Search

Background: Britain’s National Surveys of Sexual Attitudes and Lifestyles (Natsal) have been undertaken decennially since 1990 and provide a key data source underpinning sexual and reproductive health (SRH) policy. The COVID-19 pandemic disrupted many aspects of sexual lifestyles, triggering an urgent need for population-level data on sexual behaviour, relationships, and service use at a time when gold-standard in-person, household-based surveys with probability sampling were not feasible. We designed the Natsal-COVID study to understand the impact of COVID-19 on the nation’s SRH and assessed the sample representativeness. Methods: Natsal-COVID Wave 1 data collection was conducted four months (29/7-10/8/2020) after the announcement of Britain’s first national lockdown (23/03/2020). This was an online web-panel survey administered by survey research company, Ipsos MORI. Eligible participants were resident in Britain, aged 18-59 years, and the sample included a boost of those aged 18-29. Questions covered participants’ sexual behaviour, relationships, and SRH service use. Quotas and weighting were used to achieve a quasi-representative sample of the British general population. Participants meeting criteria of interest and agreeing to recontact were selected for qualitative follow-up interviews. Comparisons were made with contemporaneous national probability surveys and Natsal-3 (2010-12) to understand bias. Results: 6,654 participants completed the survey and 45 completed follow-up interviews. The weighted Natsal-COVID sample was similar to the general population in terms of gender, age, ethnicity, rurality, and, among sexually-active participants, numbers of sexual partners in the past year. However, the sample was more educated, contained more sexually-inexperienced people, and included more people in poorer health. Conclusions: Natsal-COVID Wave 1 rapidly collected quasi-representative population data to enable evaluation of the early population-level impact of COVID-19 and lockdown measures on SRH in Britain. Although sampling was less representative than the decennial Natsals, Natsal-COVID will complement national surveillance data and Natsal-4 (planned for 2022).

BackgroundSharing 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 findingsWe 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.ConclusionsNearly 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 registrationISRCTN: ISRCTN96189403.

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.

Background: Sexual health entails the absence of disease and the ability to lead a pleasurable and safe sex life. In Britain, ethnic inequalities in diagnoses of sexually transmitted infections (STI) persist; however, the reasons for these inequalities, and ethnic variations in other markers of sexual health, remain poorly understood. We investigated ethnic differences in hypothesised explanatory factors such as socioeconomic factors, substance use, depression, and sexual behaviours, and whether they explained ethnic variations in sexual health markers (reported STI diagnoses, attendance at sexual health clinics, use of emergency contraception, and sexual function). Methods: We analysed probability survey data from Britain's third National Survey of Sexual Attitudes and Lifestyles (Natsal-3; n=15 162, conducted in 2010–12). Reflecting Britain's current ethnic composition, we included in our analysis participants who identified in 2011 as belonging to one of the following seven largest ethnic groups: white British, black Caribbean, black African, Indian, Pakistani, white other, and mixed ethnicity. We calculated age-standardised estimates and age-adjusted odds ratios for all explanatory factors and sexual health markers for all these ethnic groups with white British as the reference category. We used multivariable regression to examine the extent to which adjusting for explanatory factors explained ethnic variations in sexual health markers. Findings: We included 14 563 (96·0%) of the 15 162 participants surveyed in Natsal-3. Greater proportions of black Caribbean, black African, and Pakistani people lived in deprived areas than those of other ethnic groups (36·9–55·3% vs 16·4–29·4%). Recreational drug use was highest among white other and mixed ethnicity groups (25·6–27·7% in men and 10·3–12·9% in women in the white other and mixed ethnicity groups vs 4·1–15·6% in men and 1·0–11·2% in women of other ethnicities). Compared with white British men, the proportions of black Caribbean and black African men reporting being sexually competent at sexual debut were lower (32·9% for black Caribbean and 21·9% for black African vs 47·4% for white British) and the number of partners in the past 5 years was greater (median 2 [IQR 1–4] for black Caribbean and 2 [1–5] for black African vs 1 [1–2] for white British), and although black Caribbean and black African men reported greater proportions of concurrent partnerships (26·5% for black Caribbean and 38·9% for black African vs 14·8% for white British), these differences were not significant after adjusting for age. Compared with white British women, the proportions of black African and mixed ethnicity women reporting being sexually competent were lower (18·0% for black African and 35·3% for mixed ethnicity vs 47·9% for white British), and mixed ethnicity women reported larger numbers of partners in the past 5 years (median 1 [IQR 1–4] vs 1 [1–2]) and greater concurrency (14·3% vs 8·0%). Reporting STI diagnoses was higher in black Caribbean men (8·7%) and mixed ethnicity women (6·7%) than white British participants (3·6% in men and 3·2% in women). Use of emergency contraception was most commonly reported among black Caribbean women (30·7%). Low sexual function was most common among women of white other ethnicity (30·1%). Adjustment for explanatory factors only partly explained inequalities among some ethnic groups relative to white British ethnicity but did not eliminate ethnic differences in these markers. Interpretation: Ethnic inequalities in sexual health markers exist, and they were not fully explained by differences in their broader determinants. Holistic interventions addressing modifiable risk factors and targeting ethnic groups at risk of poor sexual health are needed. Funding: Medical Research Council, the Wellcome Trust, the Economic and Social Research Council, UK Department of Health, and The National Institute for Health Research.

