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.

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.

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.

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.

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.

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.

Elevated Blood Mitochondrial DNA in Early Life Among Uninfected Children Exposed to Human Immunodeficiency Virus and Combination Antiretroviral Therapy in utero.

BACKGROUND: Combination antiretroviral therapy (cART) during pregnancy prevents vertical transmission, but many antiretrovirals cross the placenta and several can affect mitochondria. Exposure to maternal human immunodeficiency virus (HIV) and/or cART could have long-term effects on children who are HIV exposed and uninfected (CHEU). Our objective was to compare blood mitochondrial DNA (mtDNA) content in CHEU and children who are HIV unexposed and uninfected (CHUU), at birth and in early life. METHODS: Whole-blood mtDNA content at birth and in early life (age 0-3 years) was compared cross-sectionally between CHEU and CHUU. Longitudinal changes in mtDNA content among CHEU was also evaluated. RESULTS: At birth, CHEU status and younger gestational age were associated with higher mtDNA content. These remained independently associated with mtDNA content in multivariable analyses, whether considering all infants, or only those born at term. Longitudinally, CHEU mtDNA levels remained unchanged during the first 6 months of life, and gradually declined thereafter. A separate age- and sex-matched cross-sectional analysis (in 214 CHEU and 214 CHUU) illustrates that the difference in mtDNA between the groups remains detectable throughout the first 3 years of life. CONCLUSION: The persistently elevated blood mtDNA content observed among CHEU represents a long-term effect, possibly resulting from in utero stresses related to maternal HIV and/or cART. The clinical impact of altered mtDNA levels is unclear.

The promises and pitfalls of sex difference research.

Funding agencies in North America and Europe are recognizing the importance of the integration of sex differences into basic and clinical research. Although these mandates are in place to improve our knowledge of health for both men and women, there have been a number of implementation issues that require vigilance on the part of funders and the research community. Here we discuss issues on simple inclusion of both sexes in studies to specialisation of sex differences with attention paid to statistics and the need for sex-specific treatments. We suggest differing mandates need to be considered regarding simple integration versus the need for studies in the specialisation of sex differences and/or the need for research that recognises the importance of male-specific or female-specific factors that influence subsequent health such as menstruation, menopause or pregnancy.

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.

Urinary symptoms and quality of life in women living with HIV: a cross-sectional study.

INTRODUCTION AND HYPOTHESIS: To determine prevalence and quality of life impact of lower urinary tract symptoms (LUTS) in women living with HIV (WLWH). METHODS: Cross-sectional urinary questionnaires were included in a multicenter national prospective study of the HPV vaccine in WLWH. Demographic and clinical information was abstracted from the parent study. The Urinary Distress Inventory (UDI-6) and Urinary Impact Questionnaire (UIQ-7) were administered. Wilcoxon rank sum, two-sample chi-square or Fisher's exact tests were used as appropriate to compare women with UDI-6 score ≥ 25 to those with lower UDI-6 scores on demographic and HIV-related factors. Significant categorical variables were followed up with logistic regression to estimate odds ratios (OR). RESULTS: One hundred seventy-seven women completed urinary questionnaires (85.5% of cohort). Median age was 44.1 (37.2-50.6). Mean CD4 count was 621 (410-785), and 132 women (74.6%) were virologically suppressed. Median UDI-6 score was 4.2 (0-25). Fifty-one women (28.8%) had a UIQ-7 score > 0. Among those with a UDI-6 score of at least 25, median UIQ-7 was 9.5 (0-47.6). UDI-6 ≥ 25 was significantly associated with increasing age, higher BMI, Canada as country of origin, peri-/postmenopausal status (OR 3.37, 95% CI = 1.71 to 6.75) and being parous (OR 2.92, 95% CI = 1.27 to 7.59) (all p < 0.05). HIV-related factors were not associated with UDI-6 ≥ 25. CONCLUSIONS: LUTS were common, but we did not demonstrate a negative impact on quality of life in this sample of WLWH. Large comparative studies are needed to determine whether HIV is a risk factor for bothersome LUTS in women.

