Cast versus functional brace in the rehabilitation of patients treated for an ankle fracture: protocol for the UK study of ankle injury rehabilitation (AIR) multicentre randomised trial

IntroductionEach year in the UK over 120 000 people fracture their ankle. It is not known what the best rehabilitation strategy is for these people. Traditionally standard care has involved immobilisation in a plaster cast but an alternative is a functional brace, which can be removed to allow early movement. This paper details the protocol for a multicentre randomised trial of plaster cast immobilisation versus functional bracing for patients with an ankle fracture.Methods and analysisWe will recruit adults with a fractured ankle, for which the treating clinician would consider plaster cast to be a reasonable management option. Randomisation will be on a 1:1 basis, stratified by centre, operative or non-operative management and age. Participants will be allocated to either plaster cast or a functional brace, both treatments are widely used. To have 90% power to detect a difference of 10 points on the primary outcome (Olerud and Molander Ankle Score) at the primary outcome time point (16 weeks), we need to randomise a minimum of 478 people. Quality of life and resource use will be collected at 6, 10, 16, 24 weeks and 12, 18, 24 months. The differences between treatment groups will be assessed on an intention-to-treat basis. The economic evaluation will adhere to the recommendations of the National Institute for Health and Care Excellence reference case.Ethics, registration and disseminationNational Research Ethic Committee approved this study on 4 July 2017 (17/WM/0239). The first site opened to recruitment 9 October 2017. The results of this trial will be submitted to a peer-reviewed journal and will inform clinical practice.Trial registration numberISRCTN15537280; Pre-results.

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Optimising outcomes of exercise and corticosteroid injection in patients with subacromial pain (impingement) syndrome: a factorial randomised trial

British Journal of Sports Medicine ◽

10.1136/bjsports-2019-101268 ◽

2020 ◽

pp. bjsports-2019-101268

Author(s):

Edward Roddy ◽

Reuben O Ogollah ◽

Raymond Oppong ◽

Irena Zwierska ◽

Praveen Datta ◽

...

Keyword(s):

Primary Outcome ◽

Corticosteroid Injection ◽

Randomised Trial ◽

Clinical Effectiveness ◽

Impingement Syndrome ◽

Ultrasound Guided ◽

Exercise Interventions ◽

Intention To Treat ◽

Registration Number ◽

And Function

ObjectivesTo compare the clinical effectiveness of (1) physiotherapist-led exercise versus an exercise leaflet, and (2) ultrasound-guided subacromial corticosteroid injection versus unguided injection for pain and function in subacromial pain (formerly impingement) syndrome (SAPS).MethodsThis was a single-blind 2×2 factorial randomised trial. Adults with SAPS were randomised equally to one of four treatment groups: (1) ultrasound-guided corticosteroid injection and physiotherapist-led exercise, (2) ultrasound-guided corticosteroid injection and an exercise leaflet, (3) unguided corticosteroid injection and physiotherapist-led exercise and (4) unguided corticosteroid injection and an exercise leaflet. The primary outcome was the Shoulder Pain and Disability Index (SPADI), collected at 6 weeks, 6 and 12 months and compared at 6 weeks for the injection interventions and 6 months for the exercise interventions by intention to treat.ResultsWe recruited 256 participants (64 treatment per group). Response rates for the primary outcome were 94% at 6 weeks, 88% at 6 months and 80% at 12 months. Greater improvement in total SPADI score was seen with physiotherapist-led exercise than with the exercise leaflet at 6 months (adjusted mean difference −8.23; 95% CI −14.14 to -2.32). There were no significant differences between the injection groups at 6 weeks (−2.04; −7.29 to 3.22), 6 months (−2.36; −8.16 to 3.44) or 12 months (1.59; −5.54 to 8.72).ConclusionsIn patients with SAPS, physiotherapist-led exercise leads to greater improvements in pain and function than an exercise leaflet. Ultrasound guidance confers no additional benefit over unguided corticosteroid injection.Trial registration numberISRCTN42399123.

