Trial Protocol Research Articles

Effect of individualized anesthesia and analgesia on postoperative pain in patients stratified for pain sensitivity: A study protocol for the PeriOPerative individualization trial randomized controlled trial.

Despite advancements in surgical and anesthesia techniques, acute and persistent postoperative pain are still a common challenge. Postoperative pain has direct effects on individual patient care and outcome, as well as putting strain on limited health care resources. Several prediction methods for postoperative pain have been described. One such method is the assessment of pain during peripheral venous cannulation (VCP). It is not known if different approaches to anesthesia and analgesia, depending on the evaluation of risk for postoperative pain, can improve outcome. The aim of this study is to evaluate if individualized anesthesia and analgesia can affect postoperative pain and recovery after surgery, in patients stratified by VCP. Adult patients scheduled for laparoscopic surgery undergo pain-sensitivity stratification using VCP on the day of surgery. Patients scoring VCP ≥2.0 on the visual analogue scale (pain-sensitive) are randomized to multimodal anaesthesia and analgesia with opioids or standard of care. Patients scoring VCP ≤1.9 (pain-tolerant) are randomized to opioid-free anaesthesia or standard of care. The primary outcome is acute postoperative pain measured with numeric rating scale in the postoperative care unit. Secondary outcomes include analysis of pain after 24 h, persistent postoperative pain and quality of recovery. Individualized perioperative pain management has the potential to improve patient care. This study will examine the impact of different anesthesia and analgesia regimes, in patients with differing pain sensitivity, on postoperative pain. Prospectively posted at ClinicalTrials.gov, identifier NCT04751812.

Explanation for substandard of care comparators in rheumatology randomised trial protocols

Explanation for substandard of care comparators in rheumatology randomised trial protocols

A Protocol for the Validation of Novel Sham Acupuncture in Patients Who Have Had a Stroke

Background: A sham control group enhances the quality of clinical trials by controlling for the placebo effect. To ensure rigorous blinding to enhance the quality of clinical trials on acupuncture treatment it is important to develop a more sophisticated sham needle. Discrepancies in perceived needling sensation and treatment expectations between patients and healthy volunteers may affect study outcomes. Thus, it may be inappropriate to generalize the findings of a sham needle validation study in healthy adults to patients who have had a stroke. Therefore, this is a protocol for a clinical trial in patients who have had a stroke to validate a newly developed sham needle to be used in double-blind trials.Methods: Sixty-six patients who have had a stroke will be randomly assigned to the verum or sham needle group using a 1:1 ratio. As the verum and sham needles are identical in appearance, both participants and practitioners will be unaware of the needle type used for acupuncture treatment. After the acupuncture procedure, the participants will be asked whether they believe they received the verum or sham acupuncture treatment and indicate penetration, pain, and de qi sensation for each acupuncture point. A between-group comparison of needle-related adverse events will be performed.Discussion: This double-blind randomized controlled trial will be the first study to validate a newly developed sham acupuncture needle for patients who have had a stroke. The results of this study may inform clinical trial study design for acupuncture treatment of patients who have had a stroke.

E-EARLY TOGETHER Intervention for Infants at High Risk of Cerebral Palsy: Randomized Controlled Trial Protocol.

The purpose of this study is to evaluate the effectiveness of an early intervention program, e-EARLY TOGETHER, that combines goal-oriented training, parental coaching, environmental enrichment in a telehealth approach in a low- and middle-income country. Protocol for a randomized controlled clinical trial to evaluate the effectiveness of e-EARLY TOGETHER intervention compared to standard guidelines on outcomes related to development and performance in infants at high risk of cerebral palsy. This protocol will inform and enrich clinical practice related to early intervention in low- and middle-income countries. It is expected that the data obtained will contribute to the implementation of effective early intervention programs with positive and lasting results for the child, their family, and the community. Brazilian Registry of Clinical Trials: RBR-7WWJRQ3, registered May 10, 2023; WHO Trial Registration UTN Code U-1111-1286-4639.

