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BMJ Open Jun 2024Tranexamic acid (TXA) is an inexpensive and widely available medication that reduces blood loss and red blood cell (RBC) transfusion in cardiac and orthopaedic... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Tranexamic acid (TXA) is an inexpensive and widely available medication that reduces blood loss and red blood cell (RBC) transfusion in cardiac and orthopaedic surgeries. While the use of TXA in these surgeries is routine, its efficacy and safety in other surgeries, including oncologic surgeries, with comparable rates of transfusion are uncertain. Our primary objective is to evaluate whether a hospital-level policy implementation of routine TXA use in patients undergoing major non-cardiac surgery reduces RBC transfusion without increasing thrombotic risk.
METHODS AND ANALYSIS
A pragmatic, registry-based, blinded, cluster-crossover randomised controlled trial at 10 Canadian sites, enrolling patients undergoing non-cardiac surgeries at high risk for RBC transfusion. Sites are randomised in 4-week intervals to a hospital policy of intraoperative TXA or matching placebo. TXA is administered as 1 g at skin incision, followed by an additional 1 g prior to skin closure. Coprimary outcomes are (1) effectiveness, evaluated as the proportion of patients transfused RBCs during hospital admission and (2) safety, evaluated as the proportion of patients diagnosed with venous thromboembolism within 90 days. Secondary outcomes include: (1) transfusion: number of RBC units transfused (both at a hospital and patient level); (2) safety: in-hospital diagnoses of myocardial infarction, stroke, deep vein thrombosis or pulmonary embolism; (3) clinical: hospital length of stay, intensive care unit admission, hospital survival, 90-day survival and the number of days alive and out of hospital to day 30; and (4) compliance: the proportion of enrolled patients who receive a minimum of one dose of the study intervention.
ETHICS AND DISSEMINATION
Institutional research ethics board approval has been obtained at all sites. At the completion of the trial, a plain language summary of the results will be posted on the trial website and distributed in the lay press. Our trial results will be published in a peer-reviewed scientific journal.
TRIAL REGISTRATION NUMBER
NCT04803747.
Topics: Humans; Tranexamic Acid; Antifibrinolytic Agents; Canada; Blood Loss, Surgical; Cross-Over Studies; Erythrocyte Transfusion; Organizational Policy
PubMed: 38830735
DOI: 10.1136/bmjopen-2024-084847 -
Bone & Joint Open Jun 2024During total knee replacement (TKR), surgeons can choose whether or not to resurface the patella, with advantages and disadvantages of each approach. Recently, the...
The clinical and cost-effectiveness of elective primary total knee replacement with PAtellar Resurfacing compared to selective patellar resurfacing: a pragmatic multicentre randomized controlled Trial (PART).
AIMS
During total knee replacement (TKR), surgeons can choose whether or not to resurface the patella, with advantages and disadvantages of each approach. Recently, the National Institute for Health and Care Excellence (NICE) recommended always resurfacing the patella, rather than never doing so. NICE found insufficient evidence on selective resurfacing (surgeon's decision based on intraoperative findings and symptoms) to make recommendations. If effective, selective resurfacing could result in optimal individualized patient care. This protocol describes a randomized controlled trial to evaluate the clinical and cost-effectiveness of primary TKR with always patellar resurfacing compared to selective patellar resurfacing.
METHODS
The PAtellar Resurfacing Trial (PART) is a patient- and assessor-blinded multicentre, pragmatic parallel two-arm randomized superiority trial of adults undergoing elective primary TKR for primary osteoarthritis at NHS hospitals in England, with an embedded internal pilot phase (ISRCTN 33276681). Participants will be randomly allocated intraoperatively on a 1:1 basis (stratified by centre and implant type (cruciate-retaining vs cruciate-sacrificing)) to always resurface or selectively resurface the patella, once the surgeon has confirmed sufficient patellar thickness for resurfacing and that constrained implants are not required. The primary analysis will compare the Oxford Knee Score (OKS) one year after surgery. Secondary outcomes include patient-reported outcome measures at three months, six months, and one year (Knee injury and Osteoarthritis Outcome Score, OKS, EuroQol five-dimension five-level questionnaire, patient satisfaction, postoperative complications, need for further surgery, resource use, and costs). Cost-effectiveness will be measured for the lifetime of the patient. Overall, 530 patients will be recruited to obtain 90% power to detect a four-point difference in OKS between the groups one year after surgery, assuming up to 40% resurfacing in the selective group.
