Empiric antibiotics for peripartum bacteremia: A chart review from a quaternary Canadian centre.

OBJECTIVE: To evaluate the effectiveness of empiric antibiotic protocols for peripartum bacteremia at a quaternary institution by describing incidence, microbial epidemiology, clinical source of infection, susceptibility patterns, and maternal and neonatal outcomes. METHODS: Retrospective chart review of peripartum patients with positive blood cultures between 2010 and 2018. RESULTS: The incidence of peripartum bacteremia was 0.3%. The most cultured organisms were Escherichia coli (51, 26.7%), Streptococcus spp. (52, 27.2%), and anaerobic spp. (35, 18.3%). Of the E. coli cases, 54.9% (28), 19.6% (10), and 19.6% (10) were resistant to ampicillin, first- and third-generation cephalosporins, respectively. Clinical sources of infection included intra-amniotic infection/endometritis (115, 67.6%), upper and/or lower urinary tract infection (23, 13.5%), and soft tissue infection (8, 4.7%). Appropriate empiric antibiotics were prescribed in 137 (83.0%) cases. There were 7 ICU admissions (4.2%), 18 pregnancy losses (9.9%), 9 neonatal deaths (5.5%), and 6 cases of neonatal bacteremia (3.7%). CONCLUSION: Peripartum bacteremia remains uncommon but associated with maternal morbidity and neonatal morbidity and mortality. Current empiric antimicrobial protocols at our site remain appropriate, but continuous monitoring of antimicrobial resistance patterns is critical given the presence of pathogens resistant to first-line antibiotics.

Higher perceived stress during the COVID-19 pandemic increased menstrual dysregulation and menopause symptoms.

BACKGROUND: The increased stress the world experienced with the coronavirus disease (COVID-19) pandemic affected mental health, disproportionately affecting females. However, how perceived stress in the first year affected menstrual and menopausal symptoms has not yet been investigated. OBJECTIVES: This study evaluates the effect that the first year of the COVID-19 pandemic had on female reproductive and mental health. METHODS: Residents in British Columbia, Canada, were surveyed online as part of the COVID-19 Rapid Evidence Study of a Provincial Population-Based Cohort for Gender and Sex. A subgroup of participants (n = 4171), who were assigned female sex at birth (age 25-69 years) and were surveyed within the first 6-12 months of the pandemic (August 2020-February 2021), prior to the widespread rollout of vaccines, was retrospectively asked if they noticed changes in their menstrual or menopausal symptoms, and completing validated measures of stress, depression and anxiety. DESIGN: This is a population-based online retrospective survey. RESULTS: We found that 27.8% reported menstrual cycle disturbances and 6.7% reported increased menopause symptoms. Those who scored higher on perceived stress, depression and anxiety scales were more likely to report reproductive cycle disturbances. Free-text responses revealed that reasons for disturbances were perceived to be related to the pandemic. CONCLUSION: The COVID-19 pandemic has highlighted the need to research female-specific health issues, such as menstruation. Our data indicate that in the first year of the pandemic, almost one-third of the menstruating population reported disturbances in their cycle, which was related to percieved stress, depression and anxiety scores.

The Clinical Significance of Embryonic Chromosomal Errors in Recurrent Pregnancy Loss: an Analysis of 1107 Miscarriages.

The objective of this study was to characterize the relationship between embryonic chromosomal errors in the products of conception (POC) and maternal age, gestational age (GA) of pregnancy loss, and findings on routine recurrent pregnancy loss (RPL) workup. This is a retrospective cohort study of women with a history of ≥ 2 pregnancy losses and who underwent cytogenetic testing on the POC of a subsequent pregnancy loss at an academic tertiary RPL referral center. The association between the odds of embryonic chromosomal errors in POC and maternal age, GA of pregnancy loss, as well as RPL work up findings was investigated. A total of 1107 miscarriages were analyzed from 741 women. There was an overall linear relationship between embryonic chromosomal errors and maternal age, with a nearly twofold increase in the odds of chromosomal error with every 5-year increase in maternal age (P < 0.0001). The association between chromosomal errors and GA was also linear (P = 0.0001), with most losses having no chromosomal errors after 13 weeks' gestation. Women with ≥ 1 positive findings on routine RPL diagnostic workup had lower odds of embryonic chromosomal errors compared to those with a normal workup [OR 0.57 (95% CI = 0.41-0.80)]. Notably, the estimated prevalence of chromosomal error remained high (> 60%) in women ≥ 35 years old irrespective of findings on routine evaluation. While embryonic chromosomal errors were associated with advanced maternal age, early GA of loss, and a negative routine RPL evaluation, the prevalence of chromosomal errors remained high in all subpopulations. These findings suggest that primary cytogenetic testing on POCs should be offered at the time of second and subsequent pregnancy losses in all RPL patients.

