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.

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.

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.

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.

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.

High Prevalence and Incidence of Obsessive-Compulsive Disorder Among Women Across Pregnancy and the Postpartum.

Objective: During the perinatal period, women are at an increased risk for the onset/exacerbation of obsessive-compulsive disorder (OCD) and may experience perinatal-specific obsessions and/or compulsions. Past research has provided preliminary findings regarding the prevalence of OCD in the perinatal period but has often reported limited metrics and ignored perinatal specific symptoms. This research aimed to assess the prevalence and incidence of maternal OCD between the third trimester in pregnancy and 6 months postpartum.Methods: An unselected sample of 763 English-speaking pregnant women and new mothers participated in a longitudinal, province-wide study between their third trimester in pregnancy and 9 months postpartum. They completed 3 online questionnaires and interviews (data collected between February 9, 2014, and February 14, 2017) and were administered a diagnostic interview to determine OCD status based on DSM-5 diagnostic criteria.Results: A weighted prenatal period prevalence of 7.8% and a postpartum period prevalence of 16.9% were found. The average, prenatal, point prevalence estimate was 2.9%, and the average, postpartum, point prevalence estimate was 7.0%. Point prevalence gradually increased over the course of pregnancy and the early postpartum, attaining a peak of close to 9% at approximately 8 weeks postpartum, with a gradual decline thereafter. The cumulative incidence of new OCD diagnoses was estimated at 9% by 6 months postpartum.Conclusions: Our study suggests that when women are encouraged to report their perinatal-specific symptoms, and current diagnostic criteria are applied, estimates for perinatal OCD may be higher than previously believed.

Sex-dependent effects of prenatal food and protein restriction on offspring physiology in rats and mice: systematic review and meta-analyses.

BACKGROUND: Males and females may experience different effects of early-life adversity on life-long health. One hypothesis is that male foetuses invest more in foetal growth and relatively less in placental growth, and that this makes them susceptible to poor nutrition in utero, particularly if nutrition is reduced part-way through gestation. OBJECTIVES: Our objectives were to examine whether (1) food and/ or protein restriction in rats and mice has consistent sex-dependent effects, (2) sex-dependency differs between types of outcomes, and (3) males are more severely affected when restriction starts part-way through gestation. DATA SOURCES: PubMed and Web of Science were searched to identify eligible studies. STUDY ELIGIBILITY CRITERIA: Eligible studies described controlled experiments that restricted protein or food during gestation in rats or mice, examined physiological traits in offspring from manipulated pregnancies, and tested whether effects differed between males and females. RESULTS: Our search identified 292 articles, of which the full texts of 72 were assessed, and 65 were included for further synthesis. A majority (50) used Wistar or Sprague-Dawley rats and so these were the primary focus. Among studies in which maternal diet was restricted for the duration of gestation, no type of trait was consistently more severely affected in one particular sex, although blood pressure was generally increased in both sexes. Meta-analysis found no difference between sexes in the effect of protein restriction throughout gestation on blood pressure. Among studies restricting food in the latter half of gestation only, there were again few consistent sex-dependent effects, although three studies found blood pressure was increased in males only. Meta-analysis found that food restriction in the second half of gestation increased adult blood pressure in both sexes, with a significantly greater effect in males. Birthweight was consistently reduced in both sexes, a result confirmed by meta-analysis. CONCLUSIONS: We found little support for the hypotheses that males are more affected by food and protein restriction, or that effects are particularly severe if nutrition is reduced part-way through gestation. However, less than half of the studies tested for sex by maternal diet interactions to identify sex-dependent effects. As a result, many reported sex-specific effects may be false positives.

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.

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.

Prolonged Amenorrhea and Low Hip Bone Mineral Density in Women Living With HIV-A Controlled Cross-sectional Study.