CONCLUSION
The trial findings will provide evidence about the clinical and cost-effectiveness of always patellar resurfacing compared to selective patellar resurfacing. This will inform future NICE guidelines on primary TKR and the role of selective patellar resurfacing.
PubMed: 38828864
DOI: 10.1302/2633-1462.56.BJO-2023-0154 -
Global Mental Health (Cambridge,... 2024This study evaluated the effectiveness of Baby Friendly Spaces (BFS), a psychosocial support program for Rohingya refugee mothers of malnourished young children in...
BACKGROUND
This study evaluated the effectiveness of Baby Friendly Spaces (BFS), a psychosocial support program for Rohingya refugee mothers of malnourished young children in Bangladesh. Because BFS was already being implemented, we examined the benefit of enhancing implementation supports.
METHODS
In matched pairs, 10 sites were randomized to provide BFS treatment as usual (BFS-TAU) or to receive enhanced implementation support (BFS-IE). 600 mothers were enrolled and reported on maternal distress, functional impairment, subjective well-being and coping at baseline and 8-week follow-up. Data were analyzed using multilevel linear regression models to account for clustering; sensitivity analyses adjusted for the small number of clusters.
RESULTS
Significant within-group improvements in BFSIE were observed for distres (-.48, p = .014), functional impairment (-.30, p = .002) and subjective well-being (.92, p = .011); improvements in BFS-TAU were smaller and not statistically significant. Between-group comparisons favored BFS-IE for distress (β = -.30, p = .058) and well-being (β = .58, p = .038). Sensitivity adjustments produced p-values above .05 for all between-group comparisons.
DISCUSSION
Feasible adjustments to implementation can improve program delivery to increase impact on maternal distress and well-being. Although results should be interpreted with caution, study design limitations are common in pragmatic, field-based research.
PubMed: 38827334
DOI: 10.1017/gmh.2024.58 -
Research and Practice in Thrombosis and... May 2024Overuse of antiplatelet therapy and underuse of gastroprotection contribute to preventable bleeding in patients taking anticoagulants.
Feasibility and acceptability of patient- and clinician-level antithrombotic stewardship interventions to reduce gastrointestinal bleeding risk in patients using warfarin (Anticoagulation with Enhanced Gastrointestinal Safety): a factorial randomized controlled pilot trial.
BACKGROUND
Overuse of antiplatelet therapy and underuse of gastroprotection contribute to preventable bleeding in patients taking anticoagulants.
OBJECTIVES
(1) Determine the feasibility of a factorial trial testing patient activation and clinician outreach to reduce gastrointestinal (GI) bleeding risk in patients prescribed warfarin-antiplatelet therapy without proton pump inhibitor gastroprotection and (2) assess intervention acceptability.
METHODS
Pragmatic 2 × 2 factorial cluster-randomized controlled pilot comparing (1) a patient activation booklet vs usual care and (2) clinician notification vs clinician notification plus nurse facilitation was performed. The primary feasibility outcome was percentage of patients completing a structured telephone assessment after 5 weeks. Exploratory outcomes, including effectiveness, were evaluated using chart review, surveys, and semistructured interviews.
RESULTS
Among 47 eligible patients, 35/47 (74.5%; 95% CI, 58.6%-85.7%) met the feasibility outcome. In the subset confirmed to be high risk for upper GI bleeding, 11/29 (37.9%; 95% CI, 16.9%-64.7%) made a medication change, without differences between intervention arms. In interviews, few patients reported reviewing the activation booklet; barriers included underestimating GI bleeding risk, misunderstanding the booklet's purpose, and receiving excessive health communication materials. Clinicians responded to notification messages for 24/47 patients (51.1%; 95% CI, 26.4%-75.4%), which was lower for surgeons than nonsurgeons (22.7% vs 76.0%). Medical specialists but not surgeons viewed clinician notification as acceptable.
