bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost-effectiveness of FreeO2in patients with chronic obstructive pulmonary disease hospitalised for acute exacerbations: analysis of a pilot study in Quebec
Authors: Poder Thomas G , Kouakou Christian R C , Bouchard Pierre-Alexandre , Tremblay Véronique , Blais Sébastien , Maltais François , Lellouche François
Published: April 2023

Objective

Conduct a cost-effectiveness analysis of FreeO2technology versus manual oxygen-titration technology for patients with chronic obstructive pulmonary disease (COPD) hospitalised for acute exacerbations.

Setting

Tertiary acute care hospital in Quebec, Canada.

Participants

47 patients with COPD hospitalised for acute exacerbations.

Intervention

An automated oxygen-titration and oxygen-weaning technology.

Methods and outcomes

The costs for hospitalisation and follow-up for 180 days were calculated using a microcosting approach and included the cost of FreeO2technology. Incremental cost-effectiveness ratios (ICERs) were calculated using bootstrap resampling with 5000 replications. The main effect variable was the percentage of time spent at the target oxygen saturation (SpO2). The other two effect variables were the time spent in hyperoxia (target SpO2+5%) and in severe hypoxaemia (SpO2<85%). The resamplings were based on data from a randomised controlled trial with 47 patients with COPD hospitalised for acute exacerbations.

Results

FreeO2generated savings of 20.7% of the per-patient costs at 180 days (ie, −$C2959.71). This decrease is nevertheless not significant at the 95% threshold (P=0.13), but the effect variables all improved (P<0.001). The improvement in the time spent at the target SpO2was 56.3%. The ICERs indicate that FreeO2technology is more cost-effective than manual oxygen titration with a savings of −$C96.91 per percentage point of time spent at the target SpO2(95% CI −301.26 to 116.96).

Conclusion

FreeO2technology could significantly enhance the efficiency of the health system by reducing per-patient costs at 180 days. A study with a larger patient sample needs to be carried out to confirm these preliminary results.

Trial registration number

NCT01393015; Post-results.
Does dexmedetomidine given as a premedication or intraoperatively reduce post-hospitalisation behaviour change in children? A study protocol for a randomised controlled trial in a tertiary paediatric hospital
Authors: Lee-Archer Paul , McBride Craig , Paterson Rebecca , Reade Michael , Regli-von Ungern-Sternberg Britta , Long Deborah
Published: April 2023

Introduction

It has been reported that post-hospitalisation behaviour change (PHBC) occurs in over 50% of children undergoing a general anaesthetic and manifests as behaviours such as sleep and eating disorders, defiance of authority, nightmares, enuresis and temper tantrums. The effect is usually short-lived (2–4 weeks); however, in 5–10% of children, these behaviours can last up to 12 months. The risk factors for developing PHBC include underlying anxiety in the child or parent, a previous bad hospital experience, emergence delirium and preschool age. A recent meta-analysis of alpha-2 agonists (including dexmedetomidine) found that they effectively reduce the incidence of emergence delirium but none of the studies looked at longer term outcomes, such as PHBC.

Methods and analysis

Two-year-old to seven-year-old children requiring general anaesthesia for common day-case procedures will be randomly assigned to one of three groups: a dexmedetomidine pre medication group, an intraoperative dexmedetomidine group and a control group. Baseline anxiety levels of the parent will be recorded and the anxiety of the child during induction of anaesthesia will also be recorded using validated tools. The primary outcome will be negative behaviours after hospitalisation and these will be measured using the Post Hospitalisation Behaviour Questionnaire for Ambulatory Surgery and the Strengths and Difficulties Questionnaire. These questionnaires will be administered by a blinded researcher at days 3, 14 and 28 post surgery.

Ethics and dissemination

Ethics approval has been granted by the Children’s Health Queensland human research ethics committee (HREC/15/QRCH/248) and the University of Queensland human research ethics office (#2016001715). Any amendments to this protocol will be submitted to the ethics committees for approval.

Trial registration number

NCT12616000096459.
Association between depressive symptoms and objectively measured daily step count in individuals at high risk of cardiovascular disease in South London, UK: a cross-sectional study
Authors: Ludwig Vera M , Bayley Adam , Cook Derek G , Stahl Daniel , Treasure Janet L , Asthworth Mark , Greenough Anne , Winkley Kirsty , Bornstein Stefan R , Ismail Khalida
Published: April 2023

Objectives

Depressive symptoms are common but rarely considered a risk factor for unhealthy lifestyles associated with cardiovascular disease (CVD). This study investigates whether depressive symptoms are associated with reduced physical activity (PA) in individuals at high risk of developing CVD.

Design

Secondary analysis of the cross-sectional baseline data from a randomised controlled trial of an intensive lifestyle intervention.

Setting

135 primary care practices in South London, UK.

Participants

1742 adults, 49–74 years, 86% male at high (≥20%) risk of developing CVD in the next 10 years as defined via QRISK2 score.

Outcome measures

The main explanatory variable was depressive symptoms measured via the Patient Health Questionnaire-9 (PHQ-9). The main outcome was daily step count measured with an accelerometer (ActiGraph GT3X) stratified by weekdays and weekend days.

