bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of 6 months of hybrid closed-loop insulin delivery in adults with type 1 diabetes: a randomised controlled trial protocol
Authors: McAuley Sybil A , de Bock Martin I , Sundararajan Vijaya , Lee Melissa H , Paldus Barbora , Ambler Geoff R , Bach Leon A , Burt Morton G , Cameron Fergus J , Clarke Philip M , Cohen Neale D , Colman Peter G , Davis Elizabeth A , Fairchild Jan M , Hendrieckx Christel , Holmes-Walker D Jane , Horsburgh Jodie C , Jenkins Alicia J , Kaye Joey , Keech Anthony C , King Bruce R , Kumareswaran Kavita , MacIsaac Richard J , McCallum Roland W , Nicholas Jennifer A , Sims Catriona , Speight Jane , Stranks Stephen N , Trawley Steven , Ward Glenn M , Vogrin Sara , Jones Timothy W , O’Neal David N
Published: April 2023

Introduction

Manual determination of insulin dosing largely fails to optimise glucose control in type 1 diabetes. Automated insulin delivery via closed-loop systems has improved glucose control in short-term studies. The objective of the present study is to determine the effectiveness of 6 months’ closed-loop compared with manually determined insulin dosing on time-in-target glucose range in adults with type 1 diabetes.

Methods and analysis

This open-label, seven-centre, randomised controlled parallel group clinical trial will compare home-based hybrid closed-loop versus standard diabetes therapy in Australia. Adults aged ≥25 years with type 1 diabetes using intensive insulin therapy (via multiple daily injections or insulin pump, total enrolment target n=120) will undertake a run-in period including diabetes and carbohydrate-counting education, clinical optimisation and baseline data collection. Participants will then be randomised 1:1 either to 26 weeks of MiniMed 670G hybrid closed-loop system therapy (Medtronic, Northridge, CA, USA) or continuation of their current diabetes therapy. The hybrid closed-loop system delivers insulin automatically to address basal requirements and correct to target glucose level, while bolus doses for meals require user initiation and carbohydrate estimation. Analysis will be intention to treat, with the primary outcome time in continuous glucose monitoring (CGM) target range (3.9–10.0 mmol/L) during the final 3 weeks of intervention. Secondary outcomes include: other CGM parameters, HbA1c, severe hypoglycaemia, psychosocial well-being, sleep, cognition, electrocardiography, costs, quality of life, biomarkers of vascular health and hybrid closed-loop system performance. Semistructured interviews will assess the expectations and experiences of a subgroup of hybrid closed-loop users.

Ethics and dissemination

The study has Human Research Ethics Committee approval. The study will be conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Results will be disseminated at scientific conferences and via peer-reviewed publications.

Trial registration number

NCT12617000520336.
A Reduction in Time with Electronic Monitoring In Stroke (ARTEMIS): study protocol for a randomised multicentre trial
Authors: Koster Gaia T , Nguyen T Truc My , Groot Adrien E D , Coutinho Jonathan M , Bosch Jan , den Hertog Heleen M , van Walderveen Marianne A A , Algra Ale , Wermer Marieke J H , Roos Yvo B , Kruyt Nyika D
Published: April 2023

Introduction

Time is the most crucial factor limiting efficacy of intravenous thrombolysis (IVT) and intra-arterial thrombectomy (IAT). The delay between alarming the Emergency Medical Services (EMS) dispatch office and IVT/IAT initiation, that is, the‘total system delay’(TSD), depends on logistics and team effort. A promising method to reduce TSD is real-time audio-visual feedback to caregivers involved. With ‘A Reduction in Time with Electronic Monitoring in Stroke’ (ARTEMIS), we aim to investigate the effect of real-time audio-visual feedback on actual TSD to IVT/IAT to caregivers.

Methods and analysis

ARTEMIS is a multiregional, multicentre, randomised open end-point trial including patients ≥18 years considered IVT/IAT-eligible by the EMS dispatch office or on-site EMS personnel. Patients are electronically tracked and randomised for real-time audio-visual feedback on TSD to caregivers via premounted handhelds and tablets throughout the TSD trajectory. Primary outcome is TSD to IVT/IAT. Secondary outcomes comprise proportion of IVT/IAT-treated patients, symptomatic intracerebral haemorrhage, IVT/IAT-treated stroke mimics, clinical outcome after three months and cost-effectiveness. Separate analyses for IAT-patients with or without prior IVT, within or out of office hours and EMS region will be performed. With 75 IAT-patients and 225 IVT-patients in each arm, we will be able to demonstrate a 20 min difference in TSD to IAT and a 10 min difference in TSD to IVT (p=0.05 and power=0.8).

Ethics and dissemination

Study findings will be disseminated through peer-reviewed journals and (inter)national conference presentations.

Trial registration number

NCT02808806
Impact of body weight, low energy diet and gastric bypass on drug bioavailability, cardiovascular risk factors and metabolic biomarkers: protocol for an open, non-randomised, three-armed single centre study (COCKTAIL)
Authors: Hjelmesæth Jøran , Åsberg Anders , Andersson Shalini , Sandbu Rune , Robertsen Ida , Johnson Line Kristin , Angeles Philip Carlo , Hertel Jens Kristoffer , Skovlund Eva , Heijer Maria , Ek Anna-Lena , Krogstad Veronica , Karlsen Tor-Ivar , Christensen Hege , Andersson Tommy B , Karlsson Cecilia
Published: April 2023

Introduction

Roux-en-Y gastric bypass (GBP) is associated with changes in cardiometabolic risk factors and bioavailability of drugs, but whether these changes are induced by calorie restriction, the weight loss or surgery per se, remains uncertain. The COCKTAIL study was designed to disentangle the short-term (6 weeks) metabolic and pharmacokinetic effects of GBP and a very low energy diet (VLED) by inducing a similar weight loss in the two groups.

