Randomized Controlled Clinical Trials Research Articles

Resin infiltration versus fluoride varnish for visual improvement of white spot lesions during multibracket treatment. A randomized-controlled clinical trial

AimsThis study aimed to evaluate the visual improvement of resin infiltration of white spot lesions (WSL) during orthodontic treatment with the multibracket appliance (MBA) compared to fluoride varnish.MethodsPatients aged 12–17 years with at least one WSL with an International Caries Detection and Assessment System (ICDAS) score of 1–2 during an active MBA treatment were included and randomized to receive either resin infiltration (Icon) or fluoride application (Flairesse). Standardized digital images were obtained before, one-day, one-week, one-month, three-months and six-months after treatment using a DSLR camera and a matching polarization filter. A grey reference card was used for color standardization. A Matlab routine was used to measure the color difference between adjacent healthy enamel and treated WSL. The independent-samples t-test was used for intergroup and paired-samples t-test for intragroup comparison.ResultsImages of 116 teeth from 36 patients were analyzed. The ΔE for the “Icon” treated WSL was smaller (T1ICON = 5.0 ± 1.4) than in the fluoride group (T1Fluoride = 8.4 ± 3.2). Caries infiltration significantly improved the aesthetic appearance of WSL (p < 0.001), which remained satisfactory at six months (T5ICON = 5.2 ± 1.6).ConclusionWSL infiltration management during orthodontic treatment was superior to topical fluoridation in not only arresting the enamel lesions but also significantly improving the aesthetic appearance of demineralized regions around the brackets.Clinical relevanceWSL treatment in orthodontic patients is usually initiated after debonding. Research has shown that the earlier WSL is treated, the better the aesthetic outcome. There is limited data on the efficacy of resin infiltration of WSL during orthodontic treatment.

Evaluation of pre-heated composite resins with soft-start polymerization and conventional composite restorations in class-I carious lesions – A randomized clinical trial

BackgroundBy increasing fluidity and conversion, pre-heated composites enhance adaptability and strength, while soft-start polymerization decreases internal stresses. AimOver a period of a year, this split-mouth design, randomized controlled clinical trial (RCT) compared pre-heated composites with soft-start polymerization to conventional composites in class-I lesions, with the goal of improving restoration outcomes. Methodsand Findings: Immediately following ethical approval and registration with CTRI, 37 patients with in-formed permission who met specified inclusion and exclusion criteria for class-I lesions were chosen for enrollment. Using a 1:1 ratio, teeth were randomly assigned to Group-A (pre-heated composite with soft-start polymerization) or Group-B (traditional composite restoration). At three-time intervals, the evaluation was blinded and calibrated using Modified United States Public Health Service (USPHS) criteria: baseline, six-month, and one-year marks. Statistical analysis was performed using SPSS 21.0 and the Mann-Whitney U test for inter-group comparisons and the Friedman test for intra-group comparisons. InterpretationPre-heated composites with soft-start polymerization performed better in terms of marginal adaptation with a statistically significant difference (p = 0.019) and in terms of color match they performed better clinically (p = 0.062) at 12 months. Other variables like marginal discolouration, sec-ondary caries, anatomic form, post-operative sensitivity, surface texture and retention showed no statistically significant difference (p < 0.05). Pre-heated composites with soft-start mode performed marginally better than nanofilled composites. However, both techniques can be used to successfully restore simple class-I carious lesions.

A Comparative Clinical study of Lakshadi Lepa and Panchanimba Ghana vati in Mukhdooshika w.s.r to Acne Vulgaris

In Ayurveda, mukhadushika is mentioned under the heading of Kshudra rogas, characterized by Shalmali thorn-like eruption on the face due to vitiation of kapha, vata, and rakta in adolescence, called as mukhdushika/yuvan pidika. In this study, 2 trial drugs were taken for Mukhdooshika which has been mentioned in Samhitaas. Aims and Objective: This study is to assess the efficacy of Lakshadi Lepa and Panchanimbadi Ghana Vati along with the comparison with Acnovin ointment and capAcnovin. Materials and Methods: This study was an open randomized control clinical trial. Total 30 patients were selected and divided into 2 groups randomly 15 patients in each group, to compare the clinical efficacy of study drug Group A with study drug Group B along with kumkumadi taila nasyam for 1 month in the management of Mukhdooshika (Acne). The results of therapy have been evaluated by statistical methods in 2 steps. 1st step is evaluating within the group before and after treatment in both groups separately and in 2nd step the evaluations of inter-group/between 2 groups evaluation of both therapies. Results: In both study and control group, 0% of patient showed excellent relief. 6.66% and 13.33% patients showed marked relief in study and control groups, respectively. 60% and 40% patients showed moderate relief in study and control groups, respectively. 33.33% and 46.66% patients showed mild relief in study group and control group, respectively, and the percentage of no relief patient was zero in both groups.

