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Background Tricuspid regurgitation (TR) is common among adults with corrected tetralogy of Fallot (TOF) or pulmonary stenosis (PS) referred for pulmonary valve replacement (PVR). Yet, combined valve surgery remains controversial. Objectives This study sought to evaluate the impact of concomitant tricuspid valve intervention (TVI) on post-operative TR, length of hospital stay, and on a composite endpoint consisting of 7 early adverse events (death, reintervention, cardiac electronic device implantation, infection, thromboembolic event, hemodialysis, and readmission). Methods The national Canadian cohort enrolled 542 patients with TOF or PS and mild to severe TR who underwent isolated PVR (66.8%) or PVR+TVI (33.2%). Outcomes were abstracted from charts and compared between groups using multivariable logistic and negative binomial regression. Results Median age at reintervention was 35.3 years. Regardless of surgery type, TR decreased by at least 1 echocardiographic grade in 35.4%, 66.9%, and 92.8% of patients with pre-operative mild, moderate, and severe insufficiency. In multivariable analyses, PVR+TVI was associated with an additional 2.3-fold reduction in TR grade (odds ratio [OR]: 0.44; 95% confidence interval [CI]: 0.25 to 0.77) without an increase in early adverse events (OR: 0.85; 95% CI: 0.46 to 1.57) or hospitalization time (incidence rate ratio: 1.17; 95% CI: 0.93 to 1.46). Pre-operative TR severity and presence of transvalvular leads independently predicted post-operative TR. In contrast, early adverse events were strongly associated with atrial tachyarrhythmia, extracardiac arteriopathy, and a high body mass index. Conclusions In patients with TOF or PS and significant TR, concomitant TVI is safe and results in better early tricuspid valve competence than isolated PVR.

Background Experimental studies provide evidence of the harmful effect of human papillomavirus (HPV) infection on pregnancy, but observational studies are inconclusive. We systematically assessed the association between HPV and adverse pregnancy outcomes. Methods We searched electronic databases up to December 1, 2019. We included observational studies on the association between HPV and adverse pregnancy outcomes. We conducted a random-effect meta-analysis for each outcome and assessed heterogeneity between studies. Results From 3034 citations, we included 38 studies and quantitatively synthesized 36 studies. Human papillomavirus was significantly associated with preterm birth (age-adjusted odds ratio [aOR], 1.50; 95% confidence interval [CI], 1.19–1.88), preterm premature rupture of membranes (aOR, 1.96; 95% CI, 1.11–3.45), premature rupture of membranes (aOR, 1.42; 95% CI, 1.08–1.86), intrauterine growth restriction (aOR, 1.17; 95% CI, 1.01–1.37), low birth weight (aOR, 1.91; 95% CI, 1.33–2.76), and fetal death (aOR, 2.23; 95% CI, 1.14–4.37). No significant association was found for spontaneous abortion (aOR, 1.14; 95% CI, 0.40–3.22) and pregnancy-induced hypertensive disorders (aOR, 1.24; 95% CI, 0.80–1.92). Most of the studies were of moderate or low quality, and substantial between-studies heterogeneity remained unexplained. Conclusions We found a consistent and significant association between HPV and preterm birth and preterm premature rupture of membranes. Human papillomavirus may also be associated with intrauterine growth restriction, low birth weight, and fetal death, but findings are limited by suboptimal control of biases.

Thromboembolic events contribute greatly to morbidity and mortality following Fontan surgery for univentricular hearts.This study sought to evaluate the effect of type of Fontan surgery on thromboembolic risk.A North American multicenter retrospective cohort study enrolled 522 patients with Fontan palliation consisting of an atriopulmonary connection (APC) (21.4%), lateral tunnel (LT) (41.8%), or extracardiac conduit (EC) (36.8%). Thromboembolic complications and new-onset atrial arrhythmia were reviewed and classified by a blinded adjudicating committee. Thromboembolic risk across surgical techniques was assessed by multivariable competing-risk survival regression.Over a median follow-up of 11.6 years, 10- and 20-year freedom from Fontan conversion, transplantation, or death was 94.7% and 78.9%, respectively. New-onset atrial arrhythmias occurred in 4.4, 1.2, and 1.0 cases per 100 person-years with APC, LT, and EC, respectively. APC was associated with a 2.82-fold higher risk of developing atrial arrhythmias (p 0.001), with no difference between LT and EC (p = 0.95). A total of 71 thromboembolic events, 32 systemic and 39 venous, occurred in 12.8% of subjects, for an overall incidence of 1.1%/year. In multivariable analyses, EC was independently associated with a lower risk of systemic (hazard ratio [HR]: 0.20 vs. LT; 95% confidence interval [CI]: 0.04 to 0.97) and combined (HR: 0.34 vs. LT; 95% CI: 0.13 to 0.91) thromboembolic events. A lower incidence of combined thromboembolic events was also observed with antiplatelet agents (HR: 0.54; 95% CI: 0.32 to 0.92) but not anticoagulation (p = 0.53).The EC Fontan was independently associated with a lower thromboembolic risk after controlling for time-varying effects of atrial arrhythmias and thromboprophylaxis.

