Multicenter Randomized Clinical Trial Research Articles

Pressure injury treatment by intermittent electrical stimulation (PROTECT-2): protocol for a multicenter randomized clinical trial

BackgroundPressure ulcers account for a substantial fraction of hospital-acquired pathology, with consequent morbidity and economic cost. Treatments are largely focused on preventing further injury, whereas interventions that facilitate healing remain limited. Intermittent electrical stimulation (IES) increases local blood flow and redistributes pressure from muscle-bone interfaces, thus potentially reducing ulcer progression and facilitating healing.MethodsThe Pressure Injury Treatment by Intermittent Electrical Stimulation (PROTECT-2) trial will be a parallel-arm multicenter randomized trial to test the hypothesis that IES combined with routine care reduces sacral and ischial pressure injury over time compared to routine care alone. We plan to enroll 548 patients across various centers. Hospitalized patients with stage 1 or stage 2 sacral or ischial pressure injuries will be randomized to IES and routine care or routine care alone. Wound stage will be followed until death, discharge, or the development of an exclusion criteria for up to 3 months. The primary endpoint will be pressure injury score measured over time.DiscussionSacral and ischial pressure injuries present a burden to hospitalized patients with both clinical and economic consequences. The PROTECT-2 trial will evaluate whether IES is an effective intervention and thus reduces progression of stage 1 and stage 2 sacral and ischial pressure injuries.Trial registrationClinicalTrials.gov NCT05085288 Registered October 20, 2021.

Characteristics of Prescreened Patients Who Did Not Participate in the Zoster Eye Disease Study

Purpose: The Zoster Eye Disease Study (ZEDS) is a multicenter randomized clinical trial (RCT) funded by the National Eye Institute aiming to determine the efficacy of suppressive valacyclovir treatment in herpes zoster ophthalmicus (HZO) that enrolled fewer participants than planned (527/780, 67.6%). Understanding reasons for nonparticipation of likely eligible prescreened patients provides insights into patient populations that are not represented by ZEDS and barriers in clinical trials. Methods: In this retrospective cohort study, HZO adults likely eligible for ZEDS with a history of a typical rash and a medical record within the past year of an episode of epithelial or stromal keratitis or iritis were prescreened at activated Participating Clinical Centers from 2017 to 2022 using a standard prescreening log. De-identified data including demographic information, reasons for exclusion because of ineligibility, and patient refusal were retrospectively entered into REDCap and analyzed. Results: Prescreening logs with reasons for nonconsent (1244/1706, 72.9%) were included in the data set. Patients were excluded from the study (915/1244, 73.6%) because they did not meet all inclusion criteria (619/915, 67.7%) or met an exclusion criterion (296/915, 32.3%). Among the 12 exclusion criteria for the ZEDS study, immunocompromise (76/296, 25.7%) and renal insufficiency (50/296, 16.9%) were most frequently reported. Patient refusal to participate (327/1,244, 26.3%) was common. Conclusion: The most common reasons for ineligibility were immunocompromise and renal insufficiency. There may be benefits to long-term antiviral use in these populations not captured in ZEDS. A quarter (26.3%) of prescreened patients refused participation, showing the substantial impact of patient preferences on trial participation.

A commentary on "a new designed full process coverage robot-assisted total hip arthroplasty: a multicentre randomized clinical trial".

A commentary on "a new designed full process coverage robot-assisted total hip arthroplasty: a multicentre randomized clinical trial".

Effect of Drug Monitoring on Adherence and Blood Pressure: A Multicenter Randomized Clinical Trial.

Drug concentration in blood or urine is an acknowledged method to detect non-adherence. Observational studies suggest that informing patients about low or absent serum drug levels improves blood pressure (BP). We performed a multicenter randomized clinical trial to test the hypothesis that therapeutic drug monitoring (TDM) could improve drug adherence and BP in patients with uncontrolled hypertension and reduced adherence to antihypertensive drugs. Patients were ≥18 years on stable treatment with at least two antihypertensive agents. We planned to randomize 80 non-adherent patients with a systolic daytime ambulatory BP (ABPM) ≥135 mmHg to TDM-intervention or not. The control group and the study-personnel who measured BP remained uninformed about serum drug measurements throughout. All patients and physicians were blinded for BPs. Lifestyle advice and detailed information on disease process and importance of BP treatment were given to both groups. From 2017 to 2022, we randomized 46 diagnosed non-adherent from a total of 606 patients with uncontrolled hypertension. The TDM-group had a 6.7 (±14.5) mmHg reduction from 147.9 (±10.3) to 141.1 (±14.1) mmHg, and the control group experienced a 7.3 (±13.2) mmHg reduction from 147.1 (±9.2) to 139.1 (±17.4) mmHg, p=0.9 between groups. Adherence improved in both groups, 73% in the TDM group and 59% in the control group became adherent at three months, p=0.51. In our prospective multicenter clinical trial of uncontrolled and non-adherent hypertensive patients, we found no additional effect of therapeutic drug monitoring (TDM) on blood pressure and drug adherence compared with standard care.

