Search

Purpose: To compare the outcomes of immediate and delayed implant placement with bone-level tapered implants. Materials and Methods: In this post-market, multicenter prospective randomized controlled study with a primary endpoint of 1 year, 53 patients were randomized to receive either immediate implant placement (test group) or delayed implant placement (control group). The mean crestal bone level changes from implant loading to 12 months postloading were measured using standardized digital periapical radiographs. Changes in facial plate thickness (as measured on CBCT images), implant success and survival, implant stability, soft tissue changes, patient-centered outcomes, and adverse events were measured to assess outcomes between the test and control treatments at 12 months postloading. Results: Of the original 53 patients, 46 patients completed the study (23 in each group). Mean bone changes from loading to the 12-month follow-up were recorded with no statistically significant difference (P = .950) between the groups. The hypothesis was confirmed that immediate implant placement (test) in extraction sockets produces in similar outcomes as delayed placement (control). The test group was found to be similar to the control group (P = .022) in terms of mean changes in facial plate thickness. Implant survival and success were 95.8% in the test group and 92% in the control group. Stability in the control group was superior at the time of surgery, but there was no difference between the groups at implant loading, producing a nonsignificant P value of .563). Conclusions: This randomized controlled multicenter study showed comparable outcomes 1 year after prosthetic loading in the immediate and delayed implant placement groups. [ABSTRACT FROM AUTHOR]

Preclinical studies indicate that diverse muscarinic receptor antagonists, acting via the M1 sub-type, promote neuritogenesis from sensory neurons in vitro and prevent and/or reverse both structural and functional indices of neuropathy in rodent models of diabetes. We sought to translate this as a potential therapeutic approach against structural and functional indices of diabetic neuropathy using oxybutynin, a muscarinic antagonist approved for clinical use against overactive bladder. Studies were performed using sensory neurons maintained in vitro, rodent models of type 1 or type 2 diabetes and human subjects with type 2 diabetes and confirmed neuropathy. Oxybutynin promoted significant neurite outgrowth in sensory neuron cultures derived from adult normal rats and STZ-diabetic mice, with maximal efficacy in the 1-100 nmol/l range. This was accompanied by a significantly enhanced mitochondrial energetic profile as reflected by increased basal and maximal respiration and spare respiratory capacity. Systemic (3-10 mg/kg/day s.c.) and topical (3% gel daily) oxybutynin reversed paw heat hypoalgesia in the STZ and db/db mouse models of diabetes and reversed paw tactile allodynia in STZ-diabetic rats. Loss of nerve profiles in the skin and cornea of db/db mice was also prevented by daily topical delivery of 3% oxybutynin for 8 weeks. A randomized, double-blind, placebo-controlled interventional trial was performed in subjects with type 2 diabetes and established peripheral neuropathy. Subjects received daily topical treatment with 3% oxybutynin gel or placebo for 6 months. The a priori designated primary endpoint, significant change in intra-epidermal nerve fibre density (IENFD) in skin biopsies taken before and after 20 weeks of treatments, was met by oxybutynin but not placebo. Secondary endpoints showing significant improvement with oxybutynin treatment included scores on clinical neuropathy, pain and quality of life scales. This proof-of-concept study indicates that muscarinic antagonists suitable for long-term use may offer a novel therapeutic opportunity for treatment of diabetic neuropathy. Trial registry number: NCT03050827.

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]

Purpose: In the context of clinical research, there is an increasing need for new study designs that help to incorporate already available data. With the help of historical controls, the existing information can be utilized to support the new study design, but of course, inclusion also carries the risk of bias in the study results. Methods: To combine historical and randomized controls we investigate the Fill-it-up-design, which in the first step checks the comparability of the historical and randomized controls performing an equivalence pre-test. If equivalence is confirmed, the historical control data will be included in the new RCT. If equivalence cannot be confirmed, the historical controls will not be considered at all and the randomization of the original study will be extended. We are investigating the performance of this study design in terms of type I error rate and power. Results: We demonstrate how many patients need to be recruited in each of the two steps in the Fill-it-up-design and show that the family wise error rate of the design is kept at 5 % . The maximum sample size of the Fill-it-up-design is larger than that of the single-stage design without historical controls and increases as the heterogeneity between the historical controls and the concurrent controls increases. Conclusion: The two-stage Fill-it-up-design represents a frequentist method for including historical control data for various study designs. As the maximum sample size of the design is larger, a robust prior belief is essential for its use. The design should therefore be seen as a way out in exceptional situations where a hybrid design is considered necessary. [ABSTRACT FROM AUTHOR]

AbstractPurposeMaterials and methodsResultsConclusionsTo evaluate the efficacy of an immersive movement visualization intervention in patients with hemophilia and hemophilic knee arthropathy.Randomized, single-blind clinical study. Twenty-eight patients with hemophilia were recruited. Patients were randomized to an experimental group (four weeks of immersive movement visualization) and a control group (no intervention). The intensity of pain, pressure pain threshold in the knee, tibialis anterior muscle, lower back level, conditioned pain modulation, range of knee motion, and lower limb functionality were evaluated.There were statistically significant differences in the intergroup effect on knee pain intensity (F = 23.71; p < 0.001) and lower limb functionality (F = 7.11; p = 0.003). 42.86% of the patients in the experimental group exhibited changes greater than the minimum detectable change (MDC) in functionality. 39.29% of the patients subject to the intervention experienced changes greater than the MDC in the knee pressure pain threshold.Immersive motion visualization can improve the intensity of joint pain and functionality in patients with hemophilic knee arthropathy. Functionality, pressure pain threshold, and pain intensity improved in those patients who conducted immersive movement visualization.Implications for rehabilitationImmersive visualization of movement significantly improves intensity of joint pain, functionality, pressure pain threshold, joint health, and conditioned pain modulation in patients with hemophilic knee arthropathy.The fact that it is a therapy without potential aversive stimuli makes it a possible access pathway for patients with high levels of kinesiophobia and/or catastrophism.This low-cost, home-based technology allows its use in patients far from hemophilia reference centers or with difficult access to physiotherapy treatments.The immersive visualization of movement influences the democratization of treatment, in accordance with the WHO's Sustainable Development Goal 3 (health and well-being for all).Immersive visualization of movement significantly improves intensity of joint pain, functionality, pressure pain threshold, joint health, and conditioned pain modulation in patients with hemophilic knee arthropathy.The fact that it is a therapy without potential aversive stimuli makes it a possible access pathway for patients with high levels of kinesiophobia and/or catastrophism.This low-cost, home-based technology allows its use in patients far from hemophilia reference centers or with difficult access to physiotherapy treatments.The immersive visualization of movement influences the democratization of treatment, in accordance with the WHO's Sustainable Development Goal 3 (health and well-being for all). [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]