Maternal vaginal microbiome composition does not affect development of the infant gut microbiome in early life.

Birth mode has been implicated as a major factor influencing neonatal gut microbiome development, and it has been assumed that lack of exposure to the maternal vaginal microbiome is responsible for gut dysbiosis among caesarean-delivered infants. Consequently, practices to correct dysbiotic gut microbiomes, such as vaginal seeding, have arisen while the effect of the maternal vaginal microbiome on that of the infant gut remains unknown. We conducted a longitudinal, prospective cohort study of 621 Canadian pregnant women and their newborn infants and collected pre-delivery maternal vaginal swabs and infant stool samples at 10-days and 3-months of life. Using cpn60-based amplicon sequencing, we defined vaginal and stool microbiome profiles and evaluated the effect of maternal vaginal microbiome composition and various clinical variables on the development of the infant stool microbiome. Infant stool microbiomes showed significant differences in composition by delivery mode at 10-days postpartum; however, this effect could not be explained by maternal vaginal microbiome composition and was vastly reduced by 3 months. Vaginal microbiome clusters were distributed across infant stool clusters in proportion to their frequency in the overall maternal population, indicating independence of the two communities. Intrapartum antibiotic administration was identified as a confounder of infant stool microbiome differences and was associated with lower abundances of Escherichia coli, Bacteroides vulgatus, Bifidobacterium longum and Parabacteroides distasonis. Our findings demonstrate that maternal vaginal microbiome composition at delivery does not affect infant stool microbiome composition and development, suggesting that practices to amend infant stool microbiome composition focus factors other than maternal vaginal microbes.

Lower anti-Müllerian hormone levels are associated with HIV in reproductive age women and shorter leukocyte telomere length among late reproductive age women.

OBJECTIVES: We sought to better understand factors associated with ovarian aging in women with HIV (WWH). DESIGN: HIV has been associated with diminished fertility, younger age at menopause, and shorter leukocyte telomere length (LTL), a marker of cellular aging. We herein examine cross-sectional and longitudinal associations between LTL, anti-Müllerian hormone (AMH), and HIV. METHODS: We included WWH and HIV-negative women 12-50 years of age in the CARMA cohort with one or more study visit(s). LTL and AMH were measured by qPCR and ELISA, respectively. Women were analyzed in peak reproductive (<35 years) vs. late reproductive (≥35 years) life phases. Using multivariable mixed-effect linear or logistic regressions, we assessed factors associated with AMH and ΔAMH/year while adjusting for relevant confounders. RESULTS: WWH had shorter LTL and lower AMH levels compared to HIV-negative controls despite being of similar age. After adjusting for relevant factors, HIV was associated with 20% lower AMH levels in women under 35 years of age and shorter LTL was associated with AMH levels below 2 ng/ml among women aged 35 years or older. Longitudinally, ΔAMH/year was largely related to initial AMH level among older women, and to age in younger women. CONCLUSIONS: Factors associated with AMH change across women's reproductive lifespan. Lower AMH among peak reproductive aged WWH suggests that HIV may have an initial detrimental effect on ovarian reserve, an observation that may warrant counseling around pregnancy planning. In women aged 35 years or older, the association between shorter LTL and lower AMH suggests that the immune and reproductive aging connections are more important in this age group.

Effectiveness of a neonatal intensive care unit-specific antimicrobial stewardship program: A ten-year review.

OBJECTIVE: To evaluate the change in consumption of specific antibiotics in a neonatal intensive care unit after the implementation of an antimicrobial stewardship program (ASP). DESIGN: Retrospective cohort study between January 1, 2010, and December 31,2019. SETTING: The neonatal intensive care unit at British Columbia Women's Hospital (Vancouver Canada), a tertiary-care center. PATIENTS: Admitted neonates prescribed antibiotics. METHODS: We implemented an ASP with an early implementation phase starting in January 2014 (period 2) and a later phase starting in January 2017 (period 3). Patient demographics were collected, including birth weight, gestational age, history of necrotizing enterocolitis (NEC), and surgical operations from existing databases. Interrupted time-series analysis was used, and comparison of antibiotic days of therapy (DOT) averages were conducted across the preimplementation period (period 1), period 2, and period 3 regarding total patients and subgroups. RESULTS: We identified 4,512 infants. There was a significant decrease in DOT from 472 (95% confidence interval [CI], 431-517) in period 1 to 405 (95% CI, 367-446) in period 2 to 313 (95% CI, 280-350) in period 3. We detected a significant decrease in the use of ampicillin, aminoglycosides, cloxacillin, and linezolid but not in vancomycin or cefotaxime. Subgroup analyses of infants <1,500 g and those without NEC or surgery showed decreases in the use of cloxacillin, aminoglycosides, and linezolid. CONCLUSIONS: The implementation of an ASP was associated with a significant decrease in the overall DOT and use of certain antibiotics. This study presents important targets for ongoing ASP work.

