bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treating common mental disorder including psychotic experiences in the primary care improving access to psychological therapies programme (the TYPPEX study): protocol for a stepped wedge cluster randomised controlled trial with nested economic and process evaluation of a training package for therapists
Authors: Ashford Polly-Anna , Knight Clare , Heslin Margaret , Clark Allan B , Kanaan Mona , Patel Ushma , Stuart Freya , Kabir Thomas , Grey Nick , Murray Hannah , Hodgekins J , Reeve Nesta , Marshall Nicola , Painter Michelle , Clarke James , Russo Debra , Stochl Jan , Leathersich Maria , Pond Martin , Fowler David , French Paul , Swart Ann Marie , Dixon-Woods Mary , Byford Sarah , Jones Peter B , Perez Jesus 
Published: November 2022

IntroductionAt least one in four people treated by the primary care improving access to psychological therapies (IAPT) programme in England experiences distressing psychotic experiences (PE) in addition to common mental disorder (CMD). These individuals are less likely to achieve recovery. IAPT services do not routinely screen for nor offer specific treatments for CMD including PE. The Tailoring evidence-based psychological therapY for People with common mental disorder including Psychotic EXperiences study will evaluate the clinical and cost-effectiveness of an enhanced training for cognitive behavioural therapists that aims to address this clinical gap.Methods and analysisThis is a multisite, stepped-wedge cluster randomised controlled trial. The setting will be IAPT services within three mental health trusts. The participants will be (1) 56–80 qualified IAPT cognitive behavioural therapists and (2) 600 service users who are triaged as appropriate for cognitive behavioural therapy in an IAPT serviceandhave PE according to the Community Assessment of Psychic Experiences—Positive 15-items Scale. IAPT therapists will be grouped into eight study clusters subsequently randomised to the control-intervention sequence. We will obtain pseudonymous clinical outcome data from IAPT clinical records for eligible service users. We will invite service users to complete health economic measures at baseline, 3, 6, 9 and 12-month follow-up. The primary outcome will be the proportion of patients with common mental disorder psychotic experiences who have recovered by the end of treatment as measured by the official IAPT measure for recovery.Ethics and disseminationThe study received the following approvals: South Central—Berkshire Research Ethics Committee on 28 April 2020 (REC reference 20/SC/0135) and Health Research Authority (HRA) on 23 June 2020. An amendment was approved by the Ethics Committee on 01 October 2020 and HRA on 27 October 2020. Results will be made available to patients and the public, the funders, stakeholders in the IAPT services and other researchers.Trial registration numberNCT93895792.
Impact of the SGLT2 inhibitor empagliflozin on urinary supersaturations in kidney stone formers (SWEETSTONE trial): protocol for a randomised, double-blind, placebo-controlled cross-over trial
Authors: Schietzel Simeon , Bally Lia , Cereghetti Grazia Maria , Faller Nicolas , Moor Matthias B , Vogt Bruno , Rintelen Felix , Trelle S , Fuster Daniel 
Published: November 2022

Introduction
Kidney stones are a global healthcare problem. Given high recurrence rates and the morbidity associated with symptomatic stone disease, effective medical prophylaxis is clearly an unmet need. Explanatory analyses of randomised controlled trials with sodium/glucose cotransporter isoform 2 inhibitors indicated a 30%–50% reduced rate of stone events in patients with diabetes. Underlying mechanisms remain unclear. We aim to determine the effect of empagliflozin on urinary supersaturations in non-diabetic kidney stone formers to evaluate their therapeutic potential for recurrence prevention. We will provide first clinical trial evidence on whether urinary supersaturations are affected by empagliflozin in kidney stone formers.

Methods and analysis
The SWEETSTONE trial is a randomised, double-blind, placebo-controlled, cross-over, exploratory study to assess the impact of empagliflozin on urinary supersaturations of calcium oxalate, calcium phosphate and uric acid in kidney stone formers. We plan to include 46 non-diabetic adults (18–74 years) with ≥1 past kidney stone event and stone composition with ≥80% of calcium or ≥80% of uric acid. Patients with secondary causes of kidney stones or chronic kidney disease will be excluded. Eligible individuals will be randomised in equal proportions to receive either a 14-day treatment with 25 mg empagliflozin followed after the 2–6 weeks wash out period by a 14-day treatment with a matching placebo or the reverse procedure. Secondary outcomes will include electrolyte concentrations, renal function, mineral metabolism and glycaemic parameters, urinary volume and safety.
Results will be presented as effect measures (95% CIs) with p values and hypothesis testing for primary outcomes (significance level 0.02).

