Association between pregnancy affected by vaginal bleeding and women's mortality: A cohort study.

OBJECTIVE: To investigate the association between vaginal bleeding (VB) in pregnancy and women's mortality, using VB-unaffected pregnancies, terminations and miscarriages as comparators. DESIGN: Observational cohort study. SETTING: Nationwide registries of Denmark linked at an individual level. POPULATION OR SAMPLE: 1 354 181 women and their 3 162 317 pregnancies (1979-2017), including 70 835 VB-affected pregnancies and comparators: 2 236 359 VB-unaffected pregnancies ending in childbirth; 589 697 terminations; and 265 426 miscarriages. METHODS: We followed pregnancies until the earliest date of woman's death, emigration or end of data. MAIN OUTCOME MEASURES: All-cause and cause-specific mortality rates per 10 000 person-years (PY) and hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted using Cox proportional hazards regression for age, calendar year, pre-existing chronic conditions and socio-economic factors. RESULTS: There were 2320 deaths from any cause among women following VB-affected pregnancy (mortality rate 15.2, 95% CI 14.6-15.9 per 10 000 PY); 55 030 deaths following VB-unaffected pregnancy (mortality rate 12.7, 95% CI 12.6-12.8); 27 500 deaths following a termination (mortality rate 21.9, 95% CI 21.6-22.1), and 10 865 deaths following a miscarriage (mortality rate 19.2, 95% CI 18.8-19.6). For comparison of VB-affected versus VB-unaffected pregnancies, associations with all-cause (HR 1.14, 95% CI 1.09-1.19), natural causes (HR 1.15, 95% CI 1.09-1.22) and non-natural causes (HR 1.27, 95% CI 1.08-1.48) mortality were attenuated in a sensitivity analysis of pregnancies recorded in 1994-2017 (HR 1.00, 95% CI 0.90-1.12, HR 0.98, 95% CI 0.85-1.14 and HR 1.04, 95% CI 0.72-1.51, respectively). Contrasts with remaining comparators did not suggest increased risks of all-cause, natural or non-natural mortality causes. CONCLUSION: We found no evidence of an increased risk of women's mortality following VB-affected versus VB-unaffected pregnancy, termination or miscarriage.

Risk for adverse maternal outcomes among women with chronic hypertension.

OBJECTIVE: To determine whether longitudinal health data accounts for end-organ injury or death in the setting of chronic hypertension. DESIGN: Cohort of 64 799 deliveries to 61 854 women. SETTING: US claims data for the preiod 2008-2019. POPULATION: Women with a delivery hospitalisation and chronic hypertension. METHODS: Risk for a composite of acute end-organ injury or death during the delivery hospitalisation and 30 days postpartum was analysed. Adjusted logistic regression models were derived with discrimination for each model estimated by the C-statistic. Poisson regression was used to estimate adjusted risk ratios. Starting with models using data from pregnancy, further adjustment was performed accounting for healthcare use in the year prior to pregnancy, including hospitalisations, emergency department encounters, prescription medications and pre-pregnancy diagnoses. MAIN OUTCOME MEASURES: Acute end-organ injury or death. RESULTS: The composite outcome occurred among 5.7% of 64 799 deliveries. For patients with commercial insurance, filling non-hypertensive medications from ≥11 different classes, compared with none (adjusted risk ratio, aRR 4.07, 95% CI 2.86-5.79), three or more hospitalisations before pregnancy, compared with none (aRR 4.75, 95% CI 3.46-6.52), and chronic kidney disease diagnosed in the year before pregnancy (aRR 2.35, 95% CI 1.88, 2.94) were associated with increased risk. For pregnancies covered by commercial insurance, the C-statistic increased from 0.615 (95% CI 0.599-0.630) in the model with pregnancy data only to 0.796 (95% CI 0.783-0.808) for the model additionally including healthcare use in the year before pregnancy. Findings with Medicaid were similar. CONCLUSIONS: Prepregnancy care use predicted adverse maternal outcomes. These data may be important in risk stratification.

Geographic variation in the rate and route of hysterectomy for benign disease in the USA: A retrospective cross-sectional study.

OBJECTIVES: To describe population rate of hysterectomy for benign disease in the USA, including geographic variation across states and Hospital Service Areas (HSAs; areas defined by common patient flows to healthcare facilities). DESIGN: Cross-sectional study. SETTING: Four US states including 322 HSAs. POPULATION: A total of 316 052 cases of hysterectomy from 2012 to 2016. METHODS: We compiled annual hysterectomy cases, merged female populations, and adjusted for reported rates of previous hysterectomy. We assessed small-area variation and created multi-level Poisson regression models. MAIN OUTCOME MEASURES: Prior-hysterectomy-adjusted population rates of hysterectomy for benign disease. RESULTS: The annual population rate of hysterectomy for benign disease was 49 per 10 000 hysterectomy-eligible residents, declining slightly over time, mostly among reproductive-age populations. Rates peaked among residents ages 40-49 years, and declined with increasing age, apart from an increase with universal coverage at age 65 years. We found large differences in age-standardised population rates of hysterectomy across states (range 42.2-69.0), and HSAs (range: overall 12.9-106.3; 25th-75th percentile 44.0-64.9). Among the non-elderly population, those with government-sponsored insurance had greater variation than those with private insurance (coefficient of variation 0.61 versus 0.32). Proportions of minimally invasive procedures were similar across states (71.0-74.8%) but varied greatly across HSAs (27-96%). In regression models, HSA population characteristics explained 31.8% of observed variation in annual rates. Higher local proportions of government-sponsored insurance and non-White race were associated with lower population rates. CONCLUSIONS: We found substantial variation in rate and route of hysterectomy for benign disease in the USA. Local population characteristics explained less than one-third of observed variation.

