Digitally augmented, parent-led CBT versus treatment as usual for child anxiety problems in child mental health services in England and Northern Ireland: a pragmatic, non-inferiority, clinical effectiveness and cost-effectiveness randomised controlled trial.

BACKGROUND: Anxiety problems are common in children, yet few affected children access evidence-based treatment. Digitally augmented psychological therapies bring potential to increase availability of effective help for children with mental health problems. This study aimed to establish whether therapist-supported, digitally augmented, parent-led cognitive behavioural therapy (CBT) could increase the efficiency of treatment without compromising clinical effectiveness and acceptability. METHODS: We conducted a pragmatic, unblinded, two-arm, multisite, randomised controlled non-inferiority trial to evaluate the clinical effectiveness and cost-effectiveness of therapist-supported, parent-led CBT using the Online Support and Intervention (OSI) for child anxiety platform compared with treatment as usual for child (aged 5-12 years) anxiety problems in 34 Child and Adolescent Mental Health Services in England and Northern Ireland. We examined acceptability of OSI plus therapist support via qualitative interviews. Participants were randomly assigned (1:1) to OSI plus therapist support or treatment as usual, minimised by child age, gender, service type, and baseline child anxiety interference. Outcomes were assessed at week 14 and week 26 after randomisation. The primary clinical outcome was parent-reported interference caused by child anxiety at week 26 assessment, using the Child Anxiety Impact Scale-parent report (CAIS-P). The primary measure of health economic effect was quality-adjusted life-years (QALYs). Outcome analyses were conducted blind in the intention-to-treat (ITT) population with a standardised non-inferiority margin of 0·33 for clinical analyses. The trial was registered with ISRCTN, 12890382. FINDINGS: Between Dec 5, 2020, and Aug 3, 2022, 706 families (706 children and their parents or carers) were referred to the study information. 444 families were enrolled. Parents reported 255 (58%) child participants' gender to be female, 184 (41%) male, three (<1%) other, and one (<1%) preferred not to report their child's gender. 400 (90%) children were White and the mean age was 9·20 years (SD 1·79). 85% of families for whom clinicians provided information in the treatment as usual group received CBT. OSI plus therapist support was non-inferior for parent-reported anxiety interference on the CAIS-P (SMD 0·01, 95% CI -0·15 to 0·17; p<0·0001) and all secondary outcomes. The mean difference in QALYs across trial arms approximated to zero, and OSI plus therapist support was associated with lower costs than treatment as usual. OSI plus therapist support was likely to be cost effective under certain scenarios, but uncertainty was high. OSI plus therapist support acceptability was good. No serious adverse events were reported. INTERPRETATION: Digitally augmented intervention brought promising savings without compromising outcomes and as such presents a valuable tool for increasing access to psychological therapies and meeting the demand for treatment of child anxiety problems. FUNDING: Department for Health and Social Care and United Kingdom Research and Innovation Research Grant, National Institute for Health and Care (NIHR) Research Policy Research Programme, Oxford and Thames Valley NIHR Applied Research Collaboration, Oxford Health NIHR Biomedical Research Centre.

Cost-utility analysis of molnupiravir for high-risk, community-based adults with COVID-19: an economic evaluation of the PANORAMIC trial.

BACKGROUND: The cost-effectiveness of molnupiravir, an oral antiviral for early treatment of SARS-CoV-2, has not been established in vaccinated populations. AIM: To evaluate the cost-effectiveness of molnupiravir relative to usual care alone among mainly vaccinated community-based people at higher risk of severe outcomes from COVID-19 over 6 months. DESIGN AND SETTING: An economic evaluation of the PANORAMIC trial in the UK. METHOD: A cost-utility analysis that adopted a UK NHS and personal social services perspective and a 6-month time horizon was performed using PANORAMIC trial data. Cost-effectiveness was expressed in terms of incremental cost per quality-adjusted life year (QALY) gained. Sensitivity and subgroup analyses assessed the impacts of uncertainty and heterogeneity. Threshold analysis explored the price for molnupiravir consistent with likely reimbursement. RESULTS: In the base-case analysis, molnupiravir had higher mean costs of £449 (95% confidence interval [CI] = 445 to 453) and higher mean QALYs of 0.0055 (95% CI = 0.0044 to 0.0067) than usual care (mean incremental cost per QALY of £81 190). Sensitivity and subgroup analyses showed similar results, except for those aged ≥75 years, with a 55% probability of being cost-effective at a £30 000 per QALY threshold. Molnupiravir would have to be priced around £147 per course to be cost-effective at a £15 000 per QALY threshold. CONCLUSION: At the current cost of £513 per course, molnupiravir is unlikely to be cost-effective relative to usual care over a 6-month time horizon among mainly vaccinated patients with COVID-19 at increased risk of adverse outcomes, except those aged ≥75 years.