Invasive testing leads to significantly altered (surgical) management strategy in coronary anomalies with interarterial course: 3 year interim analysis of MuSCAT

Abstract Introduction Diagnostic work-up of patients with an anomalous aortic origin of a coronary artery (AAOCA) includes an anatomical and functional assessment. The approach to functional evaluation currently varies widely and mainly includes noninvasive assessment. Intracoronary hemodynamic assessment can potentially enhance risk assessment for myocardial ischemia and sudden cardiac death and guide management of AAOCA patients. Hence, this study aims to evaluate invasive detection of ischemia on top of the standard of care diagnostic work-up for interarterial or intraseptal AAOCA and the impact on patient management. We report the first clinical outcomes. Methods In this multicenter prospective cohort study on AAOCA, all consecutive patients of 16 years and older with AAOCA with a newly diagnosed interarterial or intraseptal course in whom diagnostic work-up according to the protocol of the MuSCAT trial was performed between January 2021 and January 2024, were included for analysis. Exclusion comprised incomplete diagnostic evaluation, hemodynamically significant concomitant congenital heart disease or obstructive coronary artery disease in the AAOCA effluence. The work-up included invasive ischemia testing using fractional flow reserve (FFR) and or instantaneous wave-free ratio (iFR)/resting full-cycle ratio (RFR) at baseline and during pharmacological stress using adenosine, adrenaline and dobutamine. Results Fifty-eight patients (50% female, median age at AAOCA diagnosis 51.5 years (IQR 44.0-59.0)) were included, Table 1. The right coronary artery was anomalous in 88%, 93% patients had an interarterial and 69% an intramural course. Non-invasive ischemia detection was positive in 12%, negative in 84% and inconclusive in 4%. Invasive hemodynamic assessment was positive for ischemia in 22%, negative in 74% and inconclusive in 3%. Class of recommendation for surgery based on ESC guidelines was I or IIa in 28% patients and IIb, III or unclassified in 72%. Invasive hemodynamic assessment changed the treatment decision in 24% of the patients; 50% with initially recommended surgical treatment and 14% with initially a conservative treatment adjudication, Figure 1. Median follow-up after initial diagnosis was 20 [IQR 10-28] months and in 56% of all patients who completed 6 months follow-up the initial symptoms alleviated. One (2%) patient underwent a percutaneous re-intervention of the operated AAOCA. Conclusions This national prospective study of invasive hemodynamic assessment in patients with AAOCA showed clinically significant impact on the adjustment of initial management strategy in 24% of the patients. No cardiac death of myocardial infarction in the AAOCA supply area occurred during follow-up. Analysis of the complete follow-up of the MuSCAT trial can further substantiate the role of additional invasive functional imaging in AAOCA.

Acupuncture-assisted lifestyle intervention improve the metabolic status and spontaneous brain activity of type 2 diabetes Mellitus patients: a randomized, clinical trial

BackgroundAggressive weight management in patients with type 2 diabetes mellitus has demonstrated numerous metabolic advantages, however, existing therapies for weight control have not reached satisfactory results. This study aimed to evaluate the efficacy and safety of acupuncture in the weight management of type 2 diabetes mellitus (T2DM) patients by using a randomized, sham-controlled clinical trial design.MethodsIn this single-blind randomized clinical trial, 102 overweight adult T2DM patients were randomized into two groups. The control group receives diet, exercise, and sham acupuncture intervention, whereas the acupuncture group receives diet and exercise and acupuncture intervention, both for 1 month. Body weight and other anthropometric and laboratory indices were assessed at baseline and endpoint, meanwhile, the body fat content and spontaneous brain activity were measured by functional magnetic resonance imaging(fMRI)as the exploratory outcomes.ResultsNo significant difference was observed between the studied parameters at the baseline. The body weight and BMI were significantly reduced both in the control and acupuncture groups after intervention, without statistical difference between the two groups. What’s interesting is that compared to the control, the acupuncture group displayed a greater improvement in central fat tissue. It notes that the acupuncture group achieved significant liver fat content reduction than the sham acupuncture group. At the same time, the spontaneous brain activity in the occipital lobe and parietal lobe significantly increased in the acupuncture group.ConclusionOne month of acupuncture treatment preferentially improved ectopic fat deposition and was accompanied by changes in brain activity compared with the control group, even before significant changes in total body weight had occurred. further studies of longer duration are necessary for validation.Trial registration: The protocol of this clinical trial is registered at the Acupuncture-Moxibustion Clinical Trial Registry (AMCTR, http://www.acmctr.org/, No. AMCTR-IOR-20000341).

