Multicenter Randomized Clinical Trial Research Articles

Survival in Patients With Recurrent Intermediate-Stage Hepatocellular Carcinoma

Transarterial chemoembolization (TACE) is commonly used to treat patients with recurrent intermediate-stage hepatocellular carcinoma (HCC) and positive microvascular invasion (MVI); however, TACE alone has demonstrated unsatisfactory survival benefits. A previous retrospective study suggested that TACE plus sorafenib (SOR-TACE) may be a better therapeutic option compared with TACE alone. To investigate the clinical outcomes of SOR-TACE vs TACE alone for patients with recurrent intermediate-stage HCC after R0 hepatectomy with positive MVI. In this phase 3, open-label, multicenter randomized clinical trial, patients with recurrent intermediate-stage HCC and positive MVI were randomly assigned in a 1:1 ratio via a computerized minimization technique to either SOR-TACE treatment or TACE alone. This trial was conducted at 5 hospitals in China, and enrolled patients from October 2019 to December 2021, with a follow-up period of 24 months. Data were analyzed from June 2023 to September 2023. Randomization to on-demand TACE (conventional TACE: doxorubicin, 50 mg, mixed with lipiodol and gelatin sponge particles [diameter: 150-350 μm]; drug-eluting bead TACE: doxorubicin, 75 mg, mixed with drug-eluting particles [diameter: 100-300 μm or 300-500 μm]) (TACE group) or sorafenib, 400 mg, twice daily plus on-demand TACE (SOR-TACE group) (conventional TACE: doxorubicin, 50 mg, mixed with lipiodol and gelatin sponge particles [diameter, 150-350 μm]; drug-eluting bead TACE: doxorubicin, 75 mg, mixed with drug-eluting particles [diameter: 100-300 μm or 300-500 μm]). The primary end point was overall survival by intention-to-treat analysis. Safety was assessed in patients who received at least 1 dose of study treatment. A total of 162 patients (median [range] age, 55 [28-75] years; 151 males [93.2%]), were randomly assigned to be treated with either SOR-TACE (n = 81) or TACE alone (n = 81). The median overall survival was significantly longer in the SOR-TACE group than in the TACE group (22.2 months vs 15.1 months; hazard ratio [HR], 0.55; P < .001). SOR-TACE also prolonged progression-free survival (16.2 months vs 11.8 months; HR, 0.54; P < .001), and improved the objective response rate when compared with TACE alone based on the modified Response Evaluation Criteria in Solid Tumors criteria (80.2% vs 58.0%; P = .002). Any grade adverse events were more common in the SOR-TACE group, but all adverse events responded well to treatment. No unexpected adverse events or treatment-related deaths occurred in this study. The results of this randomized clinical trial demonstrated that SOR-TACE achieved better clinical outcomes than TACE alone. These findings suggest that combined treatment should be used for patients with recurrent intermediate-stage HCC after R0 hepatectomy with positive MVI. ClinicalTrials.gov Identifier: NCT04103398.

Effectiveness of mailed outreach and patient navigation to promote HCC screening process completion: a multicentre pragmatic randomised clinical trial

BackgroundHepatocellular carcinoma (HCC) is plagued by failures across the cancer care continuum, leading to frequent late-stage diagnoses and high mortality. We evaluated the effectiveness of mailed outreach invitations plus patient...

Cervical cancer: Challenges and prevention strategies: A narrative review.

Human papillomavirus (HPV) infections that continue to exist are the main cause of cervical cancer (CC), two-thirds of CC occurrences worldwide are caused by HPV 16 and HPV 18, and 99.7% of CC tumors are linked to oncogenic HPV infection. To identify challenges of CC and its prevention and treatment modalities. This review examined the epidemiology, predisposing factors, genetic factors, clinical assessment methods, current treatment options, and prevention approaches for CC. We had perform a narrative data synthesis rather than a pooled analysis. A thorough literature search in pertinent databases related to CC was done with the inclusion of data that were published in the English language. Early detection of CC is of utmost importance to detect precancerous lesions at an early stage. Therefore, all responsible agencies concerned with health should make all women aware of the benefits of CC screening and educate the general public. HPV vaccination coverage is very low in resource-limited settings. To achieve the goal of eliminating CC as a public health problem in 2030, the World Health Organization will pay special attention to increasing HPV vaccination coverage throughout the world. To further improve HPV vaccine acceptability among parents and their children, safety-related aspects of the HPV vaccine should be further investigated through post-marketing surveillance and multicentre randomized clinical trials.

The moderating role of diabetes distress on the effect of a randomized eHealth intervention on glycemic control in Black adolescents with type 1 diabetes.

