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Non‐pharmacological interventions include physical activity, biofield energy therapy, reiki, Tai chi, and therapeutic touch. However, no reports analyzed the effectiveness of biofield therapy on cognition and motor function performance in adult subjects. The study aimed to investigate the impact of remote biofield energy healing therapy on cognition and motor functioning in adults with self‐perceived neuropsychological impairments. This was a randomized double‐blind clinical trial that involved 114 participants with self‐perceived neuropsychological impairments. The participants were divided into three groups (control, sham control, and biofield intervention). Cognitive and motor function scores were assessed using the NIH Toolbox at baseline (day 0), day 90, and day 180. The biofield treatment group showed significant improvements in language function (p < 0.0001), working memory (p < 0.0001), and episodic memory (p < 0.0001) scores. Other cognitive functions also improved, although not statistically significant. The biofield intervention group also demonstrated significant enhancements (p < 0.05 to p < 0.0001) in locomotion, standing balance, dexterity, grip strength, and muscle endurance. No adverse effects were reported. The results suggest that remote biofield energy therapy is a safe, noninvasive intervention that improves cognitive and motor functions in adults. Further research is needed to understand its clinical benefits. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion To evaluate the efficacy of guided bone regeneration (GBR) for the treatment of peri‐implant dehiscence defects using a synthetic bone substitute (SBS) or a deproteinized bovine bone mineral (DBBM) as a bone substitute.Patients with expected dehiscence defects following implant placement were randomized to use either SBS or DBBM together with a bioabsorbable collagen membrane over dehiscenced implant surfaces aimed for GBR. The changes in the bone defect size were measured before the GBR procedure and 6 months after implant placement at the re‐entry surgery. Secondary outcomes included peri‐implant health outcomes, implant cumulative survival rates, bone level changes, and patient‐reported outcomes (PROMs) at prosthesis delivery and 1‐year follow‐up.Of the 49 included patients, 24 were treated with SBS and 25 with DBBM. In the SBS group, the defect height (DH) at implant insertion was 5.1 ± 2.6 mm and was reduced at re‐entry to 1.3 ± 2.0 mm (74.5%). In the DBBM group, the respective changes in DH were 4.1 ± 1.7 mm and 1.5 ± 1.9 mm (63.4%). These differences were not statistically significant (p = 0.216). The complete defect resolution rate was also comparable in both groups without statistical difference (62.5% of patients (15/24) vs. 44% of patients (11/25)). Overall, the marginal bone levels remained stable during the 1‐year follow‐up in both groups.The SBS is noninferior to DBBM for simultaneous GBR to implant placement at implant sites with buccal dehiscences in terms of defect resolution and evaluated secondary outcomes (KCT0008393 − this clinical trial was not registered before participant recruitment and randomization). [ABSTRACT FROM AUTHOR]

Aim: Post‐operative pain may occur after non‐surgical root canal treatment (NSRCT). The root filling technique and choice of sealer may be contributing factors. This randomized controlled clinical trial compared post‐operative pain and analgesics intake after NSRCT using a sealer‐based obturation technique (SBO) with single‐cone gutta‐percha and calcium silicate sealer (CSS) versus a warm‐vertical compaction (WVC) technique with gutta‐percha and a resin‐based sealer (RBS). Methodology: This study was designed as a parallel‐two arm, double‐blind, randomized superiority clinical trial registered at www.clinicaltrials.gov (NCT04753138). Patients referred for NSRCT fulfilling the inclusion criteria participated in this study. Pre‐operative periapical radiographs and CBCT scans were taken and numerical rating scale (NRS) pain scores were recorded. Upon completion of canal instrumentation, participants were randomly allocated to either Group SBO: SBO with CSS or Group WVC: Warm‐vertical compaction with RBS. Post‐operative pain and analgesics intake were recorded at 1, 3 and 7 days after endodontic treatment completion. Non‐parametric Mann–Whitney U and Friedman tests and a generalized estimating equation were used to assess differences in pain scores between the groups, within each treatment group at different time points and for correlations, respectively. Results: The study included 195 participants (212 teeth). One participant declined to submit the NRS form. Therefore, 194 participants (211 teeth) were included in the final analysis (99.5% response rate). No statistically significant differences in post‐operative pain or analgesic intake existed between the two groups at any time point (p >.05). Age, pre‐operative pain, apical diagnosis and post‐operative analgesic intake were significantly related to post‐operative pain (p <.05). Conclusions: Sealer‐based obturation technique with CSS was associated with similar post‐operative pain levels and analgesics intake as WVC with RBS. Regarding post‐operative pain, SBO with CSSs may be a suitable clinical alternative. [ABSTRACT FROM AUTHOR]

Background: Post‐publication handling of integrity concerns in randomized clinical trials (RCTs) is a contentious matter. Objectives: We undertook a scoping systematic review to map the literature regarding post‐publication integrity issues in RCTs. Search Strategy and Selection Criteria: Following prospective registration (https://osf.io/pgxd8) we initially searched PubMed and Scopus but subsequently extended it to include the Cochrane Library, and Google Scholar databases without language, article type or publication time restriction until November 2022. Reviewers independently selected published articles covering any aspect of post‐publication research integrity concerns in RCTs. Data Collection and Analysis: The study findings grouped within domains relating to issues concerning post‐publication integrity were extracted in duplicate, verified by a third reviewer, and then tabulated. Main Results: The initial search captured 3159 citations, of which 89 studies were included in the review. Cross‐sectional studies constituted the majority of included studies (n = 34, 38.2%), followed by systematic reviews (n = 10, 11.2%), methodology reviews/studies (n = 9, 10.1%) and other types of descriptive studies (n = 8, 9.0%). A total of 21 articles (23.6%) covered the domain on general issues, 25 (28.1%) in the journal's instructions and policies domain, eight (9.0%) in the editorial and peer review domain, one (1.1%) in the correspondence and complaints (post‐publication peer review) domain, 12 (13.5%) in the investigation for concerns domain, six (6.7%) in the post‐investigation decisions and sanctions domain, none in the critical appraisal guidance domain, five (5.6%) in the integrity assessment in systematic reviews domain, and 26 (29.2%) in the recommendations for future research domain. A total of 12 of the selected articles (13.5%) covered two (n = 9) or three (n = 3) different domains. Conclusions: Various research integrity domains and issues covering post‐publication aspects of RCT integrity were captured and gaps were identified, mostly related with the necessary implications for all stakeholders to improve research transparency. There is an urgent need for a multistakeholder consensus towards creating specific statements for addressing post‐publication integrity concerns in RCTs. Synopsis: Existing literature concerning post‐publication integrity issues in randomized clinical trials needs consolidation. [ABSTRACT FROM AUTHOR]

Aims Methods Conclusions Digoxin is the oldest drug in cardiovascular (CV) medicine, and one trial conducted >25 years ago showed a reduction in heart failure (HF) hospitalizations but no effect on mortality. However, later studies suggested that the dose of digoxin used in that trial (and other studies) may have been too high. The DECISION (Digoxin Evaluation in Chronic heart failure: Investigational Study In Outpatients in the Netherlands) trial will examine the efficacy and safety of low‐dose digoxin in HF patients with reduced or mildly reduced left ventricular ejection fraction (LVEF) with a background of contemporary HF treatment.The DECISION trial is a randomized, double‐blind, parallel‐group, placebo‐controlled event‐driven outcome trial which will investigate the efficacy and safety of low‐dose digoxin in patients with chronic HF and LVEF <50%. Both patients with sinus rhythm and atrial fibrillation will be enrolled and will be randomized (1:1) to low‐dose digoxin or matching placebo. To maintain a target serum digoxin concentration of 0.5–0.9 ng/ml, dose adjustments are made throughout follow‐up based on serum digoxin measurements with dummy values for the placebo group. The primary endpoint is a composite of CV mortality and total HF hospitalizations or total urgent hospital visits for worsening HF, and all endpoints are adjudicated blindly by a Clinical Event Committee. The estimated sample size was 982 patients who will be followed for a median of 3 years, and in December 2023 enrolment was completed after 1002 patients.The DECISION trial will provide important evidence regarding the effect of (low‐dose) digoxin on CV mortality and total HF hospitalizations and urgent hospital visits when added to contemporary HF treatment of patients with reduced or mildly reduced LVEF.Clinical Trial Registration: ClinicalTrials.gov identifier: NCT03783429. [ABSTRACT FROM AUTHOR]

Aims Methods Conclusions There is a lack of therapies able to prevent anthracycline cardiotoxicity (AC). Remote ischaemic conditioning (RIC) has shown beneficial effects in preclinical models of AC.REmote iSchemic condItioning in Lymphoma PatIents REceiving ANthraCyclinEs (RESILIENCE) is a multinational, prospective, phase II, double‐blind, sham‐controlled, randomized clinical trial that evaluates the efficacy and safety of RIC in lymphoma patients receiving anthracyclines. Patients scheduled to undergo ≥5 chemotherapy cycles including anthracyclines and with ≥1 AC‐associated risk factors will be randomized to weekly RIC or sham throughout the chemotherapy period. Patients will undergo three multiparametric cardiac magnetic resonance (CMR) studies, at baseline, after the third cycle (intermediate CMR), and 2 months after the end of chemotherapy. Thereafter, patients will be followed up for clinical events over an anticipated median of ≥24 months. The primary endpoint is the absolute change from baseline in CMR‐based left ventricular ejection fraction (LVEF). The main secondary outcome is the incidence of AC events, defined as (1) a drop in CMR‐based LVEF of ≥10 absolute points, or (2) a drop in CMR‐based LVEF of ≥5 and <10 absolute points to a value <50%. Intermediate CMR will test the ability of T2 mapping to predict AC versus classical markers (left ventricular strain and cardiac injury biomarkers). A novel CMR sequence allowing ultrafast cine acquisition will be validated in this vulnerable population.The RESILIENCE trial will test RIC (a novel non‐invasive intervention to prevent AC) in a cohort of high‐risk patients. The trial will also test candidate markers for their capacity to predict AC and will validate a novel CMR sequence reducing acquisition time in a vulnerable population. [ABSTRACT FROM AUTHOR]