Systematic Review: Safety and Efficacy Comparison of Laser Therapy With And Other Resurfacing Technology

There is an increasing demand of almost all young and adult population for the noninvasive cosmetic procedures specially to enhance the facial appearance and the requirement has expanded all over the world. This review was designed to identify and summarize the literature/evidence from different types of research/clinical studies conducted in facial resurfacing methodologies. A systematic review was designed and conducted in relation to facial resurfacing and rejuvenating techniques using data from PubMed, MEDLINE Cochrane database and Scopus. Systematic review protocol guidelines were used for research questions, aim of the review and PICO breakdown, eligibility criteria and used search engine and extraction of data. A minimum of 17 clinical studies and reviews were identified including randomized clinical trials. Significant results have been obtained in some clinical trials about techniques of rejuvenation and some studies have elucidated contrasting evidence. In most of the work, ablative and non-ablative laser therapy had been compared and we found that some results were compatible, and others showed contrasting evidence. In conclusion, more high-quality randomized control clinical trials are needed to decide on better safety and effectiveness of ablative or non-ablative laser therapy vs conventional treatments.

Xanthan-based chlorhexidine gel effects in non-surgical periodontal therapy? A meta-analysis.

To carry out a systematic review and meta-analysis of randomized controlled clinical trials (RCTs) and controlled clinical trials (CCTs) comparing scaling and root planing (SRP) or placebo with subgingival application of xanthan-based CHX (chlorhexidine) gel as adjunct to SRP. The literature search was carried out in PubMed/MEDLINE, EMBASE, and SCOPUS; primary outcomes were probing pocket depth (PPD) reduction and gain in clinical attachment level (CAL). Overall, 15 studies were included. Three studies were judged to be at moderate risk of bias while the remaining 12 were rated at high risk of bias. A significant improvement in PPD reduction (standardized mean difference, SMD, 0.87, 95% CI, 0.41-1.34) and CAL gain (SMD = 0.84, 95% CI, 0.36-1.33) emerged for the SRP + CXH gel compared to the SRP alone group, in the presence of significant high heterogeneity among the studies. Our systematic review and meta-analysis showed that xanthan-based chlorhexidine gel as adjunct to non-surgical periodontal therapy gives benefit in terms of PPD reduction and CAL gain as compared to non-surgical periodontal therapy only. Since there was high heterogeneity among studies and the quality of the evidence is low, further studies characterized by a better methodology, adequate sample size and longer follow-up are warranted in the next future. The protocol of this scoping review was registered in the International Prospective Register of Systematic Reviews (https://www.crd.york.ac.uk/PROSPERO) with ID: CRD42023391589.

The role of acquired host immunity in periodontal diseases.

The aim of this narrative review is to relate the contribution of European researchers to the complex topic of the host immune system in periodontal disease, focusing on acquired immunity. Other chapters in this volume will address the genetics and autoantibody responses and other forms of immunity to periodontal disease. While the contribution of European authors is the focus, global literature is included in this descriptive narrative for contextual clarity, albeit many with European co-authors. The topic is relatively intense and is thus broken down into sections outlined below, tackled as descriptive narratives to enhance understanding. Any attempt at a systematic or scoping review was quickly abandoned given the descriptive nature and marked variation of approach in almost all publications. Even the most uniform area of this acquired periodontal immunology literature, antibody responses to putative pathogens in periodontal diseases, falls short of common structures and common primary outcome variables one would need and expect in clinical studies, where randomized controlled clinical trials (RCTs) abound. Addressing 'the host's role' in immunity immediately requires a discussion of host susceptibility, which necessitates consideration of genetic studies (covered elsewhere in the volume and superficially covered here).

Efficacy and safety of lurasidone for schizophrenia: A systematic review and meta‑analysis of eight short‑term, randomized, double‑blind, placebo‑controlled clinical trials.