Results

The median daily step count of the total sample was 6151 (IQR 3510) with significant differences (P<0.001) in mean daily step count between participants with low (PHQ-9 score: 0–4), mild (PHQ-9 score: 5–9) and moderate to severe depressive symptoms (PHQ-9 score: ≥10). Controlling for age, gender, ethnicity, education level, body mass index (BMI), smoking, consumption of alcohol, day of the week and season, individuals with mild depressive symptoms and those with moderate to severe depressive symptoms walked 13.3% (95% CI 18.8% to 7.9%) and 15.6% (95% CI 23.7% to 6.5%) less than non-depressed individuals, respectively. Furthermore, male gender, white ethnicity, higher education level, lower BMI, non-smoking, moderate alcohol intake, weekdays and summer season were independently associated with higher step count.

Conclusions

People at high risk of CVD with depressive symptoms have lower levels of PA.

Trial registration

NCT84864870.
Effects of high-intensity interval training on vascular function in breast cancer survivors undergoing anthracycline chemotherapy: design of a pilot study
Authors: Lee Kyuwan , Kang Irene , Mortimer Joanne E , Sattler Fred , Mack Wendy J , Fitzsimons Lindsey Avery , Salem George , Dieli-Conwright Christina M
Published: April 2023

Introduction

Cardiovascular disease (CVD) mortality is higher among breast cancer survivors (BCS) who receive chemotherapy compared with those not receiving chemotherapy. Anthracycline chemotherapy is of particular concern due to anthracycline-related impairment of vascular endothelial cells and dysregulation of the extracellular matrix. One strategy proven to offset these impairments is a form of exercise known as high-intensity interval training (HIIT). HIIT improves endothelial function in non-cancer populations by decreasing oxidative stress, the main contributor to anthracycline-induced vascular dysfunction. The purpose of this pilot study is to assess the feasibility of an 8-week HIIT, as well as the HIIT effects on endothelial function and extracellular matrix remodelling, in BCS undergoing anthracycline chemotherapy.

Methods and analysis

Thirty BCS are randomised to either HIIT, an 8-week HIIT intervention occurring three times per week (seven alternating bouts of 90% of peak power output followed by 10% peak power output), or delayed group (DEL). Feasibility of HIIT is assessed by (1) the percentage of completed exercise sessions and (2) the number of minutes of exercise completed over the course of the study. Vascular function is assessed using brachial artery flow-mediated dilation and carotid intima media thickness. Extracellular matrix remodelling is assessed by the level of matrix metalloproteinases in the plasma. A repeated-measures analysis of covariance model will be performed with group (HIIT and DEL group) and time (pre/post assessment) as independent factors. We hypothesise that HIIT will be feasible in BCS undergoing anthracycline chemotherapy, and that HIIT will improve endothelial function and extracellular matrix remodelling, compared with the DEL group. Success of this study will provide evidence of feasibility and efficacy to support a larger definitive trial which will impact cancer survivorship by decreasing anthracycline-induced vascular dysfunction, thereby benefiting cardiovascular markers that are related to CVD risk.

Ethics and dissemination

This trial was approved by the University of Southern California Institutional Review Board (HS-15–00227).

Trial registration number

NCT02454777.
Intermittent versus continuous oxygen saturation monitoring for infants hospitalised with bronchiolitis: study protocol for a pragmatic randomised controlled trial
Authors: Mahant Sanjay , Wahi Gita , Giglia Lucy , Pound Catherine , Kanani Ronik , Bayliss Ann , Roy Madan , Sakran Mahmoud , Kozlowski Natascha , Breen-Reid Karen , Lavigne Mollie , Premji Laila , Moretti Myla E , Willan Andrew R , Schuh Suzanne , Parkin Patricia C
Published: April 2023

Introduction

Bronchiolitis is the most common reason for hospitalisation in infants in developed countries. The main focus of hospital care is on supportive care, such as monitoring for hypoxia and supplemental oxygen administration, as active therapies lack effectiveness. Pulse oximetry is used to monitor hypoxia in hospitalised infants and is used either intermittently or continuously. Observational studies have suggested that continuous pulse oximetry use leads to a longer length of hospital stay in stable infants. The use of continuous pulse oximetry may lead to unnecessary clinical intervention due to readings that are of little clinical significance, false-positive readings and less reliance on the clinical status. There is a lack of high-quality evidence to guide which pulse oximetry monitoring strategy, intermittent or continuous, is superior in infants hospitalised with bronchiolitis with respect to patient and policy-relevant outcomes.

Methods and analysis

This is a multicentre, pragmatic randomised controlled trial comparing two strategies for pulse oximetry monitoring in infants hospitalised for bronchiolitis. Infants aged 1 month to 2 years presenting to Canadian tertiary and community hospitals will be randomised after stabilisation to receive either intermittent or continuous oxygen saturation monitoring on the inpatient unit until discharge. The primary outcome is length of hospital stay. Secondary outcomes include additional measures of effectiveness, acceptability, safety and cost. We will need to enrol 210 infants in order to detect a 12-hour difference in length of stay with a type 1 error rate of 5% and a power of 90%.

Ethics and dissemination

Research ethics approval has been obtained for this trial. This trial will provide data to guide hospitals and clinicians on the optimal pulse oximetry monitoring strategy in infants hospitalised with bronchiolitis. We will disseminate the findings of this study through peer-reviewed publication, professional societies and meetings.

Trial registration number

NCT02947204
Protocol for a randomised trial evaluating the comparative effectiveness of strategies to promote shared decision making for hip and knee osteoarthritis (DECIDE-OA study)
Authors: Mangla Mahima , Bedair Hany , Chang Yuchiao , Daggett Susannah , Dwyer Maureen K , Freiberg Andrew A , Mwangi Sheila , Talmo Carl , Vo Ha , Sepucha Karen
Published: April 2023

Introduction

There are several different interventions available to promote shared decision making (SDM); however, little is known about the comparative effectiveness of different approaches.

