Research priority setting in women's health: a systematic review.

BACKGROUND: Developing a shared agenda is an important step in ensuring future research has the necessary relevance. OBJECTIVE: To characterise research priority setting partnerships (PSPs) relevant to women's health. SEARCH STRATEGY: Included studies were identified by searching MEDLINE and the James Lind Alliance (JLA) database. SELECTION CRITERIA: Priority setting partnerships using formal consensus methods. DATA COLLECTION AND ANALYSIS: Descriptive narrative to describe the study characteristics, methods, and results. MAIN RESULTS: Ten national and two international PSPs were identified. All PSPs used the JLA method to identify research priorities. Nine PSPs had published a protocol. Potential research uncertainties were gathered from guidelines (two studies), Cochrane reviews (five studies), and surveys (12 studies). The number of healthcare professionals (31-287), patients (44-932), and others (33-139) who responded to the survey, and the number of uncertainties submitted (52-4767) varied. All PSPs entered confirmed research uncertainties (39-104) into interim priority setting surveys and healthcare professionals (31-287), patients (44-932), and others (33-139) responded. All PSPs entered a short list of research uncertainties into a consensus development meeting, which enabled healthcare professionals (six to 21), patients (eight to 14), and others (two to 13) to identify research priorities (ten to 15). Four PSPs have published their results. CONCLUSION: Future research priority setting studies should publish a protocol, use formal consensus development methods, and ensure their methods and results are comprehensively reported. TWEETABLE ABSTRACT: Research published in @BJOGtweets highlights future research priorities across women's health, including @FertilityTop10, @jamesmnduffy.

A cross-sectional study of Mycoplasma genitalium infection and correlates in women undergoing population-based screening or clinic-based testing for Chlamydia infection in London.

OBJECTIVE: To determine Mycoplasma genitalium infection and correlates among young women undergoing population-based screening or clinic-based testing for Chlamydia infection. DESIGN: Cross-sectional study. SETTING: National Chlamydia Screening Programme (NCSP) and two London sexually transmitted infection (STI) clinics. PARTICIPANTS: 2441 women aged 15-64 years who participated in the NCSP and 2172 women who attended two London STI clinics over a 4-month period in 2009. OUTCOME MEASURES: (1) M genitalium prevalence in defined populations (%). (2) Age-adjusted ORs (aORs) for correlates of M genitalium infection. RESULTS: The overall frequency of M genitalium and Chlamydia trachomatis was 3% and 5.4%, respectively. Co-infection was relatively uncommon (0.5% of all women); however 9% of women with C trachomatis also had M genitalium infection. M genitalium was more frequently detected in swab than urine samples (3.9 vs 1.3%, p<0.001) with a significantly higher mean bacterial load (p ≤ 0.001). Among NCSP participants, M genitalium was significantly more likely to be diagnosed in women of black/black British ethnicity (aOR 2.3, 95% CI 1.2 to 4.5, p=0.01). M genitalium and C trachomatis and were both significantly associated with multiple sexual partners in the past year (aOR 2.4, 95% CI 1.3 to 4.4, p=0.01 and aOR 2.0, 95% CI 1.4 to 2.8, p<0.01). Among STI clinic attendees, M genitalium was more common in women who were less than 25 years in age. CONCLUSIONS: M genitalium is a relatively common infection among young women in London. It is significantly more likely to be detected in vulvovaginal swabs than in urine samples. Co-infection with Chlamydia is uncommon. The clinical effectiveness of testing and treatment strategies for M genitalium needs further investigation.

Behavioural predictors of subsequent hepatitis C diagnosis in a UK clinic sample of HIV positive men who have sex with men.

OBJECTIVE: To explore the associations between self reported high risk sexual behaviours and subsequent diagnosis with hepatitis C virus (HCV) infection. METHODS: The Sex, Health and Anti-Retrovirals Project (SHARP) was a cross sectional study of sexual behaviour in HIV positive, men who have sex with men (MSM) attending a London outpatient clinic. From July 1999 to August 2000 participants completed a computer assisted self interview questionnaire (CASI) on recent sexual behaviour, recreational drug use, and detailed reporting of the last two sexual episodes involving different partners. Results were combined with routine clinic data and subsequent testing for HCV up to 21 April 2005. A new HCV diagnosis was defined as anti-HCV antibody seroconversion or positive HCV RNA following a previous negative. Incident rate ratios (IRR) were calculated using Poisson regression in Stata (version 9). Men contributed time at risk from interview until either their diagnosis or their last negative test result. RESULTS: Of the 422 men who completed questionnaires, 308 (73%) had sufficient clinical and HCV testing data available for analysis. Incident HCV infection was identified in 11 men. Unprotected anal intercourse, more than 30 sex partners in the past year, higher numbers of new anal sex partners, rimming (oro-anal sex), fisting, use of sex toys, and intranasal recreational drug use were associated with HCV. In multivariate analysis only fisting remained associated with HCV (adjusted IRR 6.27, p = 0.005). CONCLUSIONS: In this study of HIV positive MSM, fisting is strongly associated with HCV infection. Where individuals report high risk sexual behaviours, clinicians should offer appropriate testing for HCV infection.