High-flow nasal cannula oxygen therapy versus noninvasive ventilation for elderly chronic obstructive pulmonary disease patients after extubation: a noninferior randomized controlled trial protocol

IntroductionNoninvasive ventilation (NIV) is widely used for sequential extubation in patients with chronic obstructive pulmonary disease (COPD). However, NIV may cause many adverse events such as claustrophobia, facial skin compression, air leakage, bloating, and even reflux aspiration, resulting in poor patient compliance/tolerance and high failure rate, especially for older adults who are at high risk of communication difficulties and consciousness disorder. High-flow nasal cannula (HFNC) oxygen therapy is a new alternative support to NIV, but whether it can effectively reduce the rate of re-intubation after extubation in elderly patients with COPD remains controversial. The purpose of this study is to explore the safety and efficacy of HFNC versus NIV for elderly COPD patients after extubation.Methods and analysisThis study is an investigator-initiated, single-center, prospective, non-inferior, randomized controlled trial. Elderly patients (age > 65 years) who have received invasive ventilation and was diagnosed with COPD will be randomly assigned to HFNC group or NIV group immediately after extubation with a planned enrollment of 168 patients. The primary outcomes will be reintubation rates at 72 h and 7 days after extubation. Secondary outcomes will include treatment failure, post-extubation vital signs and arterial blood gases, the scores of compliance and comfort of patients, duration of respiratory support after extubation, respiratory support related adverse events, sleep quality scores, usage of sedative and analgesic drugs after extubation, and the incidence of delirium. Additionally, clinical outcomes such as ventilator-free days at 28 days post-randomization, tracheotomy rate, duration of intensive care unit (ICU) and hospital stay, ICU and hospital mortality will be evaluated.Ethics and disseminationThis study has been approved by the Ethics Committee of West China Hospital of Sichuan University (2023–2284). Informed consent is required. It is expected that a follow-up randomized controlled trial will be conducted. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences.Trial registrationThe study was retrospectively registered at ClinicalTrials.gov (ChiCTR2400087312).

Home Transcutaneous Electrical Stimulation Rehabilitation Program for Patients With Ankylosing Spondylitis: Crossover Trial.

Maintaining physical function and preserving spinal flexibility have been challenging in managing ankylosing spondylitis (AS). Most rehabilitation programs, including manual therapy, massage, hydrotherapy, and acupuncture, cannot be performed at home. The effect of transcutaneous electrical nerve stimulation (TENS) was validated in treating AS, but no home TENS system has explored its efficacy to date. This study aims to evaluate the efficacy of a home TENS system with a novel treatment program for patients with AS. The modified WeHeal TS-200 TENS and galvanic response system provided home-based TENS treatment for patients with AS. Patients were divided into a 2-month course group and a 1-month course group. After the first treatment course, patients went through a washout period for the same duration of their treatment course. Participants could decide whether to accept the second course of treatment. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Schober test, finger-to-floor flexion test, enthesis score, cytokines, chemokines, inflammatory factors, and immunoglobulins were measured to evaluate its efficacy. The clinical trial protocol (1096607481) received approval from the Ministry of Health and Welfare in Taiwan. A total of 9 patients (5 in a 2-month course group and 4 in a 1-month course group) completed the first treatment course, and 5 patients (4 in a 2-month course group and 1 in a 1-month course group) completed the sequential treatment course. The weighted results showed that patients reported an improving BASFI score (mean difference -0.9, SD 1.7; P=.03) after treatment. Looking into the trajectories, declined BASFI and BASDAI scores were noticed during treatments; this score increased during the washout period. There were improving trends in the Schober test (mean difference 1.9, SD 4.9; P=.11) and finger-to-floor flexion test (mean difference -0.6, SD 9.5; P=.79), but the results were not statistically significant. The response of cytokines, chemokines, inflammatory factors, and immunoglobulins before and after treatment did not show a consistent trend, and all results were not statistically significant (all P>.05). The home TENS device demonstrated a potential role in AS management. It may improve accessibility and adherence for patients with AS and provide remote monitoring for clinicians. Further research can compare the effectiveness of electrotherapy at home or in a medical setting and focus on integrating the home TENS system and exercise program to enhance patients' physical functions and spinal flexibility.

Effect of four hemoglobin transfusion threshold strategies in patients with acute myocardial infarction and anemia: a target trial emulation using MINT trial data

