Estimate Risk Ratios Research Articles

Sexual behaviours and risk of SARS-CoV-2 infection among MSM during the first COVID-19 lockdown

BackgroundThe social distancing measures associated with the COVID-19 pandemic had far reaching effects on sexual behavior worldwide. However, it remains unclear whether sexual contact with non-steady partners was a contributor to the spread of SARS-CoV-2. The aim of this study was to (i) describe risk factors for SARS-CoV-2 seropositivity after the first pandemic wave among people using HIV Pre-Exposure Prophylaxis (PrEP) in Zurich, Switzerland, including sexual contact with non-steady partners, and (ii) assess whether the SARS-CoV-2 seropositivity among PrEP users in this time period differed from that of a demographic matched population level comparison group.MethodsThe study was conducted between July 2020 and October 2020 as a nested cross-sectional study within two ongoing cohort studies, SwissPrEPared (all eligible PrEP users in Switzerland ≥ 18 years old) and Corona Immunitas (a series of cross-sectional and longitudinal studies measuring the SARS-CoV-2 seroprevalence across Switzerland, beginning in April 2020). All SwissPrEPared participants were recruited from Checkpoint Zurich (the main PrEP clinic in Zurich) and were men having sex with men or transgender women. Data were collected on participants’ SARS-CoV-2 antibody status, social characteristics and behavioral data after the first wave of the pandemic in Switzerland, and seroprevalence was compared with a propensity score-matched sample from the general Zurich population.ResultsOf the 218 participants enrolled, 8.7% (n = 19, 95% CI: 5.5–13.5%) were seropositive for SARS-CoV-2 during the first pandemic wave, higher than that of the general male population in Zurich aged 20–65 (5.5%, 95% CI: 3.8–8.2%). Participants on average reduced their social outings, but the seronegative were more socially active before, during, and after the first lockdown period. In a logistic model, increasing mean sexual partner count was not associated with seropositivity (OR: 1.02, 95% CI: 0.95, 1.07). The estimated risk ratio for seropositivity for the participants compared to the general Zurich population after propensity score matching was 1.46 (95% CI: 0.53, 3.99).ConclusionsOur study suggests that SARS-CoV-2 seropositivity was slightly elevated among people taking PrEP in Zurich during the first wave of the pandemic, but that socializing and sexual activity were less important than other factors in contributing to risk.

Midwifery Continuity of Care During Pregnancy, Birth, and the Postpartum Period: A Matched Cohort Study.

To compare pregnancy outcomes in a midwifery continuity of care (MCoC) model to standard midwifery care in Sweden. Matched cohort study. Public healthcare during pregnancy and childbirth, Stockholm, Sweden. Women giving birth at Karolinska University Hospital site Huddinge in Stockholm between January 1, 2019, and August 31, 2021. Data on all births including MCoC and standard care, during the time period, were retrieved from the national Swedish Pregnancy Register. Propensity score matching was applied to obtain a matched set from the standard care group for every woman in the MCoC model. Based on the matched cohort, we estimated risk ratios (RR) for binary outcomes with 95% confidence intervals (CI). Interventions during labor, mode of birth, and preterm birth (< 37 gestational weeks). Compared with standard care, women in the MCoC model were more likely to give birth spontaneously (RR 1.06 95% CI 1.02-1.10) and less likely to have an elective cesarean on maternal request (RR 0.24 95% CI 0.11-0.51). The risk of preterm birth was also reduced in the MCoC group (RR 0.51 95% CI 0.32-0.82). The MCoC model was associated with fewer medical interventions and improved pregnancy outcomes.

Diet quality in young adulthood and sleep at midlife: a prospective analysis in the Bogalusa Heart Study

