Randomized Controlled Clinical Trials Research Articles

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.

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).

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.

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.

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.

Selection of epigenetically privileged HIV-1 proviruses during treatment with panobinostat and interferon-α2a

CD4+ Tcells with latent HIV-1 infection persist despite treatment with antiretroviral agents and represent the main barrier to a cure of HIV-1 infection. Pharmacological disruption of viral latency may expose HIV-1-infected cells to host immune activity, but the clinical efficacy of latency-reversing agents for reducing HIV-1 persistence remains to be proven. Here, we show in a randomized-controlled human clinical trial that the histone deacetylase inhibitor panobinostat, when administered in combination with pegylated interferon-α2a, induces a structural transformation of the HIV-1 reservoir cell pool, characterized by a disproportionate overrepresentation of HIV-1 proviruses integrated in ZNF genes and in chromatin regions with reduced H3K27ac marks, the molecular target sites for panobinostat. By contrast, proviruses near H3K27ac marks wereactively selected against, likely due to increased susceptibility to panobinostat. These data suggest that latency-reversing treatment can increase the immunological vulnerability of HIV-1 reservoir cells and accelerate the selection of epigenetically privileged HIV-1 proviruses.

Virtual Surgical Guidance Improves Quality of Life Following Scapular Free-Flap Reconstruction of Maxillary Defects

BackgroundThe best way for maxillary reconstruction remains the subject of debate, with negative impacts on the patient’s quality of life (QOL). PurposeThis study was designed to evaluate the QOL outcomes following maxillary reconstruction using a scapular-free flap, with and without the computer-aided design and computer-aided manufacturing (CAD/CAM) technique. Study design and patientsA prospective randomized controlled clinical trial was performed following the CONSORT checklist. To be included, patients suffering from maxillary defects without previous surgery or lymph node involvement were selected. Patients with poor oncological prognosis, deficient performance status, preoperative chemotherapy, or radiotherapy, besides vascular contraindications, were excluded. Predictor variableThe predictor variable was the reconstruction technique, grouped into two equal categories. Patients were randomly assigned to reconstruction with a scapular-free flap, with the control group not utilizing a guide and the study group utilizing a CAD/CAM-customized guide. Outcome variableThe primary outcome variable was the various domains of QOL, measured using the University of Washington-QOL (UW-QOL) score, 12 months after reconstruction. Covariatesage; sex; scapular flap side; and maxillary defect tumour type, histopathology, side, length, class, sagittal, and axial differential areas were considered. AnalysesShapiro-Wilk and Kolmogorov-Smirnov tests were performed for normality. For comparisons between the two groups, Student’s t-test and Mann-Whitney test were used. The category variables were compared using the chi-square test. p ≤ 0.05 was considered statistically significant. ResultsThe sample was composed of twenty-two eligible patients, eleven in each group. The mean age of the control group was (50.09±17.14) years, and 45.45% were male, while in the study group, the mean age was (48.36±14.14) years, with 36.36% male. All the patients were evaluated, showing statistically significant differences between control and study groups in terms of pain, appearance, chewing, swallowing, speech, and shoulder (p ≤ 0.05), indicating that the scapular-free flap with a CAD/CAM osteotomy guide had improved the patient's QOL. ConclusionsThe findings of this study indicate that VSP with a CAD/CAM customized osteotomy guide using a scapular-free flap can improve QOL in maxillary reconstruction in terms of pain, appearance, chewing and swallowing food, pronouncing words, and shoulder QOL outcomes.

Theta burst stimulation: what role does it play in stroke rehabilitation? A systematic review of the existing evidence

Various post-stroke dysfunctions often result in poor long-term outcomes for stroke survivors, but the effect of conventional treatments is limited. In recent years, lots of studies have confirmed the effect of repetitive transcranial magnetic stimulation (rTMS) in stroke rehabilitation. As a new pattern of rTMS, theta burst stimulation (TBS) was proved recently to yield more pronounced and long-lasting after-effects than the conventional pattern at a shorter stimulation duration. To explore the role of TBS in stroke rehabilitation, this review summarizes the existing evidence from all the randomized controlled trials (RCTs) so far on the efficacy of TBS applied to different post-stroke dysfunctions, including cognitive impairment, visuospatial neglect, aphasia, dysphagia, spasticity, and motor dysfunction. Overall, TBS promotes the progress of stroke rehabilitation and may serve as a preferable alternative to traditional rTMS. However, it’s hard to recommend a specific paradigm of TBS due to the limited number of current studies and their heterogeneity. Further high-quality clinical RCTs are needed to determine the optimal technical settings and intervention time in stroke survivors.

