bluuebunny/crossref_metadata_2025 huggingface dataset:
Preceding Host History of Conjugative Resistance Plasmids Affects Intra- and Interspecific Transfer Potential from Biofilm
Authors: Jonsdottir Ilmur , Given Cindy , Penttinen Reetta , Jalasvuori Matti
Published: April 2023

Antimicrobial resistance (AMR) is a major global public health threat which can rapidly spread in microbial communities via conjugative plasmids. Here, we advance with evolutionary rescue via conjugation in a more natural setting, namely, biofilm, and incorporate a broad-host range plasmid RP4 to test whether intra- and interspecific host histories affect its transfer potential.
Escherichia coli
and
Klebsiella pneumoniae
hosts were seen to elicit different evolutionary influences on the RP4 plasmid, leading to clear differences in the rescue potential and underlining the significant role of the plasmid-host interactions in the spread of AMR.
A Transducing Bacteriophage Infecting Staphylococcus epidermidis Contributes to the Expansion of a Novel Siphovirus Genus and Implies the Genus Is Inappropriate for Phage Therapy
Authors: Andrews Taylor , Hoyer J. Steen , Ficken Karolyn , Fey Paul D. , Duffy Siobain , Boyd Jeffrey M.
Published: April 2023

This project describes the discovery of a culturable bacteriophage infecting
Staphylococcus epidermidis
that is a member of a rapidly growing novel siphovirus genus. A member of this genus was recently characterized and proposed for phage therapy, as there are few phages currently available to treat
S. epidermidis
infections.
Cecal Microbial Succession and Its Apparent Association with Nutrient Metabolism in Broiler Chickens
Authors: Yin Zhenchen , Ji Shuyun , Yang Jiantao , Guo Wei , Li Yulong , Ren Zhouzheng , Yang Xiaojun
Published: April 2023

The poultry industry has become a global leader in livestock farming over the past few decades. Poultry production has a large consumer market as an integrated industry producing high-protein foods.
Triple Intergenotype Recombination of Human Astrovirus 5, Human Astrovirus 8, and Human Astrovirus 1 in the Open Reading Frame 1a, Open Reading Frame 1b, and Open Reading Frame 2 Regions of the Human Astrovirus Genome
Authors: Wei Hongyu , Kumthip Kattareeya , Khamrin Pattara , Yodmeeklin Arpaporn , Jampanil Nutthawadee , Phengma Phitchakorn , Xie Zhenfeng , Ukarapol Nuthapong , Ushijima Hiroshi , Maneekarn Niwat
Published: April 2023

Recombination is one of the mechanisms that plays a crucial role in the genetic diversity and evolution of HAstV. We wished to investigate the emergence of HAstV recombinant strains and to analyze the whole-genome sequences of the putative HAstV recombinant strains detected in pediatric patients with acute gastroenteritis in 2011 to 2020.
In Vitro
and
In Vivo
Effect of the Imidazole Luliconazole against
Lomentospora prolificans
and
Scedosporium
spp.
Authors: Furnica Dan-Tiberiu , Dittmer Silke , Scharmann Ulrike , Meis Jacques F. , Steinmann Joerg , Rath Peter-Michael , Kirchhoff Lisa
Published: April 2023

Lomentospora prolificans
and
S. apiospermum
/P. boydii
are opportunistic, multidrug-resistant pathogens causing invasive infections in immunosuppressed patients and sometimes in healthy persons.
Lomentospora prolificans
is panresistant against the currently available antifungals, and both species are associated with high mortality rates. Thus, the discovery of novel antifungal drugs exhibiting an effect against these resistant fungi is crucial.
Venous thromboembolism in patients with cancer: design and rationale of a multicentre, prospective registry (Cancer-VTE Registry)
Authors: Ohashi Yasuo , Ikeda Masataka , Kunitoh Hideo , Sasako Mitsuru , Okusaka Takuji , Mukai Hirofumi , Fujiwara Keiichi , Nakamura Mashio , Kimura Tetsuya , Ibusuki Kei , Sakon Masato
Published: April 2023

Introduction

Patients with cancer are at higher risk of venous thromboembolism (VTE) than the general population as the malignancy itself and treatment modalities, including medication and surgery, contribute to the risk of developing VTE. Furthermore, patients with cancer developing VTE have a worse prognosis than those without cancer. There are no multicentre prospective data on the occurrence and treatment of VTE in patients with cancer in Japan, and data on the outcomes, complications and incidence of VTE in these patients have not been reported. In addition, Japanese patients with cancer are traditionally treated with unfractionated heparin or warfarin; however, the use of direct oral anticoagulants, which became available in 2014, has not been sufficiently examined in this patient group. Therefore, this multicentre, prospective registry has been designed to capture VTE data from Japanese patients presenting with six cancer types.

Methods and analysis

This registry will enrol 10 000 patients with colorectal, lung, stomach, breast, gynaecological (including endometrial, cervical, ovarian, fallopian tube and peritoneal) or pancreatic cancer between March 2017 and March 2019 and follow them for 1 year. We plan to collect data on the incidences of symptomatic VTE, bleeding events, stroke, systemic embolic events, incidental VTE requiring treatment in patients, overall survival and symptomatic VTE event-free survival.