Objective

To examine the impact of patient-directed and physician-directed decision support strategies on the quality of treatment decisions for hip and knee osteoarthritis (OA).

Trial design

A 2×2 factorial randomised controlled trial.

Setting

One academic medical centre, one community hospital and one orthopaedic specialty hospital.

Participants and interventions

The enrolment targets were 8 surgeons and 1120 patients diagnosed with hip or knee OA. Patients were randomly assigned to receive one of two different decision aids (DAs) stratified by site. The DAs varied in length, content and the level of detail regarding treatment options. Both DAs were available by paper or online.

Surgeons were randomly assigned to receive a report detailing patients’ goals and treatment preferences at the time of the visit or not. Eligible patients received their assigned DA before their visit and completed three surveys: before the visit (timepoint (T)1), 1-week postvisit (T2) and 6 months from either the visit date or surgery date for patients who underwent surgery (T3). Study staff and participating surgeons were not blinded, but the statistician conducting the analyses was blinded to the arms.

Main outcome measure and analysis

The primary study outcome was decision quality, the percentage of patients who were well informed and received their preferred treatment. Secondary outcomes included involvement in decision making, surgical rates, health outcomes, decision regret and satisfaction. A logistic regression model with the generalised estimating equations approach was used to compare rates of decision quality between the groups and account for the clustering of patients within providers.

Ethics and dissemination

Ethics approval was obtained through the institutional review board at the main site. The findings will be published in peer-reviewed journals.

Trial registration number

NCT02729831; Pre-results.
Open randomised trial of the (Arabin) pessary to prevent preterm birth in twin pregnancy with health economics and acceptability: STOPPIT-2—a study protocol
Authors: Norman Jane E , Norrie John , Maclennan Graeme , Cooper David , Whyte Sonia , Cunningham Burley Sarah , Smith Joel B E , Shennan Andrew , Robson Stephen C , Thornton Steven , Kilby Mark D , Marlow Neil , Stock Sarah J , Bennett Philip R , Denton Jane
Published: April 2023

Introduction

The STOPPIT-2 study aims to determine the clinical utility of the Arabin cervical pessary in preventing preterm birth in women with a twin pregnancy and a short cervix, about which there is current uncertainty. STOPPIT-2 will resolve uncertainty around effectiveness for women with a twin pregnancy and a cervical length of 35 mm or less, define adverse effects, ascertain acceptability and estimate National Health Service costs and savings.

Methods

STOPPIT-2 is a pragmatic multicentre open-label randomised controlled trial. Consenting women with twin pregnancy will have an transvaginal ultrasound scan of their cervical length performed between 18+0 and 20+6 weeks’ gestation by an accredited practitioner: women with a cervical length of ≤35 mm will be eligible for inclusion in the treatment phase of the study. The intervention by the insertion of the Arabin cervical pessary will be compared with standard treatment (no pessary).

The primary outcomes are (obstetric) spontaneous onset of labour for the mother leading to delivery before 34 weeks’ gestation and (neonatal) a composite of specific adverse outcomes or death occurring up to the end of the first 4 weeks after the estimated date of delivery to either or both babies.

We plan to recruit 500 women in the treatment phase of the study. Assuming a treatment effect of 0.6, and background rates of 35% and 18%, respectively, for each of the primary outcomes, our study has 85% power to detect a difference between the intervention and the control groups.

Analysis

Data will be analysed on the intention-to-treat principle.

Ethics

STOPPIT-2 was approved by the South East Scotland Ethics Committee 02 on 29 August 2014, reference number 14/SS/1031 IRAS ID 159610.

Dissemination

Peer reviewed journals, presentations at national and international scientific meetings.

Trial registration number

NCT98835694andNCT02235181.
TAME trial: a multi-arm phase II randomised trial of four novel interventions for malnutrition enteropathy in Zambia and Zimbabwe - a study protocol
Authors: Kelly Paul , Bell Lauren , Amadi Beatrice , Bwakura-Dangarembizi Mutsa , VanBuskirk Kelley , Chandwe Kanta , Chipunza Miyoba , Ngosa Deophine , Chulu Nivea , Hill Susan , Murch Simon , Playford Raymond , Prendergast Andrew
Published: April 2023

Introduction

Severe acute malnutrition (SAM) in children in many countries still carries unacceptably high mortality, especially when complicated by secondary infection or metabolic derangements. New therapies are urgently needed and we have identified mucosal healing in the intestine as a potential target for novel treatment approaches.

Methods and analysis

The TAME trial (Therapeutic Approaches for Malnutrition Enteropathy) will evaluate four novel treatments in an efficient multi-arm single-blind phase II design. In three hospitals in Zambia and Zimbabwe, 225 children with SAM will be randomised to one of these treatments or to standard care, once their inpatient treatment has reached the point of transition from stabilisation to increased nutritional intake. The four interventions are budesonide, bovine colostrum or N-acetyl glucosamine given orally or via nasogastric tube, or teduglutide given by subcutaneous injection. The primary endpoint will be a composite score of faecal inflammatory markers, and a range of secondary endpoints include clinical and laboratory endpoints. Treatments will be given daily for 14 days, and evaluation of the major endpoints will be at 14 to 18 days, with a final clinical evaluation at 28 days. In a subset of children in Zambia, endoscopic biopsies will be used to evaluate the effect of interventions in detail.