Risk factors associated with pelvic inflammatory disease.

OBJECTIVE: To investigate factors associated with pelvic inflammatory disease (PID). METHODS: A case-control study was used to investigate demographic and behavioural factors, and causative agents associated with PID. RESULTS: A total of 381 participants were recruited: 140 patients, and 105 and 136 controls in tubal ligation and general practice groups, respectively. When compared with a PID-free tubal ligation control group, increased risk of PID was associated with: age <25 years; age at first sexual intercourse <20 years; non-white ethnicity; not having had children; a self-reported history of a sexually transmitted disease; and exposure to Chlamydia trachomatis. When compared with a general practice control group, increased risk was associated with: age <25 years; age at first sexual intercourse <15 years; lower socioeconomic status; being single; adverse pregnancy outcome; a self-reported history of a sexually transmitted disease; and exposure to C trachomatis. Of the cases, 64% were not associated with any of the infectious agents measured in this study (idiopathic). CONCLUSIONS: A high proportion of cases were idiopathic. PID control strategies, which currently focus on chlamydial screening, have to be reviewed so that they can prevent all cases of PID. Behavioural change is a key factor in the primary prevention of PID, and potential modifiable risk factors were associated with PID.

One stop shop versus collaborative integration: what is the best way of delivering sexual health services?

OBJECTIVES: To examine various models of integrated and/or one stop shop (OSS) sexual health services (including general practice, mainstream specialist services, and designated young people's services) and explore their relative strengths and weaknesses. METHODS: Literature review and interviews with key informants involved in developing the National Strategy for Sexual Health and HIV (n = 11). RESULTS: The paper focuses on five broad perspectives (logistics, public health, users, staff, and cost). Contraceptive and genitourinary medicine issues are closely related. However, there is no agreement about what is meant by having "integrated" services, about which services should be integrated, or where integration should happen. There are concerns that OSSs will result in over-centralisation, to the disadvantage of stand alone and satellite services. OSS models are potentially more user focused, but the stigma that surrounds sexual health services may create an access barrier. From staff perspectives, the advantages are greater career opportunities and increased responsibility, while the disadvantages are concern that OSSs will result in loss of expertise and professional status. Cost effectiveness data are contradictory. CONCLUSION: Although there is a policy commitment to look at how integrated services can be better developed, more evidence is required on the impact and appropriateness of this approach.

Pupil-led sex education in England (RIPPLE study): cluster-randomised intervention trial.

BACKGROUND: Improvement of sex education in schools is a key part of the UK government's strategy to reduce teenage pregnancy in England. We examined the effectiveness of one form of peer-led sex education in a school-based randomised trial of over 8000 pupils. METHODS: 29 schools were randomised to either peer-led sex education (intervention) or to continue their usual teacher-led sex education (control). In intervention schools, peer educators aged 16-17 years delivered three sessions of sex education to 13-14 year-old pupils from the same schools. Primary outcome was unprotected (without condom) first heterosexual intercourse by age 16 years. Analysis was by intention to treat. FINDINGS: By age 16 years, significantly fewer girls reported intercourse in the peer-led arm than in the control arm, but proportions were similar for boys. The proportions of pupils reporting unprotected first sex did not differ for girls (8.4% intervention vs 8.3% control) or for boys (6.2% vs 4.7%). Stratified estimates of the difference between arms were -0.4% (95% CI -3.7% to 2.8%, p=0.79) for girls and -1.4% (-4.4% to 1.6%, p=0.36) for boys. At follow-up (mean age 16.0 years [SD 0.32]), girls in the intervention arm reported fewer unintended pregnancies, although the difference was borderline (2.3% vs 3.3%, p=0.07). Girls and boys were more satisfied with peer-led than teacher-led sex education, but 57% of girls and 32% of boys wanted sex education in single-sex groups. INTERPRETATION: Peer-led sex education was effective in some ways, but broader strategies are needed to improve young people's sexual health. The role of single-sex sessions should be investigated further.

