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Primary axillary hyperhidrosis is an idiopathic disorder that creates severe psycho-social burden due to excessive uncontrolled sweating. Various therapeutic agents have been described, but each has its own limitations. The use of fractional microneedling radiofrequency has emerged lately with promising results. This study aimed to determine the efficacy and safety of fractional microneedle radiofrequency in comparison to Botulinum toxin-A (BT-A) in patients with primary axillary hyperhidrosis. In this randomized controlled clinical trial, 20 patients (40 sides) were randomized to either fractional microneedle radiofrequency (4 sessions at 3-week intervals) or BT-A (single session), where each side received one of the treatment modalities. Efficacy was measured at 3, 6 and 12 months using Minor's starch iodine test, HDSS score, Hqol questionnaire, and patient satisfaction. Fractional microneedle radiofrequency, although showed moderate efficacy, is inferior to BT-A regarding longitudinal efficacy at 12 months, as well as patients' satisfaction. Both treatment modalities showed to be equally safe, but fractional microneedle radiofrequency procedure was substantially more painful. In conclusion, fractional microneedle radiofrequency does not offer a better substitute to BT-A in primary axillary hyperhidrosis. BT-A shows higher efficacy, is less painful, less expensive, and needs a smaller number of sessions. [ABSTRACT FROM AUTHOR]

Background and Aims Design Setting Participants Intervention and Comparator Measurements Findings Conclusions 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.Prospective parallel‐group open‐label randomized superiority trial, with assessments at baseline, 6 and 12 months.Recruitment throughout Germany via media advertisements.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.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.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.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.Residential therapy exclusively for smoking cessation is feasible and effective and could be a beneficial new treatment for smokers. [ABSTRACT FROM AUTHOR]

Objectives Materials and Methods Results Conclusion The aim of this study was to evaluate esthetic parameters in the anterior maxillary region by comparing single‐piece zirconia versus titanium narrow‐diameter implants. Additionally, clinical, radiological and patient‐reported outcome measures (PROMs) were analyzed.Thirty implants (tissue level implant) were placed in 30 patients in the maxillary esthetic sector. Depending on randomization, a zirconia (test) or titanium implant (control) was placed. Esthetic, clinical, and radiological parameters, including the implant crown esthetic index (ICAI), pink esthetic score (PES), probing pocket depth, bleeding on probing, plaque index, and marginal bone levels, were evaluated at 12, 36 and 60 months after loading.Sixty months after crown placement, no significant differences were found between groups. The ICAI values were 5.25 ± 4.21 and 4.50 ± 2.98 for the test and control groups, respectively. The corresponding PES values were 7.44 ± 1.93 and 7.43 ± 1.74 for the test and control groups, respectively. There were no significant intergroup differences for the rest of the parameters evaluated.It can be suggested that monotype zirconia implants may serve as a potential alternative to titanium implants in selected clinical scenarios. While the results demonstrated comparable esthetic, clinical, and radiological aspects for zirconia implants as compared to titanium implants after a 5‐year follow‐up period, further research with larger sample sizes and longer‐term follow‐up is recommended. [ABSTRACT FROM AUTHOR]

Objectives: The impact of the Standard Protocol Items: Recommendations for Interventional Trials of Traditional Chinese Medicine (SPIRIT-TCM) Extension 2018 statement on the reporting quality of randomized controlled trial (RCT) protocols in traditional Chinese medicine (TCM) is not clear. This review aimed to assess the reporting characteristics and quality of RCT protocols involving interventions such as Chinese herbal medicine formulas (CHMF), acupuncture, and moxibustion published in the last 3 years. Methods: We conducted an extensive search among multiple databases, including All EBM Reviews, Allied and Complementary Medicine (AMED), Embase, Ovid MEDLINE(R), PubMed, Web of Science, Google Scholar, and ClinicalTrials.gov for publications in English from 1 January 2020 to 10 August 2023. Two reviewers independently assessed the eligibility of the publications, extracted predetermined information, and evaluated the reporting based on the SPIRIT-TCM Extension 2018 checklist. Results: Of the 420 eligible protocols (comprising 163 studies on CHMF, 239 on acupuncture, and 18 on moxibustion), the average reporting compliance rate was only 35.4%. Approximately half of the assessed items fell into the category of poorly reported, demonstrating a compliance rate below 65%. Notably, reporting compliance in acupuncture and moxibustion interventional studies exhibited higher scores than compliance in CHMF studies. Conclusion: Continued, concerted, and coordinated efforts are required by journals, editors, reviewers, and investigators to improve the application and promotion of the SPIRIT-TCM Extension 2018 reporting guideline. [ABSTRACT FROM AUTHOR]

Introduction: In recent years, diverse initiatives have been carried out to control the COVID-19 pandemic, ranging from measures restricting social activities to analyzing drugs and vaccines. Studies on herbal medicines are also increasingly conducted in various countries as an adjuvant therapy or supplement. Therefore, this systematic review aimed to investigate the efficacy of herbal medicines analyzed from various countries through clinical trials with the randomized controlled trial method. The outcomes of Length of Stay (LOS), Negative Conversion Time (NCT), and Negative Conversion Rate (NCR) were the main focus. Methods: An extensive review of literature spanning from 2019 to 2023 was carried out using well-known databases including PubMed, Scopus, and Cochrane. The search included relevant keywords such as "randomized controlled trial," "COVID-19," and "herbal medicine." Results: A total of 8 articles were part of the inclusion criteria with outcomes of LOS, NCT, and NCR. In terms of LOS outcomes, all types of herbal medicines showed significant results, such as Persian Medicine Herbal (PM Herbal), Persian Barley Water (PBW), Jingyin Granules (JY granules), Reduning Injection, and Phyllanthus emblica (Amla). However, only JY granules showed significant results in NCR outcome, while JY granules and Reduning Injection showed significant results in reducing NCT. Conclusion: These findings enrich our understanding of the potential benefits of herbal medicines in influencing LOS, NCR and NCT parameters in COVID-19 patients. Herbal medicines worked to treat COVID-19 through antiviral, antiinflammatory, and immunomodulatory mechanisms. [ABSTRACT FROM AUTHOR]

Background: Learning of burn patient assessment is very important, but heart-breaking for nursing students. This study aimed to compare the effects of feedback lecture method with a serious game (BAM Game) on nursing students' knowledge and skills in the assessment of burn patients. Method: In this randomized controlled clinical trial, 42 nursing students in their 5th semester at Mashhad University of Medical Sciences School of Nursing and Midwifery, were randomly assigned to intervention (BAM game, available for two weeks) and control (feedback lecture method presented in two 90-minute sessions) groups. Two weeks after the intervention, all students were evaluated for their knowledge (using knowledge assessment test) and skills (using an Objective Structured Clinical Examination). Statistical analysis involved independent t-test, Fisher's exact test, analysis of covariance (ANCOVA), and univariable and multivariable ordinal logistic regression models. Results: Following the intervention, the skill scores were 16.4 (SD 2.2) for the intervention group and 11.8 (SD 3.8) for the control group. Similarly, the knowledge scores were 17.4 (SD 2.2) for the intervention group and 14.7 (SD 2.6) for the control group. Both differences were statistically significant (P <.001). These differences remained significant even after adjusting for various factors such as age, gender, marital status, residence, university entrance exam rank, and annual GPA (P <.05). Furthermore, the BAM game group showed significantly higher skills rank than the feedback lecture group across most stations (eight of ten) (P <.05) in the univariable analysis. Multivariable analysis also revealed a significantly higher skills score across most stations even after adjusting for the mentioned factors (P <.05). These results suggest that the BAM game group had higher skills scores over a range of 1.5 to 3.9 compared to the feedback lecture group. Conclusions: This study demonstrated that nursing students who participated in the BAM game group exhibited superior performance in knowledge acquisition and skill development, compared to those in the control group. These results underscore a significant enhancement in educational outcomes for students involved with the BAM game, confirming its utility as a potent and effective pedagogical instrument within the realm of nursing education. Trial registration: Iranian Registry of Clinical Trials: IRCT20220410054483N1, Registration date: 18/04/2022. [ABSTRACT FROM AUTHOR]

Background and Aims: The use of corticosteroids in chronic drug‐induced liver injury (DILI) is an important issue. Our previous randomized controlled trial showed that patients with chronic DILI benefited from a 48‐week steroid stepwise reduction (SSR) regimen. However, it remains unclear whether a shorter course of therapy can achieve similar efficacy. In this study, we aimed to assess whether a 36‐week SSR can achieve efficacy similar to that of 48‐week SSR. Methods: A randomized open‐label trial was performed. Eligible patients were randomly assigned to the 36‐ or 48‐week (1:1) SSR group. Liver biopsies were performed at baseline and at the end of treatment. The primary outcome was the proportion of patients with relapse rate (RR). The secondary outcomes were improvement in liver histology and safety. Results: Of the 90 participants enrolled, 84 (87.5%) completed the trial, and 62 patients (68.9%) were women. Hepatocellular damage was observed in 53.4% of the cohort. The RR was 7.1% in the 36‐week SSR group but 4.8% in the 48‐week SSR group, as determined by per‐protocol set analysis (p = 1.000). Significant histological improvements in histological activity (93.1% vs. 92.9%, p = 1.000) and fibrosis (41.4% vs. 46.4%, p =.701) were observed in both the groups. Biochemical normalization time did not differ between the two groups. No severe adverse events were observed. Conclusions: Both the 36‐ and 48‐week SSR regimens demonstrated similar biochemical response and histological improvements with good safety, supporting 36‐week SSR as a preferable therapeutic choice (ClinicalTrials.gov, NCT03266146). [ABSTRACT FROM AUTHOR]

Background: Increasingly, patients, clinicians, and regulators call for more evidence on the impact of innovative medicines on quality of life (QoL). We assessed the effects of disease-modifying therapies (DMTs) on QoL in people with multiple sclerosis (PwMS). Methods: Randomized trials assessing approved DMTs in PwMS with results for at least one outcome referred to as "quality of life" were searched in PubMed and ClinicalTrials.gov. Results: We identified 38 trials published between 1999 and 2023 with a median of 531 participants (interquartile range (IQR) 202 to 941; total 23,225). The evaluated DMTs were mostly interferon-beta (n = 10; 26%), fingolimod (n = 7; 18%), natalizumab (n = 5; 13%), and glatiramer acetate (n = 4; 11%). The 38 trials used 18 different QoL instruments, with up to 11 QoL subscale measures per trial (median 2; IQR 1–3). QoL was never the single primary outcome. We identified quantitative QoL results in 24 trials (63%), and narrative statements in 15 trials (39%). In 16 trials (42%), at least one of the multiple QoL results was statistically significant. The effect sizes of the significant quantitative QoL results were large (median Cohen's d 1.02; IQR 0.3–1.7; median Hedges' g 1.01; IQR 0.3–1.69) and ranged between d 0.14 and 2.91. Conclusions: Certain DMTs have the potential to positively impact QoL of PwMS, and the assessment and reporting of QoL is suboptimal with a multitude of diverse instruments being used. There is an urgent need that design and reporting of clinical trials reflect the critical importance of QoL for PwMS. [ABSTRACT FROM AUTHOR]

Aim: To investigate the efficacy and safety of pioglitazone compared to placebo when added to metformin plus dapagliflozin, a sodium‐glucose cotransporter‐2 (SGLT2) inhibitor, for patients with type 2 diabetes mellitus (T2DM). Materials and Methods: In a multicentre study, with a randomized, double‐blind, placebo‐controlled design, 249 Korean patients with T2DM suboptimally managed on metformin and dapagliflozin were assigned to receive either pioglitazone (15 mg daily) or placebo for 24 weeks, followed by a 24‐week pioglitazone extension. Primary outcomes included changes in glycated haemoglobin (HbA1c), with secondary outcomes assessing insulin resistance, adiponectin levels, lipid profiles, liver enzymes, body weight and waist circumference. Results: Pioglitazone administration resulted in a significant reduction in HbA1c levels (from 7.80% ± 0.72% to 7.27% ± 0.82%) compared with placebo (from 7.79% ± 0.76% to 7.69% ± 0.86%, corrected mean difference: −0.42% ± 0.08%; p < 0.01) at 24 weeks. Additional benefits from pioglitazone treatment included enhanced insulin sensitivity, increased adiponectin levels, raised high‐density lipoprotein cholesterol levels and reduced liver enzyme levels, resulting in improvement in nonalcoholic fatty liver disease liver fat score. Despite no serious adverse events in either group, pioglitazone therapy was modestly but significantly associated with weight gain and increased waist circumference. Conclusions: Adjunctive pioglitazone treatment in T2DM inadequately controlled with metformin and dapagliflozin demonstrates considerable glycaemic improvement, metabolic benefits, and a low risk of hypoglycaemia. These advantages must be weighed against the potential for weight gain and increased waist circumference. [ABSTRACT FROM AUTHOR]

Background: The effectiveness and safety of moderately hypofractionated radiotherapy (HFRT) in patients undergoing breast-conserving surgery (BCS) has been demonstrated in several pivotal randomized trials. However, the feasibility of applying simultaneous integrated boost (SIB) to the tumor bed and regional node irradiation (RNI) using modern radiotherapy techniques with HFRT needs further evaluation. Methods: This prospective, multi-center, randomized controlled, non-inferiority phase III trial aims to determine the non-inferiority of HFRT combined with SIB (HFRTsib) compared with conventional fractionated radiotherapy with sequential boost (CFRTseq) in terms of five-year locoregional control rate in breast cancer patients undergoing upfront BCS. A total of 2904 participants will be recruited and randomized in a 1:1 ratio into the HFRTsib and CFRTseq groups. All patients will receive whole breast irradiation, and those with positive axillary nodes will receive additional RNI, including internal mammary irradiation. The prescribed dose for the HFRTsib group will be 40 Gy in 15 fractions, combined with a SIB of 48 Gy in 15 fractions to the tumor bed. The CFRTseq group will receive 50 Gy in 25 fractions, with a sequential boost of 10 Gy in 5 fractions to the tumor bed. Discussion: This trial intends to assess the effectiveness and safety of SIB combined with HFRT in early breast cancer patients following BCS. The primary endpoint is locoregional control, and the results of this trial are expected to offer crucial evidence for utilizing HFRT in breast cancer patients after BCS. Trial registration: This trial was registered at ClincalTrials.gov (NCT04025164) on July 18, 2019. [ABSTRACT FROM AUTHOR]