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Study protocol for a randomised trial for atosiban versus placebo in threatened preterm birth: the APOSTEL 8 study

BMJ Open ◽

10.1136/bmjopen-2019-029101 ◽

2019 ◽

Vol 9 (11) ◽

pp. e029101 ◽

Cited By ~ 2

Author(s):

Job Klumper ◽

Wouter Breebaart ◽

Carolien Roos ◽

Christiana A Naaktgeboren ◽

Joris van der Post ◽

...

Keyword(s):

Preterm Birth ◽

Neonatal Outcome ◽

Randomised Trial ◽

Neonatal Morbidity ◽

Cervical Length ◽

Controlled Clinical Trial ◽

Intention To Treat ◽

Registration Number ◽

The Uk ◽

Double Blinded

IntroductionPreterm birth complicates >15 million pregnancies annually worldwide. In many countries, women who present with signs of preterm labour are treated with tocolytics for 48 hours. Although this delays birth, it has never been shown to improve neonatal outcome. In 2015, the WHO stated that the use of tocolytics should be reconsidered and that large placebo-controlled studies to evaluate the effectiveness of tocolytics are urgently needed.Methods and analysisWe designed an international, multicentre, randomised, double-blinded, placebo-controlled clinical trial. Women with threatened preterm birth (gestational age 30–34 weeks), defined as uterine contractions with (1) a cervical length of < 15 mm or (2) a cervical length of 15–30 mm and a positive fibronectin test or (3) in centres where cervical length measurement is not part of the local protocol: a positive fibronectin test or insulin-like growth factor binding protein-1 (Actim-Partus test) or (4) ruptured membranes, will be randomly allocated to treatment with atosiban or placebo for 48 hours. The primary outcome is a composite of perinatal mortality and severe neonatal morbidity. Analysis will be by intention to treat. A sample size of 1514 participants (757 per group) will detect a reduction in adverse neonatal outcome from 10% to 6% (alpha 0.05, beta 0.2). A cost-effectiveness analysis will be performed from a societal perspective.Ethics and disseminationThis study has been approved by the Research Ethics Committee (REC) of the Amsterdam University Medical Centres, location AMC, as well as the REC’s in Dublin and the UK. The results will be presented at conferences and published in a peer-reviewed journal. Participants will be informed about the results.Trial registration numberNederlands Trial Register (Trial NL6469).

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Hypotension in Preterm Infants (HIP) randomised trial

Archives of Disease in Childhood - Fetal and Neonatal Edition ◽

10.1136/archdischild-2020-320241 ◽

2021 ◽

pp. fetalneonatal-2020-320241

Author(s):

Eugene M Dempsey ◽

Keith J Barrington ◽

Neil Marlow ◽

Colm Patrick Finbarr O'Donnell ◽

Jan Miletin ◽

...

Keyword(s):

Brain Injury ◽

Primary Outcome ◽

Randomised Trial ◽

Intraventricular Haemorrhage ◽

Standard Group ◽

Double Blind ◽

Group Assignment ◽

Standard Management ◽

Postmenstrual Age ◽

Registration Number

ObjectiveTo determine whether restricting the use of inotrope after diagnosis of low blood pressure (BP) in the first 72 hours of life affects survival without significant brain injury at 36 weeks of postmenstrual age (PMA) in infants born before 28 weeks of gestation.DesignDouble-blind, placebo-controlled randomised trial. Caregivers were masked to group assignment.Setting10 sites across Europe and Canada.ParticipantsInfants born before 28 weeks of gestation were eligible if they had an invasive mean BP less than their gestational age that persisted for ≥15 min in the first 72 hours of life and a cerebral ultrasound free of significant (≥ grade 3) intraventricular haemorrhage.InterventionParticipants were randomly assigned to saline bolus followed by either a dopamine infusion (standard management) or placebo (5% dextrose) infusion (restrictive management).Primary outcomeSurvival to 36 weeks of PMA without severe brain injury.ResultsThe trial terminated early due to significant enrolment issues (7.7% of planned recruitment). 58 infants were enrolled between February 2015 and September 2017. The two groups were well matched for baseline variables. In the standard group, 18/29 (62%) achieved the primary outcome compared with 20/29 (69%) in the restrictive group (p=0.58). Additional treatments for low BP were used less frequently in the standard arm (11/29 (38%) vs 19/29 (66%), p=0.038).ConclusionThough this study lacked power, we did not detect major differences in clinical outcomes between standard or restrictive approach to treatment. These results will inform future studies in this area.Trial registration numberNCT01482559, EudraCT 2010-023988-17.

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Evaluating a Values-Based Intervention for Adolescence with High Nonclinical Paranoia: A Schools-Based Randomised Control Trial

Cognitive Therapy and Research ◽

10.1007/s10608-021-10278-6 ◽

2021 ◽

Author(s):

A. Parker ◽

J. Kingston

Keyword(s):

Active Control ◽

Primary Outcome ◽

Randomised Trial ◽

Self Esteem ◽

Randomised Control Trial ◽

Intention To Treat ◽

Low Intensity ◽

Time Interaction ◽

Potential Mediator

Abstract Background Paranoia in adolescents is common, but research on attenuating it is scarce. Focusing on values and enhancing value-based acts is a low intensity method for attenuating paranoia in adults. This randomised trial compared a brief (30-min, self-directed) values-plus-goals intervention to an active control for adolescents with high nonclinical paranoia (Paranoia Scale ≥ 53), delivered in schools. The study also investigated the role of self-esteem. Methods Ninety adolescents were randomly assigned to condition. Paranoia (primary outcome) and self-esteem (potential mediator) were assessed at baseline (T1), and two- (T2) and six-weeks (T3) after baseline. Results Results were analysed using intention to treat (ITT) and per protocol (PP) analysis. Using ITT analysis, the Condition*Time interaction was significant (F(2, 168) = 3.98, p = .02), paranoia was significantly lower at T3 following values-plus-goals as compared to control (d = 0.64). Differences were not significant using per protocol analysis (F(2, 106) = 1.61, p = .21). The between group effect size at T3 was (d = 0.61). The Condition*Time interaction for self-esteem was not significant (F(2, 112) = 2.86, p = .06). Conclusions Tentatively, findings suggest that a brief values-plus-goals intervention can reduce paranoia in adolescents relative to an active control.

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A partially randomised trial of pretomanid, moxifloxacin and pyrazinamide for pulmonary TB

The International Journal of Tuberculosis and Lung Disease ◽

10.5588/ijtld.20.0513 ◽

2021 ◽

Vol 25 (4) ◽

pp. 305-314

Author(s):

C. D. Tweed ◽

G. H. Wills ◽

A. M. Crook ◽

E. Amukoye ◽

V. Balanag ◽

...

Keyword(s):

Primary Outcome ◽

Randomised Trial ◽

Group Differences ◽

Pulmonary Tb ◽

Intention To Treat ◽

Tb Treatment ◽

Grade 3 ◽

To Receive ◽

Ongoing Evaluation ◽

Post Randomisation

BACKGROUND: Treatment for TB is lengthy and toxic, and new regimens are needed.METHODS: Participants with pulmonary drug-susceptible TB (DS-TB) were randomised to receive: 200 mg pretomanid (Pa, PMD) daily, 400 mg moxifloxacin (M) and 1500 mg pyrazinamide (Z) for 6 months (6Pa200MZ) or 4 months (4Pa200MZ); 100 mg pretomanid daily for 4 months in the same combination (4Pa100MZ); or standard DS-TB treatment for 6 months. The primary outcome was treatment failure or relapse at 12 months post-randomisation. The non-inferiority margin for between-group differences was 12.0%. Recruitment was paused following three deaths and not resumed.RESULTS: Respectively 4/47 (8.5%), 11/57 (19.3%), 14/52 (26.9%) and 1/53 (1.9%) DS-TB outcomes were unfavourable in patients on 6Pa200MZ, 4Pa200MZ, 4Pa100MZ and controls. There was a 6.6% (95% CI –2.2% to 15.4%) difference per protocol and 9.9% (95%CI –4.1% to 23.9%) modified intention-to-treat difference in unfavourable responses between the control and 6Pa200MZ arms. Grade 3+ adverse events affected 68/203 (33.5%) receiving experimental regimens, and 19/68 (27.9%) on control. Ten of 203 (4.9%) participants on experimental arms and 2/68 (2.9%) controls died.CONCLUSION: PaMZ regimens did not achieve non-inferiority in this under-powered trial. An ongoing evaluation of PMD remains a priority.

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Efficacy of pragmatic same-day ring prophylaxis for adult individuals exposed to SARS-CoV-2 in Switzerland (COPEP): protocol of an open-label cluster randomised trial

BMJ Open ◽

10.1136/bmjopen-2020-040110 ◽

2020 ◽

Vol 10 (11) ◽

pp. e040110

Author(s):

Mikaela Smit ◽

Annalisa Marinosci ◽

Giovanni Jacopo Nicoletti ◽

Thomas Perneger ◽

Silvio Ragozzino ◽

...

Keyword(s):

Randomised Trial ◽

Standard Of Care ◽

Cluster Randomised Trial ◽

Postexposure Prophylaxis ◽

Open Label ◽

Daily Monitoring ◽

Intention To Treat ◽

Cluster Randomised ◽

Registration Number ◽

Asymptomatic Individuals

IntroductionLopinavir/ritonavir (LPV/r) has been proposed as repurposed drugs for pre-exposure and postexposure prophylaxis as well as therapy of COVID-19. Coronavirus postexposure prophylaxis (COPEP) trial aims at assessing their efficacy as postexposure ring-prophylaxis among adults exposed to SARS-CoV-2.Methods and analysisCOPEP is a two-arm open-label cluster-randomised trial conducted in three cantons of Switzerland. Asymptomatic contacts (≥16 years) of individuals diagnosed with COVID-19 will be randomised (2:1) to either LPV/r (400 mg/100 mg two times per day) for 5 days, or a standard of care arm (no treatment). Asymptomatic individuals may be either SARS-CoV-2 positive or negative. Contacts living in the single household will form a cluster and will be randomised into the same arm. All participants will be followed-up for 21 days and undergo daily monitoring for COVID-19 symptoms. The primary endpoint is 21-day incidence of laboratory-confirmed COVID-19 with ≥1 compatible symptom, analysed in an intention-to-treat (ITT) analysis. The secondary endpoints include the 21-day incidence of COVID-19 as well as SARS-CoV-2 infection in a modified ITT analysis, excluding participants who had a positive SARS-CoV-2 RT-PCR from oropharyngeal swab and/or a positive SARS-CoV-2 IgG serology at baseline. Assuming a 21-day incidence for COVID-19 of 20% among contacts without postexposure chemoprophylaxis, to detect a relative risk reduction of 60% (ie, translating in an absolute reduction from 20% to 8%), with a power of 80%, an alpha of 5%. Accounting for design effect of cluster design of circa 1.1, we plan to enrol 200 participants to the LPV/r arm and 100 to the standard of care arm, 300 participants in total.Ethics and disseminationEthics approval has been granted by the Commission Cantonale d’Ethique de la Recherche, Ethikkommission Nordwest- und Zentralschweiz and Comitato Etico Cantonale (ref 2020-00864) and Swissmedic (2020DR3056). Results from this trial will be disseminated via journal articles and presentations at national and international conferences.Trial registration numberClinicaltrials.gov Registry (NCT04364022); Swiss National Clinical Trial Portal Registry (SNCTP 000003732).Registered report identifierCCER 2020-0864.

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SWAT 76 evaluation: randomised evaluation of sending pre-notification cards to trial participants before a face-to-face primary outcome measurement to increase attendance

F1000Research ◽

10.12688/f1000research.50890.1 ◽

2021 ◽

Vol 10 ◽

pp. 84

Author(s):

Shaun Treweek ◽

Stephanie Gallant ◽

Annie S. Anderson

Keyword(s):