Methods and analysis

This open, non-randomised, three-armed, single-centre study is performed at a tertiary care centre in Norway. It aims to compare the short-term (6 weeks) and long-term (2 years) effects of GBP and VLED on, first, bioavailability and pharmacokinetics (24 hours) of probe drugs and biomarkers and, second, their effects on metabolism, cardiometabolic risk factors and biomarkers. The primary outcomes will be measured as changes in: (1) all six probe drugs by absolute bioavailability area under the curve (AUCoral/AUCiv) of midazolam (CYP3A4 probe), systemic exposure (AUCoral) of digoxin and rosuvastatin and drug:metabolite ratios for omeprazole, losartan and caffeine, levels of endogenous CYP3A biomarkers and genotypic variation, changes in the expression and activity data of the drug-metabolising, drug transport and drug regulatory proteins in biopsies from various organs and (2) body composition, cardiometabolic risk factors and metabolic biomarkers.

Ethics and dissemination

The COCKTAIL protocol was reviewed and approved by the Regional Committee for Medical and Health Research Ethics (Ref: 2013/2379/REK sørøst A). The results will be disseminated to academic and health professional audiences and the public via presentations at conferences, publications in peer-reviewed journals and press releases and provided to all participants.

Trial registration number

NCT02386917.
Using mobile health technology and community health workers to identify and refer caesarean-related surgical site infections in rural Rwanda: a randomised controlled trial protocol
Authors: Sonderman Kristin A , Nkurunziza Theoneste , Kateera Fredrick , Gruendl Magdalena , Koch Rachel , Gaju Erick , Habiyakare Caste , Matousek Alexi , Nahimana Evrard , Ntakiyiruta Georges , Riviello Robert , Hedt-Gauthier Bethany L
Published: April 2023

Introduction

Surgical site infections (SSIs) are a significant cause of morbidity and mortality in low-income and middle-income countries, where rates of SSIs can reach 30%. Due to limited access, there is minimal follow-up postoperatively. Community health workers (CHWs) have not yet been used for surgical patients in most settings. Advancements in telecommunication create an opportunity for mobile health (mHealth) tools to support CHWs. We aim to evaluate the use of mHealth technology to aid CHWs in identification of SSIs and promote referral of patients back to healthcare facilities.

Methods and analysis

Prospective randomised controlled trial conducted at Kirehe District Hospital, Rwanda, from November 2017 to November 2018. Patients ≥18 years who undergo caesarean section are eligible. Non-residents of Kirehe District or patients who remain in hospital >10 days postoperatively will be excluded. Patients will be randomised to one of three arms. For arm 1, a CHW will visit the patient’s home on postoperative day 10 (±3 days) to administer an SSI screening protocol (fever, pain or purulent drainage) using an electronic tablet. For arm 2, the CHW will administer the screening protocol over the phone. For both arms 1 and 2, the CHW will refer patients who respond ‘yes’ to any of the questions to a health facility. For arm 3, patients will not receive follow-up care. Our primary outcome will be the impact of the mHealth-CHW intervention on the rate of return to care for patients with an SSI.

Ethics and dissemination

The study has received ethical approval from the Rwandan National Ethics Committee and Partners Healthcare. Results will be disseminated to Kirehe District Hospital, Rwanda Ministry of Health, Rwanda Surgical Society, Partners In Health, through conferences and peer-reviewed publications.

Trial registration number

NCT03311399.
Treatment options in idiopathic subglottic stenosis: protocol for a prospective international multicentre pragmatic trial
Authors: Gelbard Alexander , Shyr Yu , Berry Lynne , Hillel Alexander T , Ekbom Dale C , Edell Eric S , Kasperbauer Jan L , Lott David G , Donovan Donald T , Garrett C. Gaelyn , Sandhu Guri , Daniero James J , Netterville James L , Schindler Josh S , Smith Marshall E , Bryson Paul C , Lorenz Robert R , Francis David O
Published: April 2023

Introduction

Idiopathic subglottic stenosis (iSGS) is an unexplained progressive obstruction of the upper airway that occurs almost exclusively in adult, Caucasian women. The disease is characterised by mucosal inflammation and localised fibrosis resulting in life-threatening blockage of the upper airway. Because of high recurrence rates, patients with iSGS will frequently require multiple procedures following their initial diagnosis. Both the disease and its therapies profoundly affect patients’ ability to breathe, communicate and swallow. A variety of treatments have been advanced to manage this condition. However, comparative data on effectiveness and side effects of the unique approaches have never been systematically evaluated. This study will create an international, multi-institutional prospective cohort of patients with iSGS. It will compare three surgical approaches to determine how well the most commonly used treatments in iSGS ‘work’ and what quality of life (QOL) trade-offs are associated with each approach.