Ethics and dissemination

The study has been approved by the University of Zambia Biomedical Research Ethics Committee (006-09-17, dated 9thJuly, 2018), and the Joint Research Ethics Committee of the University of Zimbabwe (24thJuly, 2019). Caregivers will provide written informed consent for each participant. Findings will be disseminated through peer-reviewed journals, conference presentations and to caregivers at face-to-face meetings.

Trial registration number

NCT03716115.
Is inspiratory muscle training (IMT) an acceptable treatment option for people with chronic obstructive pulmonary disease (COPD) who have declined pulmonary rehabilitation (PR) and can IMT enhance PR uptake? A single-group prepost feasibility study in a home-based setting
Authors: O’Connor Cath , Lawson Rod , Waterhouse Judith , Mills Gary H
Published: April 2023

Objectives

This feasibility study aimed to assess the acceptability of inspiratory muscle training (IMT) in people with chronic obstructive pulmonary disease (COPD) who declined pulmonary rehabilitation (PR) as a potential treatment option or precursor to PR. Objectives were to assess attitudes to IMT, PR and alternatives to PR; factors influencing adherence with IMT and acceptability of outcome measures, research tools and study protocol.

Design

A pragmatic, mixed methods, prepost feasibility study was conducted. Recruitment took place over a 4-month period. Participants were followed up for a period of 6 months.

Settings

IMT sessions and assessments were conducted in the domiciliary setting.

Participants

Inclusion criteria: people over the age of 35, stable COPD, Medical Research Council Dyspnoea scale of 3 or above, declined PR. Exclusion criteria: history of spontaneous pneumothorax, incomplete recovery from a traumatic pneumothorax, asthma, known recently perforated eardrum, unstable angina, ventricular dysrhythmias, cerebrovascular event or myocardial infarction within the last 2 months. Participants were selected from a purposive sample. Of the 22 potential participants screened, 11 were recruited and interviewed. Ten participants commenced IMT. Seven participants completed the follow-up assessment.

Intervention

Eight weeks of IMT twice a day, 5 days a week with visits once weekly by a physiotherapist. Unsupervised IMT twice a day three times a week until follow-up at 6 months.

Outcomes

Acceptability of IMT and the study process was explored via semi-structured interviews. Adherence with IMT was assessed by the Powerbreathe K3 device and participant diaries. Uptake of PR was identified.

Results

IMT was found to be acceptable. Adherence was explored. Four people went on to participate in PR.

Conclusions

Feasibility was established. A randomised controlled trial is warranted to establish efficacy and cost-effectiveness of IMT in those who decline PR and IMT as an intervention to promote uptake of PR.

Trial registration number

NCT01956565; Post-results.
Laparoscopically assisted versus open oesophagectomy for patients with oesophageal cancer—the Randomised Oesophagectomy: Minimally Invasive or Open (ROMIO) study: protocol for a randomised controlled trial (RCT)
Authors: Brierley Rachel C , Gaunt Daisy , Metcalfe Chris , Blazeby Jane M , Blencowe Natalie S , Jepson Marcus , Berrisford Richard G , Avery Kerry N L , Hollingworth William , Rice Caoimhe T , Moure-Fernandez Aida , Wong Newton , Nicklin Joanna , Skilton Anni , Boddy Alex , Byrne James P , Underwood Tim , Vohra Ravi , Catton James A , Pursnani Kish , Melhado Rachel , Alkhaffaf Bilal , Krysztopik Richard , Lamb Peter , Culliford Lucy , Rogers Chris , Howes Benjamin , Chalmers Katy , Cousins Sian , Elliott Jackie , Donovan Jenny , Heys Rachael , Wickens Robin A , Wilkerson Paul , Hollowood Andrew , Streets Christopher , Titcomb Dan , Humphreys Martyn Lee , Wheatley Tim , Sanders Grant , Ariyarathenam Arun , Kelly Jamie , Noble Fergus , Couper Graeme , Skipworth Richard J E , Deans Chris , Ubhi Sukhbir , Williams Robert , Bowrey David , Exon David , Turner Paul , Daya Shetty Vinutha , Chaparala Ram , Akhtar Khurshid , Farooq Naheed , Parsons Simon L , Welch Neil T , Houlihan Rebecca J , Smith Joanne , Schranz Rachel , Rea Nicola , Cooke Jill , Williams Alexandra , Hindmarsh Carolyn , Maitland Sally , Howie Lucy , Barham Christopher Paul
Published: April 2023

Introduction

Surgery (oesophagectomy), with neoadjuvant chemo(radio)therapy, is the main curative treatment for patients with oesophageal cancer. Several surgical approaches can be used to remove an oesophageal tumour. The Ivor Lewis (two-phase procedure) is usually used in the UK. This can be performed as an open oesophagectomy (OO), a laparoscopically assisted oesophagectomy (LAO) or a totally minimally invasive oesophagectomy (TMIO). All three are performed in the National Health Service, with LAO and OO the most common. However, there is limited evidence about which surgical approach is best for patients in terms of survival and postoperative health-related quality of life.

Methods and analysis

We will undertake a UK multicentre randomised controlled trial to compare LAO with OO in adult patients with oesophageal cancer. The primary outcome is patient-reported physical function at 3 and 6 weeks postoperatively and 3 months after randomisation. Secondary outcomes include: postoperative complications, survival, disease recurrence, other measures of quality of life, spirometry, success of patient blinding and quality assurance measures. A cost-effectiveness analysis will be performed comparing LAO with OO. We will embed a randomised substudy to evaluate the safety and evolution of the TMIO procedure and a qualitative recruitment intervention to optimise patient recruitment. We will analyse the primary outcome using a multi-level regression model. Patients will be monitored for up to 3 years after their surgery.

