bluuebunny/crossref_metadata_2025 huggingface dataset:
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.
Cost-effectiveness of adding a non-invasive acoustic rule-out test in the evaluation of patients with symptoms suggestive of coronary artery disease: rationale and design of the prospective, randomised, controlled, parallel-group multicenter FILTER-SCAD trial
Authors: Bjerking Louise Hougesen , Hansen Kim Wadt , Biering-Sørensen Tor , Brønnum-Schou Jens , Engblom Henrik , Erlinge David , Haahr-Pedersen Sune Ammentorp , Heitmann Merete , Hove Jens Dahlgaard , Jensen Magnus Thorsten , Kruse Marie , Räder Sune , Strange Søren , Galatius Søren , Prescott Eva Irene Bossano
Published: November 2022

Introduction

Most patients with symptoms suggestive of chronic coronary syndrome (CCS) have no obstructive coronary artery disease (CAD) and better selection of patients to be referred for diagnostic tests is needed. The CAD-score is a non-invasive acoustic measure that, when added to pretest probability of CAD, has shown good rule-out capabilities. We aimed to test whether implementation of CAD-score in clinical practice reduces the use of diagnostic tests without increasing major adverse cardiac events (MACE) rates in patients with suspected CCS.

Methods and analysis

FILTER-SCAD is a randomised, controlled, multicenter trial aiming to include 2000 subjects aged ≥30 years without known CAD referred for outpatient assessment for symptoms suggestive of CCS. Subjects are randomised 1:1 to either the control group: standard diagnostic examination (SDE) according to the current guidelines, or the intervention group: SDE plus a CAD-score. The subjects are followed for 12 months for the primary endpoint of cumulative number of diagnostic tests and a safety endpoint (MACE). Angina symptoms, quality of life and risk factor modification will be assessed with questionnaires at baseline, 3 months and 12 months after randomisation. The study is powered to detect superiority in terms of a reduction of ≥15% in the primary endpoint between the two groups with a power of 80%, and non-inferiority on the secondary endpoint with a power of 90%. The significance level is 0.05. The non-inferiority margin is set to 1.5%. Randomisation began on October 2019. Follow-up is planned to be completed by December 2022.

Ethics and dissemination

This study has been approved by the Danish Medical Agency (2019024326), Danish National Committee on Health Research Ethics (H-19012579) and Swedish Ethical Review Authority (Dnr 2019-04252). All patients participating in the study will sign an informed consent. All study results will be attempted to be published as soon as possible.

Trial registration number

NCT04121949; Pre-results.
Pragmatic, double-blind, randomised trial evaluating the impact of red
blood cell donor sex on recipient mortality in an academic hospital
population: the innovative Trial Assessing Donor Sex (iTADS)
protocol
Authors: Fergusson Dean A , Chassé Michael , Tinmouth Alan , Acker Jason P , English Shane , Forster Alan J , Hawken Steven , Shehata Nadine , Thavorn Kednapa , Wilson Kumanan , Tuttle Angie , Perelman Iris , Cober Nancy , Maddison Heather , Tokessy Melanie
Published: November 2022

Introduction

With over 1 million units of blood transfused each year in Canada,
their use has a significant clinical and economic impact on our health
system. Adequate screening of blood donors is important to ensure the
safety and clinical benefit of blood products. Some adverse transfusion
reactions have been shown to be related to donor factors (eg, lung
injury), whereas other adverse outcomes have been theoretically related
to donor factors (mortality and infection). Our clinical trial will test
whether male donor blood leads to a greater benefit for transfusion
recipients compared with female donor blood.

Methods and analysis

We have designed a pragmatic, double-blind, randomised trial that
will allocate transfusion recipients to receive either male-only or
female-only donor transfusions. We will enrol 8850 adult patients
requiring at least one transfusion at four sites over an approximate
2-year period. Randomisation and allocation will occur in the blood bank
prior to release of the units of blood for transfusion. Our primary
outcome is mortality. An intent-to-treat analysis will be applied using
all randomised and transfused patients. The principal analysis will be a
survival analysis comparing the time from randomisation to death between
patients allocated to male donor red blood cells (RBCs) and female donor
RBCs.

