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1.  Systematic Review and Meta-Analysis of L1-VLP-Based Human Papillomavirus Vaccine Efficacy against Anogenital Pre-Cancer in Women with Evidence of Prior HPV Exposure 
PLoS ONE  2014;9(3):e90348.
Background
It is unclear whether L1-VLP-based human papillomavirus (HPV) vaccines are efficacious in reducing the likelihood of anogenital pre-cancer in women with evidence of prior vaccine-type HPV exposure. This study aims to determine whether the combined results of the vaccine trials published to date provide evidence of efficacy compared with control (hepatitis A vaccine/placebo).
Methods
A systematic review and meta-analysis was conducted. Randomized-controlled trials (RCTs) were identified from MEDLINE, Embase, Web of Science, PubMed, Cochrane Central Register of Controlled Trials and references of identified studies. The bivalent vaccine containing HPV-16 and 18 VLPs from GlaxoSmithKline Biologicals (Rixenstart, Belgium), the quadrivalent vaccine containing HPV-6, 11, 16, and 18 VLPs from Merck & Co., Inc., (Whitehouse Station, NJ USA), and the HPV-16 monovalent vaccine from Merck Research Laboratories (West Point, PA USA) were evaluated.
Findings
Three RCT reports and two post-trial cohort studies were eligible, comprising data from 13,482 women who were included in the vaccine studies but had evidence of HPV infection at study entry. Data on efficacy was synthesized using the Mantel-Haenszel weighted fixed-effect approach, or where there was heterogeneity between studies, the DerSimonian and Laird weighted random-effect approach. The mean odds ratio (OR) and 95% confidence interval (CI) for the association between Cervarix, Gardasil and HPV-16 monovalent vaccine and HPV-associated cervical intraepithelial neoplasia grade 3 or worse was 0·90 (95% CI: 0·56, 1·44). For the association between Gardasil and HPV-associated vulval/vaginal intraepithelial neoplasia grades 2–3, the overall OR and 95% CI was 2.25 (95% CI: 0·78, 6.50). Sample size and follow-up were limited.
Conclusions
There was no evidence that HPV vaccines are effective in preventing vaccine-type HPV associated pre-cancer in women with evidence of prior HPV exposure. Small effects of vaccination however cannot be excluded and a longer-term benefit in preventing re-infection remains possible.
doi:10.1371/journal.pone.0090348
PMCID: PMC3940851  PMID: 24595046
2.  Optimal CD4 Count for Initiating HIV Treatment 
Epidemiology (Cambridge, Mass.)  2014;25(2):194-202.
Supplemental Digital Content is available in the text.
Background:
In HIV infection, dynamic marginal structural models have estimated the optimal CD4 for treatment initiation to minimize AIDS/death. The impact of CD4 observation frequency and grace periods (permitted delay to initiation) on the optimal regimen has not been investigated nor has the performance of dynamic marginal structural models in moderately sized data sets—two issues that are relevant to many applications.
Methods:
To determine optimal regimens, we simulated 31,000,000 HIV-infected persons randomized at CD4 500–550 cells/mm3 to regimens “initiate treatment within a grace period following observed CD4 first
Results:
Decreasing the frequency of CD4 measurements from monthly to every 3, 6, and 12 months increased the optimal regimen from a CD4 level of 350 (10-year AIDS-free survival, 0.8657) to 410 (0.8650), 460 (0.8634), and 490 (0.8564), respectively. Under a regimen defined by x = 350 with annual CD4s, 10-year AIDS-free survival dropped to 0.8304. Extending the grace period from 1 to 3 or 6 months, with 3-monthly CD4s, maintained the optimal regimen at 410 for 3 months and increased it to 460 for 6 months. In observational studies with 3-monthly CD4s, the mean (SE) estimated optimal regimen was 402 (76), 424 (66), and 430 (63) with 1-, 3-, and 6-month grace periods; 24%, 15%, and 14% of estimated optimal regimens resulted in >0.5% lower AIDS-free survival compared with the true optimal regimen.
Conclusions:
The optimal regimen is strongly influenced by CD4 frequency and less by grace period length. Dynamic marginal structural models lack precision at moderate sample sizes.
doi:10.1097/EDE.0000000000000043
PMCID: PMC3914951  PMID: 24487204
PLoS ONE  2014;9(2):e87442.
Background
The incidence of Hodgkin lymphoma (HL) among HIV-infected individuals remains unchanged since the introduction of combination antiretroviral therapy (cART). Recent epidemiological data suggest that CD4 count decline over a year is associated with subsequent diagnosis of HL. In an era of economic austerity monitoring the efficacy of cART by CD4 counts may no longer be required where CD4 count>350 cells/µl and viral load is suppressed (<50 copies/ml).
Methods
We sought to establish among our HIV outpatient cohort whether a CD4 count decline prior to diagnosis of HL, whether any decline was greater than in patients without the diagnosis, and also whether other clinical or biochemical indices were reliably associated with the diagnosis.
Results
Twenty-nine patients with a diagnosis of HL were identified. Among 15 individuals on cART with viral load <50 copies/ml the change in CD4 over 12 months preceding diagnosis of HL was −82 cells/µl (95% CI −163 to −3; p = 0.04). Among 18 matched controls the mean change was +5 cells/µl, 95% CI −70 to 80, p = 0.89). The decline in CD4 over the previous 6–12 months was somewhat greater in cases than controls (mean difference in change −55 cells/µl, 95% CI −151 to 39; p = 0.25). In 26 (90%) patients B symptoms had been present for a median of three months (range one–12) before diagnosis of HL.