Refraining from closed reduction of displaced distal radius fractures in the emergency department—in short: the RECORDED trial

BackgroundWith roughly 45,000 adult patients each year, distal radius fractures are one of the most common fractures in the emergency department. Approximately 60% of all these fractures are displaced and require surgery. The current guidelines advise to perform closed reduction of these fractures awaiting surgery, as it may lead to post-reduction pain relief and release tension of the surrounding neurovascular structures. Recent studies have shown that successful reduction does not warrant conservative treatment, while patients find it painful or even traumatizing. The aim of this study is to determine whether closed reduction can be safely abandoned in these patients.MethodsIn this multicenter randomized clinical trial, we will randomize between closed reduction followed by plaster casting and only plaster casting. Patients aged 18 to 75 years, presenting at the emergency department with a displaced distal radial fracture and requiring surgery according to the attending surgeon, are eligible for inclusion. Primary outcome is pain assessed with daily VAS scores from the visit to the emergency department until surgery. Secondary outcomes are function assessed by PRWHE, length of stay at the emergency department, length of surgery, return to work, patient satisfaction, and complications. A total of 134 patients will be included in this study with follow-up of 1 year.DiscussionIf our study shows that patients who did not receive closed reduction experience no significant drawbacks, we might be able to reorganize the initial care for distal radial fractures in the emergency department. If surgery is warranted, the patient can be sent home with a plaster cast to await the call for admission, decreasing the time spend in the emergency room drastically.Trial registrationThis trial was registered on January 27, 2023.

A commentary on'A new designed full process coverage robot-assisted total hip arthroplasty: A multicenter randomized clinical trial'.

A commentary on'A new designed full process coverage robot-assisted total hip arthroplasty: A multicenter randomized clinical trial'.

Abstract PO4-13-04: Added Value from Patient Advocates in a Translational Working Group: the COMET Study

Abstract Introduction: A phase III multicenter prospective randomized clinical trial called “Comparing an Operation to Monitoring, with or without Endocrine Therapy (COMET)” (NCT02926911) assesses the risks/benefits of active monitoring (AM) versus surgery for women with low-risk ductal carcinoma in situ (DCIS). It is funded by the Patient-Centered Outcomes Research Institute and enrolled 997 women between 06/30/17 and 01/13/23. Research Patient Advocates (PAs) have been embedded from the study design stage and continue to provide guidance as part of the COMET leadership team. The COMET biobank is funded by independent foundations and is managed through monthly Translational Working Group (TWG) meetings. The TWG includes PAs, clinicians, pathologists, radiologists, and researchers from multiple institutions who discuss topics like categorization of biospecimens into discovery/validation sets; development of a pathology workflow/sample tracking process; use of small samples; and potential areas of future research/technologies that may improve DCIS diagnostics, prognostics, and care management. Methods: The TWG leveraged the existing Alliance Foundation Trials, LLC biobank infrastructure and facilitates the collection, submission, storage and analysis/use of blood, tissue, and breast images collected at specified timepoints and stored in central tissue/image repositories. PAs are active and integral in the TWG, assisting with logistical issues (contracts, transfer agreements, resource requests); communicating with sites; identifying study topics and biomarkers relevant to diverse patients; providing guidance on commercial predictive/prognostic tests; promoting effective stewardship of samples; ensuring overall focus remains on advancing clinical utility; and reporting translational study results to trial participants who agreed to donate samples/images. Results: Over 90% of requested samples/images have been submitted by ˃85 sites. Each patient’s biospecimens and pathology images are linked and de-identified for research. Use of artificial intelligence (AI) is being considered to assist in sample review. TWG members have complementary areas of expertise/experience and promote active stewardship for effective management of these scarce resources. PAs have played key roles concerning equitable data-sharing and acceleration of data and material transfer agreements. They have also been active in development of standards for discovery/training sets, validation test sets; communication procedures for patient cases that progress to future breast events; ways to catalog technologies (e.g., multi-omics, AI); and in research proposal review. Consensus has been achieved regarding major issues such as authorship, biospecimen custodianship, intellectual property, and criteria relevant to patient needs. Logistical barriers, including data sharing and technicalities of biospecimen release, have been resolved. The TWG also played an integral role in resolving recruitment challenges to COMET by creating standard pathology eligibility criteria, resulting in evidence-based protocol amendments that increased accrual. A retrospective review of biospecimens has been performed to determine adequacy for ensuing correlative molecular and spatial profiling studies. Conclusion: PAs help the COMET TWG set policy, and oversee biospecimen/image collection, and biobank use and sharing. PA input also facilitates equitable, transparent research studies and technology development that can improve personalized decisions for surgery versus AM in women with low-risk DCIS. PAs in the TWG aim to integrate the diagnostic and prognostic tools developed as part of the COMET study into future patient care. Citation Format: Deborah Collyar, Desiree Basila, Thomas Lynch, Stuart Schnitt, Jeffrey Marks, Siri Strand, Terry Hyslop, Sunil Badve, Mark Watson, H. T. Carisa Le-Petross, Lars Grimm, Robert West, Anna Weiss, Anna Rapperport, Lorraine King, Rachel Factor, Marc Ryser, Ann Partridge, E Shelley Hwang, Alastair Thompson. Added Value from Patient Advocates in a Translational Working Group: the COMET Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-13-04.