Lurasidone is an atypical anti-psychotic approved by the US Food and Drug Administration. It is mainly used to treat schizophrenia in adults through its antagonistic action on dopamine and 5-hydroxytryptamine receptors. The present study systematically assessed the efficacy and safety of lurasidone in the treatment of schizophrenia. Clinical, double-blind, parallel, randomized controlled trials (RCTs) of lurasidone in the treatment of schizophrenia were retrieved from PubMed\Medline, EBSCO, Embase, Cochrane Library, OVID, Web of Science and related clinical trial registration websites up to May 2023. A total of two investigators independently screened the included references and evaluated their quality. RevMan 5.3 software was used for meta-analysis of each measure outcome. The present systematic review was registered in PROSPERO (ID=CRD42018108178). A total of eight RCTs were included in the present study, including a total of 2,456 patients with schizophrenia. All eight references were randomized, double-blind and parallel control trials. All eight references were evaluated as high quality. The meta-analysis results demonstrated that there were no significant change in total Positive and Negative Syndrome Scale (PANSS) score, Clinical Global Impression of Severity (CGI-S) score and Montgomery-Asberg Depression Rating Scale (MADRS) between the 40 mg lurasidone group and the placebo group (P>0.05). However, as the dosage increased, the 80, 120 and 160 mg lurasidone groups had significant changes in total PANSS score, CGI-S score and MADRS Compared with placebo (P<0.05), although changes in MADRS in the 120 mg lurasidone group were not statistically significant (P>0.05). In terms of safety, the changes in the incidence of agitation in the 40 mg lurasidone group (P<0.05), vomiting in the 80 mg group (P<0.05) and akathisia in the 160 mg group (P<0.05) were statistically significant and there were also statistically significant changes in the incidence of akathisia, nausea, somnolence and extrapyramidal disorder among the 40, 80 and 120 mg lurasidone groups (P<0.05); No statistically significant changes in the in the incidence of other adverse reactions (P>0.05). In conclusion, existing evidence suggests that the initial dose of lurasidone for schizophrenia can be adjusted to 80 mg. As the condition aggravates, the dose can be incrementally increased to 160 mg. A dose of 160 mg lurasidone is recommended as the most efficacious and safe dose for acute schizophrenia and the risk of occurrence of akathisia, nausea, somnolence and extrapyramidal disorder is still high when lurasidone is administered at a dose of 80-120 mg. The dose should be promptly adjusted or the drug should be withdrawn if the aforementioned adverse reactions worsen. Multi-center, high-quality and long-term clinical RCTs influenced by the included references are still necessary to support the aforementioned conclusions.

Therapeutic Effect of Synbiotics (Lactobacillus reuteri, Lactobacillus rhamnosus, Bifidobacterium infantis, and Fructooligosaccharides (FOS)) on Acute Non-bloody Diarrheal Episodes in Hospitalized Children Aged Between 6 - 24 Months: Randomized Double-Blind Placebo-Controlled Trial

Background: Regarding the appropriate effect of probiotics in treating acute diarrhea and the high prevalence of non-bacterial acute diarrhea among children in the population. Objectives: The present study evaluates the effect of synbiotic drops in children with acute diarrhea, including the number of hospitalization days, daily excreted diarrhea volume, duration of diarrhea, and reduction in the number of excretions between the case and control groups. Methods: This was a prospective double-blinded and randomized-controlled clinical trial on children aged 6 - 24 months with non-bloody acute diarrhea were included. The reason for hospitalization was diarrhea. In the case group, the patients consume PediLact (Zisttakhmir, Tehran, Iran) drop (Lactobacillus rhamnosus, Lactobacillus reuteri, and bifidobacterium infantis) 109 CFU and fructooligosaccharides. PediLact drop was used with milk or lukewarm food for five days along with other routine hospital cares. The number of hospitalization days, the daily excreted diarrhea, diarrhea duration, and decreasing numbers of excretion in patients were compared. Results: In the current study, 114 children were included. The duration of hospitalization was 3.87 ± 0.9 days in the synbiotic group and 4.26 ± 0.12 days in the placebo group (P-value = 0.001). The time between the onset of diarrhea and recovery was significantly higher in the placebo group than in the synbiotic group (P = 0.032). The number of evacuations was 1.89 ± 0.13 in the synbiotic group and 2.52 ± 0.18 in the placebo group (P = 0.014).