Ethics and dissemination

All patients will provide written informed consent. Data will remain anonymous and will be collected using an online electronic data capture system. Study protocol, amendments and informed consent forms will be approved by the institutional review board/independent ethics committee at each site prior to study commencement. Results will be disseminated at national meetings and published in peer-reviewed journals.

Trial registration number

NCT000024942
DupuytrEn Treatment EffeCtiveness Trial (DETECT): a protocol for prospective, randomised, controlled, outcome assessor-blinded, three-armed parallel 1:1:1, multicentre trial comparing the effectiveness and cost of collagenase clostridium histolyticum, percutaneous needle fasciotomy and limited fasciectomy as short-term and long-term treatment strategies in Dupuytren’s contracture
Authors: Räisänen Mikko P. , Karjalainen Teemu , Göransson Harry , Reito Aleksi , Kautiainen Hannu , Malmivaara Antti , Leppänen Olli V.
Published: April 2023

Introduction

Dupuytren’s contracture (DC) is a chronic fibroproliferative disorder of the palmar fascia which leads to flexion contracture in one or more fingers. There is no definitive cure for DC, and treatment aims at relieving symptoms by releasing the contracture using percutaneous or operative techniques.

Methods and analysis

We planned a prospective, randomised, controlled, outcome assessor-blinded, three-armed parallel 1:1:1, multicentre trial comparing the effectiveness and cost of (1) collagenase clostridium histolyticum injection followed by limited fasciectomy in non-responsive cases, (2) percutaneous needle fasciotomy followed by limited fasciectomy in non-responsive cases and (3) primary limited fasciectomy during short-term and long-term follow-up for Tubiana I–III stages DC. We will recruit participants from seven national centres in Finland. Primary outcome is the rate of success in the treatment arm at 5 years after recruitment. Success is a composite outcome comprising (1) at least 50% contracture release from the date of recruitment and (2) participants in a patient-accepted symptom state (PASS). Secondary outcomes are (1) angle of contracture, (2) quick disabilities of the arm, a shoulder and hand outcome measure (QuickDASH), (3) perceived hand function, (4) EQ-5D-3L, (5) rate of major adverse events, (6) patient’s trust of the treatment, (7) global rating, (8) rate of PASS, (9) rate of minimal clinically important improvement, (10) expenses, (11) progression of disease, (12) progression-free survival, (13) favoured treatment modality, (14) patients achieving full contracture release and >50% improvement and (15) patient satisfaction with the treatment effect. Predictive factors for achieving the PASS will also be analysed.

Ethics and dissemination

The protocol was approved by the Tampere University Hospital Institutional Review Board and Finnish Medicine Agency. The study will be performed according to the principles of good clinical practice. The results of the trial will be disseminated as published articles in peer-reviewed journals.

Trial registration number

NCT03192020; Pre-results.
China Intracranial Aneurysm Project (CIAP): protocol for a prospective cohort study of interventional treatment and craniotomy for unruptured aneurysms
Authors: Chen Yunchang , Fan Haiyan , He Xuying , Guo Shenquan , Li Xifeng , He Min , Qu Yan , Yang Xinjian , Zhang Hongqi , Sun Xiaochuan , Wang Liqun , Wang Zhong , Tong Xiaoguang , Zhong Ming , Maimaitili Aisha , Tong Zhiyong , Duan Chuanzhi
Published: April 2023

Introduction

There are two approaches for the treatment of intracranial aneurysm (IA): interventional therapy and craniotomy, both of which have their advantages and disadvantages in terms of treatment efficacy. To avoid overtreatment of unruptured aneurysms (UIA), to save valuable medical resources and to reduce patient mortality and disability rate, it is vital that neurosurgeons select the most appropriate type of treatment to provide the best levels of care. In this study, we propose a refined, prospective, multicentre study for the Chinese population with strictly defined patient inclusion criteria, along with the selection of representative clinical participating centres.

Methods and analysis

This report describes a multicentre, prospective cohort study. As IA is extremely harmful if it ruptures, ethical issues need to be taken into account with regard to this study. Researchers are therefore not able to use randomised controlled trials. The study will be conducted by 12 clinical centres located in different regions of China. The trial recruitment programme begins in 2016 and is scheduled to be completed in 2020. We expect 1500 participants with UIA to be included. Clinical information relating to the participants will be recorded objectively. The primary endpoints are an evaluation of the safety and efficiency of interventional treatment and craniotomy for 6 months after surgery, with each participant completing at least 1 year of follow-up. The secondary endpoint is the evaluation of safety and efficacy of interventional therapy and craniotomy clipping when participants are treated for 12 months. We also address the success of treatment and the incidence of adverse events.

Ethics and dissemination

The research protocol and the informed consent form for participants in this study were approved by the Ethics Committee of Zhujiang Hospital of Southern Medical University (2017-SJWK-001). The results of this study are expected to be disseminated in peer-reviewed journals in 2021.