CONCLUSION
The proposed trial design and outcome ascertainment strategy were feasible, but the patient activation intervention is unlikely to be effective as designed. While clinician notification appears promising, it may not be acceptable to surgeons, findings which support further refinement and testing of a clinician notification intervention.
PubMed: 38827255
DOI: 10.1016/j.rpth.2024.102421 -
AMIA Joint Summits on Translational... 2024To automatically populate the case report forms (CRFs) for an international, pragmatic, multifactorial, response-adaptive, Bayesian COVID-19 platform trial.
OBJECTIVES
To automatically populate the case report forms (CRFs) for an international, pragmatic, multifactorial, response-adaptive, Bayesian COVID-19 platform trial.
METHODS
The locations of focus included 27 hospitals and 2 large electronic health record (EHR) instances (1 Cerner Millennium and 1 Epic) that are part of the same health system in the United States. This paper describes our efforts to use EHR data to automatically populate four of the trial's forms: baseline, daily, discharge, and response-adaptive randomization.
RESULTS
Between April 2020 and May 2022, 417 patients from the UPMC health system were enrolled in the trial. A MySQL-based extract, transform, and load pipeline automatically populated 499 of 526 CRF variables. The populated forms were statistically and manually reviewed and then reported to the trial's international data coordinating center.
CONCLUSIONS
We accomplished automatic population of CRFs in a large platform trial and made recommendations for improving this process for future trials.
PubMed: 38827056
DOI: No ID Found -
BJPsych Open Jun 2024One in 57 children are diagnosed with autism in the UK, and the estimated cost for supporting these children in education is substantial. Social Stories™ is a...
BACKGROUND
One in 57 children are diagnosed with autism in the UK, and the estimated cost for supporting these children in education is substantial. Social Stories™ is a promising and widely used intervention for supporting children with autism in schools and families. It is believed that Social Stories™ can provide meaningful social information to children that can improve social understanding and may reduce anxiety. However, no economic evaluation of Social Stories has been conducted.
AIMS
To assess the cost-effectiveness of Social Stories through Autism Spectrum Social Stories in Schools Trial 2, a multi-site, pragmatic, cluster-randomised controlled trial.
METHOD
Children with autism who were aged 4-11 years were recruited and randomised ( = 249). Costs measured from the societal perspective and quality-adjusted life-years (QALYs) measured by the EQ-5D-Y-3L proxy were collected at baseline and at 6-month follow-up for primary analysis. The incremental cost-effectiveness ratio was calculated, and the uncertainty around incremental cost-effectiveness ratios was captured by non-parametric bootstrapping. Sensitivity analyses were performed to evaluate the robustness of the primary findings.
RESULTS
Social Stories is likely to result in a small cost savings (-£191 per child, 95% CI -767.7 to 337.7) and maintain similar QALY improvements compared with usual care. The probability of Social Stories being a preferred option is 75% if society is willing to pay £20 000 per QALY gained. The sensitivity analysis results aligned with the main study outcomes.
CONCLUSIONS
Compared with usual care, Social Stories did not lead to an increase in costs and maintained similar QALY improvements for primary-aged children with autism.
PubMed: 38826027
DOI: 10.1192/bjo.2024.47 -
Heart, Lung & Circulation May 2024Physical activity (PA) and weight management are critical for cardiovascular disease (CVD) secondary prevention. However, PA adherence during or after cardiac...
An Australian Football Themed Health Behaviour Change Intervention for Men With Cardiovascular Disease is Feasible and Acceptable: Results From a Feasibility Randomised Trial.
BACKGROUND
Physical activity (PA) and weight management are critical for cardiovascular disease (CVD) secondary prevention. However, PA adherence during or after cardiac rehabilitation is low. Here, we assess the feasibility and acceptability of the Australian football-themed Aussie Fans in Training (Aussie-FIT) program and associated trial procedures when adapted for men with CVD.
