Clinical Trial Study Research Articles

A 980 nm Diode Laser as an Adjunctive Therapy on the Healing of Apical Periodontitis Following Endodontic Retreatment: A Randomized Controlled Clinical Trial Study.

Introduction: Apical periodontitis is one of the common dental diseases. Microorganisms are the main reasons for these lesions; irrigations are used to remove them, but because of limited penetration, the rinsing agents may not always kill the microorganisms. Laser irradiation is effective in canal disinfection. The goal of this study was to compare the effect of calcium hydroxide (Ca(OH)2 ) and diode laser on the improvement of apical periodontitis following root canal retreatment (RCR). Methods: Twenty-four teeth of 19 patients with periapical lesions which needed RCR were divided into two groups (Ca(OH)2 and Ca(OH)2+laser irradiation [LI]). In the first session, after gutta-percha removal, cleaning, and shaping, Ca(OH)2 was used for 10 days. In the second session, in the Ca(OH)2+LI group, the irradiation utilizing a diode laser (using non-initiated 200-µm fiber, continuous wave (CW), power output of 1W) was done. The periapical radiographic healing was assessed before the retreatment and after 3-month and 6-month follow-ups by periapical index (PAI) Qrstavik. The quantitative data were analyzed (P<0.05). Results: The initial periapical lesion score was 3.75 and 3.88 in the Ca(OH)2 and Ca(OH)2+LI groups, respectively. In the Ca(OH)2 and Ca(OH)2+LI groups, 3 months after the RCR, the average periapical lesion score was 2.94 and 3.05, respectively. In the Ca(OH)2 and CA(OH)2+LI groups, 6 months after the RCR, the average periapical lesion score was 1.80 and 1.75, respectively. No significant differences were found at the 3 and 6 months between the experimental groups. Conclusion: The diode laser can reduce the periapical lesion, but there was no significant difference between CA(OH)2+LI and Ca(OH)2 at 3-month and 6-month follow-ups.

Early Childhood Screen Use Contexts and Cognitive and Psychosocial Outcomes

The multifaceted nature of screen use has been largely overlooked in favor of a simplistic unidimensional measure of overall screen time when evaluating the benefits and risks of screen use to early childhood development. To conduct a systematic review and meta-analysis to examine associations of screen use contexts in early childhood with cognitive and psychosocial outcomes. PsycINFO, Embase, MEDLINE Ovid, ProQuest, CINAHL, Web of Science, and Scopus were searched from inception to December 31, 2023. A total of 7441 studies were initially identified. Studies were included if they examined associations between a contextual factor of screen use among children aged 0 to 5.99 years and cognitive or psychosocial development. Observational, experimental, and randomized clinical trial study designs were included. All studies were independently screened in duplicate following PRISMA guidelines. Effect sizes of associations (r) from observational studies were pooled using random-effects 3-level meta-analyses. The remaining study designs were narratively synthesized. Screen use contexts included content (child directed and age inappropriate), type (program viewing and game or app use), co-use (or solo use), background television, caregiver screen use during child routines, and purpose. Outcomes were cognitive (executive functioning, language, and academic skills) or psychosocial (internalizing and externalizing behavior problems and socioemotional competence). Overall, 100 studies (176 742 participants) were included, and of these, 64 observational studies (pooled sample sizes ranging from 711 to 69 232) were included in meta-analyses. Program viewing (n = 14; k = 48; r, -0.16; 95% CI, -0.24 to -0.08) and background television (n = 8; k = 18; r, -0.10; 95% CI, -0.18 to -0.02) were negatively associated with cognitive outcomes, while program viewing (n = 6; k = 31; r, -0.04; 95% CI, -0.07 to -0.01), age-inappropriate content (n = 9; k = 36; r, -0.11; 95% CI, -0.17 to -0.04), and caregiver screen use during routines (n = 6; k = 14; r, -0.11; 95% CI, -0.20 to -0.03) were negatively associated with psychosocial outcomes. Co-use was positively associated with cognitive outcomes (n = 8; k = 28; r, 0.14; 95% CI, 0.03 to 0.25). Findings show small to moderate effect sizes that highlight the need to consider screen use contexts when making recommendations for families, clinicians, and educators beyond screen time limits; including encouraging intentional and productive screen use, age-appropriate content, and co-use with caregivers.