Cross-sectional assessment of determinants of STIs among men who have sex with men and transgender women in Kigali, Rwanda.

BACKGROUND: STIs among men who have sex with men (MSM) and transgender women (TGW) continue to increase. In Rwanda, STI management relies on syndromic management with limited empirical data characterising the burden of specific STIs among MSM/TGW. This study evaluated the prevalence of syphilis, Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) and associated factors among MSM/TGW in Kigali. METHODS: From March to August 2018, 737 MSM/TGW >18 years were enrolled using respondent-driven sampling (RDS). Structured interviews and HIV/STI screening were conducted. Syphilis was screened with rapid plasma reagin confirmed by Treponema pallidum hemagglutination assay. CT/NG were tested by Cepheid GeneXpert. RDS-adjusted multivariable Poisson regression models with robust variance estimation were used to evaluate factors associated with any STI, and determinants of urethral and rectal STIs separately. RESULTS: Prevalence of any STI was 20% (RDS adjusted: 16.7% (95% CI: 13.2% to 20.2%)). Syphilis was 5.7% (RDS adjusted: 6.8% (95% CI: 4.3% to 9.4%)). CT was 9.1% (RDS adjusted: 6.1% (95% CI: 3.9% to 8.4%)) and NG was 8.8% (RDS adjusted: 7.1% (95% CI: 4.9% to 9.2%)). STIs were more common among older MSM and those with HIV (p<0.05). Of CT infections, 67% were urethral, 27% rectal and 6% were dual site. For NG infections, 52% were rectal, 29% urethral and 19% were dual site. Overall, 25.8% (23 of 89) of those with confirmed STI and returned for their results were symptomatic at time of testing.STI symptoms in the previous year (adjusted prevalence ratio (aPR): 1.94 (95% CI: 1.26 to 2.98)) were positively associated with any STI. Being circumcised was negatively associated with any STI (aPR: 0.47 (95% CI: 0.31 to 0.73)). HIV was positively associated with rectal STIs (aPR: 3.50 (95% CI: 1.09 to 11.21)) but negatively associated with urethral STIs. CONCLUSION: MSM/TGW, especially those living with HIV, are at high risk of STIs in Rwanda with the vast majority being asymptomatic. These data suggest the potential utility of active STI surveillance strategies using highly sensitive laboratory methods among those at high risk given the anatomical distribution and limited symptomatology of STIs observed among Rwandan MSM/TGW.

Confirmatory testing of Neisseria gonorrhoeae in a sexual health clinic: implications for epidemiology and treatment policy.

OBJECTIVES: European guidelines advise the use of dual nucleic acid amplification tests (NAAT) in order to minimise the inappropriate diagnosis of Neisseria gonorrhoeae (Ng) in urogenital samples from low prevalence areas and in extragenital specimens. In this cross-sectional study, we investigated the effect of confirmatory testing and confirmation policy on the Ng-positivity in a population visiting the sexual health clinic in Rotterdam, the Netherlands. METHODS: Apart from urogenital testing, extragenital (oropharyngeal/anorectal) testing was performed for men who have sex with men (MSM) and according to sexual exposure for women and heterosexual men. Ng detection using NAAT was performed using BD Viper and for confirmatory testing BD MAX. Sexual transmitted infection consultation data were merged with diagnostic data from August 2015 through May 2016. RESULTS: In women (n=4175), oral testing was performed in 84% and 22% were tested anally. In MSM (n=1828), these percentages were 97% and 96%, respectively. Heterosexual men (n=3089) were tested urogenitally. After confirmatory testing, oropharyngeal positivity rates decreased from 7.3% (95% CI 6.5 to 8.2) to 1.5% (95% CI 1.1 to 1.8) in women and from 13.9% (95% CI 12.3 to 15.5) to 5.4% (95% CI 4.3 to 6.4) in MSM. Anorectal positivity rates decreased from 2.6% (95% CI 1.6 to 3.7) to 1.8% (95% CI 0.9 to 2.6) in women and from 9.3% (95% CI 7.9 to 10.7) to 7.2% (95% CI 6.0 to 8.5) in MSM. Urogenital Ng-positivity rate ranged between 3.0% and 4.4% and after confirmation between 2.3% and 3.9%. When confirming oropharyngeal samples, Ng-positivity was 3.8% in women, 3.0% in heterosexual men and 12.5% in MSM. Additional confirmation of urogenital and anorectal samples led to 3.0% Ng positivity in women, 2.7% in heterosexual men and 11.4% in MSM. CONCLUSIONS: Confirmation of urogenital and anorectal samples reduced the Ng-positivity rates, especially for women. However, as there is no gold standard for the confirmation of Ng infection, the dilemma within public health settings is to choose between two evils: missing diagnoses or overtreatment. In view of the large decrease in oropharyngeal positivity, confirmation Ng-positivity in oropharyngeal samples remains essential to avoid unnecessary treatment.