METHOD
A pragmatic randomised control trial, with waitlist control arm, and follow-up measures at 3 and 6 months. Men with a CVD diagnosis and body mass index ≥25 kg/m were recruited from community and clinical settings, and randomised, following baseline measures of health and health behaviours. The intervention arm attended 12 face-to-face football-themed education and PA sessions. Feasibility (recruitment, retention, attendance, and adherence to trial procedures) was assessed via mixed methods.
RESULTS
A total of 74% (64/86) of participants expressing interest met the eligibility criteria. Of those, 49 men (mean age=61.4, standard deviation=9.5, mean body mass index=31.3, standard deviation=4.2) were randomised. Program attendance rates (87% attended ≥80% of sessions) and retention (92%) were high. Trial retention at the primary end point (3 months) was high (86%) and at the 6-month follow-ups reduced to 67%. Program and trial procedures were acceptable, except for the request to visit a pathologist for the blood draw.
CONCLUSIONS
Using a football theme and setting may be a feasible way to engage men with CVD in health behaviour change. Given the existing pilot evidence for men at risk of CVD, and that recruitment rates were under the target, trialling a program for men with or at risk of CVD is recommended.
PubMed: 38824056
DOI: 10.1016/j.hlc.2024.03.012 -
Drug and Alcohol Dependence Jul 2024To evaluate the effects of booster and no booster versions of web-based alcohol Personalised Normative Feedback (PNF) and whether descriptive norms mediated and/or... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
To evaluate the effects of booster and no booster versions of web-based alcohol Personalised Normative Feedback (PNF) and whether descriptive norms mediated and/or participant motivation moderated the effectiveness of the intervention in real world conditions (i.e. no financial incentives).
METHODS
Pragmatic randomised controlled trial with 1-, 3-, and 6-month assessments. Brazilian college students reporting alcohol use in the last 12 months (N=931) were recruited from May/2020 to December/2022 and allocated to 1) No booster/single PNF(S-PNF); 2) Booster/multiple PNF(M-PNF); or 3) Assessment-only control. We applied Helmert coding [1: Any intervention (S-PNF or M-PNF) vs. Control; and 2: S-PNF vs. M-PNF].
PRIMARY OUTCOMES
typical number of drinks/week and maximum number of drinks/week; secondary outcomes: drinking frequency and number of consequences. Three-months assessment was the primary interval. Descriptive norms were tested as mediator. Interest, importance, and readiness to change were examined as moderators.
RESULTS
Compared to control, any intervention did not influence primary outcomes at 3-months or 6-months, but did at 1-month, when reduced typical drinking (IRR:0.77, 95%CI:0.66;0.90) and maximum number of drinks (IRR:0.69, 95%CI:0.58;0.82). There was an intervention effect on the consequences at 3-months. No differences were observed between S-PNF and M-PNF. No mediation effects were found at 3-months. At 6-months, there was an indirect effect on typical drinking through norms at 3-months (b=-0.82, 95%CI:-2.03;-0.12) and effects on maximum drinks through norms at 1-month (b=-0.54, 95%CI:-1.65;-0.02). No support for moderation was found.
CONCLUSIONS
Intervention reduced alcohol drinking at 1 month only and was not effective thereafter. Mechanisms of effect remain unclear.
Topics: Humans; Male; Female; Young Adult; Students; Alcohol Drinking in College; Universities; Adolescent; Internet-Based Intervention; Internet; Feedback, Psychological; Motivation; Alcohol Drinking; Brazil; Adult; Social Norms
PubMed: 38823192
DOI: 10.1016/j.drugalcdep.2024.111337 -
BMC Medical Research Methodology May 2024Inequities in health access and outcomes exist between Indigenous and non-Indigenous populations. Embedded pragmatic randomized, controlled trials (ePCTs) can test the...