Analgesic effects of intraarticular anaesthetic lidocaine and methylprednisolone versus methylprednisolone alone following knee arthroscopy.

Knee arthroscopy is a widely practiced orthopaedic procedure known for its minimally invasive approach, allowing quicker recovery times and less postoperative discomfort than traditional open surgeries. However, managing postoperative pain remains a critical aspect of patient care and satisfaction. The main objective of this research is to examine the relationships between patient demographics (age, gender, BMI) and early postoperative outcomes, including pain, physiotherapy, and walking. Randomized data collection, clinical trial study of 2 groups of patients. The patients were split into lidocaine 1 % 16 ml + methylprednisolone 160 mg 4 ml) and (methylprednisolone only 160 mg 4 ml) groups. All patients in both groups were queried about age, gender, BMI, and pain on the first, third, and 15th days following surgery. All patients were tested for physiotherapy on the second, third, and fourth postop days. After surgery, walking was tested on the third, fourth, and fifth days. Significant differences in postoperative pain relief and physiotherapy initiation times were observed. There are notable associations between treatment groups and recovery metrics, such as pain levels and mobility on various days' post-surgery. Significant demographic influences (age, gender, BMI) on recovery outcomes are observed, particularly in walking and pain at day 15 post-operation. lidocaine and methylprednisolone improve postoperative pain relief and functional recovery in knee arthroscopy patients, with most experiencing reduced pain early post-surgery (early physiotherapy) and an expedited return to walking (decreased morbidity). Patients taking just methylprednisolone recovered slower. Age, gender, and BMI affected pain and walking abilities post-operation but not physiotherapy time, underscoring the personalised approach needed in postoperative treatment.

Comparison of the effect of dydrogesterone and natural micronized progesterone for luteal-phase support in assisted reproductive technology cycles: A single-blind randomized clinical trial study.

One of the causes of preterm labor and recurrent abortion is progesterone deficiency in the luteal phase. The aim of the study was a comparison of the effect of oral dydrogesterone and vaginal progesterone for luteal-phase support (LPS) in assisted reproductive technology cycles (ART). This randomized clinical control trial study was conducted on 207 infertile women. Samples were randomly divided into two groups. The first group received a natural micronized vaginal progesterone (MVP) of 400 mg once daily and the second group received dydrogesterone (Duphestone) 20 mg twice daily. Then chemical pregnancy, abortion, and live births were compared in two groups. The results of the study showed that the vaginal form of the drug could increase the chance of pregnancy (positive β-human chorionic gonadotropin) versus the oral form. According to the results of multiple logistic regression analysis after adjusting for other variables, the live birth rate in the vaginal group was more than five times that of the oral group (odds ratio = 5.07; 95% confidence interval = 1.24-20.65; p = 0.023). The vaginal form of the progesterone could increase the chance of pregnancy and the outcome of fertility (live birth). Thus, vaginal progesterone is effective for LPS in women undergoing fresh embryo transfer.

Overall survival with non-proportional hazards in first-line treatment for patients with metastatic colorectal cancer: Systematic review and network meta-analysis

This study aimed to identify the most effective first-line treatment for patients with metastatic colorectal cancer based on overall survival, identify the most commonly used treatment, and generate a meaningful ranking among all available treatments based on their relative effectiveness. Researchers used the ANOVA parametrization method to fit the second-order fractional polynomial network meta-analysis with a random-effect model. Using a non-proportional hazards network meta-analysis, 46 treatments were compared by considering a combination of direct and indirect evidence extracted from clinical trial studies. Included in the review were 46 trials involving 21350 patients. Between January 2000 and January 2023, researchers conducted a thorough search through Embase, PubMed/Medline, and Scopus. To undertake a secondary analysis of this data, we recreate individual patient data from published Kaplan-Meier (K-M) survival curves and assess the accuracy of that reconstruction. A random-effects model was used to evaluate the pooled overall survival and hazard ratio with a 95 percent confidence interval. The predicted survival curves for the network meta-analysis showed that GOLFIG and FOLFOX + Cetuximab treatments have higher survival, respectively. Our results provide moderate quality evidence and comparative effective estimates for various available first-line treatments for metastasis colorectal cancer based on network meta-analysis.