To compare the success rates of probing with or without monocanalicular intubation, and/or inferior turbinate fracture in resolving simple congenital nasolacrimal duct obstruction (CNLDO). A randomized, double-blind clinical trial was conducted on children aged 12–36 months exhibiting symptoms of epiphora and/or mucous discharge along with a positive fluorescein dye disappearance test (DDT). Patients were randomly assigned to one of the following interventions: (1) probing; (2) probing and monocanalicular intubation; (3) probing and inferior turbinate fracture; (4) probing, inferior turbinate fracture, and monocanalicular intubation. Participants were categorized into two age groups (12–24 months and 24–36 months) and assessed for resolution of CNLDO three months post-surgery. Success was defined as the absence of epiphora or mucopurulent discharge and a negative DDT. Among the 201 participants, 51 underwent probing alone, 53 underwent probing with intubation, 47 underwent probing with turbinate fracture, and 50 underwent probing with turbinate fracture and intubation. No significant differences were observed in age, gender, or laterality of the disease between the groups (Ps > 0.05). While there was no significant difference in success rates among interventions in both age groups (Ps > 0.05), patients aged 24–36 months who underwent interventions involving intubation exhibited a significantly higher success rate compared to those without intubation (93.0% vs. 76.2%; P = 0.018). However, this difference was not observed in patients aged 12–24 months (95.7% vs. 92.9%; P = 0.551). Incorporating interventions such as intubation and/or turbinate fracture alongside conventional probing does not significantly alter the success rate of simple CNLDO resolution in children aged 12–24 months. However, older patients (24–36 months) may derive greater benefits from interventions involving intubation. [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]

Ustekinumab (UST) is a safe and effective treatment for moderate-to-severe psoriasis. To compare efficacy, safety, pharmacokinetics (PK), and immunogenicity of the proposed UST biosimilar SB17 with reference UST in subjects with moderate-to-severe plaque psoriasis. In this randomized double-blind study, subjects were randomized to receive 45 mg of SB17 or UST subcutaneously at week 0, 4, and every 12 weeks. The primary endpoint was the percent change from baseline in Psoriasis Area and Severity Index at week 12 with an equivalence margin of [−15%, 15%]. Other secondary efficacy, safety, PK, and immunogenicity endpoints were measured through week 28. Two hundred forty-nine subjects were randomized to SB17, 254 to UST. Adjusted difference of Psoriasis Area and Severity Index change from baseline at week 12 of −0.6% (95% confidence interval; −3.780, 2.579) was within the equivalence margin. Physician's Global Assessment and Dermatology Life Quality Index were also comparable. Overall treatment-emergent adverse events were comparable (SB17: 48.2%, UST: 48.8%). The overall incidence of antidrug antibodies up to Week 28 was 13.3% with SB17 and 39.4% with UST. Data were only through week 28. SB17 was clinically biosimilar to UST up to week 28. [ABSTRACT FROM AUTHOR]

Long-term clinical outcomes of catheter ablation (CA) compared to thoracoscopic surgical ablation (SA) to treat patients with long-standing persistent atrial fibrillation (LSPAF) are not known. The purpose of this study was to compare the long-term (36-month) clinical efficacy, quality of life, and cost-effectiveness of SA and CA in LSPAF. Participants were followed up for 3 years using implantable loop recorders and questionnaires to assess the change in quality of life. Intention-to-treat analyses were used to report the findings. Of the 115 patients with LSPAF treated, 104 (90.4%) completed 36-month follow-up [CA: n = 57 (95%); SA: n = 47 (85%)]. After a single procedure without antiarrhythmic drugs, 7 patients (12%) in the CA arm and 5 (11%) in the SA arm [hazard ratio 1.22; 95% confidence interval (CI) 0.81–1.83; P =.41] were free from atrial fibrillation/tachycardia (AF/AT) ≥30 seconds at 36 months. Thirty-three patients (58%) in the CA arm and 26 (55%) in the SA arm (hazard ratio 1.04; 95% CI 0.57–1.88; P =.91) had their AF/AT burden reduced by ≥75%. The overall impact on health-related quality of life was similar, with mean quality-adjusted life year estimates of 2.45 (95% CI 2.31–2.59) for CA and 2.32 (95% CI 2.13–2.52) for SA. Estimated costs were higher for SA (mean £24,682; 95% CI £21,746–£27,618) than for CA (mean £18,002; 95% CI £15,422–£20,581). In symptomatic LSPAF, CA and SA were equally effective at achieving arrhythmia outcomes (freedom from AF/AT ≥30 seconds and ≥75% burden reduction) after a single procedure without antiarrhythmic drugs. However, SA is significantly more costly than CA. [ABSTRACT FROM AUTHOR]