Purpose: Regarding the importance of obesity concerns and trying to help obese individuals, we planned to develop an effective probiotic formula for weight control. So, this double-blind randomized clinical trial study investigated the impact of probiotics supplementation on anthropometric and biochemical parameters in obese adults. Methods: In this study, 66 obese patients with BMI in the range of 30–40 kg/m2, were enrolled and randomly assigned to either the probiotic or placebo group. They all received advice to maintain a reduction in daily caloric intake and for 3 months received two unlabeled placebo or probiotic (Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus casei and Bifidobacterium langum) capsules per day. For each participant demographic and medical history questionnaire, semi-quantitative food frequency questionnaire (FFQ), and modifiable activity questionnaire (MAQ) were completed at the beginning of the study and anthropometric and biochemical measurements were done before and after intervention. Results: At the end of the trial 25 subjects in the probiotic group and 26 subjects in the placebo group were analyzed. After the intervention, in the probiotic group, the level of fasting insulin was reduced significantly (P < 0.05). Weight, body mass index, waist circumference, and hip circumference decreased within both groups. This reduction amount's mean was higher in the probiotic group. Also, total cholesterol, triglycerides, and LDL levels were decreased, but not statistically significant. Conclusion: This study may suggest the potential of this combined probiotic supplement for treating obesity and related metabolic disorders. However, further researches are warranted for a definitive determination of its properties. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to estimate minimal clinically important difference (MCID) values for the World Health Organization Quality of Life Brief version (WHOQOL-BREF) among adults with neurofibromatosis (NF). An MCID is needed to demonstrate clinical meaningfulness of interventions for NF. Methods: We estimated MCID for the WHOQOL-BREF: the quality of life (QoL) measure recommended by the Response Evaluation in Neurofibromatosis and Schwannomatosis International Collaboration. We used data from 228 clinical trial participants with NF type 1, NF type 2-related schwannomatosis, or schwannomatosis (SCHWN) who completed 10 weeks of a virtual group mind–body program targeting resiliency or a time- and attention-matched control. Following established guidelines, we estimated MCIDs using both anchor-based and distribution-based methods for physical, psychological, social relationships, and environmental domains of the WHOQOL-BREF. Results: MCID results varied across method and QoL domain. Three anchor-based methods, average change (AC), change difference (CD), and regression (REG), yielded the most consistent and comparable MCID across QoL domains. Based on these methods, we recommend ranges for each QoL domain: Physical QoL (3.9–7.3), Psychological QoL (4.7–8.1), Social QoL (2.6–5.9), and Environmental QoL (4.1–6.6). Conclusion: Establishing a rigorous MCID for QoL in NF is a critical step toward evaluating meaningful change in response to psychosocial interventions. [ABSTRACT FROM AUTHOR]

Objective: According to the World Alzheimer's Disease Report in 2015, there were 9.9 million new cases of dementia in the world every year. At present, the number of patients suffering from dementia in China has exceeded 8 million, and it may exceed 26 million by 2040.Mild cognitive impairment (MCI) refers to the pathological state of pre-dementia with the manifestation of the progressive decline of memory or other cognitive functions but without decline of activities of daily life. It is particularly important to prevent or prolong the development of MCI into dementia. Research showing effects of rhythmic auditory stimulation based-movement training(RASMT) interventions on cognitive function is also emerging. Therefore, the present meta-analysis briefly summarize findings regarding the impacts of RASMT programs on cognitive impairment. Methods: Data from Pubmed, Embase, and Cochrane Library were utilized. The impact of RASMT on cognitive functions was evaluated using indicators such as overall cognitive status, memory, attention, and executive functions. The REVMAN5.3 software was employed to analyze bias risks integrated into the study and the meta-analysis results for each indicator. Results: A total of 1,596 studies were retrieved, of which 1,385 non-randomized controlled studies and 48 repetitive studies were excluded. After reviewing titles and abstracts of the remaining 163 articles, 133 irrelevant studies were excluded, 30 studies were downloaded and read the full text. Among 30 articles, 18 articles that did not meet the inclusion criteria were excluded, the other 12 studies were included in this meta-analysis. Utilizing the Cochrane Collaborative Network Bias Risk Assessment Scale, it was found that 11 studies explained the method of random sequence generation, nine studies did not describe allocation concealment, four were single-blinded to all researchers, and eight reported single-blinding in the evaluation of experimental results. In the meta-analysis, the main outcomes showed statistically significant differences in overall cognitive status [MD = 1.19, 95%CI (0.09, 2.29), (p < 0.05)], attention [MD = -1.86, 95%CI (-3.53, -0.19), (p < 0.05)], memory [MD = 0.71, 95%CI (0.33, 1.09), (p < 0.01)], and executive function [MD = -0.23, 95% CI (-0.44, -0.02), (p < 0.05)]. Secondary outcomes indicated no statistically significant differences in verbal fluency [MD = -0.51, 95%CI (-1.30, 0.27), (p = 0.20)], while depression [MD = -0.29, 95% CI (-0.42, -0.16), (p < 0.01)] and anxiety [MD = 0.19, 95% CI (0.06, 0.32), (p < 0.01)] exhibited statistically significant differences. The GRADEpro GDT online tool assessed the quality of evidence for the outcome measures, revealing one low-quality outcome, two moderate-quality outcomes, and one high-quality outcome in this review. Conclusion: This study shows that RASMT can improve the general cognitive status, memory, attention and executive function of patients with cognitive impairment. The quality of evidence revealed that MMSE was low, attention and memory were moderate, and executive function was high. The RAMST program (type of exercise: play percussion instruments; time of exercise: 30-60 min; frequency of exercise: 2-3 times/week; duration of exercise: more than 12 weeks) was proved to be more effective in improving cognitive function. However, the sample size is relatively insufficient, the future needs further study. [ABSTRACT FROM AUTHOR]

Objective: Diabetic peripheral neuropathy (DPN) stands as a crucial complication of diabetes, significantly affecting patients' quality of life. This study aims to elucidate the evidence distribution from clinical randomized controlled trials (RCTs) on DPN treatment with traditional Chinese medicine (TCM) through evidence mapping. Methods: A comprehensive search was conducted from January 2017 to October 2022 in databases such as Wanfang (China Online Journals), CNKI (China National Knowledge Infrastructure), VIP (China Science and Technology Journal Database), SinoMed (Chinese Biomedical Literature Database), PubMed, Web of Science, and Cochrane Library. Literature related to the treatment of DPN with TCM was selected. From the 1,229 RCTs identified over the past 6 years, relevant data were extracted. The evidence mapping approach was utilized, and trends in publications, study scales, intervention types, and evaluation indicators were analyzed using descriptive text combined with tables and bubble charts. Results: Research on the treatment of DPN with TCM is extensive. The publication trend remains relatively stable with predominantly smaller sample sizes. The main treatments encompass oral Chinese medicine and traditional external treatments. The most common evaluation indicators are neurophysiological, efficiency rate, symptom signs, neuropathy scores, and traditional Chinese symptoms, with less focus on psychological status and the ankle-brachial index (ABI). Conclusion: Shedding light on contemporary research, this study explores the current RCTs evaluating TCM's efficacy in treating DPN. The findings not only highlight the potential role of TCM in addressing diabetic complications but also underscore areas that could benefit from refined research approaches, expanded intervention methods, and broader assessment criteria. Our observations aim to inform and inspire future research directions and clinical practices concerning TCM's role in managing diabetes-associated complications. [ABSTRACT FROM AUTHOR]

BACKGROUND: The relationship between dietary modification and Multiple Sclerosis (MS)-related disability has been emphasized in several researches. AIMS: To determine whether a co-administration of anti-inflammatory-antioxidant rich diet and synbiotics might improve clinical manifestations in progressive MS patients. METHODS: The study involved 70 patients with progressive MS (primary-progressive, secondary-progressive, and progressive-relapsing) who were randomized to receive either intervention (synbiotics capsule plus an anti-inflammatory-antioxidant-rich diet) or placebo. Quality of Life (QOL), Expanded Disability Status Scale (EDSS), and depression-anxiety scores were evaluated before and after the follow-up. Analysis of covariance was performed for final analysis (SPSS v.14). RESULTS: Significant reductions were seen in EDSS (2.6±1.1 to 2.4±1.0, P < 0.001), State Anxiety Inventory (53.7±10.3 to 47.8±10.6, P < 0.001), and QOL scores after four months of intervention. No significant difference was seen across the depression severity (Δ for intervention = –2.2±5.5 vs. Δ for control = –0.6±5.7; P = 0.264). CONCLUSION: This study demonstrates that a combination of synbiotics and diet could be a promising strategy to improve severity and clinical manifestations of progressive MS. [ABSTRACT FROM AUTHOR]