BackgroundDiet and sleep are both established risk factors for cardiometabolic diseases. Prior evidence suggests a potential link between these behaviors, though longitudinal evidence for how diet associates with sleep is scarce. This study aimed to determine the prospective association between diet quality in young adulthood and multiple sleep outcomes at midlife in the Bogalusa Heart Study (BHS).MethodsThis prospective study included 593 BHS subjects with dietary assessment at the 2001–2002 visit and sleep questionnaire responses from the 2013–2016 visit, after an average of 12.7 years (baseline mean age: 36 years, 36% male, 70%/30% White and Black persons). A culturally tailored, validated food frequency questionnaire assessed usual diet. Diet quality was measured with the Alternate Healthy Eating Index (AHEI) 2010, the Healthy Eating Index (HEI) 2015, and the alternate Mediterranean (aMed) dietary score. Robust Poisson regression with log-link function estimated risk ratios (RR) for insomnia symptoms, high sleep apnea score, and having a healthy sleep pattern by quintile and per standard deviation (SD) increase in dietary patterns. Models adjusted for potential confounders including multi-level socioeconomic factors, depression, and body mass index. Trends across quintiles and effect modification by sex, race, and education were tested.ResultsHigher diet quality in young adulthood, measured by both AHEI and HEI, was associated with lower probability of having insomnia symptoms at midlife. In the adjusted model, each SD-increase in AHEI (7.8 points; 7% of score range) conferred 15% lower probability of insomnia symptoms at follow-up (RR [95% confidence interval CI]: 0.85 [0.77, 0.93]), those in Q5 of AHEI had 0.54 times the probability as those in Q1 (95% CI: 0.39, 0.75), and there was a significant trend across quintiles (trend p = 0.001). There were no significant associations between young adult diet quality and having a high sleep apnea risk or a healthy sleep pattern at follow-up.ConclusionsA healthy diet was associated with a lower probability of future insomnia symptoms. If replicated, these findings could have implications for chronic disease prevention strategies incorporating the lifestyle behaviors of sleep and diet.

Outcomes After Loss to Follow-Up for Pregnant and Postpartum Women Living With HIV and Their Children in Kenya: A Prospective Cohort Study.

Many prevention of vertical transmission (PVT) studies assess outcomes within 12 months postpartum and exclude those lost to follow-up (LTFU), potentially biasing outcomes toward those retained in care. Five public facilities in western Kenya. We recruited women living with HIV (WLH) ≥18 years enrolled in antenatal clinic (ANC). WLH retained in care (RW) were recruited during pregnancy and followed with their children through 6 months postpartum; WLH LTFU (LW, last visit >90 days) after ANC enrollment and ≤6 months postpartum were recruited through community tracing. Recontact at 3 years was attempted for all participants. Primary outcomes were retention and child HIV-free survival. Generalized linear regression was used to estimated risk ratios (RRs) for associations with becoming LTFU by 6 months postpartum, adjusting for age, education, facility, travel time to facility, gravidity, income, and new vs. known HIV positive at ANC enrollment. Three hundred thirty-three WLH (222 RW, 111 LW) were recruited from 2018 to 2019. More LW versus RW were newly diagnosed with HIV at ANC enrollment (49.6% vs. 23.9%) and not virally suppressed at study enrollment (40.9% vs. 7.7%). 6-month HIV-free survival was lower for children of LW (87.9%) versus RW (98.7%). At 3 years, 230 WLH were retained in care (including 51 previously LTFU before 6 months), 30 transferred, 70 LTFU, and 3 deceased. 3-year child HIV-free survival was 81.9% (92.0% for children of RW, 58.6% for LW), 3.7% were living with HIV, 3.7% deceased, and 10.8% had unknown HIV/vital status. Being newly diagnosed with HIV at ANC enrollment was the only factor associated with becoming LTFU (aRR 1.21, 95% CI: 1.11 to 1.31). Outcomes among those LTFU were worse than those retained in care, underscoring the importance of retention in PVT services. Some, but not all, LW re-engaged in care by 3 years, suggesting the need for PVT services must better address the barriers and transitions women experience during pregnancy and postpartum.

Associations Between Short-Term Postoperative Outcomes and Immunocompromised Status in Patients Undergoing Sacrocolpopexy.

Few data exist on the impact of immunosuppression on perioperative outcomes in women undergoing sacrocolpopexy. The objective of this study was to compare differences in 30-day perioperative morbidity in immunocompromised versus non-immunocompromised women undergoing sacrocolpopexy (SCP). We hypothesize that compared with the non-immunocompromised group, immunocompromised women undergoing SCP experience worse composite 30-day postoperative outcomes. Retrospective cohort of female patients aged 18years or older who underwent sacrocolpopexy from 2012 to 2017. Current procedural terminology (CPT) codes 57280 and 57425 identified sacrocolpopexy in the American College of Surgeons-National Surgical Quality Improvement Project database. The primary exposure was a binary indicator of immunocompromised status, and the primary outcome was a composite indicator of readmission, reoperation, or a severe adverse event 30days after surgery. Marginal standardization, a G-computation method, was used to estimate risk ratios (RR) and 95% confidence intervals (CI) representing the association between exposure and outcome. A total of 13,505 women underwent SCP between 2012 and 2017. Of those, 2,625 (19.4%) had an indicator of immunocompromised status, with diabetes and smoking being most common. The risk of the composite adverse outcome in immunocompromised women was 7.3% versus 4.6% in non-immunocompromised women. After adjusting for age, race, ethnicity, and body mass index, immunocompromised women experienced 54% increased relative risk of an adverse outcome, compared with non-immunocompromised women (RR = 1.54; 95% CI: 1.31, 1.82). Immunocompromised status, most commonly caused by diabetes and smoking, increases the risk of readmission, reoperation, and a severe adverse event within 30days of sacrocolpopexy.