Building Research Infrastructure to Develop Greater Learning Efficiencies (BRIDGE).

In this manuscript, we outline our developed version of a Learning Health System (LHS) in oncology implemented at the Department of Veterans Affairs (VA). Transferring healthcare into an LHS framework has been one of the spearpoints of VA's Central Office and given the general lack of evidence generated through randomized control clinical trials to guide medical decisions in oncology, this domain is one of the most suitable for this change. We describe our technical solution, which includes a large real-world data repository, a data science and algorithm development framework, and the mechanism by which results are brought back to the clinic and to the patient. Additionally, we propose the need for a bridging framework that requires collaboration between informatics specialists and medical professionals to integrate knowledge generation into the clinical workflow at the point of care.

DOP29 Capsule endoscopy-guided proactive treatment versus standard treatment of patients with quiescent Crohn’s Disease: The CURE-CD randomized controlled trial

Abstract Background Optimal strategies for treat-to-target in Crohn’s disease (CD) are still being sought. We aimed to examine the value of capsule endoscopy (CE) to guide proactive treatment optimization in patients with CD Methods A prospective randomized controlled clinical trial with temporally-restricted blinding. Patients with CD involving the small bowel who were in clinical remission (CDAI&amp;lt;150) for over three months were enrolled. Baseline clinical, biomarker, imaging, patency capsule and CE assessments were performed. ‘High risk’ patients, defined as CE Lewis score ≥350 were randomized to either proactive treatment optimization or continued standard care for 24 months. ‘Low risk’ patients with Lewis score&amp;lt;350 continued their standard care. All patients repeated CE every six months for 24 months. Primary outcome was the rate of clinical exacerbation (CDAI increase&amp;gt;70 points and CDAI&amp;gt;150 or hospitalization/surgery) in the standard-care versus the proactive-care sub-groups of high-risk patients, at 24 months. Secondary outcomes included risk of flare in the low-risk versus the standard-care high-risk arms, and predictive profiles for flare of calprotectin, MRI, intestinal ultrasound and Lewis score. Results Out of 118 screened patients, 60 were enrolled (20 in each of the three arms). Treatment intensification in CE-determined high-risk group, who were allocated to proactive treatment, comprised biologic dose-escalation (n=11/20), starting a biologic (8/20) or swapping a biologic (1/20) at study entry. Notably, 9/20 proactive-group patients underwent a second optimization following detected inflammation on subsequent semi-annual CE studies. Clinical exacerbation by 24 months (primary outcome) occurred in 5/20 (25%) of the high-risk proactive-treatment group versus 14/20 (70%) of the high-risk standard-care group (OR=0.14, 95%CI 0.04-0.57, p=0.006). For secondary outcomes, the rate of clinical flare in the standard-care low-risk group was numerically but not significantly lower than in standard-care high-risk group (9/20 versus 14/20, respectively, OR 0.3, 0.1-1.3, P=0.11). Among all patients continuing standard care, baseline CE Lewis score was higher among relapsers versus non-relapsers (median 450, IQR [225-900] versus 225, [135-600], respectively, p=0.03). Of 251 CE ingested, there was a single (0.4%) temporarily-retained CE, which resolved spontaneously. Conclusion In a randomized strategy-finding controlled trial, proactive treatment optimization based on CE findings in patients with CD in remission, proved safe and superior for prevention of disease exacerbation compared with continued standard care. NCT03555058

Effectiveness of promethazine on preoperative and intraoperative sequelae in cleft palate surgeries.

Anxiety and nosocomial infection are the most common reported problems in children undergoing cleft surgeries. Research shows that there is an enigma in the use of antihistamine therapy in children for the management of upper respiratory tract infection. 'Promethazine' is a first-generation H1 receptor antagonist, and antihistamine also has strong sedative effects. Our study aims at evaluating the Effectiveness of Promethazine (Phenergan) in preoperative and intra operative sequelae in cleft surgeries. This is a single-centre, parallel, randomized, double-blinded randomized control clinical trial, which was conducted among 128 children between 2 and 4 years of age undergoing cleft palate surgery under general anaesthesia. After randomization, the case group was subjected to promethazine syrup 1 mg/kg body weight twice a day, orally for 3 days. The primary outcomes were preoperative anxiety levels which were recorded by children fear scale. The secondary outcomes include preoperative sleep quality and cough rate of children which are recorded by using sleep and cough objective scale respectively. The intraoperative heart rate is monitored with an ECG connected to a monitor. Promethazine causes a reduction in the anxiety level by 70%, 64% reduction in cold and cough, improvement in sleep score by 70% and the heart rate was found to be stable throughout the surgery when compared to the control group. As the benefits of promethazine in cleft palate surgery rule over its adverse effects, promethazine is considered safe to be used as premedication for children undergoing cleft palate surgeries.

