Utilising survey data and qualitative information to inform a logic model to support older people in custody with common mental and physical health problems: Addressing the physical and mental health needs of older prisoners (the PAMHOP study).

A growing number of older people remain in custody each year resulting in an increasing number of common mental and physical health concerns. No prior evidenced-based targeted psychological interventions support this group of people, and little is known about their needs, current activities, and health-related problems. We addressed these gaps through a project involving older prisoners, prison staff and a project advisory group in one male and one female prison site in the North of England. Systematic review evidence supports the development of an implementation tool kit addressing strategies to develop and deliver interventions that are sustainable, acceptable, and feasible in the prison environment. Prison strategies need to specifically address the needs of older people in custody. Relatively inexpensive activities, with some thought to delivery and flexibility have the potential to benefit common mental and physical health, increasing quality of life, reducing high economic and social cost, mortality, and reoffending in this age group.

The effectiveness and acceptability of multimedia information when recruiting children and young people to trials: the TRECA meta-analysis of SWATs.

Background: The information provided to potential trial participants plays a crucial role in their decision-making. Printed participant information sheets for trials have received recurrent criticism as being too long and technical, unappealing and hard to navigate. An alternative is to provide information through multimedia (text, animations, video, audio, diagrams and photos). However, there is limited evidence on the effects of multimedia participant information on research recruitment rates, particularly in children and young people. Objectives: The study objectives were as follows: 1. to develop template multimedia information resources through participatory design, for use when recruiting children and young people to trials 2. to evaluate the multimedia information resources in a series of Studies Within A Trial, to test their effects on recruitment and retention rates, and participant decision-making, by comparing the provision of multimedia information resources instead of printed participant information sheets, and comparing the provision of multimedia information resources in addition to printed participant information sheets. Design: Two-phase study: 1. multimedia information resources development including qualitative study; user testing study; readability metrics; enhanced patient and public involvement 2. multimedia information resources' evaluation comprising Studies Within A Trial undertaken within host trials recruiting children and young people. Setting: United Kingdom trials involving patients aged under 18. Participants: Development phase: n = 120 (children and young people, parents, clinicians, trial personnel). Evaluation phase: n = 1906 (children and young people being asked to take part in trials). Interventions: Multimedia information resources (comprising text, audio, 'talking heads' video, trial-specific and trial-generic animations). Printed participant information sheets. Main outcome measures: Primary outcome: trial recruitment rate comparing multimedia information resource-only with printed participant information sheet-only provision. Secondary outcomes: trial recruitment rate comparing combined multimedia information resource and printed participant information sheet with printed participant information sheet-only provision; trial retention rate; quality of participant decision-making. Results for each trial were calculated and combined in a two-stage random-effects meta-analysis. Results: Phase 1 generated two multimedia information resource templates: (1) for children aged 6-11 years; (2) for children aged 12-18 years and parents. In the Phase 2 Studies Within A Trial the multimedia information resources improved trial recruitment, when compared to printed information alone [odds ratio (OR) = 1.54; 95% confidence interval (CI) 1.05 to 2.28; p = 0.03; I2 = 0%]. When printed participant information sheet-only provision was compared to combined multimedia information resource and printed participant information sheet provision, there was no effect on trial recruitment (OR = 0.89; 95% CI 0.53 to 1.50; I2 = 0%). There were no differences between multimedia information resource and printed participant information sheet on trial retention or participant decision-making quality. In a study within a hypothetical trial setting, multimedia information resource-only provision produced higher ratings of 'information was easy to understand' (Z = 3.03; p = 0.003) and 'I had confidence in decision-making' (Z = 2.00; p = 0.044) than printed participant information sheet-only provision. Limitations: It was not possible to include data from three Studies Within A Trial in the meta-analysis due to limited sample size, and questionnaire return rates were low, which reduced the strength of the findings. Conclusions: Use of multimedia information increased the rate of recruitment to trials involving children and young people compared to standard patient information sheets. Future work: There should be further evaluation of the effects of multimedia information on recruitment to trials involving children and young people. It would be valuable to assess any impacts of multimedia information resources on communication between trial recruiters, children and young people, and parents. Study registration: This trial is registered as TRECA ISRCTN 73136092 and Northern Ireland Hub for Trials Methodology Research SWAT Repository (SWAT 97). Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: 14/21/21) and is published in full in Health and Social Care Delivery Research; Vol. 11, No. 24. See the NIHR Funding and Awards website for further award information.

Clinical trials are important to National Health Service care, but it can be difficult to recruit enough people. We do not know enough about how to improve recruitment, especially when trying to recruit children and young people. People are normally told about a trial through printed information, which is often long and complex. Multimedia information (text, audio, cartoons and video) might be a better way of telling people. It is important to test whether multimedia interventions can help. One way of doing this is to run a 'Study Within A Trial' where people receive information in different ways. We created two multimedia interventions, one for parents and young people being asked for consent, and a simpler one for younger children. Some content applied to all trials, and some about the specific trial people were being asked to consider. We designed these by working closely with children and young people, parents and healthcare staff. We tested the multimedia information in six trials (although only three gave us enough data). Children, young people and their parents saw either standard printed information or our multimedia information. We then collected data on their decision-making, trial recruitment and whether people stayed in the trial. Children and young people who saw multimedia information were more likely to be recruited than those who received standard printed information. Once recruited to a trial, people given multimedia or printed information were similarly likely to remain in the trial. People's views on multimedia and printed information were also similar, but this finding could have been affected by small numbers of people returning questionnaires. Our study provides evidence that multimedia information can be used in trials with children and young people and that it increases the number of people who agree to take part, but further work is needed.

Effects of interventions on depression and anxiety in older people with physical health problems in the criminal justice system: a systematic review.