Ethics and dissemination

This study received ethical approval from the South-West Franchay Research Ethics Committee. We will submit the results for publication in a peer-reviewed journal.

Trial registration number

NCT10386621.
IMPACT study on intervening with a manualised package to achieve treatment adherence in people with tuberculosis: protocol paper for a mixed-methods study, including a pilot randomised controlled trial
Authors: Stagg Helen R , Abubakar Ibrahim , Campbell Colin NJ , Copas Andrew , Darvell Marcia , Horne Robert , Kielmann Karina , Kunst Heinke , Mandelbaum Mike , Pickett Elisha , Story Alistair , Vidal Nicole , Wurie Fatima B , Lipman Marc
Published: April 2023

Introduction

Compared with the rest of the UK and Western Europe, England has high rates of the infectious disease tuberculosis (TB). TB is curable, although treatment is for at least 6 months and longer when disease is drug resistant. If patients miss too many doses (non-adherence), they may transmit infection for longer and the infecting bacteria may develop resistance to the standard drugs used for treatment. Non-adherence may therefore risk both their health and that of others. Within England, certain population groups are thought to be at higher risk of non-adherence, but the factors contributing to this have been insufficiently determined, as have the best interventions to promote adherence. The objective of this study was to develop a manualised package of interventions for use as part of routine care within National Health Services to address the social and cultural factors that lead to poor adherence to treatment for TB disease.

Methods and analysis

This study uses a mixed-methods approach, with six study components. These are (1) scoping reviews of the literature; (2) qualitative research with patients, carers and healthcare professionals; (3) development of the intervention; (4) a pilot randomised controlled trial of the manualised intervention; (5) a process evaluation to examine clinical utility; and (6) a cost analysis.

Ethics and dissemination

This study received ethics approval on 24 December 2018 from Camberwell St. Giles Ethics Committee, UK (REC reference 18/LO/1818). Findings will be published and disseminated through peer-reviewed publications and conference presentations, published in an end of study report to our funder (the National Institute for Health Research, UK) and presented to key stakeholders.

Trial registration number

NCT95243114

Secondary identifying numbers

University College London/University College London Hospitals Joint Research Office 17/0726.

National Institute for Health Research, UK 16/88/06.
Independent medical evaluation of general practitioners’ follow-up of sick-listed patients: a cross-sectional study in Norway
Authors: Øyeflaten Irene , Maeland Silje , Haukenes Inger
Published: April 2023

Objectives

The study was designed to examine the sufficiency of general practitioners’ (GPs) follow-up of patients on sick leave, assessed by independent medical evaluators.

Design

Cross-sectional study

Setting

Primary health care in the Western part of Norway. The study reuses data from a randomised controlled trial—the Norwegian independent medical evaluation trial (NIME trial).

Participants

The intervention group in the NIME trial: Sick-listed workers having undergone an independent medical evaluation by an experienced GP at 6 months of unremitting sick leave (n=937; 57% women). In the current study, the participants were distributed into six exposure groups defined by gender and main sick leave diagnoses (women/musculoskeletal, men/musculoskeletal, women/mental, men/mental, women/all other diagnoses and men/all other diagnoses).

Outcome measure

The independent medical evaluators assessment (yes/no) of the sufficiency of the regular GPs follow-up of their sick-listed patients.

Results

Estimates from generalised linear models demonstrate a robust association between men with mental sick leave diagnoses and insufficient follow-up by their regular GP first 6 months of sick leave (adjusted relative risk (RR)=1.8, 95% CI=1.15–1.68). Compared with the reference group, women with musculoskeletal sick leave diagnoses, this was the only significant finding. Men with musculoskeletal diagnoses (adjusted RR=1.4, 95% CI=0.92–2.09); men with other diagnoses (adjusted RR=1.0, 95% CI=0.58–1.73); women with mental diagnoses (adjusted RR=1.2, 95% CI=0.75–1.77) and women with other diagnoses (adjusted RR=1.3, 95% CI=0.58–1.73).

Conclusions

Assessment by an independent medical evaluator showed that men with mental sick leave diagnoses may be at risk of insufficient follow-up by their GP. Efforts should be made to clarify unmet needs to initiate relevant actions in healthcare and work life. Avoiding marginalisation in work life is of the utmost importance.

Trial registration number

NCT02524392.
Protocol for a multicentre randomised controlled trial to investigate the effect on asthma-related quality of life from breathing retraining in patients with incomplete asthma control attending specialist care in Denmark
Authors: Andreasson Karen Hjerrild , Skou Søren Thorgaard , Ulrik Charlotte Suppli , Madsen Hanne , Sidenius Kirsten , Jacobsen Jannie Søndergaard , Assing Karin Dahl , Rasmussen Kirsten Brændholt , Porsbjerg Celeste , Thomas Mike , Bodtger Uffe
Published: April 2023

Introduction and aim

Uncontrolled asthma is a global health challenge with substantial impact on quality of life (QoL) and overall healthcare costs. Unrecognised and/or unmanaged comorbidities often contribute to presence of uncontrolled asthma. Abnormalities in breathing pattern are termed dysfunctional breathing and are not only common in asthma but also lead to asthma-like symptoms and reduced QoL, and, in keeping with this, improvement with breathing normalisation. Evidence-based guidelines recommend breathing retraining interventions as an adjuvant treatment in uncontrolled asthma. Physiotherapy-based breathing pattern modification interventions incorporating relaxation have been shown to improve asthma-related QoL in primary care patients with impaired asthma control. Despite anecdotal reports, effectiveness of breathing retraining in patients referred to secondary care with incomplete asthma control has not been formally assessed in a randomised controlled trial (RCT). We aim to investigate the effect of breathing exercises on asthma-related QoL in patients with incomplete asthma control despite specialist care.