Clinical and cost-effectiveness of nurse-delivered sleep restriction therapy for insomnia in primary care (HABIT): a pragmatic, superiority, open-label, randomised controlled trial.

BACKGROUND: Insomnia is prevalent and distressing but access to the first-line treatment, cognitive behavioural therapy (CBT), is extremely limited. We aimed to assess the clinical and cost-effectiveness of sleep restriction therapy, a key component of CBT, which has the potential to be widely implemented. METHODS: We did a pragmatic, superiority, open-label, randomised controlled trial of sleep restriction therapy versus sleep hygiene. Adults with insomnia disorder were recruited from 35 general practices across England and randomly assigned (1:1) using a web-based randomisation programme to either four sessions of nurse-delivered sleep restriction therapy plus a sleep hygiene booklet or a sleep hygiene booklet only. There was no restriction on usual care for either group. Outcomes were assessed at 3 months, 6 months, and 12 months. The primary endpoint was self-reported insomnia severity at 6 months measured with the insomnia severity index (ISI). The primary analysis included participants according to their allocated group and who contributed at least one outcome measurement. Cost-effectiveness was evaluated from the UK National Health Service and personal social services perspective and expressed in terms of incremental cost per quality-adjusted life year (QALY) gained. The trial was prospectively registered (ISRCTN42499563). FINDINGS: Between Aug 29, 2018, and March 23, 2020 we randomly assigned 642 participants to sleep restriction therapy (n=321) or sleep hygiene (n=321). Mean age was 55·4 years (range 19-88), with 489 (76·2%) participants being female and 153 (23·8%) being male. 580 (90·3%) participants provided data for at least one outcome measurement. At 6 months, mean ISI score was 10·9 (SD 5·5) for sleep restriction therapy and 13·9 (5·2) for sleep hygiene (adjusted mean difference -3·05, 95% CI -3·83 to -2·28; p<0·0001; Cohen's d -0·74), indicating that participants in the sleep restriction therapy group reported lower insomnia severity than the sleep hygiene group. The incremental cost per QALY gained was £2076, giving a 95·3% probability that treatment was cost-effective at a cost-effectiveness threshold of £20 000. Eight participants in each group had serious adverse events, none of which were judged to be related to intervention. INTERPRETATION: Brief nurse-delivered sleep restriction therapy in primary care reduces insomnia symptoms, is likely to be cost-effective, and has the potential to be widely implemented as a first-line treatment for insomnia disorder. FUNDING: The National Institute for Health and Care Research Health Technology Assessment Programme.

Platform adaptive trial of novel antivirals for early treatment of COVID-19 In the community (PANORAMIC): protocol for a randomised, controlled, open-label, adaptive platform trial of community novel antiviral treatment of COVID-19 in people at increased risk of more severe disease.