Anxiety among women experiencing medically complicated pregnancy: A systematic review and meta-analysis.

BACKGROUND: Symptoms of anxiety are common among pregnant and postpartum women, and 15%-20% of pregnancies are affected by medical complications. Despite this, little is known about the relationship of medical complications in pregnancy and women's experience of anxiety. The purpose of this research was to conduct a systematic review and meta-analysis of differences in anxiety symptom severity among women experiencing a medically complicated versus a medically uncomplicated pregnancy. METHODS: This work was guided by the PRISMA reporting process. Electronic databases MEDLINE and PsycINFO were searched to identify studies that met the inclusion criteria. An adaptation of the Newcastle-Ottawa Quality Assessment Scale for case-control studies was used to perform a quality assessment review. A random-effects meta-analysis was used to calculate the estimated average standardized mean differences. RESULTS: Based on the five studies which met our inclusion criteria, findings provide evidence of higher levels of anxiety symptoms among pregnant women experiencing a medically complicated versus a medically uncomplicated pregnancy. Despite considerable heterogeneity, all mean difference estimates are in the direction of greater anxiety in the high-risk groups. CONCLUSIONS: Women experiencing a medically complex pregnancy report higher levels of anxiety symptoms compared to women experiencing a medically uncomplicated pregnancy.

Resolution and Cooccurrence Patterns of Gardnerella leopoldii, G. swidsinskii, G. piotii, and G. vaginalis within the Vaginal Microbiome.

Gardnerella vaginalis is a hallmark of vaginal dysbiosis, but it is found in the microbiomes of women with and without vaginal symptoms and those who do not have microbiologically defined dysbiosis. G. vaginalis encompasses diverse taxa differing in attributes that are potentially important for virulence, and there is evidence that clades or subgroups within the species are differentially associated with clinical outcomes. The G. vaginalis species description was recently emended, and three new species within the genus were defined (G. leopoldii, G. swidsinskii, and G. piotii). 16S rRNA sequences for the four Gardnerella species are all >98.5% identical, and no signature sequences differentiate them. We demonstrated that Gardnerella species can be resolved using partial chaperonin 60 (cpn60) sequences, with pairwise percent identities of 87.1 to 97.8% among the type strains. Pairwise cooccurrence patterns of Gardnerella spp. in the vaginal microbiomes of 413 reproductive aged Canadian women were investigated, and several significant cooccurrences of species were identified. Abundance of G. vaginalis and G. swidsinskii was associated with vaginal symptoms of abnormal odor and discharge. cpn60 barcode sequencing can provide a rapid assessment of the relative abundance of Gardnerella spp. in microbiome samples, providing a powerful method of elucidating associations between these diverse organisms and clinical outcomes. Researchers should consider using cpn60 instead of 16S RNA for better resolution of these important organisms.

Is Pelvic Floor sEMG a Measure of Women's Sexual Response?