Objectives Materials and Methods Results Conclusions To date, no studies have exploited micro‐CT in humans to evaluate bone morphology and structure after bone augmentation with CAD/CAM‐customized titanium mesh, in mandible and maxilla. The aim of this study was to assess the composition and microstructure of bone biopsy through micro‐CT analysis.Bone augmentation at both maxillary and mandible sites was performed on 30 patients randomly treated with customized mesh, either alone (M−) or covered with resorbable membrane (M+), in both cases filled 50:50 with autogenous bone and xenograft. After 6 months, biopsies were taken and micro‐CT was performed on consecutive 1‐mm‐thick VOIs from coronal to apical side, measuring tissue volumes, trabecular thickness, spacing, and number.In both groups, irrespective of membrane use, bone tissue (M−: 29.76% vs. M+: 30.84%) and residual graft material (M−: 14.87% vs. M+: 13.11%) values were similar. Differences were site‐related (maxillary vs. mandibular) with higher percentage of bone tissue and trabecular density of low‐mineralized bone and overall bone in the mandible.The composition and structure of bone tissue, as assessed by micro‐CT after alveolar ridge augmentation using CAD/CAM‐customized titanium meshes, showed similar features regardless of whether a collagen membrane was applied. [ABSTRACT FROM AUTHOR]

Objectives: This study evaluated the clinical performance of bulk‐fill resin composite systems with different viscosities in class II cavities. Materials and Methods: A total of 80 class II restorations were performed with a single operator in 50 patients using four different bulk‐fill resin composite materials: Filtek™ Bulk Fill, Heated Filtek™ Bulk Fill, G‐ænial™ BULK Injectable, and SonicFill3. A double‐blinded randomized clinical trial was designed to evaluate the two‐year clinical performance of the four bulk‐fill composite resins using modified FDI criteria. Data were analyzed descriptively. Level of significance was set at 0.05. Differences between groups were tested using Wilcoxon‐signed‐rank and Mann–Whitney‐U test as nonparametric tests. Results: Data were analyzed using Kruskal‐Wallis, Mann–Whitney U, and Wilcoxon signed rank tests (p < 0.05). Eighty restorations were available for evaluation, with a survival function of 100%. No statistically significant differences were observed between the four groups regarding assessing esthetic, functional, and biological properties during different follow‐up periods. Conclusions: After 2 years of clinical follow‐up, the bulk‐fill composite systems with different viscosities seem to be esthetically, functionally, and biologically acceptable, with a promising clinical performance in class II cavities. [ABSTRACT FROM AUTHOR]

Objective: Cervical ectropion occurs due to the eversion of the endocervix that exposes glandular cells to the vaginal milieu. The aim of the present study was to evaluate and compare the clinical efficacy of effervescent vaginal tablets of tranexamic acid and cryotherapy in women with symptomatic cervical ectopy. Methods: The current randomized clinical trial was conducted on 92 samples of women with cervical erosive ectropion from March 20, 2022 to August 27, 2022. Participants were divided into two groups; the intervention group (n = 46) was treated with a 400 mg effervescent vaginal tablet of tranexamic acid and the control group (n = 46) underwent cryotherapy. All the patients were requested to visit weekly in the first month and then monthly for the next 3 months, and the outcomes encompass improvement of symptoms (leukorrhea, dyspareunia, pelvic pain, post‐coital bleeding, and suprapubic pain) and cervical erosive ectropion view were monitored based on repeated examinations. Results: In this study, no statistically significant difference was observed in cure rate of symptoms between study groups (P value > 0.05). Women in both the tranexamic acid and cryotherapy groups reported significant improvements in dyspareunia (34 [75%] vs 31 [67%]), pelvic pain (34 [75%] vs 34 [74%]), post‐coital bleeding (37 [81%] vs 31 [67%]), leukorrhea (36 [78%] vs 36 [78%]), suprapubic pain (32 [71%] vs 33 [73%]) disappearance of cervical ectropion tranexamic acid (40 [86%], vs 39 [84%]). Conclusion: Our findings highlighted the equal effect of tranexamic acid and cryotherapy for treating cervical ectropion. Due to the ease of use, availability, and fewer side effects of tranexamic acid, it can be a suitable alternative to cryotherapy. Trial Registration: IRCT20220115053719N1. The name of the registry: Iranian Registry of Clinical Trials. URL of registration: https://en.irct.ir/trial/61483. Synopsis: Tranexamic acid and cryotherapy are effective in cervical ectropion treatment. [ABSTRACT FROM AUTHOR]

Individuals with autism spectrum disorder (ASD) often experience lifelong social communication challenges and are more vulnerable to school bullying. Addressing their social difficulties and school bullying requires evidence‐based interventions. PEERS® (Program for the Education and Enrichment of Relational Skills) was adapted and translated for Taiwanese adolescents. This randomized controlled study aimed to examine the effectiveness of the Taiwanese version of PEERS® in reducing school bullying and enhancing social function among autistic adolescents. Twenty‐one autistic adolescents (mean age 14.29 ± 1.67 years; female n = 733.33%) were randomized to a treatment group (TG, n = 10) or a delayed treatment control group (DTG, n = 11). The outcome measures (school bullying, social challenges, social skills knowledge, and social skills performance) were assessed at baseline, post‐treatment, and follow‐up. The group and time interaction analyses revealed greater magnitudes of reduction in general school bullying (p < 0.001), victimization (p < 0.001), perpetration (p = 0.012), social challenges (p = 0.001), and peer conflicts (p < 0.001), and improvement in social knowledge (p < 0.001) in the TG group than the DTG group. The findings suggest that the PEERS® program tailored for Taiwanese adolescents is effective in reducing school bullying, decreasing social challenges, and enhancing social skills among autistic adolescents, with very large effect sizes (Cohen's d ranging from 1.19 to 2.88). Consequently, participation in the PEERS® program is recommended for adolescents with social difficulties to improve their social communication and interactions to offset school bullying and other social challenges related to adverse outcomes. Lay Summary: This study examined the effectiveness of the PEERS® program, adapted for Taiwanese autistic teenagers. The findings suggest that the program effectively improves social function and reduces the risk of bullying in school for these teens. Teenagers with social difficulties, especially those on the autism spectrum, should be encouraged to participate in the PEERS® program, which provides essential skills and strategies to cope with social difficulties and school bullying. [ABSTRACT FROM AUTHOR]

Mild cognitive impairment poses an increasing challenge to middle‐aged and elderly populations. Traditional Chinese medicinal herbs like Cistanche tubulosa and Ginkgo biloba (CG) have been proposed as potential agents to improve cognitive and memory functions. A randomized controlled trial involving 100 Chinese middle‐aged and elderly participants was conducted to investigate the potential synergistic effects of CG on cognitive function in individuals at risk of neurodegenerative diseases. Over 90 days, both CG group and placebo group received two tablets daily, with each pair of CG tablets containing 72 mg echinacoside and 27 mg flavonol glycosides. Cognitive functions were assessed using multiple scales and blood biomarkers were determined at baseline, Day 45, and Day 90. The CG group exhibited significant improvements in the scores of Mini‐Mental State Examination (26.5 at baseline vs. 27.1 at Day 90, p < 0.001), Montreal Cognitive Assessment (23.4 at baseline vs. 25.3 at Day 90, p < 0.001), and World Health Organization Quality of Life (81.6 at baseline vs. 84.2 at Day 90, p < 0.001), all surpassing scores in placebo group. Notably, both the Cognitrax matrix test and the Wechsler Memory Scale‐Revised demonstrated enhanced memory functions, including long‐term and delayed memory, after CG intervention. Moreover, cognitive‐related blood biomarkers, including total tau, pT181, pS199, pT231, pS396, and thyroid‐stimulating hormone, significantly decreased, whereas triiodothyronine and free triiodothyronine significantly increased. No treatment‐related adverse events were reported, and routine blood and urine tests remained stable. These findings indicated that CG supplementation could potentially serve as an effective supplementary solution for enhancing cognitive and memory functions. [ABSTRACT FROM AUTHOR]

