ObjectivesThere is increasing recognition that insufficient attention has been paid to the choice of outcomes measured in clinical trials. The lack of a standardized outcome classification system results in inconsistencies due to ambiguity and variation in how outcomes are described across different studies. Being able to classify by outcome would increase efficiency in searching sources such as clinical trial registries, patient registries, the Cochrane Database of Systematic Reviews, and the Core Outcome Measures in Effectiveness Trials (COMET) database of core outcome sets (COS), thus aiding knowledge discovery.Study Design and SettingA literature review was carried out to determine existing outcome classification systems, none of which were sufficiently comprehensive or granular for classification of all potential outcomes from clinical trials. A new taxonomy for outcome classification was developed, and as proof of principle, outcomes extracted from all published COS in the COMET database, selected Cochrane reviews, and clinical trial registry entries were classified using this new system.ResultsApplication of this new taxonomy to COS in the COMET database revealed that 274/299 (92%) COS include at least one physiological outcome, whereas only 177 (59%) include at least one measure of impact (global quality of life or some measure of functioning) and only 105 (35%) made reference to adverse events.ConclusionsThis outcome taxonomy will be used to annotate outcomes included in COS within the COMET database and is currently being piloted for use in Cochrane Reviews within the Cochrane Linked Data Project. Wider implementation of this standard taxonomy in trial and systematic review databases and registries will further promote efficient searching, reporting, and classification of trial outcomes.

Objectives Mortality in young people with perinatally acquired HIV infection (PHIV) following transfer to adult care has not been characterized in the UK. We conducted a multicentre audit to establish the number of deaths and associated factors. Methods Fourteen adult clinics caring for infected young people reported deaths to 30 September 2011 on a proforma. Deaths were matched to the Collaborative HIV Paediatric Study, a clinical database of HIV‐infected children in the UK/Ireland, to describe clinical characteristics in paediatric care of those who died post‐transition. Results Eleven deaths were reported from 14 clinics which cared for 248 adults with PHIV. For the 11 deaths, the median age at transfer to adult care was 17 years (range 15–21 years), and at death was 21 years (range 17–24 years). Causes of death were suicide (two patients), advanced HIV disease (seven patients) and bronchiectasis (one patient), with one cause missing. At death, the median CD4 count was 27 cells/μL (range 0–630 cells/μL); five patients were on antiretroviral therapy (ART) but only two had a viral load < 50 HIV‐1 RNA copies/mL. Nine had poor adherence when in paediatric care, continuing into adult care despite multidisciplinary support. Eight had ART resistance, although all had potentially suppressive regimens available. Nine had mental health diagnoses. Conclusions Our findings highlight the complex medical and psychosocial issues faced by some adults with PHIV, with nine of the 11 deaths in our study being associated with poor adherence and advanced HIV disease. Novel adherence interventions and mental health support are required for this vulnerable cohort.

c Triple-site testing (using pharyngeal, rectal, and urethral/first-void urine samples) for Neisseria gonorrhoeae and Chlamydia trachomatis using nucleic acid amplification tests detects greater numbers of infections among men who have sex with men (MSM). However, triple-site testing represents a cost pressure for services. MSM over 18 years of age were eligible if they requested testing for sexually transmitted infections (STIs), reported recent sexual contact with either C. trachomatis or N. gonorrhoeae, or had symptoms of an STI. Each patient underwent standard-of-care (SOC) triple-site testing, and swabs were taken to form a pooled sample (PS) (pharyngeal, rectal, and urine specimens). The PS was created using two methods during different periods at one clinic, but we analyzed the data in combination because the sensitivity of the two methods did not differ significantly for C. trachomatis (P ‫؍‬ 0.774) or N. gonorrhoeae (P ‫؍‬ 0.163). The sensitivity of PS testing (92%) was slightly lower than that of SOC testing (96%) for detecting C. trachomatis (P ‫؍‬ 0.167). For N. gonorrhoeae, the sensitivity of PS testing (90%) was significantly lower than that of SOC testing (99%) (P < 0.001). When pharynx-only infections were excluded, the sensitivity of PS testing to detect N. gonorrhoeae infections increased to 94%. Our findings show that pooling of self-taken samples could be an effective and cost-saving method, with high negative predictive values. (Interim results of this study were presented at the BASHH 2013 summer meeting.) I n the United States and Europe, genital Chlamydia trachomatis and Neisseria gonorrhoeae are the most prevalent bacterial sexually transmitted infections (STIs). In the United Kingdom, rates of gonorrhea and chlamydia among men who have sex with men (MSM) continue to rise (1), while studies highlight increases in the numbers of HIV-positive and HIV-negative MSM reporting high-risk sexual behavior since the advent of combination antiretroviral therapy (cART) (2-4).Coinfection with an STI and HIV has been shown to increase HIV transmission in epidemiological studies (5-7). Concomitant genital infections have been shown to increase shedding of HIV in the genital tract, in both vaginal secretions and seminal fluid (8, 9). Rectal C. trachomatis/N. gonorrhoeae infections have been associated with HIV acquisition in MSM (10), and it is plausible that they may also enhance HIV transmission.Nucleic acid amplification tests (NAATs) are being used increasingly to screen MSM for pharyngeal and rectal C. trachomatis/N. gonorrhoeae infections, in addition to the use of urethral or first-void urine (FVU) samples, and the use of NAATs is now recommended in national guidelines (11). While there are no NAATs licensed for use with extragenital specimens, several studies have demonstrated that NAATs perform well for the detection of both pharyngeal and rectal C. trachomatis/N. gonorrhoeae infections in . Studies evaluating the performance of these testing methodologies have demonstrated sensitivities and sp...

