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BMJ Open Jun 2024Biological disease-modifying antirheumatic drugs (bDMARDs) have revolutionised the treatment of inflammatory arthritis (IA). However, many people with IA still require...
PERI-operative biologic DMARD management: Stoppage or COntinuation during orthoPaEdic operations (the PERISCOPE trial) - a study protocol for a pragmatic, UK multicentre, superiority randomised controlled trial with an internal pilot, economic evaluation and nested qualitative study.
INTRODUCTION
Biological disease-modifying antirheumatic drugs (bDMARDs) have revolutionised the treatment of inflammatory arthritis (IA). However, many people with IA still require planned orthopaedic surgery to reduce pain and improve function. Currently, bDMARDs are withheld during the perioperative period due to potential infection risk. However, this predisposes patients to IA flares and loss of disease control. The question of whether to stop or continue bDMARDs in the perioperative period has not been adequately addressed in a randomised controlled trial (RCT).
METHODS AND ANALYSIS
PERISCOPE is a multicentre, superiority, pragmatic RCT investigating the stoppage or continuation of bDMARDs. Participants will be assigned 1:1 to either stop or continue their bDMARDs during the perioperative period. We aim to recruit 394 adult participants with IA. Potential participants will be identified in secondary care hospitals in the UK, screened by a delegated clinician. If eligible and consenting, baseline data will be collected and randomisation completed. The primary outcome will be the self-reported PROMIS-29 (Patient Reported Outcome Measurement Information System) over the first 12 weeks postsurgery. Secondary outcome measures are as follows: PROMIS - Health Assessment Questionnaire (PROMIS-HAQ), EQ-5D-5L, Disease activity: generic global Numeric Rating Scale (patient and clinician), Self-Administered Patient Satisfaction scale, Health care resource use and costs, Medication use, Surgical site infection, delayed wound healing, Adverse events (including systemic infections) and disease-specific outcomes (according to IA diagnosis). The costs associated with stopping and continuing bDMARDs will be assessed. A qualitative study will explore the patients' and clinicians' acceptability and experience of continuation/stoppage of bDMARDs in the perioperative period and the impact postoperatively.
ETHICS AND DISSEMINATION
Ethical approval for this study was received from the West of Scotland Research Ethics Committee on 25 April 2023 (REC Ref: 23/WS/0049). The findings from PERISCOPE will be submitted to peer-reviewed journals and feed directly into practice guidelines for the use of bDMARDs in the perioperative period.
TRIAL REGISTRATION NUMBER
ISRCTN17691638.
Topics: Humans; Orthopedic Procedures; United Kingdom; Antirheumatic Agents; Pragmatic Clinical Trials as Topic; Perioperative Care; Qualitative Research; Multicenter Studies as Topic; Pilot Projects; Cost-Benefit Analysis; Biological Products
PubMed: 38910007
DOI: 10.1136/bmjopen-2024-084997 -
Epilepsy Research Jun 2024Anxiety and depression are highly prevalent and impactful in epilepsy. American Academy of Neurology quality measures emphasize anxiety and depression screening and...
BACKGROUND AND OBJECTIVES
Anxiety and depression are highly prevalent and impactful in epilepsy. American Academy of Neurology quality measures emphasize anxiety and depression screening and quality of life (QOL) measurement, yet usual epilepsy care QOL and anxiety/depression outcomes are poorly characterized. The main objective was to assess 6-month QOL, anxiety and depression during routine care among adults with epilepsy and baseline anxiety or depression symptoms; these were prespecified secondary outcomes within a pragmatic randomized trial of remote assessment methods.
METHODS
Adults with anxiety or depression symptoms and no suicidal ideation were recruited from a tertiary epilepsy clinic via an electronic health record (EHR)-embedded process. Participants were randomized 1:1 to 6 month outcome collection via patient portal EHR questionnaires vs. telephone interview. This report focuses on an a priori secondary outcomes of the overall trial, focused on patient-reported health outcomes in the full sample. Quality of life, (primary health outcome), anxiety, and depression measures were collected at 3 and 6 months (Quality of Life in Epilepsy-10, QOLIE-10, Generalized Anxiety Disorder-7, Neurological Disorders Depression Inventory-Epilepsy). Change values and 95 % confidence intervals were calculated. In post-hoc exploratory analyses, patient-reported anxiety/depression management plans at baseline clinic visit and healthcare utilization were compared with EHR-documentation, and agreement was calculated using the kappa statistic.