Ethics and dissemination
The SWEETSTONE trial was approved by the Swiss ethics committee and Swissmedic. First results are expected in the fourth quarter of 2022.

Trial registration number

NCT04911660
; Pre-results.
Automated digital counselling with social network support as a novel intervention for patients with heart failure: protocol for randomised controlled trial
Authors: Peiris Rachel Grace , Ross Heather , Chan Christopher T , Poon Stephanie , Auguste Bourne Lewis , Rac Valeria E , Farkouh Michael , McDonald Michael , Kaczorowski Janusz , Code Jillianne , Duero Posada Juan , Ong Stephanie , Kobulnik Jeremy , Tomlinson George , Huszti Ella , Arcand JoAnne , Thomas Scott G , Akbari Ayub , Maunder Robert , Grover Steven , Seto Emily , Simard Anne , Pope Brad , Bains Marc , McIntyre Carmen , Torbay Chris , Syed Fatima , Nolan Robert P 
Published: November 2022

Introduction
Heart failure (HF) symptoms improve through self-care, for which adherence remains low among patients despite the provision of education for these behaviours by clinical teams. Open Access Digital Community Promoting Self-Care, Peer Support and Health Literacy (ODYSSEE–vCHAT) combines automated digital counselling with social network support to improve mortality and morbidity, engagement with self–care materials, and health-related quality of life.

Methods and analysis
Use of ODYSSEE-vCHAT via Internet-connected personal computer by 162 HF patients will be compared with a control condition over 22 months. The primary outcome is a composite index score of all-cause mortality, all-cause emergency department visits, and HF-related hospitalisation at trial completion. Secondary outcomes include individual components of the composite index, engagement with self-care materials, and patient-reported measures of physical and psychosocial well-being, disease management, health literacy, and substance use. Patients are recruited from tertiary care hospitals in Toronto, Canada and randomised on a 1:1 ratio to both arms of the trial. Online assessments occur at baseline (t=0), months 4, 8 and 12, and trial completion. Ordinal logistic regression analyses and generalised linear models will evaluate primary and secondary outcomes.

Ethics and dissemination
The trial has been approved by the research ethics boards at the University Health Network (20-5960), Sunnybrook Hospital (5117), and Mount Sinai Hospital (21-022-E). Informed consent of eligible patients occurs in person or online. Findings will be shared with key stakeholders and the public. Results will allow for the preparation of a Canada-wide phase III trial to evaluate the efficacy of ODYSSEE-vCHAT in improving clinical outcomes and raising the standard of outpatient care.

Trial registration number

NCT04966104
Cost-effectiveness of internet-delivered cognitive behavioural therapy in patients with cardiovascular disease and depressive symptoms: secondary analysis of an RCT
Authors: Mourad Ghassan , Lundgren Johan , Andersson Gerhard , Husberg Magnus , Johansson Peter 
Published: November 2022

Introduction
Cost-effectiveness evaluations of psychological interventions, such as internet-delivered cognitive behavioural therapy (iCBT) programmes, in patients with cardiovascular disease (CVD) are rare. We recently reported moderate to large effect sizes on depressive symptoms in CVD outpatients following a 9-week iCBT programme compared with an online discussion forum (ODF), in favour of iCBT. In this paper, we evaluate the cost-effectiveness of this intervention.

Methods
Cost-effectiveness analysis of a randomised controlled trial. The EQ-5D-3L was used to calculate quality-adjusted life-years (QALYs). Data on healthcare costs were retrieved from healthcare registries.

Results
At 12-month follow-up, the QALY was significantly higher in iCBT compared with the ODF group (0.713 vs 0.598, p=0.007). The mean difference of 0.115 corresponds with 42 extra days in best imaginable health status in favour of the iCBT group over the course of 1 year. Incremental cost-effectiveness ratio (ICER) for iCBT versus ODF was €18 865 per QALY saved. The cost-effectiveness plane indicated that iCBT is a cheaper and more effective intervention in 24.5% of the cases, and in 75% a costlier and more effective intervention than ODF. Only in about 0.5% of the cases, there was an indication of a costlier, but less effective intervention compared with ODF.