Copyright of Retos: Nuevas Perspectivas de Educación Física, Deporte y Recreación is the property of Federacion Espanola de Asociaciones de Docentes de Educacion Fisica and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: This randomized clinical trial evaluated the clinical outcomes of two surgical interventions for obesity treatment: single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI) and biliopancreatic diversion with duodenal switch (BPD/DS). The SADI procedure was developed as a response to the challenges posed by the BPD/DS procedure, aiming to enhance surgical efficiency, minimize postoperative risks, and maintain therapeutic efficacy. The present study primarily focused on early complications and short-term results. Methods: Fifty-six patients with a body mass index (BMI) ranging from 42 to 72 kg/m2 were randomly assigned to either the SADI or BPD/DS procedure. Parameters compared included % excess weight loss (%EWL), % total weight loss (%TWL), length of hospital stay (LOS), re-admission rates, and complications. Results: Both groups had similar demographics and baseline characteristics. SADI had a mean operating time of 109 min, significantly shorter than BPD/DS at 139 min (p < 0.001). Early complications occurred in five patients in the SADI group and in four patients in the BPD/DS group with no mortality. Median LOS was 2 days for both SADI and BPD/DS. Within 30 days, one SADI patient and three BPD/DS patients required re-admission. Serious late complications necessitating reoperation were observed in three SADI and two BPD/DS patients. After 1 year, %EWL and %TWL were similar: SADI (81.8% ± 13.6% and 40.1% ± 5.9%) and BPD/DS (84.2% ± 14.0% and 41.6% ± 6.4%). Conclusion: This trial suggests that both the SADI and BPD/DS yield comparable weight loss outcomes after 1 year, with a notable risk profile. Trial Registration: NCT 03938571 (http://www.clinicaltrials.gov) [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]

Background: Postoperative atrial fibrillation (POAF) is a common and potentially serious complication post cardiac surgery. Hypomagnesaemia is common after cardiac surgery and recent evidence indicates that supplementation of magnesium may prevent POAF. We aim to investigate the effectiveness of continuous intravenous magnesium sulphate administration in the perioperative period to prevent POAF as compared to placebo. Methods: The (POMPAE) trial is a phase 2, single-center, double-blinded randomized superiority clinical study. It aims to assess the impact of perioperative continuous intravenous magnesium administration on the occurrence of cardiac surgery-related POAF. A total of 530 patients will be included. Eligible patients will be randomized in 1:1 ratio to the intervention or placebo group with stratification based on the presence of valvular surgery. The objective of the infusion is to maintain ionized magnesium levels between 1.5 and 2.0 mmol/L. Discussion: The primary outcome measure is the incidence of de novo POAF within the first 7 days following surgery, with censoring at hospital discharge. This trial may generate crucial evidence for the prevention of POAF and reduce clinical adverse events in patients following cardiac surgery. Trial registration: The POMPAE trial was registered at ClinicalTrials.gov under the following identifier NTC05669417, https://clinicaltrials.gov/ct2/show/NCT05669417. Registered on December 30, 2022. Protocol version: Version 3.3, dated 13–01-2023. [ABSTRACT FROM AUTHOR]

Background: After a stroke, damage to the part of the brain that controls movement results in the loss of motor function. Brain-computer interface (BCI)-based stroke rehabilitation involves patients imagining movement without physically moving while the system measures the perceptual-motor rhythm in the motor cortex. Visual feedback through virtual reality and functional electrical stimulation is provided simultaneously. The superiority of real BCI over sham BCI in the subacute phase of stroke remains unclear. Therefore, we aim to compare the effects of real and sham BCI on motor function and brain activity among patients with subacute stroke with weak wrist extensor strength. Methods: This is a double-blinded randomized controlled trial. Patients with stroke will be categorized into real BCI and sham BCI groups. The BCI task involves wrist extension for 60 min/day, 5 times/week for 4 weeks. Twenty sessions will be conducted. The evaluation will be conducted four times, as follows: before the intervention, 2 weeks after the start of the intervention, immediately after the intervention, and 4 weeks after the intervention. The assessments include a clinical evaluation, electroencephalography, and electromyography using motor-evoked potentials. Discussion: Patients will be categorized into two groups, as follows: those who will be receiving neurofeedback and those who will not receive this feedback during the BCI rehabilitation training. We will examine the importance of motor imaging feedback, and the effect of patients' continuous participation in the training rather than their being passive. [ABSTRACT FROM AUTHOR]

ObjectivesMethodsResultsConclusionThis study aimed to determine the clinical efficacy of Kinesiotaping (KT) combined with a rehabilitation program to reduce symptoms and functional limitations in patients with Rotator Cuff-Related Shoulder Pain (RCRSP) in Vietnam.In total, 82 participants who were diagnosed with RCRSP were randomly allocated into two groups. Both groups received a standard rehabilitation program; additionally, the intervention group was treated with KT. Outcomes, assessed at baseline, and 3, 7, and 14 days postintervention, included pain intensity (Visual Analogue Scale, VAS), functional disability (Shoulder Pain and Disability Index, SPADI), and active range of motion (ROM).The KT group exhibited significant improvements in all outcome measures. VAS scores decreased by an average of 13.3 points in the KT group at 14 days, which was notably greater than that in the control group (95% CI: −17.77 to −8.82). SPADI scores also improved significantly in the KT group, with reductions of −11.36, −15.27, and −13.3 at days 3, 7, and 14, respectively. Regarding ROM, the KT group showed notable improvements in flexion and external rotation, with flexion ROM differences of 10.78, 10.35, and 11.8 degrees at the respective time points. No significant changes were observed in the abduction or internal rotation ROM. After adjusting for age, baseline scores, and gender, there was a statistically significant interaction between Group and Time on the VAS, SPADI, and ROM abduction.Incorporating KT into a standard rehabilitation program for RCRSP demonstrated enhanced efficacy in reducing pain and improving shoulder function. The results suggest that KT can be a valuable component of the treatment regimen for RCRSP. [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]