Sexual Orientation-Related Disparities in Neonatal Outcomes.

To evaluate whether disparities exist in adverse neonatal outcomes among the offspring of lesbian, gay, bisexual, and other sexually minoritized (LGB+) birthing people. We used longitudinal data from 1995 to 2017 from the Nurses' Health Study II, a cohort of nurses across the United States. We restricted analyses to those who reported live births (N=70,642) in the 2001 or 2009 lifetime pregnancy questionnaires. Participants were asked about sexual orientation identity (current and past) and same-sex attractions and partners. We examined preterm birth, low birth weight, and macrosomia among 1) completely heterosexual; 2) heterosexual with past same-sex attractions, partners, or identity; 3) mostly heterosexual; 4) bisexual; and 5) lesbian or gay participants. We used log-binomial models to estimate risk ratios for each outcome and weighted generalized estimating equations to account for multiple pregnancies per person over time and informative cluster sizes. Compared with completely heterosexual participants, offspring born to parents in all LGB+ groups combined (groups 2-5) had higher estimated risks of preterm birth (risk ratio 1.22, 95% CI, 1.15-1.30) and low birth weight (1.27, 95% CI, 1.15-1.40) but not macrosomia (0.98, 95% CI, 0.94-1.02). In the subgroup analysis, risk ratios were statistically significant for heterosexual participants with past same-sex attractions, partners, or identity (preterm birth 1.25, 95% CI, 1.13-1.37; low birth weight 1.32, 95% CI, 1.18-1.47). Risk ratios were elevated but not statistically significant for lesbian or gay participants (preterm birth 1.37, 95% CI, 0.98-1.93; low birth weight 1.46, 95% CI, 0.96-2.21) and bisexual participants (preterm birth 1.29, 95% CI, 0.85-1.93; low birth weight 1.24, 95% CI, 0.74-2.08). The offspring of LGB+ birthing people experience adverse neonatal outcomes, specifically preterm birth and low birth weight. These findings highlight the need to better understand health risks, social inequities, and health care experiences that drive these adverse outcomes.

Firth-Type Penalized Methods of the Modified Poisson and Least-Squares Regression Analyses for Binary Outcomes.

The modified Poisson and least-squares regression analyses for binary outcomes have been widely used as effective multivariable analysis methods to provide risk ratio and risk difference estimates in clinical and epidemiological studies. However, there is no certain evidence that assessed their operating characteristics under small and sparse data settings and no effective methods have been proposed for these regression analyses to address this issue. In this article, we show that the modified Poisson regression provides seriously biased estimates under small and sparse data settings. In addition, the modified least-squares regression provides unbiased estimates under these settings. We further show that the ordinary robust variance estimators for both of the methods have certain biases under situations that involve small or moderate sample sizes. To address these issues, we propose the Firth-type penalized methods for the modified Poisson and least-squares regressions. The adjustment methods lead to a more accurate and stable risk ratio estimator under small and sparse data settings, although the risk difference estimator is not invariant. In addition, to improve the inferences of the effect measures, we provide an improved robust variance estimator for these regression analyses. We conducted extensive simulation studies to assess the performances of the proposed methods under real-world conditions and found that the accuracies of the point and interval estimations were markedly improved by the proposed methods. We illustrate the effectiveness of these methods by applying them to a clinical study of epilepsy.

Non-differential misclassification of outcome under (near)-perfect specificity: a simulation study.

Mismeasurement of a dichotomous outcome yields an unbiased risk ratio estimate when there are no false positive cases (perfect specificity) and when sensitivity is non-differential with respect to exposure status. In studies where these conditions are expected, quantitative bias analysis may be considered unnecessary. We conducted a simulation study to explore the robustness of this special case to small departures from perfect specificity and stochastic departures from non-differential sensitivity. We observed substantial bias of the risk ratio with specificity values as high at 99.8%. The magnitude of bias increased directly with the true underlying risk ratio and was markedly stronger at lower baseline risk. Stochastic departure from non-differential sensitivity also resulted in substantial bias in most simulated scenarios; downward bias prevailed when sensitivity was higher among unexposed compared with exposed, and upward bias prevailed when sensitivity was higher among exposed compared with unexposed. Our results show that seemingly innocuous departures from perfect specificity (e.g., 0.2%) and from non-differential sensitivity can yield substantial bias of the risk ratio under outcome misclassification. We present a web tool permitting easy exploration of this bias mechanism under user-specifiable study scenarios.