The U.S. Food and Drug Administration (FDA) has launched Project Optimus to shift dose selection from the maximum tolerated dose (MTD) to the dose that produces the optimal risk‐benefit tradeoff. One approach highlighted in the FDA's guidance involves conducting a randomized phase II trial following the completion of a phase I trial, where multiple doses (typically including the MTD and one or two doses lower than the MTD) are compared to identify the optimal dose that maximizes the benefit‐risk tradeoff. This article focuses on the design of such a multiple‐dose randomized trial, specifically the determination of the sample size. We generalized the standard definitions of type I error and power to accommodate the unique characteristics of dose optimization and derived a decision rule along with an algorithm to determine the optimal sample size. The resulting design is referred to as MERIT (Multiple‐dosE RandomIzed Trial design for dose optimization based on toxicity and efficacy). Simulation studies demonstrate that MERIT has desirable operating characteristics, and a sample size between 20 and 40 per dosage arm often offers reasonable power and type I errors to ensure patient safety and benefit. To facilitate the implementation of the MERIT design, we provide software, available at https://www.trialdesign.org. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions We explored whether esketamine anesthesia during hysteroscopic surgery can reduce intraoperative hemodynamic fluctuations and improve patient benefit.A total of 170 patients undergoing hysteroscopic surgery were enrolled, and 151 patients were finally included in the analysis, among which 19 used vasoactive drugs during surgery. Patients were randomly assigned to either the esketamine anesthesia group (E group) or the sufentanil anesthesia group (S group). The primary outcomes were blood pressure and heart rate during the surgery. Secondary outcomes included resistance to laryngeal mask insertion, demand for propofol and remifentanil, nausea and vomiting, Richmond Agitation and Sedation Scale (RASS), dizziness and pain intensity after resuscitation, vasoactive medication treatment, hospitalization time and expenses.E group had a more stable heart rate, systolic blood pressure, diastolic blood pressure and mean blood pressure than the S group (p < 0.001). Patients in E group had a higher demand for propofol (p < 0.001) but better RASS scores (p < 0.001) after resuscitation. The incidence of intraoperative vasoactive medication use was higher in the S group (18.4% vs. 6.7%, p = 0.029). There were no statistically significant differences in terms of resistance to laryngeal mask insertion, remifentanil demand, time required for resuscitation, postoperative pain, dizziness, nausea or vomiting.Compared with sufentanil, esketamine‐induced anesthesia during hysteroscopic surgery can reduce intraoperative hemodynamic fluctuations and the incidence of intraoperative vasoactive medication. Although esketamine‐induced anesthesia may increase the demand for propofol during surgery, it does not affect the anesthesia recovery time and the quality of patient recovery is better. [ABSTRACT FROM AUTHOR]

Objectives: Evaluate the bleaching efficacy (BE) and tooth sensitivity (TS) of in‐office bleaching using different application tips. Methods: Forty‐eight participants were selected (split‐mouth), one to receive bleaching with an attached brush tip and one with a conventional tip. The procedure was performed with Whiteness Automixx Plus 35%. The BE was evaluated at the beginning, weekly, one and 12 months post‐bleaching with a Vita Easyshade spectrophotometer (ΔE*ab, ΔE00, and WID) and with Vita classical A1‐D4 and Vita Bleachedguide shade guides units (ΔSGU). Absolute risk and intensity of TS were recorded using the Visual Analogue Scale. The equivalence of BE was analyzed using the two one‐sided t‐tests for paired samples. The absolute risk of TS was evaluated using the McNemar test, and the TS intensity was measured with the paired t test (α = 0.05). Results: The equivalence of BE was observed for both groups in all color evaluations (p > 0.05). A lower absolute risk and intensity of TS were observed for the attached brush tip when compared with the conventional tip (p < 0.003 and p < 0.0001). Conclusion: Using an attached brush tip showed the same BE as a conventional tip. However, for the attached brush tip, there was a reduction in TS. Clinical Significance: The applicator‐attached brush tip is recommended for in‐office dental bleaching, because of the possible reduction in risk and intensity of TS. [ABSTRACT FROM AUTHOR]

Background: To evaluate the effects of antimicrobial peptides (AMPs) on Stage III Grade B periodontitis. Methods: This trial abided by the principle of consistency test, approved by ethics committee and registered in clinical trials. All qualified 51 patients with Stage III Grade B periodontitis were randomly divided into three groups: SRP group, SRP with minocycline hydrochloride (Mino group) as Control groups, and SRP with AMPs (AMP group) as the Test group. Clinical examinations and subgingival plaques were monitored at baseline and at 7 and 90 days after treatment in the SRP, SRP with AMP and Mino groups. Results: The AMP group (Test group) had a reduced PD (Periodontal probing depth) and an attachment gain significantly higher than SRP and Mino groups (Control groups) at day 90. The abundance of periodontal pathogens was decreased in the AMP group at 7 and 90 days compared with the SRP group and Mino group. Only the AMP group showed an increase the abundance of periodontal probiotics including Capnocytophaga, Gemella, and Lactobacillus at 7 and 90 days. Conclusions: This study shows that AMPs as an adjunct to SRP promote additional clinical and microbiological benefits in the treatment of Stage III Grade B periodontitis. [ABSTRACT FROM AUTHOR]

Aims Methods Conclusions Compared with those without obesity, patients with obesity‐related heart failure with preserved ejection fraction (HFpEF) have worse symptoms, haemodynamics, and outcomes. Current weight loss strategies (diet, drug, and surgical) work through decreased energy intake rather than increased expenditure and cause significant loss of skeletal muscle mass in addition to adipose tissue. This may have adverse implications for patients with HFpEF, who already have reduced skeletal muscle mass and function and high rates of physical frailty. Mitochondrial uncoupling agents may have unique beneficial effects by producing weight loss via increased catabolism rather than reduced caloric intake, thereby causing loss of adipose tissue while sparing skeletal muscle. HU6 is a controlled metabolic accelerator that is metabolized to the mitochondrial uncoupling agent 2,4‐dinotrophenol. HU6 selectively increases carbon oxidation from fat and glucose while also decreasing toxic reactive oxygen species (ROS) production. In addition to sparing skeletal muscle loss, HU6 may have other benefits relevant to obesity‐related HFpEF, including reduced specific tissue depots contributing to HFpEF; improved glucose utilization; and reduction in systemic inflammation via both decreased ROS production from mitochondria and decreased cytokine elaboration from excess, dysfunctional adipose.We describe the rationale and design of HuMAIN‐HFpEF, a Phase 2a randomized, double‐blind, placebo‐controlled, dose‐titration, parallel‐group trial in patients with obesity‐related HFpEF to evaluate the effects of HU6 on weight loss, body composition, exercise capacity, cardiac structure and function, metabolism, and inflammation, and identify optimal dosage for future Phase 3 trials.HuMAIN will test a promising novel agent for obesity‐related HFpEF. [ABSTRACT FROM AUTHOR]

In randomized clinical trials that use a long‐term efficacy endpoint, the follow‐up time necessary to observe the endpoint may be substantial. In such trials, an attractive option is to consider an interim analysis based solely on an early outcome that could be used to expedite the evaluation of treatment's efficacy. Garcia Barrado et al. (Pharm Stat. 2022; 21: 209–219) developed a methodology that allows introducing such an early interim analysis for the case when both the early outcome and the long‐term endpoint are normally‐distributed, continuous variables. We extend the methodology to any combination of the early‐outcome and long‐term‐endpoint types. As an example, we consider the case of a binary outcome and a time‐to‐event endpoint. We further evaluate the potential gain in operating characteristics (power, expected trial duration, and expected sample size) of a trial with such an interim analysis in function of the properties of the early outcome as a surrogate for the long‐term endpoint. [ABSTRACT FROM AUTHOR]

Objective Design Methods Results Conclusions Gender could impact the psychosocial outcomes and coping strategies of cancer patients and their spousal caregivers (SCs). This study aims to develop a gender‐concerned program for colorectal cancer (CRC) couple‐based mutual communication intervention (MCI) and to assess its effectiveness on the intra‐couple relationship and the individual functions of the partners.A randomized clinical trial with two study groups was utilized.A total of 144 CRC patients and their SCs were randomly assigned to either MCI or usual care (UC) groups, and all of them were required to complete the measurements at baseline and post‐intervention. The primary outcome was for mutual communication, and the secondary outcomes included dyadic coping, relationship satisfaction, anxiety, depression, benefit finding and quality of life. The data were analysed by multi‐level modelling.The MCI program was feasible and acceptable for Chinese CRC couples and was effective for the improvement of the intra‐couple relationship and the individual functions of each partner. CRC patients showed more improvement in mutual communication and dyadic coping than their SCs in the MCI group. Also, this intervention effectiveness was found to be independent of gender.The MCI program is beneficial for Chinese CRC couple's adaptation outcomes. This suggests that clinical medical staff should consider the gender tendency during the implementation of interventions. More researches are needed to extend the application of the MCI program to different participants (e.g. patients with the diagnosis of other types of cancer and their SCs). [ABSTRACT FROM AUTHOR]

