BACKGROUND:Long-term psychological treatments are recommended for people with personality disorder. Brief interventions are increasingly delivered but are of uncertain benefit. We aimed to investigate the effectiveness of a brief individual psychological intervention for people with probable personality disorder over a 12-month period. METHODS:The Structured Psychological Support (SPS) study was a multicentre, researcher-masked, randomised controlled superiority trial, conducted in seven mental health Trusts in England: Avon and Wiltshire Mental Health Partnership National Health Service (NHS) Trust, Central and North West London NHS Foundation Trust, Coventry and Warwickshire Partnership NHS Trust, Derbyshire Healthcare NHS Foundation Trust, Lincolnshire Partnership NHS Foundation Trust, Mersey Care NHS Foundation Trust, and Oxford Health NHS Foundation Trust. Participants were aged 18 years or older and had probable personality disorder identified by meeting a threshold of 4 or more on the Standardised Assessment of Personality Abbreviated Scale. We excluded those who: did not consent; had a co-existing psychotic disorder; or were already receiving psychological treatment. We assessed whether participants met criteria for borderline personality disorder using the Structured Clinical Interview for Axis II Personality Disorders and whether they had co-existing complex post-traumatic stress disorder using the International Trauma Questionnaire. We randomly assigned participants to up to ten sessions of SPS plus treatment-as-usual or enhanced treatment-as-usual (allocation ratio 1·15:1), using an independent remote system. Researchers assessing outcomes were masked to group allocation. SPS comprises up to ten individual sessions of personalised psychological support, which includes psychoeducation and psychological skills derived from evidence-based treatments (dialectical behaviour therapy and mentalisation-based treatment). Sessions were usually delivered on a fortnightly basis by staff with previous experience of working with people with personality disorder. The primary outcome was social functioning at 12 months measured using the Work and Social Adjustment Scale (WSAS). Data were analysed using multilevel mixed effects general linear regression on an intention-to-treat basis. We used multiple imputation to address missing outcomes. We undertook a parallel health economic evaluation, which included cost-effectiveness and cost-utility analyses. People with lived experience were involved in the design of the research and in the writing process. The trial was prospectively registered (ISRCTN13918289) and is now complete. FINDINGS:Between Feb 7, 2023, and Jan 31, 2024, 569 potential participants were referred for study inclusion, 34 were deemed ineligible, 56 declined to participate, and 127 were not approached. 352 potential participants provided consent, of whom 16 were deemed ineligible or withdrew. 336 participants were randomly assigned to either SPS (n=180) or treatment-as-usual (n=156). 251 (75%) participants were female, 75 (22%) were male, and ten (3%) were non-binary or other. The mean age was 34·8 years (SD 13·2; range 18-68) and 281 (84%) participants were White. 152 (84%) participants in the SPS group and 132 (85%) in the control group completed the 12-month follow-up. There was no difference between groups for the primary outcome of WSAS score (standardised coefficient 0·12 [95% CI -2·14 to 2·38]; p=0·92). The probability that SPS is cost-effective was 0·34-0·39. There were 36 serious adverse events affecting 17 participants in the SPS group and 16 in the treatment-as-usual group. None were judged to be related to study procedures. Two study participants died during the 12-month follow period, both in the SPS group. INTERPRETATION:We found no difference in social functioning over the course of 1 year among people offered a brief psychological intervention, and no evidence of cost-effectiveness. These data highlight the importance of improving access to longer-term evidence-based psychological treatment programmes for people with personality disorder. FUNDING:National Institute for Health and Care Research.

BACKGROUND:Perinatal anxiety (PNA) is experienced by about 21% of women throughout the perinatal period. Identifying women at risk of PNA through primary care patient records could enable early intervention to improve treatment outcomes. The acceptability of doing this, however, is unknown. AIM:To explore patients' and practitioners' views on identifying women at risk of developing PNA using primary care patient records. DESIGN AND SETTING:Qualitative data are presented from a mixed-methods study, which used online and in-person interviews that were conducted in England. METHOD:Semi-structured interviews were held with 19 women with lived experience of PNA and 27 healthcare professionals (HCPs). Data were analysed thematically. A patient and public involvement and engagement group were involved throughout the study. RESULTS:Both women and practitioners thought it was acceptable to identify women at increased risk of PNA using medical records, providing that sufficient acceptable help and support was in place. All participants also highlighted that an increased risk of PNA needed to be communicated sensitively, with women preferring phrasing such as 'more vulnerable' or 'more susceptible' than 'high risk'. Challenges with identifying risk factors within patient records, such as limited sharing between HCPs and poor coding, were discussed by practitioners. CONCLUSION:There are challenges to identifying risk factors within patient records. It was felt that not all possible risk factors would be recorded in primary care records. The issues of limited sharing between HCPs and poor coding were discussed by practitioners, many of whom thought that clinical intuition was a more appropriate way to assess risk.

Non-adherence to interventions is common in randomized controlled trials (RCTs), complicating the interpretation of treatment effects. The intention-to-treat (ITT) principle estimates the treatment effect of assignment to intervention but does not reflect efficacy among those who adhere. Per-protocol (PP) analyses attempt to address this but introduce selection bias by violating randomisation. The complier average causal effect (CACE) provides an efficacy estimand among compliers while preserving randomisation. This study aimed to provide an empirical comparison of ITT, PP, and CACE approaches using individual participant data (IPD) from trials of depression interventions in primary care. We analysed IPD from the Depression in General Practice (Dep-GP) collaboration, comprising seven eligible RCTs with 3,467 participants. Trials reported continuous (depression symptom scores) or binary (treatment response) outcomes. Adherence was defined within the intervention group. We conducted a two-stage IPD meta-analysis to estimate treatment effects under ITT, PP, and CACE. Results were expressed as differences in standardised mean difference (ΔSMD) for continuous outcomes and as ratios of odds ratios (ROR) for binary outcomes. One-stage mixed-effects models were performed as secondary analyses. For binary outcomes, both PP and CACE analyses produced larger effects than ITT (ROR for PP vs ITT: 1.09; 95