Introduction: Treatment of pregnancy‐associated breast cancer is complex, as providers try to balance risks to the pregnant person and the developing fetus. Given increased case fatality and increasing incidence, there is a pressing need understand the efficacy and safety of different treatment regimens in this population; however, pregnant and lactating people have traditionally been excluded from participating in randomized controlled trials (RCTs). Given recent efforts to expand the inclusion criteria for oncology RCTs, this study aimed to review the inclusion/exclusion criteria of current breast cancer RCTs to assess what proportion of trials permitted enrollment of pregnant and lactating persons. Material and methods: We conducted a comprehensive search of ClinicalTrials.gov in January 2022 to identify interventional studies of breast cancer in adults that were actively recruiting. The primary outcomes were the exclusion of pregnant and lactating people. Results: The search identified 1706 studies, of which 1451 met eligibility criteria. Overall, 69.4% and 54.8% of studies excluded pregnant and lactating people, respectively. The exclusion of pregnant and lactating persons differed by study characteristics but extended across all trial designs, locations, phases and interventions. Exclusion of pregnant and lactating persons was most common in trials where the intervention was biological (86.3%), drug (83.5%) or radiation (81.5%). Conclusions: The exclusion of pregnant and lactating people from clinical trials contributes to evidence gaps in how to treat this population. A paradigm shift is needed that focuses on how research can be used to protect pregnant people from future harms, instead of protecting pregnant people from research‐related risks. [ABSTRACT FROM AUTHOR]

Objective: To systematically review the efficacy and safety of nonsteroidal mineralocorticoid receptor antagonists (MRAs) in chronic kidney disease (CKD). Methods: We systematically searched six databases to identify randomized controlled trials (RCTs) about nonsteroidal MRAs for CKD, from inception to 22 August 2023. Two reviewers independently screened the retrieved articles, extracted data, and assessed the risk of bias of included RCTs using the Cochrane risk of bias tool. We then conducted meta-analysis of the data using Stata 17.0 software. Results: 11 RCTs (n = 15,817) were included in this meta-analysis. Compared with placebo, nonsteroidal MRAs significantly reduced the proportion of patients with =40% decline in estimated glomerular filtration rate (eGFR) from baseline [RR = 0.85, 95% CI (0.78, 0.92), p < 0.001], although the magnitude of eGFR reduction was greater [WMD = -2.83, 95% CI (-3.95, -1.72), p < 0.001]. The experimental group also had lower incidence of composite renal outcome [RR = 0.86, 95% CI (0.79, 0.93), p < 0.001] and greater reduction in urine albumin-tocreatinine ratio (UACR) from baseline [WMD = -0.41, 95% CI (-0.49, -0.32), p < 0.001], as well as reduced cardiovascular events [RR = 0.88, 95% CI (0.80, 0.95), p = 0.003]. MRAs did not increase any adverse events compared to placebo [RR = 1.00, 95% CI (0.99, 1.01), p = 0.909], but had higher incidence of hyperkalemia [RR = 2.05, 95% CI (1.85, 2.280), p < 0.001]. Compared with eplerenone, there was no significant difference in the proportion of patients with ≥40% decline in eGFR [RR = 0.57, 95% CI (0.18, 1.79), p = 0.335] or hyperkalemia [RR = 0.95, 95%CI (0.48, 1.88), p = 0.875]. Conclusion: Nonsteroidal MRAs can reduce the incidence of end-stage renal disease and cardiovascular adverse events in patients. Although there was still a risk of hyperkalemia compared to placebo, there was no significant difference in any adverse events compared to either placebo or eplerenone. It has become a new option for drug treatment of CKD patients, but more clinical trials are still needed to verify its efficacy and safety. Especially further direct comparison of the nonsteroidal MRAs to eplerenone in view of the relatively small number of patients reviewed are needed. [ABSTRACT FROM AUTHOR]

Background: Fluoridation of public water systems is known as a safe and effective strategy for preventing dental caries based on evidence from non-randomized studies. Yet 110 million Americans do not have access to a fluoridated public water system and many others do not drink tap water. This article describes the study protocol for the first randomized controlled trial (RCT) of fluoridated water that assesses its potential dental caries preventive efficacy when delivered in bottles. Methods: waterBEST is a phase 2b proof-of-concept, randomized, quadruple-masked, placebo-controlled, parallel-group trial designed to estimate the potential efficacy of fluoridated versus non-fluoridated bottled water to prevent dental caries incidence in the first 4 years of life. Two hundred children living in eastern North Carolina, USA, and aged 2–6 months at screening are being allocated at random in a 1:1 ratio to receive fluoridated (0.7 mg/L F) or non-fluoridated bottled water sourced from two local public water systems. Throughout the 3.5-year intervention, study water is delivered monthly in 5-gallon bottles to each child's home with instructions to use it whenever the child consumes water as a beverage or in food preparation. Parents are interviewed quarterly to monitor children's water consumption and health. At annual visits, the presence of dental caries is evaluated with a dental screening examination. Clippings from fingernails and toenails are collected to quantify fluoride content as a biomarker of total fluoride intake. The primary endpoint is the number of primary tooth surfaces decayed, missing, or filled due to dental caries measured by the study dentist near the time of the child's fourth birthday. Tooth decay is assessed at the threshold of macroscopic enamel loss. For the primary aim, a least-squares, generalized linear model will estimate efficacy and its one-tailed, upper 80% confidence limit. Discussion: waterBEST is the first evaluation of a randomized intervention of fluoridated drinking water in bottles to prevent dental caries in the primary dentition. This innovative method of delivering fluoridated water has the potential to prevent early childhood caries in a large segment of the US population that currently does not benefit from fluoridated public water. Trial registration: ClinicalTrials.gov NCT04893681. Registered on March 2022. Last update posted on 10 October 2023. https://clinicaltrials.gov/study/NCT04893681?cond=Dental%20Caries%20in%20Children&term=fluoride&locStr=North%20Carolina,%20USA&country=United%20States&state=North%20Carolina&distance=50&rank=1 [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Virtual reality (VR) training effectiveness in improving hip arthroplasty surgical skills requires further evaluation. We hypothesised VR training could improve accuracy and the time taken by medical students compared to a control group with only video teaching. Methods: This single-centre randomized controlled clinical trial collected data from March to June 2023. Surgically naïve volunteer undergraduate medical students performed three sessions on a VR training platform, either cup (VR-Cup=Control-Stem) or stem (VR-Stem=Control-Cup) implantation. The primary outcome was the mean difference between predefined cup inclination (60°) and stem anteversion (20°) compared to the actual implanted values in sawbones between VR and control groups. Secondary outcomes were task completion time and mistake number between the groups. Results: A total of 101 students participated (VR-Cup 47, VR-Stem 54). Groups did not significantly differ concerning age (p = 0.879), gender (p = 0.408), study year (p = 0.938), previous VR use (p = 0.269) and baseline medical and procedural knowledge. The VR-Cup implanted the cup closer to the intended target (p < 0.001) and faster than the Control-Cup group (p = 0.113). The VR-Stem implanted the stem closer to the intended target (p = 0.008) but not faster than the Control-Cup group (p = 0.661). Stem retroversion was commoner in the Control-Stem than in the VR-Stem group (p = 0.016). Conclusions: VR training resulted in higher rates of accurate procedure completion, reduced time and fewer errors compared to video teaching. VR training is an effective method for improving skill acquisition in THA. Trial registration: ClinicalTrials.gov Identifier: NCT05807828 [ABSTRACT FROM AUTHOR]

