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Background: The literature is equivocal as to whether the predicted negative mental health impact of the COVID-19 pandemic came to fruition. Some quantitative studies report increased emotional problems and depression; others report improved mental health and well-being. Qualitative explorations reveal heterogeneity, with themes ranging from feelings of loss to growth and development., Objective: This study aims to analyze free-text responses from children and young people participating in the Children and Young People With Long COVID study to get a clearer understanding of how young people were feeling during the pandemic., Methods: A total of 8224 free-text responses from children and young people were analyzed using InfraNodus, an artificial intelligence-powered text network analysis tool, to determine the most prevalent topics. A random subsample of 411 (5%) of the 8224 responses underwent a manual sentiment analysis; this was reweighted to represent the general population of children and young people in England., Results: Experiences fell into 6 main overlapping topical clusters: school, examination stress, mental health, emotional impact of the pandemic, social and family support, and physical health (including COVID-19 symptoms). Sentiment analysis showed that statements were largely negative (314/411, 76.4%), with a small proportion being positive (57/411, 13.9%). Those reporting negative sentiment were mostly female (227/314, 72.3%), while those reporting positive sentiment were mostly older (170/314, 54.1%). There were significant observed associations between sentiment and COVID-19 status as well as sex (P=.001 and P<.001, respectively) such that the majority of the responses, regardless of COVID-19 status or sex, were negative; for example, 84.1% (227/270) of the responses from female individuals and 61.7% (87/141) of those from male individuals were negative. There were no observed associations between sentiment and all other examined demographics. The results were broadly similar when reweighted to the general population of children and young people in England: 78.52% (negative), 13.23% (positive), and 8.24% (neutral)., Conclusions: We used InfraNodus to analyze free-text responses from a large sample of children and young people. The majority of responses (314/411, 76.4%) were negative, and many of the children and young people reported experiencing distress across a range of domains related to school, social situations, and mental health. Our findings add to the literature, highlighting the importance of specific considerations for children and young people when responding to national emergencies., (©Natalia K Rojas, Sam Martin, Mario Cortina-Borja, Roz Shafran, Lana Fox-Smith, Terence Stephenson, Brian C F Ching, Anaïs d'Oelsnitz, Tom Norris, Yue Xu, Kelsey McOwat, Emma Dalrymple, Isobel Heyman, Tamsin Ford, Trudie Chalder, Ruth Simmons, CLoCk Consortium, Snehal M Pinto Pereira. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 28.01.2025.)

Background: Post-COVID Condition (PCC), also known as 'Long COVID,' refers to persistent symptoms following a coronavirus 2 (SARS-CoV-2) infection. The prevalence of PCC in children and adolescents varies, impacting multiple body systems and affecting daily functioning. Specialised paediatric hubs were established in England to address the needs of young individuals with PCC. Additional local services also emerged, yet patients report challenges accessing services. To better understand the landscape of paediatric PCC services, we used a novel methodology using a web-based systematic search., Methods: A web-based search was conducted in July 2023 using DEVONagent Pro. Search terms related to Long COVID and Pediatrics in England. Eligible sources providing information on PCC services for children and young people were included. A supplementary manual search and NHS England Post-COVID Network were also consulted. Data extraction included service location, characteristics, and referral pathways. Population estimates were derived from UK Census data., Results: Among 342 identified records, 27 services met eligibility criteria, distributed unevenly across regions. Specialised hubs covered 13 locations, while additional services were concentrated in the South of England and London. Services varied in team composition, age range treated, and support offered. A lack of standardised approaches for paediatric PCC was evident., Discussion: We used a novel methodology for systematically mapping online resources, providing valuable insights into service accessibility and aiding the identification of potential gaps. We observed geographical disparities in access to paediatric PCC services and the absence of standardised approaches in managing symptoms. Given the challenges faced by young individuals seeking support for their PCC the need for equitable and standardised care became apparent. The study contributes to closing the research-practice gap and calls for further research to identify effective treatments for paediatric PCC, acknowledging the diversity of reported symptoms and the importance of tailored approaches., (© 2024. The Author(s).)