Methods and analysis

This two-armed assessor-blinded multicentre RCT will investigate the effect of physiotherapist-delivered breathing retraining on asthma QoL questionnaire (MiniAQLQ) in addition to usual specialist care, recruiting from seven outpatient departments and one specialised clinic representing all regions of Denmark during 2017–2019. We will include 190 consenting adults with incomplete asthma control, defined as Asthma Control Questionnaire 6-item score ≥0.8. Participants will randomly be allocated to either breathing exercise programme in addition to usual care (BrEX +UC) or UC alone. BrEX compiles three physiotherapy sessions and encouragement to perform home exercise daily. Both groups continue usual secondary care management. Primary outcome is between-group difference in MiniAQLQ at 6 months. Secondary outcomes include patient-reported outcome measures, spirometry and accelerometer.

Ethics and dissemination

Ethics Committee, Region Zealand (SJ-552) and Danish Data Protection Agency (REG-55–2016) approved the trial. Results will be reported in peer-reviewed scientific journals.

Trial registration number

NCT03127059.
Ascorbic Acid, Corticosteroids and Thiamine in Sepsis (ACTS) protocol and statistical analysis plan: a prospective, multicentre, double-blind, randomised, placebo-controlled clinical trial
Authors: Moskowitz Ari , Yankama Tuyen , Andersen Lars W , Huang David T , Donnino Michael W , Grossestreuer Anne V
Published: April 2023

Introduction

Septic shock is a common and highly morbid condition. To date, there is no specific therapy proven to attenuate organ injury in septic shock. Recent studies have suggested a role for the combination of ascorbic acid, corticosteroids and thiamine, although randomised data are lacking.

Methods and analysis

The Ascorbic Acid, Corticosteroids, and Thiamine in Sepsis trial is a multi-centre, double-blind, randomised, placebo-controlled clinical trial that aims to determine the impact of ascorbic acid, corticosteroids and thiamine versus placebo on organ injury and mortality in patients with septic shock. Patients are randomised to receive 1500 mg of ascorbic acid, 100 mg of thiamine and 50 mg of hydrocortisone parenterally versus matching placebo every 6 hours for 4 days. Clinical and laboratory data are collected at the time of study enrolment, at 24, 72 and 120 hours. The primary end-point for the trial is change in the Sequential Organ Failure Assessment score between enrolment and 72 hours. Additional key secondary outcomes include the incidence of renal failure and 30-day mortality.

Ethics and dissemination

The study was approved by the international review board of each participating study site. Study findings will be disseminated through peer-reviewed publications and conference presentations.

Trial registration number

The trial is registered on clinicaltrials.gov (NCT03389555). It was posted on 3 January 2018.
Seasonal malaria vaccination: protocol of a phase 3 trial of seasonal vaccination with the RTS,S/AS01Evaccine, seasonal malaria chemoprevention and the combination of vaccination and chemoprevention
Authors: Chandramohan Daniel , Dicko Alassane , Zongo Issaka , Sagara Issaka , Cairns Matthew , Kuepfer Irene , Diarra Modibo , Tapily Amadou , Issiaka Djibrilla , Sanogo Koualy , Mahamar Almahamoudou , Sompougdou Frederic , Yerbanga Serge , Thera Ismaila , Milligan Paul , Tinto Halidou , Ofori-Anyinam Opokua , Ouedraogo Jean-Bosco , Greenwood B
Published: April 2023

Introduction

Seasonal malaria chemoprevention (SMC), with sulphadoxine–pyrimethamine plus amodiaquine (SP+AQ) is effective but does not provide complete protection against clinical malaria. The RTS,S/AS01Emalaria vaccine provides a high level of protection shortly after vaccination, but this wanes rapidly. Such a vaccine could be an alternative or additive to SMC. This trial aims to determine whether seasonal vaccination with RTS,S/AS01Evaccine could be an alternative to SMC and whether a combination of the two interventions would provide added benefits.

Methods and analysis

This is an individually randomised, double-blind, placebo-controlled trial. 5920 children aged 5–17 months were enrolled in April 2017 in Mali and Burkina Faso. Children in group 1 received three priming doses of RTS,S/AS01Evaccine before the start of the 2017 malaria transmission season and a booster dose at the beginning of two subsequent transmission seasons. In addition, they received SMC SP+AQ placebo on four occasions each year. Children in group 2 received three doses of rabies vaccine in year 1 and hepatitis A vaccine in years 2 and 3 together with four cycles of SMC SP+AQ each year. Children in group 3 received RTS,S/AS01Evaccine and four courses of SMC SP+AQ. Incidence of clinical malaria is determined by case detection at health facilities. Weekly active surveillance for malaria is undertaken in a randomly selected subset of children. The prevalence of malaria is measured in surveys at the end of each transmission season. The primary endpoint is the incidence of clinical malaria confirmed by a positive blood film with a minimum parasite density of 5000 /µL. Primary analysis will be by modified intention to treat defined as children who have received the first dose of the malaria or control vaccine.

Ethics and dissemination

The protocol was approved by the national ethics committees of Mali and Burkina Faso and the London School of Hygiene and Tropical Medicine. The results will be presented to all stakeholders and published in open access journals.