Ethics and dissemination

Approval has been obtained from research ethics boards of all
involved institutions, as well as from privacy offices of Canadian Blood
Services, Institute for Clinical Evaluative Science and The Ottawa
Hospital Data Warehouse. Our findings will be published in peer-reviewed
journals and presented at relevant stakeholder conferences and
meetings.

Trial registration number

NCT03344887; Pre-results.
CATALYST trial protocol: a multicentre, open-label, phase II, multiarm
trial for an early and accelerated evaluation of the potential treatments
for COVID-19 in hospitalised adults
Authors: Veenith Tonny , Fisher Benjamin A. , Slade Daniel , Rowe Anna , Sharpe Rowena , Thickett David R. , Whitehouse Tony , Rowland Matthew , Scriven James , Parekh Dhruv , Bowden Sarah J. , Savage Joshua S. , Richards Duncan , Bion Julian , Kearns Pamela , Gates Simon
Published: November 2022

Introduction

Severe SARS-CoV-2 infection is associated with a dysregulated immune
response. Inflammatory monocytes and macrophages are crucial, promoting
injurious, proinflammatory sequelae. Immunomodulation is, therefore, an
attractive therapeutic strategy and we sought to test licensed and novel
candidate drugs.

Methods and analysis

The CATALYST trial is a multiarm, open-label, multicentre, phase II
platform trial designed to identify candidate novel treatments to
improve outcomes of patients hospitalised with COVID-19 compared with
usual care. Treatments with evidence of biomarker improvements will be
put forward for larger-scale testing by current national phase III
platform trials. Hospitalised patients >16 years with a clinical
picture strongly suggestive of SARS-CoV-2 pneumonia (confirmed by chest
X-ray or CT scan, with or without a positive reverse transcription PCR
assay) and a C reactive protein (CRP) ≥40 mg/L are eligible. The primary
outcome measure is CRP, measured serially from admission to day 14,
hospital discharge or death. Secondary outcomes include the WHO Clinical
Progression Improvement Scale as a principal efficacy
assessment.

Ethics and dissemination

The protocol was approved by the East Midlands-Nottingham 2 Research
Ethics Committee (20/EM/0115) and given urgent public health status;
initial approval was received on 5 May 2020, current protocol version
(V.6.0) approval on 12 October 2020. The MHRA also approved all protocol
versions. The results of this trial will be disseminated through
national and international presentations and peer-reviewed
publications.

Trial registration numbers

EudraCT2020-001684-89,NCT40580903.
Supporting Parenting at Home-Empowering Rehabilitation through Engagement
(SPHERE): study protocol for a randomised control trial
Authors: Grumi Serena , Borgatti Renato , Provenzi Livio
Published: November 2022

Introduction

Infants with neurodevelopmental disabilities (NDs) show emotional,
cognitive and sociointeractive dysregulation dramatically impacting on
caregiving behaviour. Early video-feedback interventions (VFIs) are
effective in promoting sensitive parenting, which in turn supports
infants’ development, even in case of ND. In the light of limited
resources of the healthcare systems, technological advances in
telemedicine may facilitate the delivery of VFI to a greater number of
families of infants with ND. To date, no study has implemented a
telemedicine VFI (TVFI) for families of infants diagnosed with
ND.

Methods and analysis

The Supporting Parenting at Home-Empowering Rehabilitation through
Engagement project is a randomised controlled trial aimed at assessing
the effectiveness of an early family-centred TVFI parenting support on
dyads with infants diagnosed with ND. It includes two arms (TVFI vs
Booklet Psychoeducational Intervention) and three assessment phases: T0,
baseline; T1, immediate postintervention; T2, 6-month
follow-up.

Ethics and dissemination

This study is funded by the Italian Ministry of Health and was
approved by the Ethics Committee (Pavia). Results will be published in
peer-reviewed journals and presented at national and international
scientific conferences.

