Randomized Clinical Trial Research Articles

Safety and efficacy of pembrolizumab, radiation therapy, and surgery versus radiation therapy and surgery for stage III soft tissue sarcoma of the extremity (SU2C-SARC032): an open-label, randomised clinical trial.

Approximately half of patients with localised, high-risk soft tissue sarcoma of the extremity develop metastases. We aimed to assess whether the addition of pembrolizumab to preoperative radiotherapy and surgery would improve disease-free survival. We completed an open-label, randomised clinical trial in patients with grade 2 or 3, stage III undifferentiated pleomorphic sarcoma or dedifferentiated or pleomorphic liposarcoma of the extremity and limb girdle. Patients were enrolled at 20 academic institutions in Australia, Canada, Italy, and the USA. Patients were randomly assigned to preoperative radiotherapy then surgery (control group) or preoperative pembrolizumab with radiotherapy (initiated 1-14 days after the first dose of pembrolizumab) then surgery and postoperative pembrolizumab (experimental group). Pembrolizumab (200 mg intravenously every 3 weeks) was administered as three neoadjuvant cycles (before, during, and after radiotherapy) and 14 or less adjuvant cycles. Primary endpoint was disease-free survival. This study is registered with ClincialTrials.gov (NCT03092323). Between Nov 18, 2017, and Nov 14, 2023, 143 participants were randomly assigned to treatment. A modified intention-to-treat analysis of 127 patients with median follow-up of 43 months showed that the experimental group (n=64) had significantly longer disease-free survival than the control group (n=63; log-rank one-sided p=0·035; hazard ratio [HR] 0·61; 90% CI 0·39-0·96). The 2-year disease-free survival increased by 15% with addition of pembrolizumab: 52% (90% CI 42-64) and 67% (90% CI 58-78) for the control and experimental groups, respectively. Disease-free survival was similarly improved with pembrolizumab for the intention-to-treat patient population (HR 0·61 [90% CI 0·39-0·95]). Grade 3 or higher adverse events occurred more frequently in the experimental group (56%) than the control group (31%). Addition of pembrolizumab to preoperative radiotherapy and surgery improves disease-free survival for patients with stage III undifferentiated pleomorphic sarcoma and pleomorphic or dedifferentiated liposarcoma of the extremity, which establishes a promising new treatment option for these patients. Stand Up to Cancer and Merck Sharp & Dohme.

Real-World, Observational, Retrospective Study to Evaluate the Effectiveness and Safety of Treatment with Sorafenib in Patients with Advanced Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) accounts for approximately 90% of liver cancer cases. Sorafenib, the first drug to demonstrate survival benefits for advanced HCC, was validated through the SHARP randomized clinical trial (RCT). While RCTs are essential for assessing new therapies, real-world studies provide additional insights into their effectiveness in routine clinical practice. This study aimed to evaluate sorafenib’s real-world effectiveness by analyzing overall survival (OS) and the time to radiological and symptomatic progression. Methods: Data from 368 patients treated with sorafenib at a Brazilian Cancer Center between 2009 and 2020 were retrospectively reviewed. Results: The median OS was 9.6 months, and the time to radiological progression was 5.3 months, similar to the SHARP trial. However, the time to symptomatic progression was shorter (2.3 months) than the SHARP study (4.1 months). In terms of safety, 27.4% of patients presented clinically relevant toxicities, and 24.5% needed to discontinue treatment due to toxicity. Conclusions: Overall, sorafenib demonstrated effectiveness in the studied population, with OS and radiological progression times comparable to SHARP study results. The difference in symptomatic progression may be due to the study’s retrospective nature and limitations.