RESULTS
Overall, 30 participants (15 per group) were recruited and analyzed, of mean age 42.5 years, with 60 % women. Mean 6-month change in QOLIE-10 overall was 2.0(95 % CI -6.8, 10.9), and there were no significant differences in outcomes between the EHR and telephone groups. Mean anxiety and depression scores were stable across follow-up (all 95 % CI included zero). Outcomes were similar regardless of whether an anxiety or depression action plan was documented. During the baseline interview, most participants with clinic visit EHR documentation indicating action to address anxiety and/or depression reported not being offered a treatment(7 of 12 with action plan, 58 %), and there was poor agreement between patient report and EHR documentation (kappa=0.22). Healthcare utilization was high: 40 % had at least one hospitalization or emergency/urgent care visit reported and/or identified via EHR, but a third (4/12) failed to self-report an EHR-identified hospitalization/urgent visit.
DISCUSSION
Over 6 months of usual care among adults with epilepsy and anxiety or depression symptoms, there was no significant average improvement in quality of life or anxiety/depression, suggesting a need for interventions to enhance routine neurology care and achieve quality of life improvement for this group.
PubMed: 38908323
DOI: 10.1016/j.eplepsyres.2024.107396 -
Implementation Science Communications Jun 2024Qualitative methods are a critical tool for enhancing implementation planning and tailoring, yet rapid turn-around of qualitative insights can be challenging in large...
BACKGROUND
Qualitative methods are a critical tool for enhancing implementation planning and tailoring, yet rapid turn-around of qualitative insights can be challenging in large implementation trials. The Department of Veterans Affairs-funded EMPOWER 2.0 Quality Enhancement Research Initiative (QUERI) is conducting a hybrid type 3 effectiveness-implementation trial comparing the impact of Replicating Effective Programs (REP) and Evidence-Based Quality Improvement (EBQI) as strategies for implementing three evidence-based practices (EBPs) for women Veterans. We describe the development of the Rapid Implementation Feedback (RIF) report, a pragmatic, team-based approach for the rapid synthesis of qualitative data to aid implementation planning and tailoring, as well as findings from a process evaluation of adopting the RIF report within the EMPOWER 2.0 QUERI.
METHODS
Trained qualitative staff conducted 125 semi-structured pre-implementation interviews with frontline staff, providers, and leadership across 16 VA sites between October 2021 and October 2022. High-priority topic domains informed by the updated Consolidated Framework for Implementation Research were selected in dialogue between EMPOWER 2.0 implementation and evaluation teams, and relevant key points were summarized for each interview to produce a structured RIF report, with emergent findings about each site highlighted in weekly written and verbal communications. Process evaluation was conducted to assess EMPOWER 2.0 team experiences with the RIF report across pre-implementation data collection and synthesis and implementation planning and tailoring.
RESULTS
Weekly RIF updates supported continuous EMPOWER 2.0 team communication around key findings, particularly questions and concerns raised by participating sites related to the three EBPs. Introducing the RIF report into team processes enhanced: team communication; quality and rigor of qualitative data; sensemaking around emergent challenges; understanding of site readiness; and tailoring of REP and EBQI implementation strategies. RIF report findings have facilitated rapid tailoring of implementation planning and rollout, supporting increased responsiveness to sites' needs and concerns.
CONCLUSIONS
The RIF report provides a structured strategy for distillation of time-sensitive findings, continuous team communication amid a complex multi-site implementation effort, and effective tailoring of implementation rollout in real-time. Use of the RIF report may also support trust-building by enhancing responsiveness to sites during pre- and early implementation.