Including questions about sexual health in the annual Health Survey for England (HSE) provides opportunities for regular measurement of key public health indicators, augmenting Britain's decennial National Survey of Sexual Attitudes and Lifestyles (Natsal). However, contextual and methodological differences may limit comparability of the findings. We examine the extent of these differences between HSE 2010 and Natsal-3 and investigate their impact on parameter estimates.Complex survey analyses of data from men and women in the 2010 HSE (n = 2,782 men and 3,588 women) and Natsal-3 undertaken 2010-2012 (n = 4,882 men and 6,869 women) aged 16-69y and resident in England, both using probability sampling, compared their characteristics, the amount of non-response to, and estimates from, sexual health questions. Both surveys used self-completion for the sexual behaviour questions but this was via computer-assisted self-interview (CASI) in Natsal-3 and a pen-and-paper questionnaire in HSE 2010.The surveys achieved similar response rates, both around 60%, and demographic profiles largely consistent with the census, although HSE participants tended to be less educated, and reported worse general health, than Natsal-3 participants. Item non-response to the sexual health questions was typically higher in HSE 2010 (range: 9-18%) relative to Natsal-3 (all

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 (350 may not have delayed diagnosis.

Background The National Surveys of Sexual Attitudes and Lifestyles COVID study (Natsal-COVID) was designed to understand the impact of COVID-19 on Britain’s sexual and reproductive health (SRH). Natsal-COVID Wave 1 survey and qualitative follow-up interviews were conducted in 2020. The Wave 2 survey was designed to capture one-year prevalence estimates for key SRH outcomes and measure changes over the first year of the pandemic. We describe the Wave 2 survey methodology and assess the sample representativeness. Methods Natsal-COVID Wave 2 was conducted March-April 2021; approximately one year after the start of Britain’s first national lockdown. Data were collected using an online web-panel survey administered by Ipsos. The sample comprised a longitudinal sample of Wave 1 participants who had agreed to re-contact plus a sample of participants residing in Britain, aged 18-59, including a boost sample comprising people aged 18-29. Questions covered reproductive health, relationships, sexual behaviour and SRH service use. Quotas and weighting were used to achieve a quasi-representative sample of the British population. Comparisons were made with recent national probability surveys, Natsal-3 (2010-12) and Natsal-COVID Wave 1 to understand bias. Results A total of 6,658 individuals completed the survey. In terms of gender, age, ethnicity, and rurality, the weighted Natsal-COVID Wave 2 sample was like the general population. Participants were less likely to be married or to report being in good health than the general population. The longitudinal sample (n=2,098) were broadly like participants who only took part in Wave 1 but were older. Among the sexually active, longitudinal participants were less likely to report multiple sexual partners or a new sexual partner in the past year compared to those who only took part in Wave 1. Conclusions Natsal-COVID collected longitudinal, quasi-representative population data to enable evaluation of the population-level impact of COVID-19 on SRH and to inform policy.

Abstract Background There are numerous approaches available to analyse data from cluster randomised trials. These include cluster-level summary methods and individual-level methods accounting for clustering, such as generalised estimating equations and generalised linear mixed models. There has been much methodological work showing that estimates of treatment effects can vary depending on the choice of approach, particularly when estimating odds ratios, essentially because the different approaches target different estimands. Methods In this manuscript, we describe the protocol for a planned re-analysis of data from a large number of cluster randomised trials. Our main objective is to examine empirically whether and how odds ratios estimated using different approaches (for both primary and secondary binary outcomes) vary in cluster randomised trials. We describe the methods that will be used to identify the datasets for inclusion and how they will be analysed and reported. Discussion There have been a number of small comparisons of empirical differences between the different approaches to analysis for CRTs. The systematic approach outlined in this protocol will allow a much deeper understanding of when there are important choices around the model approach and in which settings. This will be of importance given the heightened awareness of the importance of estimands and the specification of statistical analysis plans.