Trial registration number

The study protocol has been also registered on NIH Clinical Trials
(protocol codeNCT04656483; Pre-results).
Increased risk of COVID-19-related admissions in patients with active
solid organ cancer in the West Midlands region of the UK: a retrospective
cohort study
Authors: Akingboye Akinfemi , Mahmood Fahad , Amiruddin Nabeel , Reay Michael , Nightingale Peter , Ogunwobi Olorunseun O
Published: November 2022

Objective

Susceptibility of patients with cancer to COVID-19 pneumonitis has
been variable. We aim to quantify the risk of hospitalisation in
patients with active cancer and use a machine learning algorithm (MLA)
and traditional statistics to predict clinical outcomes and
mortality.

Design

Retrospective cohort study.

Setting

A single UK district general hospital.

Participants

Data on total hospital admissions between March 2018 and June 2020,
all active cancer diagnoses between March 2019 and June 2020 and
clinical parameters of COVID-19-positive admissions between March 2020
and June 2020 were collected. 526 COVID-19 admissions without an active
cancer diagnosis were compared with 87 COVID-19 admissions with an
active cancer diagnosis.

Primary and secondary outcome measures

30-day and 90-day post-COVID-19 survival.

Results

In total, 613 patients were enrolled with male to female ratio of
1:6 and median age of 77 years. The estimated infection rate of COVID-19
was 87 of 22 729 (0.4%) in the patients with cancer and 526 of 404 379
(0.1%) in the population without cancer (OR of being hospitalised with
COVID-19 if having cancer is 2.942671 (95% CI: 2.344522 to 3.693425);
p<0.001). Survival was reduced in patients with cancer with COVID-19
at 90 days. R-Studio software determined the association between cancer
status, COVID-19 and 90-day survival against variables using MLA.
Multivariate analysis showed increases in age (OR 1.039 (95% CI: 1.020
to 1.057), p<0.001), urea (OR 1.005 (95% CI: 1.002 to 1.007),
p<0.001) and C reactive protein (CRP) (OR 1.065 (95% CI: 1.016 to
1.116), p<0.008) are associated with greater 30-day and 90-day
mortality. The MLA model examined the contribution of predictive
variables for 90-day survival (area under the curve: 0.749); with
transplant patients, age, male gender and diabetes mellitus being
predictors of greater mortality.

Conclusions

Active cancer diagnosis has a threefold increase in risk of
hospitalisation with COVID-19. Increased age, urea and CRP predict
mortality in patients with cancer. MLA complements traditional
statistical analysis in identifying prognostic variables for outcomes of
COVID-19 infection in patients with cancer. This study provides proof of
concept for MLA in risk prediction for COVID-19 in patients with cancer
and should inform a redesign of cancer services to ensure safe delivery
of cancer care.
Adjunctive virtual reality pain relief following traumatic injury:
protocol for a randomised within-subjects clinical trial
Authors: Felix Ryan B , Rao Aniruddha , Khalid Mazhar , Wang Yang , Colloca Luana , Murthi Sarah B , Morris Nicholas A
Published: November 2022

Introduction

The annual mortality and national expense of the opioid crisis
continue to rise in the USA (130 deaths/day, $50 billion/year). Opioid
use disorder usually starts with the prescription of opioids for a
medical condition. Its risk is associated with greater pain intensity
and coping strategies characterised by pain catastrophising.
Non-pharmacological analgesics in the hospital setting are critical to
abate the opioid epidemic. One promising intervention is virtual reality
(VR) therapy. It has performed well as a distraction tool and pain
modifier during medical procedures; however, little is known about VR in
the acute pain setting following traumatic injury. Furthermore, no
studies have investigated VR in the setting of traumatic brain injury
(TBI). This study aims to establish the safety and effect of VR therapy
in the inpatient setting for acute traumatic injuries, including
TBI.