Caloric restriction (CR) modifies lifespan and aging biology in animal models. The Comprehensive Assessment of Long‐Term Effects of Reducing Intake of Energy (CALERIE™) 2 trial tested translation of these findings to humans. CALERIE™ randomized healthy, nonobese men and premenopausal women (age 21–50y; BMI 22.0–27.9 kg/m2), to 25% CR or ad‐libitum (AL) control (2:1) for 2 years. Prior analyses of CALERIE™ participants' blood chemistries, immunology, and epigenetic data suggest the 2‐year CR intervention slowed biological aging. Here, we extend these analyses to test effects of CR on telomere length (TL) attrition. TL was quantified in blood samples collected at baseline, 12‐, and 24‐months by quantitative PCR (absolute TL; aTL) and a published DNA‐methylation algorithm (DNAmTL). Intent‐to‐treat analysis found no significant differences in TL attrition across the first year, although there were trends toward increased attrition in the CR group for both aTL and DNAmTL measurements. When accounting for adherence heterogeneity with an Effect‐of‐Treatment‐on‐the‐Treated analysis, greater CR dose was associated with increased DNAmTL attrition during the baseline to 12‐month weight‐loss period. By contrast, both CR group status and increased CR were associated with reduced aTL attrition over the month 12 to month 24 weight maintenance period. No differences were observed when considering TL change across the study duration from baseline to 24‐months, leaving it unclear whether CR‐related effects reflect long‐term detriments to telomere fidelity, a hormesis‐like adaptation to decreased energy availability, or measurement error and insufficient statistical power. Unraveling these trends will be a focus of future CALERIE™ analyses and trials. [ABSTRACT FROM AUTHOR]

Objective: To compare the clinical effectiveness of V‐bend bonded retainers (BR) versus vacuum‐formed retainers (VFR) regarding their capacity to maintain treatment stability and survival rates after 12 months. Materials and Methods: Patients finishing orthodontic treatment were randomly allocated into two groups. The BR group received maxillary and mandibular BRs in the lingual surfaces of the anterior teeth. The VFR group received VFRs right after fixed appliances removal. The patients were evaluated at four time‐points: at fixed appliances removal (T0), after 3 (T1), 6 (T2) and 12 months (T3). In each time‐point digital models were obtained and analysed with the OrthoAnalyzer™ software. Treatment stability based on occlusal outcomes and retainers' survival rates were evaluated. Intergroup comparisons were performed using Mann–Whitney U‐tests. The Kaplan–Meier survival plot and the log‐rank test were employed to assess the retainers' survival. Results: Both BR and VFR groups included 25 patients. The groups were comparable regarding their baseline characteristics. Up to 6 months, both retainers were equally effective; however, after 12 months, BRs were more effective in maintaining the incisors' alignment in the maxilla and the mandible compared to the VFRs. No differences were noticed in the intercanine and intermolar widths, overjet and overbite. There were no differences regarding the retainers' survivability in both arches. Conclusions: BRs were more effective in maintaining the alignment of the incisors in the maxilla and mandible compared to VFRs after 12 months. Both retainers presented the same survival rates after the same period. [ABSTRACT FROM AUTHOR]

Objectives: This randomized clinical trial evaluated and compared the 2‐year clinical performance of two ion‐releasing bulk‐fill composites (Cention N and Surefil One) with that of a conventional bulk‐fill resin composite (Powerfil) in Class I and II cavities. Methods: Thirty‐two patients, each with 3 Class I and/or Class II cavities under occlusion, were enrolled in this trial. A total of 96 restorations were placed, 32 for each material, as follows: a self‐adhesive composite; Surefil‐one, alkasite; Cention N, and a bulk‐fill resin composite; Powerfil. The restorations were placed by a single operator. Clinical evaluation was performed at baseline (1‐week), 6‐months, 1‐year, and 2‐years by two independent examiners using the FDI criteria. Intergroup and intragroup comparisons were analyzed using the Kruskal–Wallis and Friedman Tests. Multiple comparisons between groups were analyzed using the Mann–Whitney and Wilcoxon‐rank tests. The level of significance was set at α = 0.05. Results: Twenty‐seven patients with a total of 81 restorations were evaluated at the end of the 2‐years with 84.35% recall rates. Clinical success rates were 100%, 100%, and 96.3% for Powerfil, Surefil‐one, and Cention N, respectively. Cention N showed a statistically significant (p < 0.05) decreased marginal integrity in comparison with resin composite at the 2‐year evaluation. No recurrent decay was detected in any restoration. Conclusions: Both ion‐releasing bulk‐fill composites provided acceptable clinical performance similar to bulk‐fill composite in Class I and II restorations over a 2‐year period. Clinical Relevance: The results of this trial suggests that there is a promising evidence supporting the use of ion‐releasing composites. [ABSTRACT FROM AUTHOR]

Background: Equine herpes virus type 1 (EHV‐1) infection in horses is associated with upper respiratory disease, neurological disease, abortions, and neonatal death. Objective: To determine if there is an association between the level and duration of EHV‐1 viremia and either abortion or equine herpesvirus myeloencephalopathy (EHM) in domesticated horses? Methods: A systematic review was performed searching numerous databases to identify peer reviewed reports that evaluated viremia and EHM, or viremia and abortion published before January 19, 2021. Randomized controlled trials and observational studies were assessed for risk of bias or publication quality. Results: A total of 189 unique studies were identified, of which 34 met the inclusion criteria. Thirty studies evaluated viremia and neurologic outcomes including 4 observational studies. Eight experimental studies examined viremia and abortion, which used the Ab4 and OH03 virus strains or recombinant Ab4 derivatives. Incidence rates for both EHM and abortion in experimental studies varied among the studies as did the level of evidence. Viremia was generally detectable before the onset of either EHM or abortion. Risk of bias was generally low to moderate, sample sizes were small, and multiple studies reported negative outcome data. Conclusions and Clinical Importance: The results of this study support that viremia is regularly present before EHM or abortion occurs. However, no inferences could be made about the relationship between the occurrence of either neurological signs or abortion and the magnitude or duration of viremia. [ABSTRACT FROM AUTHOR]

Background: The level of post‐operative mobilization according to Enhanced Recovery After Surgery (ERAS) guidelines is not always achieved. We investigated whether immediate mobilization increases postoperative physical activity. The objective was to evaluate the effects of immediate postoperative mobilization in the post‐anesthesia care unit (PACU) compared to standard care. Methods: This randomized controlled trial, involved 144 patients, age ≥18 years, undergoing elective colorectal surgery. Patients were randomized to mobilization starting 30 min after arrival in the PACU, or to standard care. Standard care consisted of mobilization a few hours later at the ward according to ERAS guidelines. The primary outcome was physical activity, in terms of number of steps, measured with an accelerometer during postoperative days (PODs) 1–3. Secondary outcomes were physical capacity, functional mobility, time to readiness for discharge, complications, compliance with the ERAS protocol, and physical activity 1 month after surgery. Results: With the intention‐to‐treat analysis of 144 participants (median age 71, 58% female) 47% underwent laparoscopic‐or robotic‐assisted surgery. No differences in physical activity during hospital stay were found between the participants in the intervention group compared to the standard care group (adjusted mean ratio 0.97 on POD 1 [95% CI, 0.75–1.27], p = 0.84; 0.89 on POD 2 [95% CI, 0.68–1.16], p = 0.39, and 0.90 on POD 3 [95% CI, 0.69–1.17], p = 0.44); no differences were found in any of the other outcome measures. Conclusions: Addition of the intervention of immediate mobilization to standard care did not make the patients more physically active during their hospital stay. Trial registration: ClinicalTrials.gov Identifier: NTC 03357497. [ABSTRACT FROM AUTHOR]

Background: Stromal vascular fraction (SVF) cells derived from adipose tissue and platelet‐rich plasma (PRP) are among novel treatments for androgenetic alopecia (AGA). We aimed to investigate the effect of adding SVF to PRP and compare it to administering PRP injection alone. Methods: Eighteen patients were randomly divided into two groups of nine. The PRP group was treated with PRP at all three visits at 1‐month intervals, while the SVF‐PRP group received an SVF injection on the first visit and a PRP injection on the second and third visits. Each group was evaluated at baseline and 20 weeks after the therapy's initiation. Results: Changes in mean hair diameter and hair count compared to baseline were significant in both groups. The PRP group experienced a greater increase in mean hair count than the SVF‐PRP group, and the SVF‐PRP group had a marginally greater increase in hair diameter than the PRP group. These differences were not statistically significant compared to each other. The patient and physician assessment scores exceeded the mean (on a scale from 0: poor to 3: excellent) in both groups. Conclusion: Adding one SVF injection to two PRP treatment sessions versus three PRP injections alone had no significant difference in evaluated variables. If additional research demonstrates the same results, we suggest that multiple SVF injection sessions may be required to produce a statistically significant difference compared to PRP injection alone. Moreover, considering lower cost and greater accessibility of PRP, it can be used before SVF in the treatment of AGA. [ABSTRACT FROM AUTHOR]

Objectives: Perfectionism is a common transdiagnostic problem that may lead to substantial distress and functional impairments. Cognitive behavioural therapy (CBT) is an effective treatment for perfectionism. However, the existing significant barriers to access and utilization of mental health services, including among college students, demand the development of low‐intensity accessible interventions. The aim of the present study was to evaluate the effectiveness of a low‐intensity CBT‐based self‐help gamified app developed specifically for perfectionism in a sample of college students. Methods: Participants completed assessments of perfectionism, related symptoms, emotional burden and functional impairments at pretreatment, posttreatment and at one‐month follow‐up. Results: Compared with the waitlist condition (n = 35), the app condition (n = 35) demonstrated a significant and greater reduction in perfectionism, obsessive‐compulsive symptoms, functional impairments and subjective ratings of emotional burden. Conclusions: Results suggest that a brief, daily app‐based game‐like intervention targeting maladaptive perfectionistic beliefs may be a viable, low‐cost alternative to traditional CBT treatments for vulnerable populations on college campuses. [ABSTRACT FROM AUTHOR]