We introduce AcuityBench, a benchmark for evaluating whether language models identify the appropriate urgency of care from user medical presentations. Existing health benchmarks emphasize medical question answering, broad health interactions, or narrow workflow-specific triage tasks, but they do not offer a unified evaluation of acuity identification across these settings. AcuityBench addresses this gap by harmonizing five public datasets spanning user conversations, online forum posts, clinical vignettes, and patient portal messages under a shared four-level acuity framework ranging from home monitoring to immediate emergency care. The benchmark contains 914 cases, including 697 consensus cases for standard accuracy evaluation and 217 physician-confirmed ambiguous cases for uncertainty-aware evaluation. It supports two complementary task formats: explicit four-way classification in a QA setting, and free-form conversational responses evaluated with a rubric-based judge anchored to the same framework. Across 12 frontier proprietary and open-weight models, we find substantial variation in clear-case acuity accuracy and error direction. Comparing task formats reveals a systematic tradeoff: conversational responses reduce over-triage but increase under-triage relative to QA, especially in higher-acuity cases. In ambiguous cases, no model closely matches the distribution of physician judgments, and model predictions are more concentrated than expert clinical uncertainty. We also compare expert and model adjudication on a subset of maximally ambiguous cases, using those cases to examine the role of clinical uncertainty in label disagreement. Together, these results position acuity identification as a distinct safety-critical capability and show that AcuityBench enables systematic comparison and stress-testing of how well models guide users to the right level of care in real-world health use.

Generalised anxiety disorder (GAD) is common and increasingly recognised in primary care. Although antidepressants and psychological therapies are first-line treatments, many patients have residual anxiety and limited access to therapy. Evidence for effective next-step pharmacological options for treatment resistant anxiety remains limited. This paper describes the protocol for the PETRA trial, which will evaluate the clinical and cost-effectiveness of adding pregabalin to antidepressant treatment, compared with placebo, for people with GAD who have not responded or partially responded to antidepressant treatment. PETRA is a multicentre, individually randomised, double-blind, placebo-controlled superiority trial conducted in UK primary care. Participants are recruited by the study team from approximately 150 General Practices and randomised in a 1:1 ratio, using minimisation, to either pregabalin or a matching placebo for 26 weeks (followed by a tapering period where their dosage is reduced over approximately 4 weeks). Sample size is 498. Eligible participants are adults aged 18–74 years, who have been taking antidepressant medication for at least 8 weeks, received treatment with at least one other antidepressant before their current antidepressant and meet ICD-11 criteria for GAD and score ≥ 12 on the revised clinical interview schedule (CIS-R) total score. Follow-up assessments are at 3, 6, 12, 26 and 30 weeks. Our primary outcome measure will be anxiety symptoms measured with GAD-7 at 12 weeks (continuous score). Secondary outcomes are anxiety (GAD-7) at other time points, depressive and panic symptoms, suicidal thoughts, self-rated global improvement, adherence to study medication, serious adverse events, adverse effects, alcohol consumption and benzodiazepine use, quality of life and resources and costs used. The 30-week assessment will investigate symptoms during the withdrawal from pregabalin. Exploratory analyses will include cognitive tasks. A cost-effectiveness analysis and a nested qualitative study will evaluate the implementation and intervention acceptability. The trial findings will inform primary care prescribing practice by providing an accurate and generalisable estimate of the clinical and cost-effectiveness of prescribing pregabalin to individuals with generalised anxiety who have not responded or only partially responded to antidepressant treatment. Controlled Trials ISRCTN Registry, ISRCTN 16993990, registered on 19/09/2023. First participant enrolled in January 2024.

Background: UK general practices are now required to make online consultation tools available during practice hours. Evidence shows patients increasingly use them to access mental health support under the 'digital first' approach. Whilst they may increase time-efficiency for practices, we do not know whether practitioners and patients view them as a suitable consultation mode to discuss mental health. Our aim was to explore patients' and practitioners' views and experiences of using online consultation tools for mental health, to inform their future use. Method: In-depth interviews with 20 primary care practitioners and 21 patients. A topic guide was used to ensure consistency across interviews. Interviews were audio-recorded, transcribed verbatim, and analysed thematically. There was patient and public involvement throughout. Results: Patients and practitioners said online consultation tools encouraged reflective thinking about mental health and symptom disclosure. However, patients' concerns around who might read the output meant they only provided limited information. Patients also reported online tools can be a barrier to accessing care, and those with less mental health literacy may struggle to articulate their concerns. Practitioners noted that continuity of care can be reduced when using online tools, and triage is more challenging if insufficient information is provided to determine if urgent care is needed. Conclusion: To ensure that online consultation tools do not increase inequity, they should remain part of a range of options for accessing mental health support in general practice and should not be a mandatory first step to access care. Online consultation tools can provide useful information for practitioners and may be more accessible than a telephone call for patients with anxiety or depression. However, practitioners may struggle to assess patient risk using these tools, which could mean patients do not receive the care they need. Patients might need support when first using online consultation tools and advice on who will access the information provided.

Background Online interventions can improve access to cognitive behavioural therapy (CBT). We aimed to evaluate the clinical effectiveness of a novel approach integrating therapist-delivered CBT online in reducing depressive symptoms for primary care patients in England, compared with usual care. Methods INTERACT was a two-group, parallel, pragmatic, multicentre, randomised controlled trial recruiting patients from 67 general practices in England. Eligible participants were aged 18 years or older, scored 14 or more on the Beck Depression Inventory (BDI-II), and met ICD-10 criteria for a depressive episode. Patients who were under psychiatric care or had dementia, bipolar disorder, a psychotic illness, or a recent history of alcohol or substance abuse (within the past year) were excluded. Participants were randomly assigned (1:1, stratified by centre and minimised on gender, current antidepressant use, and depression severity) using an automated remote randomisation service to receive integrated CBT in addition to usual care (intervention) or to continue with usual general practitioner care (control). Patients, therapists, and researchers were not masked to allocation. There were no restrictions on usual care treatments. Integrated CBT comprised nine therapist-led sessions, delivered online via instant messaging within the dedicated INTERACT therapy platform. All sessions were delivered one-to-one by therapists accredited as CBT practitioners and were tailored to the individual patient’s needs. Participants were followed up at 3, 6, 9, and 12 months after random assignment using self-report questionnaires. The primary outcome was depressive symptoms (BDI-II score) 6 months after random assignment, analysed using linear regression on an intention-to-treat basis without imputation for missing data. Adverse events and serious adverse events were recorded if identified as part of routine follow-up questionnaires or if reported by participants. The trial was registered with the ISRCTN registry (ISRCTN13112900) and is complete. Findings Between Jan 28, 2021, and April 27, 2023, 451 participants were screened for eligibility and randomly assigned to the intervention (n=225) or usual care (n=226). Mean age was 39·3 years (SD 14·9). 313 (69%) of participants self-reported their gender as female, 135 (30%) as male, and three (1%) as other. 381 (84%) participants self-reported their ethnicity as White, 27 (6%) as Asian or British Asian, 14 (3%) as Mixed, 14 (3%) as Black or Black British, 12 (3%) as Other, and three (1%) as Chinese. The primary analysis included 334 (74%) participants, 171 in the intervention group and 163 in the usual care (control) group, and the median time between random assignment and 6-month follow-up was 6·2 months (IQR 6·0–6·7). At 6 months, the mean BDI-II score in the intervention group was 22·5 (SD 14·4) and in the control group was 27·4 (SD 14·0; adjusted difference in means –4·4 [–7·90 to –1·9]; p=0·0006; effect size 0·43). There were 54 adverse events (33 in the intervention group and 21 in the control group) and 14 serious adverse events (twelve in the intervention group and two in the control group) during the trial. The most common adverse events were self-harm (n=6) and referrals to a mental health team (n=6). No serious adverse events were definitely or probably related to the intervention. There were no participant deaths. Interpretation Integrated CBT was effective for primary care patients with depression at 6 months. This novel mode of delivery could increase the availability of CBT and improve access for individuals who find in-person appointments difficult or inconvenient. Funding National Institute for Health and Care Research.