Background: During the COVID-19 pandemic children and young people (CYP) were socially restricted during a stage of life crucial to development, potentially putting an already vulnerable population at higher risk of loneliness, social isolation, and poorer wellbeing. The objectives of this study are to conduct an exploratory analysis into loneliness before and during the pandemic, and determine which self-reported factors are associated with loneliness., Methods and Findings: Participants from The Children with Long COVID (CLoCk) national study were invited to take part via an online survey, with a total of 31,017 participants taking part, 31,016 of which reported on their experience of loneliness. Participants retrospectively answered questions on demographics, lifestyle, physical health and mental health and loneliness before the pandemic and at the time of answering the survey. Before the pandemic 6.5% (2,006/31,016) of participants reported experiencing loneliness "Often/Always" and at the time of survey completion 17.4% (5,395/31,016) reported feeling lonelier. There was an association between meeting the research definition of long COVID and loneliness [3.49 OR, 95%CI 3.28-3.72]. CYP who reported feeling lonelier at the time of the survey than before the pandemic were assigned female at birth, older CYP, those from Black/African/Caribbean/Black British or other ethnicity groups, those that had 3-4 siblings and lived in more deprived areas., Conclusions: We demonstrate associations between multiple factors and experiences of loneliness during the pandemic. There is a need for a multi-faceted integrated approach when developing interventions targeted at loneliness. It is important to follow up the CYP involved at regular intervals to investigate the progression of their experience of loneliness over time., Competing Interests: TS is Chair of the Health Research Authority and therefore recused himself from the Research Ethics Application. TC is a member of the National Institute for Health and Care Excellence committee for long COVID. She has written self-help books on chronic fatigue and has done workshops on chronic fatigue and post infectious syndromes. TC also has a grant looking at long COVID in adults. MGS reports grants from MRC and Health Protection Research Unit in Emerging & Zoonotic Infections, University of Liverpool. He also reports a role as Independent external and non-remunerated member of Pfizer’s External Data Monitoring Committee for their mRNA vaccine program. He is Chair of Infectious Disease Scientific Advisory Board for Integrum Scientific LLC, Greensboro, NC, USA and director of MedEx Solutions Ltd. He reports minority stock ownership for Integrum Scientific LLC, Greensboro, NC, USA and majority stock ownership for MedEx Solutions Ltd. He also reports a gift from Chiesi Farmaceutici SPA to his institution of a clinical trial investigational medicinal product without encumbrance and distribution of same to trial sites. He is also a non-remunerated independent member of HMG UK Scientific Advisory Group for Emergencies (SAGE, COVID-19 Response) and HMG UK New Emerging Respiratory Virus Threats Advisory Group (NERVTAG). All remaining authors have no conflicts of interest. Data cannot be shared publicly due to ethical and legal considerations. All requests for data will be reviewed by the Children & young people with Long Covid (CLoCk) study team, to verify whether the request is subject to any intellectual property or confidentiality obligations. Requests for access to the participant-level data from this study can be submitted via email to Clock@ukhsa.gov.uk with detailed proposals for approval. A signed data access agreement with the CLoCk team is required before accessing shared data. This does not alter our adherence to PLOS ONE policies on sharing data and materials.", (Copyright: © 2023 McOwat et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: This study describes long COVID symptomatology in a national sample of 18- to 20-year-olds with Polymerase Chain Reaction (PCR)-confirmed Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) and matched test-negative controls in England. Symptoms in 18- to 20-year-olds were compared to symptoms in younger adolescents (aged 11-17 years) and all adults (18+)., Methods: A national database was used to identify SARS-CoV-2 PCR-positive 18- to 20-year-olds and test-negative controls matched by time of test, age, gender, and geographical region. Participants were invited to complete a questionnaire about their health retrospectively at time of test and also when completing the questionnaire. Comparison cohorts included children and young people with long COVID and REal-time Assessment of Community Transmission studies., Results: Of 14,986 people invited, 1,001 were included in the analysis (562 test-positive; 440 test-negative). At testing, 46.5% of test-positives and 16.4% of test-negatives reported at least one symptom. At the time of questionnaire completion (median 7 months post-testing), 61.5% of test-positives and 47.5% of test-negatives reported one or more symptoms. The most common symptoms were similar amongst test-positives and test-negatives and included tiredness (44.0%; 35.7%), shortness of breath (28.8%; 16.3%), and headaches (13.7%; 12.0%). Prevalence rates were similar to those reported by 11-17-year-olds (66.5%) and higher than those reported in all adults (37.7%). For 18- to 20-year-olds, there was no significant difference in health-related quality of life and well-being (p > .05). However, test-positives reported being significantly more tired than test-negatives (p = .04)., Discussion: Seven months after PCR test, a high proportion of test-positive and test-negative 18- to 20-year-olds reported similar symptoms to each other and to those experienced by younger and older counterparts., (Copyright © 2023 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background: We describe post-COVID symptomatology in a non-hospitalised, national sample of adolescents aged 11-17 years with PCR-confirmed SARS-CoV-2 infection compared with matched adolescents with negative PCR status., Methods: In this national cohort study, adolescents aged 11-17 years from the Public Health England database who tested positive for SARS-CoV-2 between January and March, 2021, were matched by month of test, age, sex, and geographical region to adolescents who tested negative. 3 months after testing, a subsample of adolescents were contacted to complete a detailed questionnaire, which collected data on demographics and their physical and mental health at the time of PCR testing (retrospectively) and at the time of completing the questionnaire (prospectively). We compared symptoms between the test-postive and test-negative groups, and used latent class analysis to assess whether and how physical symptoms at baseline and at 3 months clustered among participants. This study is registered with the ISRCTN registry (ISRCTN 34804192)., Findings: 23 048 adolescents who tested positive and 27 798 adolescents who tested negative between Jan 1, 2021, and March 31, 2021, were contacted, and 6804 adolescents (3065 who tested positive and 3739 who tested negative) completed the questionnaire (response rate 13·4%). At PCR testing, 1084 (35·4%) who tested positive and 309 (8·3%) who tested negative were symptomatic and 936 (30·5%) from the test-positive group and 231 (6·2%) from the test-negative group had three or more symptoms. 