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Study designRetrospective cohort study of prospectively accrued data.ObjectiveTo evaluate a large, prospective, multicentre dataset of surgically treated degenerative cervical myelopathy (DCM) cases on the contemporary risk of C5 palsy with surgical approach.Summary of background dataThe influence of surgical technique on postoperative C5 palsy after decompression for DCM is intensely debated. Comprehensive, covariate-adjusted analyses are needed using contemporary data.MethodsPatients with moderate to severe DCM were prospectively enrolled in the multicenter, randomized, Phase III CSM-Protect clinical trial and underwent either anterior or posterior decompression between Jan 31, 2012 and May 16, 2017. The primary outcome was the incidence of postoperative C5 palsy, defined as the onset of muscle weakness by at least one grade in manual muscle test at the C5 myotome with slight or absent sensory disruption after cervical surgery. Two comparative cohorts were made based on the anterior or posterior surgical approach. Multivariate hierarchical mixed-effects logistic regression was used to estimate odds ratios (OR) with 95% confidence intervals (CI) for C5 palsy.ResultsA total of 283 patients were included, and 53.4% underwent posterior decompression. The total incidence of postoperative C5 palsy was 7.4% and was significantly higher in patients who underwent posterior decompression compared with anterior decompression (11.26% vs. 3.03%, P =0.008). After multivariable regression, the posterior approach was independently associated with greater than four times the likelihood of postoperative C5 palsy ( P =0.017). Rates of C5 palsy recovery were comparable between the two surgical approaches.ConclusionThe odds of postoperative C5 palsy are significantly higher after posterior decompression compared to anterior decompression for DCM. This may influence surgical decision-making when there is equipoise in deciding between anterior and posterior treatment options for DCM.Level of evidenceTherapeutic Level-II.

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.

Aims: We explored whether esketamine anesthesia during hysteroscopic surgery can reduce intraoperative hemodynamic fluctuations and improve patient benefit. Methods: 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. Results: 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. Conclusions: 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]

For decades the greatest goal of Parkinson's disease (PD) research has often been distilled to the discovery of treatments that prevent the disease or its progression. However, until recently only the latter has been realistically pursued through randomized clinical trials of candidate disease-modifying therapy (DMT) conducted on individuals after they received traditional clinical diagnosis of PD (i.e., tertiary prevention trials). Now, in light of major advances in our understanding of the prodromal stages of PD, as well as its genetics and biomarkers, the first secondary prevention trials for PD are beginning. In this review, we take stock of DMT trials to date, summarize the breakthroughs that allow the identification of cohorts at high risk of developing a traditional diagnosis of PD, and describe key design elements of secondary prevention trials and how they depend on the prodromal stage being targeted. These elements address whom to enroll, what interventions to test, and how to measure secondary prevention (i.e., slowed progression during the prodromal stages of PD). Although these design strategies, along with the biological definition, subtype classification, and staging of the disease are evolving, all are driven by continued progress in the underlying science and integrated by a broad motivated community of stakeholders. While considerable methodological challenges remain, opportunities to move clinical trials of DMT to earlier points in the disease process than ever before have begun to unfold, and the prospects for PD prevention are nowtangible. [ABSTRACT FROM AUTHOR]

Objective: In a randomized clinical trial, we evaluated whether the STIC (Systemic Therapy Inventory of Change) measurement and feedback system (MFS), the first MFS to explicitly integrate the family systems perspective, improved outcomes in individual, couple and family therapy. Method: Nine hundred and seventy clients seeking individual, couple or family therapy, entered therapy with 93 therapists at four sites in the Chicago metropolitan area. All therapists were trained with the STIC and participated in both Treatment as Usual (TAU) and TAU with the STIC (STIC). After agreeing to participate, clients were randomly assigned to TAU or STIC. Therapists did not know the condition to which a case was assigned, until just prior to the first session. Therapy was not time-limited or constrained, except for the use of the STIC in the STIC condition. All clients were evaluated on a non-STIC multi-systemic battery of widely used outcome measures pre-and-post therapy. Results: STIC clients improved more than TAU clients regardless of treatment modality or outcome measure. Clinically significant change was also greater for STIC than TAU clients across outcome measures. Conclusion: The STIC MFS holds promise for improving outcomes beyond TAU in individual, couple, and family therapy. [ABSTRACT FROM AUTHOR]

Objective: 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. Design: A randomized clinical trial with two study groups was utilized. Methods: 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. Results: 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. Conclusions: 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]

Borderline personality disorder (BPD) is a severe mental illness, with high rates of co-morbid depression and suicidality. Despite the importance of optimizing treatment in BPD, little is known about how neural processes relate to individual treatment response. This study examines how baseline regional brain blood oxygen level dependent (BOLD) activation during a functional magnetic resonance imaging (fMRI) task of emotion regulation is related to treatment response following a six-month randomized clinical trial of Dialectical Behavior Therapy (DBT) or Selective Serotonin Reuptake Inhibitor (SSRI) treatment. Unmedicated females with BPD (N = 37), with recent suicidal behavior or self-injury, underwent an fMRI task in which negative personal memories were presented and they were asked to distance (i.e., downregulate their emotional response) or immerse (i.e., experience emotions freely). Patients were then randomized to DBT (N = 16) or SSRI (N = 21) treatment, with baseline and post-treatment depression and BPD severity assessed. BOLD activity in prefrontal cortex, anterior cingulate, and insula was associated with distancing. Baseline BOLD during distancing in dorsolateral, ventrolateral, and orbital prefrontal cortex (dlPFC, vlPFC, OFC) differentially predicted depression response across treatment groups, with higher activity predicting better response in the SSRI group, and lower activity predicting better response in the DBT group. All female samples. Findings indicate that greater prefrontal engagement during emotion regulation may predict more antidepressant benefit from SSRIs, whereas lower engagement may predict better response to DBT. These results suggest different mechanisms of action for SSRI and DBT treatment, and this may allow fMRI to guide individualized treatment selection. • Borderline personality disorder (BPD) is associated with high rates of depression. • Neural processes may offer insight into predicting antidepressant response. • Prefrontal engagement differentially predicted response to SSRI and DBT treatment. • Examining prefrontal activity may allow for more individualized treatment in BPD. [ABSTRACT FROM AUTHOR]