NHS Talking Therapies (TT) is England's main service for treating people with common mental disorders. Prior research has shown that a high proportion of people receiving TT 'high intensity' treatment have concurrent personality difficulties and that these are associated with poorer TT treatment outcomes. We developed a training workshop to enhance the skills, knowledge, and confidence of TT therapists in the treatment of this population and conducted a mixed methods evaluation to investigate whether the training was acceptable to staff and whether it had any impact on client outcomes. A quantitative survey (n=46) and qualitative interviews (n=6) were undertaken with staff and in parallel, we analysed the anonymised health outcomes of two client cohorts, treated pre-training (n=2434) and post-training (n=2358). Multi-level, difference-in-differences analyses revealed statistically significant cohort differences between the last and first scores on the domains of depression (-2.53, 95% CI: -3.02, -2.04), anxiety (-2.70, 95% CI: -3.15, -2.20), social functioning (-2.17, 95% CI: -2.88, -1.47), and phobia (-1.19; 95% CI: -0.29, -0.17). Therapists reported finding the training helpful, particularly in managing therapeutic alliances and enhancing the interpersonal effectiveness of their clients. Furthermore, the survey revealed a positive change in therapist attitudes to, skills related to, and knowledge of personality difficulties post-training. However, staff also suggested that broader structural changes and more resources are needed for TT services to better support clients with personality difficulties. Training initiatives such as this appear to be feasible and helpful for therapists, and may help to optimise client outcomes.Key learning aims To understand the potential utility of online training for therapists, in their management of clients with concurrent personality difficulties. To understand high intensity therapist perspectives on attending a workshop to support tailoring treatments for depression and anxiety in the context of personality difficulties. To reflect on enhancing treatment for clients with personality difficulties via training workshops.

Background P Risk is a new tool that aims to help GPs identify people who are at risk of developing psychosis. It uses electronic health record data on non-psychotic symptoms, medications, and sociodemographic factors. Aim To explore clinicians' and patients' views of the acceptability and usefulness of using P Risk in primary care for identifying people at risk of developing psychosis. Design & setting Qualitative study using semistructured interviews conducted with GPs, early intervention (EI) team clinicians, and patients between May and December 2023. Method Participants were recruited from Bristol and London, and three topic guides were developed to ensure consistency across interviews. Interviews were transcribed verbatim and analysed thematically. Results A total of 10 GPs, six EI clinicians, and 13 patients were interviewed. Most clinicians and patients welcomed the development of P Risk as a tool for improving the identification of people at risk of developing psychosis; however, some clinicians raised concerns about the quality of clinician coding in primary care medical records, availability of effective treatments, limited capacity of EI teams to work with people at risk, increased workload for GPs, and the negative impact on patients from being told about their risk of developing psychosis. For patients, identifying people at risk only made sense if treatment for them would be available. Interviewees said that clinicians should explain to patients what psychosis is, what it means to be at risk, which factors drive the risk, and how to address those factors. Conclusion Although most clinicians and patients welcomed the development of P Risk, there needs to be a clear pathway for assessing patients and offering treatment to those who are identified as being at risk of developing psychosis.

BACKGROUND:Young people - aged 16-24 - are high users of digital technology. Online activity can be both beneficial for mental health and harmful. Appointments in general practice (GP) or primary care talking therapy provide opportunities to discuss online activity and its impact on mental health with young people. Such conversations could have preventive value by increasing awareness of problematic behaviours, identifying risk and suggest safer use strategies. However, little is known about whether such conversations are currently delivered in primary care. AIM:To explore practitioners views on discussing online activity and its role in the mental health of young people in primary care. DESIGN AND SETTING:Qualitative study with practitioners in GP and Talking Therapy Method: Semi-structured interviews with 24 practitioners, analysed using reflexive thematic analysis. RESULTS:Practitioners recognise helpful and harmful aspects to online activity, but there is variation in whether practitioners currently ask about online activity and whether they consider conversations appropriate for primary care. Several factors may shape confidence and decision making: practitioners own understanding of the online world; unable to change the impact on mental health or signpost to services; limitations in time, confidence or topic awareness. Practitioners identified a need for guidance and training to inform conversations about online activity. CONCLUSION:There is variation in whether conversations about online activity with young people are happening in primary care. The development of best-practice resources is required to ensure conversations are acceptable to young people and effective at changing problematic online activity to improve mental health.