3 months after testing, 2038 (66·5%) who tested positive and 1993 (53·3%) who tested negative had any symptoms, and 928 (30·3%) from the test-positive group and 603 (16·2%) from the test-negative group had three or more symptoms. At 3 months after testing, the most common symptoms among the test-positive group were tiredness (1196 [39·0%]), headache (710 [23·2%]), and shortness of breath (717 [23·4%]), and among the test-negative group were tiredness (911 [24·4%]), headache (530 [14·2%]), and other (unspecified; 590 [15·8%]). Latent class analysis identified two classes, characterised by few or multiple symptoms. The estimated probability of being in the multiple symptom class was 29·6% (95% CI 27·4-31·7) for the test-positive group and 19·3% (17·7-21·0) for the test-negative group (risk ratio 1·53; 95% CI 1·35-1·70). The multiple symptoms class was more frequent among those with positive PCR results than negative results, in girls than boys, in adolescents aged 15-17 years than those aged 11-14 years, and in those with lower pretest physical and mental health., Interpretation: Adolescents who tested positive for SARS-CoV-2 had similar symptoms to those who tested negative, but had a higher prevalence of single and, particularly, multiple symptoms at the time of PCR testing and 3 months later. Clinicians should consider multiple symptoms that affect functioning and recognise different clusters of symptoms. The multiple and varied symptoms show that a multicomponent intervention will be required, and that mental and physical health symptoms occur concurrently, reflecting their close relationship., Funding: UK Department of Health and Social Care, in their capacity as the National Institute for Health Research, and UK Research and Innovation., Competing Interests: Declaration of interests TS is Chair of the Health Research Authority and therefore recused himself from the research ethics application. TC is a member of the National Institute for Health and Care Excellence committee for long COVID. She has written self-help books on chronic fatigue and has done workshops on chronic fatigue and post infectious syndromes. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The effectiveness of antiretroviral therapy (ART) depends on prompt uptake of treatment and a high level of adherence over the long-term, yet these behaviors are suboptimal. Previous interventions have significantly improved adherence but effect sizes are generally small. The aim of this article is to describe the design and content of an intervention to support uptake and adherence to treatment in HIV positive patients (SUPA intervention), utilizing cognitive behavioral and motivational interviewing (MI) techniques. The intervention was developed in line with Medical Research Council (MRC) guidance for the development of complex interventions and informed by the NICE (National Institute for Health and Care Excellence) Guidelines for adherence, empirical evidence and focus groups. Behavior change techniques were mapped to perceptual and practical barriers to uptake and adherence to ART, identified in previous research. Intervention materials were designed and later discussed within focus groups, where feedback enabled an iterative process of development. We conclude it is possible to transparently report the design and content of a theory-based intervention to increase uptake and adherence to ART. The intervention has been evaluated within a randomized controlled trial (RCT) at 10 HIV clinics in England, the results of which will be reported elsewhere., (© Society of Behavioral Medicine 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: Infection with SARS-CoV-2 is associated with fatigue and sleep problems long after the acute phase of COVID-19. In addition, there are concerns of SARS-CoV-2 infection causing psychiatric illness; however, evidence of a direct effect is inconclusive., Objective: To assess risk of risk of incident or repeat psychiatric illness, fatigue, or sleep problems following SARS-CoV-2 infection and to analyze changes according to demographic subgroups., Design, Setting, and Participants: This cohort study assembled matched cohorts using the Clinical Practice Research Datalink Aurum, a UK primary care registry of 11 923 499 individuals aged 16 years or older. Patients were followed-up for up to 10 months, from February 1 to December 9, 2020. Individuals with less than 2 years of historical data or less than 1 week follow-up were excluded. Individuals with positive results on a SARS-CoV-2 test without prior mental illness or with anxiety or depression, psychosis, fatigue, or sleep problems were matched with up to 4 controls based on sex, general practice, and year of birth. Controls were individuals who had negative SARS-CoV-2 test results. Data were analyzed from January to July 2021., Exposure: SARS-CoV-2 infection, determined via polymerase chain reaction testing., Main Outcomes and Measures: Cox proportional hazard models estimated the association between a positive SARS-CoV-2 test result and subsequent psychiatric morbidity (depression, anxiety, psychosis, or self-harm), sleep problems, fatigue, or psychotropic prescribing. Models adjusted for comorbidities, ethnicity, smoking, and body mass index., Results: Of 11 923 105 eligible individuals (6 011 020 [50.4%] women and 5 912 085 [49.6%] men; median [IQR] age, 44 [30-61] years), 232 780 individuals (2.0%) had positive result on a SARS-CoV-2 test. After applying selection criteria, 86 922 individuals were in the matched cohort without prior mental illness, 19 020 individuals had prior anxiety or depression, 1036 individuals had psychosis, 4152 individuals had fatigue, and 4539 individuals had sleep problems. After adjusting for observed confounders, there was an association between positive SARS-CoV-2 test results and psychiatric morbidity (adjusted hazard ratio [aHR], 1.83; 95% CI, 1.66-2.02), fatigue (aHR, 5.98; 95% CI, 5.33-6.71), and sleep problems (aHR, 3.16; 95% CI, 2.64-3.78). However, there was a similar risk of incident psychiatric morbidity for those with a negative SARS-CoV-2 test results (aHR, 1.71; 95% CI, 1.65-1.77) and a larger increase associated with influenza (aHR, 2.98; 95% CI, 1.55-5.75)., Conclusions and Relevance: In this cohort study of individuals registered at an English primary care practice during the pandemic, there was consistent evidence that SARS-CoV-2 infection was associated with increased risk of fatigue and sleep problems. However, the results from the negative control analysis suggest that unobserved confounding may be responsible for at least some of the positive association between COVID-19 and psychiatric morbidity.