BACKGROUND: Women living with HIV (WLWH) have higher rates of prolonged secondary amenorrhea (no flow for ≥1 year) than HIV-negative women. Both having amenorrhea and being HIV positive are associated with lower areal bone mineral density (BMD). However, their combined BMD effects remain unclear. Therefore, we investigated prolonged amenorrhea and BMD in WLWH and controls. METHODS: This cross-sectional study enrolled WLWH and HIV-negative control women aged 19-68 years of similar backgrounds. We assessed BMD (Hologic; as age- and ethnicity-matched Z-scores) in the Children and women: AntiRetrovirals and Markers of Aging cohort. Participants were stratified by amenorrhea history defined as past/present lack of menses for ≥1 year at age 45 and younger and not because of surgery, breastfeeding, pregnancy, or hormonal contraception. Hip and spine Z-scores by amenorrhea/no amenorrhea used linear models with multivariable analysis for relationships within WLWH. RESULTS: WLWH (N = 129) were similar to controls (N = 129) in age, body mass index, ethnicity, and substance use. Among WLWH, 21% experienced prolonged amenorrhea vs. 9% in controls. WLWH had significantly lower total hip (mean ± SD: -0.4 ± 0.9 vs. 0.3 ± 1.1; P < 0.001) and spine (-0.5 ± 1.3 vs. 0.2 ± 1.3; P = 0.001) Z-scores than controls. Amenorrhea was independently associated with hip (P = 0.01) but not spine (P = 0.94) BMD by multivariable linear regression. WLWH with amenorrhea had lower hip Z-scores (-0.8 ± 0.9) than those without (-0.3 ± 0.8; P = 0.01). They also had higher rates of substance use, smoking, opioid therapy, hepatitis C coinfection, and lower CD4 nadir. CONCLUSIONS: WLWH had higher rates of prolonged amenorrhea and lower BMD than controls. WLWH with amenorrhea experienced lower hip BMD Z-scores than those without. Prolonged amenorrhea is an added osteoporosis risk in WLWH.

Investigation of factors associated with spontaneous preterm birth in pregnant women living with HIV.

OBJECTIVE: To investigate factors contributing to preterm birth (PTB), including cART use and clinical and social determinants of health, in women living with HIV (WLWH) from British Columbia, Canada. DESIGN: Retrospective observational cohort. METHODS: We investigated the effect of cART use and other clinical and demographic factors on spontaneous PTB (sPTB) rates (<37 weeks gestational age) among 631 singleton pregnancies between 1997 and 2018. Exposure to cART was modelled in comparison to no exposure, exposure in the first trimester, and between regimens. Differences in sPTB risk were estimated using time-dependent Cox's proportional hazards models. RESULTS: Overall, the sPTB rate was 16%. Cumulative cART use was associated with lower risk of PTB (Wald test P = 0.02; hazard ratio = 0.98, 95% CI = 0.96-0.99) and specific cART regimens were not associated with increased risk of sPTB. Exposure in the first trimester was not associated with sPTB and for each week of cART exposure, the risk of sPTB decreased by 2%. In a multivariable model, HIV viral load and substance use remained associated with risk of sPTB, but not cART exposure. CONCLUSION: The sPTB rate among pregnant WLWH was more than three times higher than in the general population. However, sPTB was not related specifically to use of cART; in fact, cART appeared to reduce the risk of sPTB. Uncontrolled HIV replication and substance use were associated with increased risk of sPTB among pregnant WLWH. This emphasizes the important role of prenatal care, access to cART, and smoking cessation and harm reduction to reduce the risk of sPTB in WLWH.

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.

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.

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.

Exploring the live birth rates of women living with HIV in British Columbia, Canada.

OBJECTIVE: To evaluate the birth rates of women living with HIV (WLWH) compared to the general population in British Columbia (BC), Canada. METHODS: We retrospectively reviewed clinical and population level surveillance data from 1997 to 2015. Live birth rates from 1997 to 2015 among WLWH aged 15-49 years were compared with those of all BC women. Next, the number of live births among WLWH with a live birth between 1997-2012 and HIV-negative controls matched 1:3 by geocode were compared. RESULTS: WLWH had a lower birth rate compared to all BC women [31.4 (95%CI, 28.6-34.3) vs. 40.0 (39.3-40.1)/1000 person years]. Stratified by age, WLWH aged 15-24 years had a higher birth rate while WLWH aged 25-49 years had a lower birth rate than BC women (p<0.01). Between 1997 and 2015, birth rates for both populations decreased among women aged 15-24 years, and increased among women aged 25-49 years, most strikingly among WLWH 35-49 years (p<0.01). When comparing WLWH with a live birth to HIV-negative geocode matched controls, WLWH aged 15-24 years (p = 0.03) and aged 25-34 years (p<0.01) had more live births than controls while WLWH aged 35-49 years did not (p = 0.06). CONCLUSIONS: On a population level, WLWH have lower birth rates than the general population. However, this is not observed among WLWH who have ever given birth compared with matched controls, suggesting that sociodemographic factors may play an important role. WLWH are increasingly giving birth in their later reproductive years. Taken together, our data supports the integration of reproductive health and HIV care.

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.

Multidisciplinary Treatment for Provoked Vestibulodynia: Treatment Trajectories, Predictors, and Moderators of Sexual Distress and Pain.