An Update on Recent Clinical Trial Data in Bloodstream Infection

Bloodstream infections (BSIs) remain a significant source of morbidity and mortality globally, exacerbated by an ageing population and rising antimicrobial resistance (AMR). This review offers an updated evaluation of randomized clinical trials (RCTs) in BSI management from 2018 onwards, focusing on the evolving landscape of diagnostics and treatment. New rapid diagnostic technologies and shorter antimicrobial courses have transformed clinical practice, reducing the time to appropriate therapy and hospital stays. Several RCTs demonstrated that rapid phenotypic and genotypic tests shorten the time to optimal therapy, especially when paired with antimicrobial stewardship. Ongoing trials are investigating novel antimicrobial regimens and the safety of early oral switch strategies, particularly for Gram-positive and Gram-negative BSIs. Recent RCTs on Staphylococcus aureus BSI (SAB) and multidrug-resistant Gram-negative bacteria highlight advances in treatment but emphasize the need for further study into the efficacy of combination therapies and the utility of rapid diagnostics in different healthcare settings. The review also explores challenges in trail design, with adaptive and pragmatic appropriates improving the efficacy of clinical trials. Finally, this paper identifies gaps in the research, including the need for further investigation into oral step-down therapy, optimal durations, and the role of rapid diagnostics in resource-limited settings.

STOPTHEBURN: A Randomized Controlled Trial of Death Cafés for Burnout Prevention in Intensive Care Unit Employees.

Rationale: Effective interventions to prevent burnout among intensive care unit (ICU) clinicians are urgently needed. Death cafés, group discussions about death, build a sense of community and create a space for reflection on distressing events. Objective: To assess whether participation in regular death cafés can prevent burnout in ICU clinicians (physicians, nurses, pharmacists, therapists). Methods: A randomized clinical trial was conducted from July 2020 to December 2022 in 10 ICUs in Louisiana. Subjects were randomized to attend four psychotherapist-facilitated virtual death cafés or to a control arm. The primary outcome was burnout defined by the Maslach Burnout Inventory-Human Services Survey at 6 months. Depression and anxiety scores were measured, as were qualitative data on stressors, coping, and death café experience. Results: Among 340 clinicians who were screened and gave consent (171 physicians, 169 nonphysicians), 251 participated (mean age, 31.0 ± 6.8 years; 63% female; 72% White; 37% nurses, 27% residents, 25% interns, 11% other). Burnout prevalence was 19% at baseline. Of 136 participants who completed the 6-month follow-up, no significant differences were found between intervention and control for the primary outcome (18% vs. 25%; unadjusted odds ratio, 0.64; 95% confidence interval, 0.26-1.57; P = 0.33). There were no differences in anxiety or depression. Notably, the study was limited by an inability to achieve target enrollment and a high attrition rate (46%). Conclusions: Virtual death cafés were unable to reduce burnout, although the study was underpowered to detect differences between groups. Clinical trial registered with clinicaltrials.gov (NCT04347811).

The comparison of efficacy of Escitalopram and Bupropion in treatment of depression symptoms in patients with heart failure: randomized clinical trial.

This study aims to compare the effects of two medicines, Escitalopram and Bupropion, on HF patients who have depression symptoms. This double-blind randomized clinical trial study was conducted on HF patients with depression symptoms at the Heart Failure Clinics affiliated with Babol University of Medical Sciences. In this study, 80 participants were examined for depression based on the Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HDRS). They were randomly allocated into two groups of 40 participants treated with Bupropion 75mg and Escitalopram 5mg. Following the intervention, the individuals were assessed in terms of their depression score at 4, 8, and 12-week intervals. Finally, the data were analyzed using SPSS version 22.0. In the examination of Beck and Hamilton scores in the two research groups during different follow-ups, a significant decrease was found over time (P<0.001 for both medicines). While the effectiveness of the two medicines was the same at different times (P>0.05 in all cases). Comparing the side effects between the two intervention groups, the orgasm disorder (P=0.018) and sexual dysfunction (P<0.001) were reported significantly more in the Escitalopram group than in the Bupropion group. The findings of this study showed that Escitalopram has the same efficacy as Bupropion in the treatment of depression symptoms in HF patients.