Methods and analysis

A prospective pragmatic trial comparing the ‘Standard of Care’ for iSGS at multiple international institutions. Patients with a diagnosis of iSGS without clinical or laboratory evidence of vasculitis or a history of endotracheal intubation 2 years prior to symptom onset will be included in the study. Prospective evaluation of disease recurrence requiring operative intervention, validated patient-reported outcome (PRO) measures as well as patient-generated health data (mobile peak flow recordings and daily steps taken) will be longitudinally tracked for 36 months. The primary endpoint is treatment effectiveness defined as time to recurrent operative procedure. Secondary endpoints relate to treatment side effects and include PRO measures in voice, swallowing, breathing and global QOL as well as patient-generated health data.

Ethics and dissemination

This protocol was approved by the local IRB Committee of the Vanderbilt University Medical Center in July 2015. The findings of the trial will be disseminated through peer-reviewed journals, national and international conference presentations and directly to patient with iSGS via social media-based support groups.

Trial registration number

NCT02481817.
Rationale and design of a Scale-Up Project Evaluating Responsiveness to Home Exercise And Lifestyle Tele-Health (SUPER-HEALTH) in people with physical/mobility disabilities: a type 1 hybrid design effectiveness trial
Authors: Rimmer James H , Mehta Tapan , Wilroy Jereme , Lai Byron , Young Hui-Ju , Kim Yumi , Pekmezi Dorothy , Thirumalai Mohanraj
Published: April 2023

Introduction

Rates of physical inactivity among people with physical disabilities are substantially higher than in the general population and access to home-based tailored exercise programmes is almost non-existent. Using a theory-driven eHealth platform, an innovative exercise programme referred to as movement-to-music (M2M) will be delivered as a customised, home-based exercise intervention for adults with mobility disabilities.

Methods and analysis

Participants are being recruited for this type 1 hybrid design based effectiveness trial through outpatient clinics at a large rehabilitation centre and randomised to one of three groups: (1) M2M, (2) M2M plus social networking (M2Mplus) and (3) attention control (AC). The intervention includes a 12-week adoption phase, 12-week transition phase and 24-week maintenance phase, at which the collection of objective measures on exercise, fitness and self-reported measures on health will be obtained at the start of each phase and at follow-up. The study compares the effectiveness of M2M and M2Mplusin increasing physical activity (primary outcome), adherence, fitness and physical functioning compared with the AC group and examines the mediators and moderators of the treatment effect.

Ethics and dissemination

The Institutional Review Board of The University of Alabama at Birmingham granted full approval: (IRB-160923002). Dissemination of findings will include publication in peer-reviewed journals, presentations at regional, national and/or international meetings, and the National Center on Health, Physical Activity and Disability (NCHPAD,www.nchpad.org). This study will strengthen our understanding of the potential benefits of eHealth exercise interventions for people with physical disabilities and build on strategies that aim to recruit larger samples in exercise trials.

Trial registration number

NCT03024320; Pre-results.
Heart failure with preserved ejection fraction (HFpEF) pathophysiology study (IDENTIFY-HF): does increased arterial stiffness associate with HFpEF, in addition to ageing and vascular effects of comorbidities? Rationale and design
Authors: Ali Danish , Callan Nualla , Ennis Stuart , Powell Richard , McGuire Scott , McGregor Gordon , Weickert Martin O , Miller Michelle A , Cappuccio Francesco P , Banerjee Prithwish
Published: April 2023

Aims

There has been a paradigm shift proposing that comorbidities are a major contributor towards the heart failure with preserved ejection fraction (HFpEF) syndrome. Furthermore, HFpEF patients have abnormal macrovascular and microvascular function, which may significantly contribute towards altered ventricular-vascular coupling in these patients. The IDENTIFY-HF study will investigate whether gradually increased arterial stiffness (in addition to ageing) as a result of increasing common comorbidities, such as hypertension and diabetes, is associated with HFpEF.

Methods and analysis

In our observational study, arterial compliance and microvascular function will be assessed in five groups (Groups A to E) of age, sex and body mass index matched subjects (age ≥70 years in all groups):

Group A; normal healthy volunteers without major comorbidities such as hypertension and diabetes mellitus (control). Group B; patients with hypertension without diabetes mellitus or heart failure (HF). Group C; patients with hypertension and diabetes mellitus without HF. Group D; patients with HFpEF. Group E; patients with heart failure and reduced ejection fraction (parallel group). Vascular function and arterial compliance will be assessed using pulse wave velocity, as the primary outcome measure. Further outcome measures include cutaneous laser Doppler flowmetry as a measure of endothelial function, transthoracic echocardiography and exercise tolerance measures. Biomarkers include NT-proBNP, high-sensitivity troponin T, as well as serum galectin-3 as a marker of fibrosis.

Ethics and dissemination

The study was approved by the regional research ethics committee (REC), West Midland and Black Country 17/WM/0039, UK, and permission to conduct the study in the hospital was also obtained from the RDI, UHCW NHS Trust. The results will be published in peer-reviewed journals and presented in local, national and international medical society meetings.

Trial registration number

NCT03186833
Evaluation of the ‘Colli-Pee’, a first-void urine collection device for self-sampling at home for the detection of sexually transmitted infections, versus a routine clinic-based urine collection in a one-to-one comparison study design: efficacy and acceptability among MSM in Belgium
Authors: De Baetselier Irith , Smet Hilde , Abdellati Said , De Deken Bénédicte , Cuylaerts Vicky , Reyniers Thijs , Vuylsteke Bea , Crucitti Tania
Published: April 2023

Objectives

Pre-exposure prophylaxis (PrEP) users are screened bi-annual for sexually transmitted infections (STIs). A novel device, called the Colli-Pee, collects first-void urine in a standardised way and the collector tube can be easily delivered by regular post to a certified laboratory. The aim of the study was a one-to-one comparison between the STI test results obtained with the urine collected in the clinic, versus urine collected at home in a real-life setting by Men who have Sex with Men (MSM) in Belgium. The user-friendliness and acceptability of the Colli-Pee device by the users was also evaluated.