Accuracy of Event Rate and Effect Size Estimation in Major Cardiovascular Trials

For the design of a randomized clinical trial (RCT), estimation of the expected event rate and effect size of an intervention is needed to calculate the sample size. Overestimation may lead to an underpowered trial. To evaluate the accuracy of published estimates of event rate and effect size in contemporary cardiovascular RCTs. A systematic search was conducted in MEDLINE for multicenter cardiovascular RCTs associated with MeSH (Medical Subject Headings) terms for cardiovascular diseases published in the New England Journal of Medicine, JAMA, or the Lancet between January 1, 2010, and December 31, 2019. Identified trials underwent abstract review; eligible trials then underwent full review, and those with insufficiently reported data were excluded. Data were extracted from the original publication or the study protocol, and a random-effects model was used for data pooling. This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline. The primary outcome was the accuracy of event rate and effect size estimation. Accuracy was determined by comparing the observed event rate in the control group and the effect size with their hypothesized values. Linear regression was used to determine the association between estimation accuracy and trial characteristics. Of the 873 RCTs identified, 374 underwent full review and 30 were subsequently excluded, resulting in 344 trials for analysis. The median observed event rate was 9.0% (IQR, 4.3% to 21.4%), which was significantly lower than the estimated event rate of 11.0% (IQR, 6.0% to 25.0%) with a median deviation of -12.3% (95% CI, -16.4% to -5.6%; P < .001). More than half of the trials (196 [61.1%]) overestimated the expected event rate. Accuracy of event rate estimation was associated with a higher likelihood of refuting the null hypothesis (0.13 [95% CI, 0.01 to 0.25]; P = .03). The median observed effect size in superiority trials was 0.91 (IQR, 0.74 to 0.99), which was significantly lower than the estimated effect size of 0.72 (IQR, 0.60 to 0.80), indicating a median overestimation of 23.1% (95% CI, 17.9% to 28.3%). A total of 216 trials (82.1%) overestimated the effect size. In this systematic review of contemporary cardiovascular RCTs, event rates of the primary end point and effect sizes of an intervention were frequently overestimated. This overestimation may have contributed to the inability to adequately test the trial hypothesis.

Percutaneous tendon dry needling and thrust manipulation as an adjunct to multimodal physical therapy in patients with lateral elbow tendinopathy: A multicenter randomized clinical trial.