The United States Veterans Affairs (VA) Health Care System has a strong history of conducting impactful oncology randomized clinical trials (RCTs). We developed a phase II/III RCT to test the use of metastasis-directed therapy in Veterans with oligometastatic prostate cancer (OMPC)—the first VA RCT in OMPC that leverages novel imaging and advanced radiotherapy techniques. To accomplish this, we developed a clinical trial network to conduct the study. In this manuscript, we describe several challenges we encountered in study development/conduct and our strategies to address them, with the goal of helping investigators establish robust study networks to conduct clinical trials. In the study start-up, we encountered challenges in timely site activation, and leveraged project management to maximize efficiency. Additionally, there were several changes in the clinical paradigms in imaging and treatment that led to protocol amendments to ensure maximum equipoise, recruitment, and impact of the study. Specifically, we amended the trial to add de novo OMPC patients (from initially only recurrent OMPC) and expanded the study to allow up to 10 metastases (from initially five). Finally, in order to maintain local study team engagement, we developed initiatives to maximize collaboration and add value to the overall clinical program through study participation. [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]

Introduction: This study aimed to evaluate glycemic outcomes in subphenotypes of type 2 diabetes (T2D) with HbA1c > 7.0%, previously on basal insulin (pre-BI) alone (≥ 42 U/day) or on basal-bolus therapy (pre-BB), and who were switched to either basal insulin glargine 300 U/mL (IGlar-300) or 100 U/mL (IGlar-100), with or without pre-prandial insulin. Methods: Participants from EDITION 2 (pre-BI, n = 785), and EDITION 1 (pre-BB, n = 792) trials were assigned retrospectively to subphenotypes of T2D: severe insulin deficient diabetes (SIDD), mild age-related diabetes (MARD), mild obesity diabetes (MOD), and severe insulin resistant diabetes (SIRD). Key efficacy and safety parameters were analyzed at baseline, and after 26 weeks, for IGlar-300 and IGlar-100 pooled groups according to subphenotypes. Outcomes were also compared with insulin-naïve subphenotypes on oral antihyperglycemic drugs (OADs) from the EDITION 3 trial (pre-OAD, n = 858). Results: Pre-BI and pre-BB treated subphenotypes with SIDD had a higher mean HbA1c (8.9% and 9.1%) at baseline compared to those of MARD (7.7% and 7.8%) and MOD (8.1% and 8.2%) and after 26 weeks remained above target HbA1c (7.7% and 8.0%) despite mean glargine doses of 0.7 to 1.0 U/kg/day and pre-prandial insulin use in the pre-BB SIDD subgroup. Pre-BB treated individuals with MARD and MOD achieved lower HbA1c levels (6.9% and 7.2%) than the pre-BI groups (7.3% and 7.5%) despite similar mean FPG levels (123–130 mg/dL). Only 19–22% of participants with SIDD achieved HbA1c < 7.0% compared to 33–51% with MARD and MOD, respectively. Pre-BI and pre-BB treated subphenotypes experienced more hypoglycemia than pre-OAD treated subphenotypes. Conclusion: Individuals with T2D assigned post hoc to the SIDD subphenotype achieved suboptimal glycemic control with glargine regimens including basal-bolus therapy, alerting clinicians to improve further diabetes treatment, particularly post-prandial glycemic control, in individuals with SIDD. [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]

Importance and objectives The current medical paradigm of evidence-based medicine relies on clinical guidelines derived from randomized clinical trials (RCTs), but these guidelines often overlook individual variations in treatment effects. Approaches have been proposed to develop models predicting the effects of individualized management, such as predictive allocation, individualizing treatment allocation. It is currently unknown whether widespread implementation of predictive allocation could result in better population-level outcomes over guideline-based therapy. We sought to simulate the potential effect of predictive allocation using data from previously conducted RCTs. Methods and results Data from 3 RCTs (positive trial, negative trial, trial stopped for futility) in pediatric cardiology were used in a computational simulation study to quantify the potential benefits of a personalized approach based on predictive allocation. Outcomes were compared when using a universal approach vs predictive allocation where each patient was allocated to the treatment associated with the lowest predicted probability of negative outcome. Compared to results from RCTs, predictive allocation yielded absolute risk reductions of 13.8% (95% confidence interval [CI] −1.9 to 29.5), 13.9% (95% CI 4.5-23.2), and 15.6% (95% CI 1.5-29.6), respectively, corresponding to a number needed to treat of 7.3, 7.2, and 6.4. The net benefit of predictive allocation was directly proportional to the performance of the prediction models and disappeared as model performance degraded below an area under the curve of 0.55. Discussion These findings highlight that predictive allocation could result in improved group-level outcomes, particularly when highly predictive models are available. These findings will need to be confirmed in simulations of other trials with varying conditions and eventually in RCTs of predictive vs guideline-based treatment allocation. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. This study focused on evaluating the impact of a Mediterranean-type diet combined with physical exercise on CVD risk factors of high-risk individuals. A randomized clinical trial (RCT) recruited individuals (≥50 years old) with no history of acute myocardial infarction, but with high CVD risk criteria according to the SCORE2/SCORE2 OP. Anthropometric and biochemical parameters were assessed at baseline and after 12 weeks of diet and exercise intervention. Participants were randomly assigned into 3 groups: no intervention group (Group 1a), physical exercise group (Group 1b), and physical exercise (±2 h/week) plus diet group (Group 2). Briefly, the dietary intervention was based on the principles of an isocaloric Mediterranean diet (MD), with seven main meals/week centered on plant-based foods (legumes and pulses). The combined effect of exercise and the diet showed significant decrease in WC (p = 0.002), BST (p < 0.001), visceral fat (p < 0.001), and TG (p = 0.029), compared with control groups. The intervention significantly increased legume intake (p < 0.001), as well as adherence to the MD, which associates with WC decrease (p = 0.024) and visceral fat (p = 0.017). A combined intervention of exercise and diet should be endorsed as an efficient modifier of cardiometabolic parameters. [ABSTRACT FROM AUTHOR]