Background: Telephone therapist delivered CBT (TCBT) and web-based CBT (WCBT) have been shown to be significantly more clinically effective than treatment as usual (TAU) at reducing IBS symptom severity and impact at 12 months in adults with refractory IBS. In this paper we assess the cost-effectiveness of the interventions., Methods: Participants were recruited from 74 general practices and three gastroenterology centres in England. Interventions costs were calculated, and other service use and lost employment measured and costed for one-year post randomisation. Quality-adjusted life years (QALYs) were combined with costs to determine cost-effectiveness of TCBT and WCBT compared to TAU., Results: TCBT cost £956 more than TAU (95% CI, £601-£1435) and generated 0.0429 more QALYs. WCBT cost £224 more than TAU (95% CI, - £11 to £448) and produced 0.029 more QALYs. Compared to TAU, TCBT had an incremental cost per QALY of £22,284 while the figure for WCBT was £7724. After multiple imputation these ratios increased to £27,436 and £17,388 respectively. Including lost employment and informal care, TCBT had costs that were on average £866 lower than TAU (95% CI, - £1133 to £2957), and WCBT had costs that were £1028 lower than TAU (95% CI, - £448 to £2580)., Conclusions: TCBT and WCBT resulted in more QALYs and higher costs than TAU. Complete case analysis suggests both therapies are cost-effective from a healthcare perspective. Imputation for missing data reduces cost-effectiveness but WCTB remained cost-effective. If the reduced societal costs are included both interventions are likely to be more cost-effective. Trial registration ISRCTN44427879 (registered 18.11.13).

Background: Dissociative seizures are paroxysmal events resembling epilepsy or syncope with characteristic features that allow them to be distinguished from other medical conditions. We aimed to compare the effectiveness of cognitive behavioural therapy (CBT) plus standardised medical care with standardised medical care alone for the reduction of dissociative seizure frequency., Methods: In this pragmatic, parallel-arm, multicentre randomised controlled trial, we initially recruited participants at 27 neurology or epilepsy services in England, Scotland, and Wales. Adults (≥18 years) who had dissociative seizures in the previous 8 weeks and no epileptic seizures in the previous 12 months were subsequently randomly assigned (1:1) from 17 liaison or neuropsychiatry services following psychiatric assessment, to receive standardised medical care or CBT plus standardised medical care, using a web-based system. Randomisation was stratified by neuropsychiatry or liaison psychiatry recruitment site. The trial manager, chief investigator, all treating clinicians, and patients were aware of treatment allocation, but outcome data collectors and trial statisticians were unaware of treatment allocation. Patients were followed up 6 months and 12 months after randomisation. The primary outcome was monthly dissociative seizure frequency (ie, frequency in the previous 4 weeks) assessed at 12 months. Secondary outcomes assessed at 12 months were: seizure severity (intensity) and bothersomeness; longest period of seizure freedom in the previous 6 months; complete seizure freedom in the previous 3 months; a greater than 50% reduction in seizure frequency relative to baseline; changes in dissociative seizures (rated by others); health-related quality of life; psychosocial functioning; psychiatric symptoms, psychological distress, and somatic symptom burden; and clinical impression of improvement and satisfaction. p values and statistical significance for outcomes were reported without correction for multiple comparisons as per our protocol. Primary and secondary outcomes were assessed in the intention-to-treat population with multiple imputation for missing observations. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN05681227, and ClinicalTrials.gov, NCT02325544., Findings: Between Jan 16, 2015, and May 31, 2017, we randomly assigned 368 patients to receive CBT plus standardised medical care (n=186) or standardised medical care alone (n=182); of whom 313 had primary outcome data at 12 months (156 [84%] of 186 patients in the CBT plus standardised medical care group and 157 [86%] of 182 patients in the standardised medical care group). At 12 months, no significant difference in monthly dissociative seizure frequency was identified between the groups (median 4 seizures [IQR 0-20] in the CBT plus standardised medical care group vs 7 seizures [1-35] in the standardised medical care group; estimated incidence rate ratio [IRR] 0·78 [95% CI 0·56-1·09]; p=0·144). Dissociative seizures were rated as less bothersome in the CBT plus standardised medical care group than the standardised medical care group (estimated mean difference -0·53 [95% CI -0·97 to -0·08]; p=0·020). The CBT plus standardised medical care group had a longer period of dissociative seizure freedom in the previous 6 months (estimated IRR 1·64 [95% CI 1·22 to 2·20]; p=0·001), reported better health-related quality of life on the EuroQoL-5 Dimensions-5 Level Health Today visual analogue scale (estimated mean difference 6·16 [95% CI 1·48 to 10·84]; p=0·010), less impairment in psychosocial functioning on the Work and Social Adjustment Scale (estimated mean difference -4·12 [95% CI -6·35 to -1·89]; p<0·001), less overall psychological distress than the standardised medical care group on the Clinical Outcomes in Routine Evaluation-10 scale (estimated mean difference -1·65 [95% CI -2·96 to -0·35]; p=0·013), and fewer somatic symptoms on the modified Patient Health Questionnaire-15 scale (estimated mean difference -1·67 [95% CI -2·90 to -0·44]; p=0·008). Clinical improvement at 12 months was greater in the CBT plus standardised medical care group than the standardised medical care alone group as reported by patients (estimated mean difference 0·66 [95% CI 0·26 to 1·04]; p=0·001) and by clinicians (estimated mean difference 0·47 [95% CI 0·21 to 0·73]; p<0·001), and the CBT plus standardised medical care group had greater satisfaction with treatment than did the standardised medical care group (estimated mean difference 0·90 [95% CI 0·48 to 1·31]; p<0·001). No