Time to resolution of genital symptoms for uncomplicated gonorrhoea: a prospective cohort study.

OBJECTIVES: To determine the time to resolution of symptoms (TTR) following treatment of uncomplicated gonorrhoea and to identify factors associated with TTR in a cohort of sexual health clinic attendees. METHODS: Participants were recruited from 14 clinics across England into the 'Gentamicin for the Treatment of Gonorrhoea (GToG)' trial between October 2014 and November 2016. We analysed demographic, behavioural and clinical data in a subset of the GToG study cohort presenting with genital discharge and/or dysuria, who subsequently experienced microbiological clearance of Neisseria gonorrhoeae 2 weeks after treatment. Testing for gonorrhoea was performed using a nucleic acid amplification test. The results were expressed as median TTR (IQR) and HRs with 95% CIs for resolution of symptoms. RESULTS: 216 participants (89% male) with a mean age of 32 years reported genital discharge (204/216 (94%)) or dysuria (173/216 (80%)) at their baseline visit. Symptom resolution occurred in 202/216 (94%) at the 2-week follow-up appointment. The median TTR was 2 days (IQR 1-3 days). 50/216 (23%) patients presented with gonorrhoea-chlamydia coinfection at their baseline attendance and in this group symptom resolution was slower (3 days for gonorrhoea-chlamydia coinfection compared with 2 days for gonorrhoea only, HR 0.68 (95% CI 0.48 to 0.95)). TTR was also longer in women (4 days for females compared with 2 days for males, HR 0.47 (95% CI 0.29 to 0.77)). CONCLUSIONS: The time to resolution of genital symptoms following effective treatment of gonorrhoea is variable, but 90% of patients report symptom resolution within 1 week. Concurrent chlamydia infection and being female were associated with prolonged TTR.

Opposing associations of depression with sexual behaviour: implications for epidemiological investigation among gay, bisexual and other men who have sex with men.

OBJECTIVE: The aim of this report is to investigate the nature of the relationship between depression and condomless sex (CLS) among gay, bisexual and other men who have sex with men (GBMSM). METHODS: Data are from the Antiretrovirals, Sexual Transmission Risk and Attitude (ASTRA) study of people living with HIV and attending one of eight HIV outpatient clinics in England (2011-2012) and the Attitudes to and Understanding of Risk of Acquisition of HIV (AURAH) study of HIV-negative/unknown status individuals attending one of 20 genitourinary medicine clinics in England (2013-2014). This analysis included GBMSM only. For each study, the prevalence of depressive symptoms (Patient Health Questionnaire-9 score ≥10) was presented according to three categories of sex in the past 3 months (considering anal/vaginal sex with men/women and anal sex with men in separate definitions): (1) no sex, (2) condom-protected sex only and (3) CLS. Multinomial logistic regression with 'condom-protected sex only' as the reference group was used to adjust for age and (for ASTRA participants) time since HIV diagnosis. RESULTS: There were opposing associations of depression with recent sexual behaviour: the prevalence of depression was higher among those who reported no sex and those who reported CLS, compared with those who reported condom-protected sex only. Among the 2170 HIV-positive GBMSM in ASTRA, considering anal/vaginal sex with men/women, the prevalence of depressive symptoms was 32%, 20% and 28%, respectively, among men reporting no sex (n=783), condom-protected sex only (n=551) and CLS (n=836) (global p<0.001). Among the 1477 HIV-negative GBMSM in AURAH, the prevalence of depressive symptoms was 12%, 8% and 13%, respectively, for no sex (n=137), condom-protected sex only (n=487) and CLS (n=853) (global p=0.017). Patterns were similar after adjustment and when only considering anal sex between men. CONCLUSIONS: Depression may be linked both to lack of sexual activity and to sexual risk taking. When investigating associations between depression and CLS, it is important to separate out individuals reporting condom-protected sex only from those reporting no sex.

Prevalence and factors associated with HIV epidemic among female sex workers in Pakistan: results of the fifth round of integrated biological and behavioural surveillance.