Background: Sweet taste administration before dental injections helps to control associated pain in children. Aim: To evaluate the efficacy of using a sugar‐free flavor on pain perception during dental injections. Design: Children (n = 84) aged 4–9 (mean 6.71 ± 1.55) years who required buccal infiltration bilaterally participated in this split‐mouth randomized crossover study. On the test side (flavor visit), infiltration injections were applied after receiving a sugar‐free flavor. On the control side (no flavor visit), sterile water was administered. Demographic characteristics, body mass index (BMI), and sweet taste preference (STP) were recorded. Pain perception during injection was measured using heart rate (HR), sound, eyes, and motor (SEM) scale, and Wong–Baker Faces pain scale (WBFPS). Results: Most children had healthy weight (72.6%) and equal STP (32.1%). In the test side, mean HR during injection, HR differences before and during injection, and SEM scores were significantly lower (p <.001, for all). There was no significant difference in the WBFPS between both visits. Flavor had a significant effect on pain reduction (p =.001 for HR, p =.000 for SEM), whereas age, gender, BMI, STP, and treatment side did not. Treatment sequence had a significant effect on total SEM scores (p =.021); children who received the flavor during their first visit had lower SEM scores. Conclusion: Using a sugar‐free flavor before dental injections helps in reducing associated pain in children. [ABSTRACT FROM AUTHOR]

Background: Developing interventions for older adults with subjective cognitive decline (SCD) has the potential to prevent dementia in this at-risk group. Preclinical models indicate that Citrus-derived phytochemicals could benefit cognition and inflammatory processes, but results from clinical trials are still preliminary. The aim of this study is to determine the effects of long-term supplementation with Citrus peel extract on cognitive performance and inflammation in individuals with SCD. Methods: Eighty participants were randomly assigned to active treatment (400 mg of Citrus peel extract containing 3.0 mg of naringenin and 0.1 mg of auraptene) or placebo at 1:1 ratio for 36 weeks. The primary endpoint was the change in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total score across the 36-week trial period. Other cognitive outcomes included tests and scales evaluating verbal memory, attention, executive and visuospatial functions, and memory concerns. The secondary endpoint was the change of interleukin-8 (IL-8) levels over the 36-week trial period in a subsample of 60 consecutive participants. An Intention-to-treat approach with generalized linear mixed models was used for data analysis. Results: The RBANS total score showed significant improvement in both Citrus peel extract and placebo groups at 36 weeks (p for time <.001, d = 0.36, p time x treatment =.910). Significant time effects were also found in cognitive domains of short- and long-term verbal memory (p <.001) and scales of subjective memory (p <.01), with no significant time x treatment interaction. The largest effect sizes were observed in verbal memory in the placebo group (d = 0.69 in short-term, and d = 0.78 in long-term verbal memory). Increased IL-8 levels were found at 36-week follow-up in both Citrus peel extract and placebo groups (p for time =.010, d = 0.21, p time x treatment =.772). Adverse events were balanced between groups. Conclusions: In this randomized clinical trial, long-term Citrus peel extract supplementation did not show cognitive benefits over placebo in participants with SCD, possibly due to high placebo response. These findings might have specific implications for designing future nutraceutical trials in individuals experiencing SCD. Trial registration: The trial has been registered at the United States National Library of Medicine at the National Institutes of Health Registry of Clinical Trials under the code NCT04744922 on February 9th, 2021 (https://www.clinicaltrials.gov/ct2/show/NCT04744922). [ABSTRACT FROM AUTHOR]

AbstractBackgroundAimsMethodsResultsLimitationsConclusionsP-factor and mentalizing theory and research set perspectives for transdiagnostic psychiatric treatments.To test the effects of a low-cost mentalization-based health education program (the Thoughtful program) in an unselected waiting list population, from a psychiatric outpatient clinic in North Norway.Waiting list patients were randomized (1:1 allocation): 79 patients in the control group were offered standard individual assessment and treatment. Seventy-nine patients in the intervention group were offered a one-day (six-hour) group-based Thoughtful course, plus individual assessment, and treatment.During a 6-month follow-up period, the number of patients in active assessment and treatment was 66% higher in the control group than in the intervention group. Self-reported patient questionnaire scores on mentalizing, well-being and suicidal ideation scores showed no significant changes in the control group. In the intervention group, significant changes were reported: Mentalizing scores improved by 72% and well-being scores improved by 55%. Suicidal ideation scores were not significantly changed. No adverse effects were registered.The results from this study should be interpreted with caution because of a small population size and low questionnaire response rate. The follow up period was limited to 6 months. Transfer of program information from intervention group patients to control group patients could not be guaranteed. It may be considered a limitation that diagnostic pattern analysis was not included in the study.A low-cost transdiagnostic mentalization-based educational program in an outpatient psychiatry clinic may improve patient mentalizing and wellbeing without adverse effects and reduce the use of hospital services. [ABSTRACT FROM AUTHOR]

Background: The global effort to cure COVID-19 is still ongoing. Thus, a prospective, block-balanced, open-label, randomized controlled trial was conducted to evaluate how Tenofovir Alafenamide Fumarate affects hospitalized COVID-19 patients' outcomes. Methods: The intervention and control groups of 60 hospitalized COVID-19 patients were randomly allocated. Along with normal medication, the intervention group received 25 mg of tenofovir orally daily for seven days. The control group got normal therapy, including remdesivir and corticosteroids. ICU hospitalization duration, laboratory data, fever, dyspnea, arterial blood oxygen saturation with and without an oxygen face mask, mechanical ventilation, and mortality were the outcomes. Results: Sixty of 236 eligible patients between September 2020 and February 2021 were enrolled. The intervention group had a mean age (±SD) of 61.33 (±13.09) years and the control group 60.03 (±18.03). Sixteen (53.3%) intervention patients and 15 (50.0%) control patients were males. The intervention group had fewer mechanical ventilation and ICU days. Tenofovir Alafenamide Fumarate did not improve fever, dyspnea, oxygen saturation with or without a face mask or nasal cannula, or laboratory data including WBC, ESR, CRP, AST, ALT, AlkP, total and direct bilirubin, in COVID-19 patients. Conclusion: According to this pilot trial, Tenofovir Alafenamide Fumarate, along with conventional treatment, significantly reduced mechanical ventilation and ICU stay in COVID-19 patients. Further thorough research is necessary to verify this conclusion. [ABSTRACT FROM AUTHOR]