Trial registration number

NCT03133598.
Prospective, single UK centre, comparative study of the predictive values of contrast-enhanced ultrasound compared to time-resolved CT angiography in the detection and characterisation of endoleaks in high-risk patients undergoing endovascular aneurysm repair surveillance: a protocol
Authors: Roy Iain Nicholas , Chan Tze Yuan , Czanner Gabriela , Wallace Steve , Vallabhaneni Srinivasa Rao
Published: April 2023

Introduction

Diagnosis of endoleaks is imperative to prevent failure of endovascular aneurysm repairs (EVARs). The gold standard for diagnosis of endoleaks is catheter-directed subtraction angiography, which is not a practicable choice for surveillance. CT angiography (CTA) is the historical surveillance modality of choice. Concerns over cost, potential nephrotoxicity of contrast agents and repeated radiation exposure led to colour duplex ultrasound scan (CDUS) becoming an established alternative. CDUS has a lower sensitivity and specificity for endoleaks detection compared to CTA. Contrast-enhanced ultrasound scan (CEUS) represents an improvement of ultrasound imaging but comparisons against CTA report widely varying results, likely due to technical factors of CEUS and limitations of single-phase CTA.

The development of time-resolved CTA (tCTA) offers timing information that much more closely mirrors the dynamic information available from CEUS. Theoretically, these two imaging modalities have the best potential for diagnostic accuracy. The aim of this study will be to compare CEUS to tCTA and investigate the utility of other measurements available from tCTA.

Methods and analysis

This is a prospective, single UK centre, comparative study of paired binary diagnostic imaging modalities. Patients identified in routine post-EVAR surveillance as at risk of having a graft-related endoleak will undergo a CEUS and tCTA on the same day. This will allow the first comparison of CEUS to a semidynamic form of CTA. CEUS sensitivity and specificity to endoleak detection will be calculated.

Ethics and dissemination

The study has achieved ethical approval. We hope the results will define the diagnostic accuracy of CEUS in comparison to a semidynamic form of CTA, representing a methodological improvement from previous studies. Results will be submitted for presentation at national and international vascular surgeryandradiology meetings. The full results are planned to be published in a medical journal.

Trial registration number

NCT02688751
Does the age of acute care physicians impact their (1) crisis management performance and (2) learning after simulation-based education? A protocol for a multicentre prospective cohort study in Toronto and Ottawa, Canada
Authors: Alam Fahad , LeBlanc Vicki R , Baxter Alan , Tarshis Jordan , Piquette Dominique , Gu Yuqi , Filipkowska Caroline , Krywenky Ashley , Kester-Greene Nicole , Cardinal Pierre , Au Shelly , Lam Sandy , Boet Sylvain , Clinical Trials Group Perioperative Anesthesia
Published: April 2023

Introduction

The proportion of older acute care physicians (ACPs) has been steadily increasing. Ageing is associated with physiological changes and prospective research investigating how such age-related physiological changes affect clinical performance, including crisis resource management (CRM) skills, is lacking. There is a gap in the literature on whether physician’s age influences baseline CRM performance and also learning from simulation. We aim to investigate whether ageing is associated with baseline CRM skills of ACPs (emergency, critical care and anaesthesia) using simulated crisis scenarios and to assess whether ageing influences learning from simulation-based education.

Methods and analysis

This is a prospective cohort multicentre study recruiting ACPs from the Universities of Toronto and Ottawa, Canada. Each participant will manage an advanced cardiovascular life support crisis-simulated scenario (pretest) and then be debriefed on their CRM skills. They will then manage another simulated crisis scenario (immediate post-test). Three months after, participants will return to manage a third simulated crisis scenario (retention post-test). The relationship between biological age and chronological age will be assessed by measuring the participants CRM skills and their ability to learn from high-fidelity simulation.

Ethics and dissemination

This protocol was approved by Sunnybrook Health Sciences Centre Research Ethics Board (REB Number 140–2015) and the Ottawa Health Science Network Research Ethics Board (#20150173–01H). The results will be disseminated in a peer-reviewed journal and at scientific meetings.

Trial registration number

NCT02683447.
Protocol for a randomised trial of higher versus lower intensity patient–provider communication interventions to reduce antibiotic misuse in two paediatric ambulatory clinics in the USA
Authors: Goggin Kathy , Bradley-Ewing Andrea , Myers Angela L , Lee Brian R , Hurley Emily A , Delay Kirsten B , Schlachter Sarah , Ramphal Areli , Pina Kimberly , Yu David , Weltmer Kirsten , Linnemayr Sebastian , Butler Christopher C , Newland Jason G
Published: April 2023

Introduction

Children with acute respiratory tract infections (ARTIs) are prescribed up to 11.4 million unnecessary antibiotic prescriptions annually. Inadequate parent–provider communication is a chief contributor, yet efforts to reduce overprescribing have only indirectly targeted communication or been impractical. This paper describes our multisite, parallel group, cluster randomised trial comparing two feasible interventions for enhancing parent–provider communication on the rate of inappropriate antibiotic prescribing (primary outcome) and revisits, adverse drug reactions and parent-rated quality of shared decision-making, parent–provider communication and visit satisfaction (secondary outcomes).