Background: Epstein–Barr virus (EBV) and cytomegalovirus (CMV) infections can have serious consequences during the period of aplasia and lymphopenia following hematopoietic stem cell transplantation (HSCT). Large pediatric cohort studies examining the effect of antiviral prophylaxis against these viruses are scarce. The present study aimed to analyse the potential effect of antiviral prophylaxis (acyclovir and famciclovir) on active post-transplant EBV and CMV infection in a pediatric cohort of allogeneic HSCT recipients. Methods: We used data from the TREASuRE cohort, consisting of 156 patients who had a first allogeneic HSCT, enrolled in four pediatric centers in Canada between July 2013 and March 2017. Follow-up was performed from the time of transplant up to 100 days post-transplant. Adjusted hazard ratio (HR) with 95% confidence intervals (CI) for the association between antiviral prophylaxis with acyclovir and/or famciclovir and EBV and CMV DNAemia was estimated using multivariate Cox regression models. Results: The post-transplant cumulative incidence of EBV and CMV DNAemia at 100 days of follow-up were, respectively, 34.5% (95% CI: 27.6–42.6) and 19.9% (95% CI: 14.5–27.1). For acyclovir, the adjusted hazard ratio (HR) for CMV and EBV DNAemia was 0.55 (95% CI: 0.24–1.26) and 1.41 (95% CI: 0.63–3.14), respectively. For famciclovir, the adjusted HR were 0.82 (95% CI: 0.30–2.29) and 0.79 (95% CI: 0.36–1.72) for CMV and EBV DNAemia, respectively. Conclusion: The antivirals famciclovir and acyclovir did not reduce the risk of post-transplant CMV and EBV DNAemia among HSCT recipients in our pediatric population.

Background Epstein-Barr virus (EBV) can cause severe disease following hematopoietic stem cell transplant (HSCT), including post-transplant lymphoproliferative disorder (PTLD). The objective was to analyze risk factors associated with post-transplant EBV outcomes among pediatric allogeneic HSCT recipients. Methods We used data from 156 pediatric allogeneic HSCT recipients enrolled in the Canadian multicenter TREASuRE study. Cox and Prentice-Williams-Petersen models were used to analyze risk factors for post-transplant EBV events including occurrence and recurrence of EBV DNAemia, increase in EBV viral load (EBV-VL), and preemptive use of rituximab, an effective therapy against PTLD. Results Females were at higher risk for increasing EBV-VL (adjusted hazard ratio (HR) = 2.83 [95% confidence intervals (CI): 1.33-6.03]) and rituximab use (HR = 3.08 [1.14-8.30]), but had the same EBV DNAemia occurrence (HR = 1.21 [0.74-1.99]) and recurrence risks (HR=1.05 [0.70-1.58]) compared to males. EBV DNAemia was associated with recipient pre-transplant EBV seropositivity (HR = 2.47 [1.17-5.21]) and with graft from an EBV-positive donor (HR = 3.53 [1.95-6.38]). Anti-thymocyte globulin (ATG) was strongly associated with all EBV outcomes, including the use of rituximab (HR = 5.33 [1.47-19.40]). Mycophenolate mofetil (MMF) significantly decreased the risk of all EBV events including the rituximab use (HR = 0.13 [0.03-0.63]). Conclusion This study in pediatric allogeneic HSCT patients reveals a reduced risk of all EBV outcomes with the use of MMF. Risk factors for EBV events such as EBV-VL occurrence and recurrence include EBV positivity in the donor and recipient, and use of ATG, whereas risk factors for the most severe forms of EBV outcome (EBV-VL and the use of rituximab) include female sex and ATG use.

This systematic review was undertaken to identify risk factors associated with post-transplant Epstein–Barr virus (EBV) active infection and post-transplant lymphoproliferative disease (PTLD) in pediatric and adult recipients of hematopoietic stem cell transplants (HSCT). A literature search was conducted in PubMed and EMBASE to identify studies published until 30 June 2020. Descriptive information was extracted for each individual study, and data were compiled for individual risk factors, including, when possible, relative risks with 95% confidence intervals and/or p-values. Meta-analyses were planned when possible. The methodological quality and potential for bias of included studies were also evaluated. Of the 3362 titles retrieved, 77 were included (62 for EBV infection and 22 for PTLD). The overall quality of the studies was strong. Several risk factors were explored in these studies, but few statistically significant associations were identified. The use of anti-thymocyte globulin (ATG) was identified as the most important risk factor positively associated with post-transplant active EBV infection and with PTLD. The pooled relative risks obtained using the random-effect model were 5.26 (95% CI: 2.92–9.45) and 4.17 (95% CI: 2.61–6.68) for the association between ATG and post-transplant EBV infection and PTLD, respectively. Other risk factors for EBV and PTLD were found in the included studies, such as graft-versus-host disease, type of conditioning regimen or type of donor, but results are conflicting. In conclusion, the results of this systematic review indicate that ATG increases the risk of EBV infection and PTLD, but the link with all other factors is either nonexistent or much less convincing.

