A digital pathway for genetic testing in UK NHS patients with cancer: BRCA-DIRECT randomised study internal pilot.

BACKGROUND: Germline genetic testing affords multiple opportunities for women with breast cancer, however, current UK NHS models for delivery of germline genetic testing are clinician-intensive and only a minority of breast cancer cases access testing. METHODS: We designed a rapid, digital pathway, supported by a genetics specialist hotline, for delivery of germline testing of BRCA1/BRCA2/PALB2 (BRCA-testing), integrated into routine UK NHS breast cancer care. We piloted the pathway, as part of the larger BRCA-DIRECT study, in 130 unselected patients with breast cancer and gathered preliminary data from a randomised comparison of delivery of pretest information digitally (fully digital pathway) or via telephone consultation with a genetics professional (partially digital pathway). RESULTS: Uptake of genetic testing was 98.4%, with good satisfaction reported for both the fully and partially digital pathways. Similar outcomes were observed in both arms regarding patient knowledge score and anxiety, with <5% of patients contacting the genetics specialist hotline. All progression criteria established for continuation of the study were met. CONCLUSION: Pilot data indicate preliminary demonstration of feasibility and acceptability of a fully digital pathway for BRCA-testing and support proceeding to a full powered study for evaluation of non-inferiority of the fully digital pathway, detailed quantitative assessment of outcomes and operational economic analyses. TRIAL REGISTRATION NUMBER: ISRCTN87845055.

A phase IV randomised, open-label pilot study to evaluate switching from protease-inhibitor based regimen to Bictegravir/Emtricitabine/Tenofovir Alafenamide single tablet regimen in Integrase inhibitor-naïve, virologically suppressed HIV-1 infected adults harbouring drug resistance mutations (PIBIK study): study protocol for a randomised trial.

BACKGROUND: Currently recommended boosted protease-inhibitor (bPI) regimens may be associated with increased risk of cardiovascular or chronic kidney diseases; in addition, boosted regimens are particularly associated with drug-drug interactions. Since both cardiovascular and renal disease, and polypharmacy, are common in ageing people with HIV, there is a need for alternative efficacious regimens. bPI-based regimens are often the treatment of choice for individuals with pre-treatment or treatment-acquired resistance but it is plausible that carefully selected HIV-positive individuals with drug resistance, who are virologically suppressed on their current bPI regimen, could maintain virological efficacy when switched to bictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) fixed dose combination (FDC). METHODS/DESIGN: A phase IV, investigator-initiated, multicentre, open label pilot, randomised two-arm study to assess the safety and efficacy of switching from bPI regimen to B/F/TAF single tablet regimen in integrase inhibitor-naïve, virologically suppressed adults with HIV-1 infection harbouring drug resistance mutations. Eligible individuals will either continue on their bPI regimen or switch to B/F/TAF FDC. After 24 weeks, all participants in the bPI arm will be switched to B/F/TAF and followed for a further 24 weeks and all participants will be followed for 48 weeks. The primary efficacy endpoint is the proportion of participants with HIV-1 RNA < 50 copies/mL at week 24 using pure virologic response whilst the secondary efficacy endpoint is the proportion of participants with HIV-1 RNA < 50 copies/mL at Week 48. Other secondary outcome measures include between arm comparisons of drug resistance at virological failure, safety and tolerability and patient-reported outcome measures. DISCUSSION: We aim to provide preliminary evidence of the efficacy of switching to B/F/TAF in patients with virological suppression on a bPI-based regimen who harbour select drug resistance mutations. TRIAL REGISTRATION: ISRCTN 44453201 , registered 19 June 2019 and EudraCT 2018-004732-30.

Condomless sex in HIV-diagnosed men who have sex with men in the UK: prevalence, correlates, and implications for HIV transmission.