Clinical parameters that affect performance and patient satisfaction of root-retained overdentures: A systematic review of randomised controlled clinical trials.

To evaluate clinical parameters that affect the performance of root-supported overdentures (ROD) and to identify the possible factors that may affect it. ROD still serve as an alternative and successful treatment plan nowadays for partially edentulous patients. Nonetheless, there is not yet conclusive evidence about their clinical evaluation. A search strategy was developed following a PIO (Population, Intervention, Outcome) framework including an electronic search in the following databases: PubMed, Cochrane Library and Scopus. The systematic search included only randomised controlled clinical trials (RCTs), published until January 2023 in English language and was performed by two independent reviewers. Quality assessment of the included studies was conducted according to the Cochrane Risk of Bias tool. The final selection of studies included 11 RCTs. Clinically relevant variables derived from this search were: Complications, with caries being the most frequently reported, periodontal aspects and bone changes around abutment teeth. Additionally, methods and clinical suggestions for the maintenance of these restorations and patient-related outcomes were assessed. According to the risk of bias assessment, nine studies were considered of high risk, whereas only 2 of low risk. A meta-analysis was not feasible. Within the limitations of this systematic review, ROD remain a viable treatment plan, offering better denture stability and bone preservation around abutment teeth and high patient satisfaction. Thorough oral hygiene and regular follow-ups are of utmost importance. Further well-designed RCTs are necessary for firmer conclusions.

A systematic review and network meta-analysis of pharmaceutical interventions used to manage chronic pain.

It is estimated 1.5 billion of the global population suffer from chronic pain with prevalence increasing with demographics including age. It is suggested long-term exposure to chronic could cause further health challenges reducing people's quality of life. Therefore, it is imperative to use effective treatment options. We explored the current pharmaceutical treatments available for chronic pain management to better understand drug efficacy and pain reduction. A systematic methodology was developed and published in PROSPERO (CRD42021235384). Keywords of opioids, acute pain, pain management, chronic pain, opiods, NSAIDs, and analgesics were used across PubMed, Science direct, ProQuest, Web of science, Ovid Psych INFO, PROSPERO, EBSCOhost, MEDLINE, ClinicalTrials.gov and EMBASE. All randomised controlled clinical trials (RCTs), epidemiology and mixed-methods studies published in English between the 1st of January 1990 and 30th of April 2022 were included. A total of 119 studies were included. The data was synthesised using a tri-partied statistical methodology of a meta-analysis (24), pairwise meta-analysis (24) and network meta-analysis (34). Mean, median, standard deviation and confidence intervals for various pain assessments were used as the main outcomes for pre-treatment pain scores at baseline, post-treatment pain scores and pain score changes of each group. Our meta-analysis revealed the significant reduction in chronic pain scores of patients taking NSAID versus non-steroidal opioid drugs was comparative to patients given placebo under a random effects model. Pooled evidence also indicated significant drug efficiency with Botulinum Toxin Type-A (BTX-A) and Ketamine. Chronic pain is a public health problem that requires far more effective pharmaceutical interventions with minimal better side-effect profiles which will aid to develop better clinical guidelines. The importance of understanding ubiquity of pain by clinicians, policy makers, researchers and academic scholars is vital to prevent social determinant which aggravates issue.