Abstract Background The hemoglobin (Hgb) threshold at which red blood cell transfusion affords greatest benefit, without increasing transfusion-associated risks, is uncertain for patients with acute myocardial infarction (MI). The Myocardial Ischemia and Transfusion (MINT) trial recently showed a restrictive transfusion strategy (Hgb threshold <7-8g/dL) resulted in a 15% increased risk of 30-day all-cause death or recurrent MI (death/MI) compared with a liberal strategy (Hgb threshold <10g/dL) in 3,504 adults with acute MI and anemia. However, the transfusion effect at different Hgb thresholds remains uncertain. Purpose To better understand the gradient of effects from Hgb threshold transfusion triggers between 7g/dL and 10g/dL. We estimated the effects of four Hgb transfusion thresholds on 30-day death/MI and death in patients with acute MI and anemia. Methods We used data from the MINT trial and applied an innovative causal inference method, target trial emulation, to assess four Hgb thresholds. We emulated a hypothetical, 4-arm target trial of <10g/dL, <9g/dL, <8g/dL, and <7g/dL transfusion strategies in adults with acute MI and Hgb <10g/dL using a "cloning" procedure. The target trial protocol closely mirrored that of the MINT trial. We conducted a per-protocol analysis of the emulated target trial using censoring and inverse probability (IP) weighting; we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) by fitting pooled logistic regression models with a time-dependent intercept for time free of the outcomes. We estimated IP weighted Kaplan-Meier cumulative incidence curves under each strategy for 30-day outcomes. Results Of the MINT trial participants, 3,492 (99.7%) met eligibility criteria for the hypothetical target trial of four transfusion strategies. The unadjusted rate of 30-day death/MI was lowest in the <10g/dL strategy and highest in the <9g/dL strategy, and the rate of transfusions decreased monotonically as Hgb thresholds decreased. Relative to the <10g/dL strategy, the estimated HRs (95% CI) from the IP weighted model of 30-day death/MI were 1.07 (0.77-1.50) for the <9g/dL strategy, 1.14 (0.84-1.55) for the <8g/dL strategy, and 1.44 (0.99-2.09) for the <7g/dL strategy (Figure). A log-linear estimate over strategy thresholds between 7-10g/dL estimated a 1.12 (95% CI 1.00-1.27) times greater average risk of death/MI and a 1.12 (95% CI 0.92, 1.37) times greater average risk of death over 30 days for each 1g/dL decrease in the Hgb threshold. The IP weighted cumulative incidence curves showed similar increase in risk of death/MI as transfusion thresholds decreased throughout 30 days post-randomization. Conclusions Relative to a <10g/dL transfusion strategy, we estimated a progressively greater risk of 30-day death/MI as transfusion Hgb thresholds decreased within the range of 7-10g/dL. Targeting a Hgb concentration of 10g/dL in patients with a recent acute MI may avoid serious risks associated with anemia.Hazard ratios for 30-day death/MI

Clinical trial protocol for continuous glucose monitoring in critical care at Hospital Clinic of Barcelona (CGM-UCI23).

Hyperglycaemia is common in intensive care units (ICUs), with a prevalence of up to 86.2%, increasing mortality. Technology has evolved towards continuous glucose monitoring (CGM), and its use in ICUs began especially during the coronavirus pandemic (COVID-19). Various studies have evaluated the reliability of CGM, indicating that it is safe for use in critically ill patients. The aim of this study was to compare the use of CGM with point-of-care glucose (POC-G) testing in ICU. Specific objectives include evaluating the glycaemic control, the frequency of POC-G measurements, the incidence of hyperglycaemia, hypoglycaemia and morbidity and mortality at 90 days. An experimental, controlled and randomized clinical trial with a single-blind design will be conducted at Hospital Clinic of Barcelona (HCB). A sample size of 376 participants will be recruited and randomly assigned to two groups: an experimental group, where glycaemic management will be based on CGM; and a control group, where glucose will be managed through POC-G testing, with a blinded CGM. The primary variable considered will be time in range (TIR), with secondary outcomes including, time above range (TAR), time below range (TBR), number of POC-G measurements, incidence of hyperglycaemia and hypoglycaemia, and mortality. Hypothesis testing will use the Kolmogorov-Smirnov test to assess data normality, with appropriate statistical tests applied, considering a p-value <.05. The results obtained will help us understand the impact of CGM on critically ill patients. CGM could potentially reduce the workload of nurses and improve the efficiency of decision-making by the ICU team, enabling early identification and treatment of glucose complications, thereby enhancing safety. Patient safety, a reduction in patient fingerstick and a decreased care burden are the criteria that add value to this research.