Background: Primary dysmenorrhea is a leading cause of chronic cyclic pelvic pain, contributing to a reduced quality of life and sleep disturbances in women. The objective of this study was to assess the effectiveness of transcutaneous tibial nerve stimulation (TTNS) in improving the quality of life, sleep, and overall health perceptions of participants compared to a control group of women with dysmenorrhea over short-term, medium-term, and long-term periods. Methods: A single-blind, controlled clinical trial was conducted, with participants randomly assigned to an experimental group (receiving TTNS) or a control group (receiving sham TTNS). Both groups underwent 12, weekly 30 min sessions using the NeuroTrac™ PelviTone electrostimulation device. Outcomes related to quality of life, sleep deficiency, and overall improvement were evaluated at three time points: short-term (post-treatment), medium-term (1–3 months), and long-term (6 months). Results: Of the 61 participants initially randomized (31 in the experimental group and 30 in the control group), 55 completed the study and were included in the final analysis. A statistically significant improvement was observed in the experimental group in both physical and mental health components, as measured by the SF-36v2® questionnaire, following 12 weeks of intervention, compared to the control group, persisting 6 months after the intervention. Additionally, statistically significant differences in overall improvement were noted between the two groups, as measured by the PGIC questionnaire at the end of treatment (p = 0.0103) and 6 months post-treatment (p = 0.0432). Conclusions: TTNS appears to be a safe and effective strategy for enhancing quality of life and overall health in women with PD, potentially reducing the reliance on pharmacological treatments or more invasive methods. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Methods Results Conclusions To examine the impact of fluocinonide 0.05% gel formulation for the topical treatment of oral lichen planus (OLP).Through an RCT design, 47 patients with OLP were randomly allocated for topical OLP treatment with fluocinonide 0.05% (n = 23) or placebo (n = 24). Patients were examined for OLP symptoms, signs, disease severity, and extension score changes over 6‐month follow‐up.After 6 months, in comparison with placebo, patients treated with fluocinonide experienced a significant reduction of OLP symptoms (p = 0.024), signs (p = 0.014), and OLP extension score (p = 0.028). The two‐way ANOVA estimation models revealed that treatment with fluocinonide determined, at 6 months, a positive significant effect on the reduced OLP signs (p = 0.017), OLP symptoms (p = 0.026), and OLP extension score (p = 0.028). The multivariate regression analysis highlighted that anxiety, stress, and depression were significant predictors of every analyzed OLP outcome (p < 0.05 for each parameter) and that patients who had baseline anxiety, depression, and stress gained more benefits from fluocinonide at 6‐month follow‐up.Topical fluocinonide 0.05% was more efficacious compared to placebo in reducing OLP outcomes at 6‐month follow‐up. Anxiety, depression, and stress were significant predictors of OLP outcomes and positively impacted the treatment with fluocinonide at 6 months. [ABSTRACT FROM AUTHOR]

Background: Migraine headache is a major public health problem. Routine medications for migraine treatment are not useful in treating all patients and may have some side effects. The present study aimed to investigate the effect of vitamin D and probiotic co-supplementation on clinical characteristics of migraine, daily functioning, mental health outcomes, and serum levels of high-sensitivity C-reactive protein (hs-CRP). Methods: In this randomized, triple-blinded, placebo-controlled trial, patients aged 18 to 55 years diagnosed with migraine based on the International Classification of Headache Disorders-3 (ICHD-3) were randomized to either vitamin D (50,000 IU every 2 weeks) plus probiotic (4.5 × 1011 CFU per day) or placebo for 12 weeks. The Headache Impact Test (HIT-6) and Depression, Anxiety, and Stress Scale (DASS) questionnaires were administered to patients at baseline and after 12 weeks. In addition, the frequency, duration, and severity of migraine headaches per month were assessed using a self-administered 30-day headache diary at baseline and the end of the intervention. Anthropometric indices, blood pressure, and serum levels of 25-hydroxy vitamin D and hs-CRP were also examined at first and the end of the study. Results: Seventy-two migraine patients with a mean age of 37.46 ± 8.32 years were included in this trial. Probiotic and vitamin D co-supplementation compared to placebo resulted in a significant increase in serum levels of vitamin D (+ 12.86 ± 1.64 vs. + 1.12 ± 0.80 ng/mL, P < 0.001). The between-group analysis in the adjusted model showed a significantly greater reduction in migraine headache frequency (− 3.17 ± 0.84 vs. − 1.25 ± 0.34; P = 0.031) and severity (− 1.55 ± 0.35 vs. + 0.67 ± 0.29; P = 0.017) in the probiotic and vitamin D group than the placebo group. No significant difference was found between the two arms of the intervention regarding the change in headache duration, hs-CRP, scores of DASS, and HIT-6 questionnaires (P > 0.05). Conclusions: This trial showed that probiotic and vitamin D co-supplementation for 12 weeks has beneficial effects on migraine headache characteristics. Further research is needed to confirm this finding. [ABSTRACT FROM AUTHOR]

Background: Up to 1.9 million youth in the USA sustain a concussion each year, and up to 30% experience persistent post-concussive symptoms (PPCS) lasting 1 month or more. PPCS can substantially interfere with social, emotional, and academic functioning. Despite these concerns, few evidence-based treatments are available for youth with PPCS. We previously found effectiveness in treating youth with concussion using a collaborative care intervention that integrates mental health care into a medical model, with improvements in concussive symptoms and quality of life at 1 year. Using the multiphase optimization strategy (MOST) framework, we now aim to assess the contribution of each of the three components that were part of collaborative care: concussion-focused cognitive behavioral therapy (cf-CBT), parenting skills training (PST), and care management (CM). Methods: The MOST factorial design examines all three intervention components with two levels of each (present or absent), resulting in 8 possible treatment combinations. We will recruit 368 youth with PPCS from 2 geographic locations (Seattle and Dallas), randomizing them to 1 of 8 treatment groups. Youth and/or parents will attend treatment sessions via video conferencing software over 3 months, and complete surveys regarding primary outcomes (concussive symptoms and health-related quality of life) and secondary outcomes (sleep, pain, mood, and parental distress) at 6 weeks and 3, 6, and 12 months. We will also assess potential mediators and moderators to allow for future tailoring and refinement. Discussion: The overarching goal of this investigation is to determine which collaborative care components (delivered individually or in combination) are most effective in treating PPCS in concussion-exposed youth. The investigation will inform mental health screening, intervention, and referral procedures for youth and families following concussion. At the completion of this study, we will have an optimized and refined intervention for youth with PPCS ready for large-scale implementation and dissemination. Trial registration: ClinicalTrials.gov NCT06036147. Registered on September 13, 2023. [ABSTRACT FROM AUTHOR]