TRIAL REGISTRATION
Enhancing Mental and Physical Health of Women Veterans (NCT05050266); https://clinicaltrials.gov/study/NCT05050266?term=EMPOWER%202.0&rank=1 Date of registration: 09/09/2021.
PubMed: 38907331
DOI: 10.1186/s43058-024-00605-9 -
Anesthesiology Jun 2024High-dose corticosteroids have been used to attenuate the inflammatory response to cardiac surgery and cardiopulmonary bypass, but patient outcome benefits remain...
BACKGROUND
High-dose corticosteroids have been used to attenuate the inflammatory response to cardiac surgery and cardiopulmonary bypass, but patient outcome benefits remain unclear. Our primary aim was to determine whether using dexamethasone was superior to not using dexamethasone to increase the number of home days in the first 30 days after cardiac surgery. Our secondary aim was to evaluate efficiency, value and impact of the novel trial design.
METHODS
This pragmatic, international trial incorporating a prerandomized consent design favoring local practice enrolled patients undergoing cardiac surgery across 7 hospitals in Australia and The Netherlands. Patients were randomly assigned to dexamethasone, 1 mg/kg, or not (control). The primary outcome was the number of days alive and at home up to 30 days after surgery ("home days"). Secondary outcomes included prolonged mechanical ventilation (>48 h), sepsis, renal failure, myocardial infarction, stroke and death.
RESULTS
Of 2093 patients assessed for eligibility, 1951 were randomized (median age 63 years, 80% male). The median number of home days was 23.0 (IQR, 20.1 to 24.1) in the dexamethasone group and 23.1 (IQR, 20.1 to 24.6) in the no dexamethasone group; median difference 0.1 (95% CI, -0.3 to 0.5), P=0.66. The rates of prolonged mechanical ventilation, RR 0.72 (95% CI, 0.48 to 1.08), sepsis, RR 1.02 (95% CI, 0.57 to 1.82), renal failure, RR 0.94 (95% CI, 0.80 to 1.12), myocardial infarction, RR 1.20 (95% CI, 0.30 to 4.82), stroke, RR 1.06 (95% CI, 0.54 to 2.08), and death, RR 0.72 (95% CI, 0.22 to 2.35), were comparable between groups (all P>0.10). Dexamethasone reduced intensive care unit stay, median 29 (IQR, 22 to 50) h vs. 43 (24 to 72) h, P=0.004. Our novel trial design was highly efficient (89.3% enrolment).
CONCLUSIONS
Among patients undergoing cardiac surgery, high-dose dexamethasone decreased intensive care unit stay but did not increase the number of home days after surgery.
PubMed: 38904693
DOI: 10.1097/ALN.0000000000005127 -
BMJ Open Jun 2024Smoking cessation is an essential, but often overlooked aspect of diabetes management. Despite the need for tailored smoking cessation support for individuals with...
Assessing the feasibility and acceptability of a diabetes-specific nurse-led multicomponent smoking cessation intervention in diabetes education: study protocol for an open-label pragmatic randomised controlled trial.
INTRODUCTION
Smoking cessation is an essential, but often overlooked aspect of diabetes management. Despite the need for tailored smoking cessation support for individuals with diabetes, evidence of effective interventions for this cohort is limited. Additionally, individuals with diabetes do not easily adopt such interventions, resulting in low uptake and abstinence rates. This protocol describes a study that aims to assess the feasibility and acceptability of a unique smoking cessation intervention, based on the best evidence, theory and the needs of individuals with diabetes, among patients and service providers, the diabetes nurse educators.
METHODS AND ANALYSIS
This is an open-label pragmatic randomised controlled trial. Between 80 and 100 individuals with type 1 or type 2 diabetes who smoke will be recruited from the diabetes outpatients at the main acute public hospital in Malta, starting in August 2023. Participants will be randomly assigned (1:1 ratio) to the intervention or control arm for 12 weeks. The experimental intervention will consist of three to four smoking cessation behavioural support sessions based on the 5As (Ask, Advise, Assess, Assist and Arrange) algorithm, and a 6-week supply of nicotine replacement therapy. The control intervention will consist of an active referral to the Maltese National Health Service's one-to-one smoking cessation support service, which is based on motivational interviewing. The primary feasibility and acceptability outcomes include the recruitment and participation rates, resources used, problems identified by the nurses, the nurses' perceived challenges and facilitators to implementation and the nurses' and patients' acceptability of the study intervention. Data analyses will be descriptive, with quantitative feasibility and acceptability outcomes reported with 95% confidence intervals.
