Effectiveness of a mobile application for independent computerized cognitive training in patients with mild cognitive impairment: study protocol for the NeNaE Study, a randomized controlled trial.

BACKGROUND: Mild cognitive impairment (MCI) involves cognitive decline beyond typical age-related changes, but without significant daily activity disruption. It can encompass various cognitive domains as the causes of MCI are diverse. MCI as well as frequent comorbid neuropsychiatric conditions like depression and anxiety affect individuals' quality of life. Early interventions are essential, and computerized cognitive training (cCT) is an established treatment method. This paper presents the protocol for the NeuroNation MED Effectiveness Study, evaluating the self-administered mobile cCT intervention ("NeuroNation MED") in individuals with MCI to assess training effects on cognitive domains, health competence, neuropsychiatric symptoms, psychological well-being, and the general application usability. METHODS: This study protocol presents a single-blinded multicenter randomized controlled trial that will be carried out in six study centers in Germany and Luxembourg. We included adults with MCI (existing F06.7 ICD-10-GM diagnosis and TICS ≥ 21 and ≤ 32). The intervention group will use a mobile, multi-domain cCT ("NeuroNation MED") for 12 weeks. Meanwhile, the wait list control group will receive standard medical care or no care. The eligibility of volunteers will be determined through a telephone screening. After completion of the baseline examination, patients will be randomly assigned to one of the experimental conditions in a 2:1 ratio. In total, 286 participants will be included in this study. The primary outcome is the change of cognitive performance measured by the index score of the screening module of the Neuropsychological Assessment Battery. Secondary outcomes are changes in the Cognitive Failures Questionnaire, Hospital Anxiety and Depression Scale, Health-49, Health Literacy Questionnaire, among others. All of the primary and secondary outcomes will be assessed at baseline and after the 12-week post-allocation period. Furthermore, the intervention group will undergo an assessment of the System Usability Scale, and the training data of the NeuroNation MED application will be analyzed. DISCUSSION: This study aims to assess the effectiveness of a mobile self-administered cCT in enhancing cognitive abilities among individuals diagnosed with MCI. Should the findings confirm the effectiveness of the NeuroNation MED app, it may confer possible benefits for the care management of patients with MCI, owing to the accessibility, cost-effectiveness, and home-based setting it provides. Specifically, the cCT program could provide patients with personalized cognitive training, educational resources, and relaxation techniques, enabling participants to independently engage in cognitive training sessions at home without further supervision. TRIAL REGISTRATION: German Clinical Trials Register DRKS00025133. Registered on November 5, 2021.

The effect of Phytopaj ) Ferula assa-foetida L. oleo gum resin and tragacanth( in patients with COVID-19: A randomized clinical trial.

Objective: Exogenous hydrogen sulfide (H2S) has a positive effect on respiratory diseases. Oleo-gum of Ferula assa-foetida contains this compound. This study assessed the effects of Ferula assa-foetida L. oleo gum resin and tragacanth (Phytopaj) on patients with COVID-19. Materials and Methods: A randomized, single-blinded, controlled trial (RCT) phase 2 was conducted in Mashhad on hospitalized COVID-19 patients. In this RCT, 122 patients were randomly assigned to either receive a 14-day oral phytopaj plus ordinary treatment or ordinary treatment only. Changes in peripheral blood lymphocyte count (LC) and blood oxygen saturation (PO2) were the endpoints. Results: Mean±SD of PO2 in Phytopaj comparison ordinary treatment before intervention was 91.86±4.62 and 91.41±9.18, after the intervention it was 93.22±4.26 and 91.91±5.92 mmHg; before intervention, mean±SD of peripheral blood lymphocyte count was 1015.90±500.55, and 1104.28±543.61, and after intervention, it was 1652.27±921.38 and 1326.12±719.28/µL respectively. Conclusion: Phyopaj is most useful in moderate stages of Covid19, and it is not recommended for elderly patients and patients with comorbidity until more insight is gained.

Short- and long-term effects of imatinib in hospitalised COVID-19 patients: A randomised trial.

OBJECTIVES: We studied the short- and long-term effects of imatinib in hospitalised COVID-19 patients. METHODS: Participants were randomised to receive standard of care (SoC) or SoC with imatinib. Imatinib dosage was 400mg daily until discharge (max 14 days). Primary outcomes were mortality at 30 days and 1 year. Secondary outcomes included recovery, quality of life and long COVID symptoms at 1 year. We also performed a systematic review and meta-analysis of randomised trials studying imatinib for 30-day mortality in hospitalised COVID-19 patients. RESULTS: We randomised 156 patients (73 in SoC and 83 in imatinib). Among patients on imatinib, 7.2% had died at 30 days and 13.3% at 1 year and in SoC 4.1% and 8.2% (adjusted HR 1.35, 95% CI 0.47-3.90). At 1-year, self-reported recovery occurred in 79.0% in imatinib and in 88.5% in SoC (RR 0.91, 0.78-1.06). We found no convincing difference in quality of life or symptoms. Fatigue (24%) and sleep issues (20%) frequently bothered patients at one year. In the meta-analysis, imatinib was associated with a mortality risk ratio of 0.73 (0.32-1.63; low certainty evidence). CONCLUSIONS: The evidence raises doubts regarding benefit of imatinib in reducing mortality, improving recovery and preventing long COVID symptoms in hospitalised COVID-19 patients.