Design

A single-site nested substudy in a prospective PrEP demonstration project (Be-PrEP-ared) among MSM in Belgium.

Participants

A total of 473 home-based samples from 213 MSM were received with a mean age of 38.5 years.

Interventions

Participants were requested to collect a urine sample at home using the Colli-Pee device and to send it to the laboratory via regular mail.

Primary and secondary outcome measures

The presence ofChlamydia trachomatis(CT), Neisseria gonorrhoeae(NG), Mycoplasma genitalium(MG) andTrichomonas vaginalis(TV) was determined using molecular amplification assays. Agreement between test results of samples collected at the clinic and collected at home were evaluated using Cohen’s kappa statistic.

Results: TV was not detected. A very good to almost perfect agreement was found for CT, NG and MG of κ=0.75, 0.87 and 0.85, respectively. Using the Colli-Pee device only one low positive CT and two MG infections were missed, however, three additional CT, two NG and six MG infections were detected.

Conclusions

The Colli-Pee device is a feasible and convenient way to collect urine at home for STI testing. This may be particularly relevant for populations that need frequent STI testing, such as PrEP users and patients who prefer home-sampling.

Trial registration number

NCT02552914; Pre-results.
Evaluation of a personalised adherence intervention to improve photoprotection in adults with Xeroderma Pigmentosum (XP): protocol for the trial of XPAND
Authors: Walburn Jessica , Norton Sam , Sarkany Robert , Sainsbury Kirby , Araújo-Soares Vera , Morgan Myfanwy , Canfield Martha , Foster Lesley , Heydenreich Jakob , McCrone Paul , Mander Adrian , Sniehotta Falko F , Wulf Hans Christian , Weinman John
Published: April 2023

Introduction

Poor adherence to photoprotection for people with xeroderma pigmentosum (XP) can be life-threatening. A randomised controlled trial (RCT) is being conducted to test the efficacy of a personalised adherence intervention (XPAND) to reduce the level of ultraviolet radiation (UVR) reaching the face, by improving photoprotection activities in adults with XP.

Methods and analysis

A two-armed parallel groups RCT, where we randomised 24 patients with suboptimal adherence to either an intervention group who received XPAND in 2018 or a delayed intervention group who will receive XPAND in 2019. XPAND involves seven sessions, one-to-one with a facilitator, using behaviour change techniques and specially designed materials to target barriers to photoprotection. Following baseline assessment in April 2018 (t0) and intervention, the primary outcome will be measured across 21 consecutive days in June and July 2018 (t1). The primary outcome is the average daily UVR dose to the face (D-to-F), calculated by combining objective UVR exposure at the wrist (measured by a dosimeter) with face photoprotection activities recorded on a daily UVR protection diary. Secondary outcomes include average daily UVR D-to-F across 21 days in August (t2); psychosocial process variables measured by daily questions (t0, t1, t2) and self-report questionnaires (t0, t1, t2, December 2018 (t3)). Intervention cost-utility is assessed by service use and personal cost questionnaires (t0, t3). The delayed intervention control arm participants will complete three further assessments in April 2019 (t4) and June–July 2019 (t5), and December 2019 (t6) with dosimetry and UVR protection diary completed for 21 days at t4 and t5. A process evaluation will be conducted using mixed methods.

Ethics and dissemination

Ethical approval has been received from West London & GTAC REC 17/LO/2110. Results will be disseminated in peer-reviewed journals and at conferences. This study tests a novel intervention, which, if successful, will be integrated into routine care.

Trial registration number

NCT03445052
A Randomised Trial Examining Cardiovascular Morbidity and All-Cause Mortality 24 years Following General Health Checks: the Ebeltoft Health Promotion Project (EHPP)
Authors: Bernstorff Martin , Deichgræber Pia , Bruun Niels Henrik , Dalsgaard Else-Marie , Fenger-Grøn Morten , Lauritzen Torsten
Published: April 2023

Introduction

Global prevalence of risk factors for cardiovascular disease (CVD) and all-cause mortality is increasing. Treatments are available but can only be implemented if individuals at risk are identified. General health checks have been suggested to facilitate this process.

Objectives

To examine the long-term effect of population-based general health checks on CVD and all-cause mortality.

Design and setting

The Ebeltoft Health Promotion Project (EHPP) is a parallel randomised controlled trial in a Danish primary care setting.

Participants

The EHPP enrolled individuals registered in the Civil Registration System as (1) inhabitants of Ebeltoft municipality, (2) registered with a general practitioner (GP) participating in the study and (3) aged 30–49 on 1 January 1991. A total of 3464 individuals were randomised as invitees (n=2000) or non-invitees (n=1464). Of the invitees, 493 declined. As an external control group, we included 1 511 498 Danes living outside the municipality of Ebeltoft.

Interventions

Invitees were offered a general health check and, if test-results were abnormal, recommended a 15–45 min consultation with their GP. Non-invitees in Ebeltoft received a questionnaire at baseline and were offered a general health check at year 5. The external control group, that is, the remaining Danish population, received routine care only.