Conclusions
The CD4 count decline in the 12 months prior to diagnosis of Hodgkin lymphoma among HIV-infected individuals with VL<50 copies/ml on cART was not significantly different from that seen in other fully virologically suppressed individuals in receipt of cART and who did not develop HL. All those who developed HL had B symptoms and/or new palpable lymphadenopathy, suggesting that CD4 count monitoring if performed less frequently, or not at all, among those virologically suppressed individuals with CD4 counts >350 may not have delayed diagnosis.
doi:10.1371/journal.pone.0087442
PMCID: PMC3913599  PMID: 24504076
Background
Approximately 1.2 million stillbirths occur in the intrapartum period, and a further 717,000 annual neonatal deaths are caused by intrapartum events, most of which occur in resource poor settings. We aim to test the ‘double-hit’ hypothesis that maternal infection in the perinatal period predisposes to neurodevelopmental sequelae from an intrapartum asphyxia insult, increasing the likelihood of an early neonatal death compared with asphyxia alone. This is an observational study of singleton newborn infants with signs of intrapartum asphyxia that uses data from three previously conducted cluster randomized controlled trials taking place in rural Bangladesh and India.
Methods
From a population of 81,778 births in 54 community clusters in rural Bangladesh and India, we applied mixed effects logistic regression to data on 3890 singleton infants who had signs of intrapartum asphyxia, of whom 769 (20%) died in the early neonatal period. Poor infant condition at five minutes post-delivery was our proxy measure of intrapartum asphyxia. We had data for two markers of maternal infection: fever up to three days prior to labour, and prolonged rupture of membranes (PROM). Cause-specific verbal autopsy data were used to validate our findings using previously mentioned mixed effect logistic regression methods and the outcome of a neonatal death due to intrapartum asphyxia.
Results
Signs of maternal infection as indicated by PROM, combined with intrapartum asphyxia, increased the risk of an early neonatal death relative to intrapartum asphyxia alone (adjusted odds ratio (AOR) 1.28, 95% CI 1.03 – 1.59). Results from cause-specific verbal autopsy data verified our findings where there was a significantly increased odds of a early neonatal death due to intrapartum asphyxia in newborns exposed to both PROM and intrapartum asphyxia (AOR: 1.52, 95% CI 1.15 – 2.02).
Conclusions
Our data support the double-hit hypothesis for signs of maternal infection as indicated by PROM. Interventions for pregnant women with signs of infection, to prevent early neonatal deaths and disability due to asphyxia, should be investigated further in resource-poor populations where the chances of maternal infection are high.
doi:10.1186/1471-2393-13-245
PMCID: PMC3897987  PMID: 24373126
Maternal infection; Double hit hypothesis; Intrapartum-related neonatal death; Prolonged rupture of membranes; Neonatal mortality; Low-income countries; Resource-poor
Background
Sexual health problems such as unwanted pregnancy and sexually transmitted infection are important public health concerns and there is huge potential for health promotion using digital interventions. Evaluations of digital interventions are increasingly conducted online. Trial administration and data collection online offers many advantages, but concerns remain over fraudulent registration to obtain compensation, the quality of self-reported data, and high attrition.
Objective
This study addresses the feasibility of several dimensions of online trial design—recruitment, online consent, participant identity verification, randomization and concealment of allocation, online data collection, data quality, and retention at 3-month follow-up.
Methods
Young people aged 16 to 20 years and resident in the United Kingdom were recruited to the “Sexunzipped” online trial between November 2010 and March 2011 (n=2036). Participants filled in baseline demographic and sexual health questionnaires online and were randomized to the Sexunzipped interactive intervention website or to an information-only control website. Participants were also randomly allocated to a postal request (or no request) for a urine sample for genital chlamydia testing and receipt of a lower (£10/US$16) or higher (£20/US$32) value shopping voucher compensation for 3-month outcome data.
Results
The majority of the 2006 valid participants (90.98%, 1825/2006) were aged between 18 and 20 years at enrolment, from all four countries in the United Kingdom. Most were white (89.98%, 1805/2006), most were in school or training (77.48%, 1545/1994), and 62.81% (1260/2006) of the sample were female. In total, 3.88% (79/2036) of registrations appeared to be invalid and another 4.00% (81/2006) of participants gave inconsistent responses within the questionnaire. The higher value compensation (£20/US$32) increased response rates by 6-10%, boosting retention at 3 months to 77.2% (166/215) for submission of online self-reported sexual health outcomes and 47.4% (118/249) for return of chlamydia urine samples by post.
Conclusions
It was quick and efficient to recruit young people to this online trial. Our procedures for obtaining online consent, verifying participant identity, automated randomization, and concealment of allocation worked well. The optimal response rate for the online sexual health outcome measurement was comparable to face-to-face trials. Multiple methods of participant contact, requesting online data only, and higher value compensation increased trial retention at 3-month follow-up.
Trial Registration
International Standard Randomized Controlled Trial Number (ISRCTN): 55651027; http://www.controlled-trials.com/ISRCTN55651027 (Archived by WebCite at http://www.webcitation.org/6LbkxdPKf).
doi:10.2196/jmir.2668
PMCID: PMC3868980  PMID: 24334216
Internet; randomized controlled trials as topic; outcome assessment (health care); sexual health; sexually transmitted diseases; behavioral research
Lancet  2013;382(9907):1817-1829.
Summary
Background
Despite its importance to sexual health and wellbeing, sexual function is given little attention in sexual health policy. Population-based studies are needed to understand sexual function across the life course.
Methods
We undertook a probability sample survey (the third National Survey of Sexual Attitudes and Lifestyles [Natsal-3]) of 15 162 individuals aged 16–74 years who lived in Britain (England, Scotland, and Wales). Interviews were done between Sept 6, 2010, and Aug 31, 2012. We assessed the distribution of sexual function by use of a novel validated measure (the Natsal-SF), which assessed problems with individual sexual response, sexual function in a relationship context, and self-appraisal of sex life (17 items; 16 items per gender). We assess factors associated with low sexual function (defined as the lowest quintile of distribution of Natsal-SF scores) and the distribution of components of the measure. Participants reporting one or more sexual partner in the past year were given a score on the Natsal-SF (11 690 participants). 4122 of these participants were not in a relationship for all of the past year and we employed the full information maximum likelihood method to handle missing data on four relationship items.