Effect of Green Tea Supplementation on Inflammatory Markers among Patients with Metabolic Syndrome and Related Disorders: A Systematic Review and Meta-Analysis.

Several randomized controlled trials (RCTs) have investigated the potential benefits of green tea on the inflammatory process in metabolic syndrome (MetS). However, the results are inconclusive and inconsistent. In the present study, we performed a literature review and meta-analysis to evaluate the effect of green tea supplementation on inflammatory markers [e.g., tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and interleukin-6 (IL-6)] among patients with MetS and related disorders. We systematically searched for relevant publications up to March 2022 in the PubMed, Scopus, Web of Science, and SciELO databases. The review was registered with PROSPERO (CRD42022320345). Mean differences with 95% confidence intervals were pooled on the basis of the random effects model to compare the effects of green tea with placebo. We used meta-regression and subgroup analyses to determine the cause of heterogeneity and performed study quality assessment using the Grading of Recommendations Assessment, Development, and Evaluation method. We assessed publication bias using funnel plots and Egger's tests. Out of the total 15 RCTs that were included in this systematic review, 12 were chosen for the meta-analysis. The results revealed that green tea significantly decreased TNF-α levels but did not affect CRP and IL-6 levels. Subgroup analysis showed that green tea supplementation in studies lasting ≤8 weeks significantly increased CRP levels. Furthermore, meta-regression analysis demonstrated a significant association between increasing IL-6 concentration and treatment duration. According to our meta-analysis, green tea was shown to considerably lower circulating TNF-α levels. To confirm these findings, carefully planned trials are required.

Effect of acupuncture on post-stroke dysphagia: a randomized controlled trial.

Introduction: Post-stroke dysphagia (PSD) is associated with various complications that increase morbidity and mortality rates. Acupuncture has been used extensively in China to treat these complications; however, its therapeutic efficacy remains uncertain. We therefore aimed to study the clinical effects of acupuncture on PSD. Methods: Patients (n = 101) were randomly divided into acupuncture (n = 50) and rehabilitation training control (n = 51) groups based on the treatment used. Both groups were treated once daily, 6 days a week, for a total of 4 weeks. Pulse oxygen saturation (SpO2) and standardized swallowing assessment (SSA) were performed before the intervention, 2 weeks into treatment, after the intervention (4 weeks post-intervention), and at a 6-month follow-up (28 weeks). The levels of hemoglobin (Hb) and albumin (ALB), and 5-hydroxytryptamine (5-HT) and dopamine (DA) were measured before the intervention, 2 weeks into treatment, and after the intervention (4 weeks), as nutrition and swallowing function indices, respectively. Results: Following the intervention, significant differences were observed between the acupuncture and control groups. The acupuncture group exhibited considerably superior enhancements in SpO2 and SSA scores at 4 weeks (p < 0.001). Moreover, this group demonstrated significantly greater improvements in Hb, ALB, 5-HT, and DA values 4 weeks post-treatment (p < 0.001). However, sex-based differences were not observed (P > 0.005). Conclusion: Acupuncture treatment can improve the swallowing function and nutritional status of patients with PSD, and increase the levels of 5-HT and DA. These findings strongly support the efficacy of acupuncture as a therapeutic intervention in patients with PSD.Clinical trial registration: identifier, ChiCTR2100052201. (https://www.chictr.org.cn/).

Effect of l-oxiracetam and oxiracetam on memory and cognitive impairment in mild-to-moderate traumatic brain injury patients: Study protocol for a randomized controlled trial.

Objectives: Patients with traumatic brain injury (TBI) often suffer memory and cognitive impairments, and oxiracetam-like drugs are considered to have a positive impact on these symptoms potentially. However, the efficacy and safety of l-oxiracetam and oxiracetam in TBI patients have not been sufficiently investigated. Methods: The study adopts a multicenter, randomized, double-blind, parallel-group, phase 3 clinical trial design in 74 centers across 51 hospitals in China. A total of 590 TBI patients meeting criteria will be randomly allocated into three groups in a 2:2:1 ratio: l-oxiracetam group, oxiracetam group, and placebo group. The treatment period is 14 days, with a follow-up period of 90 days. The primary outcome measure is the change in the Loewenstein Occupational Therapy Cognitive Assessment score at 90 days after treatment. Secondary outcomes include changes in other cognitive assessments, neurological function, activities of daily living, and safety assessments. Discussion: There is no robust evidence to suggest that l-oxiracetam and oxiracetam can enhance memory and cognitive function in patients with mild to moderate TBI. This study has the potential to answer this crucial clinical question. Trial registration: chinadrugtrials.org.cn, identifier CTR20192539; ClinicalTrials.gov, identifier NCT04205565.