Outcome measures

HRs for CVD and all-cause mortality.

Results

Every individual randomised was analysed. When comparing invitees to non-invitees within the municipality of Ebeltoft, we found no significant effect of general health checks on CVD (HR=1.11 (0.88; 1.41)) or all-cause mortality (HR=0.93 (0.75; 1.16)). When comparing invitees to the remaining Danish population, we found similar results for CVD (adjusted HR=0.99 (0.86; 1.13)) and all-cause mortality (adjusted HR=0.96 (0.85; 1.09)).

Conclusion

We found no effect of general health checks offered to the general population on CVD or all-cause mortality.

Trial registration number

NCT001457822015-57-0002; 62908, 187.
STOP-Colitis pilot trial protocol: a prospective, open-label, randomised pilot study to assess two possible routes of faecal microbiota transplant delivery in patients with ulcerative colitis
Authors: Quraishi Mohammed Nabil , Yalchin Mehmet , Blackwell Clare , Segal Jonathan , Sharma Naveen , Hawkey Peter , McCune Victoria , Hart Ailsa L , Gaya Daniel , Ives Natalie J , Magill Laura , Loi Shrushma , Hewitt Catherine , Gerasimidis Konstantinos , Loman Nicholas James , Hansen Richard , McMullan Christel , Mathers Jonathan , Quince Christopher , Crees Nicola , Iqbal Tariq
Published: April 2023

Introduction

Imbalance of the gut microbiome is key to the pathogenesis of ulcerative colitis (UC). Faecal microbiota transplant (FMT) is the transfer of homogenised and filtered faeces from a healthy individual to the gastrointestinal tract of a patient with disease. Published datasets show a positive signal for the use of FMT to treat UC, but the optimal route and dose of FMT remain unanswered.

Methods and analysis

This prospective, multi-centre open-label, randomised pilot study will assess two possible routes of FMT delivery, via the nasogastric (NG) route or by delivery to the COLON, in 30 patients with active UC recruited from three sites in the UK. Stool will be collected from healthy screened donors, processed, frozen and stored under a Medicines and Healthcare products Regulatory Agency (MHRA) “specials” manufacturing licence held at the University of Birmingham Microbiome Treatment Centre. Thawed FMT samples will be administered to patients either via eight nasogastric infusions given initially over 4 days starting on the day of randomisation, and then again for 4 days in week 4 for foregut delivery (total of 240 g of stool) or via one colonoscopic infusion followed by seven weekly enemas according to the hindgut protocol (total of 360 g of stool). Patients will be followed up weekly for 8 weeks, and then at 12 weeks. The aims of this pilot study are (1) to determine which FMT administration route (NG or COLON) should be investigated in a randomised double-blind, placebo-controlled trial and (2) to determine if a full randomised controlled trial is feasible. The primary outcome will be a composite assessment of both qualitative and quantitative data based on efficacy (clinical response), acceptability and safety. At the end of the pilot study, decisions will be made regarding the feasibility of a full randomised double-blind, placebo-controlled trial and, if deemed feasible, which route of administration should be used in such a study.

Ethics and dissemination

Ethical approval for this study has been obtained from the East Midlands-Nottingham Research Ethics Committee (REC 17/EM/0274). At the end of the study, findings will be reported at national and international gastroenterology meetings and published in peer-reviewed journals.

Trial registration number

NCT74072945
Cerebral cortex and respiratory muscles perfusion during spontaneous breathing attempts in ventilated patients and its relation to weaning outcomes: a protocol for a prospective observational study
Authors: Louvaris Zafeiris , Van Hollebeke Marine , Dhaenens Alexander , Vanhemelen Maarten , Meersseman Philippe , Wauters Joost , Gosselink Rik , Wilmer Alexander , Langer Daniel , Hermans Greet
Published: April 2023

Introduction

In addition to the well-documented factors that contribute to weaning failure, increased energy demands of the respiratory muscles during spontaneous breathing trials (SBTs) might not be met by sufficient increases in energy supplies. This discrepancy may deprive blood and oxygen of other tissues. In this context, restrictions in perfusion of splanchnic organs and non-working muscles during SBT have been associated with weaning failure. However, alterations in perfusion of the brain during the weaning process are less well understood.

Objective and hypothesis

To investigate whether cerebral cortex perfusion evolves differentially during the transition from mechanical ventilation (MV) to spontaneous breathing between patients failing or succeeding the SBT. We hypothesise that patients failing the SBT will exhibit reduced cerebral cortex perfusion during the transition from MV to spontaneous breathing as compared with patients succeeding the SBT.

Methods and analysis

This single-centre, prospective, observational study will be conducted in a medical Intensive Care unit of University Hospital Leuven, Belgium in ready to wean patients. Blood flow index in the cerebral cortex (prefrontal area), inspiratory (scalene) and expiratory muscle (upper rectus abdominis) and a non-working muscle (thenar eminence) will be simultaneously assessed by near-infrared spectroscopy (NIRS) using the tracer indocyanine green dye. Measurements will be performed on the same day during MV and during SBT. NIRS-derived tissue oxygenation index and cardiac output (by pulse contour analyses) will be recorded continuously. Twenty patients failing an SBT are estimated to be sufficient for detecting a significant difference in the change of cerebral cortex perfusion from MV to SBT (primary outcome) between SBT failure and success patients.