BackgroundImplementation of the programmes for the Prevention of Mother to Child Transmission (PMTCT) of Human Immunodeficiency Virus (HIV) into antenatal care over the last three decades could inform implementation of interventions for other health challenges such as gestational diabetes mellitus (GDM). This study assessed PMTCT outcomes, and how GDM screening, care, and type 2 diabetes (T2DM) prevention were integrated into PMTCT in Western Cape (WC), South Africa.MethodsA convergent mixed methods and triangulation design were used. Content and thematic analysis of PMTCT-related policy documents and of 30 semi-structured interviews with HIV/PMTCT experts, health care workers and women under PMTC diagnosed with GDM complement quantitative longitudinal analysis of PMTCT implementation indicators across the WC for 2012–2017.ResultsProvincial PMTCT and Post Natal Care (PNC) documents emphasized the importance of PMTCT, but GDM screening and T2DM prevention were not covered. Data on women with both HIV and GDM were not available and GDM screening was not integrated into PMTCT. Women who attended HIV counselling and testing annually increased at 17.8% (95% CI: 12.9% - 22.0%), while women who delivered under PMTCT increased at 3.1% (95% CI: 0.6% - 5.9%) annually in the WC. All 30 respondents favour integrating GDM screening and T2DM prevention initiatives into PMTCT.ConclusionPMTCT programmes have not yet integrated GDM care. However, Western Cape PMTCT integration experience suggests that antenatal GDM screening and post-partum initiatives for preventing or delaying T2DM can be successfully integrated into PMTCT and primary care.

There is uncertainty regarding the potential virologic outcome associated with a change in antiretroviral therapy (ARV) among PLHIV who had previous documented virologic failure or who have been exposure to mono/dual nucleoside reverse transcriptase inhibitors (NRTI) therapy. The objective was to measure the potential impact of exposure to previous virologic failure or mono/dual NRTI regimen on virologic outcome of PLHIV following a switch to dolutegravir with 2 NRTIs from a viremia suppressive ARV therapy. Data from the Quebec HIV Cohort including 10219 PLHIV were collected through routine clinical care at 4 clinical sites in Montreal, Canada. This study includes patients whose ARV therapy was switched to dolutegravir with 2 NRTIs since 2013 with undetectable viral load for ≥6 months before switch. The association between exposure and post-switch virologic outcome was measured by marginal hazard ratio estimated using the Inverse probability weighting Cox model. Among the 1199 eligible PLHIV, 478 (39.9%) previously experienced at least one virologic failure or were exposed to mono/dual therapy before dolutegravir switch. Post-switch virologic failure after 30 months occurred in 4.1% (95% CI 2.1–7.9) of exposed compared to 4.1% (95% CI 2.3–7.4) in unexposed participants. The adjusted hazard ratio for the association between exposure and post-switch virologic failure was 0.84 (95% CI 0.35–2.01). Our findings suggest that switch to dolutegravir with 2 NRTIs from a suppressive therapy is a safe option for PLHIV with documented virologic failure and/or previous exposure to mono/dual NRTI therapy.

Background Switching antiretroviral regimens when human immunodeficiency virus (HIV) viremia is controlled for a new regimen is challenging when there is the potential for prior nucleoside reverse-transcriptase inhibitor (NRTI) resistance. The objective was to study virologic outcomes after switching to dolutegravir compared with remaining on a boosted protease inhibitor (protease inhibitor/ritonavir [PI/r]) regimen in people with HIV (PWH) with prior documented virologic failure and/or exposure to mono/dual NRTIs. Methods We used the Quebec HIV Cohort including 10 219 PWH whose data were collected at 4 sites in Montreal, Canada. We included all PWH with documented virologic failure or exposure to mono/dual NRTI therapy who were virologically suppressed on a PI/r-based regimen for at least 6 months on or after January 1, 2014 (n = 532). A marginal structural Cox model analysis was used to estimate the effect of the switch to dolutegravir on virologic outcome compared with remaining on PI/r. The outcome was defined as 2 consecutive viral loads (VLs) >50 copies/mL or 1 VL >50 copies/mL if it occurred at the last VL available. Results Among 532 eligible participants, 216 (40.6%) had their regimen switched to dolutegravir with 2 NRTIs, whereas 316 (59.4%) remained on the PI/r with 2 NRTIs. The weighted hazard ratio for the effect of dolutegravir switch on virologic failure compared with patients whose regimen remained on PI/r was 0.57 (95% confidence interval, 0.21–1.52). Conclusions We did not find evidence of an increased risk for virologic failure after switching to dolutegravir from PI/r among patients with previous virologic failure or prior exposure to mono/dual NRTI., Therapeutic switches to dolutegravir with 2 NRTIs provide a safe option for patients with a viremia suppressive antiretroviral regimen in the presence of prior documented virologic failure and prior exposure to mono/dual NRTI therapy.

BackgroundIntegrating Prevention of Mother-to-Child Transmission (PMTCT) programmes into routine health services under complex socio-political and health system conditions is a priority and a challenge. The successful rollout of PMTCT in sub-Saharan Africa has decreased Human Immunodeficiency Virus (HIV), reduced child mortality and improved maternal health. In South Africa, PMTCT is now integrated into existing primary health care (PHC) services and this experience could serve as a relevant example for integrating other programmes into comprehensive primary care. This study explored the perspectives of both experts or key informants and frontline health workers (FHCWs) in South Africa on PMTCT integration into PHC in the context of post-AIDS denialism using a Complex Adaptive Systems framework.MethodsA total of 20 in-depth semi-structured interviews were conducted; 10 with experts including national and international health systems and HIV/PMTCT policy makers and researchers, and 10 FHCWs including clinic managers, nurses and midwives. All interviews were conducted in person, audio-recorded and transcribed. Three investigators collaborated in coding transcripts and used an iterative approach for thematic analysis.ResultsExperts and FHCWs agreed on the importance of integrated PMTCT services. Experts reported a slow and partial integration of PMTCT programmes into PHC following its initial rollout as a stand-alone programme in the aftermath of the AIDS denialism period. Experts and FHCWs diverged on the challenges associated with integration of PMTCT. Experts highlighted bureaucracy, HIV stigma and discrimination and a shortage of training for staff as major barriers to PMTCT integration. In comparison, FHCWs emphasized high workloads, staff turnover and infrastructural issues (e.g., lack of rooms, small spaces) as their main challenges to integration. Both experts and FHCWs suggested that working with community health workers, particularly in the post-partum period, helped to address cases of loss to follow-up of women and their babies and to improve linkages to polymerase-chain reaction (PCR) testing and immunisation.ConclusionsDespite organised efforts in South Africa, experts and FHCWs reported multiple barriers for the full integration of PMTCT in PHC, especially postpartum. The results suggest opportunities to address operational challenges towards more integrated PMTCT and other health services in order to improve maternal and child health.