The demand for health care in older people involved in the criminal justice system is high. The prevalence of mental and physical health conditions for people living in prison is greater than in community populations. After systematically searching 21 databases, we found no targeted interventions to support depression or anxiety for this group of people. 24 studies (including interventions of yoga, creative-arts-based programmes, positive psychology, or mindfulness-based interventions and psychotherapy) did contain people older than 50 years, but this only represented a minority (10%) of the overall study population. No single study reported outcomes of physical health. Future interventions need to consider the needs and views of this vulnerable group. Specific gendered and coproduced interventions are required to enhance the implementation, feasibility, and acceptability of interventions that are delivered in prisons.

Providing multimedia information to children and young people increases recruitment to trials: pre-planned meta-analysis of SWATs.

BACKGROUND: Randomised controlled trials are often beset by problems with poor recruitment and retention. Information to support decisions on trial participation is usually provided as printed participant information sheets (PIS), which are often long, technical, and unappealing. Multimedia information (MMI), including animations and videos, may be a valuable alternative or complement to a PIS. The Trials Engagement in Children and Adolescents (TRECA) study compared MMI to PIS to investigate the effects on participant recruitment, retention, and quality of decision-making. METHODS: We undertook six SWATs (Study Within A Trial) within a series of host trials recruiting children and young people. Potential participants in the host trials were randomly allocated to receive MMI-only, PIS-only, or combined MMI + PIS. We recorded the rates of recruitment and retention (varying between 6 and 26 weeks post-randomisation) in each host trial. Potential participants approached about each host trial were asked to complete a nine-item Decision-Making Questionnaire (DMQ) to indicate their evaluation of the information and their reasons for participation/non-participation. Odds ratios were calculated and combined in a meta-analysis. RESULTS: Data from 3/6 SWATs for which it was possible were combined in a meta-analysis (n = 1758). Potential participants allocated to MMI-only were more likely to be recruited to the host trial than those allocated to PIS-only (OR 1.54; 95% CI 1.05, 2.28; p = 0.03). Those allocated to combined MMI + PIS compared to PIS-only were no more likely to be recruited to the host trial (OR = 0.89; 95% CI 0.53, 1.50; p = 0.67). Providing MMI rather than PIS did not impact on DMQ scores. Once children and young people had been recruited to host trials, their trial retention rates did not differ according to intervention allocation. CONCLUSIONS: Providing MMI-only increased the trial recruitment rate compared to PIS-only but did not affect DMQ scores. Combined MMI + PIS instead of PIS had no effect on recruitment or retention. MMIs are a useful tool for trial recruitment in children and young people, and they could reduce trial recruitment periods.

The effectiveness of video animations in the education of healthcare practitioners and student practitioners: a systematic review of trials.

INTRODUCTION: Video animations are increasingly available in education but without systematic evaluation. This review aimed to collate trials of animations versus other delivery, in student or qualified healthcare practitioners. METHODS: Included studies had the following features: controlled design with random or quasi-random allocation; student or qualified healthcare practitioners; comparing video animation with another format (e.g. textbook, lecture, static images); animation delivered instead of, or in addition to, another format. The primary outcome was knowledge; secondary outcomes were attitudes and cognitions, and behaviours. Multiple databases were searched from 1996-October 2022 using a defined strategy. We also undertook citation searching. Dual, independent decision-making was used for inclusion assessment, data extraction, and quality appraisal. Included studies were appraised using the Cochrane ROB2 tool. Findings were reported using narrative synthesis. RESULTS: We included 13 studies: 11 recruited student practitioners, two recruited qualified practitioners, total n = 1068. Studies evaluated cartoon animations or 2D/3D animations. Knowledge was assessed in ten studies, showing greater knowledge from animations in eight studies. Attitudes and cognitions were assessed in five studies; animations resulted in positive outcomes in three studies, no difference in one study, and worse outcomes in one study. Behaviours were assessed in three studies, animations producing positive outcomes in two studies and there was no difference in one study. Overall risk of bias was 'high' in ten studies and 'some concerns' in three. DISCUSSION: Overall the evidence base is small with mostly 'high' risk of bias. Video animations show promise in practitioner education, particularly for effects on knowledge, but bigger, better research is needed.

Does digital, multimedia information increase recruitment and retention in a children's wrist fracture treatment trial, and what do people think of it? A randomised controlled Study Within A Trial (SWAT).

OBJECTIVES: To evaluate digital, multimedia information (MMI) for its effects on trial recruitment, retention, decisions about participation and acceptability by patients, compared with printed information. DESIGN: Study Within A Trial using random cluster allocation within the Forearm Fracture Recovery in Children Evaluation (FORCE) study. SETTING: Emergency departments in 23 UK hospitals. PARTICIPANTS: 1409 children aged 4-16 years attending with a torus (buckle) fracture, and their parents/guardian. Children's mean age was 9.2 years, 41.0% were female, 77.4% were ethnically White and 90.0% spoke English as a first language. INTERVENTIONS: Participants and their parents/guardian received trial information either via multimedia, including animated videos, talking head videos and text (revised for readability and age appropriateness when needed) on tablet computer (MMI group; n=681), or printed participant information sheet (PIS group; n=728). OUTCOME MEASURES: Primary outcome was recruitment rate to FORCE. Secondary outcomes were Decision-Making Questionnaire (nine Likert items, analysed summatively and individually), three 'free text' questions (deriving subjective evaluations) and trial retention. RESULTS: MMI produced a small, not statistically significant increase in recruitment: 475 (69.8%) participants were recruited from the MMI group; 484 (66.5%) from the PIS group (OR=1.35; 95% CI 0.76 to 2.40, p=0.31). A total of 324 (23.0%) questionnaires were returned and analysed. There was no difference in total Decision-Making Questionnaire scores: adjusted mean difference 0.05 (95% CI -1.23 to 1.32, p=0.94). The MMI group was more likely to report the information 'very easy' to understand (89; 57.8% vs 67; 39.4%; Z=2.60, p=0.01) and identify information that was explained well (96; 62.3% vs 71; 41.8%). Almost all FORCE recruits were retained at the 6 weeks' timepoint and there was no difference in retention rate between the information groups: MMI (473; 99.6%); PIS (481; 99.4%). CONCLUSIONS: MMI did not increase recruitment or retention in the FORCE trial, but participants rated multimedia as easier to understand and were more likely to evaluate it positively. TRIAL REGISTRATION NUMBER: ISRCTN73136092 and ISRCTN13955395.