Effects of prenatal small-quantity lipid-based nutrient supplements on pregnancy, birth, and infant outcomes: a systematic review and meta-analysis of individual participant data from randomized controlled trials in low- and middle-income countries

BackgroundUndernutrition during pregnancy increases the risk of giving birth to a small vulnerable newborn. Small-quantity lipid-based nutrient supplements (SQ-LNSs) contain both macro- and micronutrients and can help prevent multiple nutritional deficiencies. ObjectivesWe examined the effects of SQ-LNSs provided during pregnancy compared with 1) iron and folic acid or standard of care (IFA/SOC) or 2) multiple micronutrient supplements (MMSs) and identified characteristics that modified the estimates of effects of SQ-LNSs on birth outcomes. MethodsWe conducted a 2-stage meta-analysis of individual participant data from 4 randomized controlled trials of SQ-LNSs provided during pregnancy (n = 5273). We generated study-specific and subgroup estimates of SQ-LNS compared with IFA/SOC or MMS and pooled the estimates. In sensitivity analyses, we examined whether the results differed depending on methods for gestational age dating, birth anthropometry, or study design. ResultsSQ-LNSs (compared with IFA/SOC) increased birth weight [mean difference: +49 g; 95% confidence interval (CI): 26, 71 g] and all birth anthropometric z-scores (+0.10–0.13 standard deviation); they reduced risk of low birth weight by 11%, newborn stunting by 17%, newborn wasting by 11%, and small head size by 15%. Only 2 trials compared SQ-LNSs and MMSs; P values for birth outcomes were >0.10 except for head circumference (e.g., z-score for gestational age: +0.11; 95% CI: −0.01, 0.23). Effect estimates for SQ-LNSs compared with IFA/SOC were greater among female infants and, for certain outcomes, among mothers with body mass index <20 kg/m2, inflammation, malaria, or household food insecurity. Effect estimates for SQ-LNSs compared with MMSs were greater for certain outcomes among female infants, first-born infants, and mothers <25 y. ConclusionsSQ-LNSs had positive impacts on multiple outcomes compared to IFA/SOC, but further research directly comparing SQ-LNSs and MMSs is needed. Targeting SQ-LNSs to vulnerable subgroups may be worth considering. Clinical Trial RegistryThis study was registered at PROSPERO as CRD42021283391.

Exploring the discrepancies between clinical trials and real-world data: A small-cell lung cancer study.

The potential of real-world data to inform clinical trial design and supplement control arms has gained much interest in recent years. The most common approach relies on reproducing control arm outcomes by matching real-world patient cohorts to clinical trial baseline populations. However, recent studies pointed out that there is a lack of replicability, generalisability, and consensus. In this article, we propose a novel approach that aims to explore and examine these discrepancies by concomitantly investigating the impact of selection criteria and operations on the measurements of outcomes from the patient data. We tested the approach on a dataset consisting of small-cell lung cancer patients receiving platinum-based chemotherapy regimens from a real-world data cohort (n = 223) and six clinical trial control arms (n = 1224). The results showed that the discrepancy between real-world and clinical trial data potentially depends on differences in both patient populations and operational conditions (e.g., frequency of assessments, and censoring), for which further investigation is required. Discovering and accounting for confounders, including hidden effects of differences in operations related to the treatment process and clinical trial study protocol, would potentially allow for improved translation between clinical trials and real-world data. Continued development of the method presented here to systematically explore and account for these differences could pave the way for transferring learning across clinical studies and developing mutual translation between the real-world and clinical trials to inform clinical study design.

Comparing the incidence of postoperative painful bladder spasm between malecot catheter and 3-way Foley catheter: a clinical trial.

In this study, the effect of Pezzer (as a Pezzer catheter) and three-way Foley catheters, used for suprapubic catheterization after open prostatectomy, was investigated in terms of early incidence of painful bladder spasms. In this single-blind clinical trial study, 160 patients diagnosed with LUTS/BPH were placed in two groups of 80 Pezzer catheter (Pezzer(size 28)) and three-way Foley catheters (size 24) for suprapubic catheterization. The evaluated variables in this study are age, prostate weight, narcotics dose, Spasm frequency, International Prostate Symptom Score (IPSS), visual analogue scale (VAS), catheterization period. The frequency of spasm in Foley group was significantly lower (4.4±7.26 vs. 6.28±4.4; P value=0.000). There was no significant difference between the two groups regarding the frequency of dysuria (P value=0.3). The findings of our study showed that despite slightly favourable results in using suprapubic Foley catheter compared to Pezzer catheters in patients with open prostatectomy in terms of pain and spasm frequency, there was no significant difference between the use of these two types of catheters.