EASIER trial (Erector-spinAe analgeSia for hepatopancreaticobiliary pain In the Emergency Room): a single-centre open-label cohort-based randomised controlled trial analysing the efficacy of the ultrasound-guided erector-spinae plane block compared with intravenous morphine in the treatment of acute hepatopancreaticobiliary pain in the emergency department.

BACKGROUND: Ultrasound-guided (USG) erector-spinae plane block (ESPB) may be better than intravenous opioids in treating acute hepatopancreaticobiliary (HPB) pain in the ED. METHODS: This open-label randomised controlled trial was conducted in the ED of a tertiary-care hospital between March and August 2023. All adult patients with severe HPB pain were recruited during times that a primary investigator was present. Unconsenting patients, numeric rating scale (NRS) ≤6, age ≤18 and ≥80 years, pregnant, unstable or with allergies to local anaesthetics or opioids were excluded. Patients in the intervention arm received bilateral USG ESPB with 0.2% ropivacaine at T7 level, by a trained ED consultant, and those in the control arm received 0.1 mg/kg intravenous morphine. Pain on a 10-point NRS was assessed by the investigators at presentation and at 1, 3, 5 and 10 hours after intervention by the treatment team, along with rescue analgesia requirements and patient satisfaction. Difference in NRS was analysed using analysis of co-variance (ANCOVA) and t-tests. RESULTS: 70 participants were enrolled, 35 in each arm. Mean age was 40.4±13.2 years, mean NRS at presentation in the intervention arm was 8.0±0.9 and 7.6±0.6 in the control arm. NRS at 1 hour was significantly lower in the ESPB group (ANCOVA p<0.001). At 1, 3, 5 and 10 hours, reduction of NRS in the intervention arm (7±1.6, 6.7±1.9, 6.6±1.8, 6.1±1.9) was significantly greater than the control arm (4.4±2, 4.6±1.8, 3.7±2.2, 3.8±1.8) (t-test, p<0.001). Fewer patients receiving ESPB required rescue analgesia at 5 (t-test, p=0.031) and 10 hours (t-test, p=0.04). More patients were 'very satisfied' with ESPB compared with receiving only morphine at each time period (p<0.001). CONCLUSION: ESPB is a promising alternative to morphine in those with HPB pain. TRIAL REGISTRATION NUMBER: CTRI/2023/03/050595.

Continuous Glucose Monitoring and the Effect of Liraglutide in Cardiac Surgery Patients: A Substudy of the Randomized Controlled GLOBE Trial.

OBJECTIVES: The objectives of the current research were to evaluate the accuracy and reliability of continuous glucose monitoring (CGM) in patients undergoing cardiac surgery and assess the impact of preoperative liraglutide administration on perioperative glucose control as captured by CGM. DESIGN: This was a prospective, single-center, prespecified analysis of the GLOBE trial, a randomized controlled trial comparing preoperative liraglutide treatment to placebo in patients undergoing cardiac surgery. SETTING: The work took place at a single-center academic hospital in the Netherlands. PARTICIPANTS: Twenty-five patients undergoing cardiac surgery were recruited from the hospital's cardiac surgery department. INTERVENTIONS: Participants received the Dexcom G5 CGM system from the day before surgery until discharge from the intensive care unit after surgery. Additionally, participants were randomized to receive either preoperative liraglutide or placebo. MEASUREMENTS AND MAIN RESULTS: Arterial blood gas (ABG) glucose measurements were collected as a reference and matched to CGM readings to assess accuracy and reliability. In 240 paired CGM-ABG glucose measurements, the mean absolute relative difference was 14.4 ± 12.5%. Temporary sensor interruption occurred mainly intraoperatively (92% of patients). The median duration of intraoperative sensor interruption was 65 (48-95) minutes. Liraglutide increased glycemic time in range 72% versus 47% in the control group (absolute difference 25%, 95% confidence interval -41.4 to -8.9, p = .004). CONCLUSIONS: Despite intraoperative sensor interruption, CGM seems an accurate method for semi-invasive, real-time assessment of blood glucose levels. CGM can provide a detailed observation of the pre- and postoperative glycemic trajectory, demonstrating increased time in range following perioperative liraglutide treatment compared with placebo.