GP wellbeing during the COVID-19 pandemic: a systematic review.

BACKGROUND: Doctors' organisations in the UK have reported worrying levels of work-related stress and burnout in the GP workforce for some time, and the COVID-19 pandemic has presented clear new challenges. AIM: To synthesise international evidence exploring the impact of COVID-19 on primary care doctors' mental health and wellbeing, and identify risk factors associated with their psychological wellbeing during this time. DESIGN AND SETTING: Mixed-methods systematic review. METHOD: Six bibliographic databases, Google Scholar, and MedRxiv were searched on 19 November 2020 and 3 June 2021 to identify studies of GP psychological wellbeing during the pandemic. Reference checking was also conducted. Two reviewers selected studies, extracted data, and assessed the quality of studies using standardised tools. Heterogeneity in outcomes, setting, and design prohibited statistical pooling; studies were combined using a convergent integrated thematic synthesis. RESULTS: Thirty-one studies were included. Multiple sources of stress were identified including changed working practices; risk, exposure, and inadequate personal protective equipment (PPE); information overload; pandemic preparedness; and cohesion across sectors. Studies demonstrated an impact on psychological wellbeing, with some GPs experiencing stress, burnout, anxiety, depression, fear of COVID-19, lower job satisfaction, and physical symptoms. Studies reported gender and age differences: women GPs had poorer psychological outcomes across all domains, and older GPs reported greater stress and burnout. Use of outcome measures and reporting practice varied greatly. CONCLUSION: This review of international evidence demonstrates that the COVID-19 pandemic has adversely affected GPs' wellbeing around the world. Further research could explore gender and age differences, identifying interventions targeted to these groups.

Effectiveness of tailored digital health interventions for mental health at the workplace: A systematic review of randomised controlled trials.

Mental health problems in the workplace are common and have a considerable impact on employee wellbeing and productivity. Mental ill-health costs employers between £33 billion and £42 billion a year. According to a 2020 HSE report, roughly 2,440 per 100,000 workers in the UK were affected by work-related stress, depression, or anxiety, resulting in an estimated 17.9 million working days lost. We performed a systematic review of randomised controlled trials (RCTs) to assess the effect of tailored digital health interventions provided in the workplace aiming to improve mental health, presenteeism and absenteeism of employees. We searched several databases for RCTs published from 2000 onwards. Data were extracted into a standardised data extraction form. The quality of the included studies was assessed using the Cochrane Risk of Bias tool. Due to the heterogeneity of outcome measures, narrative synthesis was used to summarise the findings. Seven RCTs (eight publications) were included that evaluated tailored digital interventions versus waiting list control or usual care to improve physical and mental health outcomes and work productivity. The results are promising to the advantage of tailored digital interventions regarding presenteeism, sleep, stress levels, and physical symptoms related to somatisation; but less for addressing depression, anxiety, and absenteeism. Even though tailored digital interventions did not reduce anxiety and depression in the general working population, they significantly reduced depression and anxiety in employees with higher levels of psychological distress. Tailored digital interventions seem more effective in employees with higher levels of distress, presenteeism or absenteeism than in the general working population. There was high heterogeneity in outcome measures, especially for work productivity; this should be a focus of attention in future studies.

The effectiveness of video animations as information tools for patients and the general public: A systematic review.

Background and objectives: Video animations are used increasingly as patient information tools; however, we do not know their value compared to other formats of delivery, such as printed materials, verbal consultations or static images. Methods: This review compares the effectiveness of video animations as information tools vs. other formats of delivery on patient knowledge, attitudes and cognitions, and behaviours. Included studies had the following features: controlled design with random or quasi-random allocation; patients being informed about any health condition or members of the public being informed about a public health topic; comparing video animation with another delivery format. Multiple digital databases were searched from 1996-June 2021. We also undertook citation searching. We used dual, independent decision-making for inclusion assessment, data extraction and quality appraisal. Included studies were appraised using the Cochrane ROB2 tool. Findings were reported using narrative synthesis. Results: We included 38 trials, focussed on: explaining medical or surgical procedures (n = 17); management of long-term conditions (n = 11); public health, health-promotion or illness-prevention (n = 10). Studies evaluated cartoon animations (n = 29), 3D animations (n = 6), or 2D animations, "white-board" animations or avatars (n = 1 each). Knowledge was assessed in 30 studies, showing greater knowledge from animations in 19 studies, compared to a range of comparators. Attitudes and cognitions were assessed in 21 studies, and animations resulted in positive outcomes in six studies, null effects in 14 studies, and less positive outcomes than standard care in one study. Patient behaviours were assessed in nine studies, with animations resulting in positive outcomes in four and null effects in the remainder. Overall risk of bias was "high" (n = 18), "some concerns" (n = 16) or "low" (n = 4). Common reasons for increased risk of bias were randomisation processes, small sample size or lack of sample size calculation, missing outcome data, and lack of protocol publication. Discussion: The overall evidence base is highly variable, with mostly small trials. Video animations show promise as patient information tools, particularly for effects on knowledge, but further evaluation is needed in higher quality studies. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?, identifier: CRD42021236296.