Aims: 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. Methods: 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. Conclusions: 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: 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. Methods: 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. Conclusions: 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]

In June–July 2022, the Randomization Working Group () conducted an online survey on the current practices in the application of randomization in clinical trials. Of 145 unique respondents, 137 (94.5%) identified themselves as statisticians. The majority of respondents were from academia and pharmaceutical companies. Permuted block randomization, with or without stratification, was the most frequently chosen method of randomization for RCTs. Interactive Web-Based Response Systems (IWRS) and "in-house" or a combination of "in-house and outsourced" randomization models were found to be most common in practice. Over 80% of respondents perceived some challenges to adoption of new randomization methods that may have more desirable properties. Over 80% of respondents identified opportunities for improving current practice, including education/training, development of standards/guidance on randomization, and adoption of validated software for generating randomization sequences. In summary, practitioners acknowledge the pivotal role of randomization in clinical trials. There are some perceived challenges to successful implementation of randomization, and there are opportunities for improving practice. [ABSTRACT FROM AUTHOR]

Objective: To compare the effects of the Muscle Energy Technique (MET) and the Bowen Technique on hamstring muscle tightness in chronic low back pain (CLBP) patients. Method: A randomized clinical trial (RCT) designed study in which 62 participants were recruited through the purposive sampling technique were divided into two groups by the lottery method. Subjects who had pain for more than six months in the back and hamstring tightness were included. The duration of the study was four months from February to May 2023 conducted at Madinah Teaching Hospital Faisalabad. Subjects in Group-A were given the Bowen technique, whereas subjects in Group-B were given the MET. Numeric pain rating scale (NPRS), Oswestry disability index (ODI), and active knee extension (AKE) tests were used for measurements of outcomes. Results: Intra-group comparison by using Friedman test revealed that both Group-A & B subject’s pain were reduced (P<0.000), their tightness in back thigh muscles were significantly reduced (P<0.000) and functional activities of subjects were also improved (P<0.000). Mann Whitney test was used to determine the between group comparison. P-value ≤ 0.05 was considered as significant. Inter Group-Analysis revealed that there was no statistically significant difference between effects of Bowen technique & MET on pain, hamstring tightness and disability as both techniques improved pain, flexibility & disability. Conclusion: This study revealed that both groups treated by MET and Bowen Technique had significantly reduced pain, improved flexibility of back thigh muscle and reduced functional disability. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer patients frequently encounter significant emotional and psychological challenges that can adversely affect their overall well-being and treatment outcomes. To address these challenges, we developed the Cancer Patient Empowerment Program (CancerPEP), a comprehensive, home-based intervention that incorporates physical exercise, nutritional guidance, and social support. CancerPEP builds on the success of the Prostate Cancer Patient Empowerment Program (PC-PEP), which has demonstrated positive effects on psychological well-being in prostate cancer patients. In this study, we also evaluated whether adding a Heart Rate Variability (HRV) biofeedback device could enhance the effectiveness of CancerPEP. Our findings indicate that while CancerPEP significantly reduced psychological distress and improved emotional well-being across cancer patients—including a breast cancer subgroup—at the end of the intervention (the 6-month point), the addition or lack of an HRV device did not significantly contribute to these improvements for the full sample. These results suggest that CancerPEP, similar to PC-PEP, is a valuable addition to standard cancer care, providing a holistic approach to support patients both mentally and emotionally. However, the inclusion of the HRV device may not be necessary to achieve these benefits. Background/Objectives: Psychological distress is a significant concern among cancer patients, negatively affecting their quality of life and adherence to treatment. The Cancer Patient Empowerment Program (CancerPEP) was developed as a comprehensive, home-based intervention aimed at reducing psychological distress by incorporating physical activity, dietary guidance, and social support. This study aimed to evaluate the feasibility, accrual and attrition rates, safety, and effectiveness of the CancerPEP intervention, with and without the biofeedback device, on psychological distress from baseline to 6 months, specifically focusing on the effects of group randomization and the difference between pre- and post-intervention results. Methods: This single-site, crossover randomized clinical trial included 104 cancer patients who were randomized to receive the CancerPEP intervention, with or without a Heart Rate Variability (HRV) biofeedback monitor. At 6 months, participants who did not receive the device were allowed to use one until the end of the year, while those who did receive the device were followed up to 12 months. Randomization was stratified by the presence or absence of clinically significant psychological distress and metastatic status. Psychological distress was assessed using the Kessler Psychological Distress Scale (K10) at baseline, 6 months, and 12 months. The primary endpoint was the presence of nonspecific psychological distress, as measured by the K10 scale at 6 months from the trial start, based on group randomization. A secondary exploratory analysis assessed psychological distress at baseline, 6 months, and 12 months for both groups, while controlling for group randomization and prognostic covariates. Prognostic covariates included age; comorbidities; time between diagnosis and randomization; treatment modality; relationship status; and use of prescribed medications for anxiety, depression, or both. An exploratory sub-analysis was conducted for the breast cancer subgroup, based on the sample size available after recruitment. The trial is registered at ClinicalTrials.gov (NCT05508412). Results: The provision of the HRV biofeedback monitor in conjunction with the CancerPEP intervention did not significantly affect the primary outcome in either the full sample or the breast cancer subgroup, indicating that the HRV biofeedback provision was not beneficial in this trial. No self-reported or otherwise discovered adverse events at the 6-month mark were observed. About 10% of participants were lost to follow-up in both the early and late HRV monitor provision groups. Participation in the CancerPEP program led to a significant reduction in psychological distress over time. The odds of psychological distress were significantly higher at the start of the trial than at the end of the intervention (aOR = 2.64, 95% CI: 1.53–4.56) or 6 months after the intervention (aOR = 2.94, 95% CI: 1.62–5.30). Similarly, in the breast cancer subgroup, distress was higher at the trial's start than at 6 months, i.e., after the intervention (aOR = 2.25, 95% CI: 1.24–4.08), or at the end of the trial at 12 months (aOR = 2.73, 95% CI: 1.35–5.52). Conclusions: CancerPEP significantly reduces psychological distress in cancer patients, with consistent improvements noted across various cancer types and stages, including benefits specifically for breast cancer patients. These findings build upon the success of the Prostate Cancer Patient Empowerment Program (PC-PEP), indicating that a similar comprehensive intervention can be advantageous for all cancer patients and may be further tailored to address specific needs. With its holistic approach—encompassing physical, dietary, and psychosocial support—CancerPEP shows promise as a vital component of survivorship care. Ongoing 24-month evaluations will yield critical data on its long-term benefits. Additionally, a randomized trial with a control group (usual care without intervention) for breast cancer patients is currently under way and could potentially guide the integration of CancerPEP into standard oncology care to enhance patient outcomes and quality of life. [ABSTRACT FROM AUTHOR]

