bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is the Thoughts and Health programme feasible in the context of Swedish
schools? A quasi-experimental controlled trial study protocol
Authors: Wikberg Carl , Augustsson Pia , Sveinsdottir Gudny , Craighead W Edward , Arnarson Erikur Örn , Marteinsdottir Ina , Lilja Josefine L 
Published: November 2022

Introduction
Clinical depression is a substantial problem among adolescents,
increasing significantly at about age 15 years. It causes impairment in
social, academic and familial relationships, as well as ongoing
cognitive and emotional difficulties for the individual. A study in
Iceland demonstrated that a cognitive–behavioural, developmentally based
intervention programme, ‘Thoughts and Health’, prevented initial
episodes of depression and/or dysthymia (DYS) (major depressive
disorder/DYS) in adolescents for up to 12 months following completion of
the programme. We would like to test the feasibility of implementing the
Icelandic method in a Swedish context and to evaluate the long-term
effects of such a programme.

Methods and analysis
A quasi-experimental controlled design, combined with qualitative
and quantitative methods, will be used to address the research
questions.
In this study, 617 children aged ~14 years will be screened for
depression, and those “at risk” for development of clinical depression
will be offered a 12 week course, ‘Thoughts and Health’. This course
aims to prevent first depression in adolescents. A comparable group of
children will function as controls.
Depending on the type of variable, baseline comparisons between the
two groups of relevant initial measures will be evaluated with t-tests
or χ2analyses. The effects of the programme on the
development of clinical levels of depression will be evaluated using the
follow-up data of 6, 12 and 18 months. Index parental depression at
baseline will be tested as a moderator in the evaluation of the effects
of the prevention programme.

Ethics and dissemination
This study is approved by the Swedish Ethical Review Board
(reference number 2019–03347) in Gothenburg.
We plan to disseminate the knowledge gained from this study by
publishing our results in peer-reviewed scientific journals and other
scholarly outlets.

Trial registration number
NCT04128644; Pre-results.
Population differences in vaccine responses (POPVAC): scientific
rationale and cross-cutting analyses for three linked, randomised controlled
trials assessing the role, reversibility and mediators of immunomodulation
by chronic infections in the tropics
Authors: Nkurunungi Gyaviira , Zirimenya Ludoviko , Natukunda Agnes , Nassuuna Jacent , Oduru Gloria , Ninsiima Caroline , Zziwa Christopher , Akello Florence , Kizindo Robert , Akello Mirriam , Kaleebu Pontiano , Wajja Anne , Luzze Henry , Cose Stephen , Webb Emily , Elliott Alison M 
Published: November 2022

Introduction
Vaccine-specific immune responses vary between populations and are
often impaired in low income, rural settings. Drivers of these
differences are not fully elucidated, hampering identification of
strategies for optimising vaccine effectiveness. We hypothesise that
urban–rural (and regional and international) differences in vaccine
responses are mediated to an important extent by differential exposure
to chronic infections, particularly parasitic infections.

Methods and analysis
Three related trials sharing core elements of study design and
procedures (allowing comparison of outcomes across the trials) will test
the effects of (1) individually randomised intervention against
schistosomiasis (trial A) and malaria (trial B), and (2) Bacillus
Calmette-Guérin (BCG) revaccination (trial C), on a common set of
vaccine responses. We will enrol adolescents from Ugandan schools in
rural high-schistosomiasis (trial A) and rural high-malaria (trial B)
settings and from an established urban birth cohort (trial C). All
participants will receive BCG on day ‘0’; yellow fever, oral typhoid and
human papilloma virus (HPV) vaccines at week 4; and HPV and
tetanus/diphtheria booster vaccine at week 28. Primary outcomes are
BCG-specific IFN-γ responses (8 weeks after BCG) and for other vaccines,
antibody responses to key vaccine antigens at 4 weeks after
immunisation. Secondary analyses will determine effects of interventions
on correlates of protective immunity, vaccine response waning, priming
versus boosting immunisations, and parasite infection status and
intensity. Overarching analyses will compare outcomes between the three
trial settings. Sample archives will offer opportunities for exploratory
evaluation of the role of immunological and ‘trans-kingdom’ mediators in
parasite modulation of vaccine-specific responses.