ETHICS AND DISSEMINATION
Ethical clearance was obtained from the Faculty of Health Sciences Research Ethics Committee, University of Malta. The study results will be disseminated through conference presentations and a publication in a peer-reviewed journal.
TRIAL REGISTRATION NUMBER
NCT05920096.
Topics: Humans; Smoking Cessation; Feasibility Studies; Pragmatic Clinical Trials as Topic; Diabetes Mellitus, Type 2; Patient Education as Topic; Diabetes Mellitus, Type 1; Patient Acceptance of Health Care
PubMed: 38904126
DOI: 10.1136/bmjopen-2023-083235 -
Frontiers in Neurology 2024Painful diabetic neuropathy (PDN) is a common chronic neurological complication of diabetes mellitus. Medications are often used to relieve pain, but with significant...
BACKGROUND
Painful diabetic neuropathy (PDN) is a common chronic neurological complication of diabetes mellitus. Medications are often used to relieve pain, but with significant side effects. Acupuncture is now a component of pragmatic and integrative treatment for PDN. An increasing number of relevant randomized controlled trials have been published in recent years, but a comprehensive meta-analysis has not yet been performed. The aim of this paper is to verify the effectiveness and safety of acupuncture for PDN by meta-analysis and trial sequential analysis (TSA).
METHODS
All participants in this study should have had a PDN diagnosis and the trial group was treated with acupuncture. Eight databases, including EMbase, PubMed, Web of science, Cochrane Library, China Biology Medicine disc (CBM), China National Knowledge Infrastructure (CNKI), Wanfang and Chongqing VIP (CQVIP) were retrieved from inception to 5 April 2023. Meta-analysis was conducted utilizing RevMan 5.3 and Stata 15.0. TSA was performed to assess the adequacy of sample size for the outcomes.
RESULTS
A total of 36 studies, comprising 2,739 PDN patients, were included. Among them, 1,393 patients were assigned to the trial group and 1,346 patients were treated in the control group. Outcomes covers the primary indicator Total effective rate (RR = 1.42, 95%CI [1.34, 1.52], < 0.00001), with 21 studies reported, Pain intensity (SMD = -1.27, 95%CI [-1.58, -0.95], p < 0.00001), with 23 studies reported, and other outcomes, including motor nerve conduction velocity (MCV; MD = 3.58, 95%CI [2.77, 4.38], < 0.00001), sensory nerve conduction velocity (SCV; MD = 3.62, 95%CI [2.75, 4.49], < 0.00001), Depression score (SMD = -1.02, 95%CI [1.58, 0.46]), Toronto clinical scoring system (TCSS; MD = -2.41, 95%CI [-3.37, -1.45], < 0.00001), Quality of life (SMD = 1.06, 95%CI [0.66, 1.46]), traditional Chinese medicine (TCM) syndrome score (MD = -4.99, 95%CI [-6.79, -3.18], < 0.00001), suggesting that acupuncture have an ameliorating effect on PDN in various respect. Egger's test revealed publication bias for four outcomes. TSA showed that as for Total effective rate, Pain Intensity, MCV and SCV, the number of included studies was sufficient to support the conclusions.
CONCLUSION
Acupuncture demonstrates significant effectiveness in improving PDN outcomes, including Total effective rate, Pain intensity, MCV, SCV, Depression score, TCSS, Quality of life, TCM syndrome score. But the Adverse events rate is no different in trail group and control group. The publication bias presented in Total effective rate, Pain intensity, MCV and SCV can be remedied by Trim and filling method.
SYSTEMATIC REVIEW REGISTRATION
Prospero, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=477295.