TNF-α inhibitor use during pregnancy and the risk of preeclampsia: population-based cohort study.

Although the clinical importance of preeclampsia is widely recognized, few treatment options are available for prevention. TNF-α inhibitors have been hypothesized to potentially prevent the disease. We aimed to examine whether exposure to TNF-α inhibitors during pregnancy reduces the risk of preeclampsia. We conducted a population-based pregnancy cohort study using nationwide samples of publicly (Medicaid data, 2000-2018) and commercially (MarketScan Research Database, 2003-2020) insured pregnant women linked to their liveborn infants. Exposure was ascertained based on a filled prescription or administration code for TNF-α inhibitors during the first and second trimester of pregnancy. The outcomes included early-onset preeclampsia, late-onset preeclampsia, and small-for-gestational age. For baseline confounding adjustment, we leveraged propensity score overlap weights to estimate risk ratios (RR). Among 4 315 658 pregnancies in the Medicaid and the MarketScan cohort, 2736 (0.063%) were exposed to TNF-α inhibitors during the first trimester and 1712 (0.040%) during the second trimester. After adjustment, the risk of early-onset preeclampsia was not decreased among mothers exposed during the first trimester compared with unexposed women with treatment indications [RR pooled : 1.25, 95% confidence interval (CI) 0.93-1.67]. Similarly, the risk of late-onset preeclampsia was not decreased among mothers exposed during the second trimester compared with unexposed women (RR pooled : 0.99, 95% CI 0.81-1.22). Contrary to the hypothesis, exposure to TNF-α inhibitors during pregnancy did not appear to be associated with a reduced risk of early-onset or late-onset preeclampsia. These findings do not support consideration of the use of TNF-α inhibitors for the prevention of preeclampsia.

Sodium-Glucose Cotransporter-2 Inhibitors, Dulaglutide, and Risk for Dementia : A Population-Based Cohort Study.

Both sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may have neuroprotective effects in patients with type 2 diabetes (T2D). However, their comparative effectiveness in preventing dementia remains uncertain. To compare the risk for dementia between SGLT2 inhibitors and dulaglutide (a GLP-1 RA). Target trial emulation study. Nationwide health care data of South Korea obtained from the National Health Insurance Service between 2010 and 2022. Patients aged 60 years or older who have T2D and are initiating treatment with SGLT2 inhibitors or dulaglutide. The primary outcome was the presumed clinical onset of dementia. The date of onset was defined as the year before the date of dementia diagnosis, assuming that the time between the onset of dementia and diagnosis was 1 year. The 5-year risk ratios and risk differences comparing SGLT2 inhibitors with dulaglutide were estimated in a 1:2 propensity score-matched cohort adjusted for confounders. Overall, 12 489 patients initiating SGLT2 inhibitor treatment (51.9% dapagliflozin and 48.1% empagliflozin) and 1075 patients initiating dulaglutide treatment were included. In the matched cohort, over a median follow-up of 4.4 years, the primary outcome event occurred in 69 participants in the SGLT2 inhibitor group and 43 in the dulaglutide group. The estimated risk difference was -0.91 percentage point (95% CI, -2.45 to 0.63 percentage point), and the estimated risk ratio was 0.81 (CI, 0.56 to 1.16). Residual confounding is possible; there was no adjustment for hemoglobin A1c levels or duration of diabetes; the study is not representative of newer drugs, including more effective GLP-1 RAs; and the onset of dementia was not measured directly. Under conventional statistical criteria, a risk for dementia between 2.5 percentage points lower and 0.6 percentage point greater for SGLT2 inhibitors than for dulaglutide was estimated to be highly compatible with the data from this study. However, whether these findings generalize to newer GLP-1 RAs is uncertain. Thus, further studies incorporating newer drugs within these drug classes and better addressing residual confounding are required. Ministry of Food and Drug Safety of South Korea.

Financial hardship after COVID-19 infection among US Veterans: a national prospective cohort study