The purpose of this study was to assess the effects of adding electrical dry needling and thrust manipulation into a multimodal program of exercise, mobilization, and ultrasound in patients with lateral elbow tendinopathy. Randomized, single-blinded, multicenter, parallel-group trial. Thirteen outpatient physical therapy clinics in nine different US states. One hundred and forty-three participants (n = 143) with lateral elbow tendinopathy were randomized. Cervical spine manipulation, extremity manipulation, and percutaneous tendon electrical dry needling plus multimodal physical therapy (n = 73) or multimodal physical therapy (n = 70) alone. The primary outcome was elbow pain intensity and disability as measured by the Patient-Rated Tennis Elbow Evaluation at baseline, 1 week, 4 weeks, and 3 months. Secondary outcomes included the Numeric Pain Rating Scale, Tennis Elbow Functional Scale, Global Rating of Change, and medication intake. The 2 × 4 analysis of covariance demonstrated that individuals with lateral elbow tendinopathy receiving electrical dry needling and thrust manipulation plus multimodal physical therapy experienced significantly greater improvements in disability (Patient-Rated Tennis Elbow Evaluation: F = 19.675; P < 0.001), elbow pain intensity (Numeric Pain Rating Scale: F = 22.769; P < 0.001), and function (Tennis Elbow Function Scale: F = 13.269; P < 0.001) than those receiving multimodal physical therapy alone at 3 months. The between-group effect size was large for pain and disability (Patient-Rated Tennis Elbow Evaluation: standardized mean difference = 1.13; 95% confidence interval: 0.78, 1.48) in favor of the electrical dry needling and thrust manipulation group. The inclusion of percutaneous tendon electrical dry needling and thrust manipulation into a multimodal program of exercise, mobilization and ultrasound was more effective than multimodal physical therapy alone in individuals with lateral elbow tendinopathy.Trial Registration: www.clinicaltrials.gov NCT03167710 May 30, 2017.

Radiation Therapy With or Without Cisplatin for Local Recurrences of Endometrial Cancer: Results From an NRG Oncology/GOG Prospective Randomized Multicenter Clinical Trial.

Pelvic recurrence is a frequent pattern of relapse for women with endometrial cancer. A randomized trial compared progression-free survival (PFS) after treatment with radiation therapy alone as compared with concurrent chemotherapy. Between February 2008 and August 2020, 165 patients were randomly assigned 1:1 to receive either radiation treatment alone or a combination of chemotherapy and radiation treatment. The primary objective of this study was to determine whether chemoradiation therapy was more effective than radiation therapy alone at improving PFS. The majority of patients had low-grade (1 or 2) endometrioid histology (82%) and recurrences confined to the vagina (86%). External beam with either the three-dimensional or intensity modulated radiation treatment technique was followed by a boost delivered with brachytherapy or external beam. Patients randomly assigned to receive chemotherapy were treated with once weekly cisplatin (40 mg/m2). Rates of acute toxicity were higher in patients treated with chemoradiation as compared with radiation treatment alone. Median PFS was longer for patients treated with radiation therapy alone as compared with chemotherapy and radiation (median PFS was not reached for RT v 73 months for chemoradiation, hazard ratio of 1.25 (95% CI, 0.75 to 2.07). At 3 years, 73% of patients treated definitively with radiation and 62% of patients treated with chemoradiation were alive and free of disease progression. Excellent outcomes can be achieved for women with localized recurrences of endometrial cancer when treated with radiation therapy. The addition of chemotherapy does not improve PFS for patients treated with definitive radiation therapy for recurrent endometrial cancer and increases acute toxicity. Patients with low-grade and vaginal recurrences who constituted the majority of those enrolled are best treated with radiation therapy alone.

Neurodevelopmental Outcomes After Late Preterm Antenatal Corticosteroids

The Antenatal Late Preterm Steroids (ALPS) trial changed clinical practice in the United States by finding that antenatal betamethasone at 34 to 36 weeks decreased short-term neonatal respiratory morbidity. However, the trial also found increased risk of neonatal hypoglycemia after betamethasone. This follow-up study focused on long-term neurodevelopmental outcomes after late preterm steroids. To evaluate whether administration of late preterm (34-36 completed weeks) corticosteroids affected childhood neurodevelopmental outcomes. Prospective follow-up study of children aged 6 years or older whose birthing parent had enrolled in the multicenter randomized clinical trial, conducted at 13 centers that participated in the Maternal-Fetal Medicine Units (MFMU) Network cycle from 2011-2016. Follow-up was from 2017-2022. Twelve milligrams of intramuscular betamethasone administered twice 24 hours apart. The primary outcome of this follow-up study was a General Conceptual Ability score less than 85 (-1 SD) on the Differential Ability Scales, 2nd Edition (DAS-II). Secondary outcomes included the Gross Motor Function Classification System level and Social Responsiveness Scale and Child Behavior Checklist scores. Multivariable analyses adjusted for prespecified variables known to be associated with the primary outcome. Sensitivity analyses used inverse probability weighting and also modeled the outcome for those lost to follow-up. Of 2831 children, 1026 enrolled and 949 (479 betamethasone, 470 placebo) completed the DAS-II at a median age of 7 years (IQR, 6.6-7.6 years). Maternal, neonatal, and childhood characteristics were similar between groups except that neonatal hypoglycemia was more common in the betamethasone group. There were no differences in the primary outcome, a general conceptual ability score less than 85, which occurred in 82 (17.1%) of the betamethasone vs 87 (18.5%) of the placebo group (adjusted relative risk, 0.94; 95% CI, 0.73-1.22). No differences in secondary outcomes were observed. Sensitivity analyses using inverse probability weighting or assigning outcomes to children lost to follow-up also found no differences between groups. In this follow-up study of a randomized clinical trial, administration of antenatal corticosteroids to persons at risk of late preterm delivery, originally shown to improve short-term neonatal respiratory outcomes but with an increased rate of hypoglycemia, was not associated with adverse childhood neurodevelopmental outcomes at age 6 years or older.

