Optimising partner notification outcomes for bacterial sexually transmitted infections: a deliberative process and consensus

Partner notification (PN) is an essential element of sexually transmitted infection (STI) control. It enables identification, treatment and advice for sexual contacts who may benefit from additional preventive interventions, such as HIV pre-exposure prophylaxis (PrEP). PN is most effective in reducing STI transmission in a population when it reaches individuals who are most likely to have a STI, and to engage in sexual behaviour that facilitates STI transmission, including having multiple and/or new sex partners. Outcomes of PN practice need to be measurable in order to inform standards. They need to address all five stages in the cascade of care: elicitation of partners, establishing contactable partners, notification, testing and treatment. In the United Kingdom, established outcome measures cover only the first three stages and do not take into account the type of sexual partnership. We report on an evidence-based process used to develop new PN outcomes and inform standards of care. We undertook a systematic literature review, evaluation of published information on types of sexual partnership, and a modified Delphi process to reach consensus. We propose six new PN outcome measures at five stages of the cascade, including stratification for sex partnership type. Our framework for PN outcome measurement has potential to contribute in other domains, notably Covid-19

A survey of current practices by the British Oculoplastic Surgery Society (BOPSS) and recommendations for delivering a sustainable multidisciplinary approach to thyroid eye disease in the United Kingdom

The Royal College of Physicians (RCP) and Thyroid Eye Disease Amsterdam Declaration Implementation Group (TEAMeD-5) have the common goal of improving access to high quality care for thyroid eye disease (TED). The TEAMeD-5 programme recommends all patients with moderate-to-severe TED should have access to multidisciplinary clinics (MDT) with combined Ophthalmology and Endocrinology expertise

Effectiveness and cost-effectiveness of implementing HIV testing in primary care in East London: protocol for an interrupted time series analysis

Introduction HIV remains underdiagnosed. Guidelines recommend routine HIV testing in primary care, but evidence on implementing testing is lacking. In a previous study, the Rapid HIV Assessment 2 (RHIVA2) cluster randomised controlled trial, we showed that providing training and rapid point-of-care HIV testing at general practice registration (RHIVA2 intervention) in Hackney led to cost-effective, increased and earlier diagnosis of HIV. However, interventions effective in a trial context may be less so when implemented in routine practice. We describe the protocol for an MRC phase IV implementation programme, evaluating the impact of rolling out the RHIVA2 intervention in a post-trial setting. We will use a longitudinal study to examine if the post-trial implementation in Hackney practices is effective and cost-effective, and a cross-sectional study to compare Hackney with two adjacent boroughs providing usual primary care (Newham) and an enhanced service promoting HIV testing in primary care (Tower Hamlets). Methods and analysis Service evaluation using interrupted time series and cost-effectiveness analyses. We will include all general practices in three contiguous high HIV prevalence East London boroughs. All adults aged 16 and above registered with the practices will be included. The interventions to be examined are: a post-trial RHIVA2 implementation programme (including practice-based education and training, external quality assurance, incentive payments for rapid HIV testing and incorporation of rapid HIV testing in the sexual health Local Enhanced Service) in Hackney; the general practice sexual health Network Improved Service in Tower Hamlets and usual care in Newham. Coprimary outcomes are rates of HIV testing and new HIV diagnoses. Ethics and dissemination The chair of the Camden and Islington NHS Research Ethics Committee, London, has endorsed this programme as an evaluation of routine care. Study results will be published in peer-reviewed journals and reported to commissioners

How can we objectively categorise partnership type? A novel classification of population survey data to inform epidemiological research and clinical practice

Abstract: Background Partnership type is a determinant of STI risk; yet, it is poorly and inconsistently recorded in clinical practice and research. We identify a novel, empirical-based categorisation of partnership type, and examine whether reporting STI diagnoses varies by the resulting typologies. Methods: Analyses of probability survey data collected from 15 162 people aged 16–74 who participated in Britain's third National Survey of Sexual Attitudes and Lifestyles were undertaken during 2010–2012. Computer-assisted self-interviews asked about participants' ≤3 most recent partners (N=14 322 partners/past year). Analysis of variance and regression tested for differences in partnership duration and perceived likelihood of sex again across 21 ‘partnership progression types’ (PPTs) derived from relationship status at first and most recent sex. Multivariable regression examined the association between reporting STI diagnoses and partnership type(s) net of age and reported partner numbers (all past year). Results: The 21 PPTs were grouped into four summary types: ‘cohabiting’, ‘now steady’, ‘casual’ and ‘ex-steady’ according to the average duration and likelihood of sex again. 11 combinations of these summary types accounted for 94.5% of all men; 13 combinations accounted for 96.9% of all women. Reporting STI diagnoses varied by partnership-type combination, including after adjusting for age and partner numbers, for example, adjusted OR: 6.03 (95% CI 2.01 to 18.1) for men with two ‘casual’ and one ‘now steady’ partners versus men with one ‘cohabiting’ partner. Conclusions: This typology provides an objective method for measuring partnership type and demonstrates its importance in understanding STI risk, net of partner numbers. Epidemiological research and clinical practice should use these methods and results to maximise individual and public health benefit