INTRODUCTION: Pelvic floor surface electromyography (sEMG) is often used in the assessment and treatment of individuals with pelvic floor abnormalities to measure muscle tone and neural control of the pelvic floor muscles (PFM); however, little is known about the role of the PFM in sexual arousal. AIM: The aim of this pilot study was to examine whether changes in deep and superficial PFM activity-assessed with sEMG-can be observed during the presentation of sexual stimuli. METHODS: Deep PFM sEMG activity was assessed with a vaginal probe. Superficial PFM activity was assessed with sEMG electrodes placed over the bulbocavernosus and perianal muscles. 15 sexually healthy women (mean age 27 years) watched a series of neutral, anxiety-evoking, and sexually explicit films. Continuous subjective sexual arousal was measured using a handheld arousometer. MAIN OUTCOME MEASURE: Changes in microvolts were measured by sEMG sensors, from neutral to anxiety-evoking and neutral to sexually explicit films. RESULTS: There was an increase in intravaginal and perianal sEMG for both the erotic and anxiety films. Bulbocavernosus sEMG responses did not differ among the 3 films. Concordance between self-reported continuous sexual arousal for the erotic film and bulbocavernosus sEMG (r = 0.349) was not significantly different than concordance using intravaginal sEMG (r = 0.293) or perianal sEMG (r = 0.236). CLINICAL IMPLICATIONS: Understanding more about which parts of the PFM respond specifically to sexual stimuli may have implications for measuring the effects of treatments aimed at improving sexual response in women. STRENGTH & LIMITATIONS: The results of this pilot study provide a preliminary understanding of which pelvic floor muscles respond to sexual stimuli. A limitation of this study was the small sample size. CONCLUSION: Taken together, these findings suggest that intravaginal and perianal sEMG respond to erotic stimuli, whereas bulbocavernosal sEMG responses do not. Hannan-Leith MN, Dayan M, Hatfield G, et al. Is Pelvic Floor Surface Electromyography a Measure of Women's Sexual Response? A Pilot Study. J Sex Med 2019;16:70-82.

Training family physicians as researchers: Outcomes over 15 years for Canada's first clinician scholar program.

OBJECTIVE: To examine characteristics at admission and subsequent academic achievements among the graduates of the first 15 years of the clinician scholar program (CSP), Canada's longest-running such program, housed at the University of British Columbia in Vancouver. DESIGN: Cross-sectional study with data gathered from program files, personal correspondence, and public sources. SETTING: Vancouver. PARTICIPANTS: Graduates of the University of British Columbia CSP from 2001 to 2015. MAIN OUTCOME MEASURES: Characteristics at admission (years since medical school graduation, previous graduate degrees) and measures of scholarly success (peer-reviewed publications, subsequent graduate degrees, and academic faculty appointments). RESULTS: We obtained data for all 40 CSP graduates. The median years since medical school graduation at admission to the CSP was 12 years (interquartile range of 8 to 19); 60% of entrants held no previous graduate degree. After CSP completion, 15% of graduates attained an academic faculty appointment and 23% published more than 2 peer-reviewed articles per year. Subsequent success was not diminished with increasing years since medical school graduation, nor was it diminished among those without a previous graduate degree. Clinician scholar program graduates who subsequently completed a graduate degree were significantly more likely (P = .01) to publish frequently. We noted a weak negative relationship between getting a subsequent degree and number of years since medical school graduation (odds ratio of 0.89, 95% CI 0.78 to 0.99, P = .04). CONCLUSION: We found family physicians interested in becoming researchers were usually highly experienced, with physicians entering the CSP a median of 12 years (interquartile range 8 to 19 years) after medical school graduation. Most went on to publish several papers and more than 20% maintained a productivity of more than 2 peer-reviewed papers per year. The mentorship program model during this first 15 years has been effective in training family physicians to begin clinician scholar careers, and has been built upon, with the introduction from 2013 to 2015 of an enhanced curriculum. Future quantitative and qualitative analysis of this program and others is important to better articulate the success of clinician scholars striving to understand and improve primary care and health for Canadians.

Leukocyte Telomere Length at Birth and During the Early Life of Children Exposed to but Uninfected With HIV After In Utero Exposure to Antiretrovirals.

Background: Maternal combination antiretroviral therapy (cART) during pregnancy could impact the health of human immunodeficiency virus (HIV)-exposed, HIV-uninfected (HEU) children, because some antiretrovirals cross the placenta and can inhibit telomerase. Our objective was to compare leukocyte telomere length (LTL) in HEU children and HIV-unexposed, HIV-uninfected (HUU) children at birth and in early life and to investigate any relationship with cART exposure. Methods: HEU and HUU children's blood LTL was compared cross-sectionally at birth, and during the first three years of life. Longitudinal HEU LTL dynamics was evaluated over that same period. Results: At birth, the LTL in HEU children (n = 114) was not shorter than that in HUU children (n = 86), but female infants had longer LTL than male infants. Maternal cART (duration or type) showed no association with shorter infant LTL. Among 214 HEU children age- and sex-matched at a 1:1 ratio to HUU children, LTL declined similarly in both groups. In a longitudinal analysis, LTL attrition in HEU children was rapid from birth to 1 year of age and gradual thereafter. Zidovudine prophylaxis did not significantly alter LTL. Conclusions: Our results indicate that from birth to 3 years of age, the LTL in HEU children is not negatively affected by exposure to maternal HIV infection and cART, at least not to the regimens used within this Canadian cohort, a reassuring finding.