Introduction: Women undergoing an induced abortion are highly fertile and at risk of subsequent unplanned pregnancy. We recently completed a randomized clinical trial showing that routine provision of intrauterine device (IUD) at the time of abortion significantly reduced the risk of subsequent abortion during a 5‐year follow up. As the use of highly effective contraception may affect all subsequent pregnancies, we analyzed the rate and distribution of all subsequent pregnancies (deliveries, miscarriages, and abortions), and the risk factors for these various pregnancy outcomes in the above‐mentioned randomized clinical trial. Material and methods: We enrolled adult women requesting first‐trimester induced abortion and candidates for IUD for post‐abortion contraception. Women (n = 751) were randomized to receive an IUD (either levonorgestrel‐releasing IUD or copper IUD) by the clinic responsible for abortion care vs. routine care of IUD provision in primary health care with oral contraceptives for interval contraception. In the present secondary analysis, we identified all deliveries, miscarriages, and abortions in the intervention (n = 375) and control (n = 373) cohorts during the 5‐year follow up using the Finnish national registries. The trial is registered at Clinical Trials (NTC01223521). Results: The overall delivery, miscarriage, and abortion rates were 42.0, 12.0 and 32.1/1000 years of follow up (yFU). Any new pregnancy occurred in 98 women in the intervention and in 129 women in the control cohort (hazard ratio 0.73, 95% confidence interval 0.56–0.95, p = 0.023). The effect of routine IUD provision in reducing pregnancies was limited to the first 2 yFU. The number of subsequent induced abortions and of women undergoing it were significantly reduced, and time to abortion was prolonged by the intervention. However, the overall number, the number of women with subsequent delivery or miscarriage, and the times to these events were not significantly affected. History of previous pregnancy (delivery or abortion) and smoking were risk factors for subsequent induced abortion, but not for delivery or miscarriage. Conclusions: Routine provision of IUD as part of abortion care did not reduce the rates of delivery or miscarriage during the 5‐year follow up. The rates of all pregnancies and the need of subsequent induced abortion were reduced by IUD provision during the first 2 yFU. [ABSTRACT FROM AUTHOR]

Background/Aim: This study aimed at comparing the regenerative potential of injectable platelet‐rich fibrin (i‐PRF) (Group 1) and platelet‐rich plasma (Group 2) scaffolds. Materials and methods: Twenty‐three patients, aged from 9 to 24 years, having 24 immature traumatized necrotic maxillary anterior teeth, were enrolled. Teeth trauma was confirmed by patients' history. Preoperative three‐dimensional scans were done. In the first visit, canals were irrigated with 1.5% sodium hypochlorite then medicated with calcium hydroxide. After 2 weeks, patients were randomly assigned into one of the treatment groups (n = 12). The platelet concentrate was applied after centrifuging 10 mL of autologous venous blood with respect to the centrifugation protocol for each platelet concentrate. Patients were recalled at 6 and 12 months posttreatment, during which clinical and radiographic examinations and assessment of pulp sensitivity were done. Three‐dimensional scanning was done after 12 months. The increase in root length and decrease in root canal diameters were calculated at three canal levels. Statistical analysis was done using the paired t‐test and the independent t‐test. The significance level was set at p <.05. Results: There was no statistically significant difference between both groups regarding the increase in root length, decrease in coronal and middle canal diameters and the response to the electric pulp tester. Group (1) showed significantly greater decrease in apical canal diameter than Group (2) (p =.008). Conclusion: I‐PRF can be considered as a valid regenerative scaffold for clinical use and with regards to the easier preparation technique, it is more recommended than platelet‐rich plasma. [ABSTRACT FROM AUTHOR]

Wound care is a complex procedure and the related research may include many variables. Deficiencies in the sample inclusion and exclusion criteria may limit the generalizability of randomized controlled trials (RCTs) for wound patients in the real world. This study aimed to evaluate deficiencies in reporting the inclusion and exclusion criteria and the characteristics of patients in RCTs of pressure injuries (PI) therapeutic interventions. We conducted a systematic methodological review in which 40 full text RCTs of PI treatment interventions published in English, from 2008 to 2020, were identified. Data on the general characteristics of the included RCTs and data about inclusion/exclusion criteria and characteristics of patients were collected. The inclusion/exclusion criteria were categorized into five domains (definition of disease, precision, safety, ethical/legal and administrative). Study duration (in weeks) was 8.0 (quartile 1: 2.0; quartile 3: 48.0); only 5.0% of the trials mentioned race, skin colour or ethnicity, and 37.5% reported the duration of the wound. Only 9 (22.5%) studies reported the drugs that the included patients were using and 10 (25.0%) RCTs reported adverse events. The presence of the five domains was observed only in 12.5% of RCTs and only 12 (30.0%) had the precision domain. Much more research is required in systematic assessments of the external validity of trials because there is substantial disparity between the information that is provided by RCTs and the information that is required by clinicians. We concluded that there are deficiencies in reporting of data related to inclusion/exclusion criteria and characteristics of patients of RCTs assessing PI therapeutic interventions. [ABSTRACT FROM AUTHOR]

Objectives: To date, no clinical studies have investigated the effect of using resorbable collagen membrane in conjunction with customized titanium mesh to promote bone formation in guided bone regeneration. Therefore, a non‐inferiority analysis (one‐sided 95% CI approach) was designed to compare the augmented bone gained using meshes with and without collagen membranes, through histological and histomorphometric investigations. Materials and Methods: Thirty patients undergoing bone augmentation procedures at both maxillary and mandible sites were randomly treated with customized titanium meshes alone (M−, n = 15) or covered with resorbable membrane (M+, n = 15), in both cases filled with autogenous bone and xenograft. After 6 months of healing, bone tissue biopsies were taken from the augmented region. The bone tissue (B.Ar), grafting material (G.Ar), and non‐mineralized tissue (NMT.Ar) areas were quantified through histomorphometric analysis, as were the osteoid area (O.Ar) and its width. Results: Collagen membrane did not appear to significantly influence the investigated parameters: B.Ar, G.Ar, NMT.Ar, and O.Ar were similar between Group M− (34.3%, 11.5%, 54.1%, 1.95 μm2, respectively) and Group M+ (35.3%, 14.6%, 50.2%, and 1.75 μm2, respectively). Considering the overall population, significantly higher rates of newly formed bone were obtained in mandibular sites, while non‐mineralized and dense connective tissue rates were higher in the maxilla (p <.05). Conclusions: The application of collagen membrane over titanium mesh did not lead to significant results. Bone formation appeared significantly different in the maxilla compared with the mandible. Additional studies are required to further investigate the issues observed. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to investigate 2‐year changes in periapical trabecular patterns in single‐rooted teeth with apical periodontitis using fractal analysis and periapical index (PAI) after root canal treatment performed with or without BioPure MTAD solution. Methodology: In this randomized clinical trial, 100 patients were selected and randomized to either the BioPure MTAD or the control groups. Initial periapical radiographs were obtained for each participant before and 2 years after root canal treatment. The region of interest in the periapical lesion around the root apex was selected from the paired periapical radiographs, and then, the fractal dimension (FD) was calculated. With regards to the classification of periapical status, PAI was labelled as "healed" (PAI ≤ 2) or "unhealed" (PAI ≥ 3). Results: After 24 months, 28 patients did not comply with the follow‐up and the data of 72 patients were compared. When the initial and the follow‐up PAI scores were compared, the decrease was statistically significant in 33 of 37 teeth (89.2%) and 32 of 35 teeth (91.4%) in the BioPure MTAD and control group, respectively. In both groups, statistically significant increases were observed in FD values after 2 years in all patients (p <.001). No significant difference was found between the two groups amongst decreased PAI scores and increased FD values. Conclusions: Root canal treatments with or without BioPure MTAD irrigation contributed to periapical healing in single‐visit root canal treatment. Two years after root canal treatment, the extent of the periapical trabecular bone radiographically increased, as the FD and PAI data revealed. [ABSTRACT FROM AUTHOR]

The sum of the longest diameter (SLD) of the target lesions is a longitudinal biomarker used to assess tumor response in cancer clinical trials, which can inform about early treatment effect. This biomarker is semicontinuous, often characterized by an excess of zeros and right skewness. Conditional two‐part joint models were introduced to account for the excess of zeros in the longitudinal biomarker distribution and link it to a time‐to‐event outcome. A limitation of the conditional two‐part model is that it only provides an effect of covariates, such as treatment, on the conditional mean of positive biomarker values, and not an overall effect on the biomarker, which is often of clinical relevance. As an alternative, we propose in this article, a marginalized two‐part joint model (M‐TPJM) for the repeated measurements of the SLD and a terminal event, where the covariates affect the overall mean of the biomarker. Our simulation studies assessed the good performance of the marginalized model in terms of estimation and coverage rates. Our application of the M‐TPJM to a randomized clinical trial of advanced head and neck cancer shows that the combination of panitumumab in addition with chemotherapy increases the odds of observing a disappearance of all target lesions compared to chemotherapy alone, leading to a possible indirect effect of the combined treatment on time to death. [ABSTRACT FROM AUTHOR]