Findings
We obtained data for 4913 men and 6777 women for the Natsal-SF. For men and women, low sexual function was associated with increased age, and, after age-adjustment, with depression (adjusted odds ratio 3·70 [95% CI 2·90–4·72] for men and 4·11 [3·36–5·04] for women) and self-reported poor health status (2·63 [1·73–3·98] and 2·41 [1·72–3·39]). Low sexual function was also associated with experiencing the end of a relationship (1·52 [1·18–1·95] and 1·77 [1·44–2·17]), inability to talk easily about sex with a partner (2·36 [1·94–2·88] and 2·82 [2·28–3·48]), and not being happy in the relationship (2·89 [2·32–3·61] and 4·10 [3·39–4·97]). Associations were also noted with engaging in fewer than four sex acts in the past 4 weeks (3·13 [2·58–3·79] and 3·38 [2·80–4·09]), having had same sex partners (2·28 [1·56–3·35] and 1·60 [1·16–2·20]), paying for sex (in men only; 2·62 [1·46–4·71]), and higher numbers of lifetime sexual partners (in women only; 2·12 [1·68–2·67] for ten or more partners). Low sexual function was also associated with negative sexual health outcomes such as experience of non-volitional sex (1·98 [1·14–3·43] and 2·18 [1·79–2·66]) and STI diagnosis (1·50 [1·06–2·11] and 1·83 [1·35–2·47]). Among individuals reporting sex in the past year, problems with sexual response were common (41·6% of men and 51·2% of women reported one or more problem) but self-reported distress about sex lives was much less common (9·9% and 10·9%). For individuals in a sexual relationship for the past year, 23·4% of men and 27·4% of women reported an imbalance in level of interest in sex between partners, and 18·0% of men and 17·1% of women said that their partner had had sexual difficulties. Most participants who did not have sex in the past year were not dissatisfied, distressed, or avoiding sex because of sexual difficulties.
Interpretation
Wide variability exists in the distribution of sexual function scores. Low sexual function is associated with negative sexual health outcomes, supporting calls for a greater emphasis on sexual function in sexual health policy and interventions.
Funding
Grants from the UK Medical Research Council and the Wellcome Trust, with support from the Economic and Social Research Council and the Department of Health.
doi:10.1016/S0140-6736(13)62366-1
PMCID: PMC3898902  PMID: 24286787
Lancet  2013;382(9907):1807-1816.
Summary
Background
Unplanned pregnancy is a key public health indicator. We describe the prevalence of unplanned pregnancy, and associated factors, in a general population sample in Britain (England, Scotland, and Wales).
Method
We did a probability sample survey, the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3), of 15 162 men and women aged 16–74 years in Britain, including 5686 women of child-bearing age (16–44 years) who were included in the pregnancy analysis, between Sept 6, 2010, and Aug 31, 2012. We describe the planning status of pregnancies with known outcomes in the past year, and report the annual population prevalence of unplanned pregnancy, using a validated, multicriteria, multi-outcome measure (the London Measure of Unplanned Pregnancy). We set the findings in the context of secular trends in reproductive health-related events, and patterns across the life course.
Findings
9·7% of women aged 16–44 years had pregnancies with known outcome in the year before interview, of which 16·2% (95% CI 13·1–19·9) scored as unplanned, 29·0% (25·2–33·2) as ambivalent, and 54·8% (50·3–59·2) as planned, giving an annual prevalence estimate for unplanned pregnancy of 1·5% (1·2–1·9). Pregnancies in women aged 16–19 years were most commonly unplanned (45·2% [30·8–60·5]). However, most unplanned pregnancies were in women aged 20–34 years (62·4% [50·2–73·2]). Factors strongly associated with unplanned pregnancy were first sexual intercourse before 16 years of age (age-adjusted odds ratio 2·85 [95% CI 1·77–4·57], current smoking (2·47 [1·46–4·18]), recent use of drugs other than cannabis (3·41 [1·64–7·11]), and lower educational attainment. Unplanned pregnancy was also associated with lack of sexual competence at first sexual intercourse (1·90 [1·14–3·08]), reporting higher frequency of sex (2·11 [1·25–3·57] for five or more times in the past 4 weeks), receiving sex education mainly from a non-school-based source (1·84 [1·12–3·00]), and current depression (1·96 [1·10–3·47]).
Interpretation
The increasing intervals between first sexual intercourse, cohabitation, and childbearing means that, on average, women in Britain spend about 30 years of their life needing to avert an unplanned pregnancy. Our data offer scope for primary prevention aimed at reducing the rate of unplanned conceptions, and secondary prevention aimed at modification of health behaviours and health disorders in unplanned pregnancy that might be harmful for mother and child.
Funding
Grants from the UK Medical Research Council and the Wellcome Trust, with support from the Economic and Social Research Council and the Department of Health.
doi:10.1016/S0140-6736(13)62071-1
PMCID: PMC3898922  PMID: 24286786
Lancet  2013;382(9907):1845-1855.
Summary
Background
Sexual violence is increasingly recognised as a public health issue. Information about prevalence, associated factors, and consequences for health in the population of Britain (England, Scotland, and Wales) is scarce. The third National Survey of Sexual Health Attitudes and Lifestyles (Natsal-3) is the first of the Natsal surveys to include questions about sexual violence and the first population-based survey in Britain to explore the issue outside the context of crime.
Methods
Between Sept 6, 2010, and Aug 31, 2012, we did a probability sample survey of women and men aged 16–74 years living in Britain. We asked participants about their experience of sex against their will since age 13 years and the circumstances surrounding the most recent occurrence. We explored associations between ever experiencing non-volitional sex and a range of sociodemographic, health, and behavioural factors. We used logistic regression to estimate age-adjusted odds ratios to analyse factors associated with the occurrence of completed non-volitional sex in women and men.
Findings
We interviewed 15 162 people. Completed non-volitional sex was reported by 9·8% (95% CI 9·0–10·5) of women and 1·4% (1·1–1·7) of men. Median age (interdecile range) at most recent occurrence was 18 years (14–32) for women and 16 years (13–30) for men. Completed non-volitional sex varied by family structure and, in women, by age, education, and area-level deprivation. It was associated with poor health, longstanding illness or disability, and treatment for mental health conditions, smoking, and use of non-prescription drugs in the past year in both sexes, and with binge drinking in women. Completed non-volitional sex was also associated with reporting of first heterosexual intercourse before 16 years of age, same-sex experience, more lifetime sexual partners, ever being diagnosed with a sexually transmitted infection, and low sexual function in both sexes, and, in women, with abortion and pregnancy outcome before 18 years of age. In most cases, the person responsible was known to the individual, although the nature of the relationship differed by age at most recent occurrence. Participants who were younger at interview were more likely to have told someone about the event and to have reported it to the police than were older participants.