Protocol for a cluster randomised controlled trial to evaluate effectiveness of a self-help group intervention to encourage smoke-free homes in slums of Kochi(Kochi Intervention for tobacco smoke free homes-KIFT)

Background Exposure to second hand smoke (SHS) is a cause for heart disease and lung cancer among non- smokers. This cluster randomized control trial will evaluate the effectiveness of a tobacco smoke free home intervention in reducing exposure to second hand smoke. Protocol The intervention will be conducted among 30 clusters in urban and peri-urban areas of Kochi, India. The sample size is 300 per arm and 15 clusters to detect a minimal difference of 0.03ng/ml in cotinine levels between groups, at 80% power with a two-sided alfa of 0.05 considering variable cluster size. A baseline survey will be undertaken to identify smokers. Data related to smoking, indoor smoking, nicotine dependence, blood pressure (BP) of smokers, morbidity experienced, and lung volume Fev1/Fev6 of smokers will be measured. Urine cotinine, morbidity, BP of spouse and child will be assessed. Air quality monitors measuring PM2.5 will be placed in homes. Trained self-help group women and frontline health workers will implement the intervention. The intervention will consist of monthly home visits to educate the smoker on the harms of second-hand smoke using 3 A’s. The circle of influencers around the smoking men will also be contacted by the members of self-help group to provide support to stop smoking within homes and to quit. They will then organize two-three meetings of community leaders and heads of women’s groups, present data on harms of SHS, and explain the rationale for establishing smoke free homes in their community for a duration of six months. After the intervention a post assessment will be conducted and this will be repeated after six months. Ethics and dissemination The trial protocol was approved by the Institutional Ethical Committee of Amrita Institute of Medical Sciences. Results will be submitted to open access peer reviewed journals and shared with other stakeholders. Trial registration CTRI/2021/06/034478

Natural frequency tree- versus conditional probability formula-based training for medical students’ estimation of screening test predictive values: a randomized controlled trial

BackgroundMedical students and professionals often struggle to understand medical test results, which can lead to poor medical decisions. Natural frequency tree-based training (NF-TT) has been suggested to help people correctly estimate the predictive value of medical tests. We aimed to compare the effectiveness of NF-TT with conventional conditional probability formula-based training (CP-FT) and investigate student variables that may influence NF-TT’s effectiveness.MethodsWe conducted a parallel group randomized controlled trial of NF-TT vs. CP-FT in two medical schools in South Korea (a 1:1 allocation ratio). Participants were randomly assigned to watch either NF-TT or CP-FT video at individual computer stations. NF-TT video showed how to translate relevant probabilistic information into natural frequencies using a tree structure to estimate the predictive values of screening tests. CP-FT video showed how to plug the same information into a mathematical formula to calculate predictive values. Both videos were 15 min long. The primary outcome was the accuracy in estimating the predictive value of screening tests assessed using multiple-choice questions at baseline, post-intervention (i.e., immediately after training), and one-month follow-up. The secondary outcome was the accuracy of conditional probabilistic reasoning in non-medical contexts, also assessed using multiple-choice questions, but only at follow-up as a measure of transfer of learning. 231 medical students completed their participation.ResultsOverall, NF-TT was not more effective than CP-FT in improving the predictive value estimation accuracy at post-intervention (NF-TT: 87.13%, CP-FT: 86.03%, p = .86) and follow-up (NF-TT: 72.39%, CP-FT: 68.10%, p = .40) and facilitating transfer of training (NF-TT: 75.54%, CP-FT: 71.43%, p = .41). However, for participants without relevant prior training, NF-TT was more effective than CP-FT in improving estimation accuracy at follow-up (NF-TT: 74.86%, CP-FT: 58.71%, p = .02) and facilitating transfer of learning (NF-TT: 82.86%, CP-FT: 66.13%, p = .04).ConclusionsIntroducing NF-TT early in the medical school curriculum, before students are exposed to a pervasive conditional probability formula-based approach, would offer the greatest benefit.Trial registrationKorea Disease Control and Prevention Agency Clinical Research Information Service KCT0004246 (the date of first trial registration: 27/08/2019). The full trial protocol can be accessed at https://cris.nih.go.kr/cris/search/detailSearch.do?seq=15616&search_page=L.

Effectiveness of an HIV peer support precision matching platform: a randomized controlled trial protocol

BackgroundPeer support is a promising and significant way for people living with HIV (PLWH) to improve their health outcomes. Matching PLWH with HIV peer volunteers can effectively stimulate and mobilize the function of peer support in health management. We develop the online platform Aspark, which features a precision matching function for PLWH and volunteers. This protocol provides a comprehensive overview of the randomized controlled trial design based on Aspark.MethodA parallel randomized controlled trial using block randomization will be conducted at the Beijing YouAn Home of Loving Care. The intervention group (n = 70) will have access to all 12 features of Aspark, including precise volunteer matching, health management tools, drug interaction queries, and medication reminders. The control group (n = 70) will have access to two features of informational support on Aspark. The outcomes of both groups will be evaluated at baseline and at 3, 6, 9, and 12 months after platform registration. The primary outcome is perceived social support. The secondary outcomes include mental symptoms, quality of life, self-efficacy, medication adherence, and health behaviors. Linear mixed models or generalized linear mixed models will be applied to test the intervention effects.DiscussionThe Aspark trial is a randomized controlled trial designed to examine the influence of a mobile health (mHealth) application that integrates peer support and precision matching to strengthen social support for PLWH in China. This trial has the potential to significantly enhance social support for PLWH while also optimizing the delivery of peer support services and fully mobilizing the role of peer support in the overall health management of PLWH.Trial registrationClinical registration number: ChiCTR2300077454.