The article presents interim trial results comparing the effectiveness of diode laser (DL) and traditional scalpel (TS) in treating oral leukoplakia (OL) concerning recurrence and malignant transformation (MT). Topics discussed include the surgical techniques employed, the rates of recurrence and malignancy observed in each treatment group, and the statistical analysis conducted to evaluate the outcomes of the two methods.

Introduction: Acute exacerbations of chronic obstructive pulmonary disease are associated with high morbidity and mortality. Telemonitoring may reduce the frequency of hospitalization. The aim of this study was to investigate the effect of telemonitoring on hospitalization rates for acute exacerbations of chronic obstructive pulmonary disease. Methods: Patients were recruited during hospitalization and equally randomized to telemonitoring or usual care. Telemonitoring participants recorded symptoms and monitored oxygen saturation, heart rate, peak expiratory flow, and body weight. Alerts were generated if readings breached thresholds. Acute exacerbations of chronic obstructive pulmonary disease hospitalizations during the 6 months intervention were compared using logistic regression, and time to first hospitalization was assessed using Cox proportional hazard modeling. The incidence rates for acute exacerbations of chronic obstructive pulmonary disease hospitalization were compared using a negative binomial regression model with between-group comparisons expressed as incidence rate ratios. The telemonitoring group was used as reference. Results: A total of 222 patients were randomized. 37/112 (33%) in the control group and 31/110 (28%) in the telemonitoring group experienced acute exacerbations of chronic obstructive pulmonary disease hospitalization during the intervention period, odds ratio of 1.26, confidence interval 0.71–2.23, p = 0.4. No difference was seen in time to first hospitalization, hazard ratio 1.23, CI 0.77–1.99, p = 0.4. The number of hospitalizations in the intervention period was 66 in the control group and 42 in the telemonitoring group, with incidence rate ratio 1.42, confidence interval 1.04–1.95, p = 0.03. Adjustment for dyspnea score, smoking, and cohabitation status did not change the results, incidence rate ratio 1.44, confidence interval 1.05–1.99, p = 0.02. Discussion: Patients who received telemonitoring experienced significantly fewer acute exacerbations of chronic obstructive pulmonary disease hospitalizations, although the overall risk of having at least one hospitalization and the time to first hospitalization was similar between the two groups. [ABSTRACT FROM AUTHOR]

Background: Growing evidence suggests the type of periodontal treatment could differentially influence the reduction of key cardiovascular risk mediators in periodontitis patients. This randomized, controlled clinical trial compared the impact of minimally invasive non‐surgical therapy (MINST) with quadrant‐wise subgingival instrumentation (Q‐SI) on C‐reactive protein (CRP) together with lipoprotein‐associated phospholipase A2 (Lp‐PLA2) levels, and clinical periodontal outcomes in patients with periodontitis. Moreover, it was evaluated if baseline CRP levels impacted the efficacy of non‐surgical periodontal therapy protocols. Methods: Forty‐two periodontitis patients were enrolled and randomly treated by means of MINST (n = 21) or Q‐SI (n = 21). The outcomes assessed were serum CRP and Lp‐PLA2, and periodontal parameters (probing depth [PD], clinical attachment level [CAL], full‐mouth bleeding score [FMBS]), at baseline and at follow‐ups at 1, 3, and 6 months and at 1 year after treatment. Results: At 1 year, MINST significantly reduced, among others, mean PD (p = 0.007), mean CAL (p = 0.007), the number of pockets >4 mm (p = 0.011) and ≥6 mm (p = 0.005), and FMBS (p = 0.048) compared to Q‐SI. Generalized multivariate analysis evidenced that high baseline CRP (p = 0.039) and FMBS (p = 0.046) levels, together with MINST treatment (p = 0.007) were significant predictors of PD reduction at 1‐year follow‐up. Moreover, the Jonckheere–Terpstra test showed that patients with high baseline CRP levels gained more benefits from MINST treatment at 1‐year follow‐up than they did from Q‐SI. Conclusion: Patients receiving MINST showed a greater reduction in CRP levels than patients with Q‐SI after 1 year of follow‐up. Moreover, patients with high baseline levels of CRP and Lp‐PLA2 gained more benefits from the MINST approach at 1‐year follow‐up. [ABSTRACT FROM AUTHOR]