significant differences in patient-reported seizure severity (estimated mean difference -0·11 [95% CI -0·50 to 0·29]; p=0·593) or seizure freedom in the last 3 months of the study (estimated odds ratio [OR] 1·77 [95% CI 0·93 to 3·37]; p=0·083) were identified between the groups. Furthermore, no significant differences were identified in the proportion of patients who had a more than 50% reduction in dissociative seizure frequency compared with baseline (OR 1·27 [95% CI 0·80 to 2·02]; p=0·313). Additionally, the 12-item Short Form survey-version 2 scores (estimated mean difference for the Physical Component Summary score 1·78 [95% CI -0·37 to 3·92]; p=0·105; estimated mean difference for the Mental Component Summary score 2·22 [95% CI -0·30 to 4·75]; p=0·084), the Generalised Anxiety Disorder-7 scale score (estimated mean difference -1·09 [95% CI -2·27 to 0·09]; p=0·069), and the Patient Health Questionnaire-9 scale depression score (estimated mean difference -1·10 [95% CI -2·41 to 0·21]; p=0·099) did not differ significantly between groups. Changes in dissociative seizures (rated by others) could not be assessed due to insufficient data. During the 12-month period, the number of adverse events was similar between the groups: 57 (31%) of 186 participants in the CBT plus standardised medical care group reported 97 adverse events and 53 (29%) of 182 participants in the standardised medical care group reported 79 adverse events., Interpretation: CBT plus standardised medical care had no statistically significant advantage compared with standardised medical care alone for the reduction of monthly seizures. However, improvements were observed in a number of clinically relevant secondary outcomes following CBT plus standardised medical care when compared with standardised medical care alone. Thus, adults with dissociative seizures might benefit from the addition of dissociative seizure-specific CBT to specialist care from neurologists and psychiatrists. Future work is needed to identify patients who would benefit most from a dissociative seizure-specific CBT approach., Funding: National Institute for Health Research, Health Technology Assessment programme., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Irritable bowel syndrome (IBS) is common, affecting 10-20% of the adult population worldwide, with many people reporting ongoing symptoms despite first-line therapies. Cognitive behavioural therapy (CBT) is recommended in guidelines for refractory IBS but there is insufficient access to CBT for IBS and uncertainty about whether benefits last in the longer term. Assessing Cognitive behavioural Therapy for IBS (ACTIB) was a large, randomised, controlled trial of two forms of CBT for patients with refractory IBS. ACTIB results showed that, at 12 months, both forms of CBT for IBS were significantly more effective than treatment as usual at reducing IBS symptom severity in adults with refractory IBS. This follow-up study aimed to evaluate 24-month clinical outcomes of participants in the ACTIB trial., Methods: In the ACTIB three-group, randomised, controlled trial, 558 adults with refractory IBS were randomly allocated to receive either therapist-delivered telephone CBT (telephone-CBT group), web-based CBT with minimal therapist support (web-CBT group), or treatment as usual (TAU group) and were followed up for 12 months. Participants were adults with refractory IBS (clinically significant symptoms for ≥12 months despite being offered first-line therapies), recruited by letter and opportunistically from 74 general practices and three gastroenterology centres in London and the south of England (UK) between May 1, 2014, and March 31, 2016. Primary outcome measures were IBS Symptom Severity Score (IBS-SSS) and Work and Social Adjustment Scale (WSAS), assessed in the intention-to-treat (ITT) population with multiple imputation. This study was a non-prespecified naturalistic follow-up and analysis of the participants of the ACTIB trial at 24 months assessing the same outcomes as the original trial. Outcome measures were completed online by participants or a paper questionnaire was posted, or telephone follow-up undertaken. The ACTIB trial is registered with the International Standard Randomised Controlled Trial Number registry, number ISRCTN44427879., Findings: 24-month follow-up of outcomes was achieved for 323 (58%) of 558 participants: 119 (64%) of 186 in the telephone-CBT group, 99 (54%) of 185 in the web-CBT group, and 105 (56%) of 187 in the TAU group. At 24 months, mean IBS-SSS was 40·5 points (95% CI 15·0 to 66·0; p=0·002) lower in the telephone-CBT group and 12·9 points (-12·9 to 38·8; p=0·33) lower in the web-CBT group than in the TAU group. The mean WSAS score was 3·1 points (1·3 to 4·9; p<0·001) lower in the telephone-CBT group and 1·9 points (0·1 to 3·7; p=0·036) lower in the web-CBT group than in the TAU group. A clinically significant IBS-SSS change (≥50 points) from baseline to 24 months was found in 84 (71%) of 119 participants in the telephone-CBT group, in 62 (63%) of 99 in the web-CBT group, and in 48 (46%) of 105 in the TAU group. In total 41 adverse events were reported between 12 to 24 months: 11 in the telephone-CBT group, 15 in the web-CBT group, and 15 in the TAU group. Of these, eight were reported as gastrointestinal related, five as psychological, and six as musculoskeletal. There were no adverse events related to treatment., Interpretation: At 24-month follow-up, sustained improvements in IBS were seen in both CBT groups compared with TAU, although some previous gains were reduced compared with the 12-month outcomes. IBS-specific CBT has the potential to provide long-term improvement in IBS, achievable within a usual clinical setting. Increasing access to CBT for IBS could achieve long-term patient benefit., Funding: UK National Institute for Health Research., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Persistent physical symptoms (PPS), also known as medically unexplained symptoms are associated with profound physical disability, psychological distress and high healthcare costs. England's annual National Health Service costs of attempting to diagnose and treat PPS amounts to approximately £3 billion. Current treatment relies on a positive