Efficacy of sucrose application in minimizing pain perception related to dental injection in children aged 3 to 9 years: a randomized control trial.

Dental fear and anxiety are significant challenges in managing behavior in children. Oral administration of sucrose or sweet-tasting solutions has shown effectiveness in reducing procedural pain in infants and neonates. This study aimed to investigate whether pre-application of sucrose solution had an effect on minimizing pain perception during injection and to assess the potential impact of the child's age and sweet preference. A randomized control clinical trial was conducted on 60 children aged 3-9 years requiring buccal infiltration injections. Following parental consent, demographic data of the children were recorded. Sweet preferences was assessed using a modified forced-choice test. Children were equally and randomly allocated into study (sucrose) and control groups using a lottery method. Sucrose solution or distilled water, respectively, was applied to the lateral surface of the tongue for 2 min. Topical anesthetic was applied at the site of injection, followed by local anesthesia administration. The children rinsed their mouths thrice with water immediately after anesthetic injection. A video was recorded during injection which was then scored by three blinded examiners on the Sound Eye Motor (SEM) scale. The children also self-evaluated using Wong-Baker Faces Pain Rating Scale (WBFPS). The mean SEM scores and WBFPS scores were analyzed using the Kruskall-Wallis test. The mean SEM score in the study group was 1.37 ± 0.61, compared to 3.17 ± 0.87 in the control group, showing a statistically significant difference (P < 0.001). Mean pain scores assessed by WBFPS in the study group were 0.60 ± 1.4, while in the control group, they were 6.27 ± 2.33, also showing a statistically significant difference (P < 0.001). Children with a sweet preference demonstrated a subjective reduction in pain perception. Application of sucrose before dental injections in children helps to minimize pain upon injection across all age groups.

Recruitment and retention of clinical trial participants: understanding motivations of patients with chronic pain and other populations.

This paper aims to present and discuss the issues, challenges, and strategies related to recruitment and retention in clinical trials involving participants with chronic pain. The randomized controlled clinical trial (RCT) is widely regarded as the gold standard for evaluating clinical interventions. However, it is crucial to acknowledge and address the challenges associated with recruiting and retaining participants. To prioritize the experience of the study population, targeted outreach strategies and a patient-centric approach are necessary. Researchers should consider incorporating recruitment and retention strategies during the study design phase. Implementing multi-pronged recruitment methods, leveraging relationships with community providers, and involving representatives of the patient population are helpful approaches. Effective communication and maintaining a professional environment are vital for optimizing engagement and supporting the successful execution of clinical trials involving participants with chronic pain.

Effectiveness of Rational Emotive Behavior Therapy (REBT) on Self-Control and Impulsivity in Male Prisoners.

Objective: Consequences of imprisonment include negative psychological effects, social stigma, and challenges for reintegrating into society. In this regard, this study aimed to investigate the effectiveness of Rational Emotive Behavior Therapy (REBT) on self-control and impulsivity among male prisoners. Method : A randomized controlled clinical trial (RCT) utilizing a design the included pretest, post-test, and follow-up assessment as well as a waiting-list control group was conducted. A total of 30 male prisoners were selected using convenience sampling and randomly assigned to experimental and waiting list control groups (the intervention group (n = 15) and the control group (n = 15)). The participants in the experimental group underwent the 12-session REBT intervention over a period of six weeks. (For six weeks). All participants responded to the Self- Control Scale (SCS) and Dysfunctional Impulsivity Questionnaire (DFIQ) as dependent variables at three time points (pretest, post-test, and one-month follow-up). A repeated measures analysis of variance was used to analyze the data. Results: The results revealed that after the implementation of the REBT intervention, the mean scores of self-control increased (P < 0.05), while the mean scores of impulsivity diminished significantly (P < 0.05). Furthermore, these changes remained relatively stable during the follow-up period (P < 0.05). Conclusion: Based on the findings of this study, it can be inferred that REBT intervention plays a significant role in diminishing self-control deficits and mitigating impulsivity among incarcerated individuals. These results present promising implications for the utilization of REBT in lowering recidivism rates.

Impact of combined propranolol and oxytocin on the process and outcomes of labor: a meta-analysis of randomized controlled trials.