Background Epstein-Barr virus (EBV) is carried in the blood of most adults, and transfusion-related infections have been reported. EBV is particularly deleterious in immunosuppressed transplant patients. The aim was to determine if EBV transmission occurred through leukodepleted blood product transfusion in pediatric recipients of hematopoietic stem cell transplants (HSCT). Study design and methods This prospective Canadian multi-center cohort study includes 156 allogeneic HSCT pediatric recipients. The association between EBV and transfusion was analyzed using Cox regressions. EBV infection, defined by a PCR+ test in the blood of seronegative recipients of an EBV-negative graft, was monitored in order to correlate the recipient EBV strain with that of the blood donors. EBV genotypes were determined by PCR amplification followed by DNA sequencing at two loci (EBNA3b and LMP1). Results No statistically significant associations were found between transfusions and EBV. One case of post-transplant EBV infection was identified among the 21 EBV-seronegative recipients receiving an EBV-negative graft. A total of 22 blood donors were retraced to determine whether the recipient's EBV strain matched that of a donor. One donor strain showed 100% sequence homology at the EBNA3b locus, but differed by one or two point mutations and by a 132-bp deletion at the LMP1 locus. The blood donor in question was alone among the 22 donors to show amplifiable virus in plasma. Blood from this donor readily produced an immortalized lymphoblastoid cell line in culture. Conclusion While considered a rare event, EBV transmission through transfusion may occur in the context of severe immunosuppression.

Background Little is known about the association between bisphenol A (BPA) or triclosan (TCS) exposure and hypertension in pregnancy. Objective To investigate potential associations between maternal urinary concentrations of BPA or TCS and gestational hypertension (GH) and preeclampsia. Study Design Among 1,909 pregnant women participating in the maternal-infant research on environmental chemicals (MIREC) study, urinary concentrations of BPA and TCS were measured in the first trimester by liquid chromatography-tandem mass spectrometry using isotope dilution. Blood pressure was measured during each trimester. Multinomial regression was performed to estimate the adjusted odds ratio (aOR) and 95% confidence intervals (CI) for the associations between these phenols and GH and preeclampsia. Results BPA and TCS were not associated with GH or preeclampsia. However, in multiparous women, BPA (0.50–1.30 µg/L) was associated with decreased risk of GH (aOR =0.45; 95%CI: 0.21–0.98) while among nulliparous women, TCS was associated with an increased risk of GH (3.60–32.60 µg/L; aOR = 2.58; 95% CI: 1.09–6.13 and > 32.60 µg/L: aOR = 2.74; 95% CI: 1.15–6.51). Conclusion BPA and TCS urinary concentrations were not associated with GH or preeclampsia; however, our results suggest an association between TCS and GH in nulliparous women. Additional studies are required to confirm our results.

Background: There is a paucity of data on the dynamics of human papillomavirus (HPV) antibodies in children. We aimed to describe the vertical transmission and clearance of antibodies against HPV6, 11, 16 and 18 in children.Methods: We used data from pregnant women recruited into the HERITAGE cohort study between 2009 and 2012 who were positive for HPV-DNA at baseline. Dried blood spots were collected during the first trimester in pregnant participants, and at birth, 6, 12, and 24 months of age in children. The level of total immunoglobulin G (IgG) against HPV6, 11, 16 and 18 were measured using Luminex immunoassays. Spearman's coefficients were used to correlate HPV antibody levels between newborns and mothers. Panel and Kaplan-Meier graphics described antibody dynamics in the first 24 months of life.Findings: Antibodies from newborns and mothers (n = 58 pairs) were moderately to highly correlated with coefficients of 0·81 (95% confidence intervals (CI):0·70–0·88), 0·68 (95% CI:0·5–0·80), 0·90 (95% CI:0·83–0·94) and 0·85 (95% CI:0·76–0·91) against HPV6, 11, 16 and 18, respectively. In newborns seropositive at birth, anti-HPV antibodies were cleared by 80% and 100% at 12 and 24 months, respectively. Only two children presented detectable HPV antibodies at 24 months. The first child had no detectable antibodies at birth and the second presented increasing levels after two undetected measures.Interpretation: Correlation between mother and newborn IgG antibodies against HPV suggests vertical transfer. Most children cleared anti-HPV antibodies within six to 12 months.Funding: The Canadian Institutes of Health Research (CIHR) Keywords: Human papillomavirus, Serology, Mother-newborn correlation, Vertically acquired immunity, Antibody clearance, Antibody dynamics