Methods/analysis

We will attempt to recruit all eligible paediatricians and nurse practitioners (currently 47) at an academic children’s hospital and a private practice. Using a 1:1 randomisation, providers will be assigned to a higher intensity education and communication skills or lower intensity education-only intervention and trained accordingly. We will recruit 1600 eligible parent–child dyads. Parents of children ages 1–5 years who present with ARTI symptoms will be managed by providers trained in either the higher or lower intensity intervention. Before their consultation, all parents will complete a baseline survey and view a 90 s gain-framed antibiotic educational video. Parent–child dyads consulting with providers trained in the higher intensity intervention will, in addition, receive a gain-framed antibiotic educational brochure promoting cautious use of antibiotics and rate their interest in receiving an antibiotic which will be shared with their provider before the visit. All parents will complete a postconsultation survey and a 2-week follow-up phone survey. Due to the two-stage nested design (parents nested within providers and clinics), we will employ generalised linear mixed-effect regression models.

Ethics/dissemination

Ethical approval was obtained from the Children’s Mercy Hospital Pediatric Institutional Review Board (#16060466). Results will be submitted for publication in peer-reviewed journals.

Trial registration number

NCT03037112; Pre-results.
Stepped wedge cluster randomised controlled trial to assess the effectiveness of an optimisation strategy for general anaesthesia on postoperative morbidity and mortality in elderly patients (the OPTI-AGED study): a study protocol
Authors: Molliex Serge , Passot Sylvie , Futier Emmanuel , Bonnefoi Marlène , Rancon Florence , Lemanach Yannick , Pereira Bruno
Published: April 2023

Introduction

Elderly patients constitute an increasingly large proportion of the high-risk surgical group. In adult patients, several specific intraoperative approaches such as cardiac output-guided haemodynamic therapy, depth of anaesthesia monitoring (DAM) or lung-protective ventilation (LPV) are designed to reduce postoperative mortality and surgical complications. However, none of these approaches has been specifically performed in the elderly, and no evaluation of a multimodal optimisation strategy for general anaesthesia has been achieved in this population.

Aims

The objective of this study is to assess, in high-risk patients aged 75 years and over undergoing high-risk surgery, the effectiveness of combined optimisation of anaesthesia involving goal-directed haemodynamic therapy (GDHT), LPV and electroencephalographic DAM on postoperative morbidity and mortality. The primary outcome of the study is a composite criterion associating major postoperative complications and mortality occurring within the 30 first postoperative days. The secondary outcomes are 1-year postoperative autonomy and mortality.

Methods and analysis

This prospective, randomised, controlled, multicentre trial using a stepped wedge cluster design will be conducted in 27 French university centres. Patients aged 75 years and over, undergoing femoral head fractures and major intraperitoneal or vascular elective surgeries will be included after informed consent. They will benefit from usual care in the ‘control group’ and from a combined optimisation of general anaesthesia involving GDHT, LPV and DAM in the ‘optimisation group’. The cluster’s crossover will be unidirectional, from control to optimisation, and randomised. Data will be recorded at inclusion, the day of surgery, 7 days, 30 days and 1year postoperatively and collected into a hosted electronic case report form. The primary outcome of the study is a composite criterion associating major postoperative complications and mortality occurring within the 30 first postoperative days. The secondary outcomes are 1- year postoperative autonomy and mortality.

Ethics and dissemination

This protocol was approved by the ethics committee Sud-Est 1 and the French regulatory agency. The finding of the trial will be disseminated through peer-reviewed journals and conferences

Trial registration number

NCT02668250
Rationale and design for the detection and neurological impact of cerebrovascular events in non-cardiac surgery patients cohort evaluation (NeuroVISION) study: a prospective international cohort study
Authors: Mrkobrada Marko , Chan Matthew T V , Cowan David , Spence Jessica , Campbell Douglas , Wang Chew Yin , Torres David , Malaga German , Sanders Robert D , Brown Carl , Sigamani Alben , Szczeklik Wojciech , Dmytriw Adam Andrew , Agid Ronit , Smith Eric E , Hill Michael D , Sharma Manas , Sharma Mukul , Tsai Scott , Mensinkai Arun , Sahlas Demetrios J , Guyatt Gordon , Pettit Shirley , Copland Ingrid , Wu William K K , Yu Simon C H , Gin Tony , Loh Pui San , Ramli Norlisah , Siow Yee Lein , Short Timothy G , Waymouth Ellen , Kumar Jonathan , Dasgupta Monidipa , Murkin John M , Fuentes Maite , Ortiz-Soriano Victor , Lindroth Heidi , Simpson Sara , Sessler Daniel , Devereaux P J
Published: April 2023

Objectives

Covert stroke after non-cardiac surgery may have substantial impact on duration and quality of life. In non-surgical patients, covert stroke is more common than overt stroke and is associated with an increased risk of cognitive decline and dementia. Little is known about covert stroke after non-cardiac surgery.

NeuroVISION is a multicentre, international, prospective cohort study that will characterise the association between perioperative acute covert stroke and postoperative cognitive function.

Setting and participants

We are recruiting study participants from 12 tertiary care hospitals in 10 countries on 5 continents.

Participants

We are enrolling patients ≥65 years of age, requiring hospital admission after non-cardiac surgery, who have an anticipated length of hospital stay of at least 2 days after elective non-cardiac surgery that occurs under general or neuraxial anaesthesia.