Conclusions
The ICER of €18 865 was lower than the cost-effectiveness threshold range of €23 400–€35 100 as proposed by the NICE guidelines, suggesting that the iCBT treatment of depressive symptoms in patients with CVD is cost-effective.

Trial registration number

NCT02778074; Post-results.
PCSK9 inhibition in patients with acute stroke and symptomatic intracranial atherosclerosis: protocol for a prospective, randomised, open-label, blinded end-point trial with vessel-wall MR imaging
Authors: Huang Yen-Chu , Chang Chia-Hao , Tsai Yuan-Hsiung , Weng Hsu-Huei , Lin Leng-Chieh , Lee Jiann-Der 
Published: November 2022

Introduction
Dual antiplatelet therapy and high-intensity statins are the mainstay treatment in patients with acute stage, symptomatic intracranial atherosclerotic stenosis (ICAS). Alirocumab is a monoclonal antibody that can inhibit proprotein convertase subtilisin–kexin type 9 and effectively lower low-density lipoprotein cholesterol levels with less side effects than statins. We hypothesise that alirocumab treatment in addition to statin therapy could stabilise intracranial plaque and reduce arterial stenosis.

Methods and analysis
In this prospective, randomised, open-label, blinded end-point study, we will use high-resolution vessel-wall MRI to evaluate the efficacy and safety of alirocumab in patients who had an acute ischaemic stroke from ICAS. We will recruit 66 patients who had an acute ischaemic stroke within 7 days of symptom onset, who had symptomatic intracranial artery stenosis (>30%) at the middle cerebral artery, basilar artery or intracranial internal carotid artery. Among them, 22 patients will be randomised to the intervention group to receive treatment with 75 mg alirocumab subcutaneously every 2 weeks for a total of 26 weeks, while those in the control group will not. All patients in both groups will receive antiplatelet agents and high-intensity statins, including 20 mg rosuvastatin or 40–80 mg atorvastatin or at the maximum tolerated dose. All of them will undergo MRI at recruitment and after 26 weeks. The primary outcomes are changes in intracranial atherosclerotic plaques in the MRI before and after 6 months treatment. This trial is being conducted at Chang Gung Memorial Hospital at Chiayi, Taiwan.

Ethics and dissemination
This trial has been approved by the Institutional Review Board of Chang Gung Memorial Hospital (approval no. 202 002 482A3). Written informed consent will be obtained from all research participants. Study results will be published as peer-reviewed articles.

Trial registration number
ClinicalTrials.gov, Identifier:NCT05001984; Pre-results.
Participant engagement in a community health worker-delivered intervention and type 2 diabetes clinical outcomes: a quasiexperimental study in MexicanAmericans
Authors: Reininger Belinda M , Lopez Juliana , Zolezzi Maria , Lee MinJae , Mitchell-Bennett Lisa A , Xu Tianlin , Park Soo Kyung , Saldana Mayra V , Perez LuBeth , Payne Lisa Y , Collier Cindy , McCormick Joseph B 
Published: November 2022