Background The potential association between the presence or replacement of dental amalgams and gestational hypertension (GH) is unclear. Objective To assess the association between the presence or replacement of dental amalgams and the risk of GH in a prospective cohort study. Methods We assessed dental amalgam status (presence or replacement), blood mercury concentrations, and measured blood pressure (BP) in 1817 pregnant women recruited in 10 Canadian cities. BP was assessed in each trimester of pregnancy and mercury concentrations in 1st and 3rd trimesters. Logistic regression analysis was performed to estimate the adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the associations between dental amalgam status and GH. Concurrent measures with systolic BP (SBP) and diastolic BP (DBP) were assessing through linear generalized estimating equations. Results Dental amalgam status was weakly statistically correlated with mercury concentrations but there was no evidence of an association with GH in women having 1–4 (aOR = 1.31 (0.92, 1.85)) or ≥ 5 dental amalgams (aOR = 1.32 (0.86, 2.04)), compared to women without amalgam reported at first trimester. Dental amalgam replacement reported in the first or third trimester was similarly not associated with GH (aOR = 0.75 (0.40, 1.42) and 0.73 (0.39, 1.34), respectively) but with SBP (beta = −1.58 (−2.95, −0.02)). Conclusion We found weak correlations between dental amalgams and blood mercury among pregnant women. However, the presence of dental amalgams or their replacement was not associated with GH but with decreased SBP for the replacement. Further studies are required.

Background Early antiretroviral therapy (ART) during pregnancy has dramatically reduced the risk of perinatal HIV transmission. However, studies have shown an association between premature delivery and the use of ART during pregnancy (particularly protease inhibitor (PI)-based therapies), which could be explained by placental dysfunction. The objective of this study was to evaluate the association of ART (class, duration of exposure and time of initiation) with placental function by using angiogenic factors placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) as biomarkers. Methods Clinical and biological data from 159 pregnant women living with HIV were analyzed. Levels of each biomarker were measured in the first and second trimester of pregnancy. After logarithmic transformation, we compared these using generalized estimating equations according to (a) the type of ART; (b) the duration of exposure to ART; and (c) the time of initiation of ART. Results After adjusting for variables such as ethnicity, maternal age, gestational age, body mass index, parity, smoking status, and sex of the fetus, we found no significant association between the class of ART (PI-based or not) and serum concentrations of PlGF or sFlt-1. Furthermore, no significant association was found between biomarker levels and the duration of ART exposure or the timing of ART initiation (pre- or post-conception). Conclusions This study suggests that first and second trimester angiogenic factor levels are not significantly associated with ART, regardless of the duration or type (with or without PI). These observations seem reassuring when considering the use of ART during early pregnancy.

Perinatal route of transmission of human papillomavirus (HPV) has been demonstrated in several small studies. We designed a large prospective cohort study (HERITAGE) to better understand perinatal HPV. The objective of this article is to present the study design and preliminary data. In the first phase of the study, we recruited 167 women in Montreal, Canada, during the first trimester of pregnancy. An additional 850 are currently being recruited in the ongoing phase. Cervicovaginal samples were obtained from mothers in the first trimester and tested for HPV DNA from 36 mucosal genotypes (and repeated in the third trimester for HPV-positive mothers). Placental samples were also taken for HPV DNA testing. Conjunctival, oral, pharyngeal and genital samples were collected for HPV DNA testing in children of HPV-positive mothers at every 3–6 months from birth until 2 years of age. Blood samples were collected in mother and children for HPV serology testing. We found a high prevalence of HPV in pregnant women (45%[95%CI:37–53%]) and in placentas (14%[8–21%]). The proportion of HPV positivity (any site) among children at birth/3-months was 11%[5–22%]. HPV was detected in children in multiple sites including the conjunctiva (5%[10–14%]). The ongoing HERITAGE cohort will help provide a better understanding of perinatal HPV. Keywords: Human papillomavirus (HPV), Perinatal transmission, Pregnancy, Placenta, Children, Persistence

Objective: To evaluate the association of antiretroviral therapy (ART) type and duration of exposure with early placental function using biomarkers of aneuploidy screening. Study design: Three hundred thirty-eight pregnant women living with HIV were enrolled in two Canadian centers. Multiple linear regressions were performed adjusting for confounding factors (race, age, gestational age, body mass index, parity, smoking, and fetal sex). Results: Women receiving ART had significantly increased second trimester alpha-fetoprotein (AFP) levels (β = 0.147, 95% CI = [0.067–0.227] for protease inhibitor-based ART and β = 0.176, 95% CI = [0.080–0.272] for ART without protease inhibitor) compared to women who received no treatment. However, there was no significant association between ART type and the levels of free β-human chorionic gonadotrophin (β-hCG), pregnancy-associated plasma protein-A (first trimester), unconjugated estriol, total hCG, and inhibin A (second trimester). No significant association was shown between biomarker levels and duration of ART exposure. Conclusion: Early placental function does not appear to be significantly affected by ART, except for AFP.