OBJECTIVES: We examined data collected as part of the fifth round of integrated biological and behavioural surveillance to determine the prevalence and factors associated with HIV infection among female sex workers (FSWs) in Pakistan. METHODS: FSWs were defined as 'all females, age 13 years and above, who receive money or goods in exchange for sexual services, regardless of the site of operation'. Data were collected between October 2016 and January 2017 in 18 cities using multistage sampling techniques to randomly select FSWs from spots facilitated by peers. Behavioural data were collected by interviewers using structured questionnaires, which was followed by obtaining finger prick blood samples tested for HIV using two rapid tests. Multivariate logistic regression analysis was done to assess independent associations of potential correlates using HIV status as dependent variable. RESULTS: We invited 5728 FSWs to participate, of which 68 refused to participate (refusal rate=1.2%). Of the 5660 FSWs who participated, 121 were HIV seropositive (weighted HIV prevalence 2.3%; 95% CI 1.9% to 2.7%) mostly concentrated within cities in Sindh. Multivariate analysis showed being uneducated/illiterate (adjusted OR (aOR) 2.1; 95% CI 1.4 to 3.4), directly dealing with clients without a pimp (aOR 1.8; 95% CI 1.1 to 2.8), non-use of condom with clients (aOR 1.8; 95% CI 1.1 to 2.8), having sexual contact with people who inject drugs (PWID) (aOR 2.2; 95% CI 1.3 to 3.7) and non-participation in HIV programmes (aOR 1.7; 95% CI 1.0 to 3.1) as factors independently associated with HIV seropositivity. CONCLUSIONS: We found a weighted national HIV prevalence of 2.3% and identified factors independently associated with HIV in FSWs. The country needs to scale up HIV prevention programmes to improve coverage, prioritising FSWs who are illiterate, work independently and have PWID as sex partners. Emphasis should be laid on strategies to improve condom use with both regular and non-regular partners.

Implementation of a standardised and quality-assured enhanced gonococcal antimicrobial surveillance programme in accordance with WHO protocols in Kampala, Uganda.

OBJECTIVES: The emergence of multidrug-resistant Neisseria gonorrhoeae (NG) is a major global health threat necessitating response and control measures. NG antimicrobial resistance (AMR) surveillance data from sub-Saharan countries is exceedingly limited. This paper aims to describe the establishment, design and implementation of a standardised and quality-assured gonococcal surveillance programme and to describe the susceptibility patterns of the cultured gonococcal isolates in Kampala, Uganda. METHODS: From March 2018 to September 2019, using the WHO Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP) protocol, consecutive males with urethral discharge syndrome were recruited from 10 surveillance sites in Kampala City, Uganda, in collaboration with the Ministry of Health. Males completed a questionnaire and provided a urethral swab specimen. Culture, identification and antimicrobial susceptibility testing (Etest) were performed. RESULTS: Of the 1013 males recruited, 73.1% (740/1013) had a positive Gram stain and 51.1% (n=518) were culture-positive for NG. Using Etest (458 isolates), the resistance to ciprofloxacin was 99.6%. Most isolates were susceptible to azithromycin, cefoxitin and gentamicin, that is, 99.8%, 98.5% and 92.4%, respectively, and all isolates were susceptible to ceftriaxone and cefixime. CONCLUSIONS: We established a standardised, quality-assured WHO EGASP. Using Etest, 458 isolates were characterised, with associated epidemiological surveillance data, in 1.5 years, which by far exceed the minimum 100 isolates per year and country requested in the WHO Global GASP, to detect AMR levels with confidence. These isolates with the epidemiological data can be used to develop population level interventions.

Global epidemiology of Neisseria gonorrhoeae in infertile populations: systematic review, meta-analysis and metaregression.

OBJECTIVE: To provide an in-depth systematic assessment of the global epidemiology of gonorrhoea infection in infertile populations. METHODS: A systematic literature review was conducted up to 29 April 2019 on international databases and WHO regional databases, and reported following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. All prevalence measures of gonorrhoea infection among infertile populations, based on primary data, qualified for inclusion. Infertile populations were broadly defined to encompass women/men undergoing infertility evaluation or treatment (infertility clinic attendees and partners). Pooled mean prevalence by relevant strata was estimated using random-effects meta-analysis. Associations with prevalence and sources of heterogeneity were explored using metaregression. Risk of bias was assessed using four quality domains. FINDINGS: A total of 147 gonorrhoea prevalence studies were identified from 56 countries. The pooled mean prevalence of current gonorrhoea infection was estimated globally at 2.2% (95% CI 1.3% to 3.2%), with the highest prevalence in Africa at 5.0% (95% CI 1.9% to 9.3%). The mean prevalence was higher for populations with tubal factor infertility (3.6%, 95% CI 0.9%-7.7%) and mixed cause and unexplained infertility (3.6%, 95% CI 0.0% to 11.6%) compared with other diagnoses, such as ovarian and non-tubal infertility (0.1%, 95% CI 0.0% to 0.8%), and for secondary (2.5%, 95% CI 0.2% to 6.5%) compared with primary (0.5%, 95% CI 0.0% to 1.7%) infertility. Metaregression identified evidence of variations in prevalence by region and by infertility diagnosis, higher prevalence in women than men and a small-study effect. There was a trend of declining prevalence by about 3% per year over the last four decades (OR=0.97, 95% CI 0.95 to 0.99). CONCLUSIONS: Gonorrhoea prevalence in infertile populations is several folds higher than that in the general population, with even higher prevalence in women with tubal factor infertility and in individuals with secondary infertility. These findings support the potential role of gonorrhoea in infertility and suggest that some infertility is possibly preventable by controlling gonorrhoea transmission. PROSPERO REGISTRATION NUMBER: CRD42018102934.