Interpretation
These data provide the first population prevalence estimates of non-volitional sex in Britain. We showed it to be mainly an experience of young age and strongly associated with a range of adverse health outcomes in both women and men.
Funding
Grants from the UK Medical Research Council and the Wellcome Trust, with support from the Economic and Social Research Council and the Department of Health.
doi:10.1016/S0140-6736(13)62300-4
PMCID: PMC3898964  PMID: 24286789
Lancet  2013;382(9907):1830-1844.
Summary
Background
Physical and mental health could greatly affect sexual activity and fulfilment, but the nature of associations at a population level is poorly understood. We used data from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3) to explore associations between health and sexual lifestyles in Britain (England, Scotland, and Wales).
Methods
Men and women aged 16–74 years who were resident in households in Britain were interviewed between Sept 6, 2010, and Aug 31, 2012. Participants completed the survey in their own homes through computer-assisted face-to-face interviews and self-interview. We analysed data for self-reported health status, chronic conditions, and sexual lifestyles, weighted to account for unequal selection probabilities and non-response to correct for differences in sex, age group, and region according to 2011 Census figures.
Findings
Interviews were done with 15 162 participants (6293 men, 8869 women). The proportion reporting recent sexual activity (one or more occasion of vaginal, oral, or anal sex with a partner of the opposite sex, or oral or anal sex or genital contact with a partner of the same sex in the past 4 weeks) decreased with age after the age of 45 years in men and after the age of 35 years in women, while the proportion in poorer health categories increased with age. Recent sexual activity was less common in participants reporting bad or very bad health than in those reporting very good health (men: 35·7% [95% CI 28·6–43·5] vs 74·8% [72·7–76·7]; women: 34·0% [28·6–39·9] vs 67·4% [65·4–69·3]), and this association remained after adjusting for age and relationship status (men: adjusted odds ratio [AOR] 0·29 [95% CI 0·19–0·44]; women: 0·43 [0·31–0·61]). Sexual satisfaction generally decreased with age, and was significantly lower in those reporting bad or very bad health than in those reporting very good health (men: 45·4% [38·4–52·7] vs 69·5% [67·3–71·6], AOR 0·51 [0·36–0·72]; women: 48·6% [42·9–54·3] vs 65·6% [63·6–67·4], AOR 0·69 [0·53–0·91]). In both sexes, reduced sexual activity and reduced satisfaction were associated with limiting disability and depressive symptoms, and reduced sexual activity was associated with chronic airways disease and difficulty walking up the stairs because of a health problem. 16·6% (95% CI 15·4–17·7) of men and 17·2% (16·3–18·2) of women reported that their health had affected their sex life in the past year, increasing to about 60% in those reporting bad or very bad health. 23·5% (20·3–26·9) of men and 18·4% (16·0–20·9) of women who reported that their health affected their sex life reported that they had sought clinical help (>80% from general practitioners; <10% from specialist services).
Interpretation
Poor health is independently associated with decreased sexual activity and satisfaction at all ages in Britain. Many people in poor health report an effect on their sex life, but few seek clinical help. Sexual lifestyle advice should be a component of holistic health care for patients with chronic ill health.
Funding
Grants from the UK Medical Research Council and the Wellcome Trust, with support from the Economic and Social Research Council and Department of Health.
doi:10.1016/S0140-6736(13)62222-9
PMCID: PMC3898988  PMID: 24286788
Lancet  2013;382(9907):1781-1794.
Summary
Background
Sexual behaviour and relationships are key components of wellbeing and are affected by social norms, attitudes, and health. We present data on sexual behaviours and attitudes in Britain (England, Scotland, and Wales) from the three National Surveys of Sexual Attitudes and Lifestyles (Natsal).
Methods
We used a multistage, clustered, and stratified probability sample design. Within each of the 1727 sampled postcode sectors for Natsal-3, 30 or 36 addresses were randomly selected and then assigned to interviewers. To oversample individuals aged 16–34 years, we randomly allocated addresses to either the core sample (in which individuals aged 16–74 years were eligible) or the boost sample (in which only individuals aged 16–34 years were eligible). Interviewers visited all sampled addresses between Sept 6, 2010, and Aug 31, 2012, and randomly selected one eligible individual from each household to be invited to participate. Participants completed the survey in their own homes through computer-assisted face-to-face interviews and self-interview. We analysed data from this survey, weighted to account for unequal selection probabilities and non-response to correct for differences in sex, age group, and region according to 2011 Census figures. We then compared data from participants aged 16–44 years from Natsal-1 (1990–91), Natsal-2 (1999–2001), and Natsal-3.
Findings
Interviews were completed with 15 162 participants (6293 men, 8869 women) from 26 274 eligible addresses (57·7%). 82·1% (95% CI 81·0–83·1%) of men and 77·7% (76·7–78·7%) of women reported at least one sexual partner of the opposite sex in the past year. The proportion generally decreased with age, as did the range of sexual practices with partners of the opposite sex, especially in women. The increased sexual activity and diversity reported in Natsal-2 in individuals aged 16–44 years when compared with Natsal-1 has generally been sustained in Natsal-3, but in men has generally not risen further. However, in women, the number of male sexual partners over the lifetime (age-adjusted odds ratio 1·18, 95% CI 1·08–1·28), proportion reporting ever having had a sexual experience with genital contact with another woman (1·69, 1·43–2·00), and proportion reporting at least one female sexual partner in the past 5 years (2·00, 1·59–2·51) increased in Natsal-3 compared with Natsal-2. While reported number of occasions of heterosexual intercourse in the past 4 weeks had reduced since Natsal-2, we recorded an expansion of heterosexual repertoires—particularly in oral and anal sex—over time. Acceptance of same-sex partnerships and intolerance of non-exclusivity in marriage increased in men and women in Natsal-3.