PubMed: 38903165
DOI: 10.3389/fneur.2024.1402458 -
British Dental Journal Jun 2024Introduction The International Caries Classification and Management System (ICCMS) was developed to standardise caries diagnosis, risk assessment and treatment decisions...
Introduction The International Caries Classification and Management System (ICCMS) was developed to standardise caries diagnosis, risk assessment and treatment decisions based on overall evidence. To evaluate its criteria in practice, a clinical trial assessed professionals' perceptions of two caries management systems.Methods A perception questionnaire was administered to two groups: one using ICCMS criteria and the other based on professional experience criteria (non-ICCMS group). The online questionnaire included quantitative scale questions to measure effort and satisfaction and two open-ended questions to collect the positive and negative perceptions of dentists by using either criteria system. The questionnaires were administered six months after the study's implementation.Results Both groups showed high levels of effort and satisfaction. Professionals using ICCMS reported more positive perceptions by citing improved diagnosis (71.4%) and standardised patient care (43%). However, they also noted negative aspects, such as increased number of questionnaires and records (58%), longer clinical sessions (43%) and higher rates of patient absenteeism (29%).Conclusion Professionals who used the ICCMS had a positive outlook on the system, with benefits seen in diagnosis and patient monitoring. However, there is room for improvement in terms of automation and simplification to enhance the professional use of the system in the clinical setting.
PubMed: 38902437
DOI: 10.1038/s41415-024-7510-9 -
International Journal of Medical... Jun 2024The surge in emergency head CT imaging and artificial intelligence (AI) advancements, especially deep learning (DL) and convolutional neural networks (CNN), have... (Review)
Review
BACKGROUND
The surge in emergency head CT imaging and artificial intelligence (AI) advancements, especially deep learning (DL) and convolutional neural networks (CNN), have accelerated the development of computer-aided diagnosis (CADx) for emergency imaging. External validation assesses model generalizability, providing preliminary evidence of clinical potential.
OBJECTIVES
This study systematically reviews externally validated CNN-CADx models for emergency head CT scans, critically appraises diagnostic test accuracy (DTA), and assesses adherence to reporting guidelines.
METHODS
Studies comparing CNN-CADx model performance to reference standard were eligible. The review was registered in PROSPERO (CRD42023411641) and conducted on Medline, Embase, EBM-Reviews and Web of Science following PRISMA-DTA guideline. DTA reporting were systematically extracted and appraised using standardised checklists (STARD, CHARMS, CLAIM, TRIPOD, PROBAST, QUADAS-2).
RESULTS
Six of 5636 identified studies were eligible. The common target condition was intracranial haemorrhage (ICH), and intended workflow roles auxiliary to experts. Due to methodological and clinical between-study variation, meta-analysis was inappropriate. The scan-level sensitivity exceeded 90 % in 5/6 studies, while specificities ranged from 58,0-97,7 %. The SROC 95 % predictive region was markedly broader than the confidence region, ranging above 50 % sensitivity and 20 % specificity. All studies had unclear or high risk of bias and concern for applicability (QUADAS-2, PROBAST), and reporting adherence was below 50 % in 20 of 32 TRIPOD items.
CONCLUSION
0.01 % of identified studies met the eligibility criteria. The evidence on the DTA of CNN-CADx models for emergency head CT scans remains limited in the scope of this review, as the reviewed studies were scarce, inapt for meta-analysis and undermined by inadequate methodological conduct and reporting. Properly conducted, external validation remains preliminary for evaluating the clinical potential of AI-CADx models, but prospective and pragmatic clinical validation in comparative trials remains most crucial. In conclusion, future AI-CADx research processes should be methodologically standardized and reported in a clinically meaningful way to avoid research waste.
PubMed: 38901270
DOI: 10.1016/j.ijmedinf.2024.105523 -
Movement Disorders Clinical Practice Jun 2024Parkinson's Disease (PD) is a progressive neurological disorder that results in potentially debilitating mobility deficits. Recently, spinal cord stimulation (SCS) has... (Review)
Review
BACKGROUND
Parkinson's Disease (PD) is a progressive neurological disorder that results in potentially debilitating mobility deficits. Recently, spinal cord stimulation (SCS) has been proposed as a novel therapy for PD gait disorders. The highest levels of evidence remain limited for SCS.