First-trimester surgical abortion practice in Canada in 2012.

OBJECTIVE: To evaluate practices among first-trimester surgical abortion facilities and providers in Canada in 2012 and examine the characteristics of the surgical abortion work force. DESIGN: Self-administered paper or electronic survey adapted from a survey previously fielded in the United States. SETTING: Canada. PARTICIPANTS: Facility administrators and physicians. MAIN OUTCOMES MEASURES: Descriptive statistics on reported first-trimester surgical abortion practice and provider demographic characteristics. RESULTS: Eighty-three percent of identified facilities (78 of 94) and 178 physicians responded. Of the respondents, 99% of facilities and 96% of physicians provided first-trimester surgical abortions. Responding facilities provided 68,154 first-trimester surgical abortions in 2012. This represented 96% of their reported total (combined medical and surgical) first-trimester abortions. More than half (55%) of responding facilities were community based, while 45% were hospital affiliated. Most physician providers were female (68%) and were family doctors (59%). Preoperatively, 96% of physicians routinely used ultrasound and 89% gave perioperative antibiotics. Almost half (48%) used manual vacuum aspiration, but less than 35% did so beyond 9 weeks after the last menstrual period. At most facilities, most procedures were performed under combined local anesthesia and intravenous sedation (73%); only 7% indicated deep sedation or general anesthesia were used exclusively. Postoperatively, 81% of physicians performed immediate tissue examination and 96% offered postabortion contraception on the same day as the abortion. Other assessed outcomes included medication regimens and cervical preparation, with a high degree of consistency among facilities and physicians. CONCLUSION: First-trimester surgical abortion providers are mostly family physicians and most are female. Practices across Canada were mostly uniform and followed evidence-based guidelines. Uptake of the most recent Canadian practice guidelines may help further standardize patient care and improve routine perioperative antibiotic use and immediate tissue examination.

Labor and delivery outcomes by delivery method in term deliveries in occiput posterior position: a population-based retrospective cohort study.

BACKGROUND: Occiput posterior is the most common malposition in labor. Deliveries in occiput posterior position have been shown to have higher rates of adverse short-term maternal and neonatal outcomes compared with deliveries in occiput anterior position. There are no guidelines providing recommendations nor summarizing risks of adverse outcomes by delivery method to inform the decision-making process in occiput posterior delivery management. Population-based studies examining the outcomes associated with various management processes of occiput posterior position at the time of labor or delivery are lacking. OBJECTIVE: This study aimed to describe the current management of term singleton occiput posterior deliveries in British Columbia, Canada and to examine the association between different management strategies and adverse outcomes by describing the rates of: occiput posterior malposition; and spontaneous vaginal delivery, operative vaginal delivery, and cesarean delivery from occiput posterior malposition. We also analyzed the rates of adverse labor and delivery outcomes stratified by fetal position and delivery mode, and the interaction effect of occiput posterior position and delivery mode on the rates of adverse outcomes. STUDY DESIGN: This was a retrospective cohort study of cephalic term singleton deliveries in British Columbia from 2004 to 2020, using the British Columbia Perinatal Data Registry. The obstetrical adverse outcome index (a composite of 10 adverse maternal or neonatal events), adverse outcome index subcomponent rates, and adverse outcome index-derived weighted scores were compared between deliveries stratified by fetal position at delivery (occiput posterior or occiput anterior) and occiput posterior deliveries stratified by delivery method. Multivariable log-binomial logistic regression was used to model the adverse outcome index score. RESULTS: Of 306,237 term births, 19% had occiput posterior position during labor, 37% of which persisted in occiput posterior position at delivery. Among occiput posterior deliveries, 27% were spontaneous vaginal deliveries, 8% vacuum, 5% forceps, 1% mixed vacuum-forceps, and 59% were cesarean delivery; this distribution differed from that of occiput anterior deliveries (P<.0001). Overall, adverse outcome index scores were significantly higher in persistent occiput posterior deliveries (8.8% had ≥1 adverse outcomes; adjusted rate ratio, 1.07 [1.01-1.14]) than in occiput posterior labors that rotated to occiput anterior deliveries; the most frequent adverse outcome was third- or fourth-degree lacerations. Neonatal adverse outcomes were also more frequent in occiput posterior delivery (4.3% vs 3.3%; adjusted rate ratio, 1.21 [1.10-1.35]), whereas maternal outcomes were similar between groups (4.8% vs 6.0%; adjusted rate ratio, 1.04 [0.96-1.13]). Among persistent occiput posterior deliveries, spontaneous vaginal delivery and cesarean delivery had the lowest proportion of deliveries with ≥1 adverse outcomes (6.1% and 6.2%), whereas forceps deliveries had the highest (38.1%); the largest contributor to the adverse outcomes were third- or fourth-degree lacerations. Among occiput posterior deliveries with any adverse outcome, cesarean delivery had the highest Severity Index score, due in part to the inclusion of third- or fourth-degree tears (which are assigned a comparatively low score) as the most common adverse event in the other vaginal delivery modes, and because of outcomes with a higher severity score being associated with cesarean delivery, such as uterine rupture (a reason for cesarean delivery) and intensive care unit admission (an outcome following cesarean delivery). Overall, in a multivariable regression model, delivery mode and the interaction between delivery mode and occiput posterior position were significant predictors of a delivery with ≥1 adverse outcomes, whereas occiput posterior position itself was not. CONCLUSION: One in five singleton deliveries at term gestation had occiput posterior position in labor; most of these rotated to occiput anterior by delivery, which had better outcomes than persistent occiput posterior deliveries. Among the latter, spontaneous vaginal delivery and cesarean delivery had the lowest frequency of adverse outcomes, whereas forceps deliveries had the highest. This study provides a robust updated analysis of birth outcomes following different occiput posterior management strategies, which can inform provider decision-making and counseling. Its observational design may limit its use for direct recommendations for management of occiput posterior malposition, yet the study helps to define the risks associated with different modes of delivery in the setting of occiput posterior malposition. With additional studies examining success rates of intermediate occiput posterior-occiput anterior rotation, other delivery management steps, and long-term outcomes, this study helps to define safe management of occiput posterior delivery.