BackgroundResearch suggests an association between COVID-19 infection and certain financial hardships in the shorter term and among single-state and privately insured samples. Whether COVID-19 is associated with financial hardship in the longer-term or among socially vulnerable populations is unknown. Therefore, we examined whether COVID-19 was associated with a range of financial hardships 18 months after initial infection among a national cohort of Veterans enrolled in the Veterans Health Administration (VHA)—the largest national integrated health system in the US. We additionally explored the association between Veteran characteristics and financial hardship during the pandemic, irrespective of COVID-19.MethodsWe conducted a prospective, telephone-based survey. Out of 600 Veterans with COVID-19 from October 2020 through April 2021 who were invited to participate, 194 Veterans with COVID-19 and 194 matched comparators without a history of infection participated. Financial hardship outcomes included overall health-related financial strain, two behavioral financial hardships (e.g., taking less medication than prescribed due to cost), and seven material financial hardships (e.g., using up most or all savings). Weighted generalized estimating equations were used to estimate risk ratios (RR) and 95% confidence intervals (CI) of financial hardship by COVID-19 status, and to assess the relationship between infection and Veteran age, VHA copay status, and comorbidity score, irrespective of COVID-19 status.ResultsAmong 388 respondents, 67% reported at least one type of financial hardship since March 2020, with 21% reporting behavioral hardships and 64% material hardships; 8% reported severe-to-extreme health-related financial strain. Compared with uninfected matched comparators, Veterans with a history of COVID-19 had greater risks of severe-to-extreme health-related financial strain (RR: 4.0, CI: 1.4–11.2), taking less medication due to cost (RR: 2.9, 95% CI: 1.0–8.6), and having a loved one take time off work to care for them (RR: 1.9, CI: 1.1–3.6). Irrespective of COVID-19 status, Veterans aged < 65 years had a greater risk of most financial hardships compared with Veterans aged ≥ 65 years.ConclusionsHealth-related financial hardships such as taking less medication due to cost and severe-to-extreme health-related financial strain were more common among Veterans with a history of COVID-19 than among matched comparators. Strategies are needed to address health-related financial hardship after COVID-19.Trial registrationNCT05394025, registered 05–27-2022.

Once-Weekly Insulin Icodec in Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Clinical Trials (ONWARDS Clinical Program).

One hundred years have passed since the discovery of insulin, which is one of the most relevant events of the 20th century. This period resulted in extraordinary progress in the development of novel molecules to improve glucose control, simplify the insulin regimen, and ameliorate the quality of life. In late March 2024, the first once-weekly basal analog Icodec was approved for diabetes mellitus, generating high expectations. Our aim was to systematically review and meta-analyze the efficacy and safety of Icodec compared to once-daily insulin analogs in type 1 (T1D) and type 2 diabetes (T2D). PubMed/MEDLINE, Cochrane Library, and ClinicalTrials.gov were searched for randomized clinical trials (RCTs). Studies were included for the synthesis according to the following prespecified inclusion criteria: uncontrolled T1D or T2D, age ≥ 18 years, insulin Icodec vs. active comparators (Degludec U100, Glargine U100, Glargine U300, and Detemir), phase 3, multicenter, double-blind or open-label RCTs, and a study duration ≥ 24 weeks. The systematic review included 4347 patients with T1D and T2D inadequately controlled (2172 randomized to Icodec vs. 2175 randomized to once-daily basal analogs). Icodec, compared to once-daily basal analogs, slightly reduced the levels of glycated hemoglobin (HbA1c) with an estimated treatment difference (ETD) of -0.14% [95%CI -0.25; -0.03], p = 0.01, and I2 68%. Patients randomized to Icodec compared to those on once-daily basal analogs had a greater probability to achieve HbA1c < 7% without clinically relevant or severe hypoglycemic events in 12 weeks from randomization with an estimated risk ratio (ERR) of 1.17, [95%CI 1.01, 1.36], p = 0.03, and I2 66%. We did not find a difference in fasting glucose levels, time in range, and time above range between Icodec and comparators. Icodec, compared to once-daily basal analogs, resulted in a slight but statistically significant weight gain of 0.62 kg [95%CI 0.25; 0.99], p = 0.001, and I2 25%. The frequency of hypoglycemic events (ERR 1.16 [95%CI 0.95; 1.41]), adverse events (ERR 1.04 [95%CI 1.00; 1.08]), injection-site reactions (ERR 1.08 [95%CI 0.62; 1.90]), and the discontinuation of treatments were similar between the two groups. Icodec was found to work better when used in a basal-only than basal-bolus regimen with an ETD in HbA1c of -0.22%, a probability of achieving glucose control of +33%, a probability of achieving glucose control without clinically relevant or severe hypoglycemia of +28%, more time spent in target (+4.55%) and less time spent in hyperglycemia (-5.14%). The risk of clinically relevant or severe hypoglycemic events was significantly higher when background glinides and sulfonylureas were added to basal analogs (ERR 1.42 [95%CI 1.05; 1.93]). Insulin Icodec is substantially non-inferior to once-daily insulin analogs in T2D, either insulin-naïve or insulin-treated. However, Icodec works slightly better than competitors when used in a basal-only rather than basal-bolus regimen. Weight gain and hypoglycemic risk are substantially low but not negligible. Patients' education, adequate lifestyle and pharmacological interventions, and appropriate therapy adjustments are essential to minimize risks. This systematic review is registered as PROSPERO CRD42024568680.