There is a lack of randomized clinical trials (RCTs) exploring the outcomes of cardiopulmonary rehabilitation programmes (CPRPs) on submaximal aerobic capacity of long COVID-19 patients (LC19Ps). This RCT aimed to evaluate the effect of an ambulatory CPRP on the 6-min walk test (6MWT) data (main outcome: 6-min walk distance (6MWD)) of LC19Ps. Conducted as a single-blinded RCT, the study included Tunisian LC19Ps with persistent dyspnoea (i.e. modified medical research council (mMRC) level ≥2) at least three months postdiagnosis. LC19Ps were randomly assigned to the intervention (IG, n = 20) or control (CG, n = 10) groups. Pre- and post-CPRP evaluations included dyspnoea assessments (Borg and mMRC scales), anthropometric data, spirometry, and 6MWT. The CPRP (i.e. 18 sessions over six weeks) encompassed warm-up, aerobic training, resistance training, respiratory exercises, and therapeutic education. The CPRP significantly improved i) dyspnoea, i.e. IG exhibited larger reductions compared to the CG in Borg (-3.5 ± 2.0 vs. -1.3 ± 1.5) and mMRC (-1.5 ± 0.8 vs. -0.1 ± 0.3) scales, and ii) 6MWD, i.e. IG demonstrated larger improvements compared to the CG in 6MWD (m, %) (168 ± 99 vs. 5 ± 45 m, 28 ± 8 vs. 1 ± 8%, respectively), and resting heart rate (bpm, % maximal predicted heart rate) (-9 ± 9 vs. 1 ± 7 bpm; -5 ± 6 vs. 0 ± 4%, respectively), with small effect sizes. In the IG, the 1.5-point decrease in mMRC and the 168 m increase in 6MWD exceeded the recommended minimal clinical important differences of 1 point and 30 m, respectively. CPRP appears to be effective in enhancing the submaximal exercise capacity of LC19Ps, particularly in improving 6MWD, dyspnoea, and resting heart rate. RCT registration: www.pactr.org; PACTR202303849880222. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy and safety of oral ibrexafungerp (HS-10366) versus placebo in Chinese patients with vulvovaginal candidiasis (VVC). Methods: A double-blind, placebo-controlled, randomized, multicenter phase III study was conducted in symptomatic VVC patients. Patients received (2:1) twice-daily oral ibrexafungerp 300 mg or matching placebo for 1 day. The primary endpoint was clinical cure (vulvovaginal signs and symptoms [VSS] score = 0) at test-of-cure (TOC) on day 11 ± 3. The secondary endpoints included mycological eradication, overall response, and clinical improvement (VSS score ≤ 1) at TOC, and vulvovaginal symptom resolution at follow-up on day 25 ± 4. Results: In total, 360 patients were included in the modified intention-to-treat set (defined as positive Candida cultured and receiving at least one study drug; 239 for ibrexafungerp, 121 for placebo). Compared with placebo, patients receiving ibrexafungerp had a significantly higher proportion of clinical cure (51.0% vs. 25.6%), mycological eradication (55.6% vs. 18.2%), overall response (33.9%, vs. 8.3%) at TOC and complete symptom resolution (74.5% vs. 39.7%, all P < 0.001) at follow-up. Subgroup analysis of clinical cure indicated that patients with C. albicans could benefit from ibrexafungerp over placebo. A similar benefit trend was also observed in those with non-albicans Candida by post-hoc analysis. Further analyses revealed similar efficacy of ibrexafungerp between patients with fluconazole non-susceptible C. albicans and fluconazole susceptible C. albicans regarding clinical cure and mycological eradication. Ibrexafungerp was generally well tolerated. Adverse events were primarily gastrointestinal and were mainly mild in severity. Conclusions: As a first-in-class antifungal agent, ibrexafungerp demonstrated promising efficacy and favorable safety for VVC treatment in Chinese patients. Chinadrugtrials.org.cn registry number: CTR20220918. [ABSTRACT FROM AUTHOR]

Background: Peanut consumption could impact cardiometabolic health through gut microbiota, a hypothesis that remains to be investigated. A randomized clinical trial in Vietnam evaluated whether peanut consumption alters gut microbiome communities. Methods: One hundred individuals were included and randomly assigned to the peanut intervention and control groups. A total of 51 participants were provided with and asked to consume 50 g of peanuts daily, while 49 controls maintained their usual dietary intake for 16 weeks. Stool samples were collected before and on the last day of the trial. After excluding 22 non-compliant participants and those who received antibiotic treatment, 35 participants from the intervention and 43 from the control were included in the analysis. Gut microbiota composition was measured by shotgun metagenomic sequencing. Associations of changes in gut microbial diversity with peanut intervention were evaluated via linear regression analysis. Linear mixed-effects models were used to analyze associations of composition, sub-community structure, and microbial metabolic pathways with peanut intervention. We also performed beta regression analysis to examine the impact of peanut intervention on the overall and individual stability of microbial taxa and metabolic pathways. All associations with false discovery rate (FDR)-corrected p-values of <0.1 were considered statistically significant. Results: No significant changes were found in α- and β-diversities and overall gut microbial stability after peanut intervention. However, the peanut intervention led to lower enrichment of five phyla, five classes, two orders, twenty-four metabolic pathways, and six species-level sub-communities, with a dominant representation of Bifidobacterium pseudocatenulatum, Escherichia coli D, Holdemanella biformis, Ruminococcus D bicirculans, Roseburia inulinivorans, and MGYG-HGUT-00200 (p < 0.05 and FDR < 0.1). The peanut intervention led to the short-term stability of several species, such as Faecalibacterium prausnitzii F and H, and a metabolic pathway involved in nitrate reduction V (p < 0.05; FDR < 0.1), known for their potential roles in human health, especially cardiovascular health. Conclusions: In summary, a 16-week peanut intervention led to significant changes in gut microbial composition, species-level sub-communities, and the short-term stability of several bacteria, but not overall gut microbial diversity and stability. Further research with a larger sample size and a longer intervention period is needed to confirm these findings and investigate the direct impact of gut-microbiome-mediated health effects of peanut consumption. Trial registration: The International Traditional Medicine Clinical Trial Registry (ITMCTR). Registration number: ITMCTR2024000050. Retrospectively Registered 24 April 2024. [ABSTRACT FROM AUTHOR]