P050 Determining the feasibility of a multi-centre randomised clinical trial to test the effectiveness of integrated symptom tracking for managing rheumatoid arthritis

Abstract Background/Aims In a series of studies, we co-developed and piloted the remote monitoring of rheumatoid arthritis (REMORA) system. REMORA enables patients to daily track symptoms via their smartphone and integrates this data into their electronic health record for discussion during routine clinic visits. This offers the opportunity to make better, and shared, treatment decisions and improve disease management. The effectiveness of integrated daily symptom tracking on clinical and patient-reported outcomes will be tested in a multi-centre stepped wedge randomised clinical trial (RCT). Here, we present the results of the REMORA feasibility study to test trial procedures and intervention delivery. Methods Across two NHS sites in the Northwest of England we aimed to recruit 60 patients, aged ≥18 years with rheumatoid arthritis (RA) or inflammatory arthritis (IA), and access to an Android/iOS smartphone with daily internet access. Participants were asked to complete a baseline web-survey and use the REMORA app to collect daily symptom reports for up to six months. Clinical care teams extracted data from participants’ medical records for all baseline and follow-up appointments, including disease activity scores. To assess feasibility, we reported recruitment rates, participants’ uptake of and adherence to daily symptom tracking, and outcome data completeness. We also compared characteristics of a) those who consented vs. trackers (defined as submitting ≥1 symptom report, i.e., successful intervention uptake), and b) high adherers (symptoms reported on &amp;gt; 60% days) vs. low adherers (symptoms reported on &amp;lt; 25% days). Results A total of 130 patients were screened across study sites, and 52 were eligible and provided consent to take part (40.0%). Of those, 32 (61.5%) initiated symptom tracking; their demographic characteristics were broadly similar to those who consented, though more people of white ethnicity appeared higher in the tracker group (93.8% (95% CI 79.2-99.2) vs 86.5% (74.2-94.4), respectively). Participants completed at least one symptom report on 63.2% of study days (2384/3771 days). We observed few differences between low vs high adherers, though low adherers (n = 6) were younger (median (IQR) years: 41.5 (34.5-55.3)) than the high engagers (n = 20; 61.0 (50.5-65.3)) and had a shorter disease duration (years: 1.0 (0-5.8) vs 3.0 (0.8-10.8)). In total, 48 consented participants had at least one follow-up appointment during the study window; 46 (95.8%) had complete primary outcome data. Conclusion Across two clinical sites, we determined that the procedures and intervention delivery designed for use within a future multi-centre stepped wedge RCT of the REMORA system were feasible for recruitment, adherence to the intervention and completion of the primary outcome. However, uptake of the intervention was lower than we hoped. To enhance intervention uptake in the main trial, we clarified inclusion criteria, improved patient information on what is required to initiate symptom tracking and modified our supporting materials. Disclosure K.L. Druce: None. M. Parkes: None. R. Bravo: None. D. Griffiths-Jones: None. S.N. van der Veer: None. W. Dixon: Consultancies; consultancy fees from Google unrelated to this work. J. McBeth: None.

The clinical value of mNGS of bronchoalveolar lavage fluid versus traditional microbiological tests for pathogen identification and prognosis of severe pneumonia (NT-BALF):study protocol for a prospective multi-center randomized clinical trial.