This study (ISRCTN17174559) aimed to explore the efficacy and safety of a kind of herbal porridge (Hou Gu Mi Xi) on the clinical symptoms of functional dyspepsia (FD). This was a single‐center, single‐dose, prospective, double‐blind, randomized controlled trial involving 64 participants with FD (35 cases and 29 controls) for 2 months of intervention and 1 month of follow‐up. The 7‐point Global Overall Symptom Scale (GOSS), 36‐Item Short Form Survey (SF‐36), and other indicators were assessed at baseline (day 0), at days 15, 30, and 60 of treatment, and at follow‐up 1 month after the end of the intervention. Many participants with FD achieved remission of their epigastric symptoms at follow‐up on the 90th day after treatment with herbal porridge compared to the placebo group (45.71% vs. 20.69%, p =.036). Furthermore, herbal porridge appeared to be effective in improving the quality of life of participants with FD, which was reflected in the rising SF‐36 scores for physical role, bodily pain, emotional role, and mental health. Although adverse events were reported, there was no overall difference in the number of adverse events between the two groups (p =.578). Herbal porridge is another effective and safe method for improving the symptoms and quality of life in patients with FD. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to test the hypothesis that use of NerveTrend™ mode of intermittent neuromonitoring (i‐IONM) during thyroidectomy may identify and prevent impending recurrent laryngeal nerve (RLN) injury. Methods: A randomized clinical trial. The primary outcome was prevalence of RLN injury on postoperative day 1. In NerveTrend™ group the i‐IONM stimulator was used for trending of amplitude and latency changes from initial vagal electromyographic baseline to tailor surgical strategy. Results: Some 264 patients were randomized into the intervention versus the control group, 132 patients each. RLN injury was found on postoperative day 1 in 5/264 (1.89%) nerves at risk (NAR) versus 12/258 (4.65%) NAR whereas staged thyroidectomy was used in 0/132 (0.00%) versus 6/132 (4.54%) patients (p = 0.067 and p = 0.029, respectively). Conclusion: The use of NerveTrend™ mode resulted in tendency towards reduced RLN injury on postoperative day 1 and significant decrease of need for a staged thyroidectomy. [ABSTRACT FROM AUTHOR]

Background Emotional symptoms are recognized as a key feature in individuals with major depressive disorder. Previously, emotional blunting has been described both as a side effect of antidepressant treatment and as a symptom of depression. Little is known about the change of emotional blunting during antidepressant treatment. Methods The PREDDICT trial is a randomized, placebo-controlled, 6-week trial on the augmentation of vortioxetine with the anti-inflammatory agent celecoxib or placebo. Presently we report on exploratory secondary outcomes of changes in emotional blunting in depression assessed with the Oxford Depression Questionnaire (ODQ) total score and subscores from baseline to 8-week, 3-month, and 6-month follow-up assessments. Results In the whole group, there was a significant improvement in the ODQ total score and all subscores after 8 weeks. After stratification of participants into the treatment groups, the ODQ total score as well as subscores related to emotional blunting as a symptom of depression (reduction in positive emotions, not caring) improved between baseline and all follow-up time points in both treatment groups. Changes in subscores considered as a side effect of antidepressants (general reduction in emotions, emotional detachment) were inconclusive in both treatment groups. Overall, the placebo-augmented group showed slightly better results in changes of emotional blunting scores than the celecoxib group as did those with elevated inflammation at screening, regardless of treatment group. Conclusions This analysis suggests favorable effects of vortioxetine on emotional blunting in both short- and long-term course. The beneficial impact of vortioxetine on emotional blunting was weaker in celecoxib-augmented patients compared with placebo, possibly due to pharmacokinetic interactions. Clinical Trials Registration: Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12617000527369p. Registered on 11 April 2017, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12617000527369p. [ABSTRACT FROM AUTHOR]

Background: Clinical trials assessing new treatment effects require a control group to compare the pure treatment effects. However, in clinical trials on regenerative medicine, rare diseases, and intractable diseases, it may be ethically difficult to assign participants to the control group. In recent years, the use of historical control data has attracted attention as a method for supplementing the number of participants in the control group. When combining historical control data with new randomized controlled trial (RCT) data, the assessment of heterogeneity using outcome data is not sufficient. Therefore, several statistical methods that consider participant outcomes and baseline characteristics, including the propensity score (PS) method have been proposed. Methods: We propose a new method considering "information on whether the data are RCT data or not" in the PS model when combining the RCT and historical control data. The performance of the proposed method in estimating the treatment effect is evaluated using simulation data. Results: When the distribution of covariates is similar between the RCT and historical control data, not much difference in performance is found between the proposed and conventional methods to estimate the treatment effect. On the other hand, when the distribution of covariates is not similar between the two kinds of data, the proposed method shows higher performance. Conclusions: Even when it is not known whether RCT and historical control data are similar, the proposed PS model is useful to estimate the treatment effect appropriately in RCTs using historical control data. [ABSTRACT FROM AUTHOR]

Background: Vancomycin is a commonly prescribed antibiotic to treat gram-positive infections. The efficacy of vancomycin is known to be directly related to the pharmacokinetic/pharmacodynamic (PK/PD) index of the area under the concentration-time curve (AUC) divided by the minimal inhibitory concentration (MIC) of the pathogen. However, in most countries, steady-state plasma concentrations are used as a surrogate parameter of target AUC/MIC, but this practice has some drawbacks. Hence, direct AUC-guided monitoring of vancomycin using model-informed precision dosing (MIPD) tools has been proposed for earlier attainment of target concentrations and reducing vancomycin-related nephrotoxicity. However, solid scientific evidence for these benefits in clinical practice is still lacking. This randomized controlled trial (RCT) aims to investigate the clinical utility of MIPD dosing of vancomycin administered via continuous infusion in hospitalized adults. Methods: Participants from 11 wards at two Belgian hospitals are randomly allocated to the intervention group or the standard-of-care comparator group. In the intervention group, clinical pharmacists perform dose calculations using CE-labeled MIPD software and target an AUC24h of 400 to 600 mg × h/L, whereas patients in the comparator group receive standard-of-care dosing and monitoring according to the institutional guidelines. The primary endpoint is the proportion of patients reaching the target AUC24h/MIC of 400–600 between 48 and 72 h after start of vancomycin treatment. Secondary endpoints are the proportion of patients with (worsening) acute kidney injury (AKI) during and until 48 h after stop of vancomycin treatment, the proportion of patients reaching target AUC24h/MIC of 400–600 between 72 and 96 h after start of vancomycin treatment, and the proportion of time within the target AUC24h/MIC of 400–600. Discussion: This trial will clarify the propagated benefits and provide new insights into how to optimally monitor vancomycin treatment. Trial registration: EudraCT number: 2021-003670-31. Registered June 28, 2021. ClinicalTrials.gov identifier: NCT05535075. Registered September 10, 2022. Protocol version 3, protocol date: April 21, 2023. [ABSTRACT FROM AUTHOR]

The purpose is to explore the analgesic effect of a single Nd:YAG laser dose after mandibular third molar extraction. This was a prospective randomized controlled clinical trial. Subjects were enrolled according to the inclusion and exclusion criteria and randomly divided into the experimental and control groups. In the experimental group, the wound was irradiated with the Nd:YAG laser (wavelength, 1064 nm; output power, 1.5 W; energy density, 45 J/cm2; and power density, 1.5/cm2, pulsed mode) immediately after mandibular third molar extraction for 120 s (30 s at each site). In the control group, the laser working tip was placed near the extraction site but not activated. The primary outcome was the visual analog scale (VAS) pain scores in both groups at 2, 4, 12, 24, 48, and 72 h and 7 days after surgery. Secondary outcomes included wound healing scores and adverse reactions. The VAS score was significantly lower in the experimental group than in the control group at 2 and 4 h after surgery, while there was no significant difference in the VAS score between the two groups at 12, 24, or 48 h or 7 days after surgery. There were no significant differences in the wound healing scores between the two groups on postoperative day 7. No adverse reactions were observed in any of the laser-irradiated areas. A single Nd:YAG laser dose was effective in reducing pain at 2 and 4 h after mandibular third molar extraction. China Clinical Trial Registry: ChiCTR2000033870 (Registration Date: 2020–6-15). [ABSTRACT FROM AUTHOR]