Accelerated partner therapy (APT) partner notification for people with Chlamydia trachomatis: protocol for the Limiting Undetected Sexually Transmitted infections to RedUce Morbidity (LUSTRUM) APT cross-over cluster randomised controlled trial

INTRODUCTION: Partner notification (PN) is a process aiming to identify, test and treat the sex partners of people (index patients) with sexually transmitted infections (STIs). Accelerated partner therapy (APT) is a PN method whereby healthcare professionals assess sex partners, by telephone consultation, before giving the index patient antibiotics and STI self-sampling kits to deliver to their sex partner(s). The Limiting Undetected Sexually Transmitted infections to RedUce Morbidity programme aims to determine the effectiveness of APT in heterosexual women and men with chlamydia and determine whether APT could affect Chlamydia trachomatis transmission at population level. METHODS AND ANALYSIS: This protocol describes a cross-over cluster randomised controlled trial of APT, offered as an additional PN method, compared with standard PN. The trial is accompanied by an economic evaluation, transmission dynamic modelling and a qualitative process evaluation involving patients, partners and healthcare professionals. Clusters are 17 sexual health clinics in areas of England and Scotland with contrasting patient demographics. We will recruit 5440 heterosexual women and men with chlamydia, aged ≥16 years.The primary outcome is the proportion of index patients testing positive for C. trachomatis 12-16 weeks after the PN consultation. Secondary outcomes include: proportion of sex partners treated; cost effectiveness; model-predicted chlamydia prevalence; experiences of APT.The primary outcome analysis will be by intention-to-treat, fitting random effects logistic regression models that account for clustering of index patients within clinics and trial periods. The transmission dynamic model will be used to predict change in chlamydia prevalence following APT. The economic evaluation will use mathematical modelling outputs, taking a health service perspective. Qualitative data will be analysed using interpretative phenomenological analysis and framework analysis. ETHICS AND DISSEMINATION: This protocol received ethical approval from London-Chelsea Research Ethics Committee (18/LO/0773). Findings will be published with open access licences. TRIAL REGISTRATION NUMBER: ISRCTN15996256

Coronavirus disease 2019 subphenotypes and differential treatment response to convalescent plasma in critically ill adults: secondary analyses of a randomized clinical trial

Purpose Benefit from convalescent plasma therapy for coronavirus disease 2019 (COVID-19) has been inconsistent in randomized clinical trials (RCTs) involving critically ill patients. As COVID-19 patients are immunologically heterogeneous, we hypothesized that immunologically similar COVID-19 subphenotypes may differ in their treatment responses to convalescent plasma and explain inconsistent findings between RCTs . Methods We tested this hypothesis in a substudy involving 1239 patients, by measuring 26 biomarkers (cytokines, chemokines, endothelial biomarkers) within the randomized, embedded, multifactorial, adaptive platform trial for community-acquired pneumonia (REMAP-CAP) that assigned 2097 critically ill COVID-19 patients to either high-titer convalescent plasma or usual care. Primary outcome was organ support free days at 21 days (OSFD-21) . Results Unsupervised analyses identified three subphenotypes/endotypes. In contrast to the more homogeneous subphenotype-2 (N = 128 patients, 10.3%; with elevated type i and type ii effector immune responses) and subphenotype-3 (N = 241, 19.5%; with exaggerated inflammation), the subphenotype-1 had variable biomarker patterns (N = 870 patients, 70.2%). Subphenotypes-2, and -3 had worse outcomes, and subphenotype-1 had better outcomes with convalescent plasma therapy compared with usual care (median (IQR). OSFD-21 in convalescent plasma vs usual care was 0 (− 1, 21) vs 10 (− 1, to 21) in subphenotype-2; 1.5 (− 1, 21) vs 12 (− 1, to 21) in suphenotype-3, and 0 (− 1, 21) vs 0 (− 1, to 21) in subphenotype-1 (test for between-subphenotype differences in treatment effects p = 0.008). Conclusions We reported three COVID-19 subphenotypes, among critically ill adults, with differential treatment effects to ABO-compatible convalescent plasma therapy. Differences in subphenotype prevalence between RCT populations probably explain inconsistent results with COVID-19 immunotherapies

The eClinical Care Pathway Framework: A novel structure for creation of online complex clinical care pathways and its application in the management of sexually transmitted infections.