OBJECTIVES: Multidisciplinary treatment programs for provoked vestibulodynia (PVD) are recommended, yet few have been evaluated. This study examined women's symptom trajectories over time, as well as baseline demographic, psychosocial and pain characteristics as predictors/ moderators of sexual pain and distress following treatment at a clinic using multidisciplinary concurrent methods. We also examined the impact of baseline variables on the probability of having low sexual distress scores following treatment. MATERIALS AND METHODS: Women attending a multidisciplinary treatment program for PVD were invited to complete questionnaires before, following, and at 6 and 18 months after program completion. Questionnaires included the Female Sexual Function Index (FSFI), Female Sexual Distress Scale (FSDS), State-Trait Anxiety Inventory (STAI), Pain Catastrophizing Scale (PCS), Painful Intercourse Self-Efficacy Scale (PISES), and Pain Vigilance and Awareness Questionnaire (PVAQ). Linear mixed-effects models evaluated the FSDS and FSFI pain subscale as criterion variables, and the other baseline variables as predictors and moderators. RESULTS: Significant improvements in sexual distress and pain were observed over time. No significant moderators were identified, but higher baseline levels of FSFI desire and arousal predicted greater improvements in sexual distress. Similarly, higher baseline levels of desire predicted greater improvements in pain. Among women distressed at baseline and with 6 month FSDS scores, 25% (n=35) were no longer sexually distressed at 6 months; higher baseline levels of desire were associated with greater probability of having low sexual distress at 6 months. DISCUSSION: Although global improvements were observed, women with poorer baseline sexual functioning were less likely to improve after multidisciplinary treatment.

Premature Spinal Bone Loss in Women Living with HIV is Associated with Shorter Leukocyte Telomere Length.

With advances in combination antiretroviral therapy (cART), people living with HIV are now surviving to experience aging. Evidence suggests that individuals living with HIV are at greater risk for low bone mineral density (BMD), osteoporosis, and fractures. Better understanding of the pathophysiology of bone health in women living with HIV (WLWH) is important for treatment strategies. The goal of this study was to explore new biological factors linked to low BMD in WLWH. Standardized BMD measures of WLWH were compared to reference values from an unselected population of women from the same geographical region of the same age range. Linear regression analysis was used to assess relationships among health-related characteristics, cellular aging (measured by leukocyte telomere length; LTL), cART, and BMD of WLWH. WLWH (n = 73; mean age 43 ± 9 years) had lower BMD Z-scores at the lumbar spine (LS) (mean difference = -0.39, p < 0.001) and total hip (TH) (-0.29, p = 0.012) relative to controls (n = 290). WLWH between 50 and 60 years (n = 17) had lower Z-scores at the LS (p = 0.008) and TH (p = 0.027) compared to controls (n = 167). Among WLWH, LS BMD was significantly associated with LTL (R² = 0.09, p = 0.009) and BMI (R² = 0.06, p = 0.042). Spinal BMD was adversely affected in WLWH. Reduction of LTL was strongly associated with lower BMD and may relate to its pathophysiology and premature aging in WLWH.

Adverse perinatal outcomes associated with crown-rump length discrepancy in in vitro fertilization pregnancies.

OBJECTIVE(S): To determine whether an association exists between small crown-rump length (CRL) and adverse obstetrical outcomes in pregnancies conceived by IVF and to compare a CRL reference based on IVF pregnancies to a reference based on spontaneous pregnancies. DESIGN: Retrospective cohort study. CRL was classified as small by comparing it with the local university hospital maternal fetal medicine standard and the Monash IVF reference chart. SETTING: University-affiliated fertility center. PATIENT(S): Singleton pregnancies conceived by IVF with ultrasounds performed between 7+0 and 8+6 weeks of gestational age. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Pregnancy loss, preterm birth, and low birth weight. RESULT(S): Included were 940 clinical pregnancies. The overall and CRL-discrepant miscarriage rates were 12.7% and 41%, respectively. When CRL was small, the maternal age-adjusted odds of miscarriage were 13.8 times higher (95% confidence interval [CI], 8.9-21.6). At age 30, small CRL was associated with a 30% risk of miscarriage, versus 61% at age 45. There was no association between small CRL and preterm birth or low birth weight. The sensitivity and specificity for predicting miscarriage from the optimal Monash cut point were 0.69 (95% CI, 0.61-0.77) and 0.84 (95% CI, 0.82-0.87), which were similar to those of the CRL reference based on spontaneous pregnancies. CONCLUSION(S): Small CRL in IVF pregnancy was strongly associated with miscarriage, especially in the context of advanced maternal age. Small CRL was not associated with preterm birth or low birth weight. A CRL reference based on IVF pregnancies was equivalent to the standard reference for predicting miscarriage.

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.