Reproducibility of ultrasound-derived fat fraction in measuring hepatic steatosis

PurposeSteatotic liver disease (SLD) has become the most common cause of chronic liver disease. Nevertheless, the non-invasive quantitative diagnosis of steatosis is still lacking in clinical practice. This study aimed to evaluate the reproducibility of the new parameter for steatosis quantification named ultrasound-derived fat fraction (UDFF).Materials and methodsThe UDFF values were independently executed by two operators in two periods. In the process, repeated measurements of the same patient were performed by the same operator under different conditions (liver segments, respiration, positions, and dietary). Finally, the results of some subjects (28) were compared with the MRI-derived proton density fat fraction (PDFF). The concordance analysis was mainly achieved by the intraclass correlation coefficient (ICC) and Bland–Altman.ResultsOne hundred-five participants were included in the study. UDFF had good reliability in measuring the adult liver (ICCintra-observer = 0.96, ICCinter-observer = 0.94). Meanwhile, the ICC of the two operators increased over time. The variable measurement states did not influence the UDFF values on the surface, but they affected the coefficient of variation (Cov) of the results. Segment 8 (S8), end-expiratory, supine, and fasting images had the most minor variability. On the other hand, the UDFF value of S8 displayed satisfied consistency with PDFF (mean difference, −0.24 ± 1.44), and the results of both S5 (mean difference: −0.56 ± 3.95) and S8 (mean difference: 0.73 ± 1.87) agreed well with the whole-liver PDFF.ConclusionUDFF measurements had good reproducibility. Furthermore, the state of S8, end-expiration, supine, and fasting might be the more stable measurement approach.Critical relevance statementUDFF is the quantitative ultrasound parameter of hepatic steatosis and has good reproducibility. It can show more robust performance under specific measurement conditions (S8, end-expiratory, supine, and fasting).Trial registrationThe research protocol was registered at the Chinese Clinical Trial Registry on October 9, 2023 (http://www.chictr.org.cn/). The registration number is ChiCTR 2300076457.Key PointsThere is a lack of non-invasive quantitative measurement options for hepatic steatosis.UDFF demonstrated excellent reproducibility in measuring hepatic steatosis.S8, end-expiratory, supine, and fasting may be the more stable measuring condition.Training could improve the operators’ measurement stability.Variable measurement state affects the repeatability of the UDFF values (Cov).Graphical

Efficacy and Safety of Intravenous Tenecteplase Before Endovascular Thrombectomy for Acute Ischemic Stroke: The Multicenter, Randomized, BRIDGE-TNK Trial Protocol.

Six randomized trials have not detected a difference between intravenous alteplase plus endovascular thrombectomy and endovascular thrombectomy alone in stroke. Tenecteplase, a recombinant human tenecteplase tissue-type plasminogen activator, is a genetically modified variant of alteplase. It is unclear whether the outcomes are different if alteplase is replaced with tenecteplase. This trial aims to determine whether intravenous tenecteplase within 4.5 hours of time last known well confers benefit in patients with acute ischemic stroke with large-vessel occlusion who undergo endovascular thrombectomy. BRIDGE-TNK (Thrombectomy With Versus Without rhTNK-tPA in Stroke) is an investigator-initiated, multicenter, prospective, randomized, open-label trial with blinded end point evaluation conducted at 40 thrombectomy-capable centers in China. This trial will randomize 544 patients with intravenous thrombolysis-eligible stroke (272 in each arm) with large-vessel occlusion within 4.5 hours of last known well to receive bridging intravenous tenecteplase with endovascular thrombectomy (tenecteplase-plus-thrombectomy group) or endovascular thrombectomy alone (thrombectomy-alone group). The primary outcome is the proportion of patients achieving functional independence, defined as a score of 0 to 2 on the modified Rankin Scale, at 90 days. Safety will be assessed via symptomatic intracranial hemorrhage at 48 hours and death at 90 days. BRIDGE-TNK will provide important data on the role of intravenous tenecteplase before endovascular thrombectomy in patients with acute ischemic stroke with large-vessel occlusion who can be treated within 4.5 hours of last known well. URL: https://clinicaltrials.gov. Unique identifier: NCT04733742.