OBJECTIVE: HIV transmission is ongoing among men who have sex with men (MSM) in the UK. Sex without a condom (condomless sex, CLS) is the main risk factor. We investigated the prevalence of and factors associated with types of CLS. METHODS: Cross-sectional questionnaire study in UK HIV clinics in 2011/2012 (ASTRA). MSM diagnosed with HIV for ≥3 months reported on anal and vaginal sex, CLS with HIV-serodifferent partners (CLS-D) and CLS with HIV-seroconcordant (CLS-C) partners in the previous 3 months. Mutually exclusive sexual behaviours were as follows: (1) Higher HIV risk CLS-D (not on antiretroviral therapy (ART) or clinic-recorded viral load(VL) >50 c/mL), (2) Other CLS-D, (3) CLS-C without CLS-D, (4) Condom-protected sex only and (5) No anal or vaginal sex. Associations were examined of sociodemographic, HIV-related, lifestyle, and other sexual measures with the five categories of sexual behaviour. We examined the prevalence of higher HIV risk CLS-D incorporating (in addition to ART and VL) time on ART, ART non-adherence, and recent sexually transmitted infections (STIs). RESULTS: Among 2189 HIV-diagnosed MSM (87% on ART), prevalence of any CLS in the past 3 months was 38.2% (95% CI 36.2% to 40.4%) and that of any CLS-D was 16.3% (14.8%-17.9%). The five-category classification was as follows: (1) Higher HIV risk CLS-D: 4.2% (3.5% to 5.2%), (2) Other CLS-D: 12.1% (10.8% to 13.5%), (3) CLS-C without CLS-D: 21.9% (20.2% to 23.7%), (4) Condom-protected sex only: 25.4% (23.6% to 27.3%) and (5) No anal or vaginal sex: 36.4% (34.3% to 38.4%). Compared with men who reported condom-protected sex only, MSM who reported any CLS in the past 3 months had higher prevalence of STIs, chemsex-associated drug use, group sex, higher partner numbers, and lifetime hepatitis C. Prevalence of higher HIV risk CLS-D ranged from 4.2% to 7.5% according to criteria included. CONCLUSION: CLS was prevalent among HIV-diagnosed MSM, but CLS-D with higher HIV transmission risk was overall low. CLS-D is no longer the most appropriate measure of HIV transmission risk behaviour among people with diagnosed HIV; accounting for VL is important.

Non-Disclosure of HIV Status and Associations with Psychological Factors, ART Non-Adherence, and Viral Load Non-Suppression Among People Living with HIV in the UK.

Disclosure of HIV status to family, friends, and a stable partner may be linked to improved health outcomes for people living with HIV. This study assessed whether non-disclosure is associated with psychological symptoms, non-adherence to antiretroviral therapy (ART), and viral load (VL) non-suppression. A total of 3258 HIV-diagnosed individuals in the UK completed the confidential ASTRA study questionnaire (2011-2012). Participants reported whether they told anyone they had HIV; to which confidant(s) (friends, family, work colleagues, stable partner) and to what extent (none, some, most/all). The prevalence and factors associated with non-disclosure were assessed. Associations between non-disclosure and the following factors were established using modified Poisson regression with adjustment for socio-demographic factors (gender, age group, ethnicity), HIV-related factors (time since HIV diagnosis, ART status), and clinic: low social support (score ≤ 12 on modified Duke-UNC FSSQ); depression and anxiety symptoms (≥10 on PHQ-9 and GAD-7 respectively); self-reported ART non-adherence in past 2 weeks/3 months; VL non-suppression (clinic-recorded VL > 50 copies/mL among those who started ART ≥ 6 months ago). Among 3233 participants with disclosure data, the prevalence of non-disclosure to anyone was 16.6 % (n/N = 61/367) among heterosexual men, 15.7 % (98/626) among women, and 5.0 % (113/2240) among MSM. MSM were more likely to disclose to some/all friends compared to family (85.8 vs. 59.9 %) while heterosexuals were less likely to disclose to friends than family (44.1 vs. 61.1 % for men, 57.5 vs. 67.1 % for women). Among 1,631 participants with a stable partner, non-disclosure to a stable partner was 4.9 % for MSM, 10.9 % for heterosexual men, and 13.0 % for women. In adjusted analyses, older age (≥60 years), non-white ethnicity, more recent HIV diagnosis, and not having a stable partner were significantly associated with overall non-disclosure for MSM and heterosexual individuals. The prevalence of low social support was 14.4 %, of depression and anxiety symptoms 27.1 and 22.0 %, respectively, of ART non-adherence 31.8 %, and of viral load non-suppression on ART 9.8 %. There was no evidence that non-disclosure overall (versus disclosure to anyone) was associated with low social support, depression or anxiety symptoms, ART non-adherence or VL non-suppression among MSM or heterosexual individuals. However, compared to MSM who disclosed to 'none' or 'some' friends and family, MSM who disclosed to 'most or all' of their friends and family were more likely to have symptoms of depression (adjusted PR = 1.4, 95 % CI 1.2-1.7), anxiety (1.3, 1.1-1.6), and to report ART non-adherence (1.3, 1.1-1.5). In this large multicentre study of people living with HIV in the UK, non-disclosure was overall low, but higher for heterosexual individuals compared to MSM. Non-disclosure was not associated with higher prevalence of adverse health measures.