Trial registration number

NCT03143218
Assessing mental stress on myocardial perfusion and myocardial blood flow in women without obstructive coronary disease: protocol for a mechanistic clinical trial
Authors: Ma Huan , Guo Lan , Fei Hongwen , Yin Han , Wang Haochen , Bai Bingqing , Liu Yuting , Wang Shuxia , Geng Qingshan , Jiang Wei
Published: April 2023

Introduction

Two-thirds of women with symptoms of angina have ‘angina with no obstructive coronary artery disease’ (ANOCA). Growing evidence supports the use of coronary artery function testing for the diagnosis of ANOCA. Research into the prevalence of mental stress-induced myocardial ischaemia (MSIMI) among women with ANOCA is lacking. MSIMI is common in clinically stable patients with coronary artery disease. It is not associated coronary stenosis but is a prognostic risk factor. Here, we describe the rationale and protocol for a mechanistic clinical trial to test the following hypotheses: (1) that MSIMI is more common in women with ANOCA women than in age-matched and sex-matched controls, and (2) MSIMI is associated with mental stress-induced myocardial blood flow (MBF) change but not with adenosine vasodilator stress-induced MBF change.

Methods and analysis

This is a mechanistic clinical trial. 84 women with confirmed ANOCA and 42 aged-matched healthy women (neither angina symptoms nor coronary stenosis) are to be recruited for mental and adenosine vasodilator stress tests. Positron emission tomography CT with ammonia N-13 will be used to evaluate the myocardial perfusion and MBF changes between stress and rest. MSIMI is defined as a summed difference score (SDS) of ≥3 and adenosine stress-induced myocardial ischaemia is defined as an SDS of ≥4. Other assessments include Reactive Hyperemia Index for microvascular endothelial function, peripheral arterial tonometry or digital vasomotor response, and a series of blood and psychometric tests.

Ethics and dissemination

This mechanistic clinical trial was approved by the Ethics Committee of Guangdong Provincial People’s Hospital. Findings will be disseminated through peer-reviewed publications and conference presentations.

Trial registration number

NCT03982901.
Phase I/II study protocol to assess safety and efficacy of adoptive cell therapy with anti-PD-1 plus low-dose pegylated-interferon-alpha in patients with metastatic melanoma refractory to standard of care treatments: the ACTME trial
Authors: van der Kooij Monique K , Verdegaal Els M E , Visser Marten , de Bruin Linda , van der Minne Caroline E , Meij Pauline M , Roozen Inge C F M , Jonker Mare A , van den Bosch Shelley , Liefers Gerrit-Jan , Speetjens Frank M , van der Burg Sjoerd H , Kapiteijn Ellen
Published: April 2023

Introduction

Treatment with anti-PD-1 immunotherapy does not lead to long-lasting clinical responses in approximately 60% of patients with metastatic melanoma. These refractory patients, however, can still respond to treatment with tumour infiltrating lymphocytes (TIL) and interferon-alpha (IFNa). A combination of TIL, pegylated-interferon-alpha (PEG-IFNa) and anti-PD-1 is expected to provide a safe, feasible and effective therapy for patients with metastatic melanoma, who are refractory to standard of care treatment options.

Methods and analysis

Patients are treated in two phases. In phase I, the safety of the combination TIL and anti-PD-1 is assessed (cohort 1) according to CTCAE 4.03 criteria. Subsequently, the safety of cotreatment with PEG-IFNa is tested in cohort 2. The efficacy will be evaluated in the second phase of the trial. Efficacy is evaluated according to RECIST 1.1 and immune-related response criteria. Clinical and immunological parameters will be evaluated for their relation with clinical responsiveness.

Ethics and dissemination

Ethical approval of the trial was obtained from the Central Committee on Research Involving Human Subjects in the Netherlands. The trial results will be shared with the scientific community at (inter)national conferences and by publication in a peer-reviewed journal.

Trial registration number

NCT03638375.
Real-world effectiveness of COVID-19 vaccines and anti-SARS-CoV-2 monoclonal antibodies against postacute sequelae of SARS-CoV-2: analysis of a COVID-19 observational registry for a diverse US metropolitan population
Authors: Tannous Jonika , Pan Alan P , Potter Thomas , Bako Abdulaziz T , Dlouhy Katharine , Drews Ashley , Sostman Henry Dirk , Vahidy Farhaan S
Published: April 2023

Objectives

We evaluated the effectiveness of COVID-19 vaccines and monoclonal antibodies (mAbs) against postacute sequelae of SARS-CoV-2 infection (PASC).

Design and setting

A retrospective cohort study using a COVID-19 specific, electronic medical record-based surveillance and outcomes registry from an eight-hospital tertiary hospital system in the Houston metropolitan area. Analyses were replicated across a global research network database.

Participants

We identified adult (≥18) patients with PASC. PASC was defined as experiencing constitutional (palpitations, malaise/fatigue, headache) or systemic (sleep disorder, shortness of breath, mood/anxiety disorders, cough and cognitive impairment) symptoms beyond the 28-day postinfection period.

Statistical analysis

We fit multivariable logistic regression models and report estimated likelihood of PASC associated with vaccination or mAb treatment as adjusted ORs with 95% CIs.