Effect of glucose-insulin-potassium on lactate levels at the end of surgery in patients undergoing cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy: study protocol for a randomized controlled trial

IntroductionCytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has been established as an effective treatment for peritoneal cancer (PC). However, this kind of combination therapy is associated with a high lactate level. Moreover, studies have suggested that the rate of complications early after surgery directly increased with elevated lactate levels. Glucose-insulin-potassium (GIP), a potent cardioprotective intervention, has been demonstrated to adjust blood glucose (BG) levels and reduce lactate levels. However, the insulin-glucose ratio should be adjusted according to the surgery performed. Here, we aimed to evaluate the advantages of using modified GIP during CRS/HIPEC to reduce the lactate level at the end of surgery and further reduce the incidence of early postoperative complications.Methods and analysisThe modified GIP versus conventional management during surgery study is a single-center, randomized, single-blinded outcome assessment clinical trial of 80 patients with PC who are between 18 and 64 years old and undergoing CRS/HIPEC. Participants will be randomly allocated to receive modified GIP or conventional treatment (1:1). The primary outcome will be the plasma lactate level at the end of surgery. The secondary outcomes will include the highest levels and fluctuation ranges of lactate and BG during surgery, extubation time, APACHE-II score 24 h after surgery, postoperative defecation and exhaust time, postoperative lactate clearance time, postoperative liver and kidney function, incidence of complications within 7 days after surgery, length of intensive care unit stay (LIS), length of hospital stay (LHS), and total cost of hospitalization.Ethics and disseminationThe trial protocol was approved by the Scientific Research Ethics Committee of Beijing Shijitan Hospital Affiliated with Capital Medical University, approval number sjtky11-1x-2022(118). The results will be published in international peer-reviewed journals.Trial registrationChiCTR2200057258. Registered on March 5, 2022.

A study of intersphincteric resection rate following robotic-assisted total mesorectal excision versus laparoscopic-assisted total mesorectal excision for patients with middle and low rectal cancer: study protocol for a multicenter randomized clinical trial

IntroductionRobotic-assisted complete mesorectal excision (RATME) is increasingly being used by colorectal surgeons. Most surgeons consider RATME a safe method, and believe it can facilitate total mesorectal excision (TME) in rectal cancer, and may potentially have advantages over intersphincteric resection (ISR) and anus preservation. Therefore, this trial was designed to investigate whether RATME has technical advantages and can increase the ISR rate compared with laparoscopic-assisted TME (LATME) in patients with middle and low rectal cancer.Methods and analysisThis is a multicenter, superiority, randomized controlled trial designed to compare RATME and LATME in middle and low rectal cancer. The primary endpoint is the ISR rate. The secondary endpoints are coloanal anastomosis (CAA) rate, conversion to open surgery, conversion to transanal TME (TaTME), abdominoperineal resection (APR) rate, postoperative morbidity and mortality within 30 days, pathological outcomes, long-term survival outcomes, functional outcomes, and quality of life. In addition, certain measurements will be conducted to ensure quality and safety, including centralized photography review and semiannual assessment.DiscussionThis trial will clarify if RATME improves ISR and promotes anus preservation in patients with mid- and low-rectal cancer. Furthermore, this trial will provide evidence on the optimal treatment strategies for RATME and LATME in patients with mid- and low-rectal cancer regarding improved operational safety.Trial registrationClinicalTrials.gov NCT06105203. Registered on October 27, 2023.

Protocol for a prospective randomized trial of surgical versus conservative management for unstable fractures of the distal radius in patients aged 65 years and older.