Chronic pelvic pain in an interdisciplinary setting: 1-year prospective cohort.

BACKGROUND: Chronic pelvic pain affects ∼15% of women, and presents a challenging problem for gynecologists due to its complex etiology involving multiple comorbidities. Thus, an interdisciplinary approach has been proposed for chronic pelvic pain, where these multifactorial comorbidities can be addressed by different interventions at a single integrated center. Moreover, while cross-sectional studies can provide some insight into the association between these comorbidities and chronic pelvic pain severity, prospective longitudinal cohorts can identify comorbidities associated with changes in chronic pelvic pain severity over time. OBJECTIVE: We sought to describe trends and factors associated with chronic pelvic pain severity over a 1-year prospective cohort at an interdisciplinary center, with a focus on the role of comorbidities and controlling for baseline pain, demographic factors, and treatment effects. STUDY DESIGN: This was a prospective 1-year cohort study at an interdisciplinary tertiary referral center for pelvic pain and endometriosis, which provides minimally invasive surgery, medical management, pain education, physiotherapy, and psychological therapies. Exclusion criteria included menopause or age >50 years. Sample size was 296 (57% response rate at 1 year; 296/525). Primary outcome was chronic pelvic pain severity at 1 year on an 11-point numeric rating scale (0-10), which was categorized for ordinal regression (none-mild 0-3, moderate 4-6, severe 7-10). Secondary outcomes included functional quality of life and health utilization. Baseline comorbidities were endometriosis, irritable bowel syndrome, painful bladder syndrome, abdominal wall pain, pelvic floor myalgia, and validated questionnaires for depression, anxiety, and catastrophizing. Multivariable ordinal regression was used to identify baseline comorbidities associated with the primary outcome at 1 year. RESULTS: Chronic pelvic pain severity decreased by a median 2 points from baseline to 1 year (6/10-4/10, P < .001). There was also an improvement in functional quality of life (42-29% on the pain subscale of the Endometriosis Health Profile-30, P < .001), and a reduction in subjects requiring a physician visit (73-36%, P < .001) or emergency visit (24-11%, P < .001) in the last 3 months. On multivariable ordinal regression for the primary outcome, chronic pelvic pain severity at 1 year was independently associated with a higher score on the Pain Catastrophizing Scale at baseline (odds ratio, 1.10; 95% confidence interval, 1.00-1.21, P = .04), controlling for baseline pain, treatment effects (surgery), age, and referral status. CONCLUSION: Improvements in chronic pelvic pain severity, quality of life, and health care utilization were observed in a 1-year cohort in an interdisciplinary setting. Higher pain catastrophizing at baseline was associated with greater chronic pelvic pain severity at 1 year. Consideration should be given to stratifying pelvic pain patients by catastrophizing level (rumination, magnification, helplessness) in research studies and in clinical practice.

Prospective Cohort of Deep Dyspareunia in an Interdisciplinary Setting.