Background Cognitive–behavioural therapy is an effective treatment for depression. A key question is how to increase access. Engagement with cognitive–behavioural therapy-based computerised interventions is poor, and programmes are inflexible and impersonal. Innovative use of technology and integration of online materials could increase engagement and widen access. Objectives To develop and evaluate a novel approach to delivering cognitive–behavioural therapy for depression integrating therapist-led sessions and online cognitive–behavioural therapy materials. Design and methods The INTEgrated theRApist and online CbT for depression research programme comprised four work packages. The first developed the online therapy platform and materials, and training for therapists. This comprised a series of studies: a systematic review and network meta-analysis to compare the effectiveness of different types and components of cognitive–behavioural therapy; a Delphi study focused on the effective components of cognitive–behavioural therapy; a decision model to evaluate the cost-effectiveness of different formats of delivering cognitive–behavioural therapy; a survey of accredited cognitive–behavioural therapy therapists asking about their use and views of different resources used in cognitive–behavioural therapy; and iterative design work aimed at understanding the design requirements for the platform. The prototype platform was then evaluated in a pilot study, with subsequent final refinement. The second and third work packages evaluated the clinical and cost-effectiveness of the intervention compared with usual general practitioner care in a multicentre randomised controlled trial (with a parallel economic evaluation) over 12 months in primary care patients with depression. The fourth examined the intervention’s acceptability through a nested qualitative study of patients, therapists and supervisors. Setting The randomised controlled trial was based in United Kingdom primary care in Bristol, London and York. Participants Patients aged ≥ 18 years experiencing depressive symptoms in primary care were eligible for the randomised controlled trial. Interventions In the randomised controlled trial, participants were individually randomised to: (1) integrated cognitive–behavioural therapy (in addition to usual general practitioner care); or (2) to continue with usual general practitioner care. Main outcome measures The primary outcome for the randomised controlled trial was depressive symptoms measured using the Beck Depression Inventory, version 2 at 6 months post randomisation. Secondary outcomes included response and remission (based on Beck Depression Inventory, version 2 score), depressive symptoms (Patient Health Questionnaire-9), anxiety symptoms (Generalised Anxiety Disorder-7), function (Work and Social Adjustment Scale), quality of life (EuroQol-5 Dimensions, five-level version), and costs of interventions and wider services. Results Work package 1: the network meta-analysis found no evidence of effect for any content components or combinations of components. There was uncertainty around estimates of cost-effectiveness for different treatment modalities and intensities. Effective components of cognitive–behavioural therapy were identified through the Delphi study, and resources used by therapists identified through a survey of United Kingdom cognitive–behavioural therapy practitioners. Key requirements of an online platform identified through iterative design work were: (1) overcoming depression-related barriers; (2) supporting engagement; (3) reinforcing learning and skill acquisition. In a pilot study with 18 primary care patients, patients said that the integrated approach made therapy more accessible. Therapists commented on the flexibility of the approach. Not all participants engaged with between-session tasks and some technical issues were experienced. Platform refinements were made prior to the randomised controlled trial. Work package 2: overall, 451 patients were recruited to the INTEgrated theRApist and online CbT for depression randomised controlled trial. Participants were predominantly female (n = 313, 69%) and, on average, aged 39 years. The mean Beck Depression Inventory, version 2 score at baseline was 32.8, indicative of severe depression. Most had a history of depression (nearly half having had five or more prior episodes of depression), were taking antidepressants (70%) and the duration of the current episode of depression was ≥ 2 years for 51% of participants. In the intervention group, 14 individuals (6.2%) had no therapy sessions and 137 participants (60.9%) completed therapy (received at least 9 sessions or reached an agreed end of therapy with their therapist in fewer than 9 sessions). Including the above 14 individuals, 88 (39.1%) either withdrew from therapy (n = 50) or were discharged for non-attendance (n = 38). In total 334 patients (171 integrated cognitive–behavioural therapy; 163 usual care) were included in the primary analysis. The intervention group had a Beck Depression Inventory, version 2 score that was, on average, 4.4 points lower (less depressed) than the usual care group at 6 months [difference in means: −4.4 (95% confidence interval −7.0 to −1.9); p = 0.001]. In repeated-measures analyses using data from 6 and 12 months, individuals in the intervention group had a Beck Depression Inventory, version 2 score that was, on average, 3.8 points lower than those in the usual care group (95% confidence interval −6.1 to −1.5; p = 0.001). The intervention group had a twofold increased odds of response and remission, fewer symptoms of depression (Patient Health Questionnaire-9) and anxiety (Generalised Anxiety Disorder-7), and improved functioning (Work and Social Adjustment Scale). Work package 3: the mean costs of integrated cognitive–behavioural therapy were £987 (standard error £14) per participant. The mean costs of usual care were estimated at £382 (standard error £57) in usual care group and £193 (standard error £42) in intervention group. In the primary analyses, costs from the National Health Service/Personal Social Services perspective were £753 (standard error £77) per participant in the usual care group and £1754 (standard error £127) in the intervention group, with adjusted incremental costs of £1009 (95% confidence interval £737 to £1286). The mean quality-adjusted life-years were 0.554 (standard error 0.017) in the usual care group and 0.597 (standard error 0.017) in the intervention group, with adjusted incremental quality-adjusted life-years at 0.033 (95% confidence interval −0.002 to 0.059). The incremental cost-effectiveness ratio was £30,576 per quality-adjusted life-year gain. Complete-case analysis from the National Health Service/Personal Social Services perspective showed a slightly more favourable picture with an incremental cost-effectiveness ratio at £22,421. Work package 4: through interviews with trial participants and therapists, we found that the integrated approach helped patients manage their depression. Platform benefits included the opportunity to review transcripts and to support homework tasks. Typing allowed reflection and a focused discussion. Less could be covered than during an in-person session. Patients who did not complete therapy struggled with typing and found cognitive–behavioural therapy too demanding. Limitations In the trial, the 6-month follow-up rate was slightly below the original target. Conclusions Integrated cognitive–behavioural therapy is an effective and acceptable treatment for patients with depression. There was uncertainty around the cost-effectiveness of the intervention. This novel mode of delivery could increase the availability of cognitive–behavioural therapy and access for those who find it difficult to attend appointments in person. Future work To examine whether effects are sustained long term and to understand which aspects of the platform lead to improvements. Study registration This study is registered as ISRCTN14850613 (phase 2 pilot study) and ISRCTN13112900 (RCT). Funding This award was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research Programme (NIHR award ref: RP-PG-0514-20012) and is published in full in Programme Grants for Applied Research; Vol. 14, No. 13. See the NIHR Funding and Awards website for further award information. Plain language summary There is a high demand for talking therapies such as cognitive–behavioural therapy for depression. Cognitive–behavioural therapy can be delivered by computers or online as written guidance that can be worked through with or without support. These computerised therapy packages are inexpensive and convenient but are not as effective or as engaging as having a therapist. They do not allow treatment to be tailored for the individual. We built an online therapy platform. This combined live therapist sessions with online materials to help patients practise outside the sessions. In the first session, patients and therapists met by videocall. Thereafter, they communicated by typing during live online therapy sessions. We worked with stakeholders to develop integrated cognitive–behavioural therapy. Patients could receive between 9 and 12 sessions of therapy. We evaluated integrated cognitive–behavioural therapy in three ways: We recruited 451 patients with depression and randomly allocated them to either integrated cognitive–behavioural therapy or to continue with usual general practitioner care. Those allocated to therapy were less depressed and more likely to have recovered after 6 and 12 months. This means we can be confident that this is a clinically effective treatment. We assessed whether integrated cognitive–behavioural therapy was good value for money. Although patients felt better, the treatment just failed to meet criteria for value for money. However, the average cost of integrated cognitive–behavioural therapy was similar to the cost of therapy in National Health Service talking therapy services. In-depth interview study: we asked patients and therapists about the treatment. They found it acceptable. Patients who completed the therapy valued being able to talk to a therapist and had learnt skills to manage their depression. Reviewing the record of therapy sessions helped them complete homework tasks and track progress. While less could be covered in a session compared with in-person therapy, the slower pace allowed room for reflection. This also meant therapists used more focused questions. Some patients found it difficult to express themselves through typing. Scientific summary Some text in this section is reproduced from Tallon D, Thomas L, Brabyn S, Ching BCF, Hahn JS, Jude B, et al. Integrated therapist and online CBT for depression in primary care (INTERACT): study protocol for a multi-centre randomised controlled trial. Trials 2023;24:421. https://doi.org/10.1186/s13063-023-07396-9). This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) licence, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: https://creativecommons.org/licenses/by/4.0/. The text below includes minor additions and formatting changes to the original text. Background Cognitive–behavioural therapy (CBT) is an effective treatment for depression and recommended by the National Institute for Health and Care Excellence (NICE). A key question for commissioners and healthcare providers is how to increase access. Cognitive–behavioural therapy-based computerised CBT interventions form part of the stepped care pathway for depression but are not an alternative to high-intensity CBT as they lack flexibility and are impersonal. Cognitive–behavioural therapy delivered online using instant messaging is clinically and cost-effective. Developing materials that are integrated with modern technologies yet permit the therapist to tailor treatment to the individual is critical. Ready access to such materials could facilitate engagement with tasks that take place outside therapy sessions and increase effectiveness. In 2020–1, 90% of UK households had a home computer and 84% of over 16-year-olds private use of a smartphone. Innovative use of technological developments and integration of online materials into therapy offers the potential to increase engagement and widen access to populations that are difficult to reach (e.g. those who are disabled or have difficulty attending appointments for other reasons). Our intervention integrates therapist-led sessions and online CBT materials in a novel approach to the treatment of depression. Aims and objectives The aim of the INTEgrated theRApist and online CbT for depression (INTERACT) programme was to develop [work package (WP) 1] and evaluate (WPs2–4) an integrated approach to delivering CBT for depression in primary care (integrated CBT). The specific aims of the WPs are listed below. Work package 1: intervention development To identify clinical and cost-effective components of CBT to inform the development of the intervention. To develop an online platform to support the delivery of integrated CBT. To develop the online CBT materials. To develop a training package for therapists. Work package 2: randomised controlled trial To examine the clinical effectiveness of an integrated approach to delivering CBT for depression over 12 months’ follow-up. Work package 3: economic evaluation To examine the cost-effectiveness of the integrated CBT intervention. Work package 4: qualitative evaluation To explore patients’, therapists’ and supervisors’ views and experiences of using an integrated approach to delivering CBT for depression. To understand patients’ reasons for completing or not completing integrated therapy. To assess patients’, therapists’ and supervisors’ views on how this novel approach affects the therapist-patient relationship. Methods and results Work package 1: intervention development Systematic review and network meta-analysis of cognitive–behavioural therapy components We conducted a systematic review of randomised controlled trials (RCTs) in adults with depression, which included a CBT intervention, to compare the effectiveness of different types of therapy, different components and combinations of components and aspects of