Association between rectal douching and HIV acquisition: the mediating role of condom use and rectal bleeding in a national online sample of Chinese men who have sex with men.

OBJECTIVES: Previous studies have demonstrated that rectal douching (RD) is associated with HIV acquisition among men who have sex with men (MSM). However, the precise mechanism underlying the association between RD and HIV remains unclear. METHODS: We recruited participants over WeChat from October 2017 to October 2018. Respondents received mailed HIV self-testing kits, uploaded images of HIV self-test results and completed an online electronic questionnaire simultaneously. The questionnaire assessed sociodemographic characteristics, RD practices and sexual risk behaviours. HIV status was measured as the result of the HIV self-testing. The Baron and Kenny statistical method was used to assess the association between RD and HIV, controlling for condomless anal intercourse (CAI) and rectal bleeding. RESULTS: Of 1365 participants, 39.93% (545/1365) reported RD in the past 6 months, 60.07% had multiple male sexual partners and 43.08% had CAI in the past 6 months. The prevalence of HIV, based on self-testing, was 3.37% (46/1365). Multivariable logistic analysis showed RD was significantly associated with bottom sexual role (adjusted OR (aOR) 14.0; 95% CI 9.8 to 20.2), having multiple male sexual partners (aOR 1.8; 95% CI 1.4 to 2.2), CAI (aOR 1.3; 95% CI 1.0 to 1.6), rectal bleeding (aOR 2.0; 95% CI 1.6 to 2.6) and HIV infection (aOR 1.9; 95% CI 1.0 to 3.4). Baron and Kenny analysis found both CAI (aOR 2.2; 95% CI 1.2 to 4.1) and rectal bleeding (aOR 1.9; 95% CI 1.0 to 3.4) play a mediating role in the association between RD and HIV. CONCLUSIONS: Our study results confirmed the relationship between RD and HIV, and found CAI and rectal bleeding mediated HIV infection in Chinese MSM who douched. Strategies should be encouraged to strengthen health education and reduce high-risk sexual behaviour in order to reduce the risk of HIV in MSM who use enemas. Rectal microbicides may represent an efficient means of providing HIV prophylaxis among MSM.

Prevalence of and risk factors for curable sexually transmitted infections on Bubaque Island, Guinea Bissau.

OBJECTIVES: Complications from sexually transmitted infections (STIs) can result in severe morbidity and mortality. To date, no STI population studies have been conducted on the Bijagos Islands, Guinea Bissau. Our objective was to estimate the prevalence of and identify risk factors for Chlamydia trachomatis (Ct), Neisseria gonorrhoea (Ng), Mycoplasma genitalium (Mg), Trichomonas vaginalis (Tv) and Treponema pallidum (Tp) on Bubaque, the most populated island. METHODS: A cross-sectional survey was conducted on the island of Bubaque among people aged 16-49 years. Participants were asked to answer a questionnaire on STI risk factors, to provide urine samples (men and women) and vaginal swabs (women) for PCR testing for Ct, Ng, Mg and Tv, and to provide dry blood spots for Tp particle agglutination assays. Data were analysed to estimate the prevalence of STIs and logistic regression was used to identify risk factors. RESULTS: In total, 14.9% of participants were found to have a curable STI, with the highest prevalence being observed for Tv (5.9%) followed by Ct (3.8%), Ng (3.8%), Mg (1.9%) and Tp (0.8%). Significant risk factors for having any STI included being female, younger age and concurrent partnership. Having had a previous STI that was optimally treated was a protective factor. CONCLUSIONS: This study demonstrates that there is a considerable burden of STI on the Bijagos Islands, stressing the need for diagnostic testing to facilitate early detection and treatment of these pathogens to stop ongoing transmission. Moreover, these results indicate the need to conduct further research into the STI burden on the Bijagos Islands to help inform and develop a national STI control strategy.

Does being on HIV antiretroviral therapy increase the risk of syphilis? An analysis of a large national cohort of MSM living with HIV in England 2009-2016.

OBJECTIVE: A resurgence in bacterial STIs, notably syphilis, among gay, bisexual and other men who have sex with men (MSM) has been detected in England. A Canadian modelling study postulated that antiretroviral therapy (ART) may increase susceptibility to syphilis. We assess the association between ART and syphilis incidence in a comprehensive national cohort of MSM living with HIV in England. METHODS: National surveillance data were used to create a cohort of MSM attending for both HIV and STI care in England between 2009 and 2016. Survival analysis was used to calculate the incidence of infectious syphilis during periods on and off ART. Multivariable Poisson regression was used to assess the association between ART use and syphilis, after adjustment for potential confounders, including, as a proxy measure for high-risk behaviour, being diagnosed with >1 other STI prior to a syphilis diagnosis. RESULTS: 19 428 HIV diagnosed MSM contributed 112 960 person-years of follow-up from 2009 to 2016. The overall rate of syphilis was 78.0 cases per 1000 person-years follow-up. Syphilis rates were higher among men receiving ART (36.8) compared with those who did not (28.4) (absolute rate difference 4.7 cases per 1000 person-years). Multivariable analysis showed no statistical association between receiving ART and syphilis. Increased risk of syphilis was found in MSM aged 25-34 (HR 1.89, 95% CI 1.43 to 2.51) and in those diagnosed with two other STIs (HR 5.83, 95% CI 5.37 to 6.32). CONCLUSION: While we observed a small increase in the rate of syphilis among those on ART, when adjusting for potential confounding factors, including a proxy measure for high-risk behaviour, there was no evidence of an increased risk of syphilis in MSM receiving ART. High-risk sexual behaviour markers were the main risk factors for syphilis, and our results highlight the need for STI prevention interventions in MSM living with HIV to target these particularly high-risk sexual networks.