Efficacy and safety of Tongxin formula in the treatment of coronary microvascular disease: A randomized, double-blind, placebo-controlled clinical trial study

ObjectiveThe objective of this study was to evaluate the efficacy and safety of Tongxin Formula in the treatment of coronary microvascular disease. MethodsWe conducted a randomized, double-blind, placebo-controlled study simultaneously in two hospitals, consisting of 80 participants. Using a random number table, we assigned patients to the treatment and control groups. Patients in both groups received conventional Western medicine for coronary microvascular disease. In addition, those in the treatment group received Tongxin formula granules, while those in the control group received a placebo. The treatment course for both groups was three months, and the follow-up duration was six months. The primary efficacy indicators were coronary blood flow reserve and cardiovascular adverse events; the secondary efficacy indicators were the traditional Chinese medicine (TCM) syndrome score, the angina symptom score, the Seattle Angina Questionnaire (SAQ) score, left ventricular function, and adverse reactions. ResultsAfter treatment, patients in the treatment group showed significantly higher variation in the coronary flow reserve (CFR) levels (CFR >2) and improvement of diastolic function (peak filling rate, or PFR >2.5) than those in the control group (P < 0.05). After 6 months of follow-up, the incidence of cardiovascular events in the treatment group was significantly lower than that in the control group (P < 0.05). After 3 months of treatment and 6 months of follow-up, the total effective rates of TCM symptoms and angina symptoms, as well as the total SAQ standard scores, in the treatment group were higher than those in the control group (P < 0.05). There were no serious adverse reactions in either group before or after treatment, and there was no significant change (P > 0.05). ConclusionWe found that Tongxin Formula combined with conventional Western medicine can significantly improved the level of coronary blood flow reserve, reduced the occurrence of cardiovascular adverse events, improved the clinical symptoms of patients, and enhanced the quality of life of patients with coronary microvascular disease with favorable safety.

Effects of MIND diet and propolis supplementation on metabolic syndrome indices and cognitive function among patients with metabolic syndrome in Isfahan, Iran, 2024. A rationale and study protocol for randomized controlled trial.

Metabolic syndrome (MetS) is the main general and clinical health challenge worldwide. Based on the National Cholesterol Education Program, if the person has three or more indices containing: elevated fasting blood sugar, high levels of triglycerides, hypertension, low levels of high-density lipoprotein cholesterol, and central obesity, he suffers MetS. The Mediterranean-Dietary Approaches to Stop Hypertension (DASH) Intervention for Neurodegenerative Delay diet is a novel diet that with the specific aim of safeguarding cognitive function. Propolis is a resinous substance produced by bees from the combination of buds and secretions of plants with saliva and bee enzymes. After propolis supplementation, a significant reduction in fasting plasma glucose levels and lipid profiles has been observed. Considering the importance of chronic diseases like MetS on health, the role of the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet and propolis supplement that will improve blood sugar, blood lipid, anthropometric indicators, blood pressure, and cognitive function, and limited contradictory studies, we decided to conduct this study. This study, which is a randomized controlled clinical trial study, will be conducted on adults with MetS who will visit Hazrat Ali Health Center in Isfahan. Participants must provide informed consent before engaging in the study. Demographic data such as age, gender, and medical history will be recorded. Then, anthropometric indices, MetS indices, and cognitive function will be measured in all subjects. The study participants will be divided into three groups and will be controlled for 12 weeks. We will have a MIND diet + placebo group, a MIND diet + propolis supplement group, and a control group that will receive a microcrystalline cellulose placebo and usual dietary advice. At the end of the intervention, all indices will be assessed again. The data obtained in the study will be analyzed at descriptive and analytical levels by the statistical software SPSS26. The present study's protocol was approved by the Iranian Registry of Clinical Trials (www.irct.ir) on 3/28/2023 and a registration reference is IRCT20230105057054N1.