delivery used in CBT for depression. Outcomes were pooled using standard and component-level network meta-analysis (NMA). Among 91 studies included, there was strong evidence that CBT interventions resulted in a larger short-term decrease in depressive symptoms compared with treatment as usual (TAU). The standardised difference in mean change for face-to-face (F2F) CBT compared with TAU was −1.11 [95% credible interval −1.62 to −0.60]; for hybrid CBT was −1.06 (−2.05 to −0.08); and for multimedia CBT was −0.59 (−1.20 to 0.02). A wait list control was detrimental compared with TAU [0.72 (0.09 to 1.35)]. While multimedia and hybrid CBT may be as effective as F2F CBT, there was substantial uncertainty in the estimates of treatment effectiveness. We found no evidence of specific effects of any content components or combination of components. Delphi Study on effective components of cognitive–behavioural therapy We aimed to establish an expert consensus on the effective components of CBT for adults with depression. An international panel of CBT experts (n = 120) was invited to participate in an online survey. In round 1, experts rated the effectiveness of 35 items covering both content and process components of CBT. In a second round, experts rerated components to reach a consensus. Of those invited, 32 participated in round 1 and 21 also provided data in round 2. Consensus was achieved in relation to nine content components (that facilitate behaviour change) and three process components (procedures for therapy delivery). Generic therapeutic competences comprised five of the nine content components. There was less agreement about the effectiveness of cognitive components of CBT. Cost-effectiveness of different formats for delivery of cognitive–behavioural therapy for depression We developed a decision model to evaluate the cost-effectiveness of F2F CBT, multimedia CBT and hybrid CBT, given in addition to TAU, in comparison with TAU alone. F2F and hybrid CBTs were modelled by treatment intensity defined by combinations of number and length of CBT sessions. The model covered an average treatment period of 4 months with a 5-year follow-up period to extrapolate long-term cost-effectiveness. The model inputs were derived from our NMA and the literature. The primary outcome was quality-adjusted life-years (QALYs). All CBT modes given in addition to TAU were more cost-effective than TAU alone. Probabilistic sensitivity analyses found that F2F CBT with intensities of six 30-minute sessions and sixteen 60-minute sessions had the highest probability of being cost-effective. However, neither option reached 50% probability of being most cost-effective (32.5% and 31.1%, respectively). There was substantial uncertainty around estimates. Development of the online therapy platform This comprised: (1) an iterative design stage, (2) a pilot study and (3) final refinement. In phase 1, we held individual interviews, prototype testing sessions, platform walkthroughs and workshops with stakeholders aimed at understanding the design requirements for the platform. Feedback informed the intervention design. Three requirements were identified for integrated CBT therapy platforms: (1) features to overcome depression-related barriers; (2) features that support engagement; and (3) that reinforce learning and support the acquisition and learning of new skills. Therapists highlighted the importance of collaborative working, and the impact of technology on therapists’ workflow and workload, and its potential in supporting clients’ engagement. In phase 2, we conducted a pilot study to evaluate usability and user experience of the intervention. Patients with depression were recruited from primary care and offered a course of integrated therapy using the newly developed platform. Qualitative interviews were conducted with patients, including those who completed and withdrew from therapy. Eighteen patients with depression were recruited from primary care. Of these, 10 completed therapy. Initial interviews were conducted with 13 patients (after 3–6 therapy sessions), and 9 ‘end of therapy’ interviews were completed. Patients appreciated the first session being F2F so they could meet their therapist and build rapport. Typing limited the amount discussed during online sessions, but some patients noted it aided focus and promoted reflection. Patients said that the integrated approach made therapy more accessible, but not all patients engaged with between-session tasks. Some found the worksheets too complex. Usage data showed that patients reviewed transcripts of the instant messaging therapy sessions and commented that these were a useful learning aid. Some technical issues were experienced that sometimes led to lower engagement. Phase 3 involved final refinement of the platform following feedback from patients, therapists and wider stakeholders, and input from the multidisciplinary study team. Platform security was assessed. Development of cognitive–behavioural therapy materials for the online platform We conducted a survey of 3665 accredited UK CBT therapists asking about their use and views of resources commonly described in CBT manuals. Overall, 994 individuals (27%) responded and a further 33 completed the questionnaire online. Over 85% of respondents used symptom measures, lists of problems/goals, activity schedules, behavioural activation diaries/plans, and case formulation worksheets ‘frequently’ or ‘very frequently’. Selection of platform materials was based on: therapist survey findings; the competency framework for CBT for depression; Delphi findings; and systematic review and NMA findings. Most worksheets were selected from resources already available and familiar to therapists. Development of a training package for therapists Training for the therapists employed for WP1.3 – phase 2 was developed and delivered with CBT experts in the research team and supported by the therapists’ supervisor. Online training for the RCT included lectures covering the trial background, therapy protocol, managing risk, and role play. Work package 2: randomised controlled trial We conducted a pragmatic RCT of 451 patients with depression from 67 general practices in 3 UK sites. Patients aged ≥ 18 years, scoring ≥ 14 on the Beck Depression Inventory, version 2 (BDI-II) and who met International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) criteria for depression were eligible. Patients were individually randomised to either integrated CBT [in addition to usual care (UC)] or to continue with usual general practitioner care (UC). The primary outcome was BDI-II score at 6 months post randomisation. Secondary outcomes included response and remission (based on BDI-II), other measures of depression and anxiety [Patient Health Questionnaire-9 items (PHQ-9)/Generalised Anxiety Disorder-7 (GAD-7)], function [Work and Social Adjustment Scale (WSAS)], EuroQol-5 Dimensions, five-level version, and costs of interventions and wider services at 6 and 12 months. The primary analyses were of 334 patients (171 integrated CBT; 163 UC). Those in the intervention group had a BDI-II score that was, on average, 4.4 points lower (less depressed) than those in the UC group at 6 months {difference in means: −4.4 [95% confidence interval (CI) −7.0 to −1.9]; p = 0.001}. In repeated-measures analyses using data from 6 and 12 months, the intervention group had a BDI-II score that was, on average, 3.8 points lower than the UC group (95% CI −6.1 to −1.5, p = 0.001). The intervention group had a twofold increased odds of response (≥ 50% improvement in symptoms) and remission (BDI-II score < 10), fewer symptoms of depression (PHQ-9) and anxiety (GAD-7), and less functional impairment (WSAS). Work package 3: economic evaluation We assessed cost-effectiveness from three perspectives: NHS and Personal Social Services (PSS); participants and their informal carers; and societal. Costs were collected accordingly. The primary analysis was an incremental cost–utility analysis of integrated CBT over and above UC, over 12 months from an NHS and PSS perspective. The incremental cost-effectiveness ratio (ICER) was calculated by dividing incremental costs by incremental QALYs. The mean costs of integrated CBT were £987 [standard error (SE) £14] per participant. The mean costs of UC were estimated at £382 (SE £57) in the UC group and £193 (SE £42) in the intervention group. In the primary analysis, costs from the NHS/PSS perspective were £753 (SE £77) per participant in the UC group and £1754 (SE £127) in the intervention group, with adjusted incremental costs of £1009 (95% CI £737 to £1286). The mean QALYs were 0.554 (SE 0.017) in the UC group and 0.597 (SE 0.017) in the intervention group, with adjusted incremental QALYs at 0.033 (95% CI −0.002 to 0.059). The ICER was £30,576 per QALY gain (probability of cost-effectiveness from £20,000 to £30,000: 13%–39%). Complete-case analysis (CCA) from NHS/PSS perspective showed a slightly more favourable picture with ICER at £22, 421 (probability of cost-effectiveness: 37%–66%). Work package 4: qualitative evaluation A qualitative study was nested within the main trial. We interviewed 30 patients (20 who received the intervention and 10 from UC), 9 therapists and 3 therapist supervisors. Data were analysed using thematic analysis. The combination of one-to-one sessions with a therapist and having access to integrated online CBT resources enabled patients to better manage their depression. Benefits included the opportunity to review transcripts to clarify homework tasks and track progress in managing their depression. Those who completed therapy valued talking to a therapist and accessing CBT resources within a single platform. Those who did not complete therapy found it difficult to express themselves through typing and found the CBT approach too demanding. As typing limited what could be covered in a single session, therapists restricted the session agenda and asked more focused questions. Conclusions Developing an integrated approach to delivering cognitive–behavioural therapy Based on the systematic review and NMA of trials of CBT interventions, we found no evidence of specific effects of any content components or combinations of components of CBT interventions to inform the platform development. Our decision model showed that there was uncertainty around estimates of cost-effectiveness for different treatment modalities and intensities limiting the extent to which this work could inform the intervention design. Through our survey of CBT therapists, we identified the most frequently used resources. The Delphi study provided insight into the generic therapeutic competences that CBT experts agreed on. In the absence of evidence on the effective or cost-effective components of CBT from the earlier systematic review, NMA and decision model, the findings from the survey and Delphi study were used to map and identify the CBT resources required within our online platform that aligned with the CBT competences framework. Iterative development of the online therapy platform resulted in a prototype platform that was acceptable to patients and therapists. Integrated CBT was provided to a small sample of depressed patients recruited from primary care. Effectiveness, cost-effectiveness and acceptability of an integrated approach to delivering cognitive–behavioural therapy Integrated CBT was effective in reducing depressive symptoms in primary care patients with depression. Benefits were also seen for the outcomes of response and remission in depressive symptoms, and symptoms of anxiety. Improvements were maintained over 12 months. The intervention was not cost-effective based on the current thresholds used by NICE. However, the intervention cost included training costs that would be unlikely to be maintained at the same level if the intervention was rolled out in NHS services. Further, once trained, therapists could treat more patients (beyond the study sample) which would reduce the per-patient training cost and may make the longer-term cost–benefit more favourable. The intervention was acceptable to patients and therapists. The qualitative study highlighted the importance of establishing patient and therapist goals and expectations about what can be achieved in CBT mediated by typing. Some patients are comfortable communicating via typing and are motivated to utilise online resources between sessions. Exploring the benefits and challenges of integrated CBT with patients will enable them to make an informed choice about referral for this novel therapy. Implications for health care The COVID-19 pandemic resulted in many services moving to remote delivery of therapy. There has also been a proliferation of mental health apps in recent years, but with little empirical evidence to support their use. The integrated approach that we have developed is of proven effectiveness. While the intervention was just above the upper limit in terms of accepted thresholds of value for money, the costs of training may be over-estimated compared to those incurred if this intervention was implemented within the NHS. Importantly, the approach was acceptable to patients and therapists and as such offers the potential to increase access for those who find it difficult to attend therapy appointments in person. Recommendations for research Future research needs to examine The longer-term clinical and cost-effectiveness of integrated cognitive–behavioural therapy Studies of in-person CBT have found that CBT is a clinically and cost-effective intervention over four years. Evidence is thus needed to quantify and substantiate the long-term gain for this integrated CBT approach. Which aspects of the platform led to improvements in depression This may enable refinement of the intervention to increase benefits. Study registration This study is registered as ISRCTN14850613 (phase 2 pilot study) and ISRCTN13112900 (RCT). Funding This award was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research Programme (NIHR award ref: RP-PG-0514-20012) and is published in full in Programme Grants for Applied Research; Vol. 14, No. 13. See the NIHR Funding and Awards website for further award information.