Background: Premature ejaculation is one of the most common male sexual dysfunction, affecting approximately 30% of men. The aim of this study is to evaluate the efficacy and at the same time the safety of the cranial electrotherapy stimulation (CES) device in treatment of premature ejaculation disorder. Methods: Based on a randomized clinical trial, two groups were included in the study, so that the first group was treated with sertraline along with an ATANG (AT-9 model) CES, and the second group with sertraline and inactive the CES device (as the placebo group). The state of premature ejaculation after treatment (using the Premature Ejaculation Diagnostic Tool (PEDT) questionnaire) was evaluated and compared for both groups. Results: In the intervention and placebo groups, the average score of the PEDT questionnaire before the intervention did not differ significantly between the two groups (p-value equal to 0.93). However, the average score of the PEDT questionnaire after the intervention for CES group and placebo group was 10.28 ± 1.93 and 13.23 ± 3.05, respectively, which demonstrated a significant decrease in the intervention group (p-value equal to 0.01). Conclusion: The use of CES device as a complementary treatment along with routine drug treatment (sertraline) is associated with a significant improvement in the condition of premature ejaculation of patients. Trial registration: Name of the registry: IRCT Iranian Registry of Clinical Trials. Trial registration number: IRCT20210621051657N1. Date of registration: December 11, 2022. URL of trial registry record: https://en.irct.ir/trial/57201. [ABSTRACT FROM AUTHOR]

Background: The distal transradial access (dTRA) has become an attractive and alternative access to the conventional transradial access (TRA) for cardiovascular interventional diagnosis and/or treatment. There was a lack of randomized clinical trials to evaluate the effect of the dTRA on the long-term radial artery occlusion (RAO). Methods: This was a prospective, randomized controlled study. The primary endpoint was the incidence of long-term RAO at 3 months after discharge. The secondary endpoints included the successful puncture rate, puncture time, and other access-related complications. Results: The incidence of long-term RAO was 0.8% (3/361) for dTRA and 3.3% (12/365) for TRA (risk ratio = 0.25, 95% confidence interval = 0.07–0.88, P = 0.02). The incidence of RAO at 24 h was significantly lower in the dTRA group than in the TRA group (2.5% vs. 6.7%, P < 0.01). The puncture success rate (96.0% vs. 98.5%, P = 0.03) and single puncture attempt (70.9% vs. 83.9%, P < 0.01) were significantly lower in the dTRA group than in the TRA group. However, the number of puncture attempts and puncture time were higher in the dTRA group. The dTRA group had a lower incidence of bleeding than the TRA group (1.5% vs. 6.0%, P < 0.01). There was no difference in the success rate of the procedure, total fluoroscopy time, or incidence of other access-related complications between the two groups. In the per-protocol analysis, the incidence of mEASY type ≥ II haematoma was significantly lower in the dTRA group, which was consistent with that in the as-treated analysis. Conclusions: The dTRA significantly reduced the incidence of long-term RAO, bleeding or haematoma. Trial registration: ClinicalTrials.gov identifer: NCT05253820. [ABSTRACT FROM AUTHOR]

This Phase IV placebo-controlled clinical trial was designed to demonstrate the efficacy and safety of the product Neurodoron (Kalium phosporicum comp., KPC) in patients with neurasthenia. This monocenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial (registration number: DRKS00003261) was conducted in an outpatient German trial site. Women and men aged 18 and above were randomized to receive either KPC or placebo if they reported typical symptoms of neurasthenia and a severe psychiatric disorder could be excluded. The primary objectives were a reduction in characteristic symptoms of nervous exhaustion and perceived stress as well as improvement in general health status after 6 weeks of treatment. In total, 204 patients underwent screening, 78 were randomized in each treatment group, and 77 patients each received treatment (intention-to-treat (ITT) population = 154 patients). For none of the primary efficacy variables, an advantage in favor of KPC could be demonstrated in the pre-specified analysis (p-values between 0.505–0.773, Student's t-test). In a post-hoc analysis of intra-individual differences after 6 weeks treatment, a significant advantage of KPC vs. placebo was shown for characteristic symptoms of nervous exhaustion (irritability (p = 0.020); nervousness (p = 0.045), Student's t-test). Adverse event (AE) rates were similar between treatment groups, in both groups six AEs were assessed as causally related to treatment (severity mild or moderate). No AE resulted in discontinuation of treatment. Trial treatment was well tolerated with only a few and minor AEs reported, confirming the markedly good safety of KPC. A significant improvement of neurasthenia was seen for the total study population at the end of the treatment period. Superiority of KPC vs. placebo could not be demonstrated with the pre-specified analysis with regards to a sum score of 12 typical symptoms, perceived stress, or general health status. However, the explorative post-hoc analysis revealed that KPC is superior to placebo in the characteristic symptoms irritability and nervousness. KPC could therefore be a beneficial treatment option for symptomatic relief of neurasthenia. [ABSTRACT FROM AUTHOR]

The severe coronavirus disease 2019 (COVID-19) is associated with increased levels of blood interleukin (IL)-6. Therefore, it is hypothesized that modulating the levels or effects of IL-6 could diminish airway inflammation and alter the course of COVID-19. We conducted a controlled, randomized, double-blind clinical trial on hospitalized patients with severe COVID-19 in Iran. The patients were randomly distributed by block randomization to take either standard-of-care (SOC) plus 1 or 2 doses of tocilizumab 8 mg/kg or SOC alone. The endpoint was defined by clinical improvement and discharge. We enrolled 40 patients (20 patients in each group) from 10 July to 10 December 2020. After randomization, 1 patient in the SOC arm and 3 patients in the tocilizumab arm refused to participate and were eliminated from the study. The mean age of participants was 59.62±15.80 in the tocilizumab group (8 women and 9 men) and 63.52±12.83 years old in the SOC group (9 women and 10 men) groups. The number of patients who recovered did not differ significantly between the tocilizumab and SOC groups (12 [70.6%][70.6%] vs. 15 [78.9%]), respectively). Hospitalization rates were also similar between the groups (Log-rank test, p=0.615; hazard ratio, 0.83; 95% CI [0.39–1.78]). The results show that tocilizumab could not be a beneficial agent for treating severe cases of COVID-19 patients and would not significantly improve clinical outcomes. [ABSTRACT FROM AUTHOR]

We examined whether a housing voucher intervention influenced adolescent risky sexual behavior (RSB) across 15 years in the Moving to Opportunity Study. Low-income families in public housing that resided in 5 cities were randomized to one of three treatment groups: a housing voucher to move to low-poverty neighborhoods (i.e., < 10% poverty rate), a Sect. 8 voucher but no housing relocation counseling, or a control group that could remain in public housing. Youth and their caregivers completed baseline surveys, as well as two uniform follow-ups: interim (2001–2002; 4–7 years after baseline) and final (2008–2010; 10–15 years after baseline). Approximately 4,600 adolescents (50.5% female) aged 13–20 years participated at the final timepoint. Adolescents reported on their RSB, including condom use, other contraceptive use, early sexual initiation (< 15 years old), and 2+ sexual partners in the past year. We modeled each indicator separately and as part of a composite index. We tested baseline health vulnerabilities as potential effect modifiers. The low-poverty voucher group and the Sect. 8 voucher group were combined due to homogeneity of their effects. Applying intent-to-treat (ITT) regression analyses, we found no significant main effects of voucher receipt (vs. control) on any RSB. However, we found protective effects of voucher receipt on RSB among youth with health problems that limited activity, and youth < 7 at baseline but adverse effects among females, youth > 7 at baseline, and youth who were suspended/expelled from school. Results highlight the importance of understanding how housing interventions differentially influence adolescent health and behaviors. [ABSTRACT FROM AUTHOR]