The current understanding of the placebo response in vitiligo is limited. Nonetheless, it is difficult to compare the outcomes of vitiligo trials if the repigmentation rates in placebo patients vary significantly. We conducted a meta‐analysis of the placebo response in vitiligo trials. Overall, repigmentation rates in patients receiving placebo were 22%, ranging substantially from 0 to 60%. Repigmentation (>25%) was still relatively common for placebo (9.35%), but fell to 5% when >50% improvement was analyzed. Higher frequencies of placebo responses correlated with more repigmentation in the intervention groups. Facial vitiligo and sunlight exposure was linked to higher placebo responses. Roughly estimating the amount of improvement using quartiles (0–25, 25%–50%, 50%–75%, 75%–100% repigmentation) resulted in higher placebo rates compared to other assessment methods. In clinical studies with older patients, the ratio of placebo reactions to treatment responses was higher. This is likely because clinical trials with older patients reported less repigmentation after treatment than studies with younger patients. The percentual difference in affected body surface area during the study period ranged from 6.2% worsening to 17.6% improvement in the placebo groups. This high variability in placebo responses illustrates the need for standardized outcome measures and more head‐to‐head trials in vitiligo. [ABSTRACT FROM AUTHOR]

Clinicians report primarily using functional behavioral assessment (FBA) methods that do not include functional analyses. However, studies examining the correspondence between functional analyses and other types of FBAs have produced inconsistent results. In addition, although functional analyses are considered the gold standard, their contribution toward successful treatment compared with other FBA methods remains unclear. This comparative effectiveness study, conducted with 57 young children with autism spectrum disorder, evaluated the results of FBAs that did (n = 26) and did not (n = 31) include a functional analysis. Results of FBAs with and without functional analyses showed modest correspondence. All participants who completed functional communication training achieved successful outcomes regardless of the type of FBA conducted. [ABSTRACT FROM AUTHOR]

Aim: This investigation aimed to evaluate the 1‐year survival of implants placed after staged lateral alveolar ridge augmentation using equine‐derived collagenated xenogeneic bone blocks (CXBBs) or autogenous bone block (ABB). Materials and Methods: Fifty patients who underwent lateral augmentation in a previous trial were included. The primary outcome measure was implant survival at the 1‐year follow‐up, and secondary outcomes included implant success, peri‐implant clinical and volumetric parameters, pink aesthetic scores (PES) and patient‐reported outcome measures. Data analysis involved Fisher's exact test, the Mann–Whitney U‐test and the Wilcoxon signed‐rank test. Results: In this study, no late implant failures were observed. The cumulative survival rates were 78.6% for the CXBB group and 90.9% for the ABB group, with no difference between the groups. Similarly, the success rates were 53.6% and 63.6%, respectively, showing no significant difference. Peri‐implant clinical and volumetric parameters indicated the presence of healthy peri‐implant tissues surrounding implants placed in both CXBB‐ and ABB‐augmented sites. PES were 8.5 and 11.0 for implants placed in CXBB‐ and ABB‐augmented sites, respectively. Furthermore, patient satisfaction rates were high and similar between the groups. Conclusions: Dental implants placed in both CXBB‐ and ABB‐augmented ridges demonstrated no statistically significant differences in clinical, volumetric and aesthetic outcomes, along with high patient satisfaction rates. [ABSTRACT FROM AUTHOR]

Aims: To compare pharmacokinetics (PK) and safety of heat‐stable inhaled (IH) oxytocin with intramuscular (IM) oxytocin in women in third stage of labour (TSL), the primary endpoint being PK profiles of oxytocin IH and secondary endpoint of safety. Methods: A phase 1, randomized, cross‐over study was undertaken in 2 UK and 1 Australian centres. Subjects were recruited into 2 groups: Group 1, women in TSL; Group 2, nonpregnant women of childbearing potential (Cohort A, combined oral contraception; Cohort B, nonhormonal contraception). Participants were randomized 1:1 to: Group 1, oxytocin 10 IU (17 μg) IM or oxytocin 240 IU (400 μg) IH immediately after delivery; Group 2, oxytocin 5 IU (8.5 μg) intravenously and oxytocin 240 IU (400 μg) IH at 2 separate dosing sessions. Results: Participants were recruited between 23 November 2016 to 4 March 2019. In Group 1, 17 participants were randomized; received either IH (n = 9) or IM (n = 8) oxytocin. After IH and IM administration, most plasma oxytocin concentrations were below quantification limits (2 pg/mL). In Group 2 (n = 14), oxytocin IH concentrations remained quantifiable ≤3 h postdose. Adverse events were reported in both groups, with no deaths reported: Group 1, IH n = 3 (33%) and IM n = 2 (25%); Group 2, n = 14 (100%). Conclusion: Safety profiles of oxytocin IH and IM were similar. However, PK profiles could not be established for oxytocin IH or IM in women in TSL, despite using a highly sensitive and specific assay. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to test the usefulness of an add‐on serious video game approach (i.e., Playmancer) to treatment as usual (TAU) on reducing impulsive behaviours and psychopathology in individuals diagnosed with an eating disorder (ED). Method: Thirty‐seven patients diagnosed with an ED according to the DSM‐5 were included in the present randomized clinical trial (RCT; study record 35,405 in ClinicalTrials.gov) and were randomly assigned to either the TAU or TAU + Playmancer group. All participants completed a clinical interview. Impulsivity (UPPS‐P self reported questionnaire and Stroop task) and general psychopathology (SCL‐90‐R) measures were assessed at: baseline, 4 weeks into treatment, at the end of TAU (after 16 weeks), and follow‐up (2 years). In addition, patients in the experimental group underwent a total of nine sessions with Playmancer over the span of 3 weeks. Results: Patients in both treatment groups (TAU + Playmancer or TAU) improved on Stroop task performance and psychological distress. Additionally, patients in TAU‐Playmancer improved on the impulsive trait domain of lack of perseverance. No statistical differences were found regarding treatment outcomes (i.e., treatment adherence and remission of eating symptomatology) when comparing the two treatment groups. Conclusion: Our results suggest that the impulsivity associated with EDs should be addressed and could be modified, as some facets of trait impulsivity improved after Playmancer add‐on treatment. Yet, there were no significant differences in treatment outcomes when comparing the two groups and further research needs to be conducted. Highlights: Certain eating disorders (EDs) are characterised by high levels of impulsivity.Serious video games may enhance standard treatments (such as cognitive‐behavioural therapy).Playmancer sessions, along with standard treatment, are useful in reducing certain impulsive traits in patients with EDs. [ABSTRACT FROM AUTHOR]

Background: A 13‐year follow‐up was conducted of a short‐term investigation of the use of living cellular construct (LCC) versus free gingival graft (FGG) for keratinized tissue width (KTW) augmentation in natural dentition, to evaluate the long‐term outcomes and assess the changes occurring since the end of the original 6‐month study. Methods: Twenty‐four subjects out of the original 29 enrolled participants were available at the 13‐year follow‐up. The primary endpoint was the number of sites demonstrating stable clinical outcomes from 6 months to 13 years (defined as KTW gain, stability, or ≤0.5 mm of KTW loss, together with reduction, stability, or increase of probing depth, and recession depth [REC] ≤0.5 mm). Secondary outcomes included the assessment of KTW, attached gingiva width (AGW), REC, clinical attachment level, esthetics, and patient‐reported outcomes at the 13‐year visit, assessing the changes from baseline to 6 months. Results: Nine sites per group (42.9%) were found to have maintained stable (≤0.5 mm or improved) clinical outcomes from 6 months to 13 years. No significant differences were observed for the clinical parameters between LCC and FGG from 6 months to 13 years. However, the longitudinal mixed model analysis showed that FGG delivered significantly better clinical outcomes over 13 years (p < 0.01). LCC‐treated sites exhibited superior esthetic outcomes compared to FGG‐treated sites at 6 months and 13 years (p < 0.01). Patient‐evaluated esthetics were significantly higher for LCC over FGG (p < 0.01). Patient overall treatment preference was also in favor of LCC (p < 0.01). Conclusions: A similar stability of the treatment outcomes from 6 months to 13 years was found for LCC‐ and FGG‐treated sites, with both approaches shown to be effective in augmenting KTW and AGW. However, superior clinical outcomes were found for FGG over 13 years, while LCC was associated with better esthetics and patient‐reported outcomes than FGG. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this randomized clinical trial was to evaluate the desensitizing and remineralizing effect of a new zinc‐hydroxyapatite‐based paste in sites affected by molar–incisor hypomineralization (MIH), by assessing dental sensitivity, tooth wear, and periodontal indexes. Materials and Methods: Twenty‐five patients with presence of 1 enamel demineralization of permanent molars and incisors in two different quadrants were recruited. After professional dental hygiene, a domiciliary hydroxyapatite‐based paste was assigned and recommended to be applied on 2 MIH teeth in one random quadrant (test group), while the 2 contralateral MIH teeth did not undergo paste application (control group). The following primary outcomes were assessed: Plaque Control Record (PCR), Bleeding Index (BI), MIH Treatment Need Index (MIH‐TNI), and Schiff Air Index (SAI). Results: No significant inter‐ and intragroup differences were found for PI and BI, except for both intragroup T0–T1. For MIH‐TNI, significant intergroup differences were detectable in the test group after 9 months of treatment. For SAI values, no significant differences were found in the control group, while in the test group, significant lower values were found after 1 and 3 months since baseline, respectively. Conclusions and Clinical Relevance: Biomimetic zinc‐hydroxyapatite showed a desensitizing effect when used to treat MIH. [ABSTRACT FROM AUTHOR]