LQD was an open-label randomised trial comparing lithium versus quetiapine augmentation of antidepressants in treatment-resistant depression (TRD). In the primary analysis, quetiapine was more effective at reducing depressive symptoms. Conduct a secondary analysis of LQD to examine anxiolysis of Quetiapine compared to Lithium and examine baseline anxiety as a moderator of antidepressant effects. Using linear mixed-models we examined the difference between lithium and quetiapine in anxiety (GAD-7) at 8, 26 and 52 weeks. We modified the main trial’s linear mixed-model with an interaction term for baseline anxiety to estimate the differences in area under the curve (AUC) between treatments for three baseline anxiety levels across the 52 weeks. There was little difference between the anxiolysis of quetiapine compared to lithium at 8 (-0.07, p = 0.92), 26 (-0.71, p = 0.30) or 52 weeks (-0.05, p = 0.95). For those with severe baseline anxiety, participants taking quetiapine showed a greater reduction in depressive symptoms than lithium (AUC − 111.6 (95

BACKGROUND:About 30% of patients with depression treated with antidepressant medication do not respond sufficiently to the first agents used. Pramipexole might usefully augment antidepressant medication in such cases of treatment-resistant depression, but data on its effects and tolerability are scarce. We aimed to assess the efficacy and tolerability of pramipexole augmentation of ongoing antidepressant treatment, over 48 weeks, in patients with treatment-resistant depression. METHODS:We did a multicentre, double-blind, placebo-controlled randomised trial in which adults with resistant major depressive disorder were randomly assigned (1:1; using an online randomisation system) to 48 weeks of pramipexole (titrated to 2·5 mg) or placebo added to their ongoing antidepressant medication. The study was conducted in nine National Health Service Trusts in England. Participants, investigators, and researchers involved in recruitment and assessment were masked to group allocation, and the central pharmacy team dispensing the medication was not masked. The primary outcome was change from baseline to week 12 in the total score of the 16-item Quick Inventory of Depressive Symptomology self-report version (QIDS-SR16). The primary analysis was performed on the intention-to-treat population that included all eligible, randomly assigned participants. People with lived experience were involved in the design, oversight, and interpretation of the study. The trial was registered with ISCTRN (ISRCTN84666271) and EudraCT (2019-001023-13) and is complete. FINDINGS:Between Feb 16 and May 29, 2024, 217 participants attended a screening visit, of whom 66 were excluded due to ineligibility. 151 participants were randomly assigned (75 to the pramipexole group and 75 to the placebo group, after one participant was found to be ineligible after randomisation). 84 (56%) participants were female and 66 (44%) were male and the mean age of participants was 44·9 years (SD 14·0). Ethnicity data were not available. The mean QIDS-SR16 total score at baseline was 16·4 (SD 3·4) in the pramipexole group and 16·2 (3·5) in the placebo group. The mean dose of pramipexole received at week 12 was 2·3 mg (SD 0·45). Adjusted mean decrease from baseline to week 12 of the QIDS-SR16 total score was 6·4 (SD 4·9) for the pramipexole group and 2·4 (4·0) for the placebo group; the mean difference between groups was -3·91 (95% CI -5·37 to -2·45; p<0·0001). Termination of trial treatment due to adverse events was more frequent in the pramipexole group (15 participants [20%]) than in the placebo group (four participants [5%]), with reported adverse events consistent with known side-effects of pramipexole, in particular nausea, headache, and sleep disturbance or somnolence. INTERPRETATION:In this trial involving participants with treatment-resistant depression, pramipexole augmentation of antidepressant treatment, at a target dose of 2·5 mg, demonstrated a reduction in symptoms relative to placebo at 12 weeks but was associated with some adverse effects. These results suggest that pramipexole is a clinically effective option for reducing symptoms in patients with treatment-resistant depression. Future trials directly comparing pramipexole with existing treatments for this disorder are needed. FUNDING:National Institute of Health and Care Research, Efficacy and Mechanism Evaluation Programme.