Exploring the Challenges of Recruiting Older People for a Randomised Trial Assessing the Feasibility of Treating White Coat Hypertension in the UK General Practices: A Mixed-methods study.

INTRODUCTION: There is a recognised association between white coat hypertension (WCH) and adverse cardiovascular outcomes in older adults. However, there is no consensus on the management of WCH in this group. The objective of the Hypertension in the Very Elderly Trial (HYVET-2) study was to assess the feasibility of randomising 100 patients > 75years with WCH from General Practice in the UK to treatment or usual care. The study did not randomise any patients. In this follow-up study, we sought to explore the reasons for not recruiting. METHODS: Furthermore, using a mixed-methods study design, staff from 29 General Practice (GP) sites and the Clinical Research Network (CRN) in Kent, Surrey, and Sussex (KSS), UK, were sent an online questionnaire about local research facilities and infrastructure, and HYVET-2 study methodology and target population demographics. RESULTS: Nineteen (19) individuals responded to the online questionnaires (15 primary care staff, 4 CRN staff). Moreover, using a framework approach, we identified six themes summarising challenges to HYVET-2 recruitment. These themes are established approaches of primary care towards managing WCH in older people, target patient demographics, study design complexity, patient- facing study documents, limited research resources in primary care, and identification of eligible patients using existing coding. CONCLUSION: Our experience showed that recruiting older people from primary care to a WCH study was not feasible. A national scoping survey amongst primary care physicians in the UK, as well as robust patient and public involvement (PPI) targeting older people with WCH, might improve recruitment in future studies addressing the management of WCH in older people.

Investigating the effect of providing monetary incentives to participants on completion rates of referred co-respondents: An embedded randomized controlled trial.

Background: The use of a second informant (co-respondent) is a common method of identifying potential bias in outcome data (e.g., parent-report child outcomes). There is, however, limited evidence regarding methods of increasing response rates from co-respondents. The use of financial incentives is associated with higher levels of engagement and follow-up data collection in online surveys. This study investigated whether financial incentives paid to index participants in an online trial of a parenting-focused intervention, would lead to higher levels of co-respondent data collection. Methods: A study within a trial (SWAT) using a parallel group RCT design. Participants in the host study (an RCT of an online intervention) were randomised into one of two SWAT arms: received/did not receive a £15 voucher when referred co-respondent completed baseline measures. Primary outcome was completion (No/Yes) of Spence Children's Anxiety Scale (SCAS or SCAS-Pre) at baseline. Additional analysis explored impact of incentives on data quality. Results: Intention to treat analysis of 899 parents (183 co-respondents) in the no-incentive arm, and 911 parents (199 co-respondents) in incentive arm. Nomination of co-respondents was similar between incentive arms. The RR for the incentive arm compared to the no incentive arm was 1.13 (95% CI: 0.91 to 1.41, p = 0.264) indicating that incentives did not impact completion of outcomes by consented co-respondents. There were no indications of different data quality between arms. Discussion: The finding that payment of financial incentives to index participant does not lead to greater levels of co-respondent outcome completion suggests that careful consideration should be made before allocating resources in this way in future trials. Trial registration: The host study was registered at Study Record | ClinicalTrials.gov and the SWAT study was registered in the SWAT Store | The Northern Ireland Network for Trials Methodology Research (qub.ac.uk): SWAT number 143: Filetoupload,1099612,en.pdf (qub.ac.uk).

Preventing the spread of HIV infection.

Approximately 96,000 people are living with HIV in the UK, a quarter of whom are unaware they are infected. While in some parts of the world the number of people newly infected with HIV has fallen, in the UK in 2011 there was a rise in the number of men who have sex with men being diagnosed. HIV prevention strategies are a public health priority, while ongoing research into HIV testing in all clinical settings remains a priority. This article explores preventive measures that can be used to reduce the spread of HIV and offers advice on how nurses can contribute to these.