Aquatic high-intensity interval training improves cardiometabolic profile and physical fitness in active middle-age and older adults: quasi-randomized clinical trial study

Introduction: aquatic exercises have been increasingly suggested to the population. Despite evidence on the benefits of high-intensity interval training in aquatic environments, scientific production still needs to be improved. Research involving middle-aged and older individuals usually seeks physiological responses from the assumption that they are sedentary. Objective: to assess the physical fitness, lipid profile, and glycemic control of active middle-aged and older adults undergoing aquatic high-intensity interval training associated or not with intense water walking. Methods: it is a quasi-randomized clinical trial composed of 45 active middle-aged and older adults subdivided into two groups with aquatic high-intensity interval training in the absence (AHIIT) or presence (AHIITW) of intense water walking. Participants were dosed with biochemical parameters, bioimpedance analysis, and physical and cardiopulmonary tests at the intervention’s beginning and end. Results: both groups showed increased HDL, reduced LDL, and hemoglobin glycated, with increased endurance and strength of upper and lower limbs. The AHIIT group showed a lean mass gain and fat mass decline compared to the AHIITW. The intense walking promoted an increase in oxygen ventilatory equivalent, maximum oxygen consumption, and the task metabolic equivalent at values like the AHIIT. Conclusion: our findings indicate that high-intensity aquatic training holds the potential to enhance the lipid profile of individuals. However, the incorporation of pool walking into the training regimen did not lead to any notable differences in this regard. Conversely, the inclusion of pool aquatic exercises did result in improved functional capacity among participants. Brazilian Registry of Clinical Trials (ReBEC): #RBR-99b6jr6

Comparing the Effects of Midazolam and Ondansetron in Postoperative Nausea and Vomiting

Background: Nausea and vomiting after a cesarean section (CS) are among the common side effects that cause dissatisfaction among doctors. The aim of this study was to compare the effects of intravenous midazolam and ondansetron on the reduction of nausea and vomiting after spinal anesthesia in CS. Methods: This double-blind clinical trial study was conducted on CS candidates who underwent spinal anesthesia (N=80). After spinal anesthesia, the patients were randomly divided into two groups. Midazolam was administered to one group and ondansetron to the other group. The severity of nausea, the severity of vomiting, and the degree of satisfaction were recorded during surgery and recovery. Results: No significant difference was observed between the two groups in terms of the severity of nausea and vomiting. In addition, the results demonstrated that the level of satisfaction in the midazolam group was higher than that in the ondansetron group, but this difference was not statistically significant (P&lt;0.05). Conclusion: The results of this study showed that midazolam can reduce nausea and vomiting. On the other hand, the results confirmed that both ondansetron and midazolam can have the same effects on reducing nausea and vomiting.

Home-based telerehabilitation in multiple sclerosis: a scoping review

BackgroundIntroducing home-based telerehabilitation (TR) approaches helps clinical experts to choose appropriate and effective interventions and researchers identify knowledge gaps to design clinical trial studies and systematic reviews.PurposeThis study aimed to...

The effect of laughter yoga and music intervention on depression, anxiety, and stress in the Rafsanjan-Iran aged: a randomized clinical trial study

Objectives This study aimed to compare the effects of laughter yoga and music intervention on depression, anxiety, and stress in aged individuals referred to Rafsanjan health centers. Method In this 3-arm randomized clinical trial, 91 depressed aged participants aged 60–75 years, referred to Rafsanjan health centers, were randomly assigned to intervention and control groups. The study followed a parallel group design with an allocation ratio of 1:1. The laughter yoga intervention was conducted twice a week for eight weeks, and music intervention consisted of 30-min sessions twice a week for eight weeks. The control group received no intervention (‘No treatment’ concurrent control). Assessments for depressive symptoms (primary outcome), anxiety, and stress were conducted at baseline, post-intervention, and one month after the intervention. Results A total of 84 patients were analyzed in three groups included the laughter yoga intervention (n = 31), music intervention (n = 25), or control group (n = 28). Repeated measures ANOVA revealed a significant decrease in depressive and anxiety symptoms (p < 0.001) from pre-test to post-test and one-month follow-ups. The greatest impact of the intervention programs on stress was observed immediately after the intervention, but stress increased one month after the intervention programs (p = 0.125). Conclusion Both laughter yoga and music interventions proved effective in improving depression, anxiety, and stress in aged individuals. However, laughter yoga intervention demonstrated a superior effect and better acceptance among elders.