Primary and secondary outcome measures

Patients are recruited before elective non-cardiac surgery, and their cognitive function is measured using the Montreal Cognitive Assessment (MoCA) instrument. After surgery, a brain MRI study is performed between postoperative days 2 and 9 to determine the presence of acute brain infarction. One year after surgery, the MoCA is used to assess postoperative cognitive function. Physicians and patients are blinded to the MRI study results until after the last patient follow-up visit to reduce outcome ascertainment bias.

We will undertake a multivariable logistic regression analysis in which the dependent variable is the change in cognitive function 1 year after surgery, and the independent variables are acute perioperative covert stroke as well as other clinical variables that are associated with cognitive dysfunction.

Conclusions

The NeuroVISION study will characterise the epidemiology of covert stroke and its clinical consequences. This will be the largest and the most comprehensive study of perioperative stroke after non-cardiac surgery.

Trial registration number

NCT01980511
Protocol for a phase II, open-label exploratory study investigating the efficacy of fesoterodine for treatment of adult patients with spinal cord injury suffering from neurogenic detrusor overactivity for amelioration of autonomic dysreflexia
Authors: Walter Matthias , Ramirez Andrea L , Lee Amanda HX , Rapoport Daniel , Kavanagh Alex , Krassioukov Andrei V
Published: April 2023

Introduction

Managing and preventing risk factors associated with cardiovascular and cerebrovascular impairment is well studied in able-bodied individuals. However, individuals with spinal cord injury (SCI) at or above the spinal segment T6 are prone to experience autonomic dysreflexia (AD) but also to suffer from neurogenic detrusor overactivity (NDO). Treatment of NDO would not only improve lower urinary tract function but could also reduce the severity and frequency of life-threatening episodes of AD. Fesoterodine, an antimuscarinic drug, has been successfully employed as a first-line treatment for detrusor overactivity in individuals without an underlying neurological disorder. Thus, our aim is to investigate the efficacy of fesoterodine to improve NDO and ameliorate AD in individuals with SCI.

Methods and analysis

This phase II, open-label exploratory, non-blinded, non-randomised, single-centre study will investigate the efficacy of fesoterodine to improve NDO and ameliorate AD in individuals with chronic SCI at or above T6. During screening, we will interview potential candidates (with a previous history of NDO and AD) and assess their injury severity. At baseline, we will perform cardiovascular and cerebrovascular monitoring (blood pressure (BP), heart rate and cerebral blood flow velocity) during urodynamics (UDS) and 24-hour ambulatory BP monitoring (ABPM) during daily life to assess severity and frequency of AD episodes (ie, maximum increase in systolic BP). The primary outcome is a reduction of artificially induced (during UDS) and spontaneous (during daily life) episodes of AD as a display of treatment efficacy. To answer this, we will repeat UDS and 24-hour ABPM during the last cycle of the treatment phase (12 weeks overall, ie, three cycles of 4 weeks each). At the end of each treatment cycle, participants will be asked to answer standardised questionnaires (AD symptoms and quality of life) and present bladder and bowel diaries, which will provide additional subjective information.

Ethics and dissemination

The University of British Columbia Research Ethics Boards (H15-02364), Vancouver Coastal Health Research Institute (V15-02364) and Health Canada (205857) approved this study. The findings of the study will be published in peer-reviewed journals and presented at national and international scientific meetings. This protocol adheres to the Standard Protocol Items: Recommendations for Interventional Trials and CONsolidated Standards Of Reporting Trials statements.

Trial registration number

NCT02676154; Pre-results.
Phase 3 diagnostic evaluation of a smart tablet serious game to identify autism in 760 children 3–5 years old in Sweden and the United Kingdom
Authors: Millar Lindsay , McConnachie Alex , Minnis Helen , Wilson Philip , Thompson Lucy , Anzulewicz Anna , Sobota Krzysztof , Rowe Philip , Gillberg Christopher , Delafield-Butt Jonathan
Published: April 2023

Introduction

Recent evidence suggests an underlying movement disruption may be a core component of autism spectrum disorder (ASD) and a new, accessible early biomarker. Mobile smart technologies such as iPads contain inertial movement and touch screen sensors capable of recording subsecond movement patterns during gameplay. A previous pilot study employed machine learning analysis of motor patterns recorded from children 3–5 years old. It identified those with ASD from age-matched and gender-matched controls with 93% accuracy, presenting an attractive assessment method suitable for use in the home, clinic or classroom.

Methods and analysis

This is a phase III prospective, diagnostic classification study designed according to the Standards for Reporting Diagnostic Accuracy Studies guidelines. Three cohorts are investigated: children typically developing (TD); children with a clinical diagnosis of ASD and children with a diagnosis of another neurodevelopmental disorder (OND) that is not ASD. The study will be completed in Glasgow, UK and Gothenburg, Sweden. The recruitment target is 760 children (280 TD, 280 ASD and 200 OND). Children play two games on the iPad then a third party data acquisition and analysis algorithm (Play.Care, Harimata) will classify the data as positively or negatively associated with ASD. The results are blind until data collection is complete, when the algorithm’s classification will be compared against medical diagnosis. Furthermore, parents of participants in the ASD and OND groups will complete three questionnaires: Strengths and Difficulties Questionnaire; Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations Questionnaire and the Adaptive Behavioural Assessment System-3 or Vineland Adaptive Behavior Scales-II. The primary outcome measure is sensitivity and specificity of Play.Care to differentiate ASD children from TD children. Secondary outcomes measures include the accuracy of Play.Care to differentiate ASD children from OND children.