As per the American Society for Colposcopy and Cervical Pathology guidelines, human papillomavirus (HPV) testing is currently used as part of cervical cancer screening and during colposcopy follow-up. The present project evaluated if the application of acetic acid (AA) impacts HPV test results. Methods We conducted a prospective nonrandomized interventional study. Participants referred for colposcopy were eligible if immunocompetent, older than 18 years, and not pregnant. Women in group A (controls) received 2 consecutive HPV tests without application of AA. Women in group B had a first HPV sample collected before the application of AA and a second sample collected 3 minutes after application of AA. Samples were tested for HPV DNA with Hybrid Capture 2 (HC2) according to the manufacturer's instructions. Results From October 17, 2012, to January 10, 2013, approximately 101 women were recruited in 2 colposcopy clinics. In each group, concordance was 98%, with only 1 participant having discordant results (testing negative on the first sample and positive on the second sample). We found no statistically significant difference in relative light units(RLUs) between groups (median of difference, - 0.02 vs -0.05 RLU; p = .93). Conclusions The results of this study suggest that acetic acid at concentrations of 3% to 5% and sequential cervical sampling do not modify the result of HPV testing by Hybrid Capture 2.

Objective: Use of preexposure prophylaxis (PrEP) for HIV raises concerns about sexually transmitted infection (STI) incidence because of decreased condom use among MSM. This study examines whether PrEP is associated with STIs in the 12 months following PrEP prescription relative to the 12 months prior to PrEP and if STI rates are higher among PrEP users relative to individuals receiving postexposure prophylaxis (PEP). Design: Retrospective cohort study including PrEP users with more than 12 months of follow-up before PrEP prescription and individuals receiving PEP from 2010 to 2015 at Clinique l’Actuel (Montréal, Canada). Methods: Incidence of chlamydia, gonorrhoea, syphilis and hepatitis C virus over 12 months was compared before and after PrEP; and for PrEP versus PEP users using Poisson models to generate incidence rate ratios (IRRs) with 95% confidence intervals (CIs) and adjusted IRRs (aIRRs) controlling for frequency of STI-screening visits. Models comparing PrEP and PEP users were further adjusted for age and education. Results: One hundred and nine PrEP and 86 PEP users were included. Increased rates of STIs were observed in the 12 months after PrEP relative to the 12 months prior (IRR: 1.72, CI: 1.22–2.41; aIRR: 1.39, CI 0.98–1.96). PrEP users were also at higher STI risk relative to PEP users (IRR: 2.18, CI: 1.46–3.24; aIRR: 1.76, CI: 1.14–2.71). Conclusion: Increased rates of STIs among individuals after initiation of PrEP may suggest greater risk behaviours during the first year on PrEP. Further studies are needed to measure long-term trends in STI acquisition following PrEP initiation.

Background The global scale-up of Prevention of mother-to-child transmission (PMTCT) services is credited for a 52% worldwide decline in new HIV infections among children between 2001 and 2012. However, the epidemic continues to challenge maternal and paediatric HIV control efforts in Sub Saharan Africa (SSA), with repercussions on other health services beyond those directly addressing HIV and AIDS. This systematised narrative review describes the effects of PMTCT programs on other health care services and the implications for improving health systems in SSA as reported in the existing articles and scientific literature. The following objectives framed our review: 1. To describe the effects of PMTCT on health care services and systems in SSA and assess whether the PMTCT has strengthened or weakened health systems in SSA 2. To describe the integration of PMTCT and its extent within broader programs and health systems. Methods Articles published in English and French over the period 1st January 2007 (the year of publication of WHO/UNICEF guidelines on global scale-up of the PMTCT) to 31 November 2016 on PMTCT programs in SSA were sought through searches of electronic databases (Medline and Google Scholar). Articles describing the impact (positive and negative effects) of PMTCT on other health care services and those describing its integration in health systems in SSA were eligible for inclusion. We assessed 6223 potential papers, reviewed 225, and included 57. Results The majority of selected articles offered arguments for increased health services utilisation, notably of ante-natal care, and some evidence of beneficial synergies between PMTCT programs and other health services especially maternal health care, STI prevention and early childhood immunisation. Positive and negative impact of PMTCT on other health care services and health systems are suggested in thirty-two studies while twenty-five papers recommend more integration and synergies. However, the empirical evidence of impact of PMTCT integration on broader health systems is scarce. Underlying health system challenges such as weak physical and human resource infrastructure and poor working conditions, as well as social and economic barriers to accessing health services, affect both PMTCT and the health services with which PMTCT interacts. Conclusions PMTCT services increase to some extent the availability, accessibility and utilisation of antenatal care and services beyond HIV care. Vertical PMTCT programs work, when well-funded and well-managed, despite poorly functioning health systems. The beneficial synergies between PMTCT and other services are widely suggested, but there is a lack of large-scale evidence of this.

HPV vaccination efficacy has been shown in clinical trials but it is important to verify population level vaccine effectiveness (VE). We aimed to explore VE and herd effect using HPV infection data from a cohort study of Canadian pregnant women. We analyzed the baseline data of the HERITAGE study, which includes pregnant women recruited in Montreal between 2010-2012 and 2015–2016. Cervicovaginal samples self-collected in the first trimester were tested for 36 HPV types. Vaccination status was self-reported. VE and 95% confidence intervals (CI) were estimated by comparing the prevalence of HPV between vaccinated and unvaccinated women. Herd effect was explored by comparing HPV prevalence in unvaccinated women between the 2 recruitment periods. Adjusted ORs (95%CI) were estimated using exact logistic regression. The proportion of vaccinated women with at least one dose of 4vHPV was 7.5%. Although most of them were vaccinated after the onset of sexual activity, a high VE was found for HPV-16/18 (86.1% (95%CI: 15.0–99.7)). For HPV-6/11/16/18 and for HPV-31/33/45, VE was 61.9% (-23.5–92.6) and 57.0% (-47.7–92.0%), respectively. We also observed a non-statistically significant reduction in the prevalence of HPV-6/11/16/18 and HPV-31/33/45 among unvaccinated women recruited during the second recruitment period (adjusted OR: 0.8 (0.4–1.8) and 0.8 (0.3–1.7), respectively).