The effect of supportive counseling on self-esteem of infertile women after in vitro fertilization (IVF) failure: a randomized controlled trial study

BackgroundThe unsuccessful treatment of infertility can lead to heightened levels of negative emotions, which are often associated with various psychological consequences. These consequences may include a decrease in self-confidence, feelings of loneliness, reduced self-esteem, and even discontinuation of treatment. Therefore, it is crucial to implement interventions that can help improve these consequences for women who have experienced IVF failure. The present study aimed to examine the effect of supportive counseling on self-esteem of infertile women after IVF failure.Methodsthis randomized clinical trial study was conducted on 63 infertile women after IVF failure, referred to Milad Infertility Center in Mashhad in 2021. In the intervention group, the researcher provided individual supportive counseling sessions. These sessions took place over a span of four weeks, with each session lasting 60 min (One session every week). Data collection was conducted both before and one month after the study using Eysenck self-esteem Questionnaire. Data were analyzed using SPSS25, as well as statistical tests such as chi-square, independent t-test, Paired t-test and Mann-Whitney tests. A significance level of less than 5% was considered.ResultsThe study found no significant difference in mean scores of self-esteem between the two groups before the study (p = 0.823). However, after one month, the intervention group had significantly higher self-esteem scores (24.3 ± 18.55) compared to the control group (21.74 ± 5.62) (p = 0.043) Moreover, Based on the Within-group comparison, there was a 2.43 ± 3.24 point increase in self-esteem scores of the intervention group after one month, while the control group showed a -0.33 ± 3.72 point decrease.ConclusionSupportive counseling was found to be effective in improving self-esteem following IVF failure. As a result, it can be recommended as an effective, affordable, and low-risk counseling approach for women who have experienced IVF failure. By offering supportive counseling, it is possible to help prevent and alleviate the psychological consequences associated with IVF failure.Trial registrationThis research project was registered at the Iranian Registry of Clinical Trials with code IRCT20210407050883N1- Date of registration 2021-05-25.

Amyloid and Tau Prediction of Cognitive and Functional Decline in Unimpaired Older Individuals: Longitudinal Data from the A4 and LEARN Studies

BackgroundConverging evidence suggests that markers of Alzheimer’s disease (AD) pathology in cognitively unimpaired older individuals are associated with high risk of cognitive decline and progression to functional impairment. The Anti-Amyloid Treatment in Asymptomatic Alzheimer’s disease (A4) and Longitudinal Evaluation of Amyloid and Neurodegeneration Risk (LEARN) Studies enrolled a large cohort of cognitively normal older individuals across a range of baseline amyloid PET levels. Recent advances in AD blood-based biomarkers further enable the comparison of baseline markers in the prediction of longitudinal clinical outcomes.ObjectivesWe sought to evaluate whether biomarker indicators of higher levels of AD pathology at baseline predicted greater cognitive and functional decline, and to compare the relative predictive power of amyloid PET imaging, tau PET imaging, and a plasma P-tau217 assay.DesignAll participants underwent baseline amyloid PET scan, plasma P-tau217; longitudinal cognitive testing with the Primary Alzheimer Cognitive Composite (PACC) every 6 months; and annual functional assessments with the clinical dementia rating (CDR), cognitive functional index (CFI), and activities of daily living (ADL) scales. Baseline tau PET scans were obtained in a subset of participants. Participants with elevated amyloid (Aβ+) on screening PET who met inclusion/exclusion criteria were randomized to receive placebo or solanezumab in a double-blind phase of the A4 Study over 240+ weeks. Participants who did not have elevated amyloid (Aβ−) but were otherwise eligible for the A4 Study were referred to the companion observational LEARN Study with the same outcome assessments over 240+ weeks.SettingThe A4 and LEARN Studies were conducted at 67 clinical trial sites in the United States, Canada, Japan and Australia.ParticipantsOlder participants (ages 65–85) who were cognitively unimpaired at baseline (CDR-GS=0, MMSE 25–30 with educational adjustment, and Logical Memory scores within the normal range LMIIa 6–18) were eligible to continue in screening. Aβ+ participants were randomized to either placebo (n=583) or solanezumab (n=564) in the A4 Study. A subset of Aβ+ underwent tau PET imaging in A4 (n=350). Aβ− were enrolled into the LEARN Study (n=553).MeasurementsBaseline 18-F Florbetapir amyloid PET, 18-F Flortaucipir tau PET in a subset and plasma P-tau217 with an electrochemiluminescence (ECL) immunoassay were evaluated as predictors of cognitive (PACC), and functional (CDR, CFI and ADL) change. Models were evaluated to explore the impact of baseline tertiles of amyloid PET and tertiles of plasma P-tau217 on cognitive and functional outcomes in the A4 Study compared to LEARN. Multivariable models were used to evaluate the unique and common variance explained in longitudinal outcomes based on baseline predictors, including effects for age, gender, education, race/ethnic group, APOEε4 carrier status, baseline PACC performance and treatment assignment in A4 participants (solanezumab vs placebo).ResultsHigher baseline amyloid PET CL and P-tau217 levels were associated with faster rates of PACC decline, and increased likelihood of progression to functional impairment (CDR 0.5 or higher on two consecutive measurements), both across LEARN Aβ− and A4 Aβ+ (solanezumab and placebo arms). In analyses considering all baseline predictor variables, P-tau217 was the strongest predictor of PACC decline. Among participants in the highest tertiles of amyloid PET or P-tau217, >50% progressed to CDR 0.5 or greater. In the tau PET substudy, neocortical tau was the strongest predictor of PACC decline, but plasma P-tau217 contributed additional independent predictive variance in commonality variance models.ConclusionsIn a large cohort of cognitively unimpaired individuals enrolled in a Phase 3 clinical trial and companion observational study, these findings confirm that higher baseline levels of amyloid and tau markers are associated with increased rates of cognitive decline and progression to functional impairment. Interestingly, plasma P-tau217 was the best predictor of decline in the overall sample, superior to baseline amyloid PET. Neocortical tau was the strongest predictor of cognitive decline in the subgroup with tau PET, suggesting that tau deposition is most closely linked to clinical decline. These findings indicate that biomarkers of AD pathology are useful to predict decline in an older asymptomatic population and may prove valuable in the selection of individuals for disease-modifying treatments.