Hydroxychloroquine and Pre-eclampsia in a Diverse Cohort of Women With Systemic Lupus Erythematosus.

Patients with systemic lupus erythematosus (SLE) are at risk for pregnancy complications such as pre-eclampsia and eclampsia. These clinically important complications are associated with maternal morbidity, mortality, and postpartum cardiovascular disease. Some studies suggest that hydroxychloroquine (HCQ) may reduce pre-eclampsia risk in lupus pregnancy. Using a cohort of pregnant patients with prevalent SLE at Kaiser Permanente Northern California (KPNC), we investigated whether HCQ treatment in early pregnancy reduced the risk of pre-eclampsia or eclampsia. Among pregnant patients with SLE from 2011 to 2020, we assessed HCQ treatment from three months before pregnancy through the first trimester. HCQ exposure was defined multiple ways to account for adherence and duration of treatment. Propensity scores accounted for multiple confounders and modified Poisson models estimated risk ratios (RRs) and 95% confidence intervals of the association between HCQ treatment and pre-eclampsia or eclampsia. Effect modification by pregestational hypertension, history of nephritis, and antiphospholipid antibody (aPL) status was investigated through stratified analysis. There were 399 pregnancies among 324 patients with SLE at KPNC between 2011 and 2020. Considering multiple exposure definitions, we consistently found a null association between HCQ and pre-eclampsia or eclampsia. The RRs were consistently lower among nullipara patients, and RRs were consistently protective but not statistically significant among the high-risk subgroup of patients with a history of nephritis, aPL positivity, or pregestational hypertension (for both nullipara and multipara patients). Although this study found no reduced risk of HCQ on pre-eclampsia or eclampsia, residual confounding may be attenuating the effect despite an integrated health care delivery system setting with detailed clinical data.

The Association of Adverse Pregnancy Outcomes With Overactive Bladder Anticholinergics.

The pregnancy safety and teratogenicity of overactive bladder (OAB) anticholinergic medications in humans are unknown. The aim of this study was to determine if the use of OAB anticholinergics during pregnancy was associated with adverse pregnancy outcomes or congenital malformation. Using routinely collected health care data from Ontario, Canada, we conducted a retrospective cohort study and identified women aged 18-45 years who gave birth between 2004 and 2022 and were eligible for provincial drug benefits. We used gestational age and birth dates to approximate conception dates. The primary exposure was filling a prescription for an OAB anticholinergic during pregnancy (compared with nonusers). The coprimary outcomes were pregnancy complication (which included preterm birth or low birth weight) and congenital malformation. Poisson regression models with generalized estimating equations and inverse probability of treatment weighting were used to estimate risk ratios (RRs). We identified 138,271 births, of which 479 (0.3%) had exposure to an OAB anticholinergic, for a median of 60 (interquartile range, 30-120) days. The most common OAB anticholinergic was oxybutynin (84%). In the weighted cohort, the risk of a pregnancy complication was significantly elevated (RR, 1.65; 95% confidence interval [CI], 1.40-1.95; P < 0.01; absolute risk difference + 9.9% [95% CI, +5.9, +13.9]), with a dose-response relationship close to statistical significance (P = 0.07). The risk of congenital malformations with OAB anticholinergic use was not significant (RR, 1.24; 95% CI, 0.85-1.80; P = 0.26). Pregnant women who take OAB anticholinergic medications have a higher risk of pregnancy complications, but not congenital malformations, compared with non-OAB anticholinergic users. This information can be used when counseling women of child-bearing age about these medications.

Target trial emulation of preconception serum vitamin D status on fertility outcomes: a couples-based approach

To evaluate associations between preconception 25-hydroxyvitamin D (25(OH)D) levels and biomarkers in female and male partners on live birth (LB), pregnancy loss, and semen quality. Secondary analysis using the folic acid and zinc supplementation trial of couples seeking infertility treatment at four US centers (2013-2017). A target trial emulation framework was applied to estimate associations. Couples were observed for 9 months or through pregnancy. Clinics that provide reproductive endocrinology and infertility care in the US. Couples seeking infertility treatment. Preconception concentrations of 25(OH)D (primary) and associated biomarkers: vitamin D binding protein, calcium, free vitamin D, bioavailable vitamin D. Live birth and pregnancy loss were ascertained via self-report and medical records. Semen quality was ascertained 6 months after enrollment. Log-binomial regression estimated risk ratios and 95% confidence intervals (CIs). Individual and joint models and effect measure modification by preconception body mass index were considered. Among 2,370 couples, 19.5% of females and 29.9% of males were 25(OH)D deficient. Females with sufficient status had a 28%-higher likelihood of LB than deficient females (95% CI, 1.05-1.56). Female and male 25(OH)D status were associated with LB among those with normal body mass index (sufficient vs. deficient: female adjusted risk ratio [aRR], 1.39; 95% CI, 1.00-1.99; male aRR, 1.51; 95% CI, 1.01-2.25) and among obese female partners (sufficient vs. deficient: aRR, 1.33; 95% CI, 0.95-1.85). Couples whose both partners had higher 25(OH)D status had increased likelihood of LB (both not deficient vs. both deficient aRR, 1.26; 95% CI, 1.00-1.58). No associations were observed with pregnancy loss or semen quality. Similar results were found for all biomarkers except calcium. Preconception vitamin D status and bioavailability impact fertility among couples seeking infertility therapy, likely unrelated to semen quality. Body mass index stratified analyses demonstrated heterogeneous associations. NCT01857310.