Background: In the general population, a higher omega‐3 polyunsaturated fatty acids intake is associated with lower levels of several psychological symptoms, especially depression. However, the existing evidence in cancer is equivocal. Methods: This phase IIB double‐blind, placebo‐controlled trial was aimed at comparing the effects of eicosapentaenoic acid monoacylglyceride (MAG‐EPA) supplementation and high oleic acid sunflower oil (HOSO; placebo) on depression levels (primary outcome) and other symptoms (anxiety, fear of cancer recurrence, fatigue, insomnia, perceived cognitive impairments; secondary outcomes). Participants, recruited in a prostate cancer clinic, were randomized to MAG‐EPA (3.75 g daily; n = 65) or HOSO (3.75 g daily; n = 65) for 1 year post‐radical prostatectomy (RP), starting 4–10 weeks before surgery. Patients completed self‐report scales at baseline (before RP) and 3, 6, 9, and 12 months after: Hospital Anxiety and Depression Scale (HADS), Fear of Cancer Recurrence Inventory (FCRI), Insomnia Severity Index (ISI), Fatigue Symptom Inventory (FSI), and Functional Assessment of Cancer Therapy—Cognitive Function (FACT‐Cog). Results: Analyses showed significant reductions in HADS‐depression, HADS‐anxiety, FCRI, ISI, FSI‐number of days, and FACT‐Cog‐impact scores over time. A significant group‐by‐time interaction was obtained on FACT‐Cog‐Impact scores only; yet, the temporal change was significant in HOSO patients only. Conclusions: Several symptoms significantly decreased over time, mainly within the first months of the study. However, MAG‐EPA did not produce greater reductions than HOSO. Omega‐3 supplementation does not seem to improve psychological symptoms of men treated with RP. [ABSTRACT FROM AUTHOR]

Background: The results of vital pulp treatments in permanent teeth have been encouraging. Currently, pulpotomy treatment for permanent teeth primarily utilizes mineral trioxide aggregate (MTA) as the dressing material, followed by calcium hydroxide. While other calcium‐silicate‐based cements have been suggested for pulpotomy, there is a limited number of studies evaluating their long‐term effectiveness. Objectives: The objective of this systematic review and meta‐analysis was to evaluate the success rate of pulpotomies performed on permanent teeth, comparing the use of ProRoot MTA with that of calcium hydroxide and other bioceramic materials. Methods: A comprehensive search was conducted in several electronic databases, including PubMed, Cochrane Library, Scopus, Web of Science, Embase and Science Direct until December 2022. The search was guided by PICOS criteria, including only randomized clinical trials (RCTs) that evaluated the success rate of pulpotomy treatments in permanent teeth using ProRoot MTA in comparison to calcium hydroxide and other bioceramic materials. The quality of the included studies was assessed using the RoB‐2 tool to evaluate the risk of bias, and relevant data were extracted and analysed in RevMan software 5.3 using fixed‐effect models. The GRADE tool was used to determine the overall quality of evidence. Results: The initial search retrieved 1072 studies and, after eliminating duplicates, 677 studies were screened and 28 studies were considered for eligibility. In the final selection process, 16 studies were included in the systematic review, with 10 being determined as having a high risk of bias. Pulpotomy showed an overall mean success rate of 92% after 1 year. The meta‐analysis indicated a significantly higher success rate for pulpotomies utilizing MTA in comparison with calcium hydroxide, while no significant difference was seen between MTA and calcium‐enriched mixture (CEM) or Biodentine. The GRADE assessment revealed an overall low level of evidence for the included studies. Discussion: Most randomized controlled trials exhibited a significant absence of control over confounding factors. Conclusions: This systematic review and meta‐analysis demonstrate that pulpotomy is a highly effective treatment for managing permanent teeth. The results indicate that the success rate of pulpotomy using ProRoot MTA is significantly higher than when using calcium hydroxide. However, the certainty of evidence supporting these findings is low, and there is a need for well‐designed RCTs to assess the long‐term outcomes of pulpotomy using newer bioceramic materials. Registration: This systematic review was registered in the PROSPERO database (registration number CRD42023393970). [ABSTRACT FROM AUTHOR]

Background: Randomized clinical trials (RCTs) are experiencing a crisis of confidence in their trustworthiness. Although a comprehensive literature search yielded several reviews on RCT integrity, an overarching overview is lacking. Objectives: The authors undertook a scoping umbrella review of the research integrity literature concerning RCTs. Search strategy and selection criteria: Following prospective registration (https://osf.io/3ursn), two reviewers independently searched PubMed, Scopus, The Cochrane Library, and Google Scholar, without language or time restrictions, until November 2021. The authors included systematic reviews covering any aspect of research integrity throughout the RCT lifecycle. Data collection and analysis: The authors assessed methodological quality using a modified AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews) tool and collated the main findings. Main results: A total of 55 relevant reviews, summarizing 6001 studies (median per review, 63; range, 8–1106) from 1964 to 2021, had an overall critically low quality of 96% (53 reviews). Topics covered included general aspects (15%), design and approval (22%), conduct and monitoring (11%), reporting (38%), postpublication concerns (2%), and future research (13%). The most common integrity issues covered were ethics (18%) and transparency (18%). Conclusions: Low‐quality reviews identified various integrity issues across the RCT lifecycle, emphasizing the importance of high ethical standards and professionalism while highlighting gaps in the integrity landscape. Multistakeholder consensus is needed to develop specific RCT integrity standards. Synopsis: The trustworthiness of randomized clinical trials (RCTs) is experiencing a crisis of confidence. A multistakeholder consensus is needed to create specific RCT integrity standards. [ABSTRACT FROM AUTHOR]

Aim: Surgical site infection (SSI) is one of the most common postoperative complications in gastrointestinal surgery. To clarify the superiority of 1.5% olanexidine, we conducted a randomized prospective clinical trial that enrolled patients undergoing gastrointestinal surgery with operative wound classes II–IV. Methods: To evaluate the efficacy of 1.5% olanexidine in preventing SSIs relative to 10% povidone‐iodine, we enrolled 298 patients in each group. The primary outcome was a 30‐day SSI, and the secondary outcomes were incidences of superficial and deep incisional SSI and organ/space SSI. In addition, subgroup analyses were performed. Results: The primary outcome of the overall 30‐day SSI occurred in 38 cases (12.8%) in the 1.5% olanexidine group and in 53 cases (18.0%) in the 10% povidone‐iodine group (adjusted risk ratio: 0.716, 95% confidence interval: 0.495–1.057, p = 0.083). Organ/space SSI occurred in 18 cases (6.1%) in the 1.5% olanexidine group and in 31 cases (10.5%) in the 10% povidone‐iodine group, with a significant difference (adjusted risk ratio: 0.587, 95% confidence interval: 0.336–0.992, p = 0.049). Subgroup analyses revealed that SSI incidences were comparable in scheduled surgery (relative risk: 0.809, 95% confidence interval: 0.522–1.254) and operative wound class II (relative risk: 0.756, 95% confidence interval: 0.494–1.449) in 1.5% olanexidine group. Conclusion: Our study revealed that 1.5% olanexidine reduced the 30‐day overall SSI; however, the result was not significant. Organ/space SSI significantly decreased in the 1.5% olanexidine group. Our results indicate that 1.5% olanexidine has the potential to prevent SSI on behalf of povidone‐iodine. [ABSTRACT FROM AUTHOR]

Low circulating vitamin D levels are more prevalent in Black than White individuals. We analyzed the Women's Health Initiative (WHI) calcium plus vitamin D (CaD) randomized clinical trial extended follow‐up data to evaluate associations between calcium plus vitamin D supplementation and incident cancer, cardiovascular disease (CVD), and cause‐specific mortality endpoints among Black women. Intent‐to‐treat analysis was performed. Among 3325 Black women in the CaD trial who were randomized into either daily calcium (1000 mg of calcium carbonate) plus vitamin D (400 IU D3) or placebos for an average of 7 years, there were 813 deaths, 588 incident cancers, and 837 CVD events during an average of 15.7 years of follow up (52 230 total person‐years). Using Cox's proportional hazards models, we calculated hazard ratios and their confidence intervals for outcomes ascertained during the trial period, posttrial follow‐up period and overall periods combined. We found that total mortality, cause‐specific mortality, and total cancer incidence were almost identical between CaD and placebo groups. These results suggest that calcium plus vitamin D supplementation does not reduce risks of cancer, CVD, or other major causes of death in Black women overall and, thus, other medical, behavioral or social interventions should be considered to narrow health disparities related to these outcomes. However, other finer endpoints, such as colorectal cancer, warrants further investigation. [ABSTRACT FROM AUTHOR]