Interpretation
Sexual lifestyles in Britain have changed substantially in the past 60 years, with changes in behaviour seeming greater in women than men. The continuation of sexual activity into later life—albeit reduced in range and frequency—emphasises that attention to sexual health and wellbeing is needed throughout the life course.
Funding
Grants from the UK Medical Research Council and the Wellcome Trust, with support from the Economic and Social Research Council and the Department of Health.
doi:10.1016/S0140-6736(13)62035-8
PMCID: PMC3899021  PMID: 24286784
Lancet  2013;382(9907):1795-1806.
Summary
Background
Population-based estimates of prevalence, risk distribution, and intervention uptake inform delivery of control programmes for sexually transmitted infections (STIs). We undertook the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3) after implementation of national sexual health strategies, and describe the epidemiology of four STIs in Britain (England, Scotland, and Wales) and the uptake of interventions.
Methods
Between Sept 6, 2010 and Aug 31, 2012, we did a probability sample survey of 15 162 women and men aged 16–74 years in Britain. Participants were interviewed with computer-assisted face-to-face and self-completion questionnaires. Urine from a sample of participants aged 16–44 years who reported at least one sexual partner over the lifetime was tested for the presence of Chlamydia trachomatis, type-specific human papillomavirus (HPV), Neisseria gonorrhoeae, and HIV antibody. We describe age-specific and sex-specific prevalences of infection and intervention uptake, in relation to demographic and behavioural factors, and explore changes since Natsal-1 (1990–91) and Natsal-2 (1999–2001).
Findings
Of 8047 eligible participants invited to provide a urine sample, 4828 (60%) agreed. We excluded 278 samples, leaving 4550 (94%) participants with STI test results. Chlamydia prevalence was 1·5% (95% CI 1·1–2·0) in women and 1·1% (0·7–1·6) in men. Prevalences in individuals aged 16–24 years were 3·1% (2·2–4·3) in women and 2·3% (1·5–3·4) in men. Area-level deprivation and higher numbers of partners, especially without use of condoms, were risk factors. However, 60·4% (45·5–73·7) of chlamydia in women and 43·3% (25·9–62·5) in men was in individuals who had had one partner in the past year. Among sexually active 16–24-year-olds, 54·2% (51·4–56·9) of women and 34·6% (31·8–37·4) of men reported testing for chlamydia in the past year, with testing higher in those with more partners. High-risk HPV was detected in 15·9% (14·4–17·5) of women, similar to in Natsal-2. Coverage of HPV catch-up vaccination was 61·5% (58·2–64·7). Prevalence of HPV types 16 and 18 in women aged 18–20 years was lower in Natsal-3 than Natsal-2 (5·8% [3·9–8·6] vs 11·3% [6·8–18·2]; age-adjusted odds ratio 0·44 [0·21–0·94]). Gonorrhoea (<0·1% prevalence in women and men) and HIV (0·1% prevalence in women and 0·2% in men) were uncommon and restricted to participants with recognised high-risk factors. Since Natsal-2, substantial increases were noted in attendance at sexual health clinics (from 6·7% to 21·4% in women and from 7·7% to 19·6% in men) and HIV testing (from 8·7% to 27·6% in women and from 9·2% to 16·9% in men) in the past 5 years.
Interpretation
STIs were distributed heterogeneously, requiring general and infection-specific interventions. Increases in testing and attendance at sexual health clinics, especially in people at highest risk, are encouraging. However, STIs persist both in individuals accessing and those not accessing services. Our findings provide empirical evidence to inform future sexual health interventions and services.
Funding
Grants from the UK Medical Research Council and the Wellcome Trust, with support from the Economic and Social Research Council and the Department of Health.
doi:10.1016/S0140-6736(13)61947-9
PMCID: PMC3899025  PMID: 24286785
PLoS ONE  2013;8(10):e78402.
Introduction
Respondent-driven sampling (RDS) is a variant of a link-tracing design intended for generating unbiased estimates of the composition of hidden populations that typically involves giving participants several coupons to recruit their peers into the study. RDS may generate biased estimates if coupons are distributed non-randomly or if potential recruits present for interview non-randomly. We explore if biases detected in an RDS study were due to either of these mechanisms, and propose and apply weights to reduce bias due to non-random presentation for interview.
Methods
Using data from the total population, and the population to whom recruiters offered their coupons, we explored how age and socioeconomic status were associated with being offered a coupon, and, if offered a coupon, with presenting for interview. Population proportions were estimated by weighting by the assumed inverse probabilities of being offered a coupon (as in existing RDS methods), and also of presentation for interview if offered a coupon by age and socioeconomic status group.
Results
Younger men were under-recruited primarily because they were less likely to be offered coupons. The under-recruitment of higher socioeconomic status men was due in part to them being less likely to present for interview. Consistent with these findings, weighting for non-random presentation for interview by age and socioeconomic status group greatly improved the estimate of the proportion of men in the lowest socioeconomic group, reducing the root-mean-squared error of RDS estimates of socioeconomic status by 38%, but had little effect on estimates for age. The weighting also improved estimates for tribe and religion (reducing root-mean-squared-errors by 19–29%), but had little effect for sexual activity or HIV status.
Conclusions
Data collected from recruiters on the characteristics of men to whom they offered coupons may be used to reduce bias in RDS studies. Further evaluation of this new method is required.
doi:10.1371/journal.pone.0078402
PMCID: PMC3814964  PMID: 24205221
Lancet  2013;381(9879):1736-1746.
Summary
Background
Maternal and neonatal mortality rates remain high in many low-income and middle-income countries. Different approaches for the improvement of birth outcomes have been used in community-based interventions, with heterogeneous effects on survival. We assessed the effects of women’s groups practising participatory learning and action, compared with usual care, on birth outcomes in low-resource settings.
Methods
We did a systematic review and meta-analysis of randomised controlled trials undertaken in Bangladesh, India, Malawi, and Nepal in which the effects of women’s groups practising participatory learning and action were assessed to identify population-level predictors of effect on maternal mortality, neonatal mortality, and stillbirths. We also reviewed the cost-effectiveness of the women’s group intervention and estimated its potential effect at scale in Countdown countries.