Ethics and dissemination
Ethics approval has been obtained from relevant Ugandan and UK
ethics committees. Results will be shared with Uganda Ministry of
Health, relevant district councils, community leaders and study
participants. Further dissemination will be done through conference
proceedings and publications.

Trial registration numbers
NCT60517191,NCT62041885,NCT10482904.
Complex interventions to implement a diabetic retinopathy care pathway in
the public health system in Kerala: the Nayanamritham study protocol
Authors: Sivaprasad Sobha , Netuveli Gopalakrishnan , Wittenberg Raphael , Khobragade Rajan , Sadanandan Rajeev , Gopal Bipin , Premnazir Lakshmi , Conroy Dolores , Srinath Jyotsna , Ramakrishnan Radha , George Simon , Sahasranamam Vasudeva Iyer 
Published: November 2022

Introduction
Using a type 2 hybrid effectiveness-implementation design, we aim to
pilot a diabetic retinopathy (DR) care pathway in the public health
system in Kerala to understand how it can be scaled up to and sustained
in the whole state.

Methods and analysis
Currently, there is no systematic DR screening programme in Kerala.
Our intervention is a teleophthalmology pathway for people with diabetes
in the non-communicable disease registers in 16 family health centres.
The planned implementation strategy of the pathway will be developed
based on the discrete Expert Recommendations for Implementing Change
taxonomy. We will use both quantitative data from a cross-sectional
study and qualitative data obtained from structured interviews, surveys
and group discussions with stakeholders to report the effectiveness of
the DR care pathway and evaluation of the implementation
strategy.
We will use logistic regression models to assess crude associations
DR and sight-threatening diabetic retinopathy and fractional polynomials
to account for the form of continuous covariates to predict uptake of DR
screening. The primary effectiveness outcome is the proportion of
patients in the non-communicable disease register with diabetes screened
for DR over 12 months. Other outcomes include cost-effectiveness,
safety, efficiency, patient satisfaction, timeliness and equity. The
outcomes of evaluation of the implementation strategies include
acceptability, feasibility, adoption, appropriateness, fidelity,
penetration, costs and sustainability. Addition of more family health
centres during the staggered initial phase of the programme will be
considered as a sign of acceptability and feasibility. In the long term,
the state-wide adoption of the DR care pathway will be considered as a
successful outcome of the Nayanamritham study.

Ethics and dissemination
The study was approved by Indian Medical Research Council
(2018-0551) dated 13 March 2019. Study findings will be disseminated
through scientific publications and the report will inform adoption of
the DR care pathway by Kerala state in future.

Trial registration number
NCT28942696.
Protocol for a cost–utility analysis of neurostimulation and intensive camp-based therapy for children with perinatal stroke and hemiparesis based on a multicentre clinical trial
Authors: Berrigan Patrick , Hodge Jacquie , Kirton Adam , Moretti Myla E , Ungar Wendy J , Zwicker Jennifer D 
Published: November 2022

Introduction
Perinatal stroke leads to cerebral palsy (CP) and lifelong disability for thousands of Canadian children. Hemiparesis, referring to impaired functionality in one side of the body, is a common complication of perinatal stroke. Standard long-term care for hemiparetic CP focuses on rehabilitation therapies. Early research suggests that patients with hemiparesis may benefit from adjunctive neuromodulation treatments such as transcranial direct current stimulation (tDCS). tDCS uses electric current to stimulate targeted areas of the brain non-invasively, potentially enhancing the effects of motor learning therapies. This protocol describes an economic evaluation to be conducted alongside a randomised controlled trial (RCT) to assess the incremental cost of tDCS added to a camp-based therapy compared with camp-based therapy alone per quality-adjusted life year (QALY) gained in children with hemiparetic CP.

Methods and analysis
The Stimulation for Perinatal Stroke Optimising Recovery Trajectories (SPORT) trial is a multicentre RCT evaluating tDCS added to a 2-week camp-based therapy for children aged 6–18 years with perinatal ischaemic stroke and disabling hemiparetic CP affecting the upper limb. Outcomes are assessed at baseline, 1 week, 2 months and 6 months following intervention. Cost and quality of life data are collected at baseline and 6 months and results will be used to conduct a cost–utility analysis (CUA). The evaluation will be conducted from the perspectives of the public healthcare system and society. The CUA will be conducted over a 6-month time horizon.