Direct Cost ◽

Primary Outcome ◽

Outcome Measurement ◽

Behavioural Change ◽

Risk Difference ◽

Secondary Outcome ◽

Face To Face ◽

Intention To Treat ◽

The Uk ◽

Trial Participants

Background: Retention is considered the second highest trial methods priority in the UK after recruitment. Methods: This Study Within A Trial (SWAT) evaluated whether sending a pre-notification card around one month before a face-to-face primary outcome measurement visit compared to not sending the card increased trial retention. The SWAT was a two-arm, parallel randomised (1:1 allocation ratio), stratified by centre, study. It was embedded within the ActWELL host trial, which evaluated whether women receiving lifestyle change counselling from volunteer coaches improved outcomes including weight and physical activity. The text on the card was not developed using formal behavioural change theory but did target factors thought to influence attendance. The SWAT primary outcome was the difference in the proportion of participants attending the host trial primary outcome measurement visit. The secondary outcome was the direct cost of sending cards. Host trial participants and research staff at the primary outcome visit were blind to the SWAT. Analysis was intention-to-treat. GRADE was used the assess the certainty of evidence. Results: 558 host trial participants took part in the SWAT and were included in the analysis. Sending a pre-notification card may result in a slight increase in attendance at a face-to-face primary outcome measurement visit: risk difference = 3.3% (95% confidence interval = -3.0% to 9.6%). This is GRADE low certainty evidence. A recording error meant it was unclear whether 17 participants allocated to the card were actually sent one but a sensitivity analysis did not change the overall result or conclusion. The direct cost of producing and sending the cards was £192 GBP (€213 EUR; $260 USD). Discussion: Trialists could consider using pre-notification as they may gain a slight increase in retention to face-to-face trial measurement visits but further evaluations are needed.

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Appendectomy during the COVID-19 pandemic in Italy: a multicenter ambispective cohort study by the Italian Society of Endoscopic Surgery and new technologies (the CRAC study)

Updates in Surgery ◽

10.1007/s13304-021-01126-z ◽

2021 ◽

Author(s):

Alberto Sartori ◽

Mauro Podda ◽

Emanuele Botteri ◽

Roberto Passera ◽

Ferdinando Agresta ◽

...

Keyword(s):

Acute Appendicitis ◽

Open Surgery ◽

Primary Outcome ◽

New Technologies ◽

Operative Management ◽

Complication Rates ◽

Conversion To Open Surgery ◽

Registration Number ◽

Non Operative Management ◽

Pandemic Wave

AbstractMajor surgical societies advised using non-operative management of appendicitis and suggested against laparoscopy during the COVID-19 pandemic. The hypothesis is that a significant reduction in the number of emergent appendectomies was observed during the pandemic, restricted to complex cases. The study aimed to analyse emergent surgical appendectomies during pandemic on a national basis and compare it to the same period of the previous year. This is a multicentre, retrospective, observational study investigating the outcomes of patients undergoing emergent appendectomy in March–April 2019 vs March–April 2020. The primary outcome was the number of appendectomies performed, classified according to the American Association for the Surgery of Trauma (AAST) score. Secondary outcomes were the type of surgical technique employed (laparoscopic vs open) and the complication rates. One thousand five hundred forty one patients with acute appendicitis underwent surgery during the two study periods. 1337 (86.8%) patients met the inclusion criteria: 546 (40.8%) patients underwent surgery for acute appendicitis in 2020 and 791 (59.2%) in 2019. According to AAST, patients with complicated appendicitis operated in 2019 were 30.3% vs 39.9% in 2020 (p = 0.001). We observed an increase in the number of post-operative complications in 2020 (15.9%) compared to 2019 (9.6%) (p < 0.001). The following determinants increased the likelihood of complication occurrence: undergoing surgery during 2020 (+ 67%), the increase of a unit in the AAST score (+ 26%), surgery performed > 24 h after admission (+ 58%), open surgery (+ 112%) and conversion to open surgery (+ 166%). In Italian hospitals, in March and April 2020, the number of appendectomies has drastically dropped. During the first pandemic wave, patients undergoing surgery were more frequently affected by more severe appendicitis than the previous year's timeframe and experienced a higher number of complications. Trial registration number and date: Research Registry ID 5789, May 7th, 2020

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Cast versus functional brace in the rehabilitation of patients treated non-operatively for a rupture of the Achilles tendon: protocol for the UK study of tendo achilles rehabilitation (UK STAR) multi-centre randomised trial

BMJ Open ◽

10.1136/bmjopen-2017-019628 ◽

2017 ◽

Vol 7 (10) ◽

pp. e019628 ◽

Cited By ~ 5

Author(s):

Juul Achten ◽

Nick R Parsons ◽

Rebecca L Kearney ◽

Michael Maia Schlüssel ◽

Anna S Liew ◽

...