Background: Chuna manual therapy (CMT), a Korean manual therapy technique predominantly used for treating low back pain (LBP) and related disorders, lacks well-conceived research focusing on its comparative effectiveness, safety, and economic evaluation, particularly with respect to complex CMT with established CMT diagnostic algorithms. This study aims to illustrate a protocol for a randomized clinical study for comparative effectiveness and cost-effectiveness of complex CMT with simple CMT and usual care. Methods: This is a protocol for a three-armed, multicenter, assessor-blinded, pragmatic, randomized controlled trial study. A total of 81 patients suffering from non-acute LBP with pelvic biomechanical lesions (PBL), characterized by a pain duration of at least two weeks and a Numeric Rating Scale (NRS) score of 5 or higher, will be recruited from two Korean medicine hospitals. These participants will be randomly assigned to one of three groups: complex CMT plus usual care (UC; n = 27), simple CMT plus UC (n = 27), or UC groups (n = 27). They will undergo treatment for 4 weeks, and follow-up assessments will be performed 8 weeks after treatment completion. The primary outcome will be the NRS score of LBP, and secondary outcomes will include the Oswestry Disability Index, Patient Global Impression of Change, credibility and expectancy questionnaire, three-dimensional posture analysis indicators, quality of life assessment, economic evaluation, and safety assessments. Discussion: This will be the first study to assess the comparative effectiveness, safety, and cost-effectiveness of complex CMT compared to UC and simple/complex CMT in patients with LBP and PBL. We will also analyze useful diagnostic methods to help in clinical practice for CMT diagnosis. Trial registration: Clinical Research Information Service (CRIS), KCT0009210. Registered on February 28, 2024. [ABSTRACT FROM AUTHOR]

BACKGROUND Drug concentration in blood or urine is an acknowledged method to detect nonadherence. Observational studies suggest that informing patients about low or absent serum drug levels improves blood pressure (BP). We performed a multicenter randomized clinical trial to test the hypothesis that therapeutic drug monitoring (TDM) could improve drug adherence and BP in patients with uncontrolled hypertension (HT). METHODS Patients were ≥18 years on stable treatment with at least 2 antihypertensive agents. We planned to randomize 80 nonadherent patients with a systolic daytime ambulatory BP ≥135 mm Hg to TDM intervention or not. The control group and the study personnel who measured BP remained uninformed about serum drug measurements throughout. All patients and physicians were blinded for BPs. Lifestyle advice and detailed information on the disease process and the importance of BP treatment were given to both groups. RESULTS From 2017 to 2022, we randomized 46 diagnosed nonadherent from a total of 606 patients with uncontrolled HT. The TDM group had a 6.7 (±14.5) mm Hg reduction from 147.9 (±10.3) to 141.1 (±14.1) mm Hg, and the control group experienced a 7.3 (±13.2) mm Hg reduction from 147.1 (±9.2) to 139.1 (±17.4) mm Hg, P  = 0.9 between groups. Adherence improved in both groups, 73% in the TDM group and 59% in the control group became adherent at 3 months, P  = 0.51. CONCLUSIONS In our prospective multicenter clinical trial of uncontrolled and nonadherent hypertensive patients, we found no additional effect of TDM on BP and drug adherence compared with standard care. CLINICAL TRIALS REGISTRATION Trial Number NCT03209154 , www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

One of the most promising approaches to correct periodontal bone defects and achieve periodontal regeneration is platelet-rich fibrin (PRF). This systematic review and meta-analysis aimed to evaluate the regeneration of periodontal bone defects using PRF compared to other regenerative treatments. The data search and retrieval process followed the PRISMA guidelines. An electronic search of MEDLINE, Cochrane, and PubMed databases was performed, selecting exclusively randomized clinical trials where the following were measured: probing depth reduction (PD), clinical attachment level gain (CAL), and radiographic bone fill (RBF). Out of 284 selected articles, 32 were chosen based on inclusion criteria. The use of platelet-rich fibrin (PRF) + open flap debridement (OFD), PRF + metformin, PRF + platelet-rich plasma (PRP), and PRF + OFD/bone graft (BG) significantly reduced PD and improved CAL and RBF. However, the combination of PRF + BG, PRF + metformin, and PRF + STATINS reduced CAL. The intervention of PRF combined with different treatments such as metformin, OFD, PRP, BG, and STATINS has a significant impact on improving PD and CAL. The use of PRF significantly improved the regeneration of periodontal bone defects compared to other treatments. [ABSTRACT FROM AUTHOR]

Background: Robot-assisted radical prostatectomy (RARP) gains increasing popularity in the surgical management of prostate cancer (PCa) but is challenged by its prohibitive expense. A domestic robotic system has been developed to address this issue, but data comparing the self-developed robot with the widely used robot is lacking. We performed a randomized clinical trial to compare KD-SR-01® and DaVinci® robots in terms of perioperative, short-term oncological and functional outcomes in RARP. Materials and methods: We prospectively enrolled patients with clinically localized PCa. Patients were randomized to undergo either KD-SR-01®-RARP (K-RARP) or DaVinci®-RARP (D-RARP) by the same surgical team. The baseline, perioperative, short-term oncologic and urinary functional data were collected and compared. Results: We enrolled 39 patients, including 20 patients undergoing K-RARP and 19 undergoing D-RARP. Demographic and tumor characteristics were comparable between groups. All surgeries were performed successfully with no conversion to open. The operative time was similar (P = 0.095) and K-RARP offered less volume of intraoperative bleeding (P < 0.001). Four patients in the K-RARP group and three in the D-RARP group developed postoperative complications (P = 0.732). Patients undergoing K-RARP had less volume of drainage (P = 0.022). Positive surgical margins were observed in three patients undergoing K-RARP and five undergoing D-RARP (P = 0.451). During the follow up, one patient receiving K-RARP group and two receiving D-RARP group had measurable prostate specific antigen (P = 0.605). Urine leakage, urinary control and pad usage were comparable between groups at six weeks post-surgery. Conclusions: The two surgical robots yielded similar results in feasibility, safety and short-term oncologic and functional efficacy for RARP. Trial registration: The trial has been registered at www.chictr.org.cn with a registration number of ChiCTR2200057000 on 25th February 2022. [ABSTRACT FROM AUTHOR]

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]