This study examined the prevalence of three human herpesviruses (HHV), namely HHV-4 (Epstein-Barr virus/EBV), HHV-6b and HHV-7 in leucoreduced blood products obtained from the Sainte-Justine Hospital blood bank. A total of 100 specimens, including 34 red blood cell concentrates, 33 platelet bags and 33 plasma units, were collected and screened by a sensitive PCR assay using virus-specific primers. Positive units were then retested by quantitative PCR. Of the 100 specimens, one platelet unit tested positive for EBV.

IntroductionMulti-morbidity, defined as the co-existence of more than one chronic condition in one person, has been increasing due to comorbid non-communicable and infectious chronic diseases (CNCICDs). Type 2 diabetes (T2D) and gestational diabetes mellitus (GDM) incidences within the CNCICDs conditions are increasing and overwhelming already weak and under-resourced healthcare systems in Africa. There is then an urgent need for the integrated management of CNCICDs. We aim to review the integrated management of T2D and GDM within multi-morbidity conditions in Africa.MethodsStudies that have assessed the integrated management of T2D and GDM within multi-morbidity conditions in Africa will be considered based on the Population, Intervention, Comparator and Outcome method: population (adult diagnosed with T2D and GDM, who also have other diseases, non-communicable diseases (NCDs) and infectious, in public primary and secondary healthcare facilities in Africa); Intervention (integrated management of T2D and GDM, also suffering from other diseases in Africa), Comparator (Unintegrated management of T2D and GDM in Africa) and Outcomes (integrated management of T2D and GDM in Africa). The following databases Cochrane Library, MEDLINE, PubMed and SCOPUS, the WHO International Clinical Trials Registry Platform, among others will be searched. Two reviewers (JCM and MW) will independently screen, select eligible studies and extract data. Discrepancies will be resolved by consensus or by a discussion with the third author (AR). Quality of included studies will be assessed using both the newly developed tool, ‘the Cochrane Collaboration Risk of Bias Tool’ and ‘Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I)”. A narrative synthesis of extracted data and meta-analysis, if necessary will be conducted and then reported according to the preferred reporting items for systematic review and meta-analysis.Ethics consideration and disseminationBy only using the published data, there is no ethics approval required for this study. This systematic review will be included in JCM’s PhD thesis and its findings will also be disseminated through peer-reviewed publication and conference presentation.PROSPERO registration numberCRD42016046630.

Background Parity is well established as a risk factor for cervical cancer. It is not clear, however, how pregnancy influences the natural history of HPV infection and cervical neoplasia. Our objective was to study the risk of HPV infection and cervical squamous intraepithelial lesions (SIL) after pregnancy. Methods We used the Ludwig-McGill cohort study which includes 2462 women recruited in Sao Paulo, Brazil in 1993–97 and followed for up to 10 years. Cellular specimens were collected every 4–6 months for Pap cytology and HPV detection and genotyping by a polymerase chain reaction protocol. Study nurses recorded pregnancy occurrence during follow-up. HPV and Pap results from pregnant women were available before and after, but not during pregnancy. The associations between pregnancy and post-partum HPV infection/SIL were studied using generalized estimating equation models with logistic link. Adjusted odds ratios (OR) were estimated with empirical adjustment for confounding. Results We recorded 122 women with a history of pregnancy during follow-up. Of these, 29 reintegrated the cohort study after delivery. No association between HPV and pregnancy was found. A single SIL case (high grade SIL) occurred post-partum. Likewise, there was no association between pregnancy and risk of low grade SIL or any-grade SIL at the next visit (adjusted OR = 0.84, 95 % CI: 0.46-15.33) after controlling for confounders. Conclusions No associations were found between pregnancy and HPV or LSIL. The single observed case of HSIL post-partum was more than would be expected based on the rate of these abnormalities among non-pregnant women. As this association was found with only one case, caution is required in the interpretation of these results.