ObjectivesThis study helps to fill the existing research gap related to participant engagement in behavioural interventions and diabetes management. We examined type 2 diabetes control over time among Mexican Americans by level of engagement in a chronic care management (CCM) program that included community health worker (CHW)-delivered multilevel interventions. The programme complemented clinical care and promoted behaviour changes to improve diabetes self-management.DesignQuasiexperimental study.SettingThe study was implemented in the Rio Grande Valley region in the USA. Recruitment was conducted in clinics and community events. All other visits were provided in participant homes and community locations.Participants5649 adults (aged ≥18 years) with poorly controlled type 2 diabetes who enrolled in a community-delivered CCM programme between September 2013 and 2018.InterventionsThe intervention comprised two components: CHW home visits conducted every 3 months and diabetes self-management education (DSME) classes provided in community locations.Primary outcome measuresThe primary outcome was haemoglobin A1c (HbA1c) measured at baseline every 3 months for up to 24 months. We first examined changes in HbA1c levels over time. The number of completed CHW and DSME encounters was used to classify participants into engagement groups—high engagement defined as ≥10 encounters (n=2952); low engagement defined as 1–9 encounters (n=2697). We used univariable and multivariable longitudinal linear regression models with a generalised estimating equation method. We tested interactions between engagement groups and time.ResultsParticipants’ mean HbA1c decreased from 10.20% at baseline to 8.93% (p<0.0001) at 3 months, remaining stable thereafter. Changes in HbA1c were statistically different between the engagement groups. High engagement participants had lower HbA1c levels over the first 15 months of the follow-up period compared with low engagement participants, as compared at 3 months (−0.44%, 95% CI −0.57% to –0.31%; p<0.0001), 6 months (−0.31%, 95% CI −0.43% to –0.14%; p<0.0001), 9 months (−0.27%, 95% CI −0.42% to –0.13%; p=0.0001), 12 months (−0.23%, 95% CI −0.37% to –0.08%; p=0.0025) and 15 months (−0.32%, 95% CI −0.54% to –0.10%; p=0.0040). At months 18, 21 and 24, the HbA1c differences were not statistically significant (18 months: −0.34%, 95% CI −0.77% to 0.08%; p=0.1086; 21 months: −0.22%, 95% CI −1.00% to 0.56%; p=0.5721; 24 months: −0.42%, 95% CI −1.38% to 0.55%; p=0.3966).ConclusionsHigher engagement in the CCM programme delivered by CHWs and coordinated with clinical care was associated with beneficial improvements in type 2 diabetes control, but both engagement groups showed strong improvements.
Prevalence, pathophysiology, prediction and health-related quality of life of long COVID: study protocol of the longitudinal multiple cohort CORona Follow Up (CORFU) study
Authors: Ghossein-Doha Chahinda , Wintjens Marieke S J N , Janssen Emma B N J , Klein Dorthe , Heemskerk Stella C M , Asselbergs Folkert W , Birnie Erwin , Bonsel Gouke J , van Bussel Bas C T , Cals Jochen W L , Ten Cate Hugo , Haagsma Juanita , Hemmen Bena , van der Horst Iwan C C , Kietselaer Bastiaan L J H , Klok Frederikus A , de Kruif Martijn D , Linschoten Marijke , van Santen Susanne , Vernooy Kevin , Willems Loes H , Westerborg Rosa , Warle Michiel , van Kuijk Sander M J 
Published: November 2022

IntroductionThe variety, time patterns and long-term prognosis of persistent COVID-19 symptoms (long COVID-19) in patients who suffered from mild to severe acute COVID-19 are incompletely understood. Cohort studies will be combined to describe the prevalence of long COVID-19 symptoms, and to explore the pathophysiological mechanisms and impact on health-related quality of life. A prediction model for long COVID-19 will be developed and internally validated to guide care in future patients.Methods and analysisData from seven COVID-19 cohorts will be aggregated in the longitudinal multiple cohort CORona Follow Up (CORFU) study. CORFU includes Dutch patients who suffered from COVID-19 at home, were hospitalised without or with intensive care unit treatment, needed inpatient or outpatient rehabilitation and controls who did not suffer from COVID-19. Individual cohort study designs were aligned and follow-up has been synchronised. Cohort participants will be followed up for a maximum of 24 months after acute infection. Next to the clinical characteristics measured in individual cohorts, the CORFU questionnaire on long COVID-19 outcomes and determinants will be administered digitally at 3, 6, 12, 18 and 24 months after the infection. The primary outcome is the prevalence of long COVID-19 symptoms up to 2 years after acute infection. Secondary outcomes are health-related quality of life (eg, EQ-5D), physical functioning, and the prevalence of thromboembolic complications, respiratory complications, cardiovascular diseases and endothelial dysfunction. A prediction model and a patient platform prototype will be developed.Ethics and disseminationApproval was obtained from the medical research ethics committee of Maastricht University Medical Center+ and Maastricht University (METC 2021-2990) and local committees of the participating cohorts. The project is supported by ZonMW and EuroQol Research Foundation. Results will be published in open access peer-reviewed scientific journals and presented at (inter)national conferences.Trial registration numberNCT05240742.
Melatonin for sleep disorders in children with neurodevelopmental disorders: protocol for a systematic review with meta-analysis and Trial Sequential Analysis of randomised clinical trials
Authors: Jørgensen Caroline Kamp , Hermann Rikke , Juul Sophie , Faltermeier Pascal , Horowitz Mark , Moncrieff Joanna , Gluud Christian , Jakobsen Janus Christian 
Published: November 2022