This is a repository copy of A core outcome set for clinical trials of chemoradiotherapy interventions for anal cancer (CORMAC): a patient and health-care professional consensus..

IntroductionThe incidence of anal squamous cell carcinoma (ASCC) has increased threefold in the last 30 years. Initial treatment is chemoradiotherapy, associated with short-term and long-term side effects. Future therapy innovations aim to reduce morbidity in treatment of early tumours while maintaining treatment efficacy, and to escalate treatment intensity in locally advanced tumours with acceptable quality of life (QoL). However, all phase III randomised controlled trials to-date have utilised different primary outcomes, which hinders evidence synthesis and presents challenges to the selection of optimal outcomes in future trials. No trial comprehensively assessed long-term side effects and QoL, suggesting outcomes reflecting issues important to patients are under-represented. This project aims to determine the priority outcomes for all stakeholders and reach agreement on a standardised core set of outcomes to be measured and reported on in all future ASCC trials.Methods and analysisA systematic review will identify all outcomes reported in trials and observational studies of chemoradiotherapy as primary treatment for ASCC. Outcomes of importance to patients will be identified through patient interviews. The long list of outcomes generated from the systematic review and interviews will be used to create a two-round Delphi process, including key stakeholders (patients and healthcare professionals). The results of the Delphi will be discussed at a face-to-face consensus meeting. Discussion will focus on outcomes that did not achieve consensus through the Delphi process and conclude with anonymous voting to ratify the final core outcome set (COS).Ethics and disseminationThe final COS will feed directly into the PersonaLising Anal cancer radioTherapy dOse (PLATO) national anal cancer trials and the Association of coloproctologists of Great Britain and Ireland (ACPGBI) supported national anal cancer database. Utilisation of the COS will increase the relevance of research output to all stakeholders and increase the capacity for data synthesis between trials. This study has ethical approval and is registered with the Core Outcome Measures in Effectiveness Trials (COMET) initiative.Trial registration numberPROSPERO registration ID: CRD42016036540

The present series demonstrates that MACRS and HIPEC is a feasible and safe alternative to the open procedure with the advantage of smaller abdominal wounds and comparable morbidity and inpatient stay. Longer follow-up is needed to assess the impact on disease progression.

Objective The objectives of this nested study were to (1) assess whether changes in scores between rounds altered the final degree of consensus achieved in three Delphi surveys conducted as part of COS development projects (anal, gastric, and prostate cancer), and (2) explore participants’ reasons for changing scores between rounds. Study Design and Setting All Delphi surveys were conducted online using DelphiManager software and included healthcare professionals and participating patients. Participants were invited to give a free-text reason whenever they changed their score across an important threshold on a 1–9 Likert scale (1–3 not important, 4–5 important, 7–9 critically important). Reasons for score change were coded by four researchers independently using an inductive-iterative approach. Results In all three Delphi surveys, the number of outcomes reaching criteria for consensus was greater in R2 than R1. Twelve themes and 23 subthemes emerged from 2298 discrete reasons given for score change. The most common reasons for the change were “time to reflect” (482 responses, 23%) and vicarious thinking (424, 21%), with 68% (291) of vicarious thinking attributed to seeing other participant’s scores. Conclusion Our findings support conducting a Delphi survey over the use of a single questionnaire where building consensus is the objective. Time to reflect and vicarious thinking, facilitated by seeing other participant’s scores, were important drivers of score change. How results are presented to participants between rounds and the duration of and time between rounds in a Delphi survey may, therefore, influence the results and should be clearly reported.

AimSix Phase III randomized trials have determined the effectiveness of chemoradiotherapy as primary treatment for anal squamous cell carcinoma (ASCC), but outcomes reported in these trials varied widely, hindering evidence synthesis. To improve reporting in all future trials, we aim to develop a core outcomes set (COS). As the first stage of COS development, we undertook a systematic review to summarize the outcomes reported in studies evaluating chemoradiotherapy for ASCC.MethodSystematic literature searches identified studies evaluating radiotherapy or chemoradiotherapy for ASCC. Outcomes and accompanying definitions were extracted verbatim and categorized into domains.ResultsFrom 5170 abstracts, we identified 95 eligible studies, reporting 1192 outcomes and 533 unique terms. We collapsed these terms into 86 standardized outcomes and five domains: survival; disease activity; life impact [including quality of life (QoL)]; delivery of care; and toxicity. The most commonly reported domains were survival and disease activity, reported in 74 (86%) and 54 (62%) studies, respectively. No outcome was reported in every publication. Over half (43/86) of the standardized outcome terms were reported in fewer than five studies, and 21 (25%) were reported in a single study only. There was wide variation in definitions of disease‐free survival, colostomy‐free survival and progression‐free survival (PFS). Anal continence was reported in only 35 (41%) studies.ConclusionOutcomes reported in studies evaluating chemoradiotherapy for ASCC were heterogenous and definitions varied widely. Outcomes likely to be important to patients, such as ano‐rectal function, toxicity and QoL, have been neglected. A COS for future trials will address these issues.