diagnosis, life-style advice and drug therapy. However, many patients continue to suffer from ongoing symptoms and general practitioners (GPs) are challenged to find effective treatments. Training GPs in basic cognitive behavioural skills and providing self-help materials to patients could be useful, but availability in primary care settings is limited., Methods and Analysis: A cluster randomised waiting list, controlled trial will be conducted to assess the feasibility of an integrated approach to care in general practice. Approximately 240 patients with PPS will be recruited from 8 to 12 GP practices in London. GP practices will be randomised to 'integrated GP care plus treatment as usual' or waiting list control. Integrated GP care plus treatment as usual will include GP training in cognitive behavioural skills, GP supervision and written and audio visual materials for both GPs and participants. The primary objectives will be assessment of trial and intervention feasibility. Secondary objectives will include estimating the intracluster correlation coefficient for potential outcome measures for cluster effects in a sample size calculation. Feasibility parameters and identification of suitable primary and secondary outcomes for future trial evaluations will be assessed prerandomisation and at 12 and 24 weeks' postrandomisation, using a mixed-methods approach., Ethics and Dissemination: Ethical approval was granted by the Camberwell St Giles Ethics Committee. Results will be disseminated via peer-reviewed publications and conference presentations. This trial will inform researchers, clinicians, patients and healthcare providers about the feasibility and potential cost-effectiveness of an integrated approach to managing PPS in primary care., Trial Registration Number: NCT02444520; Pre-results., Competing Interests: Competing interests: MHotopf reported grants from Innovative Medicines Initiative and European Federation of Pharmaceutical Industries and Associations, outside the submitted work. In addition, TC and RM-M declared the following; organisational financial interests: TC received ad hoc payments for conducting workshops on evidence-based treatments for persistent physical symptoms. TC has received grants from NIHR programme grants, HTA, RfPB, Guy’s and St Thomas Charity, King’s Challenge Fund, Muscular Dystrophy, Multiple Sclerosis Society. King’s College London received payment from Taylor and Francis for editorial role. RM-M currently receives grant funding from NIHR programme grants, Breast Cancer Now, Crohn’s and Colitis UK, and National MS Society. In the previous 36 months, RM-M received funding from MS society UK and NIHR HTA. In 2019, payments from Taylor and Francis to King’s College London for RMM’s role as Editor of Health Psychology Review. Payments for adhoc lectures and workshops on long-term conditions. Personal financial interests: TC is the author of several self-help books on chronic fatigue and received royalties in the past. TC received expenses and ad hoc payment for role as external examiner NUI Galway and Waterford Institute of Technology. TC received expenses for keynote speeches at UK Society for Behavioural Medicine, BABCP Conferences (travel and accommodation). TC received ad hoc payments for conducting workshops on evidence-based treatments for persistent physical symptoms. RM-M received payments for her role as National Advisor to NHS England for Increasing Access to Psychological Therapies (IAPT) for people with long-term conditions from 2011 to 2016. RM-M received ad hoc payments for workshop training in IBS in 2017 and 2018 and this will continue in 2019. RM-M receives ad hoc consultancy payments from Mahana therapeutics and this is likely to continue in 2019. RM-M has stock options in Mahana therapeutics. RM-M received travel expenses for keynote speech to Internal Society of Behavioural Medicine. In 2019, RM-M will be a keynote speaker for Association for Researchers in Psychology and Health (the Netherlands), European Health Psychology Society Annual Conference (Croatia) and the 9th World Congress of Behavioural and Cognitive Therapies (Germany). Travel and accommodation expenses will be reimbursed., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Mortality associated with chronic fatigue syndrome is uncertain. We investigated mortality in individuals diagnosed with chronic fatigue syndrome in secondary and tertiary care using data from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) Clinical Record Interactive Search (CRIS) register., Methods: We calculated standardised mortality ratios (SMRs) for all-cause, suicide-specific, and cancer-specific mortality for a 7-year observation period using the number of deaths observed in SLaM records compared with age-specific and sex-specific mortality statistics for England and Wales. Study participants were included if they had had contact with the chronic fatigue service (referral, discharge, or case note entry) and received a diagnosis of chronic fatigue syndrome., Findings: We identified 2147 cases of chronic fatigue syndrome from CRIS and 17 deaths from Jan 1, 2007, to Dec 31, 2013. 1533 patients were women of whom 11 died, and 614 were men of whom six died. There was no significant difference in age-standardised and sex-standardised mortality ratios (SMRs) for all-cause mortality (SMR 1·14, 95% CI 0·65-1·85; p=0·67) or cancer-specific mortality (1·39, 0·60-2·73; p=0·45) in patients with chronic fatigue syndrome when compared with the general population in England and Wales. This remained the case when deaths from suicide were removed from the analysis. There was a significant increase in suicide-specific mortality (SMR 6·85, 95% CI 2·22-15·98; p=0·002)., Interpretation: We did not note increased all-cause mortality in people with chronic fatigue syndrome, but our findings show a substantial increase in mortality from suicide. This highlights the need for clinicians to be aware of the increased risk of completed suicide and to assess suicidality adequately in patients with chronic fatigue syndrome., Funding: National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London., (Copyright © 2016 Roberts et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.)

