sustainable Development Goals. Existing strategies appear to be insufficient. One proposed alternative strategy, Service Delivery Redesign for Maternal and Neonatal Health (SDR), centers on strengthening higher level health facilities to provide rapid, definitive care in case of delivery and post-natal complications, and then promoting delivery in these hospitals, rather than in primary care facilities. However to date, SDR has not been piloted or evaluated., Methods: We will use a prospective, non-randomized stepped-wedge design to evaluate the effectiveness and implementation of Service Delivery Redesign for Maternal and Neonatal Health in Kakamega County, Kenya., Discussion: This protocol describes a hybrid effectiveness/implementation evaluation study with an adaptive design. The impact evaluation ("effectiveness") study focuses on maternal and newborn health outcomes, and will be accompanied by an implementation evaluation focused on program reach, adoption, and fidelity., (© 2022. The Author(s).)

Competing Interests: Financial Disclosure Alisa Beth Goldberg disclosed that money was paid to her institution from Merck and to her directly from UpToDate. Isabel Fulcher received payment as a statistical consultant at Planned Parenthood League of Massachusetts. Jennifer Fortin is employed by Planned Parenthood League of Massachusetts. Rebecca Hofer disclosed that she was employed as a research assistant during the time of the study. She received an hourly wage from Planned Parenthood, including for work related to the study discussed as well as for other studies. She is no longer employed there and received no compensation for reviewing and contributing to the manuscript. In addition, she owns a number of different independent stocks and mutual funds that she has had for many years prior to the current work. These were purchased by her and her family and are not related to the current research. Alex Cottrill disclosed that the original study the Letter to the Editor addresses was funded by a grant paid to the authors' institution from the Society for Family Planning Research Fund. Dr. Cottrill was employed full-time by Planned Parenthood League of Massachusetts (where this study was based) during the 36 months before the original submission. Dr. Cottrill's salary was partly funded by our SFPRF grant during that time. Dr. Cottrill is still on the payroll at PPLM per diem but has not been paid through that grant since. Daniele Roncari received payment from Organon as a trainer for Nexplanon. The other authors did not report any potential conflicts of interest.

Background: Many children in low- and middle-income countries fail to reach their cognitive potential, with experiences before age 3 critical in shaping long-term development. Zanzibar's Jamii ni Afya program is the first national, digitally enabled community health volunteer (CHV) program promoting early childhood development (ECD) following the Nurturing Care Framework within an integrated maternal and child healthcare package. Using program baseline data, we explored home environment, caregivers' parenting, health and nutrition knowledge and practices, and ECD outcomes in Zanzibar., Methods: We conducted a national household survey among 499 children aged 18-29 months using two-stage cluster sampling in February 2019. The primary outcome was child development score measured using the Caregiver Reported Early Developmental Index (CREDI), with higher scores representing higher levels of child development. We analyzed CREDI scores, along with MICS questions on parenting knowledge, practices, and characteristics of the home environment. We developed multivariate regression models to assess associations between caregiver-child interactions, knowledge of dietary diversity, and ECD., Results: Ten percent of children had overall CREDI z-scores 2 standard deviations [SD] or more below the global reference population mean, with 28% of children at risk of developmental delay with z-scores 1 SD or more below the mean. Cognitive and language domains were of highest concern (10.2 and 12.7% with z-score < - 2 SD). In 3-day recall, 75% of children engaged in ≥4 early stimulating activities with all caregivers averaging 3 total hours of play. CREDI scores were positively associated with greater frequency of caregivers' engagement (β = 0.036, p = 0.002, 95%CI = [0.014, 0.058]), and dietary diversity knowledge (β = 0.564, p < 0.001, 95%CI = [0.281, 0.846])., Conclusions: Our findings demonstrate a positive association between both the frequency of caregiver child interactions and knowledge of adequate dietary diversity, and ECD outcomes. This aligns with global evidence that promoting early stimulation, play and learning opportunities, and dietary diversity can improve developmental outcomes. Further study is needed to establish causal relationships and assess the impact of ECD programming in Zanzibar., (© 2022. The Author(s).)