Ethics and dissemination

Ethics approval was obtained from the local ethical committee (Ethische Commissie Onderzoek UZ/KU Leuven protocol ID: S60516). Results from this study will be presented at scientific meetings and congresses and published in peer-reviewed journals.

Trial registration number

NCT03240263.
Standardised self-management kits for children with type 1 diabetes: pragmatic randomised trial of effectiveness and cost-effectiveness
Authors: Noyes Jane , Allen Davina , Carter Cynthia , Edwards Deborah , Edwards Rhiannon Tudor , Russell Daphne , Russell Ian T , Spencer Llinos Haf , Sylvestre Yvonne , Whitaker Rhiannon , Yeo Seow Tien , Gregory John W
Published: April 2023

Objective

To estimate the effectiveness of standardised self-management kits for children with type 1 diabetes.

Design

Pragmatic trial with randomisation ratio of two intervention: one control. Qualitative process evaluation.

Setting

11 diabetes clinics in England and Wales.

Participants

Between February 2010 and August 2011, we validly randomised 308 children aged 6–18 years; 201 received the intervention.

Intervention

We designed kits to empower children to achieve glycaemic control, notably by recording blood glucose and titrating insulin. The comparator was usual treatment.

Outcome measures at 3 and 6 months

Primary: Diabetes Pediatric Quality of Life Inventory (PedsQL). Secondary: HbA1c; General PedsQL; EQ-5D; healthcare resource use.

Results

Of the five Diabetes PedsQL dimensions, Worry showed adjusted scores significantly favouring self-management kits at 3 months (mean child-reported difference =+5.87; Standard error[SE]=2.19; 95% confidence interval [CI]) from +1.57 to +10.18; p=0.008); but Treatment Adherence significantly favoured controls at 6 months (mean child-reported difference=−4.68; SE=1.74; 95%CI from −8.10 to −1.25; p=0.008). Intervention children reported significantly worse changes between 3 and 6 months on four of the five Diabetes PedsQL dimensions and on the total score (mean difference=−3.20; SE=1.33; 95% CI from −5.73 to −0.67; p=0.020). There was no evidence of change in HbA1c; only 18% of participants in each group achieved recommended levels at 6 months. No serious adverse reactions attributable to the intervention or its absence were reported.

Use of kits was poor. Few children or parents associated blood glucose readings with better glycaemic control. The kits, costing £185, alienated many children and parents.

Conclusions

Standardised kits showed no evidence of benefit, inhibited diabetes self-management and increased worry. Future research should study relationships between children and professionals, and seek new methods of helping children and parents to manage diabetes.

Trial registration number

NCT17551624.
Protocol for a longitudinal, prospective cohort study investigating the biology of uterine fibroids and endometriosis, and patients’ quality of life: the FENOX study
Authors: Tapmeier Thomas Theodor , Nazri Hannah Mohamed , Subramaniam Kavita S , Manek Sanjiv , Garbutt Kurtis , Flint Emma J , Cheuk Cecilia , Hubbard Carol , Barrett Kelly , Shepherd Emily , Zondervan Krina T , Becker Christian Malte
Published: April 2023

Introduction

Millions of women suffer from the consequences of endometriosis and uterine fibroids, with fibroids the cause for over 50% of hysterectomies in the USA, and direct costs for their treatment estimated at between US$4 and US$9 billion. Endometriosis commonly affects millions of women worldwide predominantly during reproductive age, with severe menstrual and non-menstrual pain and subfertility the main symptoms. Due to the ‘unhappy triad’ of endometriosis—lack of awareness, lack of clinically relevant biomarkers and the unspecific nature of symptoms—women wait on average for 8–12 years before the definitive endometriosis diagnosis is made. Treatment options for both conditions are not satisfactory at the moment, especially with a view to preserving fertility for the women and families affected. In the Fibroids and Endometriosis Oxford (FENOX) study, we combine the investigation of fibroids and endometriosis, and plan to collect high-quality tissue samples and medical data of participants over a time frame of 5 years after surgical intervention.

Methods and analysis

Biological samples such as blood, saliva, urine, fat, peritoneal fluid and—if found—endometrial tissue or fibroids as well as detailed clinical and intraoperative data will be collected from women undergoing surgery and participating in the study after informed consent. We plan to recruit up to 1200 participants per disease arm (ie, endometriosis and uterine fibroids) over 5 years. Participants will fill in detailed and validated questionnaires on their medical history and quality of life, with follow-ups for 5 years. Enrolment started on 2 April 2018, and FENOX will close on 31 March 2028. We will analyse the biological samples using state-of-the-art molecular biology methods and correlate the findings with the medical records and questionnaire data.

Ethics and dissemination

The findings will be published in high-ranking journals in the field and presented at national and international conferences.

Trial registration number

NCT13560263.
Referral to Slimming World in UK Stop Smoking Services (SWISSS) versus stop smoking support alone on body weight in quitters: results of a randomised controlled trial
Authors: Lycett Deborah , Aveyard Paul , Farmer Andrew , Lewis Amanda , Munafò Marcus
Published: April 2023

Introduction

Most people who stop smoking gain weight. Dietary modification may seem an obvious solution, but food restriction may increase cigarette craving and smoking relapse.

Trial design

An unblinded parallel randomised controlled trial.