Toe-in and toe-out gait retraining interventions for individuals with knee osteoarthritis trial: A pilot randomised clinical trial

BackgroundGait retraining, through altering foot progression angle, has the potential to reduce pain and offload the medial tibiofemoral compartment in people with knee osteoarthritis. This pilot study aimed to evaluate the feasibility of toe-in and toe-out gait retraining on self-reported pain and physical function, and proxy measures of medial knee load, in individuals with medial knee osteoarthritis. MethodsTwenty participants with symptomatic medial knee osteoarthritis were randomly allocated to receive either toe-in or toe-out gait retraining for six-weeks, consisting of weekly clinician-supervised sessions and ≥ 30 min of daily self-practice. Feedback was guided by wearable sensors and a pressure-sensitive mat. Primary outcomes included recruitment rate, data completeness, adverse events, adherence, achievability, and intervention acceptability. Secondary outcomes were proxy measures of medial knee load, self-reported pain and physical function. Differences in feasibility and self-reported outcomes were interpreted via sample t-test using intention-to-treat analysis. The effect of the intervention group on knee biomechanics was evaluated using linear mixed modelling. FindingsRecruitment was acceptable (n = 4/month) with excellent data completeness (93 %) and attendance (82 %). Acceptability was moderate and similar between groups. There were no differences in average knee pain and physical function between groups over time, and both groups reduced maximum knee pain following the intervention (35 % improvement, p = 0.012). There were no differences in biomechanical outcomes between groups over time. InterpretationToe-in and toe-out gait retraining is feasible and improves pain in people with knee osteoarthritis. A full-scale randomised clinical trial is warranted and should consider individualising the intervention.

Peripapillary ovoid mass-like structure (PHOMS): prevalence, risk factors, and development over time in Danish myopic children

BackgroundOn optical coherence tomography (OCT) scans of the optic nerve head, peripapillary hyperreflective ovoid mass-like structures (PHOMS) are sometimes seen as a sign of axonal distension. The phenomenon has been reported more frequently in myopic subjects. We investigated PHOMS-prevalence in a myopic pediatric cohort, associated risk factors, and PHOMS development over 18 months during low-dose atropine treatment. MethodsIn this post hoc analysis of an investigator-initiated, placebo-controlled, randomized clinical trial, 97 6- to 12-year-old myopic participants were randomized to 0.1% atropine for 6 months, then 0.01% for 18 months (N = 33), 0.01% for 24 months (N = 32) or placebo for 24 months (N = 32). Primary outcome was presence of PHOMS. Secondary outcome was mean nasal PHOMS diameter measured on OCT B-scan. Outcomes were reported at baseline, 6, and 18 months. Logistic regression and linear mixed modelling were performed. ResultsPHOMS were present in 26% of participants (n = 25), and 52% (n = 13) had bilateral presentation. Optic disk tilt (OR = 10.81; 95% CI, 3.58-32.58 [P < 0.001]) and longer axial length (AL) (OR = 2.06; 95% CI, 1.02-4.17 [P = 0.04]) increased the risk of having PHOMS. Greater increase in nasal peripapillary choroidal thickness over time was associated with smaller PHOMS diameter at 18 months (P = 0.05). ConclusionsPHOMS were common in our cohort of children with myopia. Longer AL increases the risk of, but not size of, PHOMS. The diameter of PHOMS seemed stable over time and unaffected by low-dose atropine.