Investigating the effect of providing monetary incentives to participants on completion rates of referred co-respondents: An embedded randomized controlled trial. Study within a trial (SWAT) protocol.

Background: Parent-report questionnaires are a common method of generating data on child outcomes in mental health studies. A second report from another person who knows the child (co-respondent) is implemented to reduce bias and increase objectivity. The success of this approach is dependent on the engagement of co-respondents, which can be difficult. Financial incentives are used to increase data return in clinical trials, and to promote referral rates in online marketing. This protocol describes the use of an embedded randomised controlled trial (RCT) to investigate the effect of financial incentives on rates of co-respondent data completion. In the host RCT (of an online intervention designed to reduce the impact of a parent's anxiety on their child) index participants (i.e. parents) are asked to invite a co-respondent to complete measures on the index child. This study will test the hypothesis that providing monetary incentives to index participants will increase the outcome measure completion rate of co-respondents. Methods: Embedded RCT of two parallel groups. Participants in the intervention arm will be sent a £10 voucher if their chosen co-respondent completes online baseline measures. Participants in the control arm will not be offered payment regardless of their chosen co-respondent's behaviour. 1754 participants will take part. Analysis will compare co-respondent outcome measure completion rates between the two arms at baseline and follow-up. Conclusion: Findings from this study will provide evidence on the impact of offering payment to index participants on return rates of co-respondent data. This will inform resource allocation within future clinical trials.

Hepmarc: A 96 week randomised controlled feasibility trial of add-on maraviroc in people with HIV and non-alcoholic fatty liver disease.

OBJECTIVES: Maraviroc may reduce hepatic inflammation in people with HIV and non-alcoholic fatty liver disease (HIV-NAFLD) through CCR5-receptor antagonism, which warrants further exploration. METHODS: We performed an open-label 96-week randomised-controlled feasibility trial of maraviroc plus optimised background therapy (OBT) versus OBT alone, in a 1:1 ratio, for people with virologically-suppressed HIV-1 and NAFLD without cirrhosis. Dosing followed recommendations for HIV therapy in the Summary of Product Characteristics for maraviroc. The primary outcomes were safety, recruitment and retention rates, adherence and data completeness. Secondary outcomes included the change in Fibroscan-assessed liver stiffness measurements (LSM), controlled attenuation parameter (CAP) and Enhanced Liver Fibrosis (ELF) scores. RESULTS: Fifty-three participants (53/60, 88% of target) were recruited; 23 received maraviroc plus OBT; 89% were male; 19% had type 2 diabetes mellitus. The median baseline LSM, CAP & ELF scores were 6.2 (IQR 4.6-7.8) kPa, 325 (IQR 279-351) dB/m and 9.1 (IQR 8.6-9.6) respectively. Primary outcomes: all individuals eligible after screening were randomised; there was 92% (SD 6.6%) adherence to maraviroc [target >90%]; 83% (95%CI 70%-92%) participant retention [target >65%]; 5.5% of data were missing [target <20%]. There were noo Serious Adverse Reactions; mild-moderate intensity Adverse Reactions were reported by five participants (5/23, 22% (95%CI 5%-49%)) [target <10%]. All Adverse Reactions resolved. Secondary outcomes: no important differences were seen by treatment group for the change from baseline in LSM, CAP or ELF scores. CONCLUSIONS: This feasibility study provides preliminary evidence of maraviroc safety amongst people with HIV-NAFLD, and acceptable recruitment, retention, and adherence rates. These data support a definitive randomised-controlled trial assessing maraviroc impact on hepatic steatosis and fibrosis. TRIAL REGISTRATION: Clinical trial registry: ISCRTN, registration number 31461655.

Why some MSM present late for HIV testing: a qualitative analysis.