To systematically review the impact of propranolol combined with oxytocin on the process and outcomes of labor. A comprehensive literature search was performed across multiple databases, including China National Knowledge Infrastructure (CNKI), VIP, Wanfang, China Biomedical Literature Database, PubMed, Embase, and the Cochrane Library. All publicly published randomized controlled trials (RCTs) of propranolol combined with oxytocin compared to the use of oxytocin alone in labor were collected. After screening the literature and extracting data, the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0 recommended bias risk assessment tool was used to assess the quality of the included studies. A meta-analysis was conducted using RevMan 5.3 software, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to rate the quality of evidence for outcome measures. Meta-analysis results showed that the group receiving propranolol combined with oxytocin was more capable of reducing the cesarean section rate (eight studies, 815 women, RR = 0.67, 95% CI (0.53, 0.86), P = 0.001) and shortening the duration of the latent phase (two studies, 206 women, MD =  - 1.20, 95% CI (- 1.97, - 0.43), P = 0.002) and the duration of the active phase on day 1 (two studies, 296 women, MD =  - 0.69, 95% CI (- 0.83, - 0.54), P < 0.00001), compared to the oxytocin monotherapy group. No significant difference was found between the two groups in terms of the 5-min Apgar score (five studies, 609 women, MD =  - 0.05, 95% CI (- 0.14, 0.04), P = 0.32) and the rate of admissions to the Neonatal Intensive Care Unit (NICU) (three studies, 359 women, RR = 0.82, 95% CI (0.38, 1.79), P = 0.62). The combined use of propranolol and oxytocin can significantly reduce the cesarean section rate, shorten the duration of the latent phase and the duration of the active phase on day 1, and is safe. However, due to the limitations, the conclusions of this article still need to be verified by large-sample, multicenter, rigorously designed high-quality clinical RCTs. Registration number is INPLASY202390107.

Re: Autologous Platelet Rich Plasma (A-PRP) Combined with Pelvic Floor Muscle Training for the Treatment of Female Stress Urinary Incontinence (SUI): A Randomized Control Clinical Trial

Re: Autologous Platelet Rich Plasma (A-PRP) Combined with Pelvic Floor Muscle Training for the Treatment of Female Stress Urinary Incontinence (SUI): A Randomized Control Clinical Trial

[Evidence map of clinical research on Chinese patent medicines for post-acute myocardial infarction heart failure].

An evidence map was established to comprehensively sort out the clinical research in the treatment of post-acute myocardial infarction heart failure(P-AMI-HF) with Chinese patent medicines, so as to reveal the distribution of evidence in this field. CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, and EMbase were searched for the randomized controlled trial(RCT), systematic reviews/Meta-analysis, and guidelines/consensus in this field. The evidence was analyzed and displayed in the form of a combination of text, charts, bubble charts, and bar charts, and the quality of RCT, systematic reviews/Meta-analysis, and guidelines/consensus were evaluated by RoB 1.0, AMSTAR2, and AGREE Ⅱ, respectively. A total of 163 RCTs, 4 systematic reviews/Meta-analysis, 1 network Meta-analysis, 2 observational studies, and 5 guidelines/consensus were included. In recent years, the total number of publications in this field has shown an upward trend. There were a variety of Chinese patent medicines in the treatment of P-AMI-HF, among which Shenfu Injection received the most attention. The clinical RCT and systematic reviews/Meta-analysis generally had poor quality, and the RCT mostly had a small size, a single center, and a short cycle. The outcome indicators mainly included cardiac function indicators, myocardial injury markers, total response rate, hemodynamic indicators, and safety indicators, while the characteristic efficacy indicators of TCM received insufficient attention. The development processes of some guidelines/consensus lack standardization, which compromised their authority and rationality. Chinese patent medicines have advantages in the treatment of P-AMI-HF, while there are also problems, which remain to be solved by more high-quality evidence. That is, more large-sample and multi-center clinical studies should be carried out in the future, and the formulation process of relevant systematic reviews/Meta-analysis and guideline/consensus should be standardized and the quality of evidence should be improved. In this way, the effectiveness and safety of Chinese patent medicines in the treatment of P-AMI-HF can be explored.