The Association of Emotion Regulation Flexibility and Negative and Positive Affect in Daily Life.

In contrast to traditional classifications of emotion regulation (ER) strategies as either uniformly maladaptive or adaptive, recent theoretical models emphasize that adaptability is determined by greater ER flexibility (i.e., the ability to flexibly implement and adjust ER strategies based on the context). This study is the first to empirically test the two central perspectives of ER flexibility on affect. A sample of 384 adults (M age=38.58 years, SD=13.82) residing predominantly in North America completed daily diaries for 14 days. We found evidence that theoretical components of ER flexibility, as defined by greater context sensitivity in the selection of ER strategies, greater ER strategy repertoire, enhanced responsivity to affective feedback, and ER-environmental covariation, were associated with adaptive affective outcomes (i.e., reduced negative affect and/or increased positive affect). This study highlights the importance of examining ER flexibility and its consequences as a critical component of ER. Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-022-00132-7.

Vaginal microbiota associated with oncogenic HPV in a cohort of HPV-vaccinated women living with HIV.

BACKGROUND: Women living with HIV (WLWH) experience higher rates of human papillomavirus (HPV) infection and cervical cancer than women without HIV. Changes in the vaginal microbiome have been implicated in HPV-related disease processes such as persistence of high-risk HPV infection but this has not been well defined in a population living with HIV. METHODS: Four hundred and 20 girls and WLWH, age ≥9, across 14 clinical sites in Canada were enrolled to receive three doses of quadrivalent HPV vaccine for assessment of vaccine immunogenicity. Blood, cervical cytology, and cervico-vaginal swabs were collected. Cervico-vaginal samples were tested for HPV DNA and underwent microbiota sequencing. RESULTS: Principal component analysis (PCA) and hierarchical clustering generated community state types (CSTs). Relationships between taxa and CSTs with HPV infection were examined using mixed-effects logistic regressions, Poisson regressions, or generalized linear mixed-effects models, as appropriate. Three hundred and fifty-six cervico-vaginal microbiota samples from 172 women were sequenced. Human papillomavirus DNA was detected in 211 (59%) samples; 110 (31%) contained oncogenic HPV. Sixty-five samples (18%) were taken concurrently with incident oncogenic HPV infection and 56 (16%) were collected from women with concurrent persistent oncogenic HPV infection. CONCLUSIONS: No significant associations between taxa, CST, or microbial diversity and HPV-related outcomes were found. However, we observed weak associations between a dysbiotic microbiome and specific species, including Gardnerella, Porphyromonas, and Prevotella species, with incident HPV infection.

Barriers To Accessing Contraception and Cervical and Breast Cancer Screening During COVID-19: A Prospective Cohort Study.