Although initiatives are under way in the UK to diagnose HIV infection early, late presentation is still a major issue and often results in serious health complications for the individual and has implications for society, including high costs and increased rates of transmission. Intervention strategies in the UK have aimed at increasing testing opportunities but still a significant proportion of those with HIV infection either decline testing or continue to test late. The main objective of this study is to identify ideas and themes as to why testing was not carried out earlier in men who have sex with men (MSM) who presented with late HIV infection. Semi-structured interviews were carried out with MSM presenting late with a CD4 cell count of <200. A structured framework approach was used to analyse the data collected and generate ideas as to why they did not seek testing earlier. Seventeen MSM were interviewed and four main themes were identified: psychological barriers, including fear of illness and dying, stigma surrounding testing for HIV and in living with a positive diagnosis, perceived low risk for contracting HIV despite participants reporting having a good understanding of HIV and its transmission and strong views that a more active approach by healthcare services, including general practice, is necessary if the uptake of HIV testing is to increase. Late presentation with HIV infection continues to be a problem in the UK despite government initiatives to expand opportunities for testing. Recurring themes for late testing were a low perceived risk for HIV infection and a fear of HIV and a positive diagnosis. Population-targeted health promotion alongside a more proactive approach by healthcare professionals and making HIV testing more convenient and accessible may result in earlier testing.

Reducing New Chlamydia Infection Among Young Men by Promoting Correct and Consistent Condom Use: Protocol for a Randomized Controlled Trial.

BACKGROUND: The health, social, and economic costs of sexually transmitted infections (STIs) represent a major public health concern. Young people are considered one of the groups most at risk for acquiring and transmitting STIs. Correct and consistent condom use has been shown to be the most effective method for reducing STIs; however, condoms are often not used properly. Evidence shows that brief behavior change interventions that focus on skills, communication, and motivation to acquire safe sex practices should be adopted into routine care to reduce STIs. Funding for sexual health services in England has declined dramatically, so novel ways of reducing clinic attendance are being sought. The home-based intervention strategy (HIS-UK) to promote condom use among young men has shown promise in feasibility and pilot studies by demonstrating high acceptability of the intervention in participant and health professional feedback, including aiding men to find condoms they like and feel more confident when using condoms. OBJECTIVE: The aim of this study is to determine the effectiveness and cost-effectiveness of HIS-UK when compared to usual condom distribution care among young men. METHODS: The 3 trial arms consisting of "e-HIS" (HIS-UK delivered digitally), "ProHIS" (HIS-UK delivered face-to-face), and control condition (usual National Health Service [NHS] care) will be compared against the following 3 primary outcomes: the extent to which correct and consistent condom use is increased; improvement of condom use experiences (pleasure as well as fit and feel); and decrease in chlamydia test positivity. Eligibility criteria include men aged 16-25 years at risk of STIs through reporting of condom use errors (ie, breakage or slippage) or condomless penile-vaginal or penile-anal intercourse with casual or new sexual partners during the previous 3 months. Prospective participants will be recruited through targeted advertisements and an opportunistic direct approach at selected sexual health and genitourinary medicine services and university-associated health centers and general practitioner practices. Community and educational establishments will be used to further advertise the study and signpost men to recruitment sites. Participants will be randomly allocated to 1 of 3 trial arms. A repeated measures design will assess the parallel arms with baseline and 12 monthly follow-up questionnaires after intervention and 3 chlamydia screening points (baseline, 6, and 12 months). RESULTS: Recruitment commenced in March 2020. Due to the COVID-19 pandemic, the study was halted and has since reopened for recruitment in Summer 2021. A 30-month recruitment period is planned. CONCLUSIONS: If effective and cost-effective, HIS-UK can be scaled up into routine NHS usual care to reduce both STI transmission in young people and pressure on NHS resources. This intervention may further encourage sexual health services to adopt digital technologies, allowing for them to become more widely available to young people while decreasing health inequalities and fear of stigmatization. TRIAL REGISTRATION: ISRCTN Registry ISRCTN11400820; https://www.isrctn.com/ISRCTN11400820.

Effectiveness of a Web-Based Intervention to Prevent Anxiety in the Children of Parents With Anxiety: Protocol for a Randomized Controlled Trial.