Evaluating the use of multimedia information when recruiting adolescents to orthodontics research: A randomised controlled trial.

OBJECTIVE: To compare two methods of providing information about the Bone Anchored Maxillary Protraction (BAMP) trial: standard printed information and multimedia websites, for their quality and ease of understanding, and impact on decision-making. DESIGN: Randomised controlled trial. SETTING: Orthodontic outpatient clinic in the UK. METHODS: Participants were 109 adolescents (aged 11-14 years) attending for orthodontic treatment. While awaiting treatment they were asked to imagine being recruited to the BAMP clinical trial. They were individually randomised to receive the printed or the multimedia website information (comprising text, animations and 'talking head' videos). After reading or viewing the information, they completed a 9-item Likert scale Decision-Making Questionnaire (DMQ) (score range 0-36) plus three free-text questions on their evaluation of the information. RESULTS: A total of 104 participants completed the questionnaire. Mean total DMQ scores were higher (more positive) in the website group (28.1 vs. 27.0), although the difference was small and not statistically significant (P = 0.20). Analysis of individual questionnaire items showed two statistically significant differences: the website information had higher ratings on 'easy to understand' (Z = 3.03; P = 0.003) and 'confidence in decision-making' (Z = 2.00; P = 0.044). On the three free-text questions, more positive and fewer negative comments were made about the websites than the printed information. CONCLUSION: In this hypothetical trial setting, adolescent patients found that trial information conveyed on a multimedia website was easier to understand and made them more confident in their decision about trial participation. Their subjective evaluations of the website were also more positive and less negative than about the printed information. Multimedia information has the potential to increase the quality of engagement and information exchange when seeking consent for research.

The RESPECT study: a feasibility randomised controlled trial of a sexual health promotion intervention for people with serious mental illness in community mental health services in the UK.

BACKGROUND: People with serious mental illness (SMI) have sexual health needs but there is little evidence to inform effective interventions to address them. In fact, there are few studies that have addressed this topic for people with SMI outside USA and Brazil. Therefore, the aim of the study was to establish the acceptability and feasibility of a trial of a sexual health promotion intervention for people with SMI in the UK. METHOD: The RESPECT study was a two-armed randomised controlled, open feasibility trial (RCT) comparing Sexual health promotion intervention (3 individual sessions of 1 h) (I) or treatment as usual (TAU) for adults aged 18 or over, with SMI, within community mental health services in four UK cities. The main outcome of interest was the percentage who consented to participate, and retained in each arm of the trial, retention for the intervention, and completeness of data collection. A nested qualitative study obtained the views of participants regarding the acceptability of the study using individual telephone interviews conducted by lived experience researchers. RESULTS: Of a target sample of 100, a total of 72 people were enrolled in the trial over 12 months. Recruitment in the initial months was low and so an extension was granted. However this extension meant that the later recruited participants would only be followed up to the 3 month point. There was good retention in the intervention and the study as a whole; 77.8% of those allocated to intervention (n = 28) received it. At three months, 81.9% (30 I; 29 TAU) and at 6 months, 76.3% (13 I and 16 TAU) completed the follow-up data collection. No adverse events were reported. There was good completeness of the data. The sexual health outcomes for the intervention group changed in favour of the intervention. Based on analysis of the qualitative interviews, the methods of recruitment, the quality of the participant information, the data collection, and the intervention were deemed to be acceptable to the participants (n = 22). CONCLUSIONS: The target of 100 participants was not achieved within the study's timescale. However, effective strategies were identified that improved recruitment in the final few months. Retention rates and completeness of data in both groups indicate that it is acceptable and feasible to undertake a study promoting sexual health for people with SMI. A fully powered RCT is required to establish effectiveness of the intervention in adoption of safer sex. STUDY REGISTRATION: ISRCTN Registry ISRCTN15747739 prospectively registered 5th July 2016.

Poor allocation concealment methods are associated with heterogeneity in age and statistical significance of the primary outcome: Review of recent trials published in four general medical journals.

OBJECTIVE: To assess the association of the quality of allocation concealment with heterogeneity in age, the P value of the primary outcome and statistical significance of the primary outcome. STUDY DESIGN AND SETTING: We extracted data from articles published in four major medical journals in 2017 and 2018 that reported the results of randomized controlled trials. The outcome measures were the quality of allocation concealment used in the trial, the P value of the primary outcome, whether the P value of the primary outcome was statistically significant and the level of heterogeneity in age between the treatment groups (measured using the I2 statistic). The association between the quality of allocation concealment and the P value of the primary outcome was assessed using a kernel density plot, while the association between the quality of allocation concealment and whether the P value was statistically significant was assessed using logistic regression. RESULTS: Trials that used inadequate concealment methods were more likely to report statistically significant findings than trials that used good or adequate methods (OR 1.90; 95% CI: 0.91 to 3.95; P = .09). The values of I2 for trials that used good, adequate, inadequate and unclear concealment methods were 0%, 1.0%, 32.6%, and 93.8%, respectively. CONCLUSION: There is evidence of an association between poor allocation concealment methods and statistical significance of the primary outcome. Trials that use inadequate allocation concealment methods are more likely to have statistically significant P values compared with trials using good or adequate allocation concealment methods.

Sexual health promotion in people with severe mental illness: the RESPECT feasibility RCT.