Background: Our objective was to assess differences in TB treatment outcomes between individuals who were HIV negative, HIV positive on anti-retroviral treatment (ART) and HIV positive not on ART, at TB treatment initiation at a rural district hospital in Eastern Cape, South Africa., Methods: This was a retrospective cohort study of individuals diagnosed with TB between January 2017 and April 2020 at a district hospital. Adults 15 years and over with reported HIV status and treatment outcome were included (N = 711). A categorical outcome with three levels was considered: unfavorable, down referral, and success. We report descriptive statistics for the association between HIV and ART status and treatment outcome using Chi-square and Fisher's exact tests. A multinomial baseline logit model was used to estimate odds ratios for treatment outcomes., Results: Overall, 59% of included patients were HIV positive with 75% on ART. Eighty-eight patients 12% had an unfavorable outcome. Half of all patients were down referred with an additional 37% having a successful outcome. Individuals without HIV were more likely to be down referred (versus unfavorable) compared to individuals with untreated HIV (2.90 OR, 1.36, 6.17 95% CI). There was a greater likelihood for individuals without HIV having a successful TB treatment outcome compared to individuals with untreated HIV (4.98 OR, 2.07, 11.25 95% CI)., Conclusion: The majority of individuals had positive TB treatment outcomes (down referred or success). However, people without HIV had nearly five times greater odds of having successful outcomes than those with untreated HIV., Competing Interests: The authors have declared that no competing interests exist.

Background: Surgical scrubbing, gowning, and gloving is challenging for medical trainees to learn in the operating room environment. Currently, there are few reliable or valid tools to evaluate a trainee's ability to scrub, gown and glove. The objective of this study is to test the reliability and validity of a checklist that evaluates the technique of surgical scrubbing, gowning and gloving (SGG)., Methods: This Institutional Review Board-approved study recruited medical students, residents, and fellows from an academic, tertiary care institution. Trainees were stratified based upon prior surgical experience as novices, intermediates, or experts. Participants were instructed to scrub, gown and glove in a staged operating room while being video-recorded. Two blinded raters scored the videos according to the SGG checklist. Reliability was assessed using the intraclass correlation coefficient for total scores and Cohen's kappa for item completion. The internal consistency and discriminant validity of the SGG checklist were assessed using Cronbach alpha and the Wilcoxon rank sum test, respectively., Results: 56 participants were recruited (18 novices, 19 intermediates, 19 experts). The intraclass correlation coefficient demonstrated excellent inter-rater reliability for the overall checklist (0.990), and the Cohen's kappa ranged from 0.598 to 1.00. The checklist also had excellent internal consistency (Cronbach's alpha 0.950). A significant difference in scores was observed between all groups (p < 0.001)., Conclusion: This checklist demonstrates a high inter-rater reliability, discriminant validity, and internal consistency. It has the potential to enhance medical education curricula.

Background: To test the feasibility of benchmarking the care of women with pregnancies complicated by hyperglycaemia., Methods: A retrospective audit of volunteer diabetes services in Australia and New Zealand involving singleton pregnancies resulting in live births between 2014 and 2020. Ranges are shown and compared across services., Results: The audit included 10,144 pregnancies (gestational diabetes mellitus (GDM) = 8696; type 1 diabetes (T1D) = 435; type 2 diabetes (T2D) = 1013) from 11 diabetes services. Among women with GDM, diet alone was used in 39.4% (ranging among centres from 28.8-57.3%), metformin alone in 18.8% (0.4-43.7%), and metformin and insulin in 10.1% (1.5-23.4%); when compared between sites, all p < 0.001. Birth was by elective caesarean in 12.1% (3.6-23.7%) or emergency caesarean in 9.5% (3.5-21.2%) (all p < 0.001). Preterm births (<37 weeks) ranged from 3.7% to 9.4% ( p < 0.05), large for gestational age 10.3-26.7% ( p < 0.001), admission to special care nursery 16.7-25.0% ( p < 0.001), and neonatal hypoglycaemia (<2.6 mmol/L) 6.0-27.0% ( p < 0.001). Many women with T1D and T2D had limited pregnancy planning including first trimester hyperglycaemia (HbA1c > 6.5% (48 mmol/mol)), 78.4% and 54.6%, respectively ( p < 0.001)., Conclusion: Management of maternal hyperglycaemia and pregnancy outcomes varied significantly. The maintenance and extension of this benchmarking service provides opportunities to identify policy and clinical approaches to improve pregnancy outcomes among women with hyperglycaemia in pregnancy.