Effect of social exclusion on the risk of teenage pregnancy: development of hypotheses using baseline data from a randomised trial of sex education.

STUDY OBJECTIVE: The UK government argues that "social exclusion" increases risk of teenage pregnancy and that educational factors may be dimensions of such exclusion. The evidence cited by the government is limited to reporting that socioeconomic disadvantage and educational attainment influence risk. Evidence regarding young people's attitude to school is not cited, and there is a lack of research concerning the UK. This paper develops hypotheses on the relation between socioeconomic and educational dimensions of social exclusion, and risk of teenage pregnancy, by examining whether dislike of school and socioeconomic disadvantage are associated with cognitive/behavioural risk measures among 13/14 year olds in English schools. DESIGN: Analysis of data from the baseline survey of a study of sex education. SETTING AND PARTICIPANTS: 13/14 year old school students from south east England. MAIN RESULTS: The results indicate that socioeconomic disadvantage and dislike of school are associated with various risk factors, each with a different pattern. Those disliking school, despite having comparable knowledge to those liking school, were more likely to have sexual intercourse, expect sexual intercourse by age 16, and expect to be parents by the age of 20. For most associations, the crude odds ratios (ORs) and the ORs adjusted for the other exposure were similar, suggesting that inter-confounding between exposures was limited. CONCLUSIONS: It is hypothesised that in determining risk of teenage pregnancy, the two exposures are independent. Those disliking school might be at greater risk of teenage pregnancy because they are more likely to see teenage pregnancy as inevitable or positive.

A school-based randomized controlled trial of peer-led sex education in England.

This article discusses the design of an ongoing cluster-randomized trial comparing two forms of school-based sex education in terms of educational process and sexual health outcomes. Twenty-nine schools in southern England have been randomized to either peer-led sex education or to continue with their traditional teacher-led sex education. The primary objective is to determine which form of sex education is more effective in promoting young people's sexual health. The trial includes an unusually detailed evaluation of the process of sex education as well as the outcomes. The sex education programs were delivered in school to pupils ages 13-14 years who are being followed until ages 19-20. Major trial outcomes are unprotected sexual intercourse and regretted intercourse by age 16 and cumulative incidence of abortion by ages 19-20. We discuss the rationale behind various aspects of the design, including ethical issues and practical challenges of conducting a randomized trial in schools, data linkage for key outcomes to reduce bias, and integrating process and outcome measures to improve the interpretation of findings.

Is use of antiretroviral therapy among homosexual men associated with increased risk of transmission of HIV infection?

BACKGROUND/OBJECTIVE: There is concern that use of highly active antiretroviral therapy (HAART) may be linked to increased sexual risk behaviour among homosexual men. We investigated sexual risk behaviour in HIV positive homosexual men and the relation between use of HAART and risk of HIV transmission. METHODS: A cross sectional study of 420 HIV positive homosexual men attending a London outpatient clinic. Individual data were collected from computer assisted self interview, STI screening, and clinical and laboratory databases. RESULTS: Among all men, sexual behaviour associated with a high risk of HIV transmission was commonly reported. The most frequently reported type of partnership was casual partners only, and 22% reported unprotected anal intercourse with one or more new partners in the past month. Analysis of crude data showed that men on HAART had fewer sexual partners (median 9 versus 20, p=0.28), less unprotected anal intercourse (for example, 36% versus 27% had insertive unprotected anal intercourse with a new partner in the past year, p=0.03) and fewer acute sexually transmitted infections (33% versus 19%, p=0.004 in the past 12 months) than men not on HAART. Self assessed health status was similar between the two groups: 72% on HAART and 75% not on HAART rated their health as very or fairly good, (p=0.55). In multivariate analysis, differences in sexual risk behaviour between men on HAART and men not on HAART were attenuated by adjustment for age, time since HIV infection. CD4 count and self assessed health status. CONCLUSION: HIV positive homosexual men attending a London outpatient clinic commonly reported sexual behaviour with a high risk of HIV transmission. However, behavioural and clinical risk factors for HIV transmission were consistently lower in men on HAART than men not on HAART. Although use of HAART by homosexual men with generally good health is not associated with higher risk behaviours, effective risk reduction interventions targeting known HIV positive homosexual men are still urgently needed.

A cognitive behavioural intervention to reduce sexually transmitted infections among gay men: randomised trial.