BACKGROUND: People with serious mental illness have sexual health needs, but there is limited evidence regarding effective interventions to promote their sexual health. OBJECTIVES: To develop a sexual health promotion intervention for people with serious mental illness, and to conduct a feasibility trial in order to establish the acceptability and parameters for a fully powered trial. DESIGN: A two-armed randomised controlled, open feasibility study comparing usual care alone with usual care plus the adjunctive intervention. SETTING: Five community mental health providers in Leeds, Barnsley, Brighton and London. PARTICIPANTS: Adults aged ≥ 18 years with serious mental illness and receiving care from community mental health teams. INTERVENTIONS: A remote, web-based computer randomisation system allocated participants to usual care plus the RESPECT (Randomised Evaluation of Sexual health Promotion Effectiveness informing Care and Treatment) intervention (three sessions of 1 hour) (intervention arm) or usual care only (control arm). The intervention was an interactive manualised package of exercises, quizzes and discussion topics focusing on knowledge, motivation and behavioural intentions to adopt safer sexual behaviours. MAIN OUTCOME MEASURES: Feasibility parameters including establishing the percentage of people who were eligible, consented and were retained in each arm of the trial, retention for the intervention, as well as the completeness of the data collection. Data were collected on knowledge, motivation to adopt safer sexual behaviour, sexual behaviour, sexual stigma, sexual health service use and quality of life. Data were collected at baseline and then at 3 months and 6 months post randomisation. RESULTS: Of a target of 100 participants, 72 people participated in the trial over 12 months. Of the 36 participants randomised to the intervention arm, 27 received some of the intervention (75.0%). At 3 months, 59 of the 72 participants completed follow-up questionnaires (81.9%) (30 participants from the intervention arm and 29 participants from the control arm). Only the first 38 participants were followed up at 6 months. However, data were collected on 29 out of 38 participants (76.3% retention): 13 in the intervention arm and 16 in the control arm. No adverse events were reported. Participant feedback confirmed that both the design and the intervention were acceptable. The economic analysis indicated high completion rates and completeness of data among participants who continued the trial. CONCLUSIONS: Despite the limitations, the findings suggest that it is both acceptable and feasible to undertake a sexual health promotion study for people with serious mental illness. FUTURE WORK: A fully powered randomised controlled trial would be required to establish the clinical effectiveness of the intervention. TRIAL REGISTRATION: Current Controlled Trials ISRCTN15747739. 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. 23, No. 65. See the NIHR Journals Library website for further project information.

A team of researchers, mental health and sexual health workers, and people with lived experience of mental health problems developed an intervention to help people with serious mental health problems to increase their knowledge and understanding of sexual health, including types of contraception, using condoms safely and sexually transmitted infections, and to consider safety and assertiveness in intimate relationships. This was delivered over three sessions of 1 hour by a specifically trained mental health worker. We recruited 72 people from community mental health services to take part in a study to test the intervention and see whether or not we could collect information about their sexual behaviour using questionnaires. Initially, the numbers of people volunteering for the study were very small. We found that recruitment increased when we shifted to a more direct approach (rather than asking clinical staff to promote the study to people on their caseloads). The direct approach included talking to people who use services directly in clinics and at service user events, and by sending study information by post. We were not able to recruit the numbers that we aimed to (72/100 participants) in the timescale of the study, but the majority of the people who were recruited actively participated in the trial and were generally happy to attend follow-up appointments to complete more questionnaires. Most of those who were allocated to the intervention attended all three sessions. Overall, people found that being a participant of the study was comfortable and safe (acceptable) and we found that it was possible to undertake this type of study within mental health services. We have learnt a lot about how we could run this study on a larger scale. Such a study would allow us to see if the intervention makes a difference to sexual behaviour and increases access to sexual health services for people with serious mental illness.

Adjunctive colposcopy technologies for assessing suspected cervical abnormalities: systematic reviews and economic evaluation.

BACKGROUND: Dynamic Spectral Imaging System (DySIS)map (DySIS Medical Ltd, Edinburgh, UK) and ZedScan (Zilico Limited, Manchester, UK) can be used adjunctively with conventional colposcopy, which may improve the detection of cervical intraepithelial neoplasia (CIN) and cancer. OBJECTIVES: To systematically review the evidence on the diagnostic accuracy, clinical effectiveness and implementation of DySISmap and ZedScan as adjuncts to standard colposcopy, and to develop a cost-effectiveness model. METHODS: Four parallel systematic reviews were performed on diagnostic accuracy, clinical effectiveness issues, implementation and economic analyses. In January 2017 we searched databases (including MEDLINE and EMBASE) for studies in which DySISmap or ZedScan was used adjunctively with standard colposcopy to detect CIN or cancer in women referred to colposcopy. Risk of bias was assessed with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool. Summary estimates of diagnostic accuracy were calculated using bivariate and other regression models when appropriate. Other outcomes were synthesised narratively. A patient-level state-transition model was developed to evaluate the cost-effectiveness of DySISmap and ZedScan under either human papillomavirus (HPV) triage or the HPV primary screening algorithm. The model included two types of clinics ['see and treat' and 'watchful waiting' (i.e. treat later after confirmatory biopsy)], as well as the reason for referral (low-grade or high-grade cytological smear). Sensitivity and scenario analyses were undertaken. RESULTS: Eleven studies were included in the diagnostic review (nine of DySISmap and two of ZedScan), three were included in the clinical effectiveness review (two of DySISmap and one of ZedScan) and five were included in the implementation review (four of DySISmap and one of ZedScan). Adjunctive DySISmap use was found to have a higher sensitivity for detecting CIN grade 2+ (CIN 2+) lesions [81.25%, 95% confidence interval (CI) 72.2% to 87.9%] than standard colposcopy alone (57.91%, 95% CI 47.2% to 67.9%), but with a lower specificity (70.40%, 95% CI 59.4% to 79.5%) than colposcopy (87.41%, 95% CI 81.7% to 91.5%). (Confidential information has been removed.) The base-case cost-effectiveness results showed that adjunctive DySISmap routinely dominated standard colposcopy (it was less costly and more effective). The only exception was for high-grade referrals in a watchful-waiting clinic setting. The incremental cost-effectiveness ratio for ZedScan varied between £272 and £4922 per quality-adjusted life-year. ZedScan also dominated colposcopy alone for high-grade referrals in see-and-treat clinics. These findings appeared to be robust to a wide range of sensitivity and scenario analyses. LIMITATIONS: All but one study was rated as being at a high risk of bias. There was no evidence directly comparing ZedScan with standard colposcopy. No studies directly compared DySIS and ZedScan. CONCLUSIONS: The use of adjunctive DySIS increases the sensitivity for detecting CIN 2+, so it increases the number of high-grade CIN cases that are detected. However, it also reduces specificity, so that more women with no or low-grade CIN will be incorrectly judged as possibly having high-grade CIN. The evidence for ZedScan was limited, but it appears to increase sensitivity and decrease specificity compared with colposcopy alone. The cost-effectiveness of both adjunctive technologies compared with standard colposcopy, under both the HPV triage and primary screening algorithms, appears to be favourable when compared with the conventional thresholds used to determine value in the NHS. FUTURE WORK: More diagnostic accuracy studies of ZedScan are needed, as are studies assessing the diagnostic accuracy for women referred to colposcopy as part of the HPV primary screening programme. STUDY REGISTRATION: This study is registered as PROSPERO CRD42017054515. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Naloxone for opioid-exposed newborn infants.