Background Sexually transmitted infection (STI) risk is determined both by partner numbers and partnership characteristics. Studies describing only recent partnership(s) overestimate long-term partnerships and underestimate the contribution of casual partnerships to STI transmission in populations. We describe all heterosexual partnerships in the past year in terms of partnership type, age and geographical mixing and how these characteristics relate to condom use. Methods Probability sample survey of 11 161 men and women aged 16–44 resident in Britain, 1999–2001. Computer-assisted self-interviews asked respondents about partner numbers and detailed questions about their three most recent partnerships. We weight these data to represent partnerships for which detailed questions were not asked to present estimates for the population of partnerships. Results Of 15 488 heterosexuals partnerships, 39.1% (95% CI 36.6–41.7%) of mens partnerships were ‘not (yet) regular’ vs 20.0% (95% CI 18.2–21.9%) of womens partnerships. While condoms were used at last sex in 37.1% (95% CI 35.0–39.3%) of mens and 28.8% (95% CI 27.1–30.6%) of womens partnerships, and for 55.3% (95% CI 52.6–58.0%) of first sex with new partners, these proportions declined with age. When partnerships involved an age difference of 5+ years [26.2% (95% CI 23.0–29.6%) of mens and 36.5% (95% CI 33.0–40.1%) of womens partnerships], condoms were less commonly used at first sex than when partners were closer in age [44.1% (95% CI 39.1–48.4%) vs 60.8% (95% CI 57.3–64.2%)]. Sex occurred within 24 h in 23.4% (95% CI 19.7–27.5%) of mens and 10.7% (95% CI 8.3–13.6%) of womens partnerships. Conclusions A substantial minority of partnerships in the population is casual. The proportion of partnerships not protected by condoms is high, especially for partnerships involving larger age differences and people in their 30s and 40s. Condom use with new partners needs to be promoted among all age-groups. [ABSTRACT FROM AUTHOR]

Abstract 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).

Abstract Background The classification of phase 3 trials as superiority or non-inferiority has become routine, and it is widely accepted that there are important differences between the two types of trial in their design, analysis and interpretation. Main text There is a clear rationale for the superiority/non-inferiority framework in the context of regulatory trials. The focus of our article is non-regulatory trials with a public health objective. First, using two examples from infectious disease research, we show that the classification of superiority or non-inferiority trials is not always straightforward. Second, we show that several arguments for different approaches to the design, analysis and interpretation of superiority and non-inferiority trials are unconvincing when examined in detail. We consider, in particular, the calculation of sample size (and the choice of delta or the non-inferiority margin), intention-to-treat versus per-protocol analyses, and one-sided versus two-sided confidence intervals. We argue that the superiority/non-inferiority framework is not just unnecessary but can have a detrimental effect, being a barrier to clear scientific thought and communication. In particular, it places undue emphasis on tests for significance or non-inferiority at the expense of estimation. We emphasise that these concerns apply to phase 3 non-regulatory trials in general, not just to those where the classification of the trial as superiority or non-inferiority is ambiguous. Conclusions Guidelines and statistical practice should abandon the sharp division between superiority and non-inferiority phase 3 non-regulatory trials and be more closely aligned to the clinical and public health questions that motivate the trial.

Abstract Background There has been some debate in the literature as to whether baseline values of a measurement of interest at treatment initiation should be treated as an outcome variable as part of a model for longitudinal change or instead used as a predictive variable with respect to the response to treatment. We develop a new approach that involves a combined statistical model for all pre- and post-treatment observations of the biomarker of interest, in which the characteristics of response to treatment are treated as a function of the ‘true’ value of the biomarker at treatment initiation. Methods The modelling strategy developed is applied to a dataset of CD4 counts from patients in the UK Register of HIV Seroconverters (UKR) cohort who initiated highly active antiretroviral therapy (HAART). The post-HAART recovery in CD4 counts for each individual is modelled as following an asymptotic curve in which the speed of response to treatment and long-term maximum are functions of the ‘true’ underlying CD4 count at initiation of HAART and the time elapsed since seroconversion. Following previous research in this field, the models developed incorporate non-stationary stochastic process components, and the possibility of between-patient differences in variability over time was also considered. Results A variety of novel models were successfully fitted to the UKR dataset. These provide reinforcing evidence for findings that have previously been reported in the literature, in particular that there is a strong positive relationship between CD4 count at initiation of HAART and the long-term maximum in each patient, but also reveal potentially important features of the data that would not have been easily identified by other methods of analysis. Conclusion Our proposed methodology provides a unified framework for the analysis of pre- and post-treatment longitudinal biomarker data that will be useful for epidemiological investigations and simulations in this context. The approach developed allows use of all relevant data from observational cohorts in which many patients are missing pre-treatment measurements and in which the timing and number of observations vary widely between patients.