Background: To examine the role of psychological distress, negative life events, social support and lack of fitness (using breathlessness on exertion as a proxy) in the development of new onset fatigue in a primary care population., Method: Adults between the ages of 18 and 45 years who were registered with five general practices in South East England were asked to complete a fatigue questionnaire and the 12-item General Health Questionnaire. Between 1 and 12 months later, subjects who visited the general practitioner (GP) with a suspected viral infection were recruited to the study and asked to complete measures of fatigue, psychological distress, life events, social support and allergies (stage 2). The next person to present to the GP with a complaint other than a viral illness was recruited as a control. Factors assessed at stage 2 that were associated with the development of fatigue were examined with stepwise logistic regression., Results: Acute fatigue was not associated with a viral illness. Negative life events and breathlessness on exertion (interpreted as lack of fitness) were associated with incident cases of fatigue. However, when controlling for concurrent psychological distress, the independent association of negative life events disappeared., Conclusions: Psychological distress was strongly associated with new onset fatigue and hence emphasizes the significance of psychological distress as a concomitant complaint in fatigue. Further, the salient association between breathlessness and fatigue may indicate the need to recommend exercise as a therapeutic strategy to improve physical fitness in the primary care setting.

Objective: The Chalder Fatigue Scale (CFQ) is a widely used instrument to assess fatigue in both clinical and nonclinical settings. Psychometric properties of the scale and discriminative abilities were examined., Methods: A total of 361 patients with CFS and 1615 individuals in the community were assessed with the CFQ. Principal component analysis (PCA) was used to explore the structure of the scale. Receiver-operating characteristic curve (ROC) was used to investigate the discriminative properties., Results: Two components, physical and mental fatigue, were identified in the CFS patient group and in the general population samples. Area under the curve for ROC was .91. The fatigue scale effectively discriminates, at high scores, between CFS patients and the general population., Conclusion: Physical and mental fatigue are clearly separable components of fatigue. The CFQ can discriminate reliably between clinical and nonclinical conditions., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Objectives: To develop a brief measure of the therapy process and use it to examine which therapeutic ingredients were associated with outcome in a sample of patients from a randomized controlled trial (RCT) of cognitive behaviour therapy (CBT) versus counselling for patients with chronic fatigue in primary care. It was hypothesized that the two therapies would be clearly distinguishable and that in terms of process variables, the therapeutic alliance would be important in predicting outcome., Design: The data for this study were collected alongside a RCT in primary care and included audiotaped therapy sessions. These tapes were assessed by two independent raters using a newly devised measure in order to evaluate therapy process and its relationship with outcome., Methods: Tapes from 71 patients participating in the RCT were assessed to form the basis of the process analysis. Outcome was self-reported fatigue symptoms at 6 months follow-up. Data reduction was achieved via a principal component analysis (PCA). Factors were entered into a multiple regression analysis to produce a final model of predictors of outcome., Results: The process measure showed that although the treatments could be distinguished, there was some overlap between them. The key predictor of a good fatigue outcome was emotional processing, including the expression, acknowledgement and acceptance of emotional distress., Conclusion: A new process measure was developed successfully which now warrants further testing. It was able to assess treatment adherence and unpack, and distinguish the common factor which predicted outcome across therapy modalities. The findings lend preliminary support to the view that the specific techniques associated with particular 'brand names' of therapy are not necessarily the 'active ingredients' that help patient's change within the primary care setting. Emotional processing predicted outcome for patients with chronic fatigue and therefore future research might explore this in more depth, in order to understand better how it can be facilitated.

Background: The objective of this study was to examine factors that predicted outcome in a chronically fatigued group of patients who were randomized to cognitive behaviour therapy or counselling in primary care., Method: Illness perceptions, attributions, fatigue, disability and demographic variables were recorded at assessment and levels of fatigue and disability were measured at 6 months post randomization. Logistic regression was used to examine associations., Results: Factors that predicted a poor outcome (four or more on the fatigue questionnaire) were: poor social adjustment at assessment; the patients self-report that they had never seen the GP for an emotional reason; a physical illness attribution; and, a long perceived future illness duration., Conclusions: Patients who are more psychologically minded are more likely to improve with psychological treatments in primary care. General practitioners need to assess this before referring to an appropriate therapist.

Background: There is a paucity of evidence relating to the cost-effectiveness of alternative treatment responses to chronic fatigue., Aim: To compare the relative costs and outcomes of counselling versus cognitive behaviour therapy (CBT) provided in primary care settings for the treatment of fatigue., Design of Study: A randomised controlled trial incorporating a cost-consequences analysis., Setting: One hundred and twenty-nine patients from 10 general practices across London and the South Thames region who had experienced symptoms of fatigue for at least three months., Method: An economic analysis was performed to measure costs of therapy, other use of health services, informal care-giving, and lost employment. The principal outcome measure was the Fatigue Questionnaire; secondary measures were the Hospital Anxiety and Depression Scale and a social adjustment scale., Results: Although the mean cost of treatment was higher for the CBT group (164 Pounds, standard deviation = 67) than the counselling group (109 Pounds, SD = 49; 95% confidence interval = 35 to 76, P < 0.001), a comparison of change scores between baseline and six-month assessment revealed no statistically significant differences between the two groups in terms of aggregate health care costs, patient and family costs or incremental cost-effectiveness (cost per unit of improvement on the fatigue score)., Conclusions: Counselling and CBT both led to improvements in fatigue and related symptoms, while slightly reducing informal care and lost productivity costs. Counselling represents a less costly (and more widely available) intervention but no overall cost-effectiveness advantage was found for either form of therapy.