BACKGROUND: Naloxone, a specific opioid antagonist, is available for the treatment of newborn infants with cardiorespiratory or neurological depression that may be due to intrauterine exposure to opioid. It is unclear whether newborn infants may benefit from this therapy and whether naloxone has any harmful effects. OBJECTIVES: To determine the effect of naloxone on the need for and duration of neonatal unit stay in infants of mothers who received opioid analgesia prior to delivery or of mothers who have used a prescribed or non-prescribed opioid during pregnancy. SEARCH METHODS: We searched the following databases in February 2018: the Cochrane Central Register of Controlled Trials (the Cochrane Library 2018, Issue 1), MEDLINE (OvidSP), MEDLINE In process & Other Non-Indexed Citations (OvidSP), Embase (OvidSP), CINAHL (EBSCO), Maternity and Infant Care (OvidSP), and PubMed. We searched for ongoing and completed trials in the WHO International Clinical Trials Registry Platform and the EU Clinical Trials Register. We checked the reference lists of relevant articles to identify further potentially relevant studies. SELECTION CRITERIA: Randomised controlled trials comparing the administration of naloxone versus placebo, or no drug, or another dose of naloxone to newborn infants with suspected or confirmed in utero exposure to opioid. DATA COLLECTION AND ANALYSIS: We extracted data using the standard methods of Cochrane Neonatal with separate evaluation of trial quality and data extraction by two review authors and synthesis of data using risk ratio, risk difference, and mean difference. MAIN RESULTS: We included nine trials, with 316 participants in total, that compared the effects of naloxone versus placebo or no drug in newborn infants exposed to maternal opioid analgesia prior to delivery. None of the included trials investigated infants born to mothers who had used a prescribed or non-prescribed opioid during pregnancy. None of these trials specifically recruited infants with cardiorespiratory or neurological depression. The main outcomes reported were measures of respiratory function in the first six hours after birth. There is some evidence that naloxone increases alveolar ventilation. The trials did not assess the effect on the primary outcomes of this review (admission to a neonatal unit and failure to establish breastfeeding). AUTHORS' CONCLUSIONS: The existing evidence from randomised controlled trials is insufficient to determine whether naloxone confers any important benefits to newborn infants with cardiorespiratory or neurological depression that may be due to intrauterine exposure to opioid. Given concerns about the safety of naloxone in this context, it may be appropriate to limit its use to randomised controlled trials that aim to resolve these uncertainties.

Certolizumab pegol and secukinumab for treating active psoriatic arthritis following inadequate response to disease-modifying antirheumatic drugs: a systematic review and economic evaluation.