This article explores the future of clinical trials in cardiovascular disease research. It emphasizes the significance of randomized controlled trials (RCTs) in enhancing cardiovascular outcomes, while also acknowledging the obstacles and areas that need improvement. These include the necessity for increased funding, the utilization of innovative trial designs, the integration of digital technologies, and the implementation of trial results into clinical practice. The article stresses the importance of collaboration and the exploration of new approaches to enhance the efficiency and effectiveness of clinical trials in cardiovascular research. Additionally, the article discusses the benefits and challenges of promptly and accurately publishing and disseminating clinical trial results. It highlights the importance of timely publication in informing medical practice and improving patient care, while also recognizing the challenges, such as rigorous peer review and potential bias in reporting results. The article provides insights into the current landscape of clinical trial publication and offers recommendations for improving the process. [Extracted from the article]

Background: Severe acute respiratory syndrome coronavirus 2 will coexist with humans for a long time, and it is therefore important to develop effective treatments for coronavirus disease 2019 (COVID-19). Recent studies have demonstrated that antiviral therapy is a key factor in preventing patients from progressing to severe disease, even death. Effective and affordable antiviral medications are essential for disease treatment and are urgently needed. Azvudine, a nucleoside analogue, is a potential low-cost candidate with few drug interactions. However, validation of high-quality clinical studies is still limited. Methods: This is a multicentre, randomized, double-blind, placebo-controlled phase III clinical trial involving 1096 adult patients with mild-to-moderate symptoms of COVID-19 who are at high risk for progression to severe COVID-19. Patients will be randomized to (1) receive azvudine tablets 5 mg daily for a maximum of 7 days or (2) receive placebo five tablets daily. All participants will be permitted to use a standard treatment strategy except antiviral therapy beyond the investigational medications. The primary outcome will be the ratio of COVID-19-related critical illness and all-cause mortality among the two groups within 28 days. Discussion: The purpose of this clinical trial is to determine whether azvudine can prevent patients at risk of severe disease from progressing to critical illness and death, and the results will identify whether azvudine is an effective and affordable antiviral treatment option for COVID-19. Trial registration: ClinicalTrials.gov NCT05689034. Registered on 18 January 2023. [ABSTRACT FROM AUTHOR]

To determine whether early switch to oral antibiotic treatment in adults with neutropenic sepsis at low risk of complications is non-inferior to switching later. This non-inferiority, parallel-group, randomized, open-label clinical trial enrolled UK adults hospitalized with neutropenic sepsis. Participants were randomly assigned to either switch to oral ciprofloxacin plus co-amoxiclav within 12–24 hours or to continue intravenous treatment for at least 48 hours. The primary outcome was a composite measure of treatment failure, 14 days after randomization. The non-inferiority margin was 15%. There were 129 participants from 16 centres and 125 were assessed for the primary outcome. Of these, 113 patients completed protocolized treatment and comprised the per-protocol population. In total, 9 (14.1%) of 64 patients in the standard care arm met the primary end point, compared with 15 (24.6%) of 61 in the early switch arm, giving a risk difference of 10.5% (1-sided 95% CI, −∞% to 22%; p 0.14). In the per-protocol population, 8 (13.3%) of the 60 patients in the standard care arm met the primary end point, compared with 9 (17%) of 53 in the intervention arm giving a risk difference of 3.7% (one-sided 95% CI, −∞% to 14.8%; p 0.59). Duration of hospital stay was shorter in the intervention arm (median 2 [inter-quartile range (IQR) 2–3] vs. 3 days [IQR 2–4]; p 0.002). Although non-inferiority of early oral switch was found in the per-protocol population, the intervention was not non-inferior in the intent-to-treat population. [ABSTRACT FROM AUTHOR]

It is important for young people to be aware of job profiles and activities in the professional world. Bringing the education system closer to the professional world is vital for them to make decisions about their academic and professional futures. Programs developed to connect 15‐year‐old students who in Spain are in year 4 of their Compulsory Secondary Education, and Research Support Units within the Health Research Institutes of the Hospitals and the Clinical Research Support Platforms of the Carlos III Institute of Health are a good opportunity to highlight the role of biostatistics in clinical trials. The aim of this article is to share the outcomes of and learnings from an interactive workshop for 15‐year‐old students on biostatistics and clinical trials conducted within the 4°ESO + Empresa program and directed by the Scientific Support Unit of the Health Research Institute of Hospital 12 de Octubre in Madrid, Spain. [ABSTRACT FROM AUTHOR]

Introduction: Schema therapy (ST) reduces depressive symptoms, but clinical trials have not investigated its effectiveness for patients suffering from severe forms of depression and high rates of comorbidities. There is high demand for exploring and improving treatments for this patient group. The objective of the current study was to evaluate whether ST is more effective than individual supportive therapy (IST) and noninferior compared with cognitive behavioral therapy (CBT) in treating depression. Methods: For this clinical trial, medicated patients were recruited in inpatient and day clinic settings. The major inclusion criteria were age between 18 and 75 years and primary diagnosis of depression without psychotic symptoms. A total of 292 participants were randomized to ST, CBT, or IST and received 7 weeks of psychotherapy (up to 14 individual and 14 group sessions). The primary outcome was change in depression severity after treatment measured by Beck Depression Inventory-II. Primary test for efficacy was superiority of ST over IST. Secondary test was noninferiority of ST compared with CBT. Multilevel modeling was conducted. The results at 6-month follow-up were explored. Results: Across treatment, ST was not superior to IST. Secondary outcome analyses and completer analyses showed similar results. However, ST showed clinically relevant noninferiority compared with CBT. Conclusion: ST for depression as part of a psychiatric care program showed clinical noninferiority compared to CBT, without being superior to IST. ST represents a potentially useful addition to the therapeutic repertoire for the treatment of depression but its efficacy, including long-term efficacy, should be evaluated further. [ABSTRACT FROM AUTHOR]

This document is a commentary on a comparative randomized clinical trial that evaluated the efficacy and safety of tacrolimus versus hydrocortisone as a topical treatment for atopic dermatitis in children. The authors commend the study for comparing the effects of these treatments and providing useful data on adverse events. However, they raise concerns about the trial duration, choice of primary outcomes, randomization process, sample size rationale, lack of blinding, implausibility of skin atrophy data, and ethical concerns. The authors suggest that better reporting following the CONSORT statement could have rectified some of these concerns. [Extracted from the article]

Background: Cardiac rehabilitation (CR) is essential in reducing cardiovascular mortality and morbidity. High-intensity interval training (HIIT) has emerged as a promising exercise intervention for enhancing clinical outcomes in cardiac patients. This study aimed to investigate the effects of two short-term exercise-based programs employing HIIT and moderate-intensity continuous training (MICT) in comparison to a control group concerning blood pressure, body composition, and blood biomarkers in patients diagnosed with coronary artery disease (CAD). Methods: Seventy-two CAD patients (14% women) underwent randomization into three groups: HIIT, MICT, and control. The training programs encompassed six weeks of supervised treadmill exercises, conducted thrice weekly. MICT targeted ≈70–75% of peak heart rate (HRpeak), while HIIT was tailored to ≈85–95% of HRpeak. The control group received guidance on adopting healthy lifestyles. Outcome measurements included evaluations of blood pressure, body composition, and blood biomarkers. Results: In contrast to MICT, the HIIT exhibited superior improvements in body fat mass (Δ%HIIT: 4.5%, p < 0.001 vs. Δ%MICT: 3.2%, p < 0.001), waist circumference (Δ%HIIT: 4.1%, p = 0.002 vs. Δ%MICT: 2.5%, p = 0.002), hemoglobin A1c (HbA1c) (Δ%HIIT: 10.4%, p < 0.001 vs. Δ%MICT: 32.3%, p < 0.001) and thyrotropin (TSH) (Δ%HIIT: 16.5%, p = 0.007 vs. Δ%MICT: 3.1%, p = 0.201). Both HIIT and MICT induced significant enhancements across all variables compared to the control group. Conclusions: HIIT and MICT emerged as effective modalities for enhancing systolic and diastolic function, body composition, and blood biomarkers in CAD patients, with HIIT demonstrating incremental improvements over MICT. The absence of participation in exercise-based programs following cardiovascular events yielded less favorable outcomes. HIIT holds promise as an adjunct intervention in CR programs for CAD patients. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03538119.