OBJECTIVE: This study sought to examine how access to contraception and cervical and breast cancer screening in British Columbia, Canada, has been affected by the COVID-19 pandemic. METHODS: From August 2020 to March 2021, 3691 female residents of British Columbia (age 25-69 y) participated in this study. We used generalized estimating equations to analyze the proportion of females accessing contraception and the proportion having difficulty accessing contraception across the different phases of pandemic control measures, and logistic regression to analyze attendance at cervical and breast cancer screening. We added sociodemographic and biological variables individually into the models. Self-reported barriers to accessing contraception and attending screening were summarized. RESULTS: During phases with the highest pandemic controls, self-reported access to contraception was lower (OR 0.94; 95% CI 0.90-0.98; P = 0.005) and difficulty with access was higher (OR 2.74; 95% CI 1.54-4.88; P = 0.001). A higher proportion of adults aged 25-34 years reported difficulty accessing contraception than those aged 35-39 years (P < 0.0001), and participants identifying as Indigenous had higher odds of access difficulties (OR 5.56; 95% CI 2.44-12.50; P < 0.001). Of those who required screening during the COVID-19 pandemic, 62% and 54.5% did not attend at least one of their cervical or breast screening appointments, respectively. Those with a history of breast cancer had significantly higher odds of self-reporting having attended their mammogram appointment compared with those without a history of breast cancer (OR 5.62; 95% CI 2.69-13.72; P < 0.001). The most common barriers to screening were difficulty getting an appointment and appointments being considered non-urgent. CONCLUSIONS: The COVID-19 pandemic has uniquely affected access to contraception and cancer screening participation for various subgroups. Self-reported data present potential avenues for mitigating barriers.

Association of SARS-CoV-2 Infection During Pregnancy With Maternal and Perinatal Outcomes.

Importance: There are limited high-quality, population-level data about the effect of SARS-CoV-2 infection on pregnancy using contemporaneous comparator cohorts. Objectives: To describe maternal and perinatal outcomes associated with SARS-CoV-2 infection in pregnancy and to assess variables associated with severe disease in the pregnant population. Design, Setting, and Participants: CANCOVID-Preg is an observational surveillance program for SARS-CoV-2-affected pregnancies in Canada. This analysis presents exploratory, population-level data from 6 Canadian provinces for the period of March 1, 2020, to October 31, 2021. A total of 6012 pregnant persons with a positive SARS-CoV-2 polymerase chain reaction test result at any time in pregnancy (primarily due to symptomatic presentation) were included and compared with 2 contemporaneous groups including age-matched female individuals with SARS-CoV-2 and unaffected pregnant persons from the pandemic time period. Exposure: SARS-CoV-2 infection during pregnancy. Incident infections in pregnancy were reported to CANCOVID-Preg by participating provinces/territories. Main Outcomes and Measures: Maternal and perinatal outcomes associated with SARS-CoV-2 infection as well as risk factors for severe disease (ie, disease requiring hospitalization, admission to an intensive care unit/critical care unit, and/or oxygen therapy). Results: Among 6012 pregnant individuals with SARS-CoV-2 in Canada (median age, 31 [IQR, 28-35] years), the greatest proportion of cases were diagnosed at 28 to 37 weeks' gestation (35.7%). Non-White individuals were disproportionately represented. Being pregnant was associated with a significantly increased risk of SARS-CoV-2-related hospitalization compared with SARS-CoV-2 cases among all women aged 20 to 49 years in the general population of Canada (7.75% vs 2.93%; relative risk, 2.65 [95% CI, 2.41-2.88]) as well as an increased risk of intensive care unit/critical care unit admission (2.01% vs 0.37%; relative risk, 5.46 [95% CI, 4.50-6.53]). Increasing age, preexisting hypertension, and greater gestational age at diagnosis were significantly associated with worse maternal outcomes. The risk of preterm birth was significantly elevated among SARS-CoV-2-affected pregnancies (11.05% vs 6.76%; relative risk, 1.63 [95% CI, 1.52-1.76]), even in cases of milder disease not requiring hospitalization, compared with unaffected pregnancies during the same time period. Conclusions and Relevance: In this exploratory surveillance study conducted in Canada from March 2020 to October 2021, SARS-CoV-2 infection during pregnancy was significantly associated with increased risk of adverse maternal outcomes and preterm birth.

An analysis of neuroscience and psychiatry papers published from 2009 and 2019 outlines opportunities for increasing discovery of sex differences.