BACKGROUND: Several biologic therapies are approved by the National Institute for Health and Care Excellence (NICE) for psoriatic arthritis (PsA) patients who have had an inadequate response to two or more synthetic disease-modifying antirheumatic drugs (DMARDs). NICE does not specifically recommend switching from one biologic to another, and only ustekinumab (UST; STELARA®, Janssen Pharmaceuticals, Inc., Horsham, PA, USA) is recommended after anti-tumour necrosis factor failure. Secukinumab (SEC; COSENTYX®, Novartis International AG, Basel, Switzerland) and certolizumab pegol (CZP; CIMZIA®, UCB Pharma, Brussels, Belgium) have not previously been appraised by NICE. OBJECTIVE: To determine the clinical effectiveness and cost-effectiveness of CZP and SEC for treating active PsA in adults in whom DMARDs have been inadequately effective. DESIGN: Systematic review and economic model. DATA SOURCES: Fourteen databases (including MEDLINE and EMBASE) were searched for relevant studies from inception to April 2016 for CZP and SEC studies; update searches were run to identify new comparator studies. REVIEW METHODS: Clinical effectiveness data from randomised controlled trials (RCTs) were synthesised using Bayesian network meta-analysis (NMA) methods to investigate the relative efficacy of SEC and CZP compared with comparator therapies. A de novo model was developed to assess the cost-effectiveness of SEC and CZP compared with the other relevant comparators. The model was specified for three subpopulations, in accordance with the NICE scope (patients who have taken one prior DMARD, patients who have taken two or more prior DMARDs and biologic-experienced patients). The models were further classified according to the level of concomitant psoriasis. RESULTS: Nineteen eligible RCTs were included in the systematic review of short-term efficacy. Most studies were well conducted and were rated as being at low risk of bias. Trials of SEC and CZP demonstrated clinically important efficacy in all key clinical outcomes. At 3 months, patients taking 150 mg of SEC [relative risk (RR) 6.27, 95% confidence interval (CI) 2.55 to 15.43] or CZP (RR 3.29, 95% CI 1.94 to 5.56) were more likely to be responders than patients taking placebo. The NMA results for the biologic-naive subpopulations indicated that the effectiveness of SEC and CZP relative to other biologics and each other was uncertain. Limited data were available for the biologic-experienced subpopulation. Longer-term evidence suggested that these newer biologics reduced disease progression, with the benefits being similar to those seen for older biologics. The de novo model generated incremental cost-effectiveness ratios (ICERs) for three subpopulations and three psoriasis subgroups. In subpopulation 1 (biologic-naive patients who had taken one prior DMARD), CZP was the optimal treatment in the moderate-severe psoriasis subgroup and 150 mg of SEC was optimal in the subgroups of patients with mild-moderate psoriasis or no concomitant psoriasis. In subpopulation 2 (biologic-naive patients who had taken two or more prior DMARDs), etanercept (ETN; ENBREL®, Pfizer Inc., New York City, NY, USA) is likely to be the optimal treatment in all subgroups. The ICERs for SEC and CZP versus best supportive care are in the region of £20,000-30,000 per quality-adjusted life-year (QALY). In subpopulation 3 (biologic-experienced patients or patients in whom biologics are contraindicated), UST is likely to be the optimal treatment (ICERs are in the region of £21,000-27,000 per QALY). The optimal treatment in subpopulation 2 was sensitive to the choice of evidence synthesis model. In subpopulations 2 and 3, results were sensitive to the algorithm for Health Assessment Questionnaire-Disability Index costs. The optimal treatment is not sensitive to the use of biosimilar prices for ETN and infliximab (REMICADE®, Merck Sharp & Dohme, Kenilworth, NJ, USA). CONCLUSIONS: SEC and CZP may be an effective use of NHS resources, depending on the subpopulation and subgroup of psoriasis severity. There are a number of limitations to this assessment, driven mainly by data availability. FUTURE WORK: Trials are needed to inform effectiveness of biologics in biologic-experienced populations. STUDY REGISTRATION: This study is registered as PROSPERO CRD42016033357. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

A systematic review on the clustering and co-occurrence of multiple risk behaviours.

BACKGROUND: Risk behaviours, such as smoking and physical inactivity account for up to two-thirds of all cardiovascular deaths, and are associated with substantial increased mortality in many conditions including cancer and diabetes. As risk behaviours are thought to co-occur in individuals we conducted a systematic review of studies addressing clustering or co-occurrence of risk behaviours and their predictors. As the main aim of the review was to inform public health policy in England we limited inclusion to studies conducted in the UK. METHODS: Key databases were searched from 1990 to 2016. We included UK based cross-sectional and longitudinal studies that investigated risk behaviours such as smoking, physical inactivity, unhealthy diet. High heterogeneity precluded meta-analyses. RESULTS: Thirty-seven studies were included in the review (32 cross-sectional and five longitudinal). Most studies investigated unhealthy diet, physical inactivity, alcohol misuse, and smoking. In general adult populations, there was relatively strong evidence of clustering between alcohol misuse and smoking; and unhealthy diet and smoking. For young adults, there was evidence of clustering between sexual risk behaviour and smoking, sexual risk behaviour and illicit drug use, and sexual risk behaviour and alcohol misuse. The strongest associations with co-occurrence and clustering of multiple risk behaviours were occupation (up to 4-fold increased odds in lower SES groups) and education (up to 5-fold increased odds in those with no qualifications). CONCLUSIONS: Among general adult populations, alcohol misuse and smoking was the most commonly identified risk behaviour cluster. Among young adults, there was consistent evidence of clustering found between sexual risk behaviour and substance misuse. Socio-economic status was the strongest predictor of engaging in multiple risk behaviours. This suggests the potential for interventions targeting multiple risk behaviours either sequentially or concurrently particularly where there is evidence of clustering. In addition, there is potential for intervening at the social or environmental level due to the strong association with socio-economic status.

Glutamine supplementation to prevent morbidity and mortality in preterm infants.

BACKGROUND: Glutamine is a conditionally essential amino acid. Endogenous biosynthesis may be insufficient for tissue needs in states of metabolic stress. Evidence exists that glutamine supplementation improves clinical outcomes in critically ill adults. It has been suggested that glutamine supplementation may also benefit preterm infants. OBJECTIVES: To determine the effects of glutamine supplementation on mortality and morbidity in preterm infants. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, 2015, Issue 12), MEDLINE, EMBASE and Maternity and Infant Care (to December 2015), conference proceedings and previous reviews. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that compared glutamine supplementation versus no glutamine supplementation in preterm infants at any time from birth to discharge from hospital. DATA COLLECTION AND ANALYSIS: We extracted data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by two review authors. We synthesised data using a fixed-effect model and reported typical relative risk, typical risk difference and weighted mean difference. MAIN RESULTS: We identified 12 randomised controlled trials in which a total of 2877 preterm infants participated. Six trials assessed enteral glutamine supplementation and six trials assessed parenteral glutamine supplementation. The trials were generally of good methodological quality. Meta-analysis did not find an effect of glutamine supplementation on mortality (typical relative risk 0.97, 95% confidence interval 0.80 to 1.17; risk difference 0.00, 95% confidence interval -0.03 to 0.02) or major neonatal morbidities including the incidence of invasive infection or necrotising enterocolitis. Three trials that assessed neurodevelopmental outcomes in children aged 18 to 24 months and beyond did not find any effects. AUTHORS' CONCLUSIONS: The available trial data do not provide evidence that glutamine supplementation confers important benefits for preterm infants.