Methods and analysis

In this randomised within-subjects clinical study, immersive VR
therapy will be compared with two controls in patients with traumatic
injury, including TBI. Affective measures including pain
catastrophising, trait anxiety and depression will be captured prior to
beginning sessions. Before and after each session, we will capture pain
intensity and unpleasantness, additional affective measures and
physiological measures associated with pain response, such as heart rate
and variability, pupillometry and respiratory rate. The primary outcome
is the change in pain intensity of the VR session compared with
controls.

Ethics and dissemination

Dissemination of this protocol will allow researchers and funding
bodies to stay abreast in their fields through exposure to research not
otherwise widely publicised. Study protocols are compliant with federal
regulation and University of Maryland Baltimore’s Human Research
Protections and Institutional Review Board (protocol number
HP-00090603). Study results will be published on completion of enrolment
and analysis, and deidentified data can be shared by request to the
corresponding author.

Trial registration number

NCT04356963; Pre-results.
Global mapping of exercise interventions among COVID-19 survivors: protocol for a scoping review
Authors: Sinha Mukesh Kumar , Soman Ajith , K Vaishali , Kovela Rakesh Krishna , Lakshminarayanan Monisha , Amin Revati , Verma Ashwani
Published: November 2022

Introduction

The COVID-19 pandemic has posed an unparalleled threat to all dimensions of human health and well-being. The Pan American Health Organization has acknowledged the crucial role of rehabilitation therapies for COVID-19 and emphasised the importance of exercise programmes for COVID-19 survivors. This scoping review outlines our strategy for systematically reviewing published and unpublished literature to investigate the volume of evidence for exercise interventions for COVID-19 survivors.

Methods and analysis

This scoping review will be conducted based on the framework developed by Arksey and O'Malley. Six databases (PubMed/Medline, Scopus, Web of Science, Cochrane Central, ProQuest and CINAHL) will be searched in August 2022 and articles will be considered for inclusion published till July 2022. Studies will be screened by two independent reviewers at the title/abstract and full-text screening stages, as well as data extraction and critical assessment. Data will be extracted in a data extraction form and presented as figures and tables with narratives. This scoping review will give a thorough understanding of the current literature on exercise interventions for COVID-19 survivors, as well as identify knowledge gaps that will guide future research. Preliminary searches will be conducted after the publication of this scoping review protocol.

Ethics and dissemination

No human or animal participants were involved in this review. Therefore, ethical committee approval is not required. Transparency will be followed at every review stage. Review findings will be disseminated through peer-review publications or through conference presentations.
Numbers and types of neurological emergencies in England and the influence of socioeconomic deprivation: a retrospective analysis of hospital episode statistics data
Authors: Jackson Michael , Szczepaniak Marta , Wall Jasmine , Maskery Mark , Mummery Catherine , Morrish Paul , Williams Adrian , Knight Joanne , Emsley Hedley C A
Published: November 2022

Objectives

In this first large-scale analysis of neurological emergency admissions in England, we determine the number and types of emergency admissions with neurological emergency diagnostic codes, how many are under the care of a neurologist or neurosurgeon and how such admissions vary by levels of deprivation.

Design

Retrospective empirical research employing a derived list of neurological emergency diagnostic codes

Setting

This study used the Hospital Episode Statistics data set for the financial year 2019/2020 based on 17 million in-year inpatient admissions in England including 6.5 million (100%) emergency admissions with any diagnosis codes.

Results

There were 1.4 million (21.2%) emergency inpatient admissions with a mention of any neurological code, approx. 248 455 (3.8%) with mention of a specific neurological emergency code from the derived list, and 72 485 (1.1%) included such a code as the primary reason for admission. The highest number of in-year admissions for adults was for epilepsy (145 995), with epilepsy as the primary diagnostic code in 15 945 (10.9%). Acute nerve root/spinal cord syndrome (41 215), head injury (29 235) and subarachnoid haemorrhage (18 505) accounted for the next three highest number of admissions. 3230 (1.4%) in-year emergency hospital admissions with mention of a neurological emergency code were under the care of a neurologist or neurosurgeon, with only 1315 (0.9%) admissions with mention of an epilepsy code under a neurologist. There was significant variation for epilepsy and functional neurological disorders (FNDs) in particular by Index of Multiple Deprivation decile. The association between deprivation and epilepsy and FND was significant with p-values of 2.5e-6 and 1.5e-8, respectively.