A randomized control clinical trial of brief supportive psychotherapy in acute coronary syndrome patients: focus on neutrophil-lymphocyte ratio and psychological symptoms

Background Neutrophil-lymphocyte ratio (NLR) may predict prognosis in acute coronary syndrome (ACS) patients. Psychological conditions play a role before, during and after infarction that can be treated with brief supportive psychotherapy (BSP). This study aimed to analyze effect of BSP on NLR and psychological symptoms (PS) in ACS patients. Methods This double opened clinical randomized study included ACS patients who were treated in Intensive Cardiac Care Unit (ICCU) Cipto Mangunkusumo Hospital, Jakarta in April to July 2019. The BSP was planned for 5 sessions as long as the patients were in ICCU. NLR and PS that was evaluated using hospital anxiety depression scale were measured at baseline and after last BSP or right before discharged from ICCU. Data were analyzed with independent t-test or Mann-Whitney test. Results We recruited 32 patients in BSP and 35 patients in control group. The median age was 55 (32 – 86) years old and mostly were men (75%). The median length of stay in ICCU was 5 (2-13) days. NLR was similar in BSP and control group (3.35 [2.26] vs 3.63 [1.79], p=0.346). ΔNLR was higher in BSP than control group in patients without CHF (3.87 [5.48] vs 0.33 [2.54], p=0.007) and without CAD (3.88 [4.55] vs 0.84 [2.51], p=0.014). Meanwhile, Δ depression score was higher in BSP than control group in patients with CHF (1.73 [3.58] vs -1.27 [2.8], p=0.041) and with CAD (2.08 [3.4] vs -0.8 [3.3], p=0.035). Conclusions There was influence of BSP on NLR in ACS patients without CHF or CAD, and psychological symptoms in ACS ones with CHF or CAD. This trial had registered in ClinicalTrial.gov.id with code number NCT04274205.

Ophthalmic and Systemic Factors of Acute Nonarteritic Anterior Ischemic Optic Neuropathy in the Quark207 Treatment Trial

PurposeWe describe the baseline ophthalmic and cardiovascular (CV) risk factors, reported as associated with NAION, across countries, race and sex for the Quark207 treatment trial for acute NAION. DesignProspective randomized control clinical trial ParticipantsAdults age 50-80 years old with acute NAION recruited from 80 sites across 8 countries, 191 of whom were controls.Main measuresOphthalmic features of NAION and CV risk factors MethodsWe evaluated demographics, clinical and ophthalmological data including best-corrected visual acuity (BCVA) and average visual field total deviation (TD) in affected eyes and cup:disc ratio in fellow eyes at enrollment. We report the prevalence (median and interquartile Q1, Q3) of ophthalmic features and CV risk factors, stratified by country, race, and sex. We corrected for multiple comparisons using Dunn’s test with Bonferroni correction for continuous variables and Chi-square testing with Holm-Bonferroni correction for categorical variables. ResultsThe study enrolled 500 males and 229 females, median age 60 and 61 (p=0.027) years, respectively. Participants were predominantly White (570) and Asian (149). The study eye BCVA was 71 (53, 84) characters (approximately logMAR score 0.4), and the TD for stimulus III was -16.5 dB (-22.2, -12.6) and -15.7 dB (-20.8, -10.9) for stimulus V. The vertical and horizontal cup:disc ratio was 0.1 (0.1, 0.3) for unaffected fellow eyes. The prevalence of CV risk factors varied among countries. The most notable differences were in the baseline comorbidities and ophthalmological features, which differed between the Asian and White races. Males and females differed with respect to a few clinically meaningful features. ConclusionsThe CV risk factors in our NAION cohort varied among the seven countries, race and sex but were not typically more prevalent than previously reported in the general population. Ophthalmic features, typical of NAION, were generally consistent across countries, race and sex, except for worse BCVA and TD in China. Men have a frequency of NAION twice women. Having a small cup:disc ratio in the fellow eye was the most prevalent and consistent risk factor across all demographics. This study suggests that other factors, not yet identified, may contribute to the development of NAION.

Nutrition and Disorders of Gut-Brain Interaction.

Disorders of gut-brain interaction (DGBIs) have a complex pathophysiology that is often characterized by a relationship between food ingestion and triggering of symptoms. Understanding of the underlying mechanisms and the role of nutrients as a therapeutic target are rapidly evolving. We performed a narrative review of the literature using the following keywords, their acronyms, and their associations: nutrients, disorders of gut-brain interaction; functional dyspepsia; malabsorption; irritable bowel syndrome; diarrhea; constipation. Functional dyspepsia displayed a significant correlation between volume, fat and/or wheat abundance, chemical composition of ingested food and symptoms of early satiety, fullness and weight loss. Carbohydrate malabsorption is related to enzyme deficiency throughout the GI tract. Food composition and richness in soluble vs. non-soluble fibers is related to constipation and diarrhea. The elimination of fermentable oligo-, di-, monosaccