Site staff perspectives on communicating trial results to participants: Cost and feasibility results from the Show RESPECT cluster randomised, factorial, mixed-methods trial.

BACKGROUND/AIMS: Sharing trial results with participants is an ethical imperative but often does not happen. Show RESPECT (ISRCTN96189403) tested ways of sharing results with participants in an ovarian cancer trial (ISRCTN10356387). Sharing results via a printed summary improved patient satisfaction. Little is known about staff experience and the costs of communicating results with participants. We report the costs of communication approaches used in Show RESPECT and the views of site staff on these approaches. METHODS: We allocated 43 hospitals (sites) to share results with trial participants through one of eight intervention combinations (2 × 2 × 2 factorial; enhanced versus basic webpage, printed summary versus no printed summary, email list invitation versus no invitation). Questionnaires elicited data from staff involved in sharing results. Open- and closed-ended questions covered resources used to share results and site staff perspectives on the approaches used. Semi-structured interviews were conducted. Interview and free-text data were analysed thematically. The mean additional site costs per participant from each intervention were estimated jointly as main effects by linear regression. RESULTS: We received questionnaires from 68 staff from 41 sites and interviewed 11 site staff. Sites allocated to the printed summary had mean total site costs of sharing results £13.71/patient higher (95% confidence interval (CI): -3.19, 30.60; p = 0.108) than sites allocated no printed summary. Sites allocated to the enhanced webpage had mean total site costs £1.91/patient higher (95% CI: -14, 18.74; p = 0.819) than sites allocated to the basic webpage. Sites allocated to the email list had costs £2.87/patient lower (95% CI: -19.70, 13.95; p = 0.731) than sites allocated to no email list. Most of these costs were staff time for mailing information and handling patients' queries. Most site staff reported no concerns about how they had shared results (88%) and no challenges (76%). Most (83%) found it easy to answer queries from patients about the results and thought the way they were allocated to share results with participants would be an acceptable standard approach (76%), with 79% saying they would follow the same approach for future trials. There were no significant effects of the randomised interventions on these outcomes. Site staff emphasised the importance of preparing patients to receive the results, including giving opt-in/opt-out options, and the need to offer further support, particularly if the results could confuse or distress some patients. CONCLUSIONS: Adding a printed summary to a webpage (which significantly improved participant satisfaction) may increase costs to sites by ~£14/patient, which is modest in relation to the cost of trials. The Show RESPECT communication interventions were feasible to implement. This information could help future trials ensure they have sufficient resources to share results with participants.

How did the COVID-19 pandemic affect access to condoms, chlamydia and HIV testing, and cervical cancer screening at a population level in Britain? (Natsal-COVID).

OBJECTIVES: To investigate how differential access to key interventions to reduce STIs, HIV and their sequelae changed during the COVID-19 pandemic. METHODS: British participants (18-59 years) completed a cross-sectional web survey 1 year (March-April 2021) after the initial lockdown in Britain. Quota-based sampling and weighting resulted in a quasi-representative population sample. We compared Natsal-COVID data with Natsal-3, a household-based probability sample cross-sectional survey (16-74 years) conducted in 2010-2012. Reported unmet need for condoms because of the pandemic and uptake of chlamydia testing/HIV testing/cervical cancer screening were analysed among sexually experienced participants (18-44 years) (n=3869, Natsal-COVID; n=8551, Natsal-3). ORs adjusted for age and other potential confounders describe associations with demographic and behavioural factors. RESULTS: In 2021, 6.9% of women and 16.2% of men reported unmet need for condoms because of the pandemic. This was more likely among participants: aged 18-24 years, of black or black British ethnicity, and reporting same-sex sex (past 5 years) or one or more new relationships (past year). Chlamydia and HIV testing were more commonly reported by younger participants, those reporting condomless sex with new sexual partners and men reporting same-sex partners; a very similar distribution to 10 years previously (Natsal-3). However, there were differences during the pandemic, including stronger associations with chlamydia testing for men reporting same-sex partners; with HIV testing for women reporting new sexual partners and with cervical screening among smokers. CONCLUSIONS: Our study suggests differential access to key primary and secondary STI/HIV prevention interventions continued during the first year of the COVID-19 pandemic. However, there was not strong evidence that differential access has changed during the pandemic when compared with 2010-2012. While the pandemic might not have exacerbated inequalities in access to primary and secondary prevention, it is clear that large inequalities persisted, typically among those at greatest STI/HIV risk.

Initial impacts of the COVID-19 pandemic on sexual and reproductive health service use and unmet need in Britain: findings from a quasi-representative survey (Natsal-COVID).

BACKGROUND: The COVID-19 pandemic has affected sexual and reproductive health (SRH) service use and unmet need, but the impact is unknown. We aimed to determine the proportion of participants reporting sexual risk behaviours, SRH service use and unmet need, and to assess remote sexually transmitted infection (STI) testing service use after the first national lockdown in Britain. METHODS: We used data from the National Surveys of Sexual Attitudes and Lifestyles (Natsal)-COVID cross-sectional, quasi-representative web survey (Natsal-COVID Wave 1). Adults aged 18-59 years who resided in England, Scotland, or Wales completed the survey between July 29 and Aug 10, 2020, which included questions about the approximate 4-month period after announcement of the initial lockdown in Britain (March 23, 2020). Quota-based sampling and weighting were used to achieve a quasi-representative population sample. Participants aged 45-59 years were excluded from services analysis due to low rates of SRH service use. Among individuals aged 18-44 years, we estimated reported SRH service use and inability to access, and calculated age-adjusted odds ratios (aORs) among sexually experienced individuals (those reporting any sexual partner in their lifetime) and sexually active individuals (those reporting any sexual partner in the past year). Unweighted denominators and weighted estimates are presented hereafter. FINDINGS: 6654 individuals had complete interviews and were included in the analysis. Among 3758 participants aged 18-44 years, 82·0% reported being sexually experienced, and 73·7% reported being sexually active. 20·8% of sexually experienced participants aged 18-44 years reported using SRH services in the 4-month period. Overall, 9·7% of 3108 participants (9·5% of men; 9·9% of women) reported being unable to use a service they needed, although of the participants who reported trying but not being able to use a SRH service at least once, 76·4% of participants also reported an instance of successful use. 5·9% of 1221 sexually active men and 3·6% of 1560 sexually active women reported use of STI-related services and 14·8% of 1728 sexually experienced women reported use of contraceptive services, with SRH service use highest among individuals aged 18-24 years. Sexually active participants reporting condomless sex with new partners since lockdown were much more likely to report using STI-related services than those who did not report condomless sex (aOR 23·8 [95% CI 11·6-48·9]) for men, 10·5 [3·9-28·2] for women) and, among men, were also more likely to have an unsuccessful attempt at STI-service use (aOR 13·3 [5·3-32·9]). Among 106 individuals who reported using STI testing services, 64·4% accessed services remotely (telephone, video, or online). Among 2581 women aged 25-59 years, 2·4% reported cervical screening compared with an estimated 6% in a comparable 4-month period before the pandemic. INTERPRETATION: Many people accessed SRH care during the initial lockdown; however, young people and those reporting sexual risk behaviours reported difficulties in accessing services and thus such services might need to address a backlog of need. FUNDING: Wellcome Trust, The Economic and Social Research Council, The National Institute for Health Research, Medical Research Council/Chief Scientist Office and Public Health Sciences Unit, and UCL Coronavirus Response Fund.

Testing approaches to sharing trial results with participants: The Show RESPECT cluster randomised, factorial, mixed methods trial.

BACKGROUND: Sharing trial results with participants is an ethical imperative but often does not happen. We tested an Enhanced Webpage versus a Basic Webpage, Mailed Printed Summary versus no Mailed Printed Summary, and Email List Invitation versus no Email List Invitation to see which approach resulted in the highest patient satisfaction with how the results were communicated. METHODS AND FINDINGS: We carried out a cluster randomised, 2 by 2 by 2 factorial, nonblinded study within a trial, with semistructured qualitative interviews with some patients (ISRCTN96189403). Each cluster was a UK hospital participating in the ICON8 ovarian cancer trial. Interventions were shared with 384 ICON8 participants who were alive and considered well enough to be contacted, at 43 hospitals. Hospitals were allocated to share results with participants through one of the 8 intervention combinations based on random permutation within blocks of 8, stratified by number of participants. All interventions contained a written plain English summary of the results. The Enhanced Webpage also contained a short video. Both the Enhanced Webpage and Email contained links to further information and support. The Mailed Printed Summary was opt-out. Follow-up questionnaires were sent 1 month after patients had been offered the interventions. Patients' reported satisfaction was measured using a 5-point scale, analysed by ordinal logistic regression estimating main effects for all 3 interventions, with random effects for site, restricted to those who reported receiving the results and assuming no interaction. Data collection took place in 2018 to 2019. Questionnaires were sent to 275/384 randomly selected participants and returned by 180: 90/142 allocated Basic Webpage, 90/133 Enhanced Webpage; 91/141 no Mailed Printed Summary, 89/134 Mailed Printed Summary; 82/129 no Email List Invitation, 98/146 Email List Invitation. Only 3 patients opted out of receiving the Mailed Printed Summary; no patients signed up to the email list. Patients' satisfaction was greater at sites allocated the Mailed Printed Summary, where 65/81 (80%) were quite or very satisfied compared to sites with no Mailed Printed Summary 39/64 (61%), ordinal odds ratio (OR) = 3.15 (1.66 to 5.98, p < 0.001). We found no effect on patient satisfaction from the Enhanced Webpage, OR = 1.47 (0.78 to 2.76, p = 0.235) or Email List Invitation, OR = 1.38 (0.72 to 2.63, p = 0.327). Interviewees described the results as interesting, important, and disappointing (the ICON8 trial found no benefit). Finding out the results made some feel their trial participation had been more worthwhile. Regardless of allocated group, patients who received results generally reported that the information was easy to understand and find, were glad and did not regret finding out the results. The main limitation of our study is the 65% response rate. CONCLUSIONS: Nearly all respondents wanted to know the results and were glad to receive them. Adding an opt-out Mailed Printed Summary alongside a webpage yielded the highest reported satisfaction. This study provides evidence on how to share results with other similar trial populations. Further research is needed to look at different results scenarios and patient populations. TRIAL REGISTRATION: ISRCTN: ISRCTN96189403.

Imiquimod versus podophyllotoxin, with and without human papillomavirus vaccine, for anogenital warts: the HIPvac factorial RCT.

BACKGROUND: The comparative efficacy, and cost-effectiveness, of imiquimod or podophyllotoxin cream, either alone or in combination with the quadrivalent HPV vaccine (Gardasil®, Merck Sharp & Dohme Corp., Merck & Co., Inc., Whitehouse Station, NJ, USA) in the treatment and prevention of recurrence of anogenital warts is not known. OBJECTIVE: The objective was to compare the efficacy of imiquimod and podophyllotoxin creams to treat anogenital warts and to assess whether or not the addition of quadrivalent human papillomavirus vaccine increases wart clearance or prevention of recurrence. DESIGN: A randomised, controlled, multicentre, partially blinded factorial trial. Participants were randomised equally to four groups, combining either topical treatment with quadrivalent human papillomavirus vaccine or placebo. Randomisation was stratified by gender, a history of previous warts and human immunodeficiency virus status. There was an accompanying economic evaluation, conducted from the provider perspective over the trial duration. SETTING: The setting was 22 sexual health clinics in England and Wales. PARTICIPANTS: Participants were patients with a first or repeat episode of anogenital warts who had not been treated in the previous 3 months and had not previously received quadrivalent human papillomavirus vaccine. INTERVENTIONS: Participants were randomised to 5% imiquimod cream (Aldara®; Meda Pharmaceuticals, Takeley, UK) for up to 16 weeks or 0.15% podophyllotoxin cream (Warticon®; GlaxoSmithKlein plc, Brentford, UK) for 4 weeks, which was extended to up to 16 weeks if warts persisted. Participants were simultaneously randomised to quadrivalent human papillomavirus vaccine (Gardasil) or saline control at 0, 8 and 24 weeks. Cryotherapy was permitted after week 4 at the discretion of the investigator. MAIN OUTCOME MEASURES: The main outcome measures were a combined primary outcome of wart clearance at week 16 and remaining wart free at week 48. Efficacy analysis was by logistic regression with multiple imputation for missing follow-up values; economic evaluation considered the costs per quality-adjusted life-year. RESULTS: A total of 503 participants were enrolled and attended at least one follow-up visit. The mean age was 31 years, 66% of participants were male (24% of males were men who have sex with men), 50% had a previous history of warts and 2% were living with human immunodeficiency virus. For the primary outcome, the adjusted odds ratio for imiquimod cream versus podophyllotoxin cream was 0.81 (95% confidence interval 0.54 to 1.23), and for quadrivalent human papillomavirus vaccine versus placebo, the adjusted odds ratio was 1.46 (95% confidence interval 0.97 to 2.20). For the components of the primary outcome, the adjusted odds ratio for wart free at week 16 for imiquimod versus podophyllotoxin was 0.77 (95% confidence interval 0.52 to 1.14) and for quadrivalent human papillomavirus vaccine versus placebo was 1.30 (95% confidence interval 0.89 to 1.91). The adjusted odds ratio for remaining wart free at 48 weeks (in those who were wart free at week 16) for imiquimod versus podophyllotoxin was 0.98 (95% confidence interval 0.54 to 1.78) and for quadrivalent human papillomavirus vaccine versus placebo was 1.39 (95% confidence interval 0.73 to 2.63). Podophyllotoxin plus quadrivalent human papillomavirus vaccine had inconclusive cost-effectiveness compared with podophyllotoxin alone. LIMITATIONS: Hepatitis A vaccine as control was replaced by a saline placebo in a non-identical syringe, administered by someone outside the research team, for logistical reasons. Sample size was reduced from 1000 to 500 because of slow recruitment and other delays. CONCLUSIONS: A benefit of the vaccine was not demonstrated in this trial. The odds of clearance at week 16 and remaining clear at week 48 were 46% higher with vaccine, and consistent effects were seen for both wart clearance and recurrence separately, but these differences were not statistically significant. Imiquimod and podophyllotoxin creams had similar efficacy for wart clearance, but with a wide confidence interval. The trial results do not support earlier evidence of a lower recurrence with use of imiquimod than with use of podophyllotoxin. Podophyllotoxin without quadrivalent human papillomavirus vaccine is the most cost-effective strategy at the current vaccine list price. A further larger trial is needed to definitively investigate the effect of the vaccine; studies of the immune response in vaccine recipients are needed to investigate the mechanism of action. TRIAL REGISTRATION: Current Controlled Trials. Current Controlled Trials ISRCTN32729817 and EudraCT 2013-002951-14. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 47. See the NIHR Journals Library website for further project information.

The HIPvac [Human papillomavirus infection: a randomised controlled trial of Imiquimod cream (5%) versus Podophyllotoxin cream (0.15%), in combination with quadrivalent human papillomavirus or control vaccination in the treatment and prevention of recurrence of anogenital warts] trial compared two commonly used creams to treat genital warts: 0.15% podophyllotoxin cream (Warticon^®; GlaxoSmithKlein plc, Brentford, UK) and 5% imiquimod cream (Aldara^®; Meda Pharmaceuticals, Takeley, UK). It also investigated whether or not a vaccine used to prevent human papillomavirus infection, quadrivalent human papillomavirus vaccine (Gardasil^®, Merck Sharp & Dohme Corp., Merck & Co., Inc., Whitehouse Station, NJ, USA), could help treat warts or prevent them from coming back in patients whose warts had been cleared. The HIPvac trial was a randomised controlled trial involving 503 patients with warts attending sexual health clinics in England and Wales. The creams and the vaccine were well tolerated; there was some soreness where the cream was applied, but no unexpected side effects. When deciding which treatment was better, we looked at whether or not the warts had cleared by 16 weeks after starting treatment and, if cleared, whether or not they returned by 48 weeks. We compared the creams against each other, and the addition of vaccine against no vaccine (a placebo injection). Patients were allowed to have cryotherapy (freezing treatment) as well, if the investigator advised this. We also calculated the value for money of each type of treatment. The two creams were very similar in how well they worked to clear the warts. One difference was that podophyllotoxin cream worked slightly quicker. The number of patients given cryotherapy was about the same for both types of cream. We had expected that recurrence of warts after treatment with imiquimod cream might be less than after treatment with podophyllotoxin cream, but, in fact, the two creams were similar. Quadrivalent human papillomavirus vaccine did not improve clearance of warts or reduce the chance of recurrence, but the result remains inconclusive. If we had been able to recuit 1000 participants as originally planned, we might have been able to be more certain about whether there was any benefit of vaccination. Further research would be needed to investigate any possible effect. The two creams offered similar value for money in treating warts. Giving patients the vaccine in addition to the cream is not good value for money at its current list price, given the uncertainty about the benefit it offers.

Human papillomavirus infection: protocol for a randomised controlled trial of imiquimod cream (5%) versus podophyllotoxin cream (0.15%), in combination with quadrivalent human papillomavirus or control vaccination in the treatment and prevention of recurrence of anogenital warts (HIPvac trial).

BACKGROUND: Anogenital warts are the second most common sexually transmitted infection diagnosed in sexual health services in England. About 90% of genital warts are caused by human papillomavirus (HPV) types 6 or 11, and half of episodes diagnosed are recurrences. The best and most cost-effective treatment for patients with anogenital warts is unknown. The commonly used treatments are self-administered topical agents, podophyllotoxin (0.15% cream) or imiquimod (5% cream), or cryotherapy with liquid nitrogen. Quadrivalent HPV (qHPV) vaccination is effective in preventing infection, and disease, but whether it has any therapeutic effect is not known. METHODS AND DESIGN: To investigate the efficacy of clearance and prevention of recurrence of external anogenital warts by topical treatments, podophyllotoxin 0.15% cream or imiquimod 5% cream, in combination with a three-dose regimen of qHPV or control vaccination. 500 adult patients presenting with external anogenital warts with either a first or subsequent episode of anogenital warts will be entered into this randomised, controlled partially blinded 2 × 2 factorial trial. DISCUSSION: The trial is expected to provide the first high-quality evidence of the comparative efficacy and cost-effectiveness of the two topical treatments in current use, as well as investigate the potential benefit of HPV vaccination, in the management of anogenital warts. TRIAL REGISTRATION: The trial was registered prior to starting recruitment under the following reference numbers: International Standard Randomized Controlled Trial Number (ISRCTN) Registry - ISRCTN32729817 (registered 25 July 2014); European Union Clinical Trials Register (EudraCT) - 2013-002951-14 (registered 26 June 2013).

Is "Sexual Competence" at First Heterosexual Intercourse Associated With Subsequent Sexual Health Status?

The timing of first sexual intercourse is often defined in terms of chronological age, with particular focus on "early" first sex. Arguments can be made for a more nuanced concept of readiness and appropriateness of timing of first intercourse. Using data from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3), conducted in 2010-2012, this study examined whether a context-based measure of first intercourse-termed sexual competence-was associated with subsequent sexual health in a population-based sample of 17-to 24-year-olds residing in Britain (n = 2,784). Participants were classified as "sexually competent" at first intercourse if they reported the following four criteria: contraceptive protection, autonomy of decision (not due to external influences), that both partners were "equally willing," and that it happened at the "right time." A lack of sexual competence at first intercourse was independently associated with testing positive for human papillomavirus (HPV) at interview; low sexual function in the past year; and among women only, reported sexually transmitted infection (STI) diagnosis ever; unplanned pregnancy in the past year; and having ever experienced nonvolitional sex. These findings provide empirical support for defining the nature of first intercourse with reference to contextual aspects of the experience, as opposed to a sole focus on chronological age at occurrence.

Medicated sex in Britain: evidence from the third National Survey of Sexual Attitudes and Lifestyles.

OBJECTIVES: To describe the prevalence of medication use to assist sexual performance in Britain and to identify associated factors. METHODS: Cross-sectional probability sample, undertaken in 2010-2012, of 15 162 people aged 16-74 years, resident in Britain, of whom, 5617 men and 8095 women reported sexual experience (ever) and 4817 men were sexually-active (reported sex in the last year). RESULTS: Ever use of medication to assist sexual performance (medicated sex) was more commonly reported by men than women (12.9% (95% CI 11.9% to 13.9%) vs 1.9% (95% CI 1.7% to 2.3%)) and associated with older age in men and younger age in women. It was associated with reporting smoking, and use of alcohol and recreational drugs, as well as unsafe sex (≥2 partners and no condom use in the last year) in both men and women. Among men, the proportion reporting medicated sex in the last year was higher among those reporting erectile difficulties (ED) than those not doing so (28.4% (95% CI 24.4% to 32.8%) vs 4.1% (95% CI 3.4% to 4.9%)). In all men, medicated sex was associated with more frequent sexual activity, meeting a partner on the internet, unsafe sex and recent sexually transmitted infections diagnosis; associations that persisted after adjusting for same-sex behaviour and ED. However, there were significant interactions with reporting ED, indicating that among men with ED, medicated sex is not associated with same-sex behaviour and ever use of recreational drugs. CONCLUSIONS: A substantial minority of people in Britain report medicated sex, and the association between medicated sex and risky sexual behaviour is not confined to high-risk groups.

Examining the potential public health benefit of offering STI testing to men in amateur football clubs: evidence from cross-sectional surveys.

BACKGROUND: In Britain, young people continue to bear the burden of sexually transmitted infections (STIs) so efforts are required, especially among men, to encourage STI testing. The SPORTSMART study trialled an intervention that sought to achieve this by offering chlamydia and gonorrhoea test-kits to men attending amateur football clubs between October and December 2012. With football the highest participation team sport among men in England, this paper examines the potential public health benefit of offering STI testing to men in this setting by assessing their sociodemographic characteristics, sexual behaviours, and healthcare behaviour and comparing them to men in the general population. METHODS: Data were collected from 192 (male) members of 6 football clubs in London, United Kingdom, aged 18-44 years via a 20-item pen-and-paper self-completion questionnaire administered 2 weeks after the intervention. These were compared to data collected from 409 men of a similar age who were resident in London when interviewed during 2010-2012 for the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3), a national probability survey that used computer-assisted-personal-interviewing with computer-assisted-self-interview. Age standardisation and multivariable regression were used to account for sociodemographic differences between the surveys. RESULTS: Relative to men in the general population, SPORTSMART men were younger (32.8 % vs. 21.7 % aged under 25 y), and more likely to report (all past year) at least 2 sexual partners (adjusted odds ratio, AOR: 3.25, 95 % CI: 2.15-4.92), concurrent partners (AOR: 2.05, 95 % CI: 1.39-3.02), and non-use of condoms (AOR: 2.17, 95 % CI: 1.39-3.41). No difference was observed in STI/HIV risk perception (AOR for reporting "not at all at risk" of STIs: 1.25, 95 % CI: 0.76-2.04; of HIV: AOR: 1.54, 95 % CI: 0.93-2.55), nor in reporting STI testing in the past year (AOR: 0.83, 95 % CI: 0.44-1.54), which was reported by only one in six men. CONCLUSIONS: Relative to young men in the general population, football club members who completed the SPORTSMART survey reported greater sexual risk behaviour but similar STI/HIV risk perception and STI testing history. Offering STI testing in amateur football clubs may therefore widen access to STI testing and health promotion messages for men at higher STI risk, which, given the minority currently testing and the popularity of football in England, should yield both individual and public health benefit.

High-Risk Human Papillomavirus (HPV) Infection and Cervical Cancer Prevention in Britain: Evidence of Differential Uptake of Interventions from a Probability Survey.

BACKGROUND: The third British National Survey of Sexual Attitudes and Lifestyles (Natsal-3) provides an opportunity to explore high-risk human papillomavirus (HR-HPV) and uptake of cervical screening and HPV vaccination in the general population. METHODS: Natsal-3, a probability sample survey of men and women ages 16 to 74, resident in Britain, interviewed 8,869 women in 2010 to 2012. We explored risk factors for HR-HPV (in urine from 2,569 sexually experienced women ages 16 to 44), nonattendance for cervical screening in the past 5 years, and noncompletion of HPV catch-up vaccination. RESULTS: HR-HPV was associated with increasing numbers of lifetime partners, younger age, increasing area-level deprivation, and smoking. Screening nonattendance was associated with younger and older age, increasing area-level deprivation (age-adjusted OR 1.91, 95% confidence interval, 1.48-2.47 for living in most vs. least deprived two quintiles), Asian/Asian British ethnicity (1.96, 1.32-2.90), smoking (1.97, 1.57-2.47), and reporting no partner in the past 5 years (2.45, 1.67-3.61 vs. 1 partner) but not with HR-HPV (1.35, 0.79-2.31). Lower uptake of HPV catch-up vaccination was associated with increasing area-level deprivation, non-white ethnicity, smoking, and increasing lifetime partners. CONCLUSIONS: Socioeconomic markers and smoking were associated with HR-HPV positivity, nonattendance for cervical screening, and noncompletion of catch-up HPV vaccination. IMPACT: The cervical screening program needs to engage those missing HPV catch-up vaccination to avoid a potential widening of cervical cancer disparities in these cohorts. As some screening nonattenders are at low risk for HR-HPV, tailored approaches may be appropriate to increase screening among higher-risk women.

Exploring the costs and outcomes of sexually transmitted infection (STI) screening interventions targeting men in football club settings: preliminary cost-consequence analysis of the SPORTSMART pilot randomised controlled trial.

BACKGROUND: The objective of this study was to compare the costs and outcomes of two sexually transmitted infection (STI) screening interventions targeted at men in football club settings in England, including screening promoted by team captains. METHODS: A comparison of costs and outcomes was undertaken alongside a pilot cluster randomised control trial involving three trial arms: (1) captain-led and poster STI screening promotion; (2) sexual health advisor-led and poster STI screening promotion and (3) poster-only STI screening promotion (control/comparator). For all study arms, resource use and cost data were collected prospectively. RESULTS: There was considerable variation in uptake rates between clubs, but results were broadly comparable across study arms with 50% of men accepting the screening offer in the captain-led arm, 67% in the sexual health advisor-led arm and 61% in the poster-only control arm. The overall costs associated with the intervention arms were similar. The average cost per player tested was comparable, with the average cost per player tested for the captain-led promotion estimated to be £88.99 compared with £88.33 for the sexual health advisor-led promotion and £81.87 for the poster-only (control) arm. CONCLUSIONS: Costs and outcomes were similar across intervention arms. The target sample size was not achieved, and we found a greater than anticipated variability between clubs in the acceptability of screening, which limited our ability to estimate acceptability for intervention arms. Further evidence is needed about the public health benefits associated with screening interventions in non-clinical settings so that their cost-effectiveness can be fully evaluated.