Early, rapid, and accurate pathogen diagnosis can help clinicians select targeted treatment options, thus improving prognosis and reducing mortality rates of severe pneumonia. Metagenomic next-generation sequencing (mNGS) has a higher sensitivity and broader pathogen spectrum than traditional microbiological tests. However, the effects of mNGS-based antimicrobial treatment procedures on clinical outcomes and cost-effectiveness in patients with severe pneumonia have not been evaluated. This is a regional, multi-center, open, prospective, randomized controlled trial to evaluate that whether the combination of mNGS and traditional testing methods could decrease 28-day call-cause mortality with moderate cost-effectiveness. A total of 192 patients with severe pneumonia will be recruited from four large tertiary hospitals in China. Bronchoalveolar lavage fluid will be obtained in all patients and randomly assigned to the study group (mNGS combined with traditional microbiological tests) or the control group (traditional microbiological tests only) in a 1:1 ratio. Individualized antimicrobial treatment and strategy will be selected according to the analysis results. The primary outcome is 28-day all-cause mortality. The secondary outcomes are ICU and hospital length of stay (LOS), ventilator-free days and ICU-free days, consistency between mNGS and traditional microbiological tests, detective rate of mNGS and traditional microbiological tests, turn-out time, time from group allocation to start of treatment, duration of vasopressor support, types and duration of anti-infective regimens, source of drug-resistant bacteria or fungi, and ICU cost. The clinical benefits of mNGS are potentially significant, but its limitations should also be considered. ChineseClinicalTrialRegistry.org, ChiCTR2300076853. Registered on 22 October 2023.

Balloon Guide Catheter Versus Non–Balloon Guide Catheter: A MR CLEAN Registry Analysis

BACKGROUND Balloon guide catheters (BGCs) are used to prevent distal emboli during endovascular treatment for acute ischemic stroke. Although literature reports benefit of BGC, these are not universally used, and randomized head‐to‐head comparisons are lacking. This study compared functional, safety, and technical outcomes between patients treated with non‐BGC and with BGC during endovascular treatment in a nationwide prospective multicenter registry. METHODS Patients from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry, 2014 to 2018), who underwent endovascular treatment with a non‐BGC or BGC, were included. Primary outcome was the modified Rankin Scale score at 90 days, and secondary outcomes included procedure time and first‐attempt successful reperfusion (extended Thrombolysis in Cerebral Infarction ≥2C). Treatment‐effect modification and subgroups were analyzed according to first‐line thrombectomy technique and different sizes of non‐BGC. RESULTS In total 2808 patients were included, and 1671 (60%) were treated with BGC. No differences in the modified Rankin Scale score at 90 days were seen between non‐BGC and BGC groups (adjusted common odds ratio [OR], 0.98 [95% CI, 0.82–1.10]). The non‐BGC was associated with faster procedure times compared with BGC (adjusted β: −2.99 [95% CI, −5.58 to −0.40]). A significant treatment effect was found between BGC use and thrombectomy technique. In subgroup analyses with stent retriever as first‐line technique, 90‐day modified Rankin Scale scores were significantly higher (more disability) in the non‐BGC group compared with the BGC group (adjusted common OR, 0.79 [95% CI, 0.65–0.96]). Direct aspiration combined with non‐BGC resulted in higher first‐attempt rates compared with BGC (adjusted OR, 1.55 [95% CI, 1.06–2.28]). CONCLUSIONS This large prospective multicenter registry showed no differences in clinical outcome between patients treated with non‐BGC and BGC. Subgroup analyses suggest that BGC outperforms the non‐BGC when stent retriever is used as first‐line technique, whereas non‐BGC outperforms the BGC when aspiration is used.

Three-Year Outcomes of Oral Antibiotics vs Intravenous and Oral Antibiotics for Uncomplicated Acute Appendicitis

Current short-term evidence has shown that uncomplicated acute appendicitis can be treated successfully with oral antibiotics alone, but longer-term results are lacking. To assess the treatment effectiveness of oral antibiotic monotherapy compared with combined intravenous (IV) and oral antibiotics in computed tomography-confirmed uncomplicated acute appendicitis at a longer-term follow-up. This secondary analysis of a predefined year 3 follow-up of the Appendicitis Acuta II (APPAC II) noninferiority, multicenter randomized clinical trial compared oral moxifloxacin with combined IV ertapenem plus oral levofloxacin and metronidazole for the treatment of uncomplicated acute appendicitis. The trial was conducted at 9 university and central hospitals in Finland from April 2017 to November 2018, with the last follow-up in November 2022. Participants included patients aged 18 to 60 years, who were randomized to receive either oral antibiotics monotherapy (n = 301) or combined IV and oral antibiotics (n = 298). Antibiotics monotherapy consisted of oral moxifloxacin, 400 mg/d, for 7 days. Combined IV and oral antibiotics consisted of IV ertapenem sodium, 1 g/d, for 2 days plus oral levofloxacin, 500 mg/d, and metronidazole, 500 mg 3 times/d, for 5 days. The primary end point was treatment success, defined as the resolution of acute appendicitis and discharge from hospital without the need for surgical intervention and no appendicitis recurrence at the year 3 follow-up evaluated using a noninferiority design. The secondary end points included late (after 1 year) appendicitis recurrence as well as treatment-related adverse events, quality of life, length of hospital stay, and length of sick leave, which were evaluated using a superiority design. After exclusions, 599 patients (mean [SD] age, 36 [12] years; 336 males [56.1%]) were randomized; after withdrawal and loss to follow-up, 582 patients (99.8%) were available for the year 3 follow-up. The treatment success at year 3 was 63.4% (1-sided 95% CI, 58.8% to ∞) in the oral antibiotic monotherapy group and 65.2% (1-sided 95% CI, 60.5% to ∞) in the combined IV and oral antibiotics group. The difference in treatment success rate between the groups at year 3 was -1.8 percentage points (1-sided 95% CI, -8.3 percentage points to ∞; P = .14 for noninferiority), with the CI limit exceeding the noninferiority margin. There were no significant differences between groups in treatment-related adverse events, quality of life, length of hospital stay, or length of sick leave. This secondary analysis of the APPAC II trial found a slightly higher appendectomy rate in patients who received oral antibiotic monotherapy; however, noninferiority of oral antibiotic monotherapy compared with combined IV and oral antibiotics could not be demonstrated. The results encourage future studies to assess oral antibiotic monotherapy as a viable treatment alternative for uncomplicated acute appendicitis. ClinicalTrials.gov Identifier: NCT03236961.