The article discusses the use of aprotinin, a pharmacologic agent that inhibits fibrinolysis, contact activation, and protease-activated receptors, in cardiac surgery patients. The European Medicines Agency suspended the marketing authorization of aprotinin in 2008 but reinstated it in 2016 for high-risk patients undergoing coronary artery bypass grafting. The article presents the results of a retrospective study comparing aprotinin with tranexamic acid in cardiac surgery patients, finding no differences in major bleeding or blood products transfused but an increased risk of thromboembolic events with aprotinin. The authors argue that more research, particularly prospective randomized clinical trials, is needed to evaluate the efficacy and safety of aprotinin and tranexamic acid in cardiac surgery. [Extracted from the article]

The excess neonatal adiposity is considered a risk factor for the development of childhood obesity and the birth weight is a marker of health throughout life. To evaluate the effect of a lifestyle intervention conducted among pregnant women with overweight on neonatal adiposity and birth weight. A total of 350 pregnant women were recruited and randomly allocated into the control (CG) and intervention (IG) groups. Pregnant women in the IG were invited to participate in three nutritional counselling sessions based on encouraging the consumption of unprocessed and minimally processed foods, rather than ultra-processed foods, following the NOVA food classification system, which categorizes foods according to the extent and purpose of industrial processing, and the regular practice of physical activity. Neonatal adiposity was estimated using a previously validated anthropometric model. Adjusted linear regression models were used to measure the effect. Adopting the modified intention-to-treat principle, data from 256 neonates were analyzed for birth weight, and data from 163 for body composition estimation. The treatment had no effect on the proportion of fat mass [β 0.52 (95 % CI −1.03, 2.06); p =.51], fat-free mass [β −0.50 (95 % CI −2.45, 1.45); p =.61] or birth weight [β 53.23 (95 % CI −87.19, 193.64); p =.46]. In the present study, the lifestyle counselling used had no effect on neonatal adiposity or birth weight. Future studies should investigate the effect of more intensive interventions. • The intervention based on NOVA did not cause an undesirable effect on foetal development. • The nutritional intervention based on NOVA did not impair neonatal anthropometry. • Future research is needed to elucidate whether maternal lifestyle intervention can influence neonatal body composition. [ABSTRACT FROM AUTHOR]

Leveraging military veterans' intimate relationships during treatment has the potential to concurrently improve posttraumatic stress disorder (PTSD) symptoms and relationship quality. Cognitive-Behavioral Conjoint Therapy (CBCT) and an 8-session Brief Cognitive-Behavioral Conjoint Therapy (bCBCT) are manualized treatments designed to simultaneously improve PTSD and relationship functioning for couples in which one partner has PTSD. Although efficacious in improving PTSD, the effects of CBCT on relationship satisfaction are small, especially among veterans. Intranasal oxytocin, which targets mechanisms of PTSD and relationship quality, may enhance the efficacy of bCBCT. The purpose of this 4-year clinical trial is to compare the outcomes of bCBCT augmented with intranasal oxytocin versus bCBCT plus placebo. We will also explore potential mechanisms of action: self-reported communication skills, empathy, and trust. We will recruit 120 dyads (i.e., veteran with PTSD and their intimate partner) from the VA San Diego Healthcare System. Veterans will be administered 40 international units of oxytocin (n = 60) or placebo (n = 60) 30 min before each of 8 bCBCT sessions delivered via telehealth. Clinical and functioning outcomes will be assessed at five timepoints (baseline, mid-treatment, post-treatment, and 3- and 6-month follow-up). Study findings will reveal the efficacy of oxytocin-assisted brief couple therapy for PTSD, which could serve as highly scalable option for couples coping with PTSD, as well as provide preliminary evidence of interpersonal mechanisms of change. ClinicalTrials.gov Identifier: NCT06194851 [ABSTRACT FROM AUTHOR]

Individuals with a history of moderate-severe traumatic brain injury (TBI) experience a significantly higher prevalence of insomnia compared to the general population. While individuals living with TBI have been shown to benefit from traditional insomnia interventions (e.g., face-to-face [F2F]), such as Cognitive Behavioral Therapy for Insomnia (CBT I), many barriers exist that limit access to F2F evidence-based treatments. Although computerized CBT-I (CCBT-I) is efficacious in terms of reducing insomnia symptoms, individuals with moderate-severe TBI may require support to engage in such treatment. Here we describe the rationale, design, and methods of a randomized controlled trial (RCT) assessing the efficacy of a guided CCBT-I program for reducing insomnia symptoms for participants with a history of moderate-severe TBI. This is an RCT of a guided CCBT-I intervention for individuals with a history of moderate-severe TBI and insomnia. The primary outcome is self-reported insomnia severity, pre- to post-intervention. Exploratory outcomes include changes in sleep misperception following CCBT-I and describing the nature of guidance needed by the Study Clinician during the intervention. This study represents an innovative approach to facilitating broader engagement with an evidence-based online treatment for insomnia among those with a history of moderate-severe TBI. Findings will provide evidence for the level and nature of support needed to implement guided CCBT-I. Should findings be positive, this study would provide support for a strategy by which to deliver guided CCBT-I to individuals with a history of moderate-severe TBI. • There is a high prevalence of sleep disorders, including insomnia, following moderate-severe traumatic brain injury (TBI). • Computerized Cognitive Behavioral Therapy for Insomnia (CCBT-I) may help address barriers to accessing traditional treatments for insomnia. • Individuals with moderate-severe TBI often have impairments that may interfere with the uptake of CCBT-I. • Provider supported CCBT-I may increase efficacy of CCBT-I among some cohorts, such as those with a history of moderate-severe TBI. • This is a randomized controlled trial of a CCBT-I intervention for individuals with current insomnia and a history of moderate-severe TBI. • Positive results could support the development of a stepped-care model of CCBT-I following moderate-severe TBI. [ABSTRACT FROM AUTHOR]

Parenting of preterm infants presents unique challenges, particularly during their transition from hospital to home. Early discharge programs can assist parents during this critical period. However, the feasibility of delivering a family-focused online discharge program remains understudied. This study was conducted to investigate the impact of a family-focused online parenting support intervention on parents' sense of competence, depression, caregiving, social support, family functioning, and the weight and length of preterm infants. We conducted a single-blind, two-arm randomized controlled trial with a repeated-measures design. Participants were recruited from a specialized tertiary hospital in China between May and December 2022. Forty-five families were randomly assigned to the intervention group and 44 to the control group. The intervention included three components: (1) two one-hour group sessions and three 30-minute individual sessions of online parenting support; (2) two follow-up telephone calls (15–30 min each) post-discharge; and (3) access to online parenting resources. Primary outcomes included parenting sense of competence, parental care ability, and preterm infants' weight and length. Secondary outcomes included depression, social support, and family functioning. Measurements were taken at baseline, preterm infant discharge, one month post-discharge, and three months post-discharge. A generalized estimating equation model was employed based on the intention-to-treat principle for outcome comparison. Parents in the intervention group showed significant improvements in parenting sense of competence (P < 0.001), parental care ability (P < 0.001), depression (P < 0.001), and social support (P = 0.002). However, no statistically significant differences were observed in preterm infants' weight and length, or in family functioning (P > 0.05). Although the intervention did not affect preterm infants' outcomes, the positive enhancements in parenting sense of competence, care ability, depression, and social support indicate that online family-focused parenting support can effectively prepare parents for hospital discharge and the early transition period. [ABSTRACT FROM AUTHOR]