Effect of the COVID-19 Lockdown on Mobile Payments for Maternal Health: Regression Discontinuity Analysis.

The COVID-19 pandemic resulted in the unprecedented popularity of digital financial services for contactless payments and government cash transfer programs to mitigate the economic effects of the pandemic. The effect of the pandemic on the use of digital financial services for health in low- and middle-income countries, however, is poorly understood. This study aimed to assess the effect of the first COVID-19 lockdown on the use of a mobile maternal health wallet, with a particular focus on delineating the age-dependent differential effects, and draw conclusions on the effect of lockdown measures on the use of digital health services. We analyzed 819,840 person-days of health wallet use data from 3416 women who used health care at 25 public sector primary care facilities and 4 hospitals in Antananarivo, Madagascar, between January 1 and August 27, 2020. We collected data on savings, payments, and voucher use at the point of care. To estimate the effects of the first COVID-19 lockdown in Madagascar, we used regression discontinuity analysis around the starting day of the first COVID-19 lockdown on March 23, 2020. We determined the bandwidth using a data-driven method for unbiased bandwidth selection and used modified Poisson regression for binary variables to estimate risk ratios as lockdown effect sizes. We recorded 3719 saving events, 1572 payment events, and 3144 use events of electronic vouchers. The first COVID-19 lockdown in Madagascar reduced mobile money savings by 58.5% (P<.001), payments by 45.8% (P<.001), and voucher use by 49.6% (P<.001). Voucher use recovered to the extrapolated prelockdown counterfactual after 214 days, while savings and payments did not cross the extrapolated prelockdown counterfactual. The recovery duration after the lockdown differed by age group. Women aged >30 years recovered substantially faster, returning to prelockdown rates after 34, 226, and 77 days for savings, payments, and voucher use, respectively. Younger women aged <25 years did not return to baseline values. The results remained robust in sensitivity analyses using ±20 days of the optimal bandwidth. The COVID-19 lockdown greatly reduced the use of mobile money in the health sector, affecting savings, payments, and voucher use. Savings were the most significantly reduced, implying that the lockdown affected women's expectations of future health care use. Declines in payments and voucher use indicated decreased actual health care use caused by the lockdown. These effects are crucial since many maternal and child health care services cannot be delayed, as the potential benefits will be lost or diminished. To mitigate the adverse impacts of lockdowns on maternal health service use, digital health services could be leveraged to provide access to telemedicine and enhance user communication with clear information on available health care access options and adherence to safety protocols.

Variations in the use of oxytocin for augmentation of labour in Sweden: a population-based cohort study

National Swedish data shows substantial variation in the use of oxytocin for augmentation of spontaneous labour between obstetric units. This study aimed to investigate if variations in the use of oxytocin augmentation are associated with maternal and infant characteristics or clinical factors. We used a cohort design including women allocated to Robson group 1 (nulliparous women, gestational week ≥ 37 + 0, with singleton births in cephalic presentation and spontaneous onset of labour) and 3 (parous women, gestational week ≥ 37 + 0, with singleton births in cephalic presentation, spontaneous onset of labour, and no previous caesarean birth). Crude and adjusted logistic regression models with marginal standardisation were used to estimate risk ratios (RR) and risk differences (RD) with 95% confidence intervals (CI) for oxytocin use by obstetric unit. An interaction analysis was performed to investigate the potential modifying effect of epidural. The use of oxytocin varied between 47 and 73% in Robson group 1, and 10% and 33% in Robson group 3. Compared to the remainder of Sweden, the risk of oxytocin augmentation ranged from 13% lower (RD − 13.0, 95% CI − 15.5 to − 10.6) to 14% higher (RD 14.0, 95% CI 12.3–15.8) in Robson group 1, and from 6% lower (RD − 5.6, 95% CI − 6.8 to − 4.5) to 18% higher (RD 17.9, 95% CI 16.5–19.4) in Robson group 3. The most notable differences in risk estimates were observed among women in Robson group 3 with epidural. In conclusion, variations in oxytocin use remained despite adjusting for risk factors. This indicates unjustified differences in use of oxytocin in clinical practice.