Tension band versus locking plate fixation for patella fractures - a protocol of a randomised controlled trial.

Following surgical management of patella fractures, patients commonly report pain; difficulties with weight-bearing tasks such as walking, running and climbing stairs; and restrictions in quality of life. Recently, a locking plate system for surgical management of patella fractures has been introduced. To date, no studies have compared standard treatment with tension band wiring with locking plate fixation in a randomised study design. We aim to compare the one-year patient-reported Knee Injury and Osteoarthritis Outcome subscale scores (KOOS5-subscales) after standard care tension band fixation with locking plate fixation for patients with patella fractures. This is a multicentre randomised and prospective clinical trial. A total of 122 patients will be included in the study, and the primary outcome will be the KOOS subscales at 12 months after surgery. Findings from the present study are expected to advance our understanding of outcome following surgical treatment of patella fractures. This study is funded, in part, by the Novo Nordisk Foundation, Denmark. gov ID: NCT04891549.

Clinical trial of tolerability, safety and immunogenicity of influenza inactivated split-vaccine Flu-M in children aged 6 to 17 years

Purpose. To evaluate the tolerability, safety and immunogenicity of influenza inactivated split flu vaccine Flu-M during single immunization of children aged 6 to 17 years.Materials and methods. A multicentre double-blind comparative randomised clinical trial of influenza inactivated split vaccine Flu-M for immunisation of children aged 6 to 17 years (the reference agent – Ultrix vaccine) was conducted. Children aged 12 to 17 years inclusive (300 children) were studied at stage I, and children aged 6 to 12 years (300 children) at stage II. Volunteers of each age category were randomised 1:1 into 2 groups comparable in sex and age, one was vaccinated with Flu-M vaccine and the other with Ultrix vaccine. The follow-up, including various laboratory and clinical tests, lasted for 28 days from the time of vaccination.Results. Both vaccines were well tolerated by children aged 12 to 17 years and by children aged 6 to 12 years. There were no severe or serious adverse events. By all criteria of immunogenicity evaluation, vaccine Flu-M was not inferior to the comparison vaccine Ultrix.Conclusion. Influenza inactivated split Flu-M vaccine produced by SPbNIIVS is approved for use for specific prophylaxis of influenza in children aged 6 to 17 years in the Russian Federation, the Republic of Belarus, Latin America and the Caribbean.The trial is registered at ClinicalTrials. gov (NCT 05317767).

7.5F Mini Flexible Ureteroscope in Retrograde Intrarenal Surgery: Initial Results from a Multicenter Randomized Clinical Trial.