An analysis of retracted studies in cardiology in the last two decades.

Background: The aim of this study is to analyze retracted studies in cardiovascular field. Methodology: PubMed and Embase databases were used to identify retracted publications from 2002 to 2022. Various characteristics of articles were retrieved, and an analysis was performed using R software. Results: We finally included 979 articles. Authors from China have the highest number of retracted studies (35.5%), followed by the USA (22.1%), and Japan (4%). The most common causes of retraction are mistakes and honest errors (24.5%) and duplicate data (17.7%). From 2002 to 2022, there has been a significant increase in retracted studies and a decrease in the impact factor of journals, number of citations, and time to retraction. Conclusion: The trend of retracting publications in cardiology is increasing.

Retracted publications are withdrawn publications. Recently, the number of retracted publications has increased. In our research, we try to find the characteristics and pattern of the retracted studies in heart published studies. PubMed and Embase databases were used to identify retracted publications from 2002 to 2022. Various characteristics of articles were retrieved, and statistical software was used to analyze them. We finally included 979 articles. Findings from our research showed authors from China, the USA, and Japan have the highest number of retracted studies. Honest errors, duplicate data, and fabricated data are common causes of retractions. From 2002 to 2022, there has been an increase in the number of retracted studies and a decrease in the impact factor of journals, the number of citations, and the time to retraction. We also compared the results between the first (2003­2012) and the second decade (SD; 2013­2022). In the SD, there are more retracted publications. We saw that in the first decade, the USA had more retractions; however, in the SD, China had more retractions. The retracted publications in the SD have less time to retract and fewer citations. There is no change regarding the funding of research or the parties' interest in conducting research. In the end, the trend of retracting publications in heart studies is increasing. Making the scientific world aware would be the most important to tackle this problem.

Optimizing Blood Pressure Management in Type 2 Diabetes: A Comparative Investigation of One-Time Versus Periodic Lifestyle Modification Counseling.

Background Type 2 diabetes mellitus (T2DM) often coexists with hypertension, significantly increasing cardiovascular risks. Lifestyle modification counseling has shown promise in managing T2DM and its comorbidities. However, the optimal frequency and structure of counseling for blood pressure control remain uncertain. Our study examines the best approach for managing blood pressure in T2DM patients by comparing the outcomes of two counseling strategies: a single session and periodic counseling over time. Methodology A total of 110 diabetic patients were enrolled, with 52 patients in each group after loss to follow-up. A randomized controlled trial compared one-time counseling (control) to six months of periodic counseling (intervention) on lifestyle modification. A weighing machine, stadiometer, 24-hour dietary recall, food frequency questionnaire, biochemical blood sugar level analysis, and telephonic follow-up were the essential tools used. The data were analyzed using SPSS version 24.0 (IBM Corp., Armonk, NY, USA), employing descriptive statistics, including frequencies, percentages, graphs, mean, and standard deviation. Statistical significance at the 5% level was tested using probability (p) calculations. The Kolmogorov-Smirnov test confirmed normal distribution (p > 0.05). Parametric tests, specifically independent t-tests, were used for between-group comparisons of continuous variables, while categorical variables were analyzed using the chi-square test or Fisher's exact test. Intragroup comparisons over time employed repeated-measures analysis of variance for continuous variables. Changes within groups after six months were assessed using paired t-tests. All statistical analyses adhered to a significance level of p < 0.05. Results The gender distribution at baseline was similar between the control (55.8% male, 44.2% female) and intervention (46.2% male, 53.8% female) groups, with no significant differences (p = 0.327). The mean weight was 66.67 ± 11.51 kg in the control group and 67.14 ± 11.19 kg in the intervention group (p = 0.835), and the body mass index was 25.61 ± 4.09 kg/m² and 26.29 ± 6.01 kg/m², respectively (p = 0.503). Clinical parameters such as fasting blood sugar, postprandial blood sugar, glycosylated hemoglobin, and blood pressure showed no significant differences between the control and intervention groups at baseline (p > 0.05). After six months, the intervention group exhibited a trend toward lower blood pressure compared to the control group, but the differences were not statistically significant. The mean systolic blood pressure was 132.15 ± 14.867 mmHg in the control group and 129.15 ± 9.123 mmHg in the intervention group (p = 0.218). Changes in blood pressure over the six-month period showed significant decreases within the intervention group, while changes in the control group did not reach statistical significance. The mean difference in systolic blood pressure in the intervention group was 5.54 ± 9.77 mmHg (p = 0.0001), indicating a notable reduction, while the control group had a smaller and statistically insignificant increase of 2.308 ± 9.388 mmHg (p = 0.082). Conclusions This study addresses a significant gap in the literature by comparing the efficacy of one-time vs. periodic counseling in T2DM management. While periodic counseling shows promise in improving diastolic blood pressure, further research is needed to understand its nuanced effects and optimize lifestyle interventions for T2DM patients.