Findings
Seven trials (119 428 births) met the inclusion criteria. Meta-analyses of all trials showed that exposure to women’s groups was associated with a 37% reduction in maternal mortality (odds ratio 0·63, 95% CI 0·32–0·94), a 23% reduction in neonatal mortality (0·77, 0·65–0·90), and a 9% non-significant reduction in stillbirths (0·91, 0·79–1·03), with high heterogeneity for maternal (I2=58·8%, p=0·024) and neonatal results (I2=64·7%, p=0·009). In the meta-regression analyses, the proportion of pregnant women in groups was linearly associated with reduction in both maternal and neonatal mortality (p=0·026 and p=0·011, respectively). A subgroup analysis of the four studies in which at least 30% of pregnant women participated in groups showed a 55% reduction in maternal mortality (0·45, 0·17–0·73) and a 33% reduction in neonatal mortality (0·67, 0·59–0·74). The intervention was cost effective by WHO standards and could save an estimated 283 000 newborn infants and 41 100 mothers per year if implemented in rural areas of 74 Countdown countries.
Interpretation
With the participation of at least a third of pregnant women and adequate population coverage, women’s groups practising participatory learning and action are a cost-effective strategy to improve maternal and neonatal survival in low-resource settings.
Funding
Wellcome Trust, Ammalife, and National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care for Birmingham and the Black Country programme.
doi:10.1016/S0140-6736(13)60685-6
PMCID: PMC3797417  PMID: 23683640
PLoS ONE  2013;8(7):e70254.
Background
There is a recognized gap in the evidence base relating to the nature and components of interventions to address the psycho-social needs of HIV positive young people. We used mixed methods research to strengthen a community support group intervention for HIV positive young people based in Harare, Zimbabwe.
Methods
A quantitative questionnaire was administered to HIV positive Africaid support group attendees. Afterwards, qualitative data were collected from young people aged 15–18 through tape-recorded in-depth interviews (n = 10), 3 focus group discussions (FGDs) and 16 life history narratives. Data were also collected from caregivers, health care workers, and community members through FGDs (n = 6 groups) and in-depth interviews (n = 12). Quantitative data were processed and analysed using STATA 10. Qualitative data were analysed using thematic analysis.
Results
229/310 young people completed the quantitative questionnaire (74% participation). Median age was 14 (range 6–18 years); 59% were female. Self-reported adherence to antiretrovirals was sub-optimal. Psychological well being was poor (median score on Shona Symptom Questionnaire 9/14); 63% were at risk of depression. Qualitative findings suggested that challenges faced by positive children include verbal abuse, stigma, and discrimination. While data showed that support group attendance is helpful, young people stressed that life outside the confines of the group was more challenging. Caregivers felt ill-equipped to support the children in their care. These data, combined with a previously validated conceptual framework for family-centred interventions, were used to guide the development of the existing programme of adolescent support groups into a more comprehensive evidence-based psychosocial support programme encompassing caregiver and household members.
Conclusions
This study allowed us to describe the lived experiences of HIV positive young people and their caregivers in Zimbabwe. The findings contributed to the enhancement of Africaid’s existing programme of support to better promote psychological well being and ART adherence.
doi:10.1371/journal.pone.0070254
PMCID: PMC3720910  PMID: 23894625
PLoS ONE  2013;8(4):e61826.
Background
The HIV Dementia Scale (HDS) and International HIV Dementia Scale (IHDS) are brief tools that have been developed to screen for and aid diagnosis of HIV-associated dementia (HAD). They are increasingly being used in clinical practice for minor neurocognitive disorder (MND) as well as HAD, despite uncertainty about their accuracy.
Methods and Findings
A systematic review of the accuracy of the HDS and IHDS was conducted. Studies were assessed on Standards for Reporting Diagnostic Accuracy criteria. Pooled sensitivity, specificity, likelihood ratios (LR) and diagnostic odds ratios (DOR) were calculated for each scale as a test for HAD or MND. We retrieved 15 studies of the HDS, 10 of the IHDS, and 1 of both scales. Thirteen studies of the HDS were conducted in North America, and 7 of the IHDS studies were conducted in sub-Saharan Africa. Estimates of accuracy were highly heterogeneous between studies for the HDS but less so for the IHDS. Pooled DOR for the HDS was 7.52 (95% confidence interval 3.75–15.11), sensitivity and specificity for HAD were estimated at 68.1% and 77.9%, and sensitivity and specificity for MND were estimated at 42.0% and 91.2%. Pooled DOR for the IHDS was 3.49 (2.12–5.73), sensitivity and specificity for HAD were 74.3% and 54.7%, and sensitivity and specificity for MND were 64.3% and 66.0%.
Conclusion
Both scales were low in accuracy. The literature is limited by the lack of a gold standard, and variation in estimates of accuracy is likely to be due to differences in reference standard. There is a lack of studies comparing both scales, and they have been studied in different populations, but the IHDS may be less specific than the HDS. These rapid tests are not recommended for diagnostic use, and further research is required to inform their use in asymptomatic screening.
doi:10.1371/journal.pone.0061826
PMCID: PMC3628906  PMID: 23613945
Epidemiology (Cambridge, Mass.)  2012;23(1):138-147.
Background
Respondent-driven sampling is a novel variant of link-tracing sampling for estimating the characteristics of hard-to-reach groups, such as HIV prevalence in sex-workers. Despite its use by leading health organizations, the performance of this method in realistic situations is still largely unknown. We evaluated respondent-driven sampling by comparing estimates from a respondent-driven sampling survey with total-population data.
Methods
Total-population data on age, tribe, religion, socioeconomic status, sexual activity and HIV status were available on a population of 2402 male household-heads from an open cohort in rural Uganda. A respondent-driven sampling (RDS) survey was carried out in this population, employing current methods of sampling (RDS sample) and statistical inference (RDS estimates). Analyses were carried out for the full RDS sample and then repeated for the first 250 recruits (small sample).