Ethics and dissemination
Ethical approval for the SPORT trial and the associated economic evaluation has been given by the research ethics boards at each of the study sites. The findings of the economic evaluation will be submitted for publication in a peer reviewed academic journal and submitted for presentation at conference.

Trial registration number

NCT03216837; Post-results
.
Protocol of the study: the effectiveness of pleuran in the treatment of acute gastroenteritis in children—a randomised, placebo-controlled, double-blind trial (EPTAGE)
Authors: Wzorek-Łyczko Katarzyna , Piwowarczyk Anna , Kuchar Ernest 
Published: November 2022

Introduction
Acute gastroenteritis is one of the most common causes of children’s morbidity and mortality globally. Oral or intravenous rehydration was proven effective in reducing the mortality rates in acute gastroenteritis, although it does not affect the course of the disease. Attempts to identify new therapeutic methods effective in reducing the symptoms of diarrhoea are of interest. Pleuran’s potential immunomodulatory effect in acute gastrointestinal infection relies on the stimulation of innate immunity. The effectiveness of pleuran (β-(1,3/1,6)-d-glucan) administration to treat acute infectious diarrhoea remains unknown. This study evaluates the efficacy of pleuran in reducing diarrhoea duration and the severity of acute gastroenteritis symptoms in children.

Methods and analysis
Our study is a randomised, double-blind, placebo-controlled superiority trial with two parallel groups and a 1:1 allocation ratio. A total of 120 children aged 2–10 years hospitalised or requiring a visit to the emergency department because of acute gastroenteritis will be randomly assigned to receive either pleuran oral suspension in the experimental group or matching placebo in the control group. The primary outcome measure will be the duration of diarrhoea. We will analyse the results in both intention-to-treat and per-protocol approaches.

Ethics and dissemination
The Bioethics Committee of The Medical University of Warsaw approved the study protocol (approval number: KB/45/2018). Written informed consent of the patients’ caregivers participating in the study will be obligatory. The results of this study will be published in a medical journal, regardless of whether they confirm or deny the research hypothesis.

Trial registration number

NCT03988257; Pre-results
.
Value of biomarkers in predicting mortality in older medical emergency
department patients: a Dutch prospective study
Authors: Zelis Noortje , Hundscheid Robin , Buijs Jacqueline , De Leeuw Peter W , Raijmakers Maarten TM , van Kuijk Sander MJ , Stassen Patricia M 
Published: November 2022

Objective
Older emergency department (ED) patients are at high risk of
mortality, and it is important to predict which patients are at highest
risk. Biomarkers such as lactate, high-sensitivity cardiac troponin T
(hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP),
D-dimer and procalcitonin may be able to identify those at risk. We
aimed to assess the discriminatory value of these biomarkers for 30-day
mortality and other adverse outcomes.

Design
Prospective cohort study. On arrival of patients, five biomarkers
were measured. Area under the curves (AUCs) and interval likelihood
ratios (LRs) were calculated to investigate the discriminatory value of
the biomarkers.

Setting
ED in the Netherlands.

Participants
Older (≥65 years) medical ED patients, referred for internal
medicine or gastroenterology.

Primary and secondary outcome measures
30-day mortality was the primary outcome measure, while other
adverse outcomes (intensive care unit/medium care unit admission,
prolonged length of hospital stay, loss of independent living and
unplanned readmission) were the composite secondary outcome
measure.

Results
The median age of the 450 included patients was 79 years (IQR
73–85). In total, 51 (11.3%) patients died within 30 days. The AUCs of
all biomarkers for prediction of mortality were sufficient to good, with
the highest AUC of 0.73 for hs-cTnT and NT-proBNP. Only for the highest
lactate values, the LR was high enough (29.0) to be applicable for
clinical decision making, but this applied to a minority of patients.
The AUC for the composite secondary outcome (intensive and medium care
admission, length of hospital stay >7 days, loss of independent
living and unplanned readmission within 30 days) was lower, ranging
between 0.58 and 0.67.

Conclusions
Although all five biomarkers predict 30-day mortality in older
medical ED patients, their individual discriminatory value was not high
enough to contribute to clinical decision making.