Background: Fatigue and psychiatric symptoms are common in the community, but their association and outcome are sparsely studied., Method: A total of 1177 patients were recruited from UK primary care on attending their general practitioner. Fatigue and psychiatric disorder was measured at three time points with the 12-item General Health Questionnaire and the 11-item Fatigue Questionnaire., Results: Total scores for fatigue and psychiatric disorder did not differ between the three time points and were closely correlated (r around 0.6). The association between non-co-morbid ('pure') fatigue and developing psychiatric disorder 6 months later was the same as that for being well and subsequent psychiatric disorder. Similarly, having non-co-morbid psychiatric disorder did not predict having fatigue any more than being well 6 months previously. Between 13 and 15% suffered from non-co-morbid fatigue at each time point and 2.5% suffered from fatigue at two time points 6 months apart. Less than 1% of patients suffered from non-co-morbid fatigue at all three time points., Conclusions: The data are consistent with the existence of 'pure' independent fatigue state. However, this state is unstable and the majority (about three-quarters) of patients become well or a case of psychiatric disorder over 6 months. A persistent, independent fatigue state lasting for 6 months can be identified in the primary-care setting, but it is uncommon of the order of 2.5%. Non-co-morbid (pure) fatigue did not predict subsequent psychiatric disorder.

Objectives: This study examined the prevalence and public health impact of chronic fatigue and chronic fatigue syndrome in primary care patients in England., Methods: There were 2376 subjects, aged 18 through 45 years. Of 214 subjects who fulfilled criteria for chronic fatigue, 185 (86%) were interviewed in the case-control study. Measures included chronic fatigue, psychological morbidity, depression, anxiety, somatic symptoms, symptoms of chronic fatigue syndrome, functional impairment, and psychiatric disorder., Results: The point prevalence of chronic fatigue was 11.3%, falling to 4.1% if comorbid psychological disorders were excluded. The point prevalence of chronic fatigue syndrome was 2.6%, falling to 0.5% if comorbid psychological disorders were excluded. Rates did not vary by social class. After adjustment for psychological disorder, being female was modestly associated with chronic fatigue. Functional impairment was profound and was associated with psychological disorder., Conclusions: Both chronic fatigue and chronic fatigue syndrome are common in primary care patients and represent a considerable public health burden. Selection bias may account for previous suggestions of a link with higher socioeconomic status.

Objective: This study assessed relationships among psychological symptoms, past and current psychiatric disorder, functional impairment, somatic symptoms, chronic fatigue, and chronic fatigue syndrome., Method: A prospective cohort study was followed by a nested case-control study. The subjects, aged 18-45 years, had been in primary care for either clinical viral infections or a range of other problems. Questionnaire measures of fatigue and psychological symptoms were completed by 1,985 subjects 6 months later; 214 subjects with chronic fatigue were then compared with 214 matched subjects without fatigue. Assessments were made with questionnaires, interviews, and medical records of fatigue, somatic symptoms, psychiatric disorder, and functional impairment., Results: Subjects with chronic fatigue were at greater risk than those without chronic fatigue for current psychiatric disorder assessed by standardized interview (60% versus 19%) or by questionnaire (71% versus 31%). Chronic fatigue subjects were more likely to have received psychotropic medication or experienced psychiatric disorder in the past. There was a trend for previous psychiatric disorder to be associated with comorbid rather than noncomorbid chronic fatigue. Most subjects with chronic fatigue syndrome also had current psychiatric disorder when assessed by interview (75%) or questionnaire (78%). Both the prevalence and incidence of chronic fatigue syndrome were associated with measures of previous psychiatric disorder. The number of symptoms suggested as characteristics of chronic fatigue syndrome was closely related to the total number of somatic symptoms and to measures of psychiatric disorder. Only postexertion malaise, muscle weakness, and myalgia were significantly more likely to be observed in chronic fatigue syndrome than in chronic fatigue., Conclusions: Most subjects with chronic fatigue or chronic fatigue syndrome in primary care also meet criteria for a current psychiatric disorder. Both chronic fatigue and chronic fatigue syndrome are associated with previous psychiatric disorder, partly explained by high rates of current psychiatric disorder. The symptoms thought to represent a specific process in chronic fatigue syndrome may be related to the joint experience of somatic and psychological distress.

Objectives: To determine the prevalence of fatigue in the general population and the factors associated with fatigue., Design: Postal survey., Setting: Six general practices in southern England., Subjects: 31,651 men and women aged 18-45 years registered with the practices., Main Outcome Measures: Responses to the 12 item general health questionnaire and a fatigue questionnaire which included self reported measures of duration, severity, and causes of fatigue., Results: 15,283 valid questionnaires were returned, giving a response rate of 48.3%, (64% after adjustment for inaccuracies in the practice registers). 2798 (18.3%) of respondents reported substantial fatigue lasting six months or longer. Fatigue and psychological morbidity were moderately correlated (r = 0.62). Women were more likely to complain of fatigue than men, even after adjustment for psychological distress. The commonest cited reasons for fatigue were psychosocial (40% of patients). Of 2798 patients with excessive tiredness, only 38 (1.4%) attributed this to the chronic fatigue syndrome., Conclusion: Fatigue is distributed as a continuous variable in the community and is closely associated with psychological morbidity.