Conclusions

This study has identified important findings in relation to the burden of neurological emergency admissions but further work is needed, with greater clinical engagement in diagnostic coding, to better understand the implications for workforce and changes to service delivery needing to be implemented.
Use of a microsimulation method for assessing dynamics of smoking status and gains in life expectancy after quitting in a longitudinal cohort of US older adults
Authors: Jia Haomiao , Lubetkin Erica
Published: November 2022

Objectives

Previous studies were unable to estimate the dynamics of smoking status in the US elderly general population, and no study has assessed the benefit of quitting in terms of resultant gains in life expectancy. We proposed a novel method to estimate the per cent of quitting in remaining lifetime, successful quitting and relapse, as well as life expectancy by participants’ baseline smoking status.

Design

Longitudinal cohort.

Setting

US community-dwelling population.

Participants

Respondents from the Medicare Health Outcome Survey Cohort 15 (baseline 2012, follow-up 2014). We included respondents who were aged ≥65 years and alive at the baseline and participated in the baseline survey (n=164 597).

Primary and secondary outcome measures

Attempt quitting, successful quitting, relapse rates and life expectancy by smoking status at age 65–95 years.

Results

Among daily smokers aged 65 years, 61% would attempt to quit during their remaining lifetime, and 31% would quit successfully. Among some days smokers aged 65 years, 69% would attempt to quit during their remaining lifetime, and 37% would quit successfully. Among recent ex-smokers aged 65 years, 53% would relapse. Life expectancy at age 65 years was 20.0 (SE=0.27), 17.2 (SE=0.30), 16.2 (SE=0.29) and 15.9 (SE=0.29) years for long time non-smokers, recent ex-smokers, some days smokers and daily smokers, respectively. Although recent ex-smokers had a higher 2-year mortality than current smokers, those who quit up to 77 years (77 years for men and 87 years for women) had a significantly longer (p<0.05) life expectancy. Sensitivity analysis demonstrated that the model assumptions had a relatively small impact on estimates with a maximum relative bias within ±7%.

Conclusions

This study provides detailed information regarding the dynamics of smoking status in an understudied and growing population and demonstrates the benefit of smoking cessation on life expectancy. Future research should focus on understanding specific predictors of smoking cessation.
Protocol for a systematic review on effective patient positioning for rapid sequence intubation
Authors: Sivajohan Asaanth , Krause Sarah CT , Hegazy Ahmed , Slessarev Marat
Published: November 2022

Introduction

Rapid sequence intubation (RSI) is an advanced airway technique to perform endotracheal intubation in patients at high risk of aspiration. Although RSI is recognised as a life-saving technique and performed by many physicians in various settings (emergency departments, intensive care units), there is still a lack of consensus on various features of the procedure, most notably patient positioning. Previously, experts have commented on the unique drawbacks and benefits of various positions and studies have been published comparing patient positions and how it can affect endotracheal intubation in the context of RSI. The purpose of this systematic review is to compile the existing evidence to understand and compare how different patient positions can potentially affect the success of RSI.

Methods and analysis

We will use MEDLINE, EMBASE and the Cochrane Library to source studies from 1946 to 2021 that evaluate the impact of patient positioning on endotracheal intubation in the context of RSI. We will include randomised control trials, case–control studies, prospective/retrospective cohort studies and mannequin simulation studies for consideration in this systematic review. Subsequently, we will generate a Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram to display how we selected our final studies for inclusion in the review. Two independent reviewers will complete the study screening, selection and extraction, with a third reviewer available to address any conflicts. The reviewers will extract this data in accordance with our outcomes of interest and display it in a table format to highlight patient-relevant outcomes and difficulty airway management outcomes. We will use the Risk of Bias tool and the Newcastle-Ottawa Scale to assess included studies for bias.