INTRODUCTION: There is an urgent need to determine the safety, effectiveness and cost-effectiveness of novel antiviral treatments for COVID-19 in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19. METHODS AND ANALYSIS: PANORAMIC is a UK-wide, open-label, prospective, adaptive, multiarm platform, randomised clinical trial that evaluates antiviral treatments for COVID-19 in the community. A master protocol governs the addition of new antiviral treatments as they become available, and the introduction and cessation of existing interventions via interim analyses. The first two interventions to be evaluated are molnupiravir (Lagevrio) and nirmatrelvir/ritonavir (Paxlovid). ELIGIBILITY CRITERIA: community-dwelling within 5 days of onset of symptomatic COVID-19 (confirmed by PCR or lateral flow test), and either (1) aged 50 years and over, or (2) aged 18-49 years with qualifying comorbidities. Registration occurs via the trial website and by telephone. Recruitment occurs remotely through the central trial team, or in person through clinical sites. Participants are randomised to receive either usual care or a trial drug plus usual care. Outcomes are collected via a participant-completed daily electronic symptom diary for 28 days post randomisation. Participants and/or their Trial Partner are contacted by the research team after days 7, 14 and 28 if the diary is not completed, or if the participant is unable to access the diary. The primary efficacy endpoint is all-cause, non-elective hospitalisation and/or death within 28 days of randomisation. Multiple prespecified interim analyses allow interventions to be stopped for futility or superiority based on prespecified decision criteria. A prospective economic evaluation is embedded within the trial. ETHICS AND DISSEMINATION: Ethical approval granted by South Central-Berkshire REC number: 21/SC/0393; IRAS project ID: 1004274. Results will be presented to policymakers and at conferences, and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN30448031; EudraCT number: 2021-005748-31.

Unmet needs for food, medicine, and mental health services among vulnerable older adults during the COVID-19 pandemic.

OBJECTIVE: To examine sociodemographic factors associated with having unmet needs in medications, mental health, and food security among older adults during the COVID-19 pandemic. DATA SOURCES AND STUDY SETTING: Primary data and secondary data from the electronic health records (EHR) in an age-friendly academic health system in 2020 were used. STUDY DESIGN: Observational study examining factors associated with having unmet needs in medications, food, and mental health. DATA COLLECTING/EXTRACTION METHODS: Data from a computer-assisted telephone interview and EHR on community-dwelling older patients were analyzed. PRINCIPLE FINDINGS: Among 3400 eligible patients, 1921 (53.3%) (average age 76, SD 11) responded, with 857 (45%) of respondents having at least one unmet need. Unmet needs for medications were present in 595 (31.0%), for food in 196 (10.2%), and for mental health services in 292 (15.2%). Racial minorities had significantly higher probabilities of having unmet needs for medicine and food, and of being referred for services related to medications, food, and mental health. Patients living in more resource-limited neighborhoods had a higher probability of being referred for mental health services. CONCLUSIONS: Age-friendly health systems (AFHS) and their recognition should include assessing and addressing social risk factors among older adults. Proactive efforts to address unmet needs should be integral to AFHS.

A randomised controlled trial to compare clinical and cost-effectiveness of an online parent-led treatment for child anxiety problems with usual care in the context of COVID-19 delivered in Child and Adolescent Mental Health Services in the UK (Co-CAT): a study protocol for a randomised controlled trial.

BACKGROUND: In the context of COVID-19, NHS Child and Adolescent Mental Health Services (CAMHS) and other children's mental health services have faced major challenges in providing psychological treatments that (i) work when delivered remotely and (ii) can be delivered efficiently to manage increases in referrals as social distancing measures have been relaxed. Anxiety problems are a common reason for referral to CAMHS, children with pre-existing anxiety problems are particularly vulnerable in the context of COVID-19, and there were concerns about increases in childhood anxiety as schools reopened. The proposed research will evaluate the clinical and cost-effectiveness of a brief online parent-led cognitive behavioural treatment (CBT) delivered by the OSI (Online Support and Intervention for child anxiety) platform with remote support from a CAMHS therapist compared to 'COVID-19 treatment as usual' (C-TAU) in CAMHS and other children's mental health services throughout the COVID-19 pandemic. METHODS: We will conduct a two-arm, multi-site, randomised controlled non-inferiority trial to evaluate the clinical and cost-effectiveness of OSI with therapist support compared to CAMHS and other child mental health services 'COVID-19 treatment as usual' (C-TAU) during the COVID-19 outbreak and to explore parent and therapists' experiences. DISCUSSION: If non-inferiority is shown, the research will provide (1) a solution for efficient psychological treatment for child anxiety disorders while social distancing (for the COVID-19 context and future pandemics); (2) an efficient means of treatment delivery as 'normal service' resumes to enable CAMHS to cope with the anticipated increase in referrals; and (3) a demonstration of rapid, high-quality evaluation and application of online interventions within NHS CAMHS to drive forward much-needed further digital innovation and evaluation in CAMHS settings. The primary beneficiaries will be children with anxiety disorders and their families, NHS CAMHS teams, and commissioners who will access a potentially effective, cost-effective, and efficient treatment for child anxiety problems. TRIAL REGISTRATION: ISRCTN ISRCTN12890382 . Registered prospectively on 23 October 2020.