Tumour necrosis factor-α inhibitors for ankylosing spondylitis and non-radiographic axial spondyloarthritis: a systematic review and economic evaluation.

BACKGROUND: Tumour necrosis factor (TNF)-α inhibitors (anti-TNFs) are typically used when the inflammatory rheumatologic diseases ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-AxSpA) have not responded adequately to conventional therapy. Current National Institute for Health and Care Excellence (NICE) guidance recommends treatment with adalimumab, etanercept and golimumab in adults with active (severe) AS only if certain criteria are fulfilled but it does not recommend infliximab for AS. Anti-TNFs for patients with nr-AxSpA have not previously been appraised by NICE. OBJECTIVE: To determine the clinical effectiveness, safety and cost-effectiveness within the NHS of adalimumab, certolizumab pegol, etanercept, golimumab and infliximab, within their licensed indications, for the treatment of severe active AS or severe nr-AxSpA (but with objective signs of inflammation). DESIGN: Systematic review and economic model. DATA SOURCES: Fifteen databases were searched for relevant studies in July 2014. REVIEW METHODS: Clinical effectiveness data from randomised controlled trials (RCTs) were synthesised using Bayesian network meta-analysis methods. Results from other studies were summarised narratively. Only full economic evaluations that compared two or more options and considered both costs and consequences were included in the systematic review of cost-effectiveness studies. The differences in the approaches and assumptions used across the studies, and also those in the manufacturer's submissions, were examined in order to explain any discrepancies in the findings and to identify key areas of uncertainty. A de novo decision model was developed with a generalised framework for evidence synthesis that pooled change in disease activity (BASDAI and BASDAI 50) and simultaneously synthesised information on function (BASFI) to determine the long-term quality-adjusted life-year and cost burden of the disease in the economic model. The decision model was developed in accordance with the NICE reference case. The model has a lifetime horizon (60 years) and considers costs from the perspective of the NHS and personal social services. Health effects were expressed in terms of quality-adjusted life-years. RESULTS: In total, 28 eligible RCTs were identified and 26 were placebo controlled (mostly up to 12 weeks); 17 extended into open-label active treatment-only phases. Most RCTs were judged to have a low risk of bias overall. In both AS and nr-AxSpA populations, anti-TNFs produced clinically important benefits to patients in terms of improving function and reducing disease activity; for AS, the relative risks for ASAS 40 ranged from 2.53 to 3.42. The efficacy estimates were consistently slightly smaller for nr-AxSpA than for AS. Statistical (and clinical) heterogeneity was more apparent in the nr-AxSpA analyses than in the AS analyses; both the reliability of the nr-AxSpA meta-analysis results and their true relevance to patients seen in clinical practice are questionable. In AS, anti-TNFs are approximately equally effective. Effectiveness appears to be maintained over time, with around 50% of patients still responding at 2 years. Evidence for an effect of anti-TNFs delaying disease progression was limited; results from ongoing long-term studies should help to clarify this issue. Sequential treatment with anti-TNFs can be worthwhile but the drug survival response rates and benefits are reduced with second and third anti-TNFs. The de novo model, which addressed many of the issues of earlier evaluations, generated incremental cost-effectiveness ratios ranging from £19,240 to £66,529 depending on anti-TNF and modelling assumptions. CONCLUSIONS: In both AS and nr-AxSpA populations anti-TNFs are clinically effective, although more so in AS than in nr-AxSpA. Anti-TNFs may be an effective use of NHS resources depending on which assumptions are considered appropriate. FUTURE WORK RECOMMENDATIONS: Randomised trials are needed to identify the nr-AxSpA population who will benefit the most from anti-TNFs. STUDY REGISTRATION: This study is registered as PROSPERO CRD42014010182. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Glutamine supplementation to prevent morbidity and mortality in preterm infants.

BACKGROUND: Glutamine is a conditionally essential amino acid. Endogenous biosynthesis may be insufficient for tissue needs in states of metabolic stress. Evidence exists that glutamine supplementation improves clinical outcomes in critically ill adults. It has been suggested that glutamine supplementation may also benefit preterm infants. OBJECTIVES: To determine the effects of glutamine supplementation on mortality and morbidity in preterm infants. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, 2015, Issue 12), MEDLINE, EMBASE and Maternity and Infant Care (to December 2015), conference proceedings and previous reviews. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that compared glutamine supplementation versus no glutamine supplementation in preterm infants at any time from birth to discharge from hospital. DATA COLLECTION AND ANALYSIS: We extracted data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by two review authors. We synthesised data using a fixed-effect model and reported typical relative risk, typical risk difference and weighted mean difference. MAIN RESULTS: We identified 12 randomised controlled trials in which a total of 2877 preterm infants participated. Six trials assessed enteral glutamine supplementation and six trials assessed parenteral glutamine supplementation. The trials were generally of good methodological quality. Meta-analysis did not find an effect of glutamine supplementation on mortality (typical relative risk 0.97, 95% confidence interval 0.80 to 1.17; risk difference 0.00, 95% confidence interval -0.03 to 0.02) or major neonatal morbidities including the incidence of invasive infection or necrotising enterocolitis. Three trials that assessed neurodevelopmental outcomes in children aged 18 to 24 months and beyond did not find any effects. AUTHORS' CONCLUSIONS: The available trial data do not provide evidence that glutamine supplementation confers important benefits for preterm infants.