BACKGROUND:Integrating therapist-led sessions and cognitive behavioural therapy (CBT) materials within one online platform may be effective for people with depression. A trial evaluating this mode of delivering CBT is being conducted. To maximise future trial recruitment and understand patients' views of health interventions, it is important to explore reasons for declining to participate. AIM:To explore patients' reasons for declining to participate in a trial of integrated online CBT for depression. DESIGN & SETTING:A mixed-methods study collecting data from patients via questionnaires and telephone interviews at three UK trial sites. METHOD:Individuals completed a short questionnaire about their reasons for not taking part in the trial. Telephone interviews further explored these reasons with a subgroup. Quantitative data were summarised using descriptive statistics. Qualitative interviews were analysed thematically. RESULTS:Of 1799 patients who responded to an invitation to participate in the trial, 40.3% declined contact. The most common reasons were not wanting: to take part in research (n = 387); therapy provided online (n = 284); to receive CBT (n = 262). Qualitative interviews with 15 'decliners' highlighted that decisions related to perceptions of eligibility, previous experiences of CBT, and uncertainty about receiving CBT online. Personal circumstances, depressive symptoms, or other mental health issues were also barriers to participation. CONCLUSION:Reasons given by primary care patients for not taking part in a trial of integrated online CBT suggest that, at the point of recruitment, it is important to discuss the patient's perceptions of their eligibility and whether they would accept the intervention being evaluated.