Vulvar quality of life index (VQLI) - A simple tool to measure quality of life in patients with vulvar disease.

BACKGROUND/OBJECTIVES: Vulvar disease leads to significant disease burden and reduced quality of life (QOL). However, vulvar disease-specific instruments to measure QOL are lacking. We developed the Vulvar Quality of Life Index (VQLI) to comprehensively and reproducibly assess symptomatic, psychosexual and physical aspects of vulvar disease. METHODS: The VQLI was inferred from a review of the literature regarding QOL of vulvar disease, and responses from a cohort of patients attending specialist clinics. Seven domains and a 15-item questionnaire were developed. This was tested and optimised prior to validation on 248 women, using a control group as a baseline. The VQLI was further tested on 157 women, and the total VQLI score was compared to a self-determined Likert global score on how vulvar disease had impacted their overall health. RESULTS: The VQLI had excellent internal consistency (Cronbach's alpha, 0.93), and test-retest reliability showed that 9/15 questions had a substantial weighted kappa value of 0.5 or above, with good intraclass correlation coefficient (0.88; CI 0.8-0.93). Spearman correlations were consistently positive. Further testing on 157 women demonstrated a significant relationship between the total VQLI score and the effect of vulvar disease on overall health, with high levels of the impact of vulvar disease on overall health associated with high total VQLI score (P < 0.001). CONCLUSIONS: The VQLI is a validated, fast and reliable tool to measure the global impact of vulvar disease on QOL and can be used to monitor response to treatment or in a research setting.

Equity effects of parenting interventions for child conduct problems: a pan-European individual participant data meta-analysis.

BACKGROUND: Childhood conduct problems are a costly public health problem and are five times more common in socially disadvantaged groups than they are in advantaged groups. Untreated, conduct problems have a poor prognosis, with increasing gaps between socioeconomic groups, and high rates of subsequent criminality. Incredible Years is a high quality parenting programme for reducing conduct problems and is widely disseminated in Europe. Many trials have shown Incredible Years to be effective but the potential effects of parenting interventions on social inequality are unknown. Some behavioural interventions (eg, smoking cessation programmes), although beneficial overall, can widen inequality gaps. Because single trials and aggregate-level meta-analyses are ill equipped for examining differential intervention (moderator) effects, we pooled individual-level trial data to assess the effects of Incredible Years on social equity. METHODS: We did a systematic review and individual participant data meta-analysis by searching CINAHL, Embase, Global Health, Medline, and PsycINFO, for studies published from inception to March 15, 2019. We also searched the Incredible Years website library and consulted with experts, including the European Incredible Years mentors' network. We included data from all completed randomised trials of the Incredible Years parenting intervention in Europe that included children aged 1-12 years, including unpublished trials, without restriction on publication year or outcome measures. We included prevention (selective or universal) and treatment or indicated prevention trials (for children diagnosed or above the clinical cutoff for conduct problems). We excluded trials or conditions within trials that were not randomised, included additional non-parenting material (eg, child-focused interventions), or were abbreviated, non-standard versions of the usual Incredible Years intervention of 12-14 weekly sessions. We requested individual participant data from the study authors. The primary outcome was child conduct problems, assessed using the Eyberg Child Behavior Inventory Intensity (ECBI-I) scale. Moderators were analysed using multilevel modelling with multiple imputation. FINDINGS: Of 15 European trials of Incredible Years parenting programmes (n=1696 children), individual participant data were unavailable for one trial and one trial did not assess the primary outcome. Children were aged 2-10 years (median 5·1), 492 (30%) of 1651 children were from an ethnic minority and 931 (58%) of 1614 were from low-income families. Families who received the Incredible Years intervention reported an overall reduction in child conduct problems (13·5 points on the ECBI-I scale, 95% CI 10·9-16·1). There were no differential effects by family disadvantage (indicated by poverty, lone parenthood, teenage parenthood, household joblessness, or low education), or ethnic minority status. INTERPRETATION: We found no evidence for differential effects by social disadvantage, suggesting that Incredible Years is unlikely to widen socioeconomic inequalities in conduct problems. Furthermore, the programme might be an important tool for reducing social disparities and improving poor long-term outcomes in disadvantaged families because follow-up studies indicate that benefits persist. Clinicians and commissioners can be reassured that the programme is similarly effective for families from different backgrounds. FUNDING: UK National Institute for Health Research.