Ethics and dissemination

This systematic review does not require ethics approval, as all patient-centred data will be reported from published studies.

PROSPERO registration number

CRD42022289773.
Prevalence of harmful traditional practices during pregnancy and associated factors in Southwest Ethiopia: a community-based cross-sectional study
Authors: Tesfaye Melkamsew , Solomon Nahom , Getachew Dawit , Biru Yemisrach Belete
Published: November 2022

Objective

To assess the prevalence of harmful traditional practices during pregnancy and associated factors in Southwest Ethiopia.

Design

A community-based cross-sectional study.

Setting

Southwest Ethiopia.

Participants

667 women who were pregnant at the time of the study or gave birth 2 years prior to the study have participated.

Outcome of the study

Harmful traditional practices during pregnancy (yes/no). Harmful traditional practices during pregnancy include abdominal massage, herbal intake or food taboos done on/by pregnant women without health professionals’ instruction.

Results

The prevalence of harmful traditional practices in the study area was 37%, 95% CI (33.4% to 40.8%). The most commonly practised activities were abdominal massage (72.9%), intake of herbs (63.9%) and food taboos (48.6%). Monthly income (AOR=3.13, 95% CI (1.83 to 5.37), p<0.001), having had no history of child death (AOR=2.74, 95% CI (1.75 to 4.29), p<0.001), women with no formal education (AOR=4.81, 95% CI (2.50 to 9.23), p<0.001), women who had antenatal care (ANC) visits during their last pregnancy (AOR=0.24, 95% CI (0.10 to 0.59), p=0.002) and being multipara (AOR=0.47, 95% CI (0.27 to 0.80), p=0.003) were significantly associated with harmful traditional practices during pregnancy.

Conclusion

Our study showed that more than one-third of women in Southwest Ethiopia practised harmful traditional practices while they were pregnant. The practices were more common among primiparas, women who had lower educational and financial status, women with no ANC visits, and women with no history of child death. Health education should be given to the community about the complications of harmful traditional practices during pregnancy.
Opioid PrEscRiptions and usage After Surgery (OPERAS): protocol for a prospective multicentre observational cohort study of opioid use after surgery
Authors:   TASMAN Collaborative
Published: November 2022

Introduction

Postoperative pain is common and frequently addressed through opioid analgesia. This practice must balance the benefits of achieving adequate pain relief against the harms of adverse effects such as opioid-induced ventilatory impairment and opioid use disorder. This student and trainee-led collaborative study aims to investigate and compare the prescription versus consumption of opioids at 7 days postdischarge after common surgical procedures and their impact on patient-reported outcomes regarding postoperative pain.

Methods and analysis

This is a prospective multicentre observational cohort study of surgical patients in Australia, Aotearoa New Zealand and select international sites, conducted by networks of students, trainees and consultants. Consecutive adult patients undergoing common elective and emergency general, orthopaedic, gynaecological and urological surgical procedures are eligible for inclusion, with follow-up 7 days after hospital discharge. The primary outcome will be the proportion of prescribed opioids consumed by patients at 7 days postdischarge. Secondary outcomes will include patient-reported quality of life and satisfaction scores, rate of non-opioid analgesic use, rate of continuing use of opioids at follow-up, rates of opioid prescription from other sources and hospital readmissions at 7 days postdischarge for opioid related side-effects or surgery-related pain. Descriptive and multivariate analyses will be conducted to investigate factors associated with opioid requirements and prescription-consumption discrepancies.

Ethics and dissemination

OPERAS has been approved in Australia by the Hunter New England Human Research Ethics Committee (Protocol 2021/ETH11508) and by the Southern Health and Disability Ethics Committee (2021 EXP 11199) in Aotearoa New Zealand. Results will be submitted for conference presentation and peer-reviewed publication. Centre-level data will be distributed to participating sites for internal audit.