Trends in hepatitis C virus seroprevalence and associated risk factors among men who have sex with men in Montréal: results from three cross-sectional studies (2005, 2009, 2018).

OBJECTIVES: To eliminate the hepatitis C virus (HCV) by 2030, Canada must adopt a microelimination approach targeting priority populations, including gay, bisexual and other men who have sex with men (MSM). Accurately describing HCV prevalence and risk factors locally is essential to design appropriate prevention and treatment interventions. We aimed to estimate temporal trends in HCV seroprevalence between 2005 and 2018 among Montréal MSM, and to identify socioeconomic, behavioural and biological factors associated with HCV exposure among this population. METHODS: We used data from three cross-sectional surveys conducted among Montréal MSM in 2005 (n=1795), 2009 (n=1258) and 2018 (n=1086). To ensure comparability of seroprevalence estimates across time, we standardised the 2005 and 2009 time-location samples to the 2018 respondent-driven sample. Time trends overall and stratified by HIV status, history of injection drug use (IDU) and age were examined. Modified Poisson regression analyses with generalised estimating equations were used to identify factors associated with HCV seropositivity pooling all surveys. RESULTS: Standardised HCV seroprevalence among all MSM remained stable from 7% (95% CI 3% to 10%) in 2005, to 8% (95% CI 1% to 9%) in 2009 and 8% (95% CI 4% to 11%) in 2018. This apparent stability hides diverging temporal trends in seroprevalence between age groups, with a decrease among MSM <30 years old and an increase among MSM aged ≥45 years old. Lifetime IDU was the strongest predictor of HCV seropositivity, and no association was found between HCV seroprevalence and sexual risk factors studied (condomless anal sex with men of serodiscordant/unknown HIV status, number of sexual partners, group sex). CONCLUSIONS: HCV seroprevalence remained stable among Montréal MSM between 2005 and 2018. Unlike other settings where HCV infection was strongly associated with sexual risk factors among MSM, IDU was the pre-eminent risk factor for HCV seropositivity. Understanding the intersection of IDU contexts, practices and populations is essential to prevent HCV transmission among MSM.

Maternal risk of hypertension 7-15 years after pregnancy: clues from the placenta.

OBJECTIVE: To assess whether pre-eclampsia (PE)-related placental/extraplacental membrane findings are linked to moderately elevated blood pressure (BP) in pregnancy and later-life hypertension. DESIGN: Prospective cohort. SETTING: 52 prenatal clinics, 5 Michigan communities. SAMPLE: The POUCH Study recruited women at 16-27 weeks' gestation (1998-2004) and studied a sub-cohort in depth. This sample (n = 490) includes sub-cohort women with detailed placental assessments and cardiovascular health evaluations 7-15 years later in the POUCHmoms follow-up study. METHODS: PE-related placental/extraplacental membrane findings (i.e. mural hyperplasia, unaltered/abnormal vessels or atherosis in decidua; infarcts) were evaluated in relation to pregnancy BP and odds of Stage 2 hypertension at follow up using weighted polytomous regression. Follow-up hypertension odds also were compared in three pregnancy BP groups: normotensives (referent) and moderately elevated BP with or without PE-related placental/extraplacental membrane findings. MAIN OUTCOME MEASURES: Stage 2 hypertension (SBP ≥140 mmHg and/or DBP ≥90 mmHg, or using antihypertensive medications) at follow up. RESULTS: After excluding women with pregnancy hypertension (i.e. chronic, PE, gestational), mural hyperplasia and unaltered/abnormal decidual vessels were each associated with Stage 2 hypertension at follow up: adjusted odds ratio (aOR) = 2.7, 95% CI 1.1-6.6, and aOR = 1.7 (95% CI 0.8-3.4), respectively. Women with moderately elevated BP in pregnancy and evidence of mural hyperplasia or unaltered/abnormal decidual vessels had greater odds of Stage 2 hypertension at follow up: aOR = 4.5 (95% CI 1.6-12.5 and aOR = 2.6, 95% CI 1.1-5.9, respectively. CONCLUSIONS: PE-related placental/extraplacental membrane findings help risk-stratify women with moderately elevated BP in pregnancy for later development of hypertension. TWEETABLE ABSTRACT: Placental findings associated with mother's risk of later-life hypertension.