Characteristics of people who rapidly and frequently reattend the emergency department for mental health needs.

OBJECTIVE: This paper identifies the characteristics of emergency department (ED) attendees with a referral to their Mental Health Liaison Service (MHLS) who are at increased risk for rapidly reattending, attending frequently, or attending intensely at this service (which is defined here as rapid and frequent reattendance). METHODS: A retrospective 5-year longitudinal study was conducted of all visitors (n=24 010) attending four busy EDs with a referral to their MHLS from the beginning of 2009 until the end of 2013. A Cox proportional hazards regression was used to identify factors associated with intense use, and a negative binomial regression was used to identify factors associated with frequent attendance. RESULTS: People with certain characteristics were more likely to make 'intense' use of mental health emergency services, which we define as shorter time to reattendance and a higher number of visits over 5 years. The people more likely to make intense use are more likely to have certain clinical diagnoses such as substance misuse, stress disorder, personality disorder and learning disability, to have certain social characteristics such as not being in a relationship, or living alone, and to have healthcare issues such as having been detained under the Mental Health Act and having a greater number of care coordinators over 5 years. CONCLUSION: Individuals with certain clinical and social characteristics were significantly more likely to reattend EDs and have referral to MHLS rapidly and frequently (i.e. intensely).

Does change in cognitive function predict change in costs of care for people with a schizophrenia diagnosis following cognitive remediation therapy?

BACKGROUND AND AIMS: Schizophrenia leads to significant personal costs matched by high economic costs. Cognitive function is a strong predictor of disabilities in schizophrenia, which underpin these costs. This study of cognitive remediation therapy (CRT), which has been shown to improve cognition and reduce disability in schizophrenia, aims to investigate associations between improvements in cognition and cost changes. METHODS: Eighty-five participants with schizophrenia were randomized to receive CRT or treatment as usual and were assessed at baseline, posttherapy, and 6 month follow-up. Four structural equation models investigated associations between changes in cognitive function and costs of care. RESULTS: All 4 models provided a good fit. Improvement in 3 individual cognitive variables did not predict total cost changes (model 1). But improvement in a single latent cognition factor was associated with a reduction in depression, which in turn was associated with reduced subsequent total costs (model 2). No significant associations with constituent daycare and special accommodation cost changes were apparent with 3 individual cognitive change variables (model 3). But improvement in a single latent cognitive change variable was associated with subsequent reductions in both daycare and special accommodation costs (model 4). CONCLUSION: This study exemplifies a method of using cost changes to investigate the effects and mechanisms of CRT and suggests that executive function change may be an important target if we are to reduce disability and resultant health and social care costs.

The role of the concentration camps in the Nazi repression of prostitutes, 1933-9.

This article uses prostitutes as a case study in order to investigate the role of the early concentration camps as centres of detention for social deviants. In contrasting the intensification of repressive policies towards prostitutes against narratives which demonstrate the unexpectedly lax treatment of these women, it explores what the reasons behind these contradictions might have been, and what this demonstrates about the development of these institutions. It asks the following questions. How and why were prostitutes interned? Which bureaucrats were responsible for incarcerating these women and what did they view the role of the camp to be? Were such policies centrally directed or the product of local decision-making? Through asking these questions, the article explores to what extent these camps were unique as mechanisms for the repression and marginalization of prostitutes.