Methods

Participants were adult smokers with a body mass index greater or equal to 23 kg/m2. Setting was National Health Service commissioned Stop Smoking Services, interventions were referral to a commercial weight management programme, plus stop smoking support (treatment group), compared with stop smoking support alone (control group). Objective was to compare weight change between interventions in smoking abstainers and not abstinent rates in all. Primary outcome was change in weight (kg) at 12 weeks. Randomisation sequence was computer generated and concealed until allocation.

Results

Seventy-six participants were recruited, 37 were randomised to the treatment group and 39 to the control group. Change in weight was analysed in long-term abstainers (13 treatment, 14 control) only because the aim was to prevent weight gain associated with smoking cessation. Abstinence was analysed on an intention-to-treat basis (37 treatment, 39 control). At 12 weeks weight gain was less in the treatment than the control group with an adjusted mean difference of −2.3 kg 95% CI (−4.4 to -0.1). Craving scores were lower (Mood and Physical Symptoms Scale craving domain −1.6 (–2.7 to –0.5)) and quit rates were higher in the treatment than the control group (32% vs 21%), although the trial was not powered to superiority in cravings and quit rates. No adverse events or side effects were reported.

Conclusion

In people who are obese and want to quit smoking, these data provide modest encouragement that providing weight management at the time of quitting may be helpful. Those who are not obese, but who are informed about potential weight gain during their quit attempt, were uninterested in a weight management programme.

Trial registration number

NCT65705512
Risk factors and clinical outcomes of functional decline during hospitalisation in very old patients with acute decompensated heart failure: an observational study
Authors: Yaku Hidenori , Kato Takao , Morimoto Takeshi , Inuzuka Yasutaka , Tamaki Yodo , Ozasa Neiko , Yamamoto Erika , Yoshikawa Yusuke , Kitai Takeshi , Kato Masashi , Ikeda Tomoyuki , Furukawa Yutaka , Nakagawa Yoshihisa , Sato Yukihito , Kuwahara Koichiro , Kimura Takeshi
Published: April 2023

Objective

To investigate the prevalence and risk factors of functional decline during hospitalisation and its relationship with postdischarge outcomes in very old patients with acute decompensated heart failure (ADHF) hospitalisation.

Design

Prospective cohort study between 1 October 2014 and 31 March 2016.

Setting

A physician-initiated, multicentre study of consecutive patients admitted for ADHF in 19 hospitals throughout Japan.

Participants

Among 3555 patients hospitalised for ADHF (median age (IQR), 80 (71–86) years; 1572 (44%) women), functional decline during the index hospitalisation occurred in 528 patients (15%).

Primary and secondary outcomes

The primary outcome measure was a composite of all-cause death or heart failure (HF) hospitalisation after discharge. The secondary outcome measures were all-cause death, HF hospitalisation, and a composite of all-cause death or all-cause hospitalisation.

Results

The independent risk factors for functional decline included age ≥80 years (OR 2.71; 95% CI 2.09 to 3.51), female (OR 1.32; 95% CI 1.05 to 1.67), prior stroke (OR 1.67; 95% CI 1.28 to 2.19), dementia (OR 2.26; 95% CI 1.74 to 2.95), ambulatory before admission (OR 1.74; 95% CI 1.29 to 2.35), elevated body temperature (OR 1.91; 95% CI 1.31 to 2.79), New York Heart Association class III or IV on admission (OR 1.54; 95% CI 1.07 to 2.22), decreased albumin levels (OR 1.76; 95% CI 1.32 to 2.34), hyponatraemia (OR 1.49; 95% CI 1.10 to 2.03) and renal dysfunction (OR 1.55; 95% CI 1.22 to 1.98), after multivariable adjustment. The cumulative 1-year incidence of the primary outcome in the functional decline group was significantly higher than that in the no functional decline group (50% vs 31%, log-rank p<0.001). After adjusting for baseline characteristics, the higher risk of the functional decline group relative to the no functional decline group remained significant (adjusted HR 1.46; 95% CI 1.24 to 1.71; p<0.001).

Conclusions

Independent risk factors of functional decline in very old patients with ADHF were related to both frailty and severity of HF. Functional decline during ADHF hospitalisation was associated with unfavourable postdischarge outcomes.

Trial registration number

NCT02334891UMIN000015238.
Randomised controlled pilot feasibility trial of an early intervention programme for young infants with neurodevelopmental impairment in Uganda: a study protocol
Authors: Nampijja Margaret , Webb Emily , Nanyunja Carol , Sadoo Samantha , Nalugya Ruth , Nyonyintono James , Muhumuza Anita , Ssekidde Moses , Katumba Kenneth , Magnusson Brooke , Kabugo Daniel , Cowan Frances M , Martinez-Biarge Miriam , Zuurmond Maria , Morgan Cathy , Lester Deborah , Seeley Janet , Tann Cally J
Published: April 2023

Introduction

Early intervention programmes (EIPs) for infants with neurodevelopmental impairment have been poorly studied especially in low-income settings. We aim to evaluate the feasibility and acceptability of a group participatory EIP, the ‘ABAaNA EIP’, for young children with neurodevelopmental impairment in Uganda.