Introduction: The benefit of aspirin in preventing preeclampsia is increasingly recognized; however, its mechanism of action remains unclear. Nonobstetric studies have described an anti-inflammatory effect of aspirin through the 15-epilipoxin-A4 pathway (aspirin-triggered lipoxin [ATL]). However, the anti-inflammatory mechanism of aspirin in the prevention of preeclampsia remains unknown., Objective/hypothesis: To examine (1) the difference in longitudinal endogenous lipoxin-A4 (En-Lipoxin-A4) concentration in low-risk (LR) and high-risk (HR) pregnancies, and (2) the effect of aspirin on endogenous ATL concentration and the associated effect on cytokine profile of HR women., Methods: Plasma from 220 HR women was collected at 12, 16, 20, 24, 28, 32, and 36 weeks of gestation. Adherence to aspirin was biochemically verified. Plasma En-Lipoxin-A4 and ATL concentrations were analyzed using liquid chromatography mass spectrometry, and cytokines, interleukin (IL)-10, tumor necrosis factor-α, interferon-γ, IL-8, and IL-1β, with the high-sensitivity multibead Luminex® assay., Results: HR women have up to 70% lower plasma concentration of En-Lipoxin-A4 (P < 0.001) than LR women. HR women with adequate aspirin adherence (HR-AA) (n = 82) had higher plasma concentration of ATL (P < .001), lower concentration of IL-8 from 16 to 36 weeks of gestation (P < .001), and increased IL-10 concentration from 16 to 28 weeks of gestation (P = .03) compared with high-risk women who were not on aspirin (HR-NA). HR-AA who did not develop preeclampsia had higher plasma En-lipoxin-A4 (P < .001), ATL (P = .02), and IL-10 concentrations (P < .001) with lower IL-8 concentration (P = .004) than HR women who developed preeclampsia., Discussion: Plasma concentration of En-Lipoxin-A4 is lower in HR women than in LR controls. Adequate adherence with aspirin results in an increase in ATL and IL-10 with reduced IL-8 plasma concentration. This study suggests a potential anti-inflammatory role of aspirin through the ATL pathway with prophylactic aspirin in HR pregnant women., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This is the full version of the Australasian Diabetes in Pregnancy Society (ADIPS) 2020 guideline for pre-existing diabetes and pregnancy. The guideline encompasses the management of women with pre-existing type 1 diabetes and type 2 diabetes in relation to pregnancy, including preconception, antepartum, intrapartum and postpartum care. The management of women with monogenic diabetes or cystic fibrosis-related diabetes in relation to pregnancy is also discussed., (© 2020 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Aspirin nonadherence and its associated increase in cardiovascular and cerebrovascular events is well described; however, the prevalence of aspirin nonadherence among high-risk pregnant women at risk of preeclampsia and its influence on clinical outcomes remains unclear. Our study examined the prevalence of aspirin nonadherence and resistance among high-risk pregnant women quantitatively (platelet function analyzer 100 and plasma salicylic acid) and clinical outcomes relative to adherence. High-risk pregnant women were recruited across 3 centers in the South West Sydney Local Health District. Simultaneous clinic data, blood sample, and self-reported adherence assessment were prospectively collected at 4-week intervals from 12 to 36 weeks of gestation. Nonadherence was defined as normal platelet function analyzer 100 and nondetectable plasma salicylic acid in <90% of time points. Value of <90% is based on current data. Two hundred twenty women were recruited over 25 months. No woman was aspirin resistant, and 63 (44%) women demonstrated inadequate adherence. Women with inadequate adherence had higher incidence of early-onset preeclampsia (17% versus 2%; odds ratio [OR], 1.9 [95% CI, 1.1-8.7]; P =0.04), late-onset preeclampsia (41% versus 5%; OR, 4.2 [95% CI, 1.4-19.8]; P =0.04), intrauterine growth restriction (29% versus 5%; OR, 5.8; [95% CI, 1.2-8.3]; P =0.001), preterm delivery (27% versus 10%; OR, 5.2 [95% CI, 1.5-8.7]; P =0.008), and higher likelihood of increase in antihypertensives antenatally (60% versus 10%; OR, 4.6 [95% CI, 1.2-10.5]; P =0.003). Kaplan-Meier analysis demonstrated lower incidence of premature delivery in the ≥90% adherent group (HR, 0.3 [95% CI, 0.2-0.5]; P <0.001).Kappa coefficient agreement between qualitative and quantitative assessment of adherence was moderate (κ=0.48; SE=0.029; P <0.0001). Our data demonstrates that aspirin is an effective prophylactic agent with an absolute risk reduction of 51% (number needed to treat, 2) when adherence is ≥90%, compared with women with inadequate adherence. Women who were <90% adherent had higher rates of preeclampsia, intrauterine growth restriction, preterm delivery, and increase in antenatal antihypertensive requirements. Self-reported adherence does not accurately reflect actual adherence.