OBJECTIVE: To determine the effectiveness of a brief cognitive behavioural intervention in reducing the incidence of sexually transmitted infections among gay men. DESIGN: Randomised controlled trial with 12 months' follow up. SETTING: Sexual health clinic in London. PARTICIPANTS: 343 gay men with an acute sexually transmitted infection or who reported having had unprotected anal intercourse in the past year. MAIN OUTCOME MEASURES: Number of new sexually transmitted infections diagnosed during follow up and self reported incidence of unprotected anal intercourse. RESULTS: 72% (361/499) of men invited to enter the study did so. 90% (308/343) of participants returned at least one follow up questionnaire or re-attended the clinic and requested a check up for sexually transmitted infections during follow up. At baseline, 37% (63/172) of the intervention group and 30% (50/166) of the control group reported having had unprotected anal intercourse in the past month. At 12 months, the proportions were 27% (31/114) and 32% ( 39/124) respectively (P=0.56). However, 31% (38/123) of the intervention group and 21% (35/168) of controls had had at least one new infection diagnosed at the clinic (adjusted odds ratio 1.66, 95% confidence interval 1.00 to 2.74). Considering only men who requested a check up for sexually transmitted infections, the proportion diagnosed with a new infection was 58% (53/91) for men in the intervention group and 43% (35/81) for men in the control group (adjusted odds ratio 1.84, 0.99 to 3.40). Using a regional database that includes information from 23 sexual health clinics in London, we determined that few participants had attended other sexual health clinics. CONCLUSIONS: This behavioural intervention was acceptable and feasible to deliver, but it did not reduce the risk of acquiring a new sexually transmitted infection among these gay men at high risk. Even carefully designed interventions should not be assumed to bring benefit. It is important to evaluate their effects in randomised trials with objective clinical end points.

Evaluation of behavioural interventions in HIV/STI prevention.

There is an urgent need for well designed randomised trials to assess the impact of behavioural interventions at both individual and community levels in developed and developing countries. The relative lack of such studies partly reflects the particular challenges of applying randomised trials in this area. Although there are obvious differences between clinical and behavioural interventions, the principles underlying successful evaluation are not fundamentally different. Experience gained from clinical trial methodology over the past two decades should be applied and further developed to tackle the demands and challenges of evaluating behavioural interventions in HIV/STI prevention.

Risk of cancer in patients with HIV disease. London African HIV/AIDS Study Group.

The aim of this study was to compare cancer incidence in a cohort of HIV-infected patients with the incidence rates in the population of South East England. Data collected for a retrospective cohort study of 2048 HIV-infected patients were analysed to examine the incidence of cancer. Cases of cancer occurring in South East England from 1985-1995 were obtained from the Thames Cancer Registry. Standardized incidence ratios were calculated by comparison of the observed number of cases for each cancer type in HIV-infected non-Africans with the numbers expected, calculated from the age and sex specific registration rates for the South East England population using person-years of observation. The crude incidence rates of cancer were calculated for HIV-infected Africans. The incidence of non-AIDS defining cancers such as Hodgkin's disease (standardized incidence ratio 22; 95% CI: 3-80) and anal cancer (standardized incidence ratio 125; 95% CI: 3-697) were significantly increased for non-African males with HIV disease. Anal cancer was also significantly increased for non-African females (standardized incidence ratio 1667; 95% CI: 43-9287). Kaposi's sarcoma (KS) was the commonest cancer among HIV-infected Africans and males had an incidence which was nearly 3 times that of females. There is evidence to suggest that the risks for other non-AIDS defining cancers were significantly increased in persons with HIV disease which may have implications for HIV/AIDS surveillance.

Evaluation of self-taken samples for the presence of genital Chlamydia trachomatis infection in women using the ligase chain reaction assay.

The aim of this study was to evaluate the sensitivity and acceptability of self-taken vulval-introital (VI) samples, first-catch urine (FCU) samples and clinician-obtained cervical samples for the presence of genital Chlamydia trachomatis infections in women using the ligase chain reaction (LCR) assay. One hundred and four patients were enrolled, of whom 54 patients had chlamydial DNA in at least one of the samples tested. The sensitivity of the cervical sample was 96.3%, vulval-introital sample in LCR buffer 92.6%, vulval-introital swab collected dry 88.9%, FCU stored at +2-8 degrees C 81.5%, FCU stored at room temperature 77.8% and FCU stored with 2% w/v boric acid at room temperature 87.0%. Self-taken vulval-introital LCR samples were shown to be an acceptable alternative to a clinician-obtained LCR sample. The addition of boric acid may overcome the need for a continuous cold chain for FCU samples.