Purpose: Although overall success rates for treating obstructive sleep apnea (OSA) with an oral appliance (OA) are high, they are significantly higher among females. To verify published data, the study's purpose was to evaluate a participant sample after one year of OA use. The primary outcome was treatment response, with responders defined as having an apnea-hypopnea index (AHI) < 10 at follow-up and/or reduced by ≥50% of baseline. Secondary measures were from standardized questionnaires. Methods: A sample of 314 participants, predominately with moderate-to-severe OSA, were enrolled and instructed to use an OA every night. At baseline and one-year follow-up, polygraphic recordings and questionnaires, including sleepiness (measured using the Epworth sleepiness scale) and quality-of-life (measured using the Functional Outcomes of Sleep Questionnaire), were collected. Results: Among the 314 participants, 192 completed the one-year evaluation: 51 females (27%) and 141 males (73%). Overall, OA treatment resulted in 78% and 77% responders among females and males, respectively. Neither the difference in improvement nor the absolute change in AHI differed significantly based on gender, at any OSA severity level. There were no significant gender differences in sleepiness or quality of life. Treatment-related adverse reactions were more common among females. Conclusion: Both females and males with OSA respond well to OA therapy, with nonsignificant gender differences in outcomes. Thus, the hypothesis that females respond better to OA treatment is rejected. [ABSTRACT FROM AUTHOR]

The ageing population creates concerns and challenges worldwide. The large number of older adults (aged over 65) in Hong Kong continues to rise as people live longer. This may result in heavy burdens on public services and problems such as a shortage of medical resources. The purpose of this study is to implement a physical literacy-based intervention among older adults in Hong Kong in order to achieve the goal of health promotion. A two-arm cluster randomized controlled trial will be employed in this proposed study. Ten daycare centers for the older adults in Hong Kong will be invited to participate in this study. The intervention group will receive functional fitness training and mastering physical literacy class twice a week with buddy peer support, and they will be asked to keep a reflective writing journal on a daily basis for 12 weeks in total. Participants will be evaluated at baseline (week 0), post-intervention (week 12), and at 6-week follow-up (week 18). This will consist of objective and self-reported measures covering elements within physical literacy (i.e., physical competence, motivation and confidence, knowledge and understanding) and also physical activity levels on an individual basis. The study intends to introduce a conceptual framework of physical literacy for the older adults through an intervention that allows older people to develop daily behaviour habits, which should promote active ageing for the older adults and greater self-esteem in later life. After this study, participants may share their positive experiences, and encourage their peers in the community to become physically literate in the future. In the long run, due to the feasibility and sustainability of these potential programs, this proposed study has the potential to connect seniors through social engagement and contribute to healthy living. Clinical trial approval from the National Library of Medicine (Reference number: NCT06137859). [ABSTRACT FROM AUTHOR]

Background: The Diabetes Telemedicine Mediterranean Diet (DiaTeleMed) Study is a fully remote randomized clinical trial evaluating personalized dietary management in individuals with type 2 diabetes (T2D). The study aims to test the efficacy of a personalized behavioral approach for dietary management of moderately controlled T2D, versus a standardized behavioral intervention that uses one-size-fits-all dietary recommendations, versus a usual care control (UCC). The primary outcome will compare the impact of each intervention on the mean amplitude of glycemic excursions (MAGE). Methods: Eligible participants are between 21 and 80 years of age diagnosed with moderately controlled T2D (HbA1c: 6.0 to 8.0%) and managed on lifestyle alone or lifestyle plus metformin. Participants must be willing and able to attend virtual counseling sessions and log meals into a dietary tracking smartphone application (DayTwo), and wear a continuous glucose monitor (CGM) for up to 12 days. Participants are randomized with equal allocation (n = 255, n = 85 per arm) to one of three arms: (1) Personalized, (2) Standardized, or (3) UCC. Measurements occur at 0 (baseline), 3, and 6 months. All participants receive isocaloric energy and macronutrient targets to meet Mediterranean diet guidelines, in addition to 14 intervention contacts over 6 months (4 weekly then 10 biweekly) to cover diabetes self-management education. The first 4 UCC intervention contacts are delivered via synchronous videoconferences followed by educational video links. Participants in Standardized receive the same educational content as those in the UCC arm, following the same schedule. However, all intervention contacts are conducted via synchronous videoconferences, paired with Social Cognitive Theory (SCT)-based behavioral counseling, plus dietary self-monitoring of planned meals using a mobile app that provides real-time feedback on calories and macronutrients. Participants in the Personalized arm receive all elements of the Standardized intervention, in addition to real-time feedback on predicted post-prandial glycemic response (PPGR) to meals and snacks logged into the mobile app. Discussion: The DiaTeleMed Study aims to address an important gap in the current landscape of precision nutrition by determining the contributions of behavioral counseling and personalized nutrition recommendations on glycemic control in individuals with T2D. The fully remote methodology of the study allows for scalability and innovative delivery of personalized dietary recommendations at a population level. Trial registration: ClinicalTrials.gov NCT05046886. Registered on September 16, 2021. [ABSTRACT FROM AUTHOR]