Factors associated with time to presentation for individuals with symptomatic uncomplicated genital gonorrhoea: a cross sectional cohort study of GToG trial participants.

OBJECTIVES: To determine the variation in the time from onset of symptoms to clinical presentation (time to presentation [TTP]) in a cohort of sexual health attendees with symptomatic uncomplicated genital gonorrhoea and to identify factors associated with TTP. METHODS: Participants were recruited from 14 clinics across England into the 'Gentamicin for the Treatment of Gonorrhoea (GToG)' trial between October 2014 and November 2016. Multivariable analysis was performed using prospectively collected demographic, behavioural and clinical data in a subset of the GToG study cohort presenting with genital discharge and/or dysuria who tested positive for Neisseria gonorrhoeae using a nucleic acid amplification test. The results were expressed as geometric mean ratios (GMR) with 95% CI for time to presentation after onset of symptoms. RESULTS: 316 participants (269 men and 47 women) with a median age of 27.6 years (IQR 23.0-34.8) were included. 194 (61%) were Caucasian, 29 (9%) Black African, 27 (9%) Asian and 66 (21%) of other ethnicities. Median TTP was 3 days for men (IQR 2-7) and 14 days for women (IQR 7-21). Participants reported genital discharge (297/316 [94%]), dysuria (251/316 [79%]), both genital discharge and dysuria (232/316 [73%]) and other concurrent symptoms 76/316 (24%) (e.g., rectal bleeding or genital itching). 45/316 (14%) participants reported sexual contact while symptomatic, of whom TTP was more than 7 days in 32/45 (71%). A longer TTP was associated with gender (female cf. male, GMR 2.34 [1.67 to 3.26]), no prior history of gonorrhoea (GMR 1.46 [1.15 to 1.86]), 'regular' or 'ex-regular' sexual relationship (regular cf. one off GMR 1.35 [1.05 to 1.72]); ex-regular cf. one off GMR 1.88 [1.12 to 3.14]), and being heterosexual (GMR 1.69 [1.31 to 2.19]). CONCLUSION: Specific demographic and behavioural factors are associated with a longer TTP in individuals with symptomatic genital gonorrhoea. Detailed knowledge of these factors can be used to prioritise and optimise gonorrhoea management and prevention.

Novel bacterial vaginosis-associated organisms mediate the relationship between vaginal douching and pelvic inflammatory disease.

OBJECTIVES: We sought to determine whether the relationship between a history of vaginal douching and pelvic inflammatory disease (PID) is mediated by endometrial infection with one or more novel bacterial vaginosis (BV)-associated organisms among Atopobium vaginae, the BV-associated bacterium 1 (BVAB1), neathia (Leptotrichia) amnionii and Sneathia sanguinegens. METHODS: We first conducted log-binomial regression analyses to identify risk factors for endometrial infection in 535 adolescent and adult women with clinically suspected PID in the PID Evaluation and Clinical Health (PEACH) study. We then examined whether endometrial infection by the BV-associated organisms mediated the association between a history of vaginal douching and histologically confirmed PID using inverse probability weighted marginal structural models. RESULTS: Vaginal douching was significantly associated with endometrial infection with one or more of the targeted BV-associated organisms (relative risk (RR) 1.21, 95% CI: 1.08 to 1.35). The total effect estimate suggested that vaginal douching increased the risk of endometritis by 24% (RR 1.24, 95% CI: 1.03 to 1.49). The controlled direct effect of this association was attenuated with endometrial infection by one or more BV-associated organisms (adjusted RR (aRR) 1.00, 95% CI: 0.57 to 1.74) and endometrial infection by all four BV-associated organisms (aRR 0.95, 95% CI: 0.53 to 1.70) as intermediate variables. CONCLUSIONS: Endometrial infection with one or more of the novel BV-associated organisms partially mediated the relationship between vaginal douching and histologically confirmed endometritis in the PEACH study. Frequent vaginal douching may confer risk for endometritis through increasing the risk of endometrial infection by novel-BV-associated organisms. Other potential pathways should be explored.

Increases in pharyngeal Neisseria gonorrhoeae positivity in men who have sex with men, 2011-2015: observational study.