Background:Lithium and several atypical antipsychotics are the recommended first-line augmentation options for treatment-resistant depression; however, few studies have compared them directly, and none for longer than 8 weeks. Consequently, there is little evidence-based guidance for clinicians when choosing an augmentation option for patients with treatment-resistant depression. Objectives:This trial examined whether it is more clinically and cost-effective to prescribe lithium or quetiapine augmentation therapy for patients with treatment-resistant depression over 12 months. Design:This was a parallel group, multicentre, pragmatic, open-label superiority trial comparing the clinical and cost-effectiveness of lithium versus quetiapine augmentation of antidepressant medication in treatment-resistant depression. Participants were randomised 1 : 1 at baseline to the decision to prescribe either lithium or quetiapine. Setting:Six National Health Service trusts in England. Participants:Eligible participants were aged ≥ 18 years, met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for major depressive disorder, scored ≥ 14 on the 17-item Hamilton Depression Rating Scale and whose depression had had an inadequate response to at least two therapeutic antidepressant treatment trials in the current episode, with a current antidepressant treatment at or above the therapeutic dose for ≥ 6 weeks. Patients with a history of psychosis or bipolar disorder were excluded. Patients were judged suitable for either treatment. Interventions:After randomisation, pre-prescribing safety checks were undertaken as per standard care and trial clinicians decided whether to proceed with prescribing the allocated medication. Trial clinicians received recommendations for titration and dosing in line with current clinical guidelines; however, dosing regimens could be altered according to tolerability and response. Participants were followed up using weekly self-report questionnaires and 8-, 26- and 52-week research visits. Main outcome measures:The co-primary outcome measures were depressive symptom severity over 52 weeks, measured weekly using the self-rated Quick Inventory of Depressive Symptomatology, and time to all-cause treatment discontinuation of the trial medication. Economic analyses compared costs between the two treatment arms over 52 weeks, from a National Health Service and Personal Social Services perspective, and a societal perspective. Results:Two hundred and twelve participants were randomised, 107 to quetiapine and 105 to lithium. The quetiapine arm showed a significantly greater reduction in depressive symptoms than the lithium arm over 52 weeks (quetiapine vs. lithium area under the differences curve = -68.36, 95% confidence interval: -129.95 to -6.76, p = 0.0296). Median days to discontinuation did not significantly differ between the two arms (quetiapine = 365.0, interquartile range = 57.0-365.0, lithium = 212.0, interquartile range = 21.0-365.0), p = 0.1196. Quetiapine was more cost effective than lithium. Thirty-two serious adverse events were recorded, only one of which was deemed possibly related to the intervention (lithium). Limitations:The trial was unblinded, therefore expectancies regarding the trial medications may have influenced the results. Further, there was substantial missing data for some of the secondary outcome measures. Conclusions:As well as being more cost-effective, quetiapine may be a more clinically effective augmentation option for treatment-resistant depression. Future work:Examining predictors of treatment response, including clinical, sociodemographic and biological factors, will help establish whether there are additional factors to consider when choosing an augmentation treatment for treatment-resistant depression. Trial registration:This trial is registered as ISRCTN16387615. Funding:This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/222/02) and is published in full in Health Technology Assessment; Vol. 29, No. 12. See the NIHR Funding and Awards website for further award information.

OBJECTIVES:This study aims to establish and evaluate validity data for pediatric difficult intravenous access (DIVA) scores in low-resource emergency care settings within low- to middle-income countries (LMIC). We also sought to explore associated factors for DIVA that could contribute to a modified pediatric DIVA score with optimal performance in our setting. METHODS:We performed a prospective cross-sectional study in children aged 0 to 15 years who required urgent or emergent peripheral intravenous access (PIVA) over a 10-month period in a large university hospital in Bangkok, Thailand. DIVA was defined as a failure of PIVA on the first attempt. For each candidate DIVA model, receiver operating characteristic curves were constructed, and the area under the curves was calculated. Additional candidate predictive factors of patients and providers were collected and analyzed using a logistic regression model. RESULTS:Among a convenience sample of 392 children enrolled, the DIVA rate was 30.1%. Three-variable DIVA (DIVA3) and 4-variable DIVA scores (DIVA4) demonstrated similar test characteristics in our population in identifying patients with first attempt failure rate of at least 50%. Vein visibility, vein palpability, younger age, and history of DIVA were statistically significant factors related to DIVA. Through the inclusion of 4 factors associated with DIVA, the LMIC-DIVA score was developed and exhibited superior discriminative ability compared with the DIVA3 and DIVA4 scores. The area under the curves for LMIC-DIVA, DIVA3, and DIVA4 were 0.79 (95% CI=0.74-0.83), 0.65 (95% CI=0.59-0.70), and 0.62 (95% CI=0.56-0.67), respectively. CONCLUSION:This study provides external validation data for DIVA3 and DIVA4 scores in the LMIC setting. The novel modified 4-variable LMIC-DIVA score improves test characteristics and accuracy in identifying pediatric DIVA in our population.