Rosmarinic acid modulates purinergic signaling and induces apoptosis in melanoma cells.

Cancer cases have increased worldwide. Cutaneous melanoma (CM), a highly metastatic skin cancer, largely contributes to global statistical cancer death data. Research has shown that rosmarinic acid (RA) is a promising phenolic compound with antineoplastic properties. Thus, we investigated the effects of RA on apoptosis-inducing in melanoma cells, purinergic signaling modulation, and cytokine levels. We treated SK-MEL-28 cells for 24h with different concentrations of RA and assessed the apoptosis, CD39, CD73, and A2A expression, and cytokine levels. We found RA-induced apoptosis in melanoma cells. Regarding the purinergic system, we verified that RA downregulated the expression of CD73 and A2A, specially at high concentrations of treatment. Additionally, RA increased IL-6, IL-4, IL-10, IFN-γ, and TNF-α levels. Our in vitro results confirm RA's potential to be used to induce melanoma cell apoptosis, having CD73 and A2A as targets when reversion of immune suppression is desired. Further studies in animal models and clinical trials focusing on RA's modulation of purinergic signaling in melanoma are required.

Cytomegaloviral Infections in Recipients of Chimeric Antigen Receptor T-Cell Therapy: An Observational Study With Focus on Oncologic Outcomes.

Patients with B-cell lymphoma and acute lymphoblastic leukemia (ALL) who receive chimeric antigen receptor T-cell (CAR-T) therapy may experience clinically significant cytomegalovirus infection (CS-CMVi). However, risk factors for CS-CMVi are not well defined. The aims of our study were to identify risk factors for CS-CMVi and the association between CS-CMVi and nonrelapse mortality (NRM) in lymphoma and ALL patients after CAR-T therapy. We performed a retrospective single-center cohort analysis of CAR-T recipients between January 2018 and February 2021 for treatment of lymphoma and ALL. We collected data on demographics, oncologic history, CAR-T therapy-related complications, and infectious complications within 1 year of therapy. Of 230 patients identified, 22 (10%) had CS-CMVi. At 1 year following CAR-T therapy, 75 patients (33%) developed relapsed disease and 95 (41%) died; NRM at 1 year was 37%. On Cox regression analysis, Asian or Middle Eastern race (adjusted hazard ratio [aHR], 13.71 [95% confidence interval {CI}, 5.41-34.74]), treatment of cytokine release syndrome/immune effector cell-associated neurotoxicity syndrome with steroids (aHR, 6.25 [95% CI, 1.82-21.47]), lactate dehydrogenase at time of CAR-T therapy (aHR, 1.09 [95% CI, 1.02-1.16]), and CMV surveillance (aHR, 6.91 [95% CI, 2.77-17.25]) were independently associated with CS-CMVi. CS-CMVi was independently associated with NRM at 1 year after CAR-T therapy (odds ratio, 2.49 [95% CI, 1.29-4.82]). Further studies of immunologic correlatives and clinical trials to determine the efficacy of prophylactic strategies are needed to understand the role of CS-CMVi and post-CAR-T mortality.

