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Annals of Surgery Open : Perspectives... Jun 2024
Response to: Comment on "Effects of a Pragmatic Home-Based Exercise Program Concurrent With Neoadjuvant Therapy on Physical Function of Patients With Pancreatic Cancer: The PancFit Randomized Clinical Trial".
PubMed: 38911649
DOI: 10.1097/AS9.0000000000000435 -
Hepatobiliary Surgery and Nutrition Jun 2024Immune checkpoint inhibitor (ICI)-based therapy has achieved impressive success in various cancer types. Several ICIs have been unprecedentedly approved as the treatment... (Review)
Review
BACKGROUND AND OBJECTIVE
Immune checkpoint inhibitor (ICI)-based therapy has achieved impressive success in various cancer types. Several ICIs have been unprecedentedly approved as the treatment regimens for advanced hepatocellular carcinoma (HCC) in recent decade. Meanwhile, numerous clinical trials are being performed to exploit more ICIs into initially unresectable HCC and postoperative HCC to expectantly induce adequate tumor downstaging for further resection or implement adjuvant treatment for relapse-free survival, respectively. In this review, we aim to summarize some pragmatic histomorphologic, immunohistochemical, and molecular pathologic parameters which promisingly indicate the response of neoadjuvant/conversion ICI-related therapy and predict the efficacy of adjuvant/therapeutic ICI-related therapy for HCC.
METHODS
We searched PubMed using the terms hepatocellular carcinoma, immunotherapy, immune checkpoint inhibitor, immune checkpoint blockade, conversion therapy, neoadjuvant therapy, adjuvant therapy, biomarker, pathologic evaluation, pathologic assessment till February 2023.
KEY CONTENT AND FINDINGS
Although there is no consensus regarding the pathologic evaluation of relevant HCC specimens, it is encouraging that a few of studies have concentrated on this field, and moreover, the methods and parameters noted on other cancer types are also worthy of reference. For the pathologic assessment of HCC specimens underwent immunotherapy, a suitable sampling scheme, identifying immunotherapy-related pathologic response, and quantification of pathologic response rate should be emphasized. For the patients of HCC who are scheduled to receive immunotherapy, tumor-infiltrating lymphocyte, intratumoral tertiary lymphoid structure, programmed cell death ligand 1, , microsatellite instability and mismatch repair, tumor mutational burden and tumor neoantigen, as well as some other signaling pathways are the potential predictive biomarkers of treatment response of ICI.
CONCLUSIONS
The management of HCC in the era of immunotherapy arises a brand-new pathological challenge that is to provide an immunotherapy-related diagnostic report. Albeit many related researches are preclinical or insufficient, they may tremendously alter the immunotherapy strategy of HCC in future.
PubMed: 38911201
DOI: 10.21037/hbsn-22-527 -
Acta Oncologica (Stockholm, Sweden) Jun 2024The Precision Oncology Platform (POP) trial represents the effort of the Portuguese Oncology Institute of Porto (IPO Porto) for joining other leading European...
BACKGROUND AND PURPOSE
The Precision Oncology Platform (POP) trial represents the effort of the Portuguese Oncology Institute of Porto (IPO Porto) for joining other leading European institutions in both 'Personalised Cancer Medicine for all EU citizens' (PCM4EU), and 'PRecisIon Cancer MEdicine RepurpOsing SystEm Using Pragmatic Clinical Trials' (PRIME-ROSE) consortia, enabling the development of the Portuguese version of the Drug Rediscovery Protocol (DRUP)-like Clinical Trial (DLCT), based on the experience of the DRUP trial developed in The Netherlands.
PATIENTS/MATERIAL AND METHODS
The POP trial is a phase II, pragmatic multicentric, non-randomised, open-label study, designed entirely like the other DLCTs. Its primary objective is to describe anti-tumour activity of targeted anticancer drugs in patients with advanced malignancies harbouring actionable molecular alterations. The primary endpoint is disease control rate (DCR). Secondary endpoints encompass treatment-related grade ≥3 adverse events, objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Exploratory objectives will assess biomarkers, resource use and costs, and patient-reported outcome measures (PROMs).
INTERPRETATION
The POP trial will offer access to innovative treatments for patients without further therapeutic options and provide evidence on efficacy and safety of molecularly-guided treatments. Methodologically, it represents a pioneer approach in Portugal, including a pay-for-performance model embedded in the clinical trial. The POP trial represents a unique opportunity to integrate clinical research within cancer care, pursuing an evidence-based precision oncology strategy, and facilitating its rational and cost-effective implementation into the Portuguese healthcare system.
Topics: Humans; Precision Medicine; Portugal; Neoplasms; Antineoplastic Agents; Medical Oncology; Clinical Trials, Phase II as Topic; Molecular Targeted Therapy
PubMed: 38910310
DOI: 10.2340/1651-226X.2023.33322 -
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 -
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 -
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 -
BMJ Surgery, Interventions, & Health... 2024Assess the effect of a modified muscle sparing posterior approach; SPAIRE (Save Piriformis and Internus, Repairing Externus), in hip hemiarthroplasty for displaced...
Clinical effectiveness of a modified muscle sparing posterior technique compared with a standard lateral approach in hip hemiarthroplasty for displaced intracapsular fractures (HemiSPAIRE): a multicenter, parallel-group, randomized controlled trial.
OBJECTIVES
Assess the effect of a modified muscle sparing posterior approach; SPAIRE (Save Piriformis and Internus, Repairing Externus), in hip hemiarthroplasty for displaced intracapsular fractures on postoperative mobility and function compared with a standard lateral approach.
DESIGN
Pragmatic, superiority, multicenter, parallel-group, randomized controlled trial (with internal pilot). Participants, ward staff, and research staff conducting postoperative assessments were blinded to allocation. A CTU allocated treatments centrally using computer-generated lists.
SETTING
Six hospitals in Southwest England, recruiting November 25, 2019-April 25, 2022.
PARTICIPANTS
244 adults (≥60 years) requiring hip hemiarthroplasty (122 allocated to each approach). 90 and 85 participants allocated to SPAIRE and lateral, respectively, had primary outcome data within the prespecified data collection window.
INTERVENTIONS
Surgery using SPAIRE or standard lateral approach. Follow-up 3 days and 120 days postoperation.
MAIN OUTCOME MEASURE
Oxford Hip Score (OHS), via telephone at 120 days. Secondary outcomes: function and mobility (3 days), pain (3 days, 120 days), discharge destination, length of hospital stay, complications and mortality (within 120 days), quality of life and place of residence (120 days).
RESULTS
Participants' mean age was 84.6 years (SD 7.2); 168 (69%) were women. Primary outcome: little evidence of a difference in OHS at 120 days; adjusted mean difference (SPAIRE-lateral) -1.23 (95% CI -3.96 to 1.49, p=0.37). Secondary outcomes: indication of lower participant-reported pain at 3 days in SPAIRE arm; no differences between arms for remaining outcomes.
CONCLUSIONS
Participants' mobility and function are similar in the short term (3 days) and longer term (120 days), whether receiving the SPAIRE or lateral approach. Neither approach confers benefit over the other in terms of length of hospital stay, return to prefracture residence, survival within 120 days, or quality of life at 120 days. Participants receiving SPAIRE approach may experience less pain in the early postoperative period. Modifying the posterior approach in hip hemiarthroplasty to the SPAIRE approach gives equivalent patient outcomes to the lateral approach within 120 days.
TRIAL REGISTRATION NUMBER
NCT04095611.
PubMed: 38895600
DOI: 10.1136/bmjsit-2023-000251