Mitoquinone mesylate as post-exposure prophylaxis against SARS-CoV-2 infection in humans: an exploratory single center pragmatic open label non-randomized pilot clinical trial with matched controls

An ongoing important need exists to rapidly develop novel therapeutics for COVID-19 that will retain antiviral efficacy in the setting of rapidly evolving SARS-CoV-2 variants and potential future development of resistance of SARS-COV-2 to remdesivir and protease inhibitors. To date, there is no FDA-approved treatment for post-exposure prophylaxis against SAR-CoV-2. We have shown that the mitochondrial antioxidant mitoquinone/mitoquinol mesylate (Mito-MES), a dietary supplement, has antiviral activity against SARS-CoV-2 invitro and in SARS-CoV-2 infected K18-hACE2 mice. In this exploratory, pragmatic open label clinical trial (ClinicalTrials.gov identifier NCT05381454), we studied whether Mito-MES is an effective post-exposure prophylaxis treatment in people who had high-grade unmasked exposures to SARS-CoV-2 within 5 days prior to study entry. Participants were enrolled in real-world setting in Los Angeles, United States between May 1 and December 1, 2022 and were assigned to either mito-MES 20mg daily for 14 days (n=40) or no mito-MES (controls) (n=40). The primary endpoint was development of SARS-CoV-2 infection based on 4 COVID-19 diagnostic tests [rapid antigen tests (RATs) or PCR] performed during the study period (14 days post exposure). Out of 40 (23 females; 57.5%) study participants who took Mito-MES, 12 (30%) developed SARS-CoV-2 infection compared to 30 of the 40 controls (75%) (difference-45.0%, 95% confidence intervals (CI):-64.5%,-25.5%). Out of 40 (19 females; 47.5%) study participants in the control group, 30 (75.0%) had at least one positive COVID-19 diagnostic test and 23 (57.5%) were symptomatic. With regards to key secondary outcomes, among symptomatic SARS-CoV-2 infections, the median duration of viral symptoms was lower in the Mito-MES group (median 3.0, 95% CI 2.75, 3.25) compared to the control group (median 5.0, 95% CI 4.0, 7.0). None of the study participants was hospitalized or required oxygen therapy. Mito-MES was well tolerated and no serious side effect was reported in any study participant. This work describes antiviral activity of mito-MES in humans. Mito-MES was well tolerated in our study population and attenuated transmission of SARS-CoV-2 infection. Given established safety of Mito-MES in humans, our results suggest that randomized control clinical trials of Mito-MES as post-exposure prophylaxis against SARS-CoV-2 infection are warranted. This work was supported in part by National Institutes of Health grant R01AG059501 (TK), National Institutes of Health grant R01AG059502 04S1 (TK), NIH/National Center for Advancing Translational Sciences (NCATS) UCLA CTSI Grant Number UL1TR001881 and California HIV/AIDS Research Program grant OS17-LA-002 (TK).

Risk of major adverse cardiovascular events and stroke associated with treatment with GLP-1 or the dual GIP/GLP-1 receptor agonist tirzepatide for type 2 diabetes: A systematic review and meta-analysis.

Mounting evidence suggests that glucagon-like-peptide-1 receptor-agonists (GLP-1 RAs) attenuate cardiovascular-risk in type-2 diabetes (T2DM). Tirzepatide is the first-in-class, dual glucose-dependent-insulinotropic-polypeptide GIP/GLP-1 RA approved for T2DM. A systematic review and meta-analysis of randomized-controlled clinical trials (RCTs) was performed to estimate: (i) the incidence of major adverse cardiovascular events (MACE); and (ii) incidence of stroke, fatal, and nonfatal stroke in T2DM-patients treated with GLP-1 or GIP/GLP-1 RAs (vs placebo). Thirteen RCTs (9 and 4 on GLP-1 RAs and tirzepatide, respectively) comprising 65,878 T2DM patients were included. Compared to placebo, GLP-1RAs or GIP/GLP-1 RAs reduced MACE (OR: 0.87; 95% CI: 0.81-0.94; p < 0.01; I2 = 37%), all-cause mortality (OR: 0.88; 95% CI: 0.82-0.96; p < 0.01; I2 = 21%) and cardiovascular-mortality (OR: 0.88; 95% CI: 0.80-0.96; p < 0.01; I2 = 14%), without differences between GLP-1 versus GIP/GLP-1 RAs. Additionally, GLP-1 RAs reduced the odds of stroke (OR: 0.84; 95% CI: 0.76-0.93; p < 0.01; I2 = 0%) and nonfatal stroke (OR: 0.85; 95% CI: 0.76-0.94; p < 0.01; I2 = 0%), whereas no association between fatal stroke and GLP-1RAs was uncovered (OR: 0.80; 95% CI: 0.61-1.05; p = 0.105; I2 = 0%). In secondary analyses, GLP-1 RAs prevented ischemic stroke (OR: 0.74; 95% CI: 0.61-0.91; p < 0.01; I2 = 0%) and MACE-recurrence, but not hemorrhagic stroke (OR: 0.92; 95% CI: 0.51-1.66; p = 0.792; I2 = 0%). There was no association between GLP-1RAs or GIP/GLP-1 RAs and fatal or nonfatal myocardial infarction. GLP-1 and GIP/GLP-1 RAs reduce cardiovascular-risk and mortality in T2DM. While there is solid evidence that GLP-1 RAs significantly attenuate the risk of ischemic stroke in T2DM, dedicated RCTs are needed to evaluate the efficacy of novel GIP/GLP-1 RAs for primary and secondary stroke prevention.