The SPORTSMART study: a pilot randomised controlled trial of sexually transmitted infection screening interventions targeting men in football club settings.

BACKGROUND: Uptake of chlamydia screening by men in England has been substantially lower than by women. Non-traditional settings such as sports clubs offer opportunities to widen access. Involving people who are not medically trained to promote screening could optimise acceptability. METHODS: We developed two interventions to explore the acceptability and feasibility of urine-based sexually transmitted infection (STI) screening interventions targeting men in football clubs. We tested these interventions in a pilot cluster randomised control trial. Six clubs were randomly allocated, two to each of three trial arms: team captain-led and poster STI screening promotion; sexual health adviser-led and poster STI screening promotion; and poster-only STI screening promotion (control/comparator). Primary outcome was test uptake. RESULTS: Across the three arms, 153 men participated in the trial and 90 accepted the offer of screening (59%, 95% CI 35% to 79%). Acceptance rates were broadly comparable across the arms: captain-led: 28/56 (50%); health professional-led: 31/46 (67%); and control: 31/51 (61%). However, rates varied appreciably by club, precluding formal comparison of arms. No infections were identified. Process evaluation confirmed that interventions were delivered in a standardised way but the control arm was unintentionally 'enhanced' by some team captains actively publicising screening events. CONCLUSIONS: Compared with other UK-based community screening models, uptake was high but gaining access to clubs was not always easy. Use of sexual health advisers and team captains to promote screening did not appear to confer additional benefit over a poster-promoted approach. Although the interventions show potential, the broader implications of this strategy for UK male STI screening policy require further investigation.

Should Tyrosine Kinase Inhibitors Be Considered for Advanced Non-Small-Cell Lung Cancer Patients With Wild Type EGFR? Two Systematic Reviews and Meta-Analyses of Randomized Trials.

Guidance concerning tyrosine kinase inhibitors (TKIs) for patients with wild type epidermal growth factor receptor (EGFR) and advanced non-small-cell lung cancer (NSCLC) after first-line treatment is unclear. We assessed the effect of TKIs as second-line therapy and maintenance therapy after first-line chemotherapy in two systematic reviews and meta-analyses, focusing on patients without EGFR mutations. Systematic searches were completed and data extracted from eligible randomized controlled trials. Three analytical approaches were used to maximize available data. Fourteen trials of second-line treatment (4388 patients) were included. Results showed the effect of TKIs on progression-free survival (PFS) depended on EGFR status (interaction hazard ratio [HR], 2.69; P = .004). Chemotherapy benefited patients with wild type EGFR (HR, 1.31; P < .0001), TKIs benefited patients with mutations (HR, 0.34; P = .0002). Based on 12 trials (85% of randomized patients) the benefits of TKIs on PFS decreased with increasing proportions of patients with wild type EGFR (P = .014). Six trials of maintenance therapy (2697 patients) were included. Results showed that although the effect of TKIs on PFS depended on EGFR status (interaction HR, 3.58; P < .0001), all benefited from TKIs (wild type EGFR: HR, 0.82; P = .01; mutated EGFR: HR, 0.24; P < .0001). There was a suggestion that benefits of TKIs on PFS decreased with increasing proportions of patients with wild type EGFR (P = .11). Chemotherapy should be standard second-line treatment for patients with advanced NSCLC and wild type EGFR. TKIs might be unsuitable for unselected patients. TKIs appear to benefit all patients compared with no active treatment as maintenance treatment, however, direct comparisons with chemotherapy are needed.

Uptake of the HPV vaccination programme in England: a cross-sectional survey of young women attending sexual health services.