Effectiveness of Virtual Yoga for Chronic Low Back Pain

Chronic low back pain (CLBP) is a common condition with substantial impact on patients, in the form of physical and emotional suffering; health care costs; productivity; and health care professional burden. Although clinical guidelines recommend use of nonpharmacologic treatments first, such as yoga, there is a gap between guidelines and implementation in clinical practice. To compare the effects of virtual yoga classes vs a wait-list control on CLBP intensity, back-related function, sleep quality, and pain medication use. Single-blinded, 24-week, 2-arm, randomized clinical trial conducted from May 3, 2022, through May 23, 2023, comparing live streamed yoga classes (the yoga now group) with a wait-list control (the yoga later group, in which participants were offered the virtual intervention after the study but without assessments) among adults with CLBP. Adults 18 to 64 years of age with CLBP were recruited from the Cleveland Clinic Employee Health Plan, a large health system self-insured health plan. Inclusion criteria included a mean LBP intensity score of at least 4 on an 11-point numerical rating scale (scores ranged from 0 to 10, with higher scores indicating worse pain) and daily back pain interference about half or more of the days. Twelve consecutive weekly, 60-minute, virtual, live streamed hatha yoga group classes. Coprimary outcomes were mean pain intensity in the previous week on the 11-point numerical rating scale and back-related function as assessed using the 23-point modified Roland Morris Disability Questionnaire ([RMDQ], with higher scores reflecting poorer function) at 12 weeks. Secondary and exploratory outcomes included these measures at 24 weeks, pain medication use, and PROMIS sleep quality assessed using the Sleep Disturbance Short Form 8a, item 1 (scores ranged from 0 to 4, with higher scores reflecting better sleep quality). Analyses followed the intention-to-treat principle. Among 140 participants enrolled (yoga now = 71; yoga later = 69), the mean (SD) age was 47.8 (11.7) years and most were female (113 [80.7%]) and college-educated (103 [73.5%]). Mean (SD) baseline pain intensity (5.7 [1.5]) and RMDQ ([12.1 [4.4]) scores reflected moderate back pain and impairment. At week 12, yoga now compared with yoga later had greater reductions in mean pain intensity (-1.5 [95% CI, -2.2 to -0.7] points; P < .001) and mean RMDQ (-2.8 [95% CI, -4.3 to -1.3] points; P < .001) scores. At 24 weeks, the improvements in pain (mean change, -2.3 [95% CI, -3.1 to -1.6] points; P < .001) and RMDQ (mean change, -4.6 [95% CI, -6.1 to -3.1] points; P < .001) scores were sustained. At 12 weeks, yoga now participants reported 21.4 (95% CI, 5.2-37.6) absolute percentage points less use of any analgesic medication during the past week than yoga later participants and at 24 weeks, 21.2 absolute percentage points (95% CI, 5.2%-37.3%). Improvements in sleep quality were greater for participants in yoga now than among participants in yoga later at 12 weeks (mean change, 0.4 [95% CI, 0.1-0.7] points; P = .008) and 24 weeks (mean change, 0.4 [95% CI, 0.1-0.7] points; P = .005). Results of this randomized clinical trial of 140 adults with CLBP who were members of a large health system self-insured health plan suggest that virtual yoga classes may be a feasible, safe, and effective treatment option. ClinicalTrials.gov Identifier: NCT05319691.

Effect of electroacupuncture on internal carotid artery blood flow in patients undergoing laparoscopic gallbladder surgery:A randomized clinical trial

BackgroundLittle is known about the effect of electroacupuncture (EA) on cerebral blood flow. We investigated this question in patients undergoing laparoscopic cholecystectomy, hypothesizing that EA would increase cerebral blood flow during surgery. MethodsEighty-two patients undergoing laparoscopic cholecystectomy were randomly divided into receiving electroacupuncture and intravenous anesthesia (EA+IA) and receving intravenous anesthesia alone (IA). The patients in EA+IA were treated with EA at Baihui (GV 20), Shuigou (GV 26), unilateral Neiguan (PC 6) and unilateral Zusanli (ST 36) points 20 min before anesthesia until the end of the operation. The patients in IA received intravenous anesthesia alone. The internal carotid artery blood flow (Q), mean arterial pressure (MAP), end-tidal carbon dioxide pressure (PETCO2) and heart rate (HR) were recorded respectively before anesthesia induction (T1), 2 min after anesthesia induction (T2), 1 min after pneumoperitoneum (T3), 1 min after head-up tilt (T4) and after anesthesia resuscitation (T5). ResultsThe internal carotid artery blood flow was significantly higher in EA+IA (mean [SD], T3, 294.0 [89.6] ml/min; T4, 303.8 [90.6] ml/min) than in IA (mean [SD], T3, 246.4 [80.9] ml/min; T4, 253.5 [78.4] ml/min) at T3 and T4 (P < 0.05). There was no difference in blood flow between the two groups at T2 and T5. As compared with baseline (T1), the internal carotid artery blood flow decreased at T2-T4 in two groups (P < 0.05). There were no differences in MAP, PETCO2, and HR between the two groups. ConclusionElectroacupuncture intervention could reduce the decline of internal carotid artery blood flow in patients undergoing laparoscopic cholecystectomy. ChiCTR: 2100041761.