A community challenge to predict clinical outcomes after immune checkpoint blockade in non-small cell lung cancer

BackgroundPredictive biomarkers of immune checkpoint inhibitor (ICI) efficacy are currently lacking for non-small cell lung cancer (NSCLC). Here, we describe the results from the Anti–PD-1 Response Prediction DREAM Challenge, a crowdsourced initiative that enabled the assessment of predictive models by using data from two randomized controlled clinical trials (RCTs) of ICIs in first-line metastatic NSCLC.MethodsParticipants developed and trained models using public resources. These were evaluated with data from the CheckMate 026 trial (NCT02041533), according to the model-to-data paradigm to maintain patient confidentiality. The generalizability of the models with the best predictive performance was assessed using data from the CheckMate 227 trial (NCT02477826). Both trials were phase III RCTs with a chemotherapy control arm, which supported the differentiation between predictive and prognostic models. Isolated model containers were evaluated using a bespoke strategy that considered the challenges of handling transcriptome data from clinical trials.ResultsA total of 59 teams participated, with 417 models submitted. Multiple predictive models, as opposed to a prognostic model, were generated for predicting overall survival, progression-free survival, and progressive disease status with ICIs. Variables within the models submitted by participants included tumor mutational burden (TMB), programmed death ligand 1 (PD-L1) expression, and gene-expression–based signatures. The best-performing models showed improved predictive power over reference variables, including TMB or PD-L1.ConclusionsThis DREAM Challenge is the first successful attempt to use protected phase III clinical data for a crowdsourced effort towards generating predictive models for ICI clinical outcomes and could serve as a blueprint for similar efforts in other tumor types and disease states, setting a benchmark for future studies aiming to identify biomarkers predictive of ICI efficacy.Trial registration: CheckMate 026; NCT02041533, registered January 22, 2014.CheckMate 227; NCT02477826, registered June 23, 2015.

“A COMPARATIVE CLINICAL STUDY TO EVALUATE THE EFFICACY OF NIMBAADI LEPA IN THE MANAGEMENT OF PRASUTAA YONI KSHATA WITH SPECIAL REFERENCE TO EPISIOTOMY WOUND.”

Prasutaa Yoni Kshata comes under the category of Sadyovrana, subcategorized as Chinna / Kshta Vrana (cut wound). Despite the rich blood supply of the perineum, which facilitates easy wound healing, there is still a risk of contamination by lochia, faeces, urine, etc., so there is a need for proper care of episiotomy wounds to avoid complications. Study design: An open-labelled randomised control clinical trial with pre-and post-test designs. Materials and methods: 40 Females who underwent normal vaginal delivery with episiotomy were selected and randomly divided into two groups of 20 each. In Group A, Nimbaadi Lepa was applied on the surface of a su-tured episiotomy wound with 1/4th Angula (0.44cms approx.) thickness, and in Group B (control) Kumari Majja with Haridra Lepa was applied two times a day for seven days. Follow-ups: on the 7th and 15th day. Results ob-tained were tabulated and statistically analysed using the Friedman, Wilcoxon signed rank, and Mann- Whitney U tests. Both groups showed statistically significant results within the group. Comparison between 2 groups shows Nimbaadi Lepa is slightly more effective than Kumari Majja with Haridra Lepa. Conclusion: Both the formulations proved effective on statistical value in terms of Vrana shodhana, Vrana ropana, Vedanasthapana, and Shothahara properties for episiotomy wound healing.