In recent years, laminate veneer restorations should be considered as a minimally invasive treatment option for several aesthetic reasons. This study compared direct composite veneers' and indirect ceramic laminate veneers' longevity in multiple diastema closures. A total of 28 patients with a mean age of 26 years received 60 direct resin composite (Estelite Asteria; n = 14) and 60 indirect ceramic veneers (IPS e.max Press; n = 14) on the maxillary anterior teeth with diastema closure. Veneers were evaluated at baseline and thereafter every 6 months for up to 2 years using USPHS criteria. Data were analyzed with Fisher's exact and chi-squared tests, while Kaplan–Meier curve was used to assess time to event. In total, three failures were observed in the form of debonding (n = 1) and fracture (n = 2) in the indirect ceramic veneers. No significant difference was observed between the survival rates of composite and ceramic veneers (Estelite Asteria: 93.4%, IPS e.max Press: 95%; p > 0.05). The overall survival rate was 94.2% (Kaplan–Meier). Staining (n = 11) and roughness (n = 14) were frequently observed for the resin composite veneers up to the final recall. Thereby, the preliminary results from this clinical trial comparing two veneer materials indicated that their survival rates were statistically similar. However, surface quality changes were more frequent in the composite veneer material. [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]

Background: One single-center randomized clinical trial showed that INTELLiVENT-adaptive support ventilation (ASV) is superior to conventional ventilation with respect to the quality of ventilation in post-cardiac surgery patients. Other studies showed that this automated ventilation mode reduces the number of manual interventions at the ventilator in various types of critically ill patients. In this multicenter study in patients post-cardiac surgery, we test the hypothesis that INTELLiVENT-ASV is superior to conventional ventilation with respect to the quality of ventilation. Methods: "POStoperative INTELLiVENT-adaptive support VEntilation in cardiac surgery patients II (POSITiVE II)" is an international, multicenter, two-group randomized clinical superiority trial. In total, 328 cardiac surgery patients will be randomized. Investigators screen patients aged > 18 years of age, scheduled for elective cardiac surgery, and expected to receive postoperative ventilation in the ICU for longer than 2 h. Patients either receive automated ventilation by means of INTELLiVENT-ASV or ventilation that is not automated by means of a conventional ventilation mode. The primary endpoint is quality of ventilation, defined as the proportion of postoperative ventilation time characterized by exposure to predefined optimal, acceptable, and critical (injurious) ventilatory parameters in the first two postoperative hours. One major secondary endpoint is ICU team staff workload, captured by the ventilator software collecting manual settings on alarms. Patient-centered endpoints include duration of postoperative ventilation and length of stay in ICU. Discussion: POSITiVE II is the first international, multicenter, randomized clinical trial designed to confirm that POStoperative INTELLiVENT-ASV is superior to non-automated conventional ventilation and secondary to determine if this closed-loop ventilation mode reduces ICU team staff workload. The results of POSITiVE II will support intensive care teams in their choices regarding the use of automated ventilation in postoperative care of uncomplicated cardiac surgery patients. Trial registration: Clinicaltrials.gov NCT06178510. Registered on December 4, 2023. [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]

• This study examines an immune mechanism that contributes to the antidepressant effects of whole-body hyperthermia. • Whole-body hyperthermia led to an acute, time-limited increase in the ratio of interleukin-6 (IL-6):soluble IL-6 receptor. • Increased ratio of IL-6:soluble IL-6 receptor was associated with the anti-depressant effect of whole-body hyperthermia. There is urgent need for novel antidepressant treatments that confer therapeutic benefits via engagement with identified mechanistic targets. The objective of the study was to determine whether activation of the classical anti-inflammatory interleukin-6 signaling pathways is associated with the antidepressant effects of whole-body hyperthermia. A 6-week, randomized, double-blind study compared whole-body hyperthermia with a sham condition in a university-based medical center. Medically healthy participants aged 18–65 years who met criteria for major depressive disorder, were free of psychotropic medication use, and had a baseline 17-item Hamilton Depression Rating Scale score ≥ 16 were randomized with 1-to-1 allocation in blocks of 6 to receive whole-body hyperthermia or sham. Of 338 individuals screened, 34 were randomized, 30 received interventions and 26 had ≥ 2 blood draws and depressive symptom assessments. Secondary data analysis examined change in the ratio of IL-6:soluble IL-6 receptor pre-intervention, post-intervention, and at weeks 1 and 4. Hierarchical linear modeling tested whether increased IL-6:soluble IL-6 receptor ratio post-intervention was associated with decreased depressive symptom at weeks 1, 2, 4 and 6 for those randomized to whole-body hyperthermia. Twenty-six individuals were randomized to whole-body hyperthermia [ n = 12; 75 % female; age = 37.9 years (SD = 15.3) or sham [ n = 14; 57.1 % female; age = 41.1 years (SD = 12.5). When compared to the sham condition, active whole-body hyperthermia only increased the IL-6:soluble IL-6 receptor ratio post-treatment [ F (3,72) = 11.73, p <.001], but not pre-intervention or at weeks 1 and 4. Using hierarchical linear modeling, increased IL-6:sIL-6R ratio following whole-body hyperthermia moderated depressive symptoms at weeks 1, 2, 4 and 6, such that increases in the IL-6:soluble IL-6 receptor ratio were associated with decreased depressive symptoms at weeks 1, 2, 4 and 6 for those receiving the active whole-body hyperthermia compared to sham treatment (B = –229.44 , t = -3.82, p <.001). Acute activation of classical intereukin-6 signaling might emerge as a heretofore unrecognized novel mechanism that could be harnessed to expand the antidepressant armamentarium. [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]