OBJECTIVES: The U.K. human papilloma virus (HPV) vaccination programme requires 80% uptake to have a significant impact on cervical cancer rates. Uptake in the first three years of the programme was 66%. We report the results of a cross-sectional survey of young women attending sexual health services (SHS) in England, reviewing HPV vaccination uptake and prevalence of HPV-related risk factors. METHODS: An anonymous questionnaire surveyed women aged 13-19 attending 19 hospital-based and 13 community-based SHS across England, March-August 2011. Data were analysed using multiple logistic regression. RESULTS: 2247 questionnaires were completed. Compared with national data, respondents had higher smoking rates (48% vs. 14% of 15 year olds), coitarche under-16 (52% vs. 38%), previous sexually transmitted infections (STIs) (25% vs. 4%) and a higher proportion not in education, employment or training (NEETs) (8% vs. 2% of 16 year olds). Seventy-four per cent had been offered the vaccination, with significantly lower offer rates in London, non-white ethnicities, 17-19 year olds, NEETs, smokers and those with previous STIs (all p<0.05 in multivariate analysis). Sixty-five per cent of those offered, completed, with significantly lower completion rates in London, non-white ethnicities, 17-19 year olds, NEETs, smokers and those with previous STIs (all p<0.05 in multivariate analysis). Overall completion rate was 47%. CONCLUSIONS: We observed lower vaccination offer and completion rates and higher prevalence of HPV-related risk factors compared with national data. The highest risk individuals were the least likely to have been offered or to have completed the course. This survey highlights an opportunity for primary prevention by routinely offering the HPV vaccine to eligible women attending SHS.

A declining CD4 count and diagnosis of HIV-associated Hodgkin lymphoma: do prior clinical symptoms and laboratory abnormalities aid diagnosis?

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.

Methodology of the third British National Survey of Sexual Attitudes and Lifestyles (Natsal-3).

BACKGROUND: Data from the first two National Surveys of Sexual Attitudes and Lifestyles, carried out in 1990-1991 (Natsal-1) and 1999-2001 (Natsal-2), have been extensively used to inform sexual health policy in Britain over the past two decades. Natsal-3 was carried out from September 2010 to August 2012 in order to provide up-to-date measures of sexual lifestyles and to extend the scope of the previous studies by including an older age group (up to 74 years), an extended range of topics and biological measures. METHODS: We describe the methods used in Natsal-3, which surveyed the general population in Britain aged 16-74 years (with oversampling of younger adults aged 16-34 years). RESULTS: Overall, 15 162 interviews were completed, with a response rate of 57.7% and a cooperation rate of 65.8%. The response rate for the boost sample of ages 16-34 years was 64.8%, only marginally lower than the 65.4% achieved for Natsal-2, which surveyed a similar age range (16-44). The data were weighted by age, gender and region to reduce possible bias. Comparisons with census data show the weighted sample to provide good representation on a range of respondent characteristics. The interview involved a combination of face-to-face and self-completion components, both carried out on computer. Urine samples from 4550 sexually-experienced participants aged 16-44 years were tested for a range of STIs. Saliva samples from 4128 participants aged 18-74 years were tested for testosterone. CONCLUSIONS: Natsal-3 provides a high quality dataset that can be used to examine trends in sexual attitudes and behaviours over the past 20 years.

Consistency in reporting sensitive sexual behaviours in Britain: change in reporting bias in the second and third National Surveys of Sexual Attitudes and Lifestyles (Natsal-2 and Natsal-3).

OBJECTIVES: Britain's second National Survey of Sexual Attitudes and Lifestyles (Natsal-2) was conducted in 1999-2001 and the third (Natsal-3) was conducted in 2010-2012 to update prevalence estimates of sexual behaviours and assess changes over time. We investigated whether there was a change in reporting bias between these two cross-sectional surveys. METHODS: We analysed data from the 'common birth cohort' of participants born during 1956-1983, who were eligible to take part in Natsal-2 (n=10 764) and Natsal-3 (n=6907). We compared estimates for outcomes that occurred before Natsal-2 and expected these to be consistent between surveys if no change in reporting bias had occurred. RESULTS: A greater proportion of non-white men and women were in Natsal-3 consistent with demographic changes in Britain. Reporting behaviours was largely consistent between surveys for men. Fewer women in Natsal-3 reported early first intercourse or having child(ren) before age 20; they were also more likely to report not discussing sex with their parents at age 14. Men and women in Natsal-3 were more likely to report tolerant attitudes towards same-sex partnerships but less tolerance towards unfaithfulness in marriage and one-night-stands. CONCLUSIONS: We found little evidence of change in reporting bias among men since Natsal-2. Among women, a modest change in reporting bias was observed for a small number of experiences, possibly due to changes in participation, social acceptability and methodological differences between surveys. Changes in the reporting of sexual behaviours and attitudes over time observed in the wider Natsal-3 study are therefore likely to largely reflect real changes in the population.

Prevalence, risk factors, and uptake of interventions for sexually transmitted infections in Britain: findings from the National Surveys of Sexual Attitudes and Lifestyles (Natsal).

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.

The prevalence of unplanned pregnancy and associated factors in Britain: findings from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3).

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.