Background: Non-adherence with medications in pregnancy is increasingly recognized and often results in a higher rate of preventable maternal and fetal morbidity and mortality. Non-adherence with prophylactic aspirin amongst high-risk pregnant women is associated with higher incidence of preeclampsia, preterm delivery and intrauterine growth restriction. Yet, the factors that influences adherence with aspirin in pregnancy, from the women's perspective, remains poorly understood., Objective: The study is aimed at understanding the factors, from the women's perspective, that influenced adherence with prophylactic aspirin in their pregnancy., Study Design: A sequential-exploratory designed mixed methods quantitative (n = 122) and qualitative (n = 6) survey of women with recent high-risk pregnancy necessitating antenatal prophylactic aspirin was utilized. Women recruited underwent their antenatal care in one of three high-risk pregnancy clinics within the South Western Sydney Local Health District, Australia. The quantitative study was done through an electronic anonymous survey and the qualitative study was conducted through a face-to-face interview. Data obtained was analysed against women's adherence with aspirin utilizing phi correlation (φ) with significance set at <0.05., Results: Two key themes, from the women's perspective, that influenced their adherence with aspirin in pregnancy were identified; (1) pill burden and non-intention omission (2) communication and relationship with health care provider (HCP). Pill burden and its associated non-intentional omission, both strongly corelated with reduced adherence (Φ = 0.8, p = 0.02, Φ = 0.8, p<0.01) whilst the use of reminder strategies minimized accidental omission and improved adherence (Φ = 0.9, p<0.01). Consistent communication between HCPs and a good patient-HCP relationship was strongly associated with improved adherence (Φ = 0.7, p = 0.04, Φ = 0.9, p = <0.01) and more importantly was found to play an important role in alleviating factors that had potentials to negatively influence adherence with aspirin in pregnancy., Conclusion: This study identified factors that both positively and negatively influenced adherence with aspirin amongst high-risk pregnant women. Is highlights the importance in recognizing the impact of pill burden in pregnancy and the need to counsel women on the utility of reminder strategies to minimize non-intentional omission. Importantly, it emphasizes on the importance of a positive patient-HCP relationship through effective and consistent communication to achieve the desired maternal and fetal outcomes., Competing Interests: The authors have declared that no competing interests exist.

Background: Most maternal health programs in low- and middle- income countries estimate gestational age to provide appropriate antenatal care at the correct times throughout the pregnancy. Although various gestational dating methods have been validated in research studies, the performance of these methods has not been evaluated on a larger scale, such as within health systems. The objective of this research was to investigate the magnitude and impact of errors in estimated delivery dates on health facility delivery among women enrolled in a maternal health program in Zanzibar., Methods: This study included 4225 women who were enrolled in the Safer Deliveries program and delivered before May 31, 2017. The exposure of interest was error in estimated delivery date categorized as: severe overestimate, when estimated delivery date (EDD) was 36 days or more after the actual delivery date (ADD); moderate overestimate, when EDD was 15 to 35 days after ADD; accurate, when EDD was 6 days before to 14 days after ADD; and underestimate, when EDD was 7 days or more before ADD. We used Chi-squared tests to identify factors associated with errors in estimated delivery dates. We performed logistic regression to assess the impact of errors in estimated delivery dates on health facility delivery adjusting for age, district of residence, HIV status, and occurrence of past home delivery., Results: In our data, 28% of the estimated delivery dates were a severe overestimate, 23% moderate overestimate, 41% accurate, and 8% underestimate. Compared to women with an accurate delivery date, women with a moderate or severe overestimate were significantly less likely to deliver in a health facility (OR = 0.71, 95% CI: [0.59, 0.86]; OR = 0.74, 95% CI: [0.61, 0.91]). When adjusting for multiple confounders, women with moderate overestimates were significantly less likely to deliver in a health facility (AOR = 0.76, 95% CI: [0.61, 0.93]); the result moved slightly towards null for women with severe overestimates (AOR = 0.84, 95% CI: [0.69, 1.03])., Conclusions: The overestimation of women's EDDs reduces the likelihood of health facility delivery. To address this, maternal health programs should improve estimation of EDD or attempt to curb the effect of these errors within their programs.