Background Children unreached by vaccination are at higher risk of poor health outcomes and India accounts for nearly a quarter of unvaccinated children worldwide. The objective of this study was to investigate compositional and contextual determinants of non-receipt of childhood vaccines in India using multilevel modelling. Methods and Findings We studied characteristics of unvaccinated children using the District Level Health and Facility Survey 3, a nationally representative probability sample containing 65 617 children aged 12–23 months from 34 Indian states and territories. We developed four-level Bayesian binomial regression models to examine the determinants of non-vaccination. The analysis considered two outcomes: completely unvaccinated (CUV) children who had not received any of the eight vaccine doses recommended by India’s Universal Immunization Programme, and children who had not received any dose from routine immunisation services (no RI). The no RI category includes CUV children and those who received only polio doses administered via mass campaigns. Overall, 4.83% (95% CI: 4.62–5.06) of children were CUV while 12.01% (11.68–12.35) had received no RI. Individual compositional factors strongly associated with CUV were: non-receipt of tetanus immunisation for mothers during pregnancy (OR = 3.65 [95% CrI: 3.30–4.02]), poorest household wealth index (OR = 2.44 [1.81–3.22] no maternal schooling (OR = 2.43 [1.41–4.05]) and no paternal schooling (OR = 1.83 [1.30–2.48]). In rural settings, the influence of maternal illiteracy disappeared whereas the role of household wealth index was reinforced. Factors associated with no RI were similar to those for CUV, but effect sizes for individual compositional factors were generally larger. Low maternal education was the strongest risk factor associated with no RI in all models. All multilevel models found significant variability at community, district, and state levels net of compositional factors. Conclusion Non-vaccination in India is strongly related to compositional characteristics and is geographically distinct. Tailored strategies are required to overcome current barriers to immunisation.

The goal of this paper is to analyze the stochastic dynamics of childhood infectious disease time series. We present an univariate time series analysis of pertussis, mumps, measles and rubella based on Box-Jenkins or AutoRegressive Integrated Moving Average (ARIMA) modeling. The method, which enables the dependency structure embedded in time series data to be modeled, has potential research applications in studies of infectious disease dynamics. Canadian chronological series of pertussis, mumps, measles and rubella, before and after mass vaccination, are analyzed to characterize the statistical structure of these diseases. Despite the fact that these infectious diseases are biologically different, it is found that they are all represented by simple models with the same basic statistical structure. Aside from seasonal effects, the number of new cases is given by the incidence in the previous period and by periodically recurrent random factors. It is also shown that mass vaccination does not change this stochastic dependency. We conclude that the Box-Jenkins methodology does identify the collective pattern of the dynamics, but not the specifics of the diseases at the biological individual level.

Background Human papillomavirus (HPV) is the most prevalent genital infection, especially in young women of reproductive age. In vitro and animal model experiments provide compelling evidence of the harmful effect of HPV on pregnancy outcomes, but results from epidemiologic studies are inconclusive. We aim to determine the strength of the relationship between adverse pregnancy outcomes (APO) and HPV infection and assess its consistency across studies, by systematically reviewing the literature. Methods The search strategy has been developed on the basis of the PICOS framework: Population (pregnant women); Exposure (HVP infection confirmed by HPV testing); Comparator (pregnant women without HPV infection); Outcomes (miscarriage, spontaneous preterm birth, low birth weight, preterm premature rupture of membranes, pregnancy-induced hypertensive disorders and intrauterine growth restriction) and Study design (observational studies). We will search three information sources: (1) electronic databases (MEDLINE, EMBASE, and EBM Reviews databases); (2) Grey literature (Google Scholar and Web of Science conference proceedings); and (3) citing and cited articles of included studies. Two reviewers (JN, NZ) will independently and in duplicate screen identified articles, select eligible studies, and extract data. Discrepancies will be resolved by consensus and otherwise by discussion with the other authors (MHM, HT). Quality of included studies will be assessed using the Effective Public Health Practice Project (EPHPP) Quality Assessment Tool for Quantitative Studies. We will narratively synthesize extracted data whether meta-analysis is conducted or not. Meta-analysis of each outcome will be performed, and where appropriate, an average measure of association will be computed. We will use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess and grade the strength of confidence in cumulative estimate. Discussion Comprehensive and high-quality evidence of a negative effect of HPV on pregnancy outcomes might be an additional motivation for HPV vaccination. Absence of such relationship could dispel anxiety and reassure HPV-infected pregnant women and clinicians. Findings of a poor level of confidence will allow identification of current knowledge gaps on HPV-pregnancy outcome relationship that need further research. Systematic review registration PROSPERO CRD42016033425 Electronic supplementary material The online version of this article (doi:10.1186/s13643-017-0443-5) contains supplementary material, which is available to authorized users.

Background Exploring the presence and role of human papillomavirus (HPV) in head and neck cancer (HNC) is a necessary step to evaluate the potential impact of HPV prophylactic vaccines. Objective To assess the prevalence and oncogenic role of HPV in HNC in Senegal. Methods This is a multicenter cross-sectional study. Paraffin-embedded blocks of cases diagnosed with invasive HNC between 2002 and 2010 were collected from 4 pathology laboratories in Senegal. Presence of HPV DNA was determined by PCR and DEIA, and genotyping performed with LiPA25. Tubulin analysis was performed to assess DNA quality. HPV DNA-positive cases were tested for p16INK4a expression. Findings A total of 117 cases were included in the analysis: 71% were men, mean age was 52 years old (SD ±18.3), and 96% of cases were squamous cell carcinoma. Analysis was performed on 41 oral cavity tumors, 64 laryngeal tumors, 5 oropharyngeal tumors and 7 pharyngeal tumors. Only four cases (3.4%; 95% CI = 0.9%-8.5%) harbored HPV DNA. HPV types detected were HPV16, HPV35 and HPV45. However, among HPV-positive cases, none showed p16INK4a overexpression. Conclusion Our findings indicate that HPV DNA prevalence in HNC in Senegal is very low, suggesting that HPV is not a strong risk factor for these cancers. Additional larger studies are needed to confirm these findings and explore other potential risk factors specific to the region.