Comparison of the efficacy and safety of vertebroplasty with different pedicle approaches for osteoporotic vertebral.

OBJECTIVE: To compare the efficacy and safety of vertebroplasty through different pedicle approaches in the treatment of osteoporotic vertebral compression fracture osteoporotic vertebral compression fractures (OVCF) by network meta-analysis. METHODS: Pubmed, Embase, Cochrane Library, Web of Science. Database for literature retrieval, retrieval time from the establishment of the database to April 2023, the randomized controlled trials of unilateral vertebroplasty (UVP), bilateral vertebroplasty (BVP), unilateral kyphoplasty (UKP), bilateral kyphoplasty (BKP), curved vertebroplasty (CVP) and curved kyphoplasty (CKP) were screened, evaluated and the data were extracted and included in the analysis. STATA 15.0 and ReMan 5.3 were used for data analysis. This study was registered in the National Institute for Health Research (NIHR) with the registration number CRD42023405181. RESULTS: This study included 16 articles with a total of 1712 patients. The order of visual analogue scale (VAS) improvement from good to bad is CVP > BVP > UVP > CKP > BKP > UKP. The order of kyphotic angles improvement from good to bad is CKP > UKP > UKP > UVP > BVP > CVP. The order of bone cement injection from less to more is UVP > CVP > UKP > CKP > BVP > BKP. The order of bone cement leakage rate from less to more is CKP > CVP > UKP > BKP > UVP > BVP. The order of X-ray exposure time from less to more is CKP > CVP > UVP > BVP > UKP > BKP. The order of operation time from less to more is CVP > UVP > UKP > CKP > BVP > BKP. CONCLUSION: For patients with kyphotic angles, kyphoplasty has unique advantages in improving kyphotic angles. But generally speaking, curved approach can optimize the distribution of bone cement through unilateral approach to achieve the orthopedic effect of bilateral approach, which is a minimally invasive technique with better curative effect and higher safety in the treatment of OVCF.

Effects of a multidomain intervention against cognitive decline on dementia risk profiles - Results from the AgeWell.de trial.

INTRODUCTION: Dementia risk scores constitute promising surrogate outcomes for lifestyle interventions targeting cognitive function. We investigated whether dementia risk, assessed using the LIfestyle for BRAin health (LIBRA) index, was reduced by the AgeWell.de intervention. METHODS: Secondary analyses of the AgeWell trial, testing a multicomponent intervention (including optimization of nutrition, medication, and physical, social, and cognitive activity) in older adults with increased dementia risk. We analyzed data from n = 461 participants with complete information on risk/protective factors comprised by LIBRA at the 24-month follow-up. Intervention effects on LIBRA and LIBRA components were assessed using generalized linear models. RESULTS: The intervention reduced LIBRA scores, indicating decreased dementia risk at follow-up (b = -0.63, 95% confidence interval [CI]: -1.14, -0.12). Intervention effects were particularly due to improvements in diet (odds ratio [OR]: 1.60, 95% CI: 1.16, 2.22) and hypertension (OR: 1.61, 95% CI: 1.19, 2.18). DISCUSSION: The AgeWell.de intervention reduced dementia risk. However, several risk factors did not improve, possibly requiring more intensive interventions. HIGHLIGHTS: The AgeWell.de intervention reduced dementia risk according to LIfestyle for BRAin health (LIBRA) scores. Beneficial effects on LIBRA are mainly due to changes in diet and blood pressure. A pragmatic lifestyle intervention is apt to reduce dementia risk in an at-risk population.

Effectiveness of residential versus outpatient therapy for smoking cessation: The START randomized clinical trial.