Ethics and dissemination

This study was approved by the West of Scotland Research Ethics Service Committee 3 and the University of Strathclyde Ethics Committee. Results will be disseminated in peer-reviewed publications and at international scientific conferences.

Trial registration number

NCT03438994
Protocol for a double-blind, randomised, placebo-controlled pilot study for assessing the feasibility and efficacy of faecal microbiota transplant in a paediatric Crohn’s disease population: PediCRaFT Trial
Authors: Pai Nikhil , Popov Jelena , Hill Lee , Hartung Emily
Published: April 2023

Introduction

Crohn’s disease (CD) is a chronic inflammatory condition with transmural involvement of the gastrointestinal tract. Extraintestinal manifestations are common, and the disease burden on patients and the healthcare system is significant. While treatment options have expanded in recent years, they have mainly focused on dampening the immune response, thus carrying notable risks associated with long-term immunosuppression. Faecal microbiota transplant (FMT) targets inflammatory bowel disease (IBD) by modifying intestinal dysbiosis. Limited adult and paediatric data have demonstrated a favourable response to FMT in IBD; however, no randomised controlled trial has yet been published in paediatrics. This double-blind, randomised, placebo-controlled pilot study will assess feasibility and efficacy outcomes of FMT in a paediatric CD population.

Methods and analysis

Forty-five patients between the ages of 3 and 17 years, with established CD or IBD unclassified, will be enrolled 2:1 to undergo FMT intervention or placebo control. Participants will undergo a colonoscopic infusion to the terminal ileum at baseline, followed by oral capsules two times per week for 6 weeks. Outcomes will be measured throughout the intervention period and 18 weeks of subsequent follow-up. Primary outcomes will assess feasibility, including patient recruitment, sample collection and rates of adverse events. Secondary outcomes will address clinical efficacy, including change in clinical response, change in urine metabolome and change in microbiome.

Ethics and dissemination

Ethics approval from the local hospital research ethics board was obtained at the primary site (McMaster Children’s Hospital, Hamilton), with ethics pending at the secondary site (Centre Hospitalier Universitaire-Sainte-Justine, Montréal). RBX7455 and RBX2660 are human donor-sourced, microbiota-based therapeutic formulations. Both RBX7455 and RBX2660 are currently undergoing clinical trials to support potential US Food and Drug Administration approval. Approval to conduct this paediatric clinical trial was obtained from Health Canada’s Biologics and Genetic Therapies Directorate. The results of this trial will be published in peer-reviewed journals and will help inform a large, multicentre trial in the future.

Trial registration number

NCT03378167; pre-results.
Study protocol for an investigation of the effectiveness of the pain toolkit for people with low back pain: double-blind randomised controlled trial
Authors: Findley Gillian , Ryan Cormac , Cartwright Amy , Martin Denis
Published: April 2023

Introduction

The Pain Toolkit is a self-management tool for people with persistent pain. It is available for use worldwide in multiple formats. To date, no studies have investigated the effectiveness of this intervention. This study aims to investigate the effectiveness of the Pain Toolkit in comparison with a simple education control for people with low back pain.

Methods and analysis

Participants who have been discharged from the North of England Regional Back Pain Pathway will be randomised using sealed, consecutively numbered opaque envelopes to receive either the Pain Toolkit and the Back Book (intervention group) or the Back Book only (control group). Both the therapist and the participant will be blind to group allocation. The primary outcome measure will be disability (Oswestry Disability Index (ODI)). Secondary outcome measures will be pain (0–10 numerical scale), healthcare use (number of healthcare professional visits) and quality of life (EuroQol-5D). Outcome measures will be completed at baseline and at 6 and 12 months. Data will be analysed using analysis of covariance, adjusting for baseline values. A change of 10 points in the ODI will be considered a clinically important change. Additionally, a subsample of participants from the intervention group will undergo semistructured interviews to explore individuals’ experience of the Pain Toolkit. Participants will be asked questions about the ease of use and acceptability of the Pain Toolkit and also for how long they used the Toolkit. The qualitative data will be analysed using thematic analysis.

Ethics and dissemination

Approval for the study was given by the Health Research Authority and the North East Newcastle, North Tyneside 2 Regional Ethics Committee (reference 18/NE/0144) and Teesside University (reference 176/17). Findings will be disseminated through peer-reviewed journals and presentation at relevant patient groups, and local, national and international conferences.

Trial registration number

NCT03791164.
Efficacy of a mindful-eating programme to reduce emotional eating in patients suffering from overweight or obesity in primary care settings: a cluster-randomised trial protocol
Authors: Morillo Sarto Hector , Barcelo-Soler Alberto , Herrera-Mercadal Paola , Pantilie Bianca , Navarro-Gil Mayte , Garcia-Campayo Javier , Montero-Marin Jesus
Published: April 2023

Introduction

Little is known about the applicability of mindfulness-based interventions in Spanish adults with overweight/obesity. The objective of the present study protocol is to describe the methods that will be used in a cluster randomised trial (CRT) that aims to evaluate the effectiveness of a mindfulness eating (ME) programme to reduce emotional eating (EE) in adults with overweight/obesity in primary care (PC) settings.