Objective: To report the initial results of an randomized clinical trail comparing the safety and efficacy between 7.5F and 9.2F flexible ureteroscope (FUS) in the management of renal calculi <2 cm. Materials and Methods: Eighty patients were enrolled and received retrograde intrarenal surgery (RIRS) with a different size FUS. The operation results and complications were compared. Results: Two cases in the 7.5F group and four cases in the 9.2F group failed to insert the 12/14F ureteral access sheath (UAS), respectively, and no significant difference (p = 0.396) was noted. However, 10/12F UAS was inserted in the 7.5F group, but not available in the 9.2F group, and thus, the 10/12F UAS inserting rate in the 7.5F group was higher than in the 9.2F group (100% vs 0%, p = 0.014), and the UAS insertion failure rate in 9.2F group was higher than in the 7.5F group (10% vs 0%, p = 0.040). The operation time in 7.5F group was shorter than the 9.2F group (35.60 ± 7.86 vs 41.05 ± 8.14, p = 0.003). Less irrigation was required in 7.5F group (813.93 ± 279.47 mL vs 1504.18 ± 385.31 mL, p = 0.000). The postoperative fever rate in 9.2F group was higher than 7.5F group (20% vs 5%, p = 0.043). There was no significant difference in sepsis (0% vs 2.5%, p = 0.314) between the two groups. No significant difference was noted in hospital stay (0.93 ± 0.49 days vs 1.14 ± 0.64 days, p = 0.099) between the two groups. The final stone-free rate (SFR) in 7.5F group was higher than 9.2F group (95% vs 80%, p = 0.043). Conclusion: The latest 7.5F mini FUS was a reliable instrument in RIRS to keep a good visualization with low requirement of irrigation, low postoperative infection complication, and also a high SFR when compared with the conventional 9.2F FUS. Clinical Trial Registration: NCT05231577.

Comparing psychological versus pharmacological treatment in emotional disorders: A network analysis.

Transdiagnostic group cognitive behavioural therapy (TD-GCBT) is more effective in improving symptoms and severity of emotional disorders (EDs) than treatment as usual (TAU; usually pharmacological treatment). However, there is little research that has examined the effects of these treatments on specific symptoms. This study used Network Intervention Analysis (NIA) to investigate the direct and differential effects of TD-GCBT + TAU and TAU on specific symptoms of anxiety and depression. Data are from a multicentre randomised clinical trial (N = 1061) comparing TD-GCBT + TAU versus TAU alone for EDs. The networks included items from the PHQ-9 (depression) and GAD-7 (anxiety) questionnaire and mixed graphical models were estimated at pre-treatment, post-treatment and 3-, 6- and 12-month follow-up. Results revealed that TD-GCBT + TAU was associated with direct effects, mainly on several anxiety symptoms and depressed mood after treatment. New direct effects on other depressive symptoms emerged during the follow-up period promoted by TD-GCBT compared to TAU. Our results suggest that the improvement of anxiety symptoms after treatment might precipitate a wave of changes that favour a decrease in depressive symptomatology. NIA is a methodology that can provide fine-grained insight into the likely pathways through which treatments exert their effects.

Partially supervised exercise programmes for fall prevention improve physical performance of older people at risk of falling: a three-armed multi-centre randomised controlled trial

BackgroundFalls have a major impact on individual patients, their relatives, the healthcare system and related costs. Physical exercise programmes that include multiple categories of exercise effectively reduce the rate of falls and risk of falling among older adults.MethodsThis 12-month, assessor-blinded, three-armed multicentre randomised clinical trial was conducted in adults aged ≥ 65 years identified as at risk of falling. Four hundred and five participants were randomly allocated into 3 groups: experimental group (n = 166) with the Test&Exercise partially supervised programme based on empowerment delivered with a tablet, illustrated manual and cards, reference group (n = 158) with the Otago partially supervised programme prescribed by a physiotherapist delivered with an illustrated manual and control group (n = 81) with the Helsana self-administrated programme delivered with cards. Experimental and reference groups received partially supervised programmes with 8 home sessions over 6 months. Control group received a self-administered program with a unique home session. The 3 groups were requested to train independently 3 times a week for 12 months. Primary outcome was the incidence rate ratio of self-reported falls over 12 months. Secondary outcomes were fear of falling, basic functional mobility and balance, quality of life, and exercise adherence.ResultsA total of 141 falls occurred in the experimental group, 199 in the reference group, and 42 in the control group. Incidence rate ratios were 0.74 (95% CI 0.49 to 1.12) for the experimental group and 0.43 (95% CI 0.25 to 0.75) for the control group compared with the reference group. The Short Physical Performance Battery scores improved significantly in the experimental group (95% CI 0.05 to 0.86; P = 0.027) and in the reference group (95% CI 0.06 to 0.86; P = 0.024) compared with the control group.ConclusionThe self-administered home-based exercise programme showed the lowest fall incidence rate, but also the highest dropout rate of participants at high risk of falling. Both partially supervised programmes resulted in statistically significant improvements in physical performance compared with the self-administered programme.Trial registrationNCT02926105. ClinicalTrials.gov. Date of registration: 06/10/2016.