INTRODUCTION: Deep dyspareunia is a common symptom in women, including in half of women with endometriosis, but little is known about its response to treatment and predictors of persistent deep dyspareunia over time. AIM: To follow up deep dyspareunia severity over a 1-year prospective cohort at an interdisciplinary center, and to identify baseline predictors of more persistent deep dyspareunia at 1 year. METHODS: Prospective 1-year cohort study at a tertiary referral center for pelvic pain and endometriosis, where a range of interdisciplinary treatments are provided at a single center (surgical, hormonal, physical, and psychological therapies). Exclusion criteria were menopause, age >50 years, and never previously sexually active. Primary outcome (deep dyspareunia severity) and secondary outcome (sexual quality of life) were followed up over 1 year. Ordinal logistic regression was performed, controlling for baseline severity of deep dyspareunia, to identify baseline predictors of deep dyspareunia severity at 1 year. MAIN OUTCOME MEASURE: Primary outcome was severity of deep dyspareunia on an 11-point numeric rating scale (0-10), categorized into absent-mild (0-3), moderate (4-6), and severe (7-10); secondary outcome was sexual quality of life measured by the Endometriosis Health Profile-30. RESULTS: 1-year follow-up was obtained for 278 subjects (56% response rate at 1 year; 278/497). Severity of deep dyspareunia improved over the 1 year (McNemar test, P < .0001): the proportion of patients in the severe category decreased from 55.0% to 30.4%, the moderate category remained similar from 17.7% to 25.0%, and the absent-mild category increased from 27.3% to 44.6%. Sexual quality of life also improved (56% to 43% on the sex subscale of the Endometriosis Health Profile-30) (Welch t test, P < .001). On ordinal regression, severity of deep dyspareunia at 1 year was independently associated with younger age (OR = 0.94, 95% CI = 0.91-0.97, P = .008), and with a higher baseline depression score on the Patient Health Questionnaire-9 (OR = 1.07, 95% CI = 1.03-1.11, P = .01). CLINICAL IMPLICATIONS: Clinicians should consider employing an interdisciplinary approach for deep dyspareunia, and screening for and treating depression symptoms in these women. STRENGTH & LIMITATIONS: Strengths of the study include its prospective nature, and assessment of deep dyspareunia specifically (as opposed to superficial dyspareunia). Limitations include non-randomized design, and the patients lost to follow-up over the 1 year. CONCLUSION: Over 1 year in an interdisciplinary setting, improvements were observed in deep dyspareunia and sexual quality of life, but younger women and those with more severe depression at baseline had more persistent deep dyspareunia at 1 year. Yong PJ, Williams C, Bodmer-Roy S, et al. Prospective Cohort of Deep Dyspareunia in an Interdisciplinary Setting. J Sex Med 2018;15:1765-1775.

Serum Soluble Transferrin Receptor Concentrations Are Elevated in Congolese Children with Glucose-6-Phosphate Dehydrogenase Variants, but Not Sickle Cell Variants or α-Thalassemia.

Background: Anemia is common in Congolese children, and inherited blood disorders may be a contributing cause. The presence of sickle cell variants, X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency and α-thalassemia, has been previously reported. G6PD A- deficiency is characterized by the co-inheritance of G6PD 376 and 202 variants and is common in sub-Saharan Africa.Objective: We aimed to measure the associations between inherited blood disorders and hemoglobin, ferritin, and soluble transferrin receptor (sTfR) concentrations in Congolese children.Methods: Venous blood was collected from 744 children aged 6-59 mo from 2 provinces. We measured biomarkers of nutritional and inflammation status and malaria. Pyrosequencing was used to detect sickle cell variants. Polymerase chain reaction was used to detect G6PD variants and α-thalassemia deletions.Results: Overall, 11% of children had a sickle cell variant, 19% of boys were G6PD A- hemizygotes, 12% and 10% of girls were G6PD A- hetero- or homozygotes, respectively, and 12% of children had α-thalassemia. Multivariable linear regression models (adjusted for age, province, altitude, malaria, and biomarkers of nutritional and inflammation status) showed that G6PD A- hemizygous boys and G6PD 376 homozygous girls had higher sTfR concentrations [geometric mean ratios (95% CIs): 1.20 (1.03, 1.39) and 1.25 (1.02, 1.53), respectively] than children with no G6PD variants. Hemoglobin and ferritin concentrations were not independently associated with any of the inherited blood disorder genotypes.Conclusions: We found that 2 G6PD variant genotypes were associated with elevated sTfR concentrations, which limits the accuracy of sTfR as a biomarker of iron status in this population.