Methods and analysis

A CRT will be conducted with approximately 76 adults with overweight/obesity from four PC health centres (clusters) in the city of Zaragoza, Spain. Health centres matched to the average per capita income of the assigned population will be randomly allocated into two groups: ‘ME +treatment as usual (TAU)’ and ‘TAU alone’. The ME programme will be composed of seven sessions delivered by a clinical psychologist, and TAU will be offered by general practitioners. The primary outcome will be EE measured by the Dutch Eating Behaviour Questionnaire (DEBQ) at post test as primary endpoint. Other outcomes will be external and restrained eating (DEBQ), binge eating (Bulimic Investigatory Test Edinburgh), eating disorder (Eating Attitude Test), anxiety (General Anxiety Disorder-7), depression (Patient Health Questionnaire-9), mindful eating (Mindful Eating Scale), dispositional mindfulness (Five Facet Mindfulness Questionnaire) and self-compassion (Self-Compassion Scale). Anthropometric measures, vital signs and blood tests will be taken. A primary intention-to-treat analysis on EE will be conducted using linear mixed models. Supplementary analyses will include secondary outcomes and 1-year follow-up measures; adjusted models controlling for sex, weight status and levels of anxiety and depression; the complier average causal effect of treatment; and the clinical significance of improvements.

Ethics and dissemination

Positive results of this study may have a significant impact on one of the most important current health-related problems. Approval was obtained from the Ethics Committee of the Regional Authority. The results will be submitted to peer-reviewed journals, and reports will be sent to participants.

Trial registration number

NCT03927534(5/2019).
Chinese multicentre prospective registry of breast cancer patient-reported outcome-reconstruction and oncoplastic cohort (PRO-ROC): a study protocol
Authors: Li Lun , Yang Benlong , Li Hongyuan , Yin Jian , Jin Feng , Han Siyuan , Liao Ning , Shi Jingping , Ling Rui , Li Zan , Ouyang Lizhi , Wang Xiang , Fu Peifen , Ouyang Zhong , Ma Binlin , Wu Xinhong , Wang Haibo , Liu Jian , Shao Zhimin , Wu Jiong
Published: April 2023

Introduction

Available patient-reported outcome (PRO) studies are mainly from single institution or of small sample size, and the variations across hospitals and regions were not fully analysed. A multicentre, prospective, patient-reported outcome-reconstruction and oncoplastic cohort (PRO-ROC) will be planned to assess the PROs of Chinese patients with breast cancer who will undergo breast reconstruction (BR) or oncoplastic breast-conserving surgery (OBCS).

Methods and analysis

The inclusion criteria are female patients with breast cancer aged >18 years old who will undergo BR or OBCS. This cohort will include at least 10 000 consecutive patients (about 5000 patients who will undergo BR and 5000 patients who will undergo OBCS). The exposures were surgery types: BR and OBCS regardless of the techniques and materials used. The primary endpoint will be PROs, which include BREAST-Q and quality of life (European Organisation for Research and Treatment (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and EORTC QoL Breast Cancer-specific version (QLQ-BR23)). All patients will be followed up to 24 months after operations. All data will be prospectively collected using an app software. Data will be analysed using SPSS and Stata software.

Ethics and dissemination

This study follows the Helsinki Declaration. All patients will be asked to sign an informed consent before enrolment. The results of this study will be presented at national and international meetings and published in a scientific peer-reviewed journal.

Trial registration number

NCT04030845.
Protocol for the feasibility and acceptability of a brief routine weight management intervention for postnatal women embedded within the national child immunisation programme: randomised controlled cluster feasibility trial with nested qualitative study (PIMMS-WL)
Authors: Parretti Helen M , Ives Natalie J , Tearne Sarah , Vince Alexandra , Greenfield Sheila M , Jolly Kate , Jebb Susan A , Frew Emma , Yardley Lucy , Little Paul , Pritchett Ruth V , Daley Amanda
Published: April 2023

Introduction

On average women retain 5 to 9 kg 1 year after giving birth which can increase the risk of later obesity and chronic diseases. Some previous trials in this population have been effective in reducing weight, but are too intensive and costly to deliver at scale. There is a need for low-cost interventions to facilitate weight loss in this population.

Methods and analysis

The primary aim is to assess the feasibility of delivering a weight management intervention for overweight/obese postnatal women within child immunisation appointments. We will conduct a randomised controlled cluster feasibility trial with a nested qualitative study to assess study recruitment and acceptability of the intervention. General practitioner practice (cluster) will be the unit of randomisation, with practices randomised to offer usual care plus the intervention or usual care only. Eighty women will be recruited. The intervention group will be offered brief support that encourages self-management of weight when attending child immunisation appointments. Practice nurses will encourage women to weigh themselves weekly and record this, and to make healthy lifestyle choices through using an online weight management programme. Women will be advised to aim for 0.5 to 1 kg/week weight loss. At each child immunisation the nurse will assess progress by weighing women. The comparator group will receive a healthy lifestyle leaflet. Data on weight, body fat, depression, anxiety, body image, eating behaviours and physical activity will be collected at baseline and follow-up. Women and nurses will be interviewed to ascertain their views about the intervention. The decision to proceed to the phase III trial will be based on prespecified stop-go criteria.