Aim: This was a double‐blind, placebo‐controlled randomized study investigating whether melatonin can protect against radiation dermatitis in women receiving radiation therapy for primary breast cancer. Methods: Patients were included before radiation therapy and followed once weekly throughout treatment with a 3‐week follow‐up. Patients applied 1 g of cream to the irradiated skin twice daily, consisting of either 25 mg/g melatonin and 150 mg/g dimethyl sulfoxide, or placebo. Our outcomes were the Radiation Therapy Oncology Group's (RTOG) acute radiation morbidity scoring criteria for skin, a pixel analysis of erythema in clinical photographs, and patients' use of corticosteroid cream. Outcomes were evaluated once weekly throughout the trial. The primary outcomes were RTOG‐score and pixel analysis at 2 weeks follow‐up. Secondary outcomes were the use of corticosteroid cream and analyses of RTOG‐scores and pixel analyses throughout the trial. Results: Sixty‐five patients were included, 17 dropped out, totaling 26 and 22 patients randomized to melatonin and placebo, respectively. RTOG‐scores and pixel analyses at 2 weeks follow‐up showed no difference p =.441 and p =.890, respectively). There was no difference in the use of corticosteroid cream (p =.055). Using logistic regression, the melatonin group had a higher likelihood of having a low RTOG‐score (p =.0016). The logistic regression showed no difference between the groups for the pixel analyses. Conclusion: Our primary outcome showed no difference in RTOG‐scores at 2 weeks follow‐up, however, the RTOG‐score over the entire duration of the study demonstrated a protective effect of melatonin. Further studies are warranted investigating higher doses of melatonin, and whether corticosteroids may influence the effect of melatonin cream against radiation dermatitis. [ABSTRACT FROM AUTHOR]

Hyperhomocysteinemia with hypertension can synergistically increase the risk of stroke. The China stroke primary prevention trial showed that combining 0.8 mg folic acid (FA) with angiotensin‐converting enzyme inhibitor (ACEI) can effectively lower plasma total homocysteine (tHcy) and blood pressure (BP); and reduce first stroke risk by additional 21% compared to ACEI alone. However, intolerance to ACEI is common in Asians and amlodipine can be alternative. This is a multicenter, randomized, double‐blind, parallel‐controlled clinical trial (RCT) which evaluated whether amlodipine combined with FA is more efficacious than amlodipine alone in lowering tHcy and BP among Chinese hypertensive with hyperhomocysteinemia and intolerance to ACEI. 351 Eligible patients were randomly assigned by 1:1:1 ratio to receive amlodipine‐FA tablet daily (amlodipine 5 mg/FA 0.4 mg, A group); amlodipine 5 mg/FA 0.8 mg tablet daily (B group); amlodipine 5 mg daily (C group, control group). Follow‐up was conducted at 2, 4, 6, and 8 weeks. The primary outcome was efficacy of lowering both tHcy and BP at the end of 8‐week treatment. Compared with C group, A group had a significantly higher rate of lowering both tHcy and BP (23.3% vs. 6.0%; Odds Ratio [OR], 8.68; 95% CI, 3.04‐24.78, P <.001); B group also had a higher rate of lowering both tHcy and BP (20.3% vs. 6.0%; OR: 5.90; 95% CI, 2.11‐16.47, P <.001). This RCT showed amlodipine combined with FA compared with amlodipine alone, each had significantly higher efficacy of lowering both tHcy and BP. No difference was found in BP‐lowering and occurrence of adverse events between the three groups. [ABSTRACT FROM AUTHOR]

Aim: Managing type 1 diabetes in young children can cause significant stress for parents. Continuous glucose monitoring (CGM) may reduce parental burden. The Strategies to Enhance CGM Use in Early Childhood (SENCE) trial randomized parents of children (ages 2 to <8 years) with type 1 diabetes to CGM with family behavioural intervention (CGM + FBI), CGM alone (Standard‐CGM) or blood glucose monitoring for 26 weeks before receiving CGM + FBI (BGM‐Crossover). This report assesses changes in psychosocial outcomes for all groups over 52 weeks. Methods: CGM + FBI (n = 45), Standard‐CGM (n = 42) and BGM‐Crossover (n = 44) participants completed psychosocial assessments at baseline, 26 weeks and 52 weeks. Repeated measures linear regression models evaluated change within and between treatment groups. Results: The BGM‐Crossover group reported improved diabetes burden (Δ −6.9, 95% CI [−11.3, −2.6], p = 0.003), fear of hypoglycaemia (Δ −6.4, CI [−10.1, −2.6], p = 0.002) and technology satisfaction (Δ 7.3, CI [2.4, 12.2], p = 0.005) from 26 to 52 weeks, similar to published findings in the CGM + FBI group over the first 26 weeks. The Standard‐CGM group reported increased technology satisfaction (Δ 7.3, CI [0.6, 14.0], p = 0.027) from baseline to 52 weeks. The CGM + FBI group reported less diabetes burden and fear of hypoglycaemia from baseline to 52 weeks, but changes were not statistically significant. Scores from 26 to 52 weeks did not deteriorate. Conclusions: Parents demonstrated psychosocial benefits following FBI that appeared to maintain without additional intervention. CGM‐focused education with behavioural support likely helps parents of young children with type 1 diabetes reduce burden and worry in the short‐ and long‐term. [ABSTRACT FROM AUTHOR]

The challenges and potential benefits of incorporating biomarkers into clinical trial designs have been increasingly discussed, in particular to develop new agents for immune‐oncology or targeted cancer therapies. To more accurately identify a sensitive subpopulation of patients, in many cases, a larger sample size—and consequently higher development costs and a longer study period—might be required. This article discusses a biomarker‐based Bayesian (BM‐Bay) randomized clinical trial design that incorporates a predictive biomarker measured on a continuous scale with pre‐determined cutoff points or a graded scale to define multiple patient subpopulations. We consider designing interim analyses with suitable decision criteria to achieve correct and efficient identification of a target patient population for developing a new treatment. The proposed decision criteria allow not only the take‐in of sensitive subpopulations but also the ruling‐out of insensitive ones on the basis of the efficacy evaluation of a time‐to‐event outcome. Extensive simulation studies are conducted to evaluate the operating characteristics of the proposed method, including the probability of correct identification of the desired subpopulation and the expected number of patients, under a wide range of clinical scenarios. For illustration purposes, we apply the proposed method to design a randomized phase II immune‐oncology clinical trial. [ABSTRACT FROM AUTHOR]

Background: Heart failure (HF) admission is used as a study endpoint in clinical trials. However, it remains unclear whether it can be a valid surrogate endpoint for mortality. Objectives: To validate whether HF admission is a valid surrogate for mortality. Methods: In PubMed and EMBASE, randomized controlled trials (RCTs) of interventions to treat patients with heart failure at the enrolment were searched on 13 April 2022. We extracted RCTs in which event numbers of both HF admission and all‐cause mortality were reported as either primary or secondary outcomes. Trial‐level correlations (R‐squared) between HF admission and mortality were assessed. We performed subgroup analyses by study year, follow‐up duration, baseline HF with reduced ejection fraction (HFrEF) or HF with preserved ejection fraction (HFpEF), and whether the intervention was pharmacological. We followed the Preferred Reporting Items for Systematic Reviews and Meta‐analyses guideline. Results: A total of 117 RCTs met the criteria for inclusion. Overall, the trial‐level R‐squared between HF admission and all‐cause mortality was 0.39 (95% confidence interval (CI), 0.26 to 0.53). However, in the subgroup analyses, the trial‐level R‐squared was increased when the follow‐up duration was ≥24 months (0.70 [95% CI: 0.55, 0.85]), when intervention was pharmacological (0.51 [95% CI: 0.34, 0.68]) and when the baseline HF type was HFrEF (0.57 [95% CI: 0.42, 0.73]). Conclusions: Our findings indicate that HF admission may not always be a valid surrogate for mortality in patients with HF. Rather, the surrogacy of HF admission may be dependent on clinical background and interventions. [ABSTRACT FROM AUTHOR]

Background and purpose: Spinal muscular atrophy (SMA) is caused by reduced levels of survival of motor neuron (SMN) protein due to deletions and/or mutations in the SMN1 gene. Risdiplam is an orally administered molecule that modifies SMN2 pre‐mRNA splicing to increase functional SMN protein. Methods: SUNFISH Part 1 was a dose‐finding study conducted in 51 individuals with types 2 and 3 SMA aged 2–25 years. A dose‐escalation method was used to identify the appropriate dose for the subsequent pivotal Part 2. Individuals were randomized (2:1) to risdiplam or placebo at escalating dose levels for a minimum 12‐week, double‐blind, placebo‐controlled period, followed by treatment for 24 months. The dose selection for Part 2 was based on safety, tolerability, pharmacokinetic, and pharmacodynamic data. Exploratory efficacy was also measured. Results: There was no difference in safety findings for all assessed dose levels. A dose‐dependent increase in blood SMN protein was observed; a median twofold increase was obtained within 4 weeks of treatment initiation at the highest dose level. The increase in SMN protein was sustained over 24 months of treatment. Exploratory efficacy showed improvement or stabilization in motor function. The pivotal dose selected for Part 2 was 5 mg for patients with a body weight ≥20 kg or 0.25 mg/kg for patients with a body weight <20 kg. Conclusions: SUNFISH Part 1 demonstrated a twofold increase in SMN protein after treatment with risdiplam. The observed safety profile supported the initiation of the pivotal Part 2 study. The long‐term efficacy and safety of risdiplam are being assessed with ongoing treatment. [ABSTRACT FROM AUTHOR]