Limitations and opportunities of whole blood bilirubin measurements by GEM premier 4000®.

BACKGROUND: Neonatal hyperbilirubinemia has traditionally been screened by either total serum bilirubin or transcutaneous bilirubin. Whole blood bilirubin (TwB) by the GEM Premier 4000® blood gas analyzer (GEM) is a relatively new technology and it provides fast bilirubin results with a small sample volume and can measure co-oximetry and other analytes. Our clinical study was to evaluate the reliability of TwB measured by the GEM and identify analytical and clinical factors that may contribute to possible bias. METHODS: 440 consecutive healthy newborn samples that had plasma bilirubin ordered for neonatal hyperbilirubinemia screening were included. TwB was first measured using the GEM, after which the remainder of the blood was spun and plasma neonatal bilirubin was measured using the VITROS 5600® (VITROS). RESULTS: 62 samples (14%) were excluded from analysis due to failure in obtaining GEM results. Passing-Bablok regression suggested that the GEM results were negatively biased at low concentrations of bilirubin and positively biased at higher concentrations relative to the VITROS results (y = 1.43x-61.13). Bland-Altman plots showed an overall negative bias of the GEM bilirubin with a wide range of differences compared to VITROS. Both hemoglobin concentration and hemolysis affected the accuracy of the GEM results. Clinically, male infants had higher mean bilirubin levels, and infants delivered by caesarean section had lower hemoglobin levels. When comparing the number of results below the 40th percentile and above the 95th percentile cut-offs in the Bhutani nomogram which would trigger discharge or treatment, GEM bilirubin exhibited poor sensitivity and poor specificity in contrast to VITROS bilirubin. CONCLUSIONS: An imperfect correlation was observed between whole blood bilirubin measured on the GEM4000® and plasma bilirubin on the VITROS 5600®. The contributors to the observed differences between the two instruments were specimen hemolysis and the accuracy of hemoglobin measurements, the latter of which affects the calculation of plasma-equivalent bilirubin. Additionally, the lack of standardization of total bilirubin calibration particularly in newborn specimens, may also account for some of the disagreement in results.

Diabetic Pharmacotherapy and Endometrial Cancer Risk Within a Publicly Funded Health Care System.

OBJECTIVE: There is conflicting evidence regarding the association between metformin and endometrial cancer risk. The objective of this study was to evaluate the association between type of diabetic pharmacotherapy and endometrial cancer risk within a population-based study. The hypothesis was that metformin was associated with the lowest risk. METHODS: This was a nested case-control study using data from the BC Cancer Registry (2000-2009) and from a province-wide prescription network (PharmaNet) since 1996. Patients were classified by drug exposure (metformin, thiazolidinediones, secretagogues, with or without insulin). The primary analysis was a conditional logistic regression to estimate the odds ratios for endometrial cancer in the drug exposure groups. Sensitivity analysis was carried out to account for uncertainty regarding various parameters. The secondary analysis evaluated the effect of dosage using a principal components analysis. RESULTS: The study cohort comprised 492 cases and 4404 controls. The primary analysis revealed no difference in endometrial cancer risk between those using metformin and those prescribed other classes of medications (OR 1.5, 95% CI 0.9 to 2.4). Women receiving all classes of medications had almost a two-fold increase in risk (OR 1.9, 95% CI 1.1 to 3.3). The secondary analysis revealed an increased risk associated with a greater duration of treatment and number of prescriptions (OR 1.3, 95% CI 1.2 to 1.4). CONCLUSION: In this population-based study, metformin was not associated with a decreased endometrial cancer risk. Women receiving multiple types of medications over a long time had the highest risk, implying that the extent of insulin resistance, rather than the effect of any specific medication, drives endometrial cancer risk.