OBJECTIVES
In this systematic review and narrative synthesis, the literature was searched using combinations of key phrases indicating spinal cord stimulation and PD.
METHODS
We included pre-clinical studies and all published clinical trials, case reports, conference abstracts as well as protocols for ongoing clinical trials. Additionally, we included trials of SCS applied to atypical parkinsonism.
RESULTS
A total of 45 human studies and trials met the inclusion criteria. Based on the narrative synthesis, a number of knowledge gaps and future avenues of potential research were identified. This review demonstrated that evidence for SCS is currently not sufficient to recommend it as an evidence-based therapy for PD related gait disorders. There remain challenges and significant barriers to widespread implementation, including issues regarding patient selection, effective outcome selection, stimulation location and mode, and in programming parameter optimization. Results of early randomized controlled trials are currently pending. SCS is prone to placebo, lessebo and nocebo as well as blinding effects which may impact interpretation of outcomes, particularly when studies are underpowered.
CONCLUSION
Therapies such as SCS may build on current evidence and be shown to improve specific gait features in PD. Early negative trials should be interpreted with caution, as more evidence will be required to develop effective methodologies in order to drive clinical outcomes.
PubMed: 38899557
DOI: 10.1002/mdc3.14143 -
Clinical Trials (London, England) Jun 2024Performing large randomized trials in anesthesiology is often challenging and costly. The clinically integrated randomized trial is characterized by simplified logistics...
BACKGROUND
Performing large randomized trials in anesthesiology is often challenging and costly. The clinically integrated randomized trial is characterized by simplified logistics embedded into routine clinical practice, enabling ease and efficiency of recruitment, offering an opportunity for clinicians to conduct large, high-quality randomized trials under low cost. Our aims were to (1) demonstrate the feasibility of the clinically integrated trial design in a high-volume anesthesiology practice and (2) assess whether trial quality improvement interventions led to more balanced accrual among study arms and improved trial compliance over time.
METHODS
This is an interim analysis of recruitment to a cluster-randomized trial investigating three nerve block approaches for mastectomy with immediate implant-based reconstruction: paravertebral block (arm 1), paravertebral plus interpectoral plane blocks (arm 2), and serratus anterior plane plus interpectoral plane blocks (arm 3). We monitored accrual and consent rates, clinician compliance with the randomized treatment, and availability of outcome data. Assessment after the initial year of implementation showed a slight imbalance in study arms suggesting areas for improvement in trial compliance. Specific improvement interventions included increasing the frequency of communication with the consenting staff and providing direct feedback to clinician investigators about their individual recruitment patterns. We assessed overall accrual rates and tested for differences in accrual, consent, and compliance rates pre- and post-improvement interventions.
RESULTS
Overall recruitment was extremely high, accruing close to 90% of the eligible population. In the pre-intervention period, there was evidence of bias in the proportion of patients being accrued and receiving the monthly block, with higher rates in arm 3 (90%) compared to arms 1 (81%) and 2 (79%, p = 0.021). In contrast, in the post-intervention period, there was no statistically significant difference between groups (p = 0.8). Eligible for randomization rate increased from 89% in the pre-intervention period to 95% in the post-intervention period (difference 5.7%; 95% confidence interval = 2.2%-9.4%, p = 0.002). Consent rate increased from 95% to 98% (difference of 3.7%; 95% confidence interval = 1.1%-6.3%; p = 0.004). Compliance with the randomized nerve block approach was maintained at close to 100% and availability of primary outcome data was 100%.
CONCLUSION
The clinically integrated randomized trial design enables rapid trial accrual with a high participant compliance rate in a high-volume anesthesiology practice. Continuous monitoring of accrual, consent, and compliance rates is necessary to maintain and improve trial conduct and reduce potential biases. This trial methodology serves as a template for the implementation of other large, low-cost randomized trials in anesthesiology.
PubMed: 38895970
DOI: 10.1177/17407745241255087