IntroductionNeurodevelopmental disorders are a group of disorders thought to be associated with the functioning of the brain and the nervous system. Children with neurodevelopmental disorders often have sleep-related comorbidities that may negatively affect quality of life for both the children and their families. Melatonin is one of the most used interventions in children with neurodevelopmental disorders and sleep disorders. Previous reviews have investigated the effects of melatonin for sleep disorders in children with neurodevelopmental disorders, but these had important limitations, such as inadequate analysis of adverse effects, small sample sizes and short follow-up.Methods and analysisThis is a protocol for a systematic review with meta-analysis and Trial Sequential Analysis of randomised clinical trials. The protocol is reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols. We will search for published and unpublished trials in the Cochrane Central Register of Controlled Trials, MEDLINE Ovid, Embase Ovid, LILACS, Science Citation Index Expanded, Conference Proceedings Citation Index-Science, PsycINFO, ClinicalTrials.gov and the International Clinical Trials Registry Platform. We will search the databases from their inception without language restrictions. We will also request clinical study reports from regulatory authorities and pharmaceutical companies. Review authors working in pairs will screen reports, extract data and conduct risk of bias assessments using the Cochrane Risk of Bias tool. We will include randomised clinical trials comparing melatonin versus placebo or no intervention for sleep disorders in children with neurodevelopmental disorders. Primary outcomes will be total sleep time and adverse effects. Secondary outcomes will be quality of life of the child and caregivers and sleep onset latency. Data will be analysed using random-effects and fixed-effect meta-analyses. Certainty of evidence will be assessed with Grading of Recommendations, Assessment, Development and Evaluation approach.Ethics and disseminationEthical approval was not required for this protocol. The systematic review will be published in a peer-reviewed journal.PROSPERO registration numberCRD42022337530.
Agile development of a digital exposure treatment for youth with chronic musculoskeletal pain: protocol of a user-centred design approach and examination of feasibility and preliminary efficacy
Authors: Harrison Lauren E , Webster Sarah N , Van Orden Amanda R , Choate Ellison , Jehl Nicole , Stinson Jennifer , Wicksell Rikard K , Darnall Beth D , Simons Laura E 
Published: November 2022

IntroductionChronic pain affects a significant number of children and impacts multiple domains including social, emotional and behavioural functioning, and negatively impacts family functioning. Roughly 5% of youth with chronic pain experience moderate to severe pain-related disability, with pain-related fear and avoidance of activities being identified as substantial barriers to treatment engagement. Evidence supports targeted psychological and physical interventions to address these barriers (eg, graded-exposure treatment), but accessibility to intervention is undermined by a shortage of services outside of urban areas, high treatment-related costs, and long provider waitlists; highlighting the need to develop digitally delivered behavioural intervention, using agile and iterative study designs that support rapid development and timely dissemination.Methods and analysisThis study seeks to develop an effective and scalable intervention for youth with chronic pain and their caregivers. This paper presents a user-centred protocol for the development and refinement of a digital exposure treatment for youth and caregivers, as well as the study design to examine feasibility and preliminary efficacy of the treatment using single-case experimental design (SCED). Assessments include daily diaries, completed from baseline and daily throughout the intervention (~6 weeks), and at 3-month follow-up, as well as self-report measures completed at baseline, end of intervention and 3-month follow-up. Primary outcomes include treatment satisfaction, treatment expectancy, adherence to daily dairies and functional disability. Secondary outcomes are pain-related fear and avoidance of activities, pain catastrophising and pain acceptance. We will present descriptive and model-based inference analyses, based on SCED reporting guidelines. We will calculate effect sizes for each individual on each outcome. We will examine mean treatment expectancy, credibility and satisfaction scores, and patient drop-out percentage.Ethics and disseminationThis study is approved by the Institutional Review Board at Stanford University (protocol #53323). Findings will be actively disseminated through peer-reviewed journals, conference presentations and social media.Trial registration numberNCT05079984.