Effect of lisinopril on progression of retinopathy in normotensive people with type 1 diabetes. The EUCLID Study Group. EURODIAB Controlled Trial of Lisinopril in Insulin-Dependent Diabetes Mellitus.

BACKGROUND: Retinopathy commonly occurs in people with type 1 diabetes. Strict glycaemic control can decrease development and progression of retinopathy only partially. Blood pressure is also a risk factor for microvascular complications. Antihypertensive therapy, especially with inhibitors of angiotensin-converting enzyme (ACE), can slow progression of nephropathy, but the effects on retinopathy have not been established. We investigated the effect of lisinopril on retinopathy in type 1 diabetes. METHODS: As part of a 2-year randomised double-blind placebo-controlled trial, we took retinal photographs at baseline and follow-up (24 months) in patients aged 20-59 in 15 European centres. Patients were not hypertensive, and were normoalbuminuric (85%) or microalbuminuric. Retinopathy was classified from photographs on a five-level scale (none to proliferative). FINDINGS: The proportion of patients with retinopathy at baseline was 65% (117) in the placebo group and 59% (103) in the lisinopril group (p = 0.2). Patients on lisinopril had significantly lower HbA1c at baseline than those on placebo (6.9% vs 7.3 p = 0.05). Retinopathy progressed by at least one level in 21 (13.2%) of 159 patients on lisinopril and 39 (23.4%) of 166 patients on placebo (odds ratio 0.50 [95% CI 0.28-0.89], p = 0.02). This 50% reduction was the same when adjusted for centre and glycaemic control (0.55 [0.30-1.03], p = 0.06). Lisinopril also decreased progression by two or more grades (0.27 [0.07-1.00], p = 0.05), and progression to proliferative retinopathy (0.18 [0.04-0.82], p = 0.03). Progression was not associated with albuminuric status at baseline. Treatment reduced retinopathy incidence (0.69 [0.30-1.59], p = 0.4). INTERPRETATION: Lisinopril may decrease retinopathy progression in non-hypertensive patients who have type 1 diabetes with little or no nephropathy. These findings need to be confirmed before changes to clinical practice can be advocated.

Screening for genital chlamydial infection.

Genital chlamydial infection is a common, sexually transmitted infection that is often asymptomatic, but associated with long term morbidity in a sizeable proportion of women. Early infection can be diagnosed reliably using noninvasive methods and treated effectively with antibiotics. The case for screening in conventional high risk settings (e.g. genito-urinary medicine and termination of pregnancy clinics) is already clear. Screening in the wider community also needs evaluating if a significant impact on the problem is to be made since chlamydial infection is widely distributed among young, sexually active people who may have little contact with health services. Studies are in progress to assess the acceptability of different screening approaches to women and men in the community and to compare performance of newer diagnostic techniques. The cost-effectiveness of community-based screening in reducing morbidity needs to be evaluated empirically in randomised trials to encourage a coherent, evidence-based screening policy in this country.

Behavioural intervention trials for HIV/STD prevention in schools: are they feasible?

OBJECTIVE: To assess the feasibility of conducting a large randomised controlled trial (RCT) of peer led intervention in schools to reduce the risk of HIV/STD and promote sexual health. METHODS: Four secondary schools in Greater London were randomly assigned to receive peer led intervention (two experimental schools) or to act as control schools. In the experimental schools, trained volunteers aged 16-17 years (year 12) delivered the peer led intervention to 13-14 year old pupils (year 9). In the control schools, year 9 pupils received the usual teacher led sex education. Questionnaire data collected from year 9 pupils at baseline included views on the quality of sex education/intervention received, and knowledge and attitudes about HIV/AIDS and other sexual matters. Focus groups were also conducted with peer educators and year 9 pupils. Data on the process of delivering sex education/intervention and on attitudes to the RCT were collected for each of the schools. Analysis focused on the acceptability of a randomised trial to schools, parents, and pupils. RESULTS: Nearly 500 parents were informed about the research and invited to examine the study questionnaire; only nine raised questions and only one pupil was withdrawn from the study. Questionnaire completion rates were around 90% in all schools. At baseline, the majority of year 9 pupils wanted more information about a wide range of sexual matters. Focus group work indicated considerable enthusiasm for peer led education, among peer educators and year 9 pupils. Class discipline was the most frequently noted problem with the delivery of the peer led intervention. CONCLUSION: Evaluation of a peer led behavioural intervention through an RCT can be acceptable to schools, pupils, and parents and is feasible in practice. In general, pupils who received the peer led intervention responded more positively than those in control schools. A large RCT of the long term (5-7 year) effects of this novel intervention on sexual health outcomes is now under way.