Sex differences exist in many neurological and psychiatric diseases, but these have not always been addressed adequately in research. In order to address this, it is necessary to consider how sex is incorporated into the design (e.g. using a balanced design) and into the analyses (e.g. using sex as a covariate) in the published literature. We surveyed papers published in 2009 and 2019 across six journals in neuroscience and psychiatry. In this sample, we find a 30% increase in the percentage of papers reporting studies that included both sexes in 2019 compared with 2009. Despite this increase, in 2019 only 19% of papers in the sample reported using an optimal design for discovery of possible sex differences, and only 5% of the papers reported studies that analysed sex as a discovery variable. We conclude that progress to date has not been sufficient to address the importance of sex differences in research for discovery and therapeutic potential for neurological and psychiatric disease.

Factors associated with contraceptive use among women living with HIV in Canada: a controlled, cross-sectional study.

BACKGROUND: Multiple contraindications to combined hormonal contraceptives (CHC) use exist. The impact of these factors on contraceptive choice, particularly among women living with HIV (WLWH), is not well understood. We measured and compared the prevalence of contraceptive use and contraindications among WLWH and women not living with HIV (controls). METHODS: We examined cross-sectional survey and medical chart data from 83 WLWH and 62 controls, aged 16-49 and sexually active, from 2013-2017. We compared the age-adjusted prevalence and types of contraceptives used in the last month and the proportion of women with CHC contraindications, including drug interactions, medical comorbidities, and smoking at ≥ 35 years old. All WLWH received care at an interdisciplinary, women-centred HIV clinic. RESULTS: Compared to controls, WLWH were older (median [IQR)] 39 [34-43] vs 31 [23-41] years; p = 0.003), had less post-secondary education (37% vs 73%; p < 0.001), and more often had household income < $15,000/year (49% vs 30%; p = 0.006). WLWH trended to higher contraceptive prevalence than controls (80% vs 63%; p = 0.06 adjusted for age). Overall hormonal contraceptive use was similar. However, despite controlling for age, WLWH used CHC less (4% vs 18%; p = 0.006) than controls, and had more frequently undergone tubal ligation (12% vs 2%; p = 0.03). WLWH also experienced more CHC contraindications (54% vs 13%; p = 0.0001), including smoking at ≥ 35 years old (30% vs 6%; p = 0.0003) or a CHC-related drug interaction (all antiretroviral related) (25% vs 0%; p = 0.0001). CONCLUSIONS: WLWH attending our interdisciplinary clinic used hormonal contraception at similar rates as controls, though with different types. Differences may reflect different distributions of CHC contraindications. CHC contraindications present barriers to accessing the full range of contraceptive choices for WLWH. Guidelines and education for care providers and WLWH regarding contraceptive choices and drug interactions are needed, especially when care is provided without the benefit of an interdisciplinary women-centered healthcare team.

BACKGROUND: There are many reasons why individuals cannot use combined hormonal contraceptives (CHC). The impact of these reasons on contraceptive choice for women living with HIV (WLWH) are poorly understood. We measured and compared the prevalence of contraceptive choice and factors that may preclude their use in WLWH. METHODS: We examined survey and medical chart data from 83 WLWH and 62 controls (women not living with HIV), aged 16­49 and sexually active, from 2013 to 2017. We compared the prevalence and types of contraceptives used in the last month and the proportion of women with factors that would not allow the use of CHC, including drug interactions, medical conditions, and smoking at ≥ 35 years old. All WLWH received care at a women-centred HIV clinic. RESULTS: Compared to controls, WLWH were older, had less post-secondary education, and more often had household income < $15,000/year. WLWH were more likely to use contraception than controls. Overall hormonal contraceptive use was similar. However, even when accounting for age, WLWH used CHC less than controls, and had more frequently undergone tubal ligation. WLWH also had more reasons that would preclude the use of CHC contraindications including smoking at ≥ 35 years old or a CHC-related drug interaction. CONCLUSIONS: WLWH attending our interdisciplinary clinic used combined hormonal contraception at similar rates as controls, though with different types. Differences may reflect the fact that WLWH more often have factors that do not allow the safe use of CHC. Guidelines and education for care providers and WLWH regarding contraceptive choices and drug interactions are needed.

Analysis of ancestry heterozygosity suggests that hybrid incompatibilities in threespine stickleback are environment dependent.

Hybrid incompatibilities occur when interactions between opposite ancestry alleles at different loci reduce the fitness of hybrids. Most work on incompatibilities has focused on those that are "intrinsic," meaning they affect viability and sterility in the laboratory. Theory predicts that ecological selection can also underlie hybrid incompatibilities, but tests of this hypothesis using sequence data are scarce. In this article, we compiled genetic data for F2 hybrid crosses between divergent populations of threespine stickleback fish (Gasterosteus aculeatus L.) that were born and raised in either the field (seminatural experimental ponds) or the laboratory (aquaria). Because selection against incompatibilities results in elevated ancestry heterozygosity, we tested the prediction that ancestry heterozygosity will be higher in pond-raised fish compared to those raised in aquaria. We found that ancestry heterozygosity was elevated by approximately 3% in crosses raised in ponds compared to those raised in aquaria. Additional analyses support a phenotypic basis for incompatibility and suggest that environment-specific single-locus heterozygote advantage is not the cause of selection on ancestry heterozygosity. Our study provides evidence that, in stickleback, a coarse-albeit indirect-signal of environment-dependent hybrid incompatibility is reliably detectable and suggests that extrinsic incompatibilities can evolve before intrinsic incompatibilities.