OBJECTIVES: Pharyngeal gonorrhoea disproportionately affects men who have sex with men (MSM). We explored temporal trends in pharyngeal gonorrhoea positivity among MSM compared with anorectal and urogenital positivity. METHODS: Data (2011-2015) were extracted from 41 publicly funded sexual health clinics participating in a national surveillance network. Positivity was defined as the proportion of first-visit testing occasions where gonorrhoea was detected. Logistic regression explored trends in positivity and correlates of positive pharyngeal tests. RESULTS: From 2011 to 2015, 24 792 MSM tested (16 710 pharyngeal, 19 810 urogenital and 15 974 anorectal first-visit tests). Pharyngeal positivity increased by 183% from 139/3509 (4.0%) in 2011 to 397/3509 (11.3%) in 2015, p-trend <0.001; urogenital positivity by 39% from 257/4615 (5.6%) to 295/3783 (7.8%), p-trend=0.006; and anorectal positivity by 87% from 160/3469 (4.6%) to 286/3334 (8.6%), p-trend <0.001. The annual temporal increase in positivity was greater in the pharynx (OR 1.33; 95% CI 1.27 to 1.38) than at urogenital (OR 1.06; 95% CI 1.02 to 1.10) and anorectal (OR 1.16; 95% CI 1.11 to 1.21) sites. Factors independently associated with pharyngeal gonorrhoea were: younger age (p<0.001), higher numbers of recent sexual partners (p-trend=0.004), contact with a person with a diagnosed STI (p<0.001), injecting drug use (p<0.001), anogenital symptoms (p<0.001) and HIV-positive status (p=0.050). CONCLUSION: Temporal increases in gonorrhoea positivity occurred at all anatomical sites, with the greatest increase in the pharynx. Risk factors could be used to help to develop testing and prevention strategies among MSM at highest risk. Strengthening sexual health service delivery, testing and surveillance remain priorities for pharyngeal gonorrhoea control.

Ethnic variations in sexual partnerships and mixing, and their association with STI diagnosis: findings from a cross-sectional biobehavioural survey of attendees of sexual health clinics across England.

OBJECTIVES: Ethnic differences in partnership types and sexual mixing patterns may contribute to elevated STI diagnosis rates among England's Black Caribbean (BC) population. We examined the differences between BC and White British/Irish (WBI) sexual health clinic (SHC) attendees' reported partnerships and sexual mixing, and whether these differences could explain ethnic inequalities in STI, focusing on attendees reporting only opposite-sex partners (past year). METHODS: We surveyed attendees at 16 SHCs across England (May to September 2016), and linked their survey responses to routinely collected data on diagnoses of bacterial STI or trichomoniasis ±6 weeks of clinic attendance ('acute STI'). Behaviourally-heterosexual BC and WBI attendees (n=1790) reported details about their ≤3 most recent opposite-sex partners (past 3 months, n=2503). We compared BC and WBI attendees' reported partnerships and mixing, in gender-stratified analyses, and used multivariable logistic regression to examine whether they independently explained differences in acute STI. RESULTS: We observed differences by ethnic group. BC women's partnerships were more likely than WBI women's partnerships to involve age-mixing (≥5 years age difference; 31.6% vs 25.5% partnerships, p=0.013); BC men's partnerships were more often 'uncommitted regular' (35.4% vs 20.7%) and less often casual (38.5% vs 53.1%) than WBI men's partnerships (p<0.001). Acute STI was higher among BC women than WBI women (OR: 2.29, 95% CI 1.24 to 4.21), with no difference among men. This difference was unaffected by partnerships and mixing: BC women compared with WBI women adjusted OR: 2.31 (95% CI 1.30 to 4.09) after adjusting for age and partner numbers; 2.15 (95% CI 1.07 to 4.31) after additionally adjusting for age-mixing, ethnic-mixing and recent partnership type(s). CONCLUSION: We found that differences in sexual partnerships and mixing do not appear to explain elevated risk of acute STI diagnosis among behaviourally-heterosexual BC women SHC attendees, but this may reflect the measures used. Better characterisation of 'high transmission networks' is needed, to improve our understanding of influences beyond the individual level, as part of endeavours to reduce population-level STI transmission.

Risk and protective factors associated with BV chronicity among women in Rakai, Uganda.

OBJECTIVES: To assess risk and protective factors associated with bacterial vaginosis (BV) chronicity ascertained by Nugent score criteria. METHODS: A longitudinal cohort study included 255 sexually experienced, postmenarcheal women who provided weekly self-collected vaginal swabs for up to 2 years. Vaginal swabs were scored using Nugent criteria and classified as normal (≤3), intermediate (4-6) and Nugent-BV (≥7). Detailed behavioural/health information were assessed every 6 months. A per-woman longitudinal summary measure of BV chronicity was defined as the percentage of each woman's weekly vaginal assessments scored as Nugent-BV over a 6-month interval. Risk and protective factors associated with BV chronicity were assessed using multiple linear regression with generalised estimating equations. RESULTS: Average BV chronicity was 39% across all follow-up periods. After adjustment, factors associated with BV chronicity included baseline Nugent-BV (ß=35.3, 95% CI 28.6 to 42.0) compared with normal baseline Nugent scores and use of unprotected water for bathing (ie, rainwater, pond, lake/stream) (ß=12.0, 95% CI 3.4 to 20.5) compared with protected water sources (ie, well, tap, borehole). Women had fewer BV occurrences if they were currently pregnant (ß=-6.6, 95% CI -12.1 to 1.1), reported consistent condom use (ß=-7.7, 95% CI -14.2 to 1.3) or their partner was circumcised (ß=-5.8, 95% CI -11.3 to 0.3). CONCLUSIONS: Factors associated with higher and lower values of BV chronicity were multifactorial. Notably, higher values of BV chronicity were associated with potentially contaminated bathing water. Future studies should examine the role of waterborne microbial agents in the pathogenesis of BV.