The Mobile lifestyle intervention for food and exercise (mLife) study: Protocol of a remote behavioral weight loss randomized clinical trial for type 2 diabetes prevention

BackgroundEmerging research has examined electronic and mobile health (e/mHealth) technologies for weight loss and manage of type 2 diabetes mellitus (T2DM), but few studies have focused specifically on ways to target social support behaviors that have proven to be effective. While gamifying an mHealth behavioral weight loss intervention holds promise to promote and sustain social support, there has been very little research in this area. The mobile Lifestyle Intervention for Food and Exercise study (mLife) was designed to test if receiving points for social support is an effective way to promote sustained weight loss. ObjectiveTo describe the design of the 12-month mLife study, a randomized clinical trial, which compares the differential long-term effect of a behavioral weight loss program with and without gamification among adults with overweight or obesity. MethodsParticipants (target N = 240) in two consecutive cohorts were randomized to either the mLife+points or mLife group. The weight loss intervention for both groups included diet and physical activity (PA) recommendations, education, daily diet logging, visualization of PA and body weight readings captured with a wearable tracker and e-scale, and facilitation of social interaction among participants. The mLife+points group earned points for social support activities. Remote follow-up assessments of weight, anthropometric measures, diet (24 h dietary recalls), PA, social support provision, receipt and enjoyment, factors driving self-monitoring adherence and study compliance/responsiveness occurred at 6 and 12-months post-baseline. ConclusionThe mLife study informs the expansion of gamification within mHealth programs to enhance social support provision and receipt during weight loss. Trial registrationThis study was registered on clintrials.gov on the 30th of October 2017, under the trial registration number: NCT05176847.

Pulmonary Atelectasis After Sedation With Propofol vs Propofol-Ketamine for Magnetic Resonance Imaging in Children

Little is known about the impact of different anesthetic agents used for routine magnetic resonance imaging (MRI) sedation on pulmonary function in children. To compare the incidence of pulmonary atelectasis after MRI sedation with propofol vs propofol-ketamine. This double-masked randomized clinical trial screened 117 consecutive pediatric patients aged 3 to 12 years with American Society of Anesthesiologists physical status I to II undergoing elective MRI under deep sedation from November 2, 2022, to April 28, 2023, at a tertiary referral center. Four patients met the exclusion criteria, and 5 patients refused to participate. The participants and outcome assessors were masked to the group allocation. During the MRI, the propofol group received 0.2 mL/kg of 1% propofol and 2 mL of 0.9% saline followed by a continuous infusion of propofol (200 μg/kg/min) and 0.9% saline (0.04 mL/kg/min). The propofol-ketamine group received 0.2 mL/kg of 0.5% propofol and 1 mg/kg of ketamine followed by a continuous infusion of propofol (100 μg/kg/min) and ketamine (20 μg/kg/min). The incidence of atelectasis assessed by lung ultrasonography examination. A total of 107 children (median [IQR] age, 5 [4-6] years; 62 male [57.9%]), with 54 in the propofol group and 53 in the propofol-ketamine group, were analyzed in this study. Notably, 48 (88.9%) and 31 (58.5%) patients had atelectasis in the propofol and propofol-ketamine groups, respectively (relative risk, 0.7; 95% CI, 0.5-0.8; P < .001). The incidence of desaturation and interruption of the MRI due to airway intervention or spontaneous movement did not significantly differ between the groups. The propofol-ketamine group showed a faster emergence time than the propofol group (15 [9-23] vs 25 [22-27] minutes in the propofol-ketamine vs propofol group; median difference in time, 9.0 minutes; 95% CI, 6.0-12.0 minutes; P < .001). No patient was withdrawn from the trial due to adverse effects. In this randomized clinical trial, the propofol-ketamine combination reduced sedation-induced atelectasis while allowing for faster emergence compared with propofol alone. cris.nih.go.kr Identifier: KCT0007699.

Impact of Rosa damascena extract capsule on the sexual function of menopausal women: a randomized clinical trial

Impact of Rosa damascena extract capsule on the sexual function of menopausal women: a randomized clinical trial

Assessment of coated orthodontic miniscrews with chlorhexidine hexametaphosphate antimicrobial nanoparticles: A randomized clinical trial

Assessment of coated orthodontic miniscrews with chlorhexidine hexametaphosphate antimicrobial nanoparticles: A randomized clinical trial

Comparison of two treatment modalities in the management of gingival enlargement during orthodontic treatment: a randomized clinical trial.