Trial registration number
NCT02946398; Results.
Integrating neuroimaging biomarkers into the multicentre, high-dose erythropoietin for asphyxia and encephalopathy (HEAL) trial: rationale, protocol and harmonisation
Authors: Wisnowski Jessica L , Bluml Stefan , Panigrahy Ashok , Mathur Amit M , Berman Jeffrey , Chen Ping-Sun Keven , Dix James , Flynn Trevor , Fricke Stanley , Friedman Seth D , Head Hayden W , Ho Chang Y , Kline-Fath Beth , Oveson Michael , Patterson Richard , Pruthi Sumit , Rollins Nancy , Ramos Yanerys M , Rampton John , Rusin Jerome , Shaw Dennis W , Smith Mark , Tkach Jean , Vasanawala Shreyas , Vossough Arastoo , Whitehead Matthew T , Xu Duan , Yeom Kristen , Comstock Bryan , Heagerty Patrick J , Juul Sandra E , Wu Yvonne W , McKinstry Robert C 
Published: November 2022

Introduction
MRI and MR spectroscopy (MRS) provide early biomarkers of brain injury and treatment response in neonates with hypoxic-ischaemic encephalopathy). Still, there are challenges to incorporating neuroimaging biomarkers into multisite randomised controlled trials. In this paper, we provide the rationale for incorporating MRI and MRS biomarkers into the multisite, phase III high-dose erythropoietin for asphyxia and encephalopathy (HEAL) Trial, the MRI/S protocol and describe the strategies used for harmonisation across multiple MRI platforms.

Methods and analysis
Neonates with moderate or severe encephalopathy enrolled in the multisite HEAL trial undergo MRI and MRS between 96 and 144 hours of age using standardised neuroimaging protocols. MRI and MRS data are processed centrally and used to determine a brain injury score and quantitative measures of lactate and n-acetylaspartate. Harmonisation is achieved through standardisation—thereby reducing intrasite and intersite variance, real-time quality assurance monitoring and phantom scans.

Ethics and dissemination
IRB approval was obtained at each participating site and written consent obtained from parents prior to participation in HEAL. Additional oversight is provided by an National Institutes of Health-appointed data safety monitoring board and medical monitor.

Trial registration number

NCT02811263; Pre-result
.
Multicentre, randomised, single-blind, parallel group trial to compare
the effectiveness of a Holter for Parkinson’s symptoms against other
clinical monitoring methods: study protocol
Authors: Rodríguez-Molinero Alejandro , Hernández-Vara Jorge , Miñarro Antonio , Pérez-López Carlos , Bayes-Rusiñol Àngels , Martínez-Castrillo Juan Carlos , Pérez-Martínez David A 
Published: November 2022

Introduction
In recent years, multiple studies have aimed to develop and validate
portable technological devices capable of monitoring the motor
complications of Parkinson’s disease patients (Parkinson’s Holter). The
effectiveness of these monitoring devices for improving clinical control
is not known.

Methods and analysis
This is a single-blind, cluster-randomised controlled clinical
trial. Neurologists from Spanish health centres will be randomly
assigned to one of three study arms (1:1:1): (a) therapeutic adjustment
using information from a Parkinson’s Holter that will be worn by their
patients for 7 days, (b) therapeutic adjustment using information from a
diary of motor fluctuations that will be completed by their patients for
7 days and (c) therapeutic adjustment using clinical information
collected during consultation. It is expected that 162 consecutive
patients will be included over a period of 6 months.
The primary outcome is the efficiency of the Parkinson’s Holter
compared with traditional clinical practice in terms of Off time
reduction with respect to the baseline (recorded through a diary of
motor fluctuations, which will be completed by all patients). As
secondary outcomes, changes in variables related to other motor
complications (dyskinesia and freezing of gait), quality of life,
autonomy in activities of daily living, adherence to the monitoring
system and number of doctor–patient contacts will be analysed. The
noninferiority of the Parkinson’s Holter against the diary of motor
fluctuations in terms of Off time reduction will be studied as the
exploratory objective.
Ethics and dissemination approval for this study has been obtained
from the Hospital Universitari de Bellvitge Ethics Committee. The
results of this study will inform the practical utility of the objective
information provided by a Parkinson’s Holter and, therefore, the
convenience of adopting this technology in clinical practice and in
future clinical trials. We expect public dissemination of the results in
2022.