Intention to Receive a COVID-19 Vaccine by HIV Status Among a Population-Based Sample of Women and Gender Diverse Individuals in British Columbia, Canada.

COVID-19 vaccination is recommended for people living with HIV (PLWH), among whom social inequities and co-morbidities may drive risks of COVID-19 infection and outcome severity. Among a provincial (British Columbia) sample, we determined the prevalence of COVID-19 vaccine intention by HIV status and assessed socio-demographic, vaccine hesitancy, and psychological predictors of vaccine intention. Individuals (25-69 years) recruited from province-wide research cohorts and the general public completed an online survey examining COVID-19 impacts (August/2020-March/2021). In an analysis restricted to women and gender diverse participants (n = 5588), we compared intention to receive a recommended COVID-19 vaccine (Very likely/Likely vs Neutral/Unlikely/Very Unlikely) by self-reported HIV status. Logistic regression models assessed the independent effect of HIV status and other factors on COVID-19 vaccine intention. Of 5588 participants, 69 (1.2%) were living with HIV, of whom 79.7% were on antiretroviral therapy. In bivariate analyses, intention to vaccinate was significantly lower among PLWH compared to participants not living with HIV (65.2% vs 79.6%; OR 0.44; 95%CI 0.32-0.60). However, this association was not statistically significant after adjustment for ethnicity, income, education, and essential worker status (aOR 0.85; 95%CI 0.48-1.55). Among PLWH, those with greater vaccine confidence, positive attitudes towards the COVID-19 vaccine, and more strongly influenced by direct and indirect social norms to vaccinate had significantly higher odds of vaccine intention. Tailored messaging is needed to build vaccine confidence, address questions about vaccine benefits, and support informed vaccination decision-making to promote COVID-19 vaccine uptake among women and gender diverse people living with HIV.

Are sex differences in cognitive impairment reflected in epigenetic age acceleration metrics?

Sex differences are well-established in Alzheimer's disease (AD) frequency and pathogenesis, but are not mechanistically understood. Accelerated epigenetic age has been associated with both cognitive aging and AD pathophysiology, but has not been studied by sex in AD or related cognitive impairment. Using the ADNI cohort, we found that none of sex, cognitive impairment diagnosis, nor load of APOEε4 alleles (strongest genetic AD risk factor) were associated with epigenetic age acceleration (DNAmAge, Intrinsic DNAmAge, PhenoAge, or GrimAge), although females exhibit more accelerated epigenetic aging using the Skin & Blood clock in the transition from normal cognition to cognitive impairment than males.

Early Neonatal Meconium Does Not Have a Demonstrable Microbiota Determined through Use of Robust Negative Controls with cpn60-Based Microbiome Profiling.

Detection of bacterial DNA within meconium is often cited as evidence supporting in utero colonization. However, many studies fail to adequately control for contamination. We aimed to define the microbial content of meconium under properly controlled conditions. DNA was extracted from 141 meconium samples and subjected to cpn60-based microbiome profiling, with controls to assess contamination throughout. Total bacterial loads of neonatal meconium, infant stool, and controls were compared by 16S rRNA quantitative PCR (qPCR). Viable bacteria within meconium were cultured, and isolate clonality was assessed by pulsed-field gel electrophoresis (PFGE). Meconium samples did not differ significantly from controls with respect to read numbers or taxonomic composition. Twenty (14%) outliers with markedly higher read numbers were collected significantly later after birth and appeared more like transitional stool than meconium. Total bacterial loads were significantly higher in stool than in meconium, which did not differ from that of sequencing controls, and correlated well with read numbers. Cultured isolates were most frequently identified as Staphylococcus epidermidis, Enterococcus faecalis, or Escherichia coli, with PFGE indicating high intraspecies diversity. Our findings highlight the importance of robust controls in studies of low microbial biomass samples and argue against meaningful bacterial colonization in utero. Given that meconium microbiome profiles could not be distinguished from sequencing controls, and that viable bacteria within meconium appeared uncommon and largely consistent with postnatal skin colonization, there does not appear to be a meconium microbiota. IMPORTANCE Much like the recent placental microbiome controversy, studies of neonatal meconium reporting bacterial communities within the fetal and neonatal gut imply that microbial colonization begins prior to birth. However, recent work has shown that placental microbiomes almost exclusively represent contamination from lab reagents and the environment. Here, we demonstrate that prior studies of neonatal meconium are impacted by the same issue, showing that the microbial content of meconium does not differ from negative controls that have never contained any biological material. Our culture findings similarly supported this notion and largely comprised bacteria normally associated with healthy skin. Overall, our work adds to the growing body of evidence against the in utero colonization hypothesis.