BACKGROUND
Inequities in health access and outcomes exist between Indigenous and non-Indigenous populations. Embedded pragmatic randomized, controlled trials (ePCTs) can test the real-world effectiveness of health care interventions. Assessing readiness for ePCT, with tools such as the Readiness Assessment for Pragmatic Trials (RAPT) model, is an important component. Although equity must be explicitly incorporated in the design, testing, and widespread implementation of any health care intervention to achieve equity, RAPT does not explicitly consider equity. This study aimed to identify adaptions necessary for the application of the 'Readiness Assessment for Pragmatic Trials' (RAPT) tool in embedded pragmatic randomized, controlled trials (ePCTs) with Indigenous communities.
METHODS
We surveyed and interviewed participants (researchers with experience in research involving Indigenous communities) over three phases (July-December 2022) in this mixed-methods study to explore the appropriateness and recommended adaptions of current RAPT domains and to identify new domains that would be appropriate to include. We thematically analyzed responses and used an iterative process to modify RAPT.
RESULTS
The 21 participants identified that RAPT needed to be modified to strengthen readiness assessment in Indigenous research. In addition, five new domains were proposed to support Indigenous communities' power within the research processes: Indigenous Data Sovereignty; Acceptability - Indigenous Communities; Risk of Research; Research Team Experience; Established Partnership). We propose a modified tool, RAPT-Indigenous (RAPT-I) for use in research with Indigenous communities to increase the robustness and cultural appropriateness of readiness assessment for ePCT. In addition to producing a tool for use, it outlines a methodological approach to adopting research tools for use in and with Indigenous communities by drawing on the experience of researchers who are part of, and/or working with, Indigenous communities to undertake interventional research, as well as those with expertise in health equity, implementation science, and public health.
CONCLUSION
RAPT-I has the potential to provide a useful framework for readiness assessment prior to ePCT in Indigenous communities. RAPT-I also has potential use by bodies charged with critically reviewing proposed pragmatic research including funding and ethics review boards.
Topics: Humans; Indigenous Peoples; Pragmatic Clinical Trials as Topic; Health Services, Indigenous; Surveys and Questionnaires; Research Design; Health Services Accessibility; Randomized Controlled Trials as Topic
PubMed: 38822242
DOI: 10.1186/s12874-024-02244-z -
American Heart Journal May 2024Aortic valve replacement in asymptomatic severe aortic stenosis is controversial. The Early valve replacement in severe ASYmptomatic Aortic Stenosis (EASY-AS) trial aims...
BACKGROUND
Aortic valve replacement in asymptomatic severe aortic stenosis is controversial. The Early valve replacement in severe ASYmptomatic Aortic Stenosis (EASY-AS) trial aims to determine whether early aortic valve replacement improves clinical outcomes, quality of life and cost-effectiveness compared to a guideline recommended strategy of 'watchful waiting'.
METHODS
In a pragmatic international, open parallel group randomized controlled trial (NCT04204915), 2844 patients with severe aortic stenosis will be randomized 1:1 to either a strategy of early (surgical or transcatheter) aortic valve replacement or aortic valve replacement only if symptoms or impaired left ventricular function develop. Exclusion criteria include other severe valvular disease, planned cardiac surgery, ejection fraction <50%, previous aortic valve replacement or life expectancy <2 years. The primary outcome is a composite of cardiovascular mortality or heart failure hospitalization. The primary analysis will be undertaken when 663 primary events have accrued, providing 90% power to detect a reduction in the primary endpoint from 27.7% to 21.6% (hazard ratio 0.75). Secondary endpoints include disability-free survival, days alive and out of hospital, major adverse cardiovascular events and quality of life.
RESULTS
Recruitment commenced in March 2020 and is open in the UK, Australia, New Zealand and Serbia. Feasibility requirements were met in July 2022, and the main phase opened in October 2022, with additional international centers in set-up.
CONCLUSIONS
The EASY-AS trial will establish whether a strategy of early aortic valve replacement in asymptomatic patients with severe aortic stenosis reduces cardiovascular mortality or heart failure hospitalization and improves other important outcomes.
PubMed: 38821453
DOI: 10.1016/j.ahj.2024.05.013