Trial registration
NCT04176302;https://clinicaltrials.gov/show/NCT04176302
Protocol for a sequential, multiple assignment, randomised trial to test
the effectiveness of message-based psychotherapy for depression compared
with telepsychotherapy
Authors: Arean Patricia , Hull Derrick , Pullmann Michael D , Heagerty Patrick J 
Published: November 2022

Introduction
Digital mental health tools have become popular alternatives to
traditional psychotherapy. One emerging form of digital mental health is
message-based care, the use of text messages or asynchronous voice or
video messaging to provide psychotherapy. There has been no research
into whether this is an effective method of psychotherapy as a
stand-alone treatment or in combination with traditional
psychotherapy.

Methods and analysis
This is a sequential, multiple assignment randomised trial to
compare message-based care, videoconference-psychotherapy and a
combination of the two treatments in 1000 depressed adults. Participants
will be recruited through Talkspace, a digital mental health company,
and randomised to receive 6 weeks of either message-based care only or
videoconference-psychotherapy only. At 6 weeks, participants will be
evaluated for their response to treatment. Those with a 50% or more
response to treatment will continue with their assigned condition. Those
who do not respond will be randomised to either monthly
videoconference-psychotherapy or weekly videoconference-psychotherapy
plus message-based care. Primary outcomes will be depression and social
functioning. We will also explore moderators of treatment
outcome.

Ethics and dissemination
The study received ethics approval from the University of Washington
Institutional Review Board. Results of this study will be presented in
peer-reviewed journals and at professional conferences.

Trial registration number
NCT04513080; Pre-results.
Multiorgan impairment in low-risk individuals with post-COVID-19
syndrome: a prospective, community-based study
Authors: Dennis Andrea , Wamil Malgorzata , Alberts Johann , Oben Jude , Cuthbertson Daniel J , Wootton Dan , Crooks Michael , Gabbay Mark , Brady Michael , Hishmeh Lyth , Attree Emily , Heightman Melissa , Banerjee Rajarshi , Banerjee Amitava 
Published: November 2022

Objective
To assess medium-term organ impairment in symptomatic individuals
following recovery from acute SARS-CoV-2 infection.

Design
Baseline findings from a prospective, observational cohort
study.

Setting
Community-based individuals from two UK centres between 1 April and
14 September 2020.

Participants
Individuals ≥18 years with persistent symptoms following recovery
from acute SARS-CoV-2 infection and age-matched healthy
controls.

Intervention
Assessment of symptoms by standardised questionnaires (EQ-5D-5L,
Dyspnoea-12) and organ-specific metrics by biochemical assessment and
quantitative MRI.

Main outcome measures
Severe post-COVID-19 syndrome defined as ongoing respiratory
symptoms and/or moderate functional impairment in activities of daily
living; single-organ and multiorgan impairment (heart, lungs, kidneys,
liver, pancreas, spleen) by consensus definitions at baseline
investigation.

Results
201 individuals (mean age 45, range 21–71 years, 71% female, 88%
white, 32% healthcare workers) completed the baseline assessment (median
of 141 days following SARS-CoV-2 infection, IQR 110–162). The study
population was at low risk of COVID-19 mortality (obesity 20%,
hypertension 7%, type 2 diabetes 2%, heart disease 5%), with only 19%
hospitalised with COVID-19. 42% of individuals had 10 or more symptoms
and 60% had severe post-COVID-19 syndrome. Fatigue (98%), muscle aches
(87%), breathlessness (88%) and headaches (83%) were most frequently
reported. Mild organ impairment was present in the heart (26%), lungs
(11%), kidneys (4%), liver (28%), pancreas (40%) and spleen (4%), with
single-organ and multiorgan impairment in 70% and 29%, respectively.
Hospitalisation was associated with older age (p=0.001), non-white
ethnicity (p=0.016), increased liver volume (p<0.0001), pancreatic
inflammation (p<0.01), and fat accumulation in the liver (p<0.05)
and pancreas (p<0.01). Severe post-COVID-19 syndrome was associated
with radiological evidence of cardiac damage (myocarditis)
(p<0.05).

Conclusions
In individuals at low risk of COVID-19 mortality with ongoing
symptoms, 70% have impairment in one or more organs 4 months after
initial COVID-19 symptoms, with implications for healthcare and public
health, which have assumed low risk in young people with no
comorbidities.

Trial registration number
NCT04369807; Pre-results.