Results

Primary analyses included 53 239 subjects (54.9% female), of whom 5929, 11.1% (95% CI 10.9% to 11.4%), experienced PASC. Both vaccinated breakthrough cases (vs unvaccinated) and mAb-treated patients (vs untreated) had lower likelihoods for developing PASC, aOR (95% CI): 0.58 (0.52–0.66), and 0.77 (0.69–0.86), respectively. Vaccination was associated with decreased odds of developing all constitutional and systemic symptoms except for taste and smell changes. For all symptoms, vaccination was associated with lower likelihood of experiencing PASC compared with mAb treatment. Replication analysis found identical frequency of PASC (11.2%, 95% CI 11.1 to 11.3) and similar protective effects against PASC for the COVID-19 vaccine: 0.25 (0.21–0.30) and mAb treatment: 0.62 (0.59–0.66).

Conclusion

Although both COVID-19 vaccines and mAbs decreased the likelihood of PASC, vaccination remains the most effective tool for the prevention of long-term consequences of COVID-19.
Influence of letermovir treatment on gut inflammation in people living with HIV on antiretroviral therapy: protocol of the open-label controlled randomised CIAO study
Authors: Royston Léna , Isnard Stéphane , Berini Carolina A. , Bu Simeng , Lakatos Peter L. , Bessissow Talat , Chomont Nicolas , Klein Marina , Lebouché Bertrand , de Pokomandy Alexandra , Kronfli Nadine , Costiniuk Cecilia T. , Thomas Rejean , Tremblay Cécile , Boivin Guy , Routy Jean-Pierre
Published: April 2023

Introduction

Chronic cytomegalovirus (CMV) infection is very frequent in people living with HIV (PLWH). High anti-CMV IgG titres, which may be linked to transient CMV replication, have been associated with earlier mortality, CD8 T-cell expansion, lower CD4/CD8 ratio and increased T-cell senescence. We previously showed that anti-CMV IgG titres correlated with gut permeability in PLWH on antiretroviral therapy (ART), which was associated with microbial translocation, systemic inflammation and non-infectious/non-AIDS comorbidities. Letermovir, a novel anti-CMV drug with a good safety profile, was recently approved for anti-CMV prophylaxis in allogeneic haematopoietic stem cell transplant recipients. A drastic and selective reduction of both low-grade replication and clinically significant CMV infections, combined with an improved immune reconstitution have been reported.In vitro, letermovir prevented CMV-induced epithelial disruption in intestinal tissues. Based on these findings, we aim to assess whether letermovir could inhibit CMV subclinical replication in CMV-seropositive PLWH receiving ART and, in turn, decrease CMV-associated gut damage and inflammation.

Method and analysis

We will conduct a multi-centre, open-label, randomised, controlled clinical trial, including a total of 60 CMV-seropositive ART-treated PLWH for at least 3 years, with a viral load <50 copies/mL and CD4+count >400 cells/µL. Forty participants will be randomised to receive letermovir for 14 weeks and 20 participants will receive standard of care (ART) alone. Plasma, pheripheral blood mononuclear cells (PBMCs), and stool samples will be collected. Colon biopsies will be collected in an optional substudy. We will assess the effect of letermovir on gut damage, microbial translocation, inflammation and HIV reservoir size.

Ethics and dissemination

The study was approved by Health Canada and the Research Ethics Boards of the McGill University Health Centre (MUHC-REB, protocol number: MP37-2022-8295). Results will be made available through publications in open access peer-reviewed journals and through the CIHR/CTN website.

Trial registration number

NCT05362916.
Wireless physical activity monitor use among adults living with HIV in a community-based exercise intervention study: a quantitative, longitudinal, observational study
Authors: Turner Joshua R , Chow Judy , Cheng Justin , Hassanali Farhanna , Sevigny Hayley , Sperduti Michael , Chan Carusone Soo , Dagenais Matthieu , O'Brien Kelly K
Published: April 2023

Objectives

Our aim was to examine wireless physical activity monitor (WPAM) use and its associations with contextual factors (age, highest education level, social support and mental health) among adults living with HIV engaged in a community-based exercise (CBE) intervention.

Design

Quantitative, longitudinal, observational study.

Setting

Toronto YMCA, Ontario, Canada.

Participants

Eighty adults living with HIV who initiated the CBE intervention.

Intervention

Participants received a WPAM to track physical activity during a 25-week CBE intervention involving thrice-weekly exercise, supervised weekly (phase 1) and a 32-week follow-up involving thrice-weekly exercise with no supervision (phase 2), completed in December 2018.

Outcome measures

Uptake was measured as participants who consented to WPAM use at initation of the intervention. Usage was defined as the proportion of days each participant had greater than 0 steps out of the total number of days in the study. We measured contextual factors using a baseline demographic questionnaire (age, highest education level), and median scores from the bimonthly administered Medical Outcomes Study-Social Support Scale and Patient Health Questionnaire (mental health), where higher scores indicated greater social support and mental health concerns, respectively. We calculated Spearman correlations between WPAM usage and contextual factors.

Results

Seventy-six of 80 participants (95%) consented to WPAM use. In phase 1, 66% of participants (n=76) and in phase 2, 61% of participants (n=64) used the WPAM at least 1 day. In phase 1, median WPAM usage was 50% (25th, 75th percentile: 0%, 87%; n=76) of days enrolled and in phase 2, 23% (0%, 76%; n=64) of days. Correlation coefficients with WPAM usage ranged from weak for age (ρ=0.26) and mental health scores (ρ=−0.25) to no correlation (highest education level, social support).

Conclusions

Most adults living with HIV consented to WPAM use, however, usage declined over time from phase 1 to phase 2. Future implementation of WPAMs should consider factors to promote sustained usage by adults living with HIV.

Trial registration number

NCT02794415.