Physical activity initiated from midlife on risk of dementia and cognitive impairment: The Health and Retirement Study.

Physical activity is associated with lower risk of dementia and cognitive impairment, but existing randomized controlled trials have shown conflicting results. As cognitive decline occurs decades before the onset of dementia, physical activity interventions initiated in late life may have missed the potential window for prevention. An ideal trial of physical activity initiated from midlife and lasts till incident dementia and cognitive impairment in late life is not feasible. We aimed to estimate the effectiveness of a hypothetical physical activity intervention initiated from midlife on reducing dementia and cognitive impairment by emulating target trials using observational data. The Health and Retirement Study was used to emulate target trials among noninstitutionalized participants aged 45 to 65 years with normal cognition who were physically inactive in the previous 2 years. Cognitive status was determined based on Langa-Weir classification of cognitive function (including immediate and delayed word recall tests, serial sevens subtraction, counting backward). Individuals were categorized as initiating physical activity or not, based on the self-reported physical activity. Intention-to-treat and per-protocol analysis were conducted with pooled logistic regression models with inverse-probability of treatment and censoring weights to estimate risk ratios (RRs), and 95% confidence intervals (95% CIs) were calculated with 200 sets of bootstrapping. Among 1505 participants (average age 57.6 ± 4.8 years, 67% women, 76.5% White), 72 cases of dementia and 409 cases of cognitive impairment occurred. After 12 years of follow-up, physical activity reduced dementia (RR = 0.70, 95% CI: 0.43, 0.99) for intention-to-treat analysis, and reduced dementia (RR = 0.51, 95% CI: 0.19, 0.99) and cognitive impairment (RR = 0.77, 95% CI: 0.61, 0.92) for per-protocol analysis. No significant reduction was found among older adults. Physical activity initiated during midlife may reduce dementia and cognitive impairment in late life, which highlights the importance of preventing cognitive outcomes at an earlier stage of life.

ZIBGLMM: Zero-Inflated Bivariate Generalized Linear Mixed Model for Meta-Analysis with Double-Zero-Event Studies.

Double-zero-event studies (DZS) pose a challenge for accurately estimating the overall treatment effect in meta-analysis. Current approaches, such as continuity correction or omission of DZS, are commonly employed, yet these ad hoc methods can yield biased conclusions. Although the standard bivariate generalized linear mixed model can accommodate DZS, it fails to address the potential systemic differences between DZS and other studies. In this paper, we propose a zero-inflated bivariate generalized linear mixed model (ZIBGLMM) to tackle this issue. This two-component finite mixture model includes zero-inflation for a subpopulation with negligible or extremely low risk. We develop both frequentist and Bayesian versions of ZIBGLMM and examine its performance in estimating risk ratios (RRs) against the bivariate generalized linear mixed model and conventional two-stage meta-analysis that excludes DZS. Through extensive simulation studies and real-world meta-analysis case studies, we demonstrate that ZIBGLMM outperforms the bivariate generalized linear mixed model and conventional two-stage meta-analysis that excludes DZS in estimating the true effect size with substantially less bias and comparable coverage probability.

The Relationship between Immunogenicity and Reactogenicity of Seasonal Influenza Vaccine Using Different Delivery Methods.

Vaccine immunogenicity and reactogenicity depend on recipient and vaccine characteristics. We hypothesized that healthy adults reporting higher reactogenicity from seasonal inactivated influenza vaccine (IIV) developed higher antibody titers compared with those reporting lower reactogenicity. We performed a secondary analysis of a randomized phase 1 trial of a trivalent IIV delivered by microneedle patch (MNP) or intramuscular (IM) injection. We created composite reactogenicity scores as exposure variables and used hemagglutination inhibition (HAI) titers as outcome variables. We used mixed-model analysis of variance to estimate geometric mean titers (GMTs) and titer fold change and modified Poisson generalized estimating equations to estimate risk ratios of seroprotection and seroconversion. Estimates of H3N2 GMTs were associated with the Systemic and Local scores among the IM group. Within the IM group, those with high reaction scores had lower baseline H3N2 GMTs and twice the titer fold change by day 28. Those with high Local scores had a greater probability of seroconversion. These results suggest that heightened reactogenicity to IM IIV is related to low baseline humoral immunity to an included antigen. Participants with greater reactogenicity developed greater titer fold change after 4 weeks, although the response magnitude was similar or lower compared with low-reactogenicity participants.