The effect of oral capsules containing Ocimum basilicum leaf extract on menopausal symptoms in women: a triple-blind randomized clinical trial

BackgroundMenopause, characterized by various physical and mental changes, is primarily caused by hormonal fluctuations, resulting in numerous complications. Recently, herbal treatments have gained significant attention for their minimal side effects compared to chemical drugs. This study aimed to investigate the effects of oral capsules containing Ocimum basilicum leaf extract (OBLE) on menopausal symptoms.MethodsThis placebo-controlled clinical trial study was conducted in 2020. The research focused on 60 menopausal women referred to Mashhad health centers. Eligible participants were administered either an OBLE 500 mg capsule or a placebo daily for 1 month. Menopause symptoms were evaluated using the Menopause Rating Scale (MRS) before, two weeks, and one month after the intervention. Data were analyzed using SPSS21, independent t, Mann–Whitney, and Friedman tests. A significance level of p < 0.05 was considered significant.ResultsThe independent t-test indicated that the mean (SD) scores of menopausal symptoms in both the OBLE and placebo groups were initially similar before the intervention (P = 0.141). Two weeks after the intervention, the menopausal symptom scores were 9.5 ± 3.5 and 11.2 ± 5.6 in the OBLE and placebo groups, respectively (P = 0.163, df = 58, t = 1.4). After one month, the menopausal symptom scores were 6.9 ± 0.3 in the OBLE group and 11.26 ± 0.6 in the placebo group (P = 0.001, df = 58, t = 3.4). This indicates a significant difference between the two groups one month after the intervention, compared to before and two weeks after the intervention. Additionally, there was a significant difference in the scores of the physical and somato-vegetative dimension between the intervention and placebo groups two weeks and one month after the intervention (P < 0.05).ConclusionThe study results suggested that taking OBLE capsules led to a decrease in the scores of menopausal symptoms. This indicates that OBLE can be considered as a safe and cost-effective medicinal plant for alleviating menopausal symptoms among women.

Effectiveness of Autologous Fat Grafting in the Treatment of Scars: A Systematic Review and Meta-Analysis.

Autologous fat transfer (AFT) has been proposed as a possible treatment for scar tissue and its associated symptoms. Its effectiveness's evidence is yet unidentified though. The aim of this meta-analysis is to evaluate the currently available evidence on the efficacy and safety of autologous fat transfer in treating post-burn and post-traumatic scars using a validated scar measurement tool. This study performed a systematic literature review in November 2023 using the following electronic databases: MEDLINE, SCOPUS, Directory of Open Access Journals (DOAJ), PUBMED, and Google Scholar. The following key terms were included: (Fat grafting OR Autologous fat transfer) AND (body scars OR body burns OR body wounds) AND (Efficacy OR Safety OR satisfaction). We evaluated articles according to predefined quality criteria. The following data wereincluded during the extraction period: patient demographics, indications for AFT, the number of AFT sessions, follow-up periods, and changes in the Patient and Observer Scar Assessment Scale (POSAS) scores, which contain both the patient and observer components. This study included 1326 patients and 23 published articles. A total of 14 prospective studies, 7 retrospective studies, and 2 Randomized clinical trials studies were evaluated. These 23 articles came from diverse global locations; the earliest was published in 1992, and the most recently published in 2022. Our findings demonstrated significant enhancements in scar characteristics from both patient and observer perspectives. Overall, AFT holds promise as a valuable treatment option for scar-related conditions as it enhances scar quality ,contributing to improved patient outcomes and satisfaction. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266.