This clinical trial aimed to evaluate and compare the effectiveness of diode laser gingivectomy, conventional gingivectomy, and nonsurgical periodontal treatment (NSPT) in the management of gingival enlargement (GE) during orthodontic treatment. forty-five healthy, orthodontic patients with labial gingival enlargement on the 6 anterior teeth were selected and randomly assigned to one of the groups (Conventional, Laser, and NSPT). Clinical parameters including clinical crown length (CCL) , periodontal pocket depth (PPD), and vertical gingival overgrowth index (vGOi) were recorded at baseline, 1 month, 3 months, and 6 months. Postoperative pain was evaluated at 1,3, and 7 days. Esthetic satisfaction and acceptance of the procedure were recorded on day 10 and repeated after 6 months. Statistically significant results were obtained for mean reduction in PPD for conventional, laser, and NSPT groups (-1.43, -.1.75, and -0.9 mm, respectively; P < 0.001), CCL gain (1.45, 1.7, and 0.38 mm, respectively; P<0.001) and mean vGOi score (-1.14, -1.29 and -0.76, respectively; P<0.001) over 6 months. Both test groups showed greater statistically significant changes in clinical parameters over 6 months compared to NSPT (P<0.001). There was a gradual decrease in postoperative pain for all three groups over 7 days, with conventional group showing statistical difference in mean pain score on days 1 and 3 compared to other groups. Both conventional and laser gingivectomies were more effective in controlling enlargement over non-surgical periodontal treatment alone at 1, 3, and 6 months. laser and conventional gingivectomies as adjunctive treatments achieved superior results when compared to NSPT alone in the treatment of GE and gingival inflammation during orthodontic treatment, with no significant clinical differences between the two treatments.

Exogenous insulin does not reduce protein catabolism in pre-diabetic cystic fibrosis patients: A randomized clinical trial

BackgroundCystic Fibrosis (CF) patients historically suffered from undernutrition, infection and inflammation. Insulin insufficiency-related protein catabolism further compromised health. We aimed to determine whether insulin improves protein catabolism in CF youth with abnormal glucose tolerance (AGT). MethodsThis double-masked, placebo-controlled trial in CF youth age 10–25 with AGT who were in their usual state of health used triple-tracer stable-isotope methodology to measure protein turnover during a baseline test meal and after four weeks of insulin/placebo treatment. Healthy controls were assessed once. CF patients were randomized 1:1:1 to once-daily long-acting insulin (0.25 U/kg/d), three-times daily rapid-acting insulin (0.5 U/15gr carbohydrate), or injectable placebo. ResultsThirty CF patients completed the study. There were no differences in any measure of protein turnover between insulin- and placebo-treated subjects, including endogenous protein breakdown (primary study endpoint). In contrast to earlier studies, protein turnover in the 37 CF patients who completed the baseline meal was normal compared to 20 healthy controls. Meal isotope appeared in plasma earlier in CF than controls, suggesting more rapid gut emptying. The study was interrupted by the pandemic; futility analysis led to study discontinuation before the planned remaining 15 CF patients were studied. ConclusionsRecent advances in CF have led to remarkable clinical improvements. In this study, CF youth with AGT had normal protein catabolism at baseline. Pre-meal or daily basal insulin therapy, while safe and well tolerated, did not significantly enhance protein turnover and does not appear to be necessary in clinically stable patients prior to development of CFRD.

EFFECTS OF TRANSCRANIAL DIRECT CURRENT STIMULATION (tDCS) ASSOCIATED WITH BALANCE TRAINING IN INDIVIDUALS WITH PARKINSON'S: STUDY PROTOCOL FOR A RANDOMIZED CLINICAL TRIAL

The present study aimed to investigate the effects of balance training associated with cerebellar tDCS on postural control in individuals with PD. This is a randomized clinical trial in which individuals were allocated to an experimental group (EG) or placebo group (PG), in which a conventional protocol of 10 Physiotherapy sessions for locomotor training and postural control was applied. In the EG, tDCS was applied, with a current setting of 1.5 mA for 20 minutes simultaneously with postural control training. In the PG, tDCS was applied in sham mode, with the same electrode positioning and the same number of sessions as the EG. The sample compared 34 individuals with PD (EG: 17; PG: 17).Cerebellar tDCS associated with balance training may help improve postural control and balance in walkers with Parkinson's Disease. The hypothesis is, if walking improve, the benefits may be accompanied by better balance and reduced fear of falling, and individuals may experience greater free-living physical activity at home and in the community.