Due to systemic inequities, Black adolescents with type 1 diabetes are more likely to have suboptimal glycemic control and high rates of diabetes distress, but tailored interventions for this population are lacking. In primary outcomes of a randomized clinical trial, a family-based eHealth intervention improved glycemic control in Black adolescents with type 1 diabetes and elevated depressive symptoms. The present study is a secondary analysis of these clinical trial data examining the moderating effect of diabetes distress on the efficacy of the intervention. Using secondary data from a multicenter randomized clinical trial (Clinicaltrials.gov [NCT03168867]), caregiver-adolescent dyads were randomly assigned to either up to three sessions of an eHealth parenting intervention (n = 75) or a standard medical care control group (n = 74). Black adolescents (10 years, 0 months to 14 years, 11 months old) with type 1 diabetes and a caregiver willing to participate were eligible. Adolescents reported their diabetes distress at baseline, and hemoglobin A1c (HbA1c) data were collected at baseline, 6-, 13-, and 18-month follow-up. No between-group contrasts emerged in a linear mixed-effects regression (p's > .09). Within-group contrasts emerged such that adolescents assigned to the intervention who reported high diabetes distress had lower HbA1c at the 18-month follow-up relative to baseline (p = .004); the 18-month decrease in HbA1c was -1.03%. Black adolescents with type 1 diabetes and high levels of diabetes distress showed significant decreases in HbA1c following a family-based eHealth intervention, suggesting diabetes distress may be a key moderator of intervention efficacy within this population.

Evaluation of the efficacy, safety, and pharmacokinetics of nanodispersible cannabidiol oral solution (150 mg/mL) versus placebo in mild to moderate anxiety subjects: A double blind multicenter randomized clinical trial

BackgroundAnxiety disorders, an increasingly prevalent global mental health illness, affected approximately 301 million individuals worldwide in 2019. There is an unmet need for the treatment of anxiety disorders, as current therapies are associated with limited response rates, residual symptoms, and adverse effects. ObjectivesTo evaluate the efficacy, safety, and pharmacokinetics of nanodispersible cannabidiol (CBD) oral solution versus placebo for the treatment of mild to moderate anxiety disorders. MethodsThis phase 3 prospective, randomized, double blind, parallel group, placebo-controlled, 15-week cohort study took place at multiple sites across India. Eligible participants were randomly assigned to one of the two treatment arms (CBD or placebo) in a 1:1 ratio. Results178 participants were randomized to receive CBD (n=89) or placebo (n=89). The study met both primary (GAD-7 and HAM-A scores) and secondary outcomes (CGI-I, CGI-S, PHQ-9 and PSQI scores). The GAD-7 score difference between the end of treatment and baseline for the CBD versus the placebo was −7.02 (S.E: 0.25, 95% CI −7.52; −6.52), p<0.0001. Similarly, the HAM-A score difference at the end of treatment compared to baseline for the CBD versus the placebo was −11.9 (S.E: 0.33, 95% CI −12.6; −11.3), p<0.0001. ConclusionsNanodispersible CBD was therapeutically safe with no serious adverse events, well tolerated, and effective for the treatment of mild to moderate anxiety disorders, as well as associated depression and sleep quality disturbances. These results pave way for probable prospective use of nanodispersible CBD formulation for various psychiatry disorders alone or in conjunction with other drugs.

Effects of Mediterranean Diet, Curcumin, and Resveratrol on Mild-to-Moderate Active Ulcerative Colitis: A Multicenter Randomized Clinical Trial.

This study aimed to investigate the effects of the Mediterranean diet (MD), combined with curcumin and resveratrol supplementation, on disease activity, serum inflammatory markers, and quality of life in patients with mild-to-moderate active ulcerative colitis (UC). This study was designed as a prospective multicenter three-arm randomized controlled trial. Participants were randomized to the MD, MD + curcumin, and MD + resveratrol groups. All participants were placed on the MD for 8 weeks. The MD + curcumin group also received 1600 mg/day of curcumin supplementation, whereas the MD + resveratrol group received 500 mg/day of resveratrol supplementation for 8 weeks. Anthropometric measurements, Truelove-Witts Index, Short Form-36, Inflammatory Bowel Disease Questionnaire, Mediterranean Diet Adherence Scale (MEDAS), and laboratory tests were performed at baseline and postintervention. Within-group comparisons showed that MD, MD + curcumin, and MD + resveratrol interventions were effective in reducing disease activity and inflammation and improving quality of life in individuals with UC (p < 0.05). Between-group comparisons revealed no significant difference in all parameters except for the pain subparameter of SF-36 and the MEDAS score (p < 0.05). The MD is an effective and safe intervention to be used in clinical practice in individuals with UC.