BACKGROUND AND AIMS: Tobacco smoking represents a major cause for preventable death and morbidity. Results from non-randomized studies suggest that smoking cessation therapy in a residential setting might be a new viable way to facilitate smoking abstinence. We aimed to test the effects of residential multicomponent group therapy for smoking cessation compared with outpatient group therapy. DESIGN: Prospective parallel-group open-label randomized superiority trial, with assessments at baseline, 6 and 12 months. SETTING: Recruitment throughout Germany via media advertisements. PARTICIPANTS: Adult smokers (≥10 cigarettes/day) randomly assigned to residential (n = 157) or outpatient (n = 158) therapy. 51.8% female; mean age 53.2 years; mean years of smoking 34.4. INTERVENTION AND COMPARATOR: Residential 9-day smoking cessation group therapy comprising six daily therapy sessions and supportive interventions for cessation and daily structure embedded in the routines of a somatic rehabilitation center, compared with weekly outpatient smoking cessation group therapy (3-7 weeks) provided in routine care courses close to the participants' places of residence, both including at least 9 h of behavioral therapy. MEASUREMENTS: Co-primary outcomes were self-reported continuous 6- and 12-month abstinence (hierarchically ordered). Primary analyses were conducted in the therapy-uptake population including participants who started therapy with sensitivity analyses in the intention-to-treat population of all randomized participants. FINDINGS: Intervention uptake rates were 87.3% (n = 137) in the residential and 60.1% (n = 95) in the outpatient group. In the therapy-uptake population, abstinence rates were 46.7% in the residential versus 26.3% in the outpatient group at 6 months (odds ratio [OR] = 2.46, 95% confidence interval [CI] = 1.39-4.33, P = 0.0019) and 39.4% versus 24.2% at 12 months (OR = 2.04, 95% CI = 1.14-3.64, P = 0.017). Biochemically validated abstinence rates at 12 months were 33.1% in the residential versus 17.4% in the outpatient group (OR = 2.35, 95% CI = 1.22-4.51, P = 0.011). In the intention-to-treat population, self-reported and biochemically validated abstinence rates at 12 months were 34.4% in the residential versus 14.6% in the outpatient group (OR = 3.08, 95% CI = 1.77-5.34, P < 0.0001) and 28.6% versus 10.3% (OR = 3.48, 95% CI = 1.85-6.52, P = 0.0001), respectively. CONCLUSIONS: Residential therapy exclusively for smoking cessation is feasible and effective and could be a beneficial new treatment for smokers.

The effect of transcranial magnetic stimulation on cognitive function in post-stroke patients: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Transcranial magnetic stimulation (TMS) is considered as a promising treatment option for post-stroke cognitive impairment (PSCI).Some meta-analyses have indicated that TMS can be effective in treating cognitive decline in stroke patients, but the quality of the studies included and the methodologies employed were less than satisfactory. Thus, this meta-analysis aimed to evaluate the efficacy and safety of TMS for treating post-stroke cognitive impairment. METHODS: We searched online databases like PubMed, Embase, Cochrane Library, and Web of Science to retrieve randomized controlled trials (RCTs) of TMS for the treatment of patients with PSCI. Two independent reviewers identified relevant literature, extracted purpose-specific data, and the Cochrane Risk of Bias Assessment Scale was utilized to assess the potential for bias in the literature included in this study. Stata 17.0 software was used for data analysis. RESULTS: A total of 10 studies involving 414 patients were included. The results of the meta-analysis showed that TMS was significantly superior to the control group for improving the overall cognitive function of stroke patients (SMD = 1.17, 95% CI [0.59, 1.75], I2 = 86.1%, P < 0.001). Subgroup analyses revealed that high-frequency rTMS (HF-rTMS), low-frequency rTMS (LF-rTMS), and intermittent theta burst stimulation (iTBS) all have a beneficial effect on the overall cognitive function of stroke patients. However, another subgroup analysis failed to demonstrate any significant advantage of TMS over the control group in terms of enhancing scores on the Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) and Rivermead Behavioral Memory Test (RBMT) scales. Nonetheless, TMS demonstrated the potential to enhance the recovery of activities of daily living in stroke patients, as indicated by the Modified Barthel Index (MBI) (SMD = 0.76; 95% CI [0.22, 1.30], I2 = 52.6%, P = 0.121). CONCLUSION: This meta-analysis presents evidence supporting the safety and efficacy of TMS as a non-invasive neural modulation tool for improving global cognitive abilities and activities of daily living in stroke patients. However, given the limited number of included studies, further validation of these findings is warranted through large-scale, multi-center, double-blind, high-quality randomized controlled trials. PROSPERO REGISTRATION NUMBER: CRD42022381034.

Pelvic floor muscle training vs radiofrequency for women with vaginal laxity: randomized clinical trial.