Trial registration number

ANZCTR (ID: ACTRN12621001451897p)
Investigating the association between IL-6 antagonist therapy and blood coagulation in critically ill patients with COVID-19: a protocol for a prospective, observational, multicentre study
Authors: Kovács Emőke Henrietta , Rottler Máté , Dembrovszky Fanni , Ocskay Klementina , Szabó László , Hegyi Péter , Molnár Zsolt , Tánczos Krisztián
Published: November 2022

Introduction

Hypercoagulation is one the main features of COVID-19. It is induced by the hyperinflammatory response that shifts the balance of haemostasis towards pro-coagulation. Interleukin-6 (IL-6) antagonist therapy has been recommended in certain subgroups of critically ill patients with COVID-19 to modulate inflammatory response. The interaction between immune response and haemostasis is well recognised. Therefore, our objective is to evaluate whether the modulation of the inflammatory response by IL-6 antagonist inflicts any changes in whole blood coagulation as assessed by viscoelastic methods in critically ill patients with COVID-19.

Methods and analysis

In this prospective observational study, we are going to collect data on inflammatory parameters and blood coagulation using the ClotPro®device. The primary outcome is the change of the fibrinolytic system measured by the Lysis Time and Lysis onset time before and after immunomodulation therapy. Data will be collected before the IL-6 antagonist administration at baseline (T0) then after 24, 48 hours, then on day 5 and 7 (T1-4, respectively). Secondary outcomes include changes in other parameters related to inflammation, blood coagulation and biomarkers of endothelial injury.

Ethics and dissemination

Ethical approval was given by the Medical Research Council of Hungary (1405-3/2022/EÜG). All participants provided written consent. The results of the study will be disseminated through peer-reviewed journals.

Trial registration number

NCT05218369; Clinicaltrials.gov.
MPrEP+ study protocol: a prospective cohort study assessing the feasibility and acceptability of an HIV pre-exposure prophylaxis (PrEP) strategy for male clients of female sex workers in Kisumu, Kenya
Authors: Mantell Joanne , Franks Julie , Zerbe Allison , Lamb Matthew R , Reed Domonique M , Omollo Dan , Lahuerta Maria , Naitore Doris , El-Sadr Wafaa M , Agot Kawango
Published: November 2022

Introduction

Male clients (MCs) are integral to sex work-driven HIV transmission dynamics as sexual partners of female sex worker (FSW). MCs contribute disproportionately to incident HIV globally and in sub-Saharan Africa, with 27% of new infections attributed to MCs of FSW and other partners of key populations. Gaps in coverage of HIV testing and prevention services for men, including MCs, are well-documented, yet research and innovative interventions to improve MC uptake of effective prevention services, including pre-exposure prophylaxis (PrEP), are scarce.

Methods and analysis

MPrEP+ is a cohort study designed to assess the feasibility and acceptability of a PrEP-focused HIV prevention strategy providing daily oral tenofovir/emtricitabine (TDF/FTC) in combination with three adherence self-management interventions: (1) use of a validated point-of-care urine drug-level assay with real-time feedback and tailored self-management counselling; (2) frequent HIV self-testing; and (3) weekly one-way text messaging. This package of interventions is being delivered to 120 MCs enrolled in the study in Kisumu, Kenya over a 6-month period. The primary outcome is PrEP adherence at 6 months as measured by PrEP drug levels. Bivariate and multivariable regression models will be used to identify predictors of PrEP adherence. We will also explore associations of sociodemographic characteristics and PrEP beliefs with PrEP adherence.

Ethics and dissemination

The study was approved by the Columbia University Irving Medical Center Institutional Review Board and the Maseno University Ethical Review Committee. Study enrolment was initiated in November 2021 with participant follow-up planned through August 2022. Study results will be submitted for publication in peer-reviewed journals. Summaries and infographics of study findings will be developed and distributed to MC, FSW and stakeholders working in HIV prevention and support for people who sell and buy sex, including Kenya’s Ministry of Health.

Trial registration number

NCT04898699; Registered on 24 May 2021.