Methods and analysis

We will conduct a pilot feasibility, single-blinded, randomised controlled trial comparing the EIP with standard care across two study sites (one urban, one rural) in central Uganda. Eligible infants (n=126, age 6–11 completed months) with neurodevelopmental impairment (defined as a developmental quotient <70 on Griffiths Scales of Mental Development, and, or Hammersmith Infant Neurological Examination score <60) will be recruited and randomised to the intervention or standard care arm. Intervention arm families will receive the 10-modular, peer-facilitated, participatory, community-based programme over 6 months. Recruited families will be followed up at 6 and 12 months after recruitment, and assessors will be blinded to the trial allocation. The primary hypothesis is that the ABAaNA EIP is feasible and acceptable when compared with standard care. Primary outcomes of interest are feasibility (number recruited and randomised at baseline) and acceptability (protocol violation of arm allocation and number of sessions attended) and family and child quality of life. Guided by the study aim, the qualitative data analysis will use a data-led thematic framework approach. The findings will inform scalability and sustainability of the programme.

Ethics and dissemination

The trial protocol has been approved by the relevant Ugandan and UK ethics committees. Recruited families will give written informed consent and we will follow international codes for ethics and good clinical practice. Dissemination will be through peer-reviewed publications, conference presentations and public engagement.

Trial registration number

NCT44380971; protocol version 3.0, 19th February 2018.
Study protocol for the Melbourne Infant Study: BCG for Allergy and Infection Reduction (MIS BAIR), a randomised controlled trial to determine the non-specific effects of neonatal BCG vaccination in a low-mortality setting
Authors: Messina Nicole L , Gardiner Kaya , Donath Susan , Flanagan Katie , Ponsonby Anne-Louise , Shann Frank , Robins-Browne Roy , Freyne Bridget , Abruzzo Veronica , Morison Clare , Cox Lianne , Germano Susie , Zufferey Christel , Zimmermann Petra , Allen Katie J , Vuillermin Peter , South Mike , Casalaz Dan , Curtis Nigel
Published: April 2023

Introduction

BCG vaccination reduces all-cause infant mortality in high-mortality settings by more than can be attributed to protection against tuberculosis. This is proposed to result from non-specific protection against non-vaccine targeted (‘off-target’) infections. There is also evidence that BCG protects against allergic diseases.

Methods and analysis

The Melbourne Infant Study: BCG for Allergy and Infection Reduction is a phase III multicentre, single-blinded, randomised controlled trial. A total of 1438 healthy neonates will be randomised to receive either BCG vaccination or no BCG vaccination in the first 10 days of life. Measures of allergy, eczema, infection and asthma will be obtained from parent-completed questionnaires 3 monthly in the first year and 6 monthly from 1 to 5 years of age, and clinical assessments at 1 and 5 years of age. Biological samples will also be collected for future immunological studies.

Analysis primary outcome

The proportion of participants with measures of allergy and infection (atopic sensitisation, eczema, lower respiratory tract infection) at 1 and 5 years of age, and asthma at 5 years of age. Secondary outcomes: (1) the proportion of participants with additional measures of allergy, eczema, asthma and infections; (2) medication use for eczema and asthma; (3) the severity and age of onset of eczema and asthma; (4) the number of episodes of infection; (5) hospitalisations for infections and (6) laboratory measures of immune responses.

Ethics and dissemination

This trial has ethical and governance approval from Mercy Health Human Research Ethics Committee (HREC, No. R12-28) and Royal Children’s Hospital HREC (No. 33025) with additional governance approval from Barwon Health and St John of God, Geelong, Victoria. Results of this trial will be published in peer-reviewed journals and presented at scientific conferences.

Trial registration number

NCT01906853
Is fascia iliaca compartment block administered by paramedics for suspected hip fracture acceptable to patients? A qualitative study
Authors: Evans Bridie Angela , Brown Alan , Fegan Greg , Ford Simon , Guy Katy , Jones Jenna , Jones Sian , Keen Leigh , Khanom Ashrafunnesa , Longo Mirella , Pallister Ian , Rees Nigel , Russell Ian T , Seagrove Anne C , Watkins Alan , Snooks Helen
Published: April 2023

Objective

To explore patients’ experience of receiving pain relief injection for suspected hip fracture from paramedics at the location of the injury.

Design

Qualitative interviews within a feasibility trial about an alternative to routine prehospital pain management for patients with suspected hip fracture.

Setting

Patients treated by paramedics in the catchment area of one emergency department in South Wales.

Participants

Six patients and one carer of a patient who received fascia iliaca compartment block (FICB).

Intervention

FICB administered to patients with suspected hip fracture by trained paramedics. We randomly allocated eligible patients to FICB—a local anaesthetic injection directly into the hip region—or usual care—most commonly morphine—using audited scratch cards.

Outcomes

Acceptability and experience of receiving FICB, assessed through interview data. We audio-recorded, with participants’ consent, and conducted thematic analysis of interview transcripts. The analysis team comprised two researchers, one paramedic and one lay member.

Results

Patients had little or no memory of being offered, consenting to or receiving FICB. They recalled the reassuring manner and high quality of care received. They accepted FICB without question. Partial or confused memory characterised experience of subsequent hospital care until surgery. They said their priorities when calling for emergency help were to receive effective care. After hospital treatment, they wanted to regain their health and mobility and resume the quality of life they experienced before their injury.

Conclusions

This study did not raise any concerns about the acceptability of FICB administered at the scene of injury by paramedics to people with suspected hip fracture. It adds to existing evidence about patient and carer experience of on-scene care for people with suspected hip fracture. Further research is needed to assess safety, effectiveness and cost effectiveness of this health technology in a new setting.

Trial registration number

NCT60065373.