Ethics and dissemination

Data will be stored securely at the University of Birmingham. Results will be disseminated through academic publications and presentations and will inform a possible phase III trial. The National Research Ethics Committee approved the study protocol.

Trial registration number

NCT12209332
Randomised controlled trial comparing hydroxyapatite coated uncemented hemiarthroplasty with cemented hemiarthroplasty for the treatment of displaced intracapsular hip fractures: a protocol for the WHITE 5 study
Authors: Fernandez Miguel Antonio , Achten Juul , Lerner Robin Gillmore , Mironov Katy , Parsons Nicholas , Dritsaki Melina , Png May E , McGibbon Alwin , Gould Jenny , Griffin Xavier , Costa Matthew L
Published: April 2023

Introduction

Hip fracture is a serious injury in adults, especially those aged over 60 years. The most common type of hip fracture (displaced intracapsular) is treated for the majority of patients with a partial hip replacement (hemiarthroplasty). The hemiarthroplasty implant can be fixed to the bone with or without bone cement. Cement is the current recommended technique but recently some risks have been identified, which could potentially be avoided by using uncemented implants. Controversy, therefore, remains about which type of hemiarthroplasty offers patients the best outcomes.

This is the protocol for a multicentre randomised controlled trial comparing cemented hemiarthroplasty versus uncemented hemiarthroplasty for patients 60 years and over with a displaced intracapsular hip fracture.

Methods and analysis

Multicentre (a minimum of seven UK hospitals), multisurgeon, parallel group, two-arm, superiority, randomised controlled trial. Patients aged 60 years and older with a displaced intracapsular hip fracture treated with hemiarthroplasty surgery are eligible. Participants will be randomly allocated on a 1:1 basis to either a cemented hemiarthroplasty or a modern hydroxyapatite coated uncemented hemiarthroplasty. Otherwise all care will be in accordance with the National Institute for Health and Care Excellence guidance. A minimum of 1128 patients will be recruited to obtain 90% power to detect a 0.075-point difference in the primary endpoint: health-related quality of life (EuroQol 5 dimensions 5 levels) at 4 months postinjury. The treatment effect will be estimated using a two-sided t-test adjusted for age, gender and cognitive impairment based on an intention-to-treat analysis. Secondary outcomes include mortality, complications including revision surgery and cause, mobility status, residential status, health-related quality of life at 1 and 12 months and health resource use. A within-trial economic analysis will be conducted.

Ethics, dissemination and funding

Wales Research Ethics Committee 5 approved the feasibility phase on 2 December 2016 (16/WA/0351) and the definitive trial on 22 November 2017 (17/WA/0383). This study is sponsored by the University of Oxford and funded by the National Institute for Health Research, Research for Patient Benefit (PB-PG-0215–36043 and PB-PG-1216–20021). A manuscript for a peer-reviewed journal will be prepared and the results shared with patients via local mechanisms at participating centres.

Trial registration number

NCT18393176
The Ohio State University Early Psychosis Intervention Center (EPICENTER) step-based care programme for individuals at clinical high risk for psychosis: study protocol for an observational study
Authors: Breitborde Nicholas J K , Guirgis Hossam , Stearns Walter , Carpenter Kristen M , Lteif Ghada , Pine Jacob G , Storey Nichole , Wastler Heather , Moe Aubrey M
Published: April 2023

Introduction

In October 2018, the Substance Abuse and Mental Health Services Administration funded 21 sites throughout the USA to develop, implement and evaluate specialised care programmes for individuals at clinical high risk for developing a psychotic disorder (CHR-P). Per the funding requirements, such programmes were required to provide ‘step-based care’—a model in which individuals are initially provided with low-intensity, non-psychosis-specific and more benign (ie, least side effects) interventions and only progress onto higher-intensity, psychosis-specific interventions with a greater risk of more severe side effects should they not meet a priori criteria for clinical response to such lower-intensity interventions. Here, we outline the evaluation component of the step-based care programme for individuals at CHR-P at The Ohio State University Early Psychosis Intervention Center (EPICENTER).

Methods and analyses

The EPICENTER CHR-P programme provides a step-based care model comprising psychotherapy, medication management, family support/education, peer support and vocational/educational support. All participants who opt to receive care at the EPICENTER will complete a standardised assessment battery as part of usual care. This battery will be administered on enrolment and will be re-administered at 6-month intervals throughout individuals’ participation in EPICENTER clinical services. Participants will have the opportunity to allow for data from these usual care assessments to be used as part of an evaluation project for this new clinical service. The primary outcome for this evaluation project is time to remission of symptomatic and functional deficits commonly experienced by individuals at CHR-P. Participants will also have the opportunity to participate in a supplemental research project designed to further evaluate treatment outcomes and patient characteristics among individuals participating in EPICENTER clinical services.

Ethics and dissemination

This project was approved by The Ohio State University Institutional Review Board. Results from this project will be disseminated through publications and presentations.

Trial registration number

NCT03970005.