The aim of this study was to identify a Bifidobacterium strain that improves the performance of Limosilactobacillus reuteri DSM 17938. Initial tests showed that Bifidobacterium longum subsp. longum strains boosted the growth of DSM 17938 during in vivo-like conditions. Further characterization revealed that one of the strains, BG-L47, had better bile and acid tolerance compared to BG-L48, as well as mucus adhesion compared to both BG-L48 and the control strain BB536. BG-L47 also had the capacity to metabolize a broad range of carbohydrates and sugar alcohols. Mapping of glycoside hydrolase (GH) genes of BG-L47 and BB536 revealed many GHs associated with plantfiber utilization. However, BG-L47 had a broader phenotypic fiber utilization capacity. In addition, B. longum subsp. longum cells boosted the bioactivity of extracellular membrane vesicles (MV) produced by L. reuteri DSM 17938 during co-cultivation. Secreted 5'-nucleotidase (5'NT), an enzyme that converts AMP into the signal molecule adenosine, was increased in MV boosted by BG-L47. The MV exerted an improved antagonistic effect on the pain receptor transient receptor potential vanilloid 1 (TRPV1) and increased the expression of the immune development markers IL-6 and IL-1ß in a peripheral blood mononuclear cell (PBMC) model. Finally, the safety of BG-L47 was evaluated both by genome safety assessment and in a human safety study. Microbiota analysis showed that the treatment did not induce significant changes in the composition. In conclusion, B. longum subsp. longum BG-L47 has favorable physiological properties, can boost the in vitro activity of L. reuteri DSM 17938, and is safe for consumption, making it a candidate for further evaluation in probiotic studies. [ABSTRACT FROM AUTHOR]

Background: Bladder drainage is systematically used in rectal cancer surgery; however, the optimal type of drainage, transurethral catheterization (TUC) or suprapubic catheterization (SPC), is still controversial. The aim was to compare the rates of urinary tract infection on the fourth postoperative day (POD4) between TUC and SPC, after rectal cancer surgery regardless of the day of removal of the urinary drain. Methods: This randomized clinical trial in 19 expert colorectal surgery centers in France and Belgium was performed between October 2016 and October 2019 and included 240 men (with normal or subnormal voiding function) undergoing mesorectal excision with low anastomosis for rectal cancer. Patients were followed at postoperative days 4, 30, and 180. Results: In 208 patients (median age 66 years [IQR 58–71]) randomized to TUC (n = 99) or SPC (n = 109), the rate of urinary infection at POD4 was not significantly different whatever the type of drainage (11/99 (11.1%) vs. 8/109 (7.3%), 95% CI, − 4.2% to 11.7%; p = 0.35). There was significantly more pyuria in the TUC group (79/99 (79.0%) vs. (60/109 (60.9%), 95% CI, 5.7–30.0%; p = 0.004). No difference in bacteriuria was observed between the groups. Patients in the TUC group had a shorter duration of catheterization (median 4 [2–5] vs. 4 [3–5] days; p = 0.002). Drainage complications were more frequent in the SPC group at all followup visits. Conclusions: TUC should be preferred over SPC in male patients undergoing surgery for mid and/or lower rectal cancers, owing to the lower rate of complications and shorter duration of catheterization. Trial registration: ClinicalTrials.gov identifier NCT02922647. [ABSTRACT FROM AUTHOR]

Background: Recruiting participants with cardiovascular disease into research during the COVID-19 pandemic was challenging, particularly those at risk of health disparities. Objective: During the pandemic, 12 cohorts of older women with cardiovascular disease were recruited from cardiology clinics into a lifestyle intervention trial to prevent cognitive decline. Objectives were to (a) describe the results of modified recruitment/screening strategies to overcome pandemic-related challenges and (b) evaluate differences in age, race, and ethnicity between patients recruited/randomized, recruited/not randomized (entered recruitment but not randomized because of being ineligible or not interested), and not recruited (clinic patients who met preliminary criteria but did not enter recruitment). Methods: This was a cross-sectional descriptive analysis. In-person study strategies proposed before the COVID-19 pandemic were modified before study onset (September 2020). Women 65 years or older with cardiovascular disease were recruited from cardiology clinics by clinicians, posted flyers, and letters mailed to patients randomly selected from electronic health record data extractions. Patients were classified as recruited/randomized, recruited/not randomized, and not recruited. Results: Of 5719 patients potentially eligible, 1689 patients entered recruitment via referral (49.1%), posted flyers (0.5%), or mailed letters (50.3%), and 253 patients were successfully recruited/randomized. Recruited/randomized participants were, on average, 72.4 years old (range, 65–90 years old), non-Hispanic White (54.2%), non-Hispanic Black (38.3%), Hispanic/Latinx (1.6%), and other/not reported (5.1%). The recruited/randomized group was significantly younger with fewer patients of Hispanic/Latinx ethnicity compared with those not recruited. Conclusions: During the pandemic, all recruitment/screening goals were met using modified strategies. Differences in sociodemographic representation indicate a need for tailored strategies. [ABSTRACT FROM AUTHOR]

Splanchnic vasoconstriction augments transfer of blood volume from the abdomen into the thorax, which may increase filling pressures and hemodynamic congestion in patients with noncompliant hearts. Therapeutic interruption of splanchnic nerve activity holds promise to reduce hemodynamic congestion in patients with heart failure with preserved ejection fraction (HFpEF). Here we describe (1) the rationale and design of the first sham-controlled, randomized clinical trial of splanchnic nerve ablation for HFpEF and (2) the 12-month results of the lead-in (open-label) trial's participants. REBALANCE-HF is a prospective, multicenter, randomized, double-blinded, sham-controlled clinical trial of endovascular, transcatheter, right-sided greater splanchnic nerve ablation for volume management (SAVM) in patients with HFpEF. The primary objectives are to evaluate the safety and efficacy of SAVM and identify responder characteristics to inform future studies. The trial consists of an open-label lead-in phase followed by the randomized, sham-controlled phase. The primary efficacy endpoint is the reduction in pulmonary capillary wedge pressure (PCWP) at 1-month follow-up compared to baseline during passive leg raise and 20W exercise. Secondary and exploratory endpoints include health status (Kansas City Cardiomyopathy Questionnaire), 6-minute walk test distance, New York Heart Association class, and NTproBNP levels at 3, 6 and 12 months. The primary safety endpoint is device- or procedure-related serious adverse events at the 1-month follow-up. The lead-in phase of the study, which enrolled 26 patients with HFpEF who underwent SAVM, demonstrated favorable safety outcomes and reduction in exercise PCWP at 1 month post-procedure and improvements in all secondary endpoints at 6 and 12 months of follow-up. The randomized phase of the trial (n = 44 SAVM; n = 46 sham) has completed enrollment, and follow-up is ongoing. REBALANCE-HF is the first sham-controlled randomized clinical trial of greater splanchnic nerve ablation in HFpEF. Initial 12-month open-label results are promising, and the results of the randomized portion of the trial will inform the design of a future pivotal clinical trial. SAVM may offer a promising therapeutic option for patients with HFpEF. NCT04592445 [ABSTRACT FROM AUTHOR]