BACKGROUND: Vaginal laxity (VL) is a complaint of excessive vaginal looseness with a prevalence ranging from 24% to 38% across studies. AIM: The study sought to compare the effect of radiofrequency (RF) and pelvic floor muscle training (PFMT) on the treatment of women with VL. METHODS: From February 2020 to December 2021, a prospective, parallel, noninferiority, randomized clinical trial was carried out in women ≥18 years of age and complaining of VL in a tertiary hospital. Two groups (RF and PFMT) were evaluated at the beginning of the study and 30 days and 6 months postintervention. A total of 42 participants per arm was sufficient to demonstrate a difference in sexual function on the Female Sexual Function Index at 90% power, 1-sided type 1 error of 0.025 with a noninferiority margin of 4 on the FSFI total score. Analysis was intention-to-treat and per-protocol based. OUTCOMES: The primary endpoint was the change of FSFI score after treatment, and the secondary outcomes were improvement in symptoms of VL and changes in questionnaire scores of sexual distress, vaginal symptoms, and urinary incontinence, in the quantification of pelvic organ prolapse, and pelvic floor muscle (PFM) contraction. RESULTS: Of 167 participants recruited, 87 were included (RF: n = 42; PFMT: n = 45). All questionnaires improved (P < .05) their total scores and subscales in both groups and during the follow-ups. After 30 days of treatment, RF was noninferior to PFMT to improving FSFI total score (mean difference -0.08 [95% confidence interval, -2.58 to 2.42]) in the per-protocol analysis (mean difference -0.46 [95% confidence interval, -2.92 to 1.99]) and in the intention-to-treat analysis; however, this result was not maintained after 6 months of treatment. PFM contraction improved significantly in both groups (RF: P = .006, 30 days; P = .049, 6 months; PFMT: P < .001, 30 days and 6 months), with better results in the PFMT group. CLINICAL IMPLICATIONS: Sexual, vaginal, and urinary symptoms were improved after 30 days and 6 months of treatment with RF and PFMT; however, better results were observed in the PFMT group after 6 months. STRENGTHS & LIMITATIONS: The present randomized clinical trial used several validated questionnaires evaluating quality of life, sexual function and urinary symptoms, in addition to assessing PFM contraction and classifying the quantification of pelvic organ prolapse aiming at anatomical changes in two follow-up periods. The limitations were the lack of a sham-controlled group (third arm) and the difficulty of blinding researchers to assess treatments due to the COVID-19 pandemic. CONCLUSION: After 30 days and 6 months of treatment, sexual, vaginal, and urinary symptoms improved with RF and PFMT; however, better results were observed in the PFMT group after 6 months. RF was noninferior to PFMT in improving FSFI total score after 30 days; however, this result was not maintained after 6 months of treatment.

Protocol for a pragmatic trial of Cannabidiol (CBD) to improve chronic pain symptoms among United States Veterans.

BACKGROUND: Chronic pain affects over 100 million Americans, with a disproportionately high number being Veterans. Chronic pain is often difficult to treat and responds variably to medications, with many providing minimal relief or having adverse side effects that preclude use. Cannabidiol (CBD) has emerged as a potential treatment for chronic pain, yet research in this area remains limited, with few studies examining CBD's analgesic potential. Because Veterans have a high need for improved pain care, we designed a clinical trial to investigate CBD's effectiveness in managing chronic pain symptoms among Veterans. We aim to determine whether CBD oral solution compared to placebo study medication is associated with greater improvement in the Patient Global Impression of Change (PGIC). METHODS: We designed a randomized, double-blind, placebo-controlled, pragmatic clinical trial with 468 participants. Participants will be randomly assigned in a 1:1 ratio to receive either placebo or a CBD oral solution over a 4-week period. The trial is remote via a smartphone app and by shipping study materials, including study medication, to participants. We will compare the difference in PGIC between the CBD and placebo group after four weeks and impacts on secondary outcomes (e.g., pain severity, pain interference, anxiety, suicide ideation, and sleep disturbance). DISCUSSION: Once complete, this trial will be among the largest to date investigating the efficacy of CBD for chronic pain. Findings from this clinical trial will contribute to a greater knowledge of CBD's analgesic potential and guide further research. Given the relative availability of CBD, our findings will help elucidate the potential of an accessible option for helping to manage chronic pain among Veterans. TRIAL REGISTRATION: This protocol is registered at clinicaltrials.gov under study number NCT06213233.

Effect of in-line filtration in newborns: study protocol of the Intravenous Neonatal Central Access Safety (INCAS) randomized controlled trial.

BACKGROUND: Particulate contamination due to infusion therapy (administration of parenteral nutrition and medications) carries a potential health risk for infants in neonatal intensive care units (NICUs). This particulate consists of metals, drug crystals, glass fragments, or cotton fibers and can be generated by drug packaging, incomplete reconstitution, and chemical incompatibilities. In-line filters have been shown to remove micro-organisms, endotoxin, air, and particles in critically ill adults and older infants, but its benefits in newborn remain to be demonstrated. Moreover, 50% of inflammatory episodes in the setting of NICUs are blood culture-negative. These episodes could be partly related to the presence of particles in the infusion lines. METHODS: A multicenter randomized single-blind controlled trial was designed. All infants admitted to NICUs for which prolonged infusion therapy is expected will be enrolled in the study and randomized to the Filter or Control arm. All patients will be monitored until discharge, and data will be analyzed according to a "full analysis set." The primary outcome is the frequency of patients with at least one sepsis-like event, defined by any association of suspected sepsis symptoms with a level of c-reactive protein (CRP) > 5 mg/L in a negative-culture contest. The frequency of sepsis, phlebitis, luminal obstruction, and the duration of mechanical ventilation and of catheter days will be evaluated as secondary outcomes. The sample size was calculated at 368 patients per arm. DISCUSSION: This is the first multicenter randomized control trial that compares in-line filtration of parenteral nutrition and other intravenous drugs to infusion without filters. Sepsis-like events are commonly diagnosed in clinical practice and are more frequent than sepsis in a positive culture contest. The risk of these episodes in the target population is estimated at 30-35%, but this data is not confirmed in the literature. If the use of in-line filters results in a significant decrease in sepsis-like events and/or in any other complications, the use of in-line filters in all intravenous administration systems may be recommended in NICUs. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05537389, registered on 12 September 2022 ( https://classic. CLINICALTRIALS: gov/ct2/show/results/NCT05537389?view=results ).