The primary aim of this study is to quantify and compare outcomes following a dorsally displaced fracture of the distal radius in elderly patients (aged ≥ 65 years) who are managed conservatively versus with surgical fixation (open reduction and internal fixation). Secondary aims are to assess and compare upper limb-specific function, health-related quality of life, wrist pain, complications, grip strength, range of motion, radiological parameters, healthcare resource use, and cost-effectiveness between the groups. A prospectively registered (ISRCTN95922938) randomized parallel group trial will be conducted. Elderly patients meeting the inclusion criteria with a dorsally displaced distal radius facture will be randomized (1:1 ratio) to either conservative management (cast without further manipulation) or surgery. Patients will be assessed at six, 12, 26 weeks, and 52 weeks post intervention. The primary outcome measure and endpoint will be the Patient-Rated Wrist Evaluation (PRWE) at 52 weeks. In addition, the abbreviated version of the Disabilities of Arm, Shoulder and Hand questionnaire (QuickDASH), EuroQol five-dimension questionnaire, pain score (visual analogue scale 1 to 10), complications, grip strength (dynamometer), range of motion (goniometer), and radiological assessments will be undertaken. A cost-utility analysis will be performed to assess the cost-effectiveness of surgery. We aim to recruit 89 subjects per arm (total sample size 178). The results of this study will help guide treatment of dorsally displaced distal radial fractures in the elderly and assess whether surgery offers functional benefit to patients. This is an important finding, as the number of elderly distal radial fractures is estimated to increase in the future due to the ageing population. Evidence-based management strategies are therefore required to ensure the best outcome for the patient and to optimize the use of increasingly scarce healthcare resources.

Effectiveness of Home-Based Self-monitoring of Blood Pressure in a Primary Care set-up of India (EASE-BP): Protocol for an Open-Label Randomized Controlled Trial.

Rising hypertension from inadequate detection, noncompliance with treatment, and poor control presents a major public health challenge. Previously, adopting the strategy of self-monitoring of blood pressure (SMBP) showed better hypertension detection, control, and medication adherence. However, evidence from India is scarce. Here, we present the trial protocol for the effectiveness of SMBP intervention in hypertension detection, blood pressure (BP) control, and medication adherence in a primary care set-up. EASE-BP is an open-label randomized trial in two distinct adult populations - part-A self-reported non-hypertensive population (total sample size: 400) and part-B known hypertensive population (total sample size: 332). The two populations will be sampled from two separate villages under the Ballabgarh Health and Demographic Surveillance System. In both the populations, participants randomized in the intervention arm will receive a validated electronic BP device and will be advised to self-monitor BP for at least twice a month (or more). Those in the control arm will be advised to monitor BP for at least twice a month (or more) at the nearby health center. Participants in both arms will receive education on hypertension and atherosclerotic disease. In addition, adult family members in the households of randomized participants will be encouraged to monitor their BP. All participants and family members will be instructed to maintain a log of BP recordings in a diary that will be provided to them. Data will be collected at baseline and then every month for three-months. The primary outcome in part-A will be the incidence of new cases of hypertension during 3 months follow-up and in part-B will be the difference in SBP and rate of medication adherence at 3 months follow-up. Secondary outcomes will include (1) uptake of the intervention, (2) any stroke, myocardial infarction, or death, (3) additional yield of new cases of hypertension among the family members, and (4) integrating the intervention into the national programs for long-term noncommunicable disease goals. EASE-BP will help understand if SMBP improves hypertension detection, BP control, and medication adherence. Consequently, this will appraise policymakers on whether provision of BP instruments may be added to the national program for hypertension prevention and control. This trial was registered under Clinical Trial Registry - India with reference number CTRI/2023/02/049949.

Dosing overground robotic gait training after spinal cord injury: a randomized clinical trial protocol

BackgroundRobotic exoskeletons have changed rehabilitation care available to people after spinal cord injury (SCI). Yet, the current evidence base is insufficient to identify the optimal dose and neurophysiological mechanism of robotic exoskeleton gait training (RGT) as an effective rehabilitation approach. This study will (1) examine whether the frequency of RGT after motor incomplete SCI impacts function and health outcomes, (2) analyze the neuroplastic effects of RGT dose, and (3) evaluate the safety, tolerability, and feasibility of delivering RGT.MethodsWe will enroll 144 participants with motor incomplete SCI admitted to inpatient rehabilitation within 6 months of SCI. Participants will be randomized based on injury severity and level into one of 3 RGT frequency groups (high, moderate, low) or none/usual care only. Participants will complete 24 RGT sessions and be assessed at admission and discharge to inpatient rehabilitation, post-RGT intervention, 1-month post-RGT, and 9-month post-SCI. Outcomes include Walking Index for Spinal Cord Injury-II, health outcomes (gait speed, Spinal Cord Independence Measure, pain, fatigue, spasticity, general health, quality of life, physical activity), and motor evoked potential amplitudes obtained using transcranial magnetic stimulation.DiscussionSuccessful completion of this study will provide an evidence-based intervention, specifically tailored to meet the unique needs of people with SCI, which supports walking recovery; maximizing health, function, and ultimately participation. The intervention will further support widespread clinical implementation of exoskeleton use during acute rehabilitation.Trial registrationClinicalTrials.gov NCT05218447. Registered on June 23, 2022.