Background: The benefit of aspirin in preventing preeclampsia is well established; however, studies over the years have demonstrated variability in outcomes with its use. Potential contributing factors to this variation in efficacy include dosing, time of dosing, and preparation of aspirin., Objective: We aimed to compare the difference in pharmacokinetics of aspirin, through its major active metabolite, salicylic acid, in pregnant women and nonpregnant women, and to examine the effect of dose (100 mg vs 150 mg), preparation (enteric coated vs non-enteric-coated), and chronotherapy of aspirin (morning vs evening) between the 2 groups., Materials and Methods: Twelve high-risk pregnant women and 3 nonpregnant women were enrolled in this study. Pregnant women were in 1 of 4 groups (100 mg enteric coated, 100 mg non-enteric-coated, 150 mg non-enteric-coated morning dosing, and 150 mg non-enteric-coated evening dosing), whereas nonpregnant women undertook each of the 4 dosing schedules with at least a 30-day washout period. Blood samples were collected at baseline (before ingestion) and at 1, 2, 4, 6, 12, and 24 hours after ingestion of aspirin. Plasma obtained was analyzed for salicylic acid levels by means of liquid chromatography-mass spectrometry. Pharmacokinetic values of area under the curve from time point 0 to 24 hours point of maximum concentration, time of maximum concentration, volume of distribution, clearance, and elimination half-life were analyzed for statistical significance with SPSS v25 software., Results: Pregnant women had a 40% ± 4% reduction in area under the curve from time point 0 to 24 hours (P < .01) and 29% ± 3% reduction in point of maximum concentration (P < .01) with a 44% ± 8% increase in clearance (P < .01) in comparison to that in nonpregnant women when 100 mg aspirin was administered. The reduction in the area under the curve from time point 0 to 24 hours, however, was minimized with the use of 150 mg aspirin in pregnant women, with which the area under the curve from time point 0 to 24 hours was closer to that achieved with the use of 100 mg aspirin in nonpregnant women. There was a 4-hour delay (P < .01) in the time of maximum concentration, a 47% ± 3% reduction in point of maximum concentration (P < .01) and a 48% ± 1% increase in volume of distribution (P < .01) with the use of 100 mg enteric-coated aspirin compared to non-enteric-coated aspirin, with no difference in the overall area under the curve. There was no difference in the pharmacokinetics of aspirin between morning and evening dosing., Conclusion: There is a reduction in the total drug metabolite concentration of aspirin in pregnancy, and therefore a dose adjustment is potentially required in pregnant women. This is likely due to the altered pharmacokinetics of aspirin in pregnancy, with an increase in clearance. There was no difference in the total drug metabolite concentration of aspirin between enteric-coated and non-enteric-coated aspirin and between morning and evening dosing of aspirin. Further pharmacodynamic and clinical studies are required to examine the clinical relevance of these pharmacokinetic findings., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Recent developments on neutral endopeptidase (NEP, EC 3.4.24.11) are described. These include (1) the development of a novel colorimetric assay with a chromogenic substrate (Glutaryl-Gly-Gly-Phe-2-naphthylamide) coupled with aminopeptidase M (EC 3.4.11.2). (2) A detergent form of the pig kidney enzyme has been purified by immuno-adsorbent chromatography and its molecular properties compared with other forms of the enzyme from rabbit kidney and pig intestine. (3) Rat kidney microvilli contain two endopeptidases of about equal activity when assayed with [125I]iodo-insulin B chain as substrate. One is similar to the rabbit and pig endopeptidases in being sensitive to inhibition by phosphoamidon. The other is insensitive to the inhibitor, though susceptible to chelating agents. The two enzymes are resolvable and have been partially characterized. (4) Endopeptidases of the phosphoramidon-sensitive type are present in various tissues in addition to the principal locations in brush borders of kidney and intestine.

Five membrane peptidases were studied by radiation inactivation analysis of pig kidney microvillar membranes. One heterodimeric enzyme, gamma-glutamyl transferase, presented a target size corresponding to the dimeric Mr. The other enzymes are known to be homodimers. Three of these, aminopeptidase A. aminopeptidase N and dipeptidyl peptidase IV, gave results clearly indicating the monomer to be the target and, hence, in this group the association of the subunits was not essential for activity. The target size for endopeptidase-24.11 was intermediate between those for monomer and dimer and its functional state was not resolved by the experiments.

The endopeptidase present in the kidney microvillar membrane (EC 3.4.24.11) has been purified by immunoadsorbent chromatography from the pig. Three physically different forms have been obtained. The toluene-trypsin solubilized form has hydrophilic properties. The detergent and detergent-trypsin forms are amphipathic. Only a small change in apparent relative molecular mass of the subunit is produced by trypsin, indicating that little of the polypeptide is removed by the proteinase. Although apparently immunologically identical, the intestinal form has slightly different molecular properties, possibly attributable to differences in glycosylation. In spite of the failure of papain and other proteinases to release the endopeptidase from the membrane, reconstitution of the purified enzyme in liposomes has shown that it is a stalked dimeric protein, thus resembling other hydrolases in this membrane. In addition to its main locations in kidney and intestinal microvilli, there is clear evidence from inhibitor and immunological studies that the enzyme has a wide distribution including membrane fractions prepared from spleen, lung aorta and myocardium.