Results
We recruited 927 household-heads. Full and small RDS samples were largely representative of the total population, but both samples under-represented men who were younger, of higher socioeconomic status, and with unknown sexual activity and HIV status. Respondent-driven-sampling statistical-inference methods failed to reduce these biases. Only 31%-37% (depending on method and sample size) of RDS estimates were closer to the true population proportions than the RDS sample proportions. Only 50%-74% of respondent-driven-sampling bootstrap 95% confidence intervals included the population proportion.
Conclusions
Respondent-driven sampling produced a generally representative sample of this well-connected non-hidden population. However, current respondent-driven-sampling inference methods failed to reduce bias when it occurred. Whether the data required to remove bias and measure precision can be collected in a respondent-driven sampling survey is unresolved. Respondent-driven sampling should be regarded as a (potentially superior) form of convenience-sampling method, and caution is required when interpreting findings based on the sampling method.
doi:10.1097/EDE.0b013e31823ac17c
PMCID: PMC3277908  PMID: 22157309
PLoS ONE  2012;7(12):e53213.
Objective
Early HIV testing and diagnosis are paramount for increasing treatment initiation among children, necessary for their survival and improved health. However, uptake of pediatric HIV testing is low in high-prevalence areas. We present data on attitudes towards pediatric testing from a nationally representative survey in Zimbabwe.
Methods
All 18–24 year olds and a proportion of 25–49 year olds living in randomly selected enumeration areas from all ten Zimbabwe provinces were invited to self-complete an anonymous questionnaire on a personal digital assistant, and 16,719 people agreed to participate (75% of eligibles).
Results
Most people think children can benefit from HIV testing (91%), 81% of people who looked after children know how to access testing for their children and 92% would feel happier if their children were tested. Notably, 42% fear that, if tested, children may be discriminated against by some community members and 28% fear their children are HIV positive. People who fear discrimination against children who have tested for HIV are more likely than their counterparts to perceive their community as stigmatizing against HIV positive people (43% vs. 29%). They are also less likely to report positive attitudes to HIV themselves (49% vs. 74%). Only 28% think it is possible for children HIV-infected at birth to live into adolescence without treatment. Approximately 70% of people (irrespective of whether they are themselves parents) think HIV-infected children in their communities can access testing and treatment.
Conclusions
Pediatric HIV testing is the essential gateway to prevention and care services. Our data indicate positive attitudes to testing children, suggesting a conducive environment for increasing uptake of pediatric testing in Zimbabwe. However, there is a need to better understand the barriers to pediatric testing, such as stigma and discrimination, and address the gaps in knowledge regarding HIV/AIDS in children.
doi:10.1371/journal.pone.0053213
PMCID: PMC3532106  PMID: 23285268
PLoS ONE  2012;7(8):e43576.
Background
Our objective was to estimate for the first time the prevalence and determinants of human immunodeficiency virus type 1 (HIV-1) and sexually transmitted infections (STIs) among male migrants in India.
Methodology/Principal Findings
We conducted a multi-stage stratified probability sample survey of migrant (defined as not born in Surat city) men aged 18 to 49 years working in the diamond and textile industries in Surat city. Behavioural and biological data were collected. Biological data included laboratory diagnosed herpes simplex virus type 2 (HSV-2), syphilis, chlamydia, gonorrhoea, Trichomonas vaginalis (together defined as ‘any STI’) and HIV-1. Likely recently acquired STIs included chlamydia, gonorrhoea, T.vaginalis and syphilis with rapid plasma reagin ≥1∶8. The response rate was 77% (845/1099). Among 841 participants, HIV-1 prevalence was 1.0%, ‘any STI’ prevalence was 9.5% and 38.9% of these STIs were likely to have been recently acquired. Being a diamond worker, Surat resident for 10+ years and recent antibiotic use were each associated with higher odds of ‘any STI’ (aORs 1.83 (95% CI 1.09–3.09), 1.98 (95% CI 1.22–3.22) and 2.57 (95% CI 1 .17–5.64), respectively) after adjusting for the other two factors and age. The main study limitation was social desirability bias for self-reported sexual behaviour; STIs were diagnosed in some self-reported virgins.
Conclusions/Significance
HIV and STI prevalence were lower than expected, but prevention interventions remain necessary in Surat since almost 40% of STIs among participants were probably recently acquired and sentinel surveillance HIV prevalence remains high. The participants had a similar HIV prevalence to Surat antenatal clinic attendees, a proxy for the general population. This suggests migrants are not always at higher risk of HIV compared to the general population in their migration destination. Our findings highlight the need to contextualise research findings from a specific setting with other local information to guide HIV/STI prevention interventions.
doi:10.1371/journal.pone.0043576
PMCID: PMC3428366  PMID: 22952708
Biometrics  2012;68(1):129-137.
Summary
Two approaches commonly used to deal with missing data are multiple imputation (MI) and inverse-probability weighting (IPW). IPW is also used to adjust for unequal sampling fractions. MI is generally more efficient than IPW but more complex. Whereas IPW requires only a model for the probability that an individual has complete data (a univariate outcome), MI needs a model for the joint distribution of the missing data (a multivariate outcome) given the observed data. Inadequacies in either model may lead to important bias if large amounts of data are missing. A third approach combines MI and IPW to give a doubly robust estimator. A fourth approach (IPW/MI) combines MI and IPW but, unlike doubly robust methods, imputes only isolated missing values and uses weights to account for remaining larger blocks of unimputed missing data, such as would arise, e.g., in a cohort study subject to sample attrition, and/or unequal sampling fractions. In this article, we examine the performance, in terms of bias and efficiency, of IPW/MI relative to MI and IPW alone and investigate whether the Rubin’s rules variance estimator is valid for IPW/MI. We prove that the Rubin’s rules variance estimator is valid for IPW/MI for linear regression with an imputed outcome, we present simulations supporting the use of this variance estimator in more general settings, and we demonstrate that IPW/MI can have advantages over alternatives. IPW/MI is applied to data from the National Child Development Study.
doi:10.1111/j.1541-0420.2011.01666.x
PMCID: PMC3412287  PMID: 22050039
Marginal model; Missing at random; Survey weighting; 1958 British Birth Cohort
Journal of Affective Disorders  2012;138(3):277-286.