Despite considerable international eHealth impetus, there is no guidance on the development of online clinical care pathways. Advances in diagnostics now enable self-testing with home diagnosis, to which comprehensive online clinical care could be linked, facilitating completely self-directed, remote care. We describe a new framework for developing complex online clinical care pathways and its application to clinical management of people with genital chlamydia infection, the commonest sexually transmitted infection (STI) in England.Using the existing evidence-base, guidelines and examples from contemporary clinical practice, we developed the eClinical Care Pathway Framework, a nine-step iterative process. Step 1: define the aims of the online pathway; Step 2: define the functional units; Step 3: draft the clinical consultation; Step 4: expert review; Step 5: cognitive testing; Step 6: user-centred interface testing; Step 7: specification development; Step 8: software testing, usability testing and further comprehension testing; Step 9: piloting. We then applied the Framework to create a chlamydia online clinical care pathway (Online Chlamydia Pathway).Use of the Framework elucidated content and structure of the care pathway and identified the need for significant changes in sequences of care (Traditional: history, diagnosis, information versus Online: diagnosis, information, history) and prescribing safety assessment. The Framework met the needs of complex STI management and enabled development of a multi-faceted, fully-automated consultation.The Framework provides a comprehensive structure on which complex online care pathways such as those needed for STI management, which involve clinical services, public health surveillance functions and third party (sexual partner) management, can be developed to meet national clinical and public health standards. The Online Chlamydia Pathway's standardised method of collecting data on demographics and sexual behaviour, with potential for interoperability with surveillance systems, could be a powerful tool for public health and clinical management.UKCRC Translational Infection Research (TIR) Initiative supported by the Medical Research Council, eSTI2 Consortium (Grant Number G0901608)

OPTIMUM study protocol: an adaptive randomised controlled trial of a mixed whole-cell/acellular pertussis vaccine schedule.

INTRODUCTION: Combination vaccines containing whole-cell pertussis antigens were phased out from the Australian national immunisation programme between 1997 and 1999 and replaced by the less reactogenic acellular pertussis (aP) antigens. In a large case-control study of Australian children born during the transition period, those with allergist diagnosed IgE-mediated food allergy were less likely to have received whole-cell vaccine in early infancy than matched population controls (OR: 0.77 (95% CI, 0.62 to 0.95)). We hypothesise that a single dose of whole-cell vaccine in early infancy is protective against IgE-mediated food allergy. METHODS AND ANALYSIS: This adaptive double-blind randomised controlled trial is investigating whether a mixed whole-cell/aP vaccine schedule prevents allergic disease in the first year of life. The primary outcome is IgE-mediated food allergy by 12 months of age. Secondary outcomes include new onset of atopic dermatitis by 6 or 12 months of age; sensitisation to at least one allergen by 12 months of age; seroconversion in anti-pertussis toxin IgG titres after vaccination with aP booster at 18 months of age; and solicited systemic and local adverse events following immunisation with pertussis-containing vaccines. Analyses will be performed using a Bayesian group sequential design. ETHICS AND DISSEMINATION: This study has been approved by the Child and Adolescent Health Service Human Research Ethics Committee, Perth, Western Australia (RGS 00019). The investigators will ensure that this trial is conducted in accordance with the principles of the Declaration of Helsinki and with the International Conference on Harmonisation Guidelines for Good Clinical Practice. Individual consent will be requested. Parents will be reimbursed reasonable travel and parking costs to attend the study visits. The dissemination of these research findings will follow the National Health and Medical Research Council of Australia Open Access Policy. TRIAL REGISTRATION NUMBER: ACTRN12617000065392p

A multicentred study to validate a consensus bleeding assessment tool developed by the biomedical excellence for safer transfusion collaborative for use in patients with haematological malignancy

Background There continues to be uncertainty about the optimal approach to documenting bleeding data in platelet transfusion trials, with a desire to apply a common assessment tool across all trials. With this in mind, a consensus bleeding assessment tool (BAT) has been developed by the Biomedical Excellence for Safer Transfusion (BEST) collaborative, based on review of data collection forms used in published randomized trials and following content validation with a range of healthcare professionals at seven haematology centres through BEST members. This study aimed to evaluate reliability and reproducibility of the consensus BAT. Methods Replicated clinical assessments of bleeding were undertaken by participants with haematological malignancies recruited at four haematology centres in an international, multicentred, observational study. Concordance of repeat assessments was calculated for agreement in site and grade of bleeding observed. Results Forty patients consented to participate, and 13 trained bleeding assessors collected these data. Bleeding assessments were carried out on 113 separate days. Of all 225 bleeding assessments, 204 were compared for grade concordance, and 160 were compared for site concordance. There was very good grade concordance (83%, 95% confidence interval 74–93%) and good bleeding site concordance (69%, 95% confidence interval 57–79%) in observations of bleeding. Discordance was primarily in relation to assessing skin bleeding. Conclusions Alongside a structured training programme, levels of concordance for a consensus BAT were high. Researchers using assessment tools for bleeding need to balance comprehensive data collection against potential loss of accuracy for some types of bleeding, such as skin findings