Influence of the Olfatín Project on the reduction of pain related to intranasal influenza vaccination, as part of a school influenza vaccination program

PurposeTo evaluate the influence of viewing the Olfatín Project video on the assessment of school LAIV-associated pain in three and four-year-old children through the Wong Baker Faces® pain classification scale. Design and methodsA three-arm randomized multicenter clinical trial with a placebo control group was carried out. The main variable measured was pain, assessed through the score on the Wong Baker Faces® Pain Rating Scale. There were a total population of 4591 children three and four-year-olds (born in 2019 and 2020) and who attended the 1st and 2nd year of early childhood education. Before the school vaccination, researchers randomly assigned participant schools corresponding to each of the basic health areas to each of the three study groups: Olfatín's video viewing, a control video viewing not related to influenza and no video viewing. ResultsNo significant differences according to sex, age or the minor's grade according to the assigned intervention were detected. 72.3% of those vaccinated assigned a 0 from the Wong Baker Faces® scale: 75.4% of those who watched Olfatín's video, 68.3% for those in Drilo's group and 72.8% for those who didn't watch any video, but without significant differences (p = 0.08). There were no significant differences either stratifying by sex. ConclusionLAIV is a painless vaccine for children, which has to be taken into account by the health authorities when planning the pediatric influenza vaccination campaign. Practice implicationsOlfatín's cartoon video can be used by professionals to create a greater experience for children and therefore a better acceptance.

A Randomized Controlled Trial of Gamification to Increase Physical Activity Among Black and Hispanic Breast and Prostate Cancer Survivors: Rationale and Design of the ALLSTAR Clinical Trial

Survivors of breast and prostate cancer, especially those that are Black and/or Hispanic, are at high risk for cardiovascular events. Physical activity can reduce the risk of cardiovascular events in cancer survivors, but Black and Hispanic people are less likely to engage in routine physical activity. Concepts from behavioral economics have been used to design scalable, low-touch, gamification interventions that increase physical activity in individuals at high risk for cardiovascular events, but the effectiveness of these strategies in Black and Hispanic survivors of breast and prostate cancer is uncertain. ALLSTAR (NCT05176756) is a pragmatic, virtual, randomized controlled trial designed to evaluate the effectiveness of a gamification intervention informed by behavioral economic concepts to increase daily physical activity in Black and Hispanic breast and prostate cancer survivors who received cardiotoxic therapies and have additional risk factors for cardiovascular disease. Patients were either referred by their cancer care team or identified by electronic health record searches; contacted by letter, email, text message and/or phone; and complete enrollment and informed consent on the Penn Way to Health online platform. Patients are then provided with a wearable fitness tracker, establish a baseline daily step count, set a goal to increase daily step count by 1500-3000 steps from baseline, and are randomized 1:1 to control or gamification. Interventions continue for 6 months, with follow-up for an additional 3 months to evaluate the durability of behavior change. The trial has met its enrollment goal of 150 participants, with a primary endpoint of change from baseline in daily steps over the 6-month intervention period. Key secondary endpoints include change from baseline in daily steps over the 3-month post-intervention follow-up period, change in moderate to vigorous physical activity over the intervention and follow-up periods, and change in patient-reported measures of physical function, fatigue, and overall quality of life. ALLSTAR is a virtual, pragmatic randomized clinical trial powered to demonstrate whether gamification is superior to control in increasing physical activity in Black and Hispanic breast and prostate cancer survivors. Its results will have important implications for strategies to promote physical activity in survivors of breast and prostate cancer, specifically among minority populations. clinicaltrials.gov; https://clinicaltrials.gov/study/NCT05176756.