Sex influences the effects of APOE genotype and Alzheimer's diagnosis on neuropathology and memory.

Alzheimer's disease (AD) is characterized by severe cognitive decline and pathological changes in the brain (brain atrophy, hyperphosphorylation of tau, and deposition of amyloid-beta protein). Females have greater neuropathology (AD biomarkers and brain atrophy rates) and cognitive decline than males, however these effects can depend on diagnosis (amnestic mild cognitive impairment (aMCI) or AD) and APOE genotype (presence of ε4 alleles). Using the ADNI database (N = 630 females, N = 830 males), we analyzed the effect of sex, APOE genotype (non-carriers or carriers of APOEε4 alleles), and diagnosis (cognitively normal (CN), early aMCI (EMCI), late aMCI (LMCI), probable AD) on cognition (memory and executive function), hippocampal volume, and AD biomarkers (CSF levels of amyloid beta, tau, and ptau). Regardless of APOE genotype, memory scores were higher in CN, EMCI, and LMCI females compared to males but this sex difference was absent in probable AD, which may suggest a delay in the onset of cognitive decline or diagnosis and/or a faster trajectory of cognitive decline in females. We found that, regardless of diagnosis, CSF tau-pathology was disproportionately elevated in female carriers of APOEε4 alleles compared to males. In contrast, male carriers of APOEε4 alleles had reduced levels of CSF amyloid beta compared to females, irrespective of diagnosis. We also detected sex differences in hippocampal volume but the direction was dependent on the method of correction. Altogether results suggest that across diagnosis females show greater memory decline compared to males and APOE genotype affects AD neuropathology differently in males and females which may influence sex differences in incidence and progression of aMCI and AD.

Baseline Hemoglobin, Hepcidin, Ferritin, and Total Body Iron Stores are Equally Strong Diagnostic Predictors of a Hemoglobin Response to 12 Weeks of Daily Iron Supplementation in Cambodian Women.

BACKGROUND: The WHO recommends daily iron supplementation for all women in areas where the population-level anemia prevalence is ≥40%, despite the fact that hemoglobin (Hb) concentration is generally considered to be a poor prognostic indicator of iron status. OBJECTIVES: In this secondary analysis, we investigated the predictive power of ten baseline hematological biomarkers towards a 12-week Hb response to iron supplementation. METHODS: Data were obtained from a randomized controlled trial of daily iron supplementation in 407 nonpregnant Cambodian women (18-45 years) who received 60 mg elemental iron as ferrous sulfate for 12 weeks. Ten baseline biomarkers were included: Hb, measured with both a hematology analyzer and a HemoCue; inflammation-adjusted ferritin; soluble transferrin receptor; reticulocyte Hb; hepcidin; mean corpuscular volume; inflammation-adjusted total body iron stores (TBIS); total iron binding capacity; and transferrin saturation. Receiver operating characteristic (ROC) curves from fitted logistic regression models were used to make discrimination comparisons and variable selection methods were used to construct a multibiomarker prognostic model. RESULTS: Only 25% (n = 95/383) of women who completed the trial experienced a 12-week Hb response ≥10 g/L. The strongest univariate predictors of a Hb response were Hb as measured with a hematology analyzer, inflammation-adjusted ferritin, hepcidin, and inflammation-adjusted TBIS (AUCROC = 0.81, 0.83, 0.82, and 0.82, respectively), and the optimal cutoffs to identify women who were likely to experience a Hb response were 117 g/L, 17.3 µg/L, 1.98 nmol/L, and 1.95 mg/kg, respectively. Hb as measured with a hematology analyzer, inflammation-adjusted ferritin, and hepcidin had the best combined predictive ability (AUCROC=0.86). Hb measured with the HemoCue had poor discrimination ability (AUCROC = 0.65). CONCLUSIONS: Baseline Hb as measured with a hematology analyzer was as strong a predictor of Hb response to iron supplementation as inflammation-adjusted ferritin, hepcidin, and inflammation-adjusted TBIS. This is positive given that the WHO currently uses the population-level anemia prevalence to guide recommendations for untargeted iron supplementation.