BACKGROUND: Anxiety is the most common childhood mental health condition and is associated with impaired child outcomes, including increased risk of mental health difficulties in adulthood. Anxiety runs in families: when a parent has anxiety, their child has a 50% higher chance of developing it themselves. Environmental factors are predominant in the intergenerational transmission of anxiety and, of these, parenting processes play a major role. Interventions that target parents to support them to limit the impact of any anxiogenic parenting behaviors are associated with reduced anxiety in their children. A brief UK-based group intervention delivered to parents within the UK National Health Service led to a 16% reduction in children meeting the criteria for an anxiety disorder. However, this intervention is not widely accessible. To widen access, a 9-module web-based version of this intervention has been developed. This course comprises psychoeducation and home practice delivered through text, video, animations, and practice tasks. OBJECTIVE: This study seeks to evaluate the feasibility of delivering this web-based intervention and assess its effectiveness in reducing child anxiety symptoms. METHODS:  This is the protocol for a randomized controlled trial (RCT) of a community sample of 1754 parents with self-identified high levels of anxiety with a child aged 2-11 years. Parents in the intervention arm will receive access to the web-based course, which they undertake at a self-determined rate. The control arm receives no intervention. Follow-up data collection is at months 6 and months 9-21. Intention-to-treat analysis will be conducted on outcomes including child anxiety, child mental health symptoms, and well-being; parental anxiety and well-being; and parenting behaviors. RESULTS: Funding was received in April 2020, and recruitment started in February 2021 and is projected to end in October 2022. A total of 1350 participants have been recruited as of May 2022. CONCLUSIONS: The results of this RCT will provide evidence on the utility of a web-based course in preventing intergenerational transmission of anxiety and increase the understanding of familial anxiety. TRIAL REGISTRATION: ClinicalTrials.gov NCT04755933; https://clinicaltrials.gov/ct2/show/NCT04755933. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/40707.

The Early Youth Engagement in first episode psychosis (EYE-2) study: pragmatic cluster randomised controlled trial of implementation, effectiveness and cost-effectiveness of a team-based motivational engagement intervention to improve engagement.

BACKGROUND: Early Intervention in Psychosis (EIP) services improve health outcomes for young people with psychosis in the medium-long term, but 25% of young people disengage in the first 12 months with costs to their mental health, families, society and the NHS. This study will evaluate the effectiveness, cost-effectiveness and implementation of a team-based motivational Early Youth Engagement (EYE-2) intervention. METHOD: The study design is a cluster randomised controlled trial (RCT) with economic evaluation, comparing the EYE-2 intervention + standardised EIP service to standardised EIP service alone, with randomisation at the team level. A process evaluation will evaluate the delivery of the intervention qualitatively and quantitatively across contexts. The setting is 20 EIP teams in 5 sites: Manchester, South London, East Anglia, Thames Valley and Hampshire. Participants are young people (14-35 years) with first episode psychosis, and EIP staff. The intervention is the team-based motivational engagement (EYE-2) intervention, delivered alongside standardised EIP services, and supported by additional training, website, booklets and social groups. The comparator is the standardised EIP service. Both interventions are delivered by EIP clinicians. The primary outcome is time to disengagement (time in days from date of allocation to care coordinator to date of last contact following refusal to engage with EIP service, or lack of response to EIP contact for a consecutive 3-month period). Secondary outcomes include mental and physical health, deaths, social and occupational function, recovery, satisfaction and service use at 6, 12, 18 and 24 months. A 12-month within-trial economic evaluation will investigate cost-effectiveness from a societal perspective and from an NHS perspective. DISCUSSION: The trial will provide the first test of an engagement intervention in standardised care, with the potential for significant impact on the mental health and wellbeing of young people and their families, and economic benefits for services. The intervention will be highly scalable, supported by the toolkit including manuals, commissioning guide, training and resources, adapted to meet the needs of the diverse EIP population, and based on an in-depth process evaluation. TRIAL REGISTRATION: ISRCTN 51629746 prospectively registered 7th May 2019. Date assigned 10th May 2019.

Protocol for a phase IV, open-label feasibility study investigating non-invasive markers of hepatic fibrosis in people living with HIV-1 and non-alcoholic fatty liver disease randomised to receiving optimised background therapy (OBT) plus maraviroc or OBT alone.