The New Nordic Renal Diet (NNRD) is a whole-food approach, tailored to meet recommended guidelines in patients with moderate chronic kidney disease (stage 3b-4). The NNRD improved various metabolic and physiological endpoints during a 26-week randomized controlled study. Here, we examined the effect of dietary intervention on health-related quality of life (HRQoL). Sixty participants were recruited (NNRD group n = 30, control group n = 30) and 58 completed the study. During the intervention, the NNRD group received food boxes, and recipes once a week. The control group continued their habitual diet. HRQoL was examined at baseline and at the end of the intervention using the validated EuroQol-5D-5L, including a 5-point scale Likert questionnaire at the end of the intervention. Assessed by the EuroQol-5D-5L questionnaire, the NNRD group experienced a reduction in pain/discomfort during the intervention by 26% [-0.44 points (95% CI; -0.73, -0.16)], compared with no change in the control group [0.25 points (95% CI; -0.02, 0.53)] and a between-group difference of -0.70 points (95% CI; -1.03, -0.37, p < 0.001). A larger decrease of body fat mass was associated with a larger decrease in pain/discomfort (p = 0.014). In addition, the NNRD group reported an overall improvement in conducting usual daily activities by 23% [-0.30-point (95% CI; -0.50, -0.11)], while no change was seen in the control group [−0.02 points (95% CI; -0.21, 0.17)], with a between-group difference -0.28 points (95% CI; -0.51, -0.06, p = 0.014). A larger decrease in 24 h urine phosphorus excretion, used as a marker of compliance, was associated with a larger improvement in conducting usual daily activities (p = 0.036). The NNRD group had a clinically relevant improvement in various HRQoL outcomes. [ABSTRACT FROM AUTHOR]

In preclinical studies, a new antituberculosis drug regimen markedly reduced the time required to achieve relapse-free cure. This study aimed to preliminarily evaluate the efficacy and safety of this four-month regimen, consisting of clofazimine, prothionamide, pyrazinamide and ethambutol, with a standard six-month regimen in patients with drug-susceptible tuberculosis. An open-label pilot randomized clinical trial was conducted among the patients with newly diagnosed bacteriologically-confirmed pulmonary tuberculosis. The primary efficacy end-point was sputum culture negative conversion. Totally, 93 patients were included in the modified intention-to-treat population. The rates of sputum culture conversion were 65.2% (30/46) and 87.2% (41/47) for short-course and standard regimen group, respectively. There was no difference on two-month culture conversion rates, time to culture conversion, nor early bactericidal activity (P > 0.05). However, patients on short-course regimen were observed with lower rates of radiological improvement or recovery and sustained treatment success, which was mainly attributed to higher percent of patients permanently changed assigned regimen (32.1% vs. 12.3%, P = 0.012). The main cause for it was drug-induced hepatitis (16/17). Although lowering the dose of prothionamide was approved, the alternative option of changing assigned regimen was chosen in this study. While in per-protocol population, sputum culture conversion rates were 87.0% (20/23) and 94.4% (34/36) for the respective groups. Overall, the short-course regimen appeared to have inferior efficacy and higher incidence of hepatitis but desired efficacy in per-protocol population. It provides the first proof-of-concept in humans of the capacity of the short-course approach to identify drug regimens that can shorten the treatment time for tuberculosis.

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.

BackgroundWith the emergence of SARS-CoV-2 variants resistant to monoclonal antibody therapies and limited global access to therapeutics, the evaluation of novel therapeutics to prevent progression to severe COVID-19 remains a critical need.MethodsSafety, clinical and antiviral efficacy of inhaled interferon-β1a (SNG001) were evaluated in a phase II randomized controlled trial on the ACTIV-2/A5401 platform (ClinicalTrials.govNCT04518410). Adult outpatients with confirmed SARS-CoV-2 infection within 10 days of symptom onset were randomized and initiated either orally inhaled nebulized SNG001 given once daily for 14 days (n = 110) or blinded pooled placebo (n = 110) between February 10 and August 18, 2021.FindingsThe proportion of participants reporting premature treatment discontinuation was 9% among SNG001 and 13% among placebo participants. There were no differences between participants who received SNG001 or placebo in the primary outcomes of treatment emergent Grade 3 or higher adverse events (3.6% and 8.2%, respectively), time to symptom improvement (median 13 and 9 days, respectively), or proportion with unquantifiable nasopharyngeal SARS-CoV-2 RNA at days 3 (28% [26/93] vs. 39% [37/94], respectively), 7 (65% [60/93] vs. 66% [62/94]) and 14 (91% [86/95] vs. 91% [83/81]). There were fewer hospitalizations with SNG001 (n = 1; 1%) compared with placebo (n = 7; 6%), representing an 86% relative risk reduction (p = 0.07). There were no deaths in either arm.InterpretationIn this trial, SNG001 was safe and associated with a non-statistically significant decrease in hospitalization for COVID-19 pneumonia.FundingThe ACTIV-2 platform study is funded by the NIH. Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number UM1 AI068634, UM1 AI068636 and UM1 AI106701. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.