Efficacy of clozapine versus standard treatment in adult individuals with intellectual disability and treatment-resistant psychosis (CLOZAID): study protocol of a multicenter randomized clinical trial.

Intellectual disability (ID) affects approximately 1% of the worldwide population and individuals with ID have a higher comorbidity with mental illness, and specifically psychotic disorders. Unfortunately, among individuals with ID, limited research has been conducted since ID individuals are usually excluded from mental illness epidemiological studies and clinical trials. Here we perform a clinical trial to investigate the effectiveness of clozapine in the treatment of resistant psychosis in individuals with ID. The article highlights the complexity of diagnosing and treating psychopathological alterations associated with ID and advocates for more rigorous research in this field. A Phase IIB, open-label, randomized, multicenter clinical trial (NCT04529226) is currently ongoing to assess the efficacy of oral clozapine in individuals diagnosed with ID and suffering from treatment-resistant psychosis. We aim to recruit one-hundred and fourteen individuals (N=114) with ID and resistant psychosis, who will be randomized to TAU (treatment as usual) and treatment-with-clozapine conditions. As secondary outcomes, changes in other clinical scales (PANSS and SANS) and the improvement in functionality, assessed through changes in the Euro-QoL-5D-5L were assessed. The main outcome variables will be analyzed using generalized linear mixed models (GLMM), assessing the effects of status variable (TAU vs. Clozapine), time, and the interaction between them. The treatment of resistant psychosis among ID individuals must be directed by empirically supported research. CLOZAID clinical trial may provide relevant information about clinical guidelines to optimally treat adults with ID and treatment-resistant psychosis and the benefits and risks of an early use of clozapine in this underrepresented population in clinical trials. Clinicaltrials.gov: NCT04529226. EudraCT: 2020-000091-37.

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.

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.

The Otto Aufranc Award: Does Hip Arthroscopy at the Time of Periacetabular Osteotomy Improve the Clinical Outcome for the Treatment of Hip Dysplasia? A Multicenter Randomized Clinical Trial

BackgroundA periacetabular osteotomy (PAO) is often sufficient to treat the symptoms and improve quality of life for symptomatic hip dysplasia. However, acetabular cartilage and labral pathologies are very commonly present, and there is a lack of evidence examining the benefits of adjunct arthroscopy to treat these. The goal of this study was to compare the clinical outcome of patients undergoing PAO with and without arthroscopy, with the primary end point being the International Hip Outcome Tool-33 at 1 year. MethodsIn a multicenter study, 203 patients who had symptomatic hip dysplasia were randomized: 97 patients undergoing an isolated PAO (mean age 27 years [range, 16 to 44]; mean body mass index of 25.1 [range, 18.3 to 37.2]; 86% women) and 91 patients undergoing PAO who had an arthroscopy (mean age 27 years [range, 16 to 49]; mean body mass index of 25.1 [17.5 to 25.1]; 90% women). ResultsAt a mean follow-up of 2.3 years (range, 1 to 5), all patients exhibited improvements in their functional score, with no significant differences between PAO plus arthroscopy versus PAO alone at 12 months postsurgery on all scores: preoperative International Hip Outcome Tool-33 score of 31.2 (standard deviation [SD] 16.0) versus 36.4 (SD 15.9), and 12 months postoperative score of 72.4 (SD 23.4) versus 73.7 (SD 22.6). The preoperative Hip disability and Osteoarthritis Outcome pain score was 60.3 (SD 19.6) versus 66.1 (SD 20.0) and 12 months postoperative 88.2 (SD 15.8) versus 88.4 (SD 18.3). The mean preoperative physical health Patient-Reported Outcomes Measurement Information System score was 42.5 (SD 8.0) versus 44.2 (SD 8.8) and 12 months postoperative 48.7 (SD 8.5) versus 52.0 (SD 10.6). There were 4 patients with PAO without arthroscopy who required an arthroscopy later to resolve persistent symptoms, and 1 patient from the PAO plus arthroscopy group required an additional arthroscopy. ConclusionsThis randomized controlled trial has failed to show any significant clinical benefit in performing hip arthroscopy at the time of the PAO at 1-year follow-up. Longer follow-up will be required to determine if hip arthroscopy provides added value to a PAO for symptomatic hip dysplasia.

Topical versus oral corticosteroids in moderate drug reaction with eosinophilia and systemic symptoms: A multicenter randomized clinical trial

Topical versus oral corticosteroids in moderate drug reaction with eosinophilia and systemic symptoms: A multicenter randomized clinical trial

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.

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.