TREATMENT OF EARLY-ONSET FETAL GROWTH RESTRICTION WITH LOW MOLECULAR WEIGHT HEPARIN DOES NOT PROLONG GESTATION: A RANDOMIZED CLINICAL TRIAL

Although there is a biological basis for it, there is scarce evidence on the effect of heparin in ameliorating placental insufficiency and maximizing gestational age at delivery among fetal growth restriction (FGR) pregnancies. To explore the effectiveness of treatment using low molecular weight heparin (LMWH) at a prophylactic dose started at the time of diagnosis in prolonging gestation in pregnancies with early-onset fetal growth restriction (FGR). This was a phase III, multicenter, triple-blind, parallel-arm randomized clinical trial conducted in two university hospitals in Spain. Singleton pregnancies qualifying for early-onset placental FGR according to the adapted Delphi consensus (20+0-31+6 weeks at diagnosis with umbilical artery Doppler with absent/reversed diastolic flow; or estimated fetal weight <10th percentile plus pulsatility index (PI) of umbilical artery Doppler >95th percentile; or estimated fetal weight <10th percentile plus mean PI of uterine artery Doppler >95th) were randomized to receive either subcutaneous treatment with bemiparin 3500 IU/0.2 mL/day or a placebo from inclusion at diagnosis to the time of delivery. The primary outcomes were prolongation of pregnancy from inclusion to live birth (days) and gestational age at live birth (days). 49 patients were included (23 in the LMWH group and 26 in the placebo group). In the LMWH group, the median prolongation of pregnancy was 42 days, while in the placebo group it was 41.5 days (median difference 0.5 days [95% CI -22.7 to 6.3] (p=0.667) and in the LMWH group, the median gestational age at delivery was 35.1 weeks, while in the placebo group, it was 34.6 weeks (median difference 0.5 weeks [95% CI -3.4 to 1.2] (p=0.639). The use of prophylactic dose LMWH started at the time of diagnosis does not prolong pregnancy in individuals with early-onset fetal restriction.

Anemia Acuity Effect on Transfusion Strategies in Acute Myocardial Infarction

In patients with acute myocardial infarction (MI), limited physiologic adaptation to acute anemia might lead to greater benefit from a liberal red blood cell (RBC) transfusion strategy. Data on such a possible benefit are lacking. To compare acute anemia with chronic anemia and post-MI outcomes and estimate the differential effect of a restrictive RBC transfusion strategy compared with a liberal strategy on post-MI outcomes according to anemia acuity. A prespecified subgroup analysis of the Myocardial Ischemia and Transfusion (MINT) multicenter randomized clinical trial was conducted in 126 hospitals in 6 countries between April 26, 2017, and April 14, 2023, with 30-day follow-up and blinded adjudication of the primary outcome. The analysis included 3144 of 3504 MINT participants (89.7%) with acute MI, a hemoglobin (Hb) level less than 10 g/dL at randomization, and a first Hb measurement available on the day of or the day following hospital admission. The MINT trial randomized participants to a restrictive (Hb <7-8 g/dL) or liberal (Hb <10 g/dL) RBC transfusion strategy. Acute anemia was defined as having a first Hb value greater than 13 g/dL (men) or 12 g/dL (women), or as having a decrease greater than or equal to 2 g/dL between the first Hb measurement and measurement at randomization. Other Hb levels were categorized as chronic anemia. The primary outcome was a composite of death or recurrent MI up to 30 days after randomization. Secondary outcomes were death, recurrent MI, cardiac death, heart failure, pulmonary complications, and major bleeding events. Intention-to-treat analysis was performed. Among 3144 included participants (mean [SD] age, 72.3 [11.6] years; 1715 [54.5%] male; 1307 [41.6%] with type 1 MI), 1078 [34.3%]) had acute anemia. Acute anemia was associated with an increased risk of death or recurrent MI (adjusted risk ratio, 1.25; 95% CI, 1.05-1.48). The effect of a restrictive RBC transfusion strategy compared with a liberal strategy was similar for participants with either acute or chronic anemia for all outcomes. In this secondary analysis of the MINT trial, acute anemia was associated with less favorable post-MI outcomes than chronic anemia but did not modify the effects of the randomized transfusion strategy. In patients with anemia and MI, the acuity of anemia should not influence the choice of transfusion trigger. ClinicalTrials.gov Identifier: NCT02981407.