538 - Physician-assessed effectiveness and patient-reported outcomes in adult and adolescent patients with atopic dermatitis in the Asian subpopulation treated with dupilumab: real-world insights 1 year into the GLOBOSTAD multinational prospective observational study

Abstract Introduction In multiple randomized controlled clinical trials, dupilumab demonstrated robust efficacy in patients with moderate-to-severe atopic dermatitis (AD). Long-term effectiveness of dupilumab in real-world AD treatment is one of the main objectives of the ongoing GLOBOSTAD study. Comprehensive data on Asian patients with moderate-to-severe AD treated with dupilumab are limited. Objectives To report patient-reported outcomes and physician-assessed AD clinical measures to evaluate disease characteristics, severity, and treatment effectiveness 1 year after initiating dupilumab treatment in Asian patients. The baseline disease severity and patient demographics have been reported previously1. Methods This 5-year, multinational, multicentre, prospective, observational study (GLOBOSTAD; NCT03992417) included Asian patients ≥12 years-old with moderate-to-severe AD who initiated dupilumab treatment based on country-specific prescribing criteria. Eczema Area and Severity Index (EASI), Scoring Atopic Dermatitis (SCORAD), Patient-Oriented Eczema Measure (POEM), Peak Pruritus Numerical Rating Scale (PP-NRS) and Dermatology Life Quality Index (DLQI) were assessed at baseline, 3 months (± 1 month), 6 months (± 2 months), and 12 months (± 2 months). Data are reported as observed in patients self-reported as Asian for enrolment/safety (N = 204; data cutoff: March 2023) and follow-up (N = 194) populations. Results During the study, EASI (&amp;gt;21 = severe; ≤7 = mild/no disease) score improved from 28.0 (12.1), mean (SD) at baseline to 7.4 (8.5) at 3 months, 5.7 (6.9) at 6 months, and was sustained until the end of observation period, 12 months, at 4.7 (7.1). Similarly, SCORAD (&amp;gt;50 = severe; &amp;lt;25 = mild/no disease) score improved from 61.5 (16.9) at baseline to 25.4 (16.6) at 3 months, 22.5(14.8) at 6 months, and further improved to 18.6 (13.3) at 12 months. During the study, patients also reported early improvements in POEM, mean (SD) from 19.1 (7.3) at baseline to 8.0 (5.8) at 3 months, 7.6 (5.5) at 6 months, and to 7.2 (5.0) at end of observation period (12 months); PP-NRS decreased from 5.7 (2.3) to 2.1 (2.2) to 1.7 (1.8), and to 1.4 (1.7) at 3 months, 6 months, and 12 months respectively; and DLQI improved from 13.2 (7.4) to 4.9 (4.6) to 4.0 (3.8), and to 4.1 (4.0) at 3 months, 6 months and 12 months respectively. Dupilumab-related adverse events were reported in 44 (21.5%) patients while 4 (2.0%) reported dupilumab-related severe adverse events. Conclusion In Asian patients, the initiation of dupilumab treatment led to early improvements in all AD outcome measures, sustained throughout the 1-year observational period. Safety and treatment effectiveness were consistent with overall population.

The effect of sham acupuncture can differ depending on the points needled in knee osteoarthritis: A systematic review and network meta-analysis

ObjectiveIn sham acupuncture-controlled acupuncture clinical trials, although sham acupuncture techniques are different from those of verum acupuncture, the same acupuncture points are often used for verum and sham acupuncture, raising the question of whether sham acupuncture is an appropriate placebo. We aimed to examine the effects of sham and verum acupuncture according to the points needled (same or different between verum and sham acupuncture) in knee osteoarthritis. MethodsTen databases were searched to find randomized controlled clinical trials (RCTs) assessing the effects of verum acupuncture with sham acupuncture or waiting lists on knee osteoarthritis. Sham acupuncture was classified as using the same acupuncture points as those in verum acupuncture (SATV) or using sham points (SATS). A frequentist network meta-analysis (NMA) was conducted, and the certainty of evidence was evaluated. ResultsA total of 10 RCTs involving 1628 participants were included. Verum acupuncture was significantly superior to SATS but not different from SATV in terms of pain reduction. Additionally, SATV was significantly superior to the waiting list. For physical function, no difference were found between verum acupuncture, SATV, and SATS. The certainty of evidence was low to moderate. ConclusionFor knee osteoarthritis, the pain reduction effect of acupuncture may differ according to the needling points of sham acupuncture, and the control group should be established according to the specific aim of the study design and treatment mechanism.