INTRODUCTION: At least 30% of people living with HIV (PLWH) infection have non-alcoholic fatty liver disease (NAFLD), which has now become a leading cause of hepatic fibrosis and cirrhosis. Management is based largely on lifestyle modifications, which are difficult to achieve, and therapeutic options are urgently needed. Maraviroc (MVC), through antagonism of CCR5 receptors, may reduce hepatic fibrosis progression and could be an effective treatment for NAFLD. However, dosing is usually two times per day, unlike most currently recommended antiretroviral therapies. This study will investigate the feasibility and acceptability of addition of MVC to combination antiretroviral therapy in PLWH and NAFLD as a treatment for NAFLD. METHODS AND ANALYSIS: This is a phase IV, randomised, open-label, non-invasive feasibility study. Sixty individuals with well-controlled HIV-1 and NAFLD will be recruited from UK HIV clinics and randomised 1:1 to receive either optimised background therapy (OBT) plus MVC or OBT alone. Follow-up will be every 24 weeks for 96 weeks. The primary outcome measures will include recruitment and retention rates, adverse events and adherence. Secondary outcomes will include changes in markers of hepatic fibrosis, including the Enhanced Liver Fibrosis score, median liver stiffness measurement and controlled attenuation parameter scores on Fibroscan, and quality of life assessments. Analyses will be performed according to intention-to-treat principles. For secondary outcomes, estimated differences and 95% CIs between the groups using a t-method will be presented for continuous variables and as exact 95% binomial CIs for categorical variables. ETHICS AND DISSEMINATION: Ethical approval was obtained through the London Dulwich UK Research Ethics Committee (reference 17/LO/2093). Results will be disseminated both through community groups and peer-reviewed scientific literature.Trial registration number SRCTN31461655. EudraCT number 2017-004141-24; Pre-results.

Reducing Implant Infection in Orthopaedics (RIIiO): a pilot study for a randomised controlled trial comparing the influence of forced air versus resistive fabric warming technologies on postoperative infection rates following orthopaedic implant surgery in adults.

BACKGROUND: Approximately 70,000 to 75,000 proximal femoral fracture repairs take place in the UK each year. Hemiarthroplasty is the preferred treatment for adults aged over 60 years. Postoperative infection affects up to 3% of patients and is the single most common reason for early return to theatre. Ultraclean ventilation was introduced to help mitigate the risk of infection, but it may also contribute to inadvertent perioperative hypothermia, which itself is a risk for postoperative infection. To counter this, active intraoperative warming is used for all procedures that take 30 min or more. Forced air warming (FAW) and resistive fabric warming (RFW) are the two principal techniques used for this purpose; they are equally effective in prevention of inadvertent perioperative hypothermia, but it is not known which is associated with the lowest infection rates. Deep surgical site infection doubles operative costs, triples investigation costs and quadruples ward costs. The Reducing Implant Infection in Orthopaedics (RIIiO) study seeks to compare infection rates with FAW versus RFW after hemiarthroplasty for hip fracture. A cost-neutral intervention capable of reducing postoperative infection rates would likely lead to a change in practice, yield significant savings for the health economy, reduce overall exposure to antibiotics and improve outcomes following hip fracture in the elderly. The findings may be transferable to other orthopaedic implant procedures and to non-orthopaedic surgical specialties. METHODS: RIIiO is a parallel group, open label study randomising hip fracture patients over 60 years of age who are undergoing hemiarthroplasty to RFW or FAW. Participants are followed up for 3 months. Definitive deep surgical site infection within 90 days of surgery, the primary endpoint, is determined by a blinded endpoint committee. DISCUSSION: Hemiarthroplasty carries a risk of deep surgical site infection of approximately 3%. In order to provide 90% power to demonstrate an absolute risk reduction of 1%, using a 5% significance level, a full trial would need to recruit approximately 8630 participants. A pilot study is being conducted in the first instance to demonstrate that recruitment and data management strategies are appropriate and robust before embarking on a large multi-centre trial. TRIAL REGISTRATION: ISRCTN, ISRCTN74612906 . Registered on 27 February 2017.

Patients' perspectives on the development of HIV services to accommodate ageing with HIV: a qualitative study.

The objective of this study was to identify the aspects of healthcare that are most valued by people with HIV and to describe their concerns and preferences for the future delivery of services for non-HIV-related illness. Twelve focus groups of people receiving HIV care were conducted in community settings in South-East England. Groups were quota sampled based on age, gender, sexual orientation and ethnicity. Data were analysed using Framework Analysis. The results showed that among the 74 respondents (61% male), a preference for maintaining all care within specialist HIV clinics was commonplace, but was highest among participants with more extensive histories of HIV and comorbidities. Participants valued care-coordination, inter-service communication and timely updates to medical notes. There were high levels of concern around HIV skills in general practices and the capacity of general practitioners to manage patient confidentiality or deal appropriately with the emotional and social challenges of living with HIV. Participants valued, and had an overall preference for, the specialist knowledge and skills of HIV services, suggesting that non-HIV-specialist services will need to build their appeal if they are to have a greater future role in the care of people with HIV. Particular concerns that should be addressed include: patient confidence in the HIV knowledge and skills of non-specialist service providers; clear processes for prescribing and referrals; improved levels of care-coordination and communication between services and increased patient confidence in the capacity of primary care to maintain confidentiality and to appreciate the stigma associated with HIV.