Reducing neuroendocrine psychosocial stress response through socio-emotional dyadic but not mindfulness online training.

Introduction: Stress-related diseases pose significant health risks and show wide prevalence. Empirical evidence suggests that contemplative practices, such as socio-emotional dyadic mental exercises, hold promise in mitigating the adverse effects of stress and promoting psychosocial well-being. This study aimed to investigate the differential effects of two online contemplative mental training programs on the psychosocial stress response: the first involved classic mindfulness practices, while the second incorporated a socio-emotional dyadic approach known as Affect Dyad. Methods: The study was conducted as part of the longitudinal CovSocial project's phase 2 in the context of the COVID-19 pandemic. 140 individuals participated in the Trier Social Stress Task (TSST), where the psychosocial stress response was assessed with cortisol saliva samples and subjective stress questionnaires in a cross-sectional design after the active training groups finished their intervention period. Participants were randomly assigned to the socio-emotional training group, mindfulness-based training group, or a control group that did not receive any training. Both training programs consisted of a ten-week intervention period with a daily 12-minute app-based mental training practice and weekly 2-hour online coaching sessions led by mental training teachers. Results: Results showed that the socio-emotional Dyad group but not the mindfulness-based group exhibited significantly lower cortisol levels at 10, 20, 30, and 40 minutes after the stressor as well as lower total cortisol output compared to the control group during the TSST, indicating a reduced hormonal stress response to a social stressor. Subjective markers did not show differences between the three groups. Discussion: These findings indicate that the daily socio-emotional dyadic practice, which emphasizes non-judgmental and empathic listening as well as the acceptance of challenging emotions in the presence of others within one's daily life context, may serve as a protective factor against the adverse effects of psychosocial stress triggered by the fear of negative social judgments. Given the high prevalence of stress-related diseases, such online mental training programs based on dyadic practices may thus represent an efficient and scalable approach for stress reduction.

Comparing the antireflux effect of laparoscopic proximal gastrectomy with double-flap technique reconstruction versus laparoscopic total gastrectomy with Roux-en-Y reconstruction for proximal early gastric cancer: study protocol for a multicentre, prospective, open-label, randomised controlled trial.

INTRODUCTION: Laparoscopic proximal gastrectomy with double flap technique (LPG-DFT) reconstruction has been used for proximal early gastric cancer in recent years. However, its feasibility and safety remain uncertain, as only a few retrospective studies have contained postoperative complications and long-term survival data. LPG-DFT for proximal early gastric cancer is still in the early stages of research. Large-scale, prospective randomised controlled trials (RCTs) are necessary to assess the value of LPG-DFT for proximal early gastric cancer. METHODS AND ANALYSIS: This study is a multicentre, prospective, open-label, RCT that investigates the antireflux effect of LPG-DFT compared with laparoscopic total gastrectomy with Roux-en-Y (LTG-RY) reconstruction for proximal early gastric cancer. A total of 216 eligible patients will be randomly assigned to the LPG-DFT group or the LTG-RY group at a 1:1 ratio using a central, dynamic and stratified block randomisation method, if inclusion criteria are met. General and clinical data will be collected when the patient is enrolled in the study and keep pace with the patient at each stage of his medical and follow-up pathway. The primary endpoint is the proportion of patients with reflux esophagitis (Los Angeles Grade B or more) within 12 months postoperatively. The secondary endpoints included intraoperative outcomes, postoperative recovery, postoperative pain assessment, pathological outcomes, postoperative quality of life, postoperative nutrition status, morbidity and mortality rate, and oncological outcomes (3-year overall survival (OS), 3-year disease-free survival (DFS), 5-year DFS and 5-year OS). ETHICS AND DISSEMINATION: The protocol is approved by the Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University ethics committee (registration number: SYSKY-2022-276-02) on 28 September 2022.We will report the positive as well as negative findings in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05890339.