Background
Maternal common mental disorders are prevalent in low-resource settings and have far-reaching consequences for maternal and child health. We assessed the prevalence and predictors of psychological distress as a proxy for common mental disorders among mothers in rural Jharkhand and Orissa, eastern India, where over 40% of the population live below the poverty line and access to reproductive and mental health services is low.
Method
We screened 5801 mothers around 6 weeks after delivery using the Kessler-10 item scale, and identified predictors of distress using multiple hierarchical logistic regression.
Results
11.5% (95% CI: 10.7–12.3) of mothers had symptoms of distress (K10 score > 15). High maternal age, low asset ownership, health problems in the antepartum, delivery or postpartum periods, caesarean section, an unwanted pregnancy for the mother, small perceived infant size and a stillbirth or neonatal death were all independently associated with an increased risk of distress. The loss of an infant or an unwanted pregnancy increased the risk of distress considerably (AORs: 7.06 95% CI: 5.51–9.04 and 1.49, 95% CI: 1.12–1.97, respectively).
Limitations
We did not collect data on antepartum depression, domestic violence or a mother's past birth history, and were therefore unable to examine the importance of these factors as predictors of psychological distress.
Conclusions
Mothers living in underserved areas of India who experience infant loss, an unwanted pregnancy, health problems in the perinatal and postpartum periods and socio-economic disadvantage are at increased risk of distress and require access to reproductive healthcare with integrated mental health interventions.
doi:10.1016/j.jad.2012.01.029
PMCID: PMC3343258  PMID: 22342117
Common mental disorder; Maternal depression; India; Rural health
Background
Respondent-driven sampling(RDS) is an increasingly widely used variant of a link tracing design for recruiting hidden populations. The role of the spatial distribution of the target population has not been robustly examined for RDS. We examine patterns of recruitment by location, and how they may have biased an RDS study findings.
Methods
Total-population data were available on a range of characteristics on a population of 2402 male household-heads from an open cohort of 25 villages in rural Uganda. The locations of households were known a-priori. An RDS survey was carried out in this population, employing current RDS methods of sampling and statistical inference.
Results
There was little heterogeneity in the population by location. Data suggested more distant contacts were less likely to be reported, and therefore recruited, but if reported more distant contacts were as likely as closer contacts to be recruited. There was no evidence that closer proximity to a village meeting place was associated with probability of being recruited, however it was associated with a higher probability of recruiting a larger number of recruits. People living closer to an interview site were more likely to be recruited.
Conclusions
Household location affected the overall probability of recruitment, and the probability of recruitment by a specific recruiter. Patterns of recruitment do not appear to have greatly biased estimates in this study. The observed patterns could result in bias in more geographically heterogeneous populations. Care is required in RDS studies when choosing the network size question and interview site location(s).
doi:10.1186/1476-072X-10-56
PMCID: PMC3215957  PMID: 22008416
Background
Clinical researchers have often preferred to use a fixed effects model for the primary interpretation of a meta-analysis. Heterogeneity is usually assessed via the well known Q and I2 statistics, along with the random effects estimate they imply. In recent years, alternative methods for quantifying heterogeneity have been proposed, that are based on a 'generalised' Q statistic.
Methods
We review 18 IPD meta-analyses of RCTs into treatments for cancer, in order to quantify the amount of heterogeneity present and also to discuss practical methods for explaining heterogeneity.
Results
Differing results were obtained when the standard Q and I2 statistics were used to test for the presence of heterogeneity. The two meta-analyses with the largest amount of heterogeneity were investigated further, and on inspection the straightforward application of a random effects model was not deemed appropriate. Compared to the standard Q statistic, the generalised Q statistic provided a more accurate platform for estimating the amount of heterogeneity in the 18 meta-analyses.
Conclusions
Explaining heterogeneity via the pre-specification of trial subgroups, graphical diagnostic tools and sensitivity analyses produced a more desirable outcome than an automatic application of the random effects model. Generalised Q statistic methods for quantifying and adjusting for heterogeneity should be incorporated as standard into statistical software. Software is provided to help achieve this aim.
doi:10.1186/1471-2288-11-41
PMCID: PMC3102034  PMID: 21473747
Purpose
North American research finds increased sexual risk-taking among teenagers with same-sex partners, but understanding of underlying processes is limited. The research carried out in the United Kingdom compares teenagers' early sexual experiences according to same- or opposite-sex partner, focusing on unwanted sex in addition to risk-taking, and exploring underlying psychosocial differences.
Methods
Multivariate analyses combined self-reported data from two randomized control trials of school sex education programs (N = 10,250). Outcomes from sexually experienced teenagers (N = 3,766) were partner pressure to have first sex and subsequent regret, and sexual risk measures including pregnancy. Covariates included self-esteem, future expectations, substance use, and communication with mother.
Results
By the time of follow-up (mean age, 16), same-sex genital contact (touching or oral or anal) was reported by 2.3% of teenagers, with the majority also reporting heterosexual intercourse. A total of 39% reported heterosexual intercourse and no same-sex genital contact. Boys were more likely to report partner pressure (Odds ratio [OR] = 2.56, 95% confidence intervals [CI] = 1.29–5.08) and regret (OR = 2.32; 95% CI = 1.39–3.86) in relation to first same-sex genital contact than first heterosexual intercourse, but girls showed no differences according to partner type. Teenagers with bisexual behavior reported greater pregnancy or partner pregnancy risk than teenagers with exclusively opposite-sex partners (girls, OR = 4.51, 95% CI = 2.35–8.64; boys, OR = 4.43, 95% CI = 2.41–8.14), partially reduced by attitudinal and behavioral differences.
Conclusions
This UK study confirms greater reporting of sexual risk-taking among teenagers with same-sex partners, and suggests that boys in this group are vulnerable to unwanted sex. It suggests limitations to the interpretation of differences, in terms of psychosocial risk factors common to all adolescents.
doi:10.1016/j.jadohealth.2010.05.010
PMCID: PMC3013202  PMID: 21185521
Sexual minority; Adolescence; Sexual behavior

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