HIV testing in patients presenting with indicator conditions in outpatient settings: offer and uptake rates, and educational and active interventions.

Approximately 13% of people living with HIV in the UK are undiagnosed which has significant implications in terms of onward transmission and late diagnosis. HIV testing guidelines recommend routine screening in anyone presenting to healthcare with an HIV indicator condition (IC); however, this does not occur routinely. This study aimed to assess the feasibility and effectiveness of using case note prompts highlighting the presence of an IC to increase HIV testing. Clinicians in three outpatient departments received case note prompts either before or after a period of clinician-led identification. Test offer and uptake rates were assessed. A parallel anonymous seroprevalence study estimated the prevalence of undiagnosed HIV. A total of 4191 patients had an appointment during the study period; 608 (14.5%) had an IC. HIV test offer was significantly higher when a prompt was inserted into notes (34.3% versus 3.2%, p < 0.001). The prevalence of diagnosed HIV in the cohort was 4.1%. No cases of undiagnosed HIV infection were identified. Despite guidelines, offer of HIV testing is low. Strategies to increase routine screening of patients presenting with an IC are needed. Individual case note prompts significantly increase HIV test offer; however, the effect is lost if the strategy is withdrawn.

An observational study of comorbidity and healthcare utilisation among HIV-positive patients aged 50 years and over.

The number of HIV-positive people aged ≥50 years is rising each year. We measured the prevalence of non-infectious illnesses and their risk factors and described healthcare use in this UK population. A cross-sectional, observational study was conducted at an outpatient HIV specialist clinic in south east England. Patients age ≥50 years were invited to complete questionnaires measuring demographics, non-infectious illnesses, medication use, lifestyle and healthcare utilisation. The response rate was 67%. Of 299 participants, 84% reported ≥1 comorbid condition and 61% reported ≥2 (multimorbidity). Most commonly reported were high cholesterol, sexual dysfunction, hypertension and depression. In multivariate analyses, age, number of years HIV-positive and duration of antiretroviral therapy remained significant predictors of comorbidity when controlling for lifestyle factors (exercise, smoking and use of recreational drugs and alcohol). Use of non-HIV healthcare services was associated with increasing comorbidity, a longer duration of HIV and recreational drug use. The majority of HIV-patients aged ≥50 years reported multiple comorbidities and this was associated with polypharmacy and increased use of non-HIV services. Further research examining the quality, safety and patient experience of healthcare is needed to inform development of services to optimally meet the needs of older HIV-positive patients.

Understanding HIV-positive patients' preferences for healthcare services: a protocol for a discrete choice experiment.

INTRODUCTION: While the care of HIV-positive patients, including the detection and management of comorbidities, has historically been provided in HIV specialist outpatient clinics, recent years have seen a greater involvement of non-HIV specialists and general practitioners (GPs). The aim of this study is to determine whether patients would prefer to see their GP or HIV physician given general symptoms, and to understand what aspects of care influence their preferences. METHODS/ANALYSIS: We have developed and piloted a discrete choice experiment (DCE) to better understand patients' preferences for care of non-HIV-related acute symptoms. The design of the DCE was informed by our exploratory research, including the findings of a systematic literature review and a qualitative study. Additional questionnaire items have been included to measure demographics, service use and experience of non-HIV illnesses and quality of life (EQ5D). We plan to recruit 1000 patients from 14 HIV clinics across South East England. Data will be analysed using random-effects logistic regression and latent class analysis. ORs and 95% CIs will be used to estimate the relative importance of each of the attribute levels. Latent class analysis will identify whether particular groups of people value the service attribute levels differently. ETHICS/DISSEMINATION: Ethical approval for this study was obtained from the Newcastle and North Tyneside Research Ethics Committee (reference number 14/NE/1193). The results will be disseminated at national and international conferences and peer-reviewed publications. A study report, written in plain English, will be made available to all participants. The Patient Advisory Group will develop a strategy for wider dissemination of the findings to patients and the public.