Betel quid (BQ) use disorder (BUD) is prevalent in many Asian countries, impacting approximately 600 million people. We conducted a randomized clinical trial to analyze the impact of MAOA genetic variations on the severity of BQ craving. This was measured using DSM-5 criteria and the Yale–Brown Obsessive–Compulsive Scale modified for betel quid use (Y-BOCS-BQ). Participants were grouped according to the severity of BUD and MAOA gene single-nucleotide polymorphism (SNP) rs5953210 genotypes. The Y-BOCS-BQ scores were assessed at baseline (week 0) and during follow-up at weeks 2, 4, 6, and 8. The AA genotype group showed significantly greater reductions in Y-BOCS-BQ at weeks 2 (p = 0.0194), 4 (p = 0.0078), 6 (p = 0.0277), and 8 (p = 0.0376) compared to the GG genotype group. Additionally, within the antidepressant group, the AA genotype showed significant reductions in the Y-BOCS-BQ scores at weeks 2 (p = 0.0313), 4 (p = 0.0134), 6 (p = 0.0061), and 8 (p = 0.0241) compared to the GG genotype. The statistical analysis revealed a significant interaction between the treatment and placebo groups based on MAOA genotypes, with the AA genotype in the treatment group exhibiting a more pronounced decrease in Y-BOCS-BQ score (p interaction <0.05) at week 6. Our study highlights the importance of considering genetic factors when developing personalized treatment plans for BUD. [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]

The risk of cardiovascular disease (CVD) is approximately doubled in subjects with hypercholesterolemia compared to those with normal blood cholesterol levels. Monacolin K (MK), the main active substance in rice fermented by the Monascus purpureus, acts on cholesterol metabolism. Rice also contains other bioactive compounds such as γ-oryzanol (OZ) and γ-aminobutyric acid (GABA). In a randomized, placebo-controlled, double-blind trial, the efficacy and tolerability of a food supplement (FS) based on an ingredient standardized to contain monacolins (4.5%), OZ, and GABA were evaluated in subjects with mild dyslipidemia. For the duration of the trial, enrolled subjects (n = 44, each group) received the FS or placebo and were instructed to use an isocaloric diet. Compared to the placebo group, after a 3 months of the FS, the mean low-density lipoprotein cholesterol and mean TC values were reduced by 19.3 and 8.3%, respectively, while the mean high-density lipoprotein cholesterol value increased by 29.3%. On average, the subjects shifted from very high to moderate CVD risk. Glucose metabolism and hepatic and renal parameters did not change after the treatment and no adverse events were reported. Guidelines to handle hypercholesterolemia with food supplements in specific clinical settings are needed to better manage mild dyslipidemia. [ABSTRACT FROM AUTHOR]

Pinus koraiensis (PK) leaf extract, derived from Korean pine byproducts, holds promise for alleviating postprandial hyperlipidemia. In this study, we investigated the potential of PK leaf extract for modulating postprandial hyperlipidemia in adults with normal or borderline fasting triglyceride levels. In a randomized, double-blind, parallel design, 70 subjects were randomly assigned to either the placebo or PK group for 4 weeks. After 4 weeks of consuming PK leaf extract, the results indicated a trend toward decreased serum apolipoprotein B-100 (ApoB100) levels 2 h after a high-fat challenge. Furthermore, significant improvements were observed in the incremental area under the curve (iAUC) at 0–4 h and 2–4 h compared to baseline, particularly among individuals with a higher body weight (>61.35 kg) and daily caloric intake (>1276.5 kcal). Based on these findings, PK leaf extract may have beneficial effects on postprandial lipoprotein metabolism, especially among individuals with a relatively high body weight and caloric intake. [ABSTRACT FROM AUTHOR]

Primary dysmenorrhea is considered one of the main causes of pelvic pain during a woman's childbearing years, resulting in poor quality of life. The objective was to evaluate the effectiveness of transcutaneous tibial nerve stimulation (TTNS) in painful symptomatology improvement and non-steroidal anti-inflammatory drug (NSAID) intake reduction in women with primary dysmenorrhea (PD) compared with a control group in the short, medium, and long terms. A single-blind, controlled clinical trial was developed. Participants were randomized to the experimental (TTNS) and control group (sham TTNS). Both groups received 12-weekly 30-min sessions with a NeuroTracTM PelviTone electrostimulation device. The intensity and severity of pain and non-steroidal anti-inflammatory drug (NSAID) intake were evaluated in the short-term (after treatment), medium-term (1–3 months), and long-term (6 months). A total of 61 participants were randomized, with a split of 31 (experimental group) and 30 (control group), but 55 participants completed the study and were analyzed. Statistically significant differences between both groups in the maximum pain intensity decrease (F = 4.88, p = 0.0043) measured with the visual analogue scale, as well as NSAID intake decrease (F = 4.68, p = 0.011) and days of their ingestion (F = 4.57, p = 0.012) occurred in the short term. Furthermore, significant decreases in the total number of NSAIDs ingested during the cycle (F = 3.82, p = 0.011) and the number of days on which patients ingested NSAIDs (F = 3.59, p = 0.015) in the medium–long term occurred. TTNS could be an effective and safe strategy to reduce pain caused by PD, which could reduce or complement the use of pharmacological techniques and other more invasive methods. [ABSTRACT FROM AUTHOR]

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]

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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.

Abstract Background Developing interventions for older adults with subjective cognitive decline (SCD) has the potential to prevent dementia in this at-risk group. Preclinical models indicate that Citrus-derived phytochemicals could benefit cognition and inflammatory processes, but results from clinical trials are still preliminary. The aim of this study is to determine the effects of long-term supplementation with Citrus peel extract on cognitive performance and inflammation in individuals with SCD. Methods Eighty participants were randomly assigned to active treatment (400 mg of Citrus peel extract containing 3.0 mg of naringenin and 0.1 mg of auraptene) or placebo at 1:1 ratio for 36 weeks. The primary endpoint was the change in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total score across the 36-week trial period. Other cognitive outcomes included tests and scales evaluating verbal memory, attention, executive and visuospatial functions, and memory concerns. The secondary endpoint was the change of interleukin-8 (IL-8) levels over the 36-week trial period in a subsample of 60 consecutive participants. An Intention-to-treat approach with generalized linear mixed models was used for data analysis. Results The RBANS total score showed significant improvement in both Citrus peel extract and placebo groups at 36 weeks (p for time