Keyword(s):

Achilles Tendon ◽

Tendon Rupture ◽

Controlled Trial ◽

Randomised Trial ◽

Achilles Tendon Rupture ◽

Plaster Cast ◽

Quality Adjusted Life Year ◽

Eligibility Criteria ◽

Usual Practice ◽

The Uk

IntroductionAchilles tendon rupture affects over 11 000 people yearly in the UK, and the incidence is increasing. Controversy remains with regard to the best rehabilitation strategy for these patients. In operatively treated patients, functional bracing provides better outcomes compared with plaster casts. However, the role of functional bracing in non-operatively managed patients is unclear. This is the protocol for a multicentre randomised trial of plaster cast immobilisation versus functional bracing for patients with a non-operatively managed Achilles tendon rupture.Methods and analysisAll adults presenting with a primary rupture of the Achilles tendon will be screened. Non-operatively treated patients will be eligible to take part in the trial. Broad eligibility criteria will ensure that the results of the study can be generalised to the wider patient population. Randomisation will be on a 1:1 basis. Both rehabilitation strategies are widely used within the National Health Service. Standardised protocols will be followed, and details of plaster material and brace will be as per the site’s usual practice.A minimum of 330 patients will be randomised to obtain 90% power to detect a difference of 8 points in Achilles Tendon Total Rupture Score at 9 months. Quality of life and resource use will be collected at 3, 6 and 9 months. The differences between treatment groups will be assessed on an intention-to-treat basis. The results of the trial-based economic evaluation will be expressed in terms of incremental cost per quality-adjusted life-year gained.Ethics and disseminationThe National Research Ethic Committee approved this study on 18 March 2016 (16/SC/0109).The National Institute for Health Research Health Technology Assessment monograph and a manuscript to a peer-reviewed journal will be submitted on completion of the trial (summer 2019). The results of this trial will substantially inform clinical practice on the clinical and cost-effectiveness of the treatment of this injury. This study has been registered on the International Standard Randomised Controlled Trial Number registry with reference noISRCTN62639639.

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The management of displaced humeral shaft fractures – A survey of UK shoulder and elbow surgeons

Shoulder & Elbow ◽

10.1177/1758573220986940 ◽

2021 ◽

pp. 175857322098694

Author(s):

Abdul Ahad ◽

Aziz Haque ◽

Alison Armstrong ◽

Amit Modi ◽

Radhakant Pandey ◽

...

Keyword(s):

Operative Treatment ◽

Online Survey ◽

Randomised Trial ◽

Operative Management ◽

Humeral Shaft ◽

Related Factors ◽

Humeral Shaft Fractures ◽

Fracture Displacement ◽

Shaft Fractures ◽

The Uk

Introduction Indications for surgical management of displaced humeral shaft fractures are not clearly established, leading to variations in practice. The aim of this study was to determine the scale of these variations in the UK practice to help design a future national trial. Methods An online survey was sent to all surgeon members of British Elbow and Shoulder Society to help define humeral shaft fractures, fracture displacement as well as indications for operative and non-operative management. Patient and injury related factors considered important when managing humeral shaft fractures were investigated. Results The survey achieved a response rate of 32% (104/327). There was a lack of consensus on definitions for humeral shaft fractures and fracture displacement. A functional brace was the most common form of non-operative treatment (63%). Majority immobilise humeral shaft fractures for 4–8 weeks or until callus are visible (62%) with a similar number considering operative treatment if adequate signs of healing are not present at around 12–16 weeks. Around half of our respondents exclusively use plates with variations in preference of approach and a minority (2%) exclusively use intra-medullary nails. Conclusion The significant variation in management of displaced humeral shaft fractures in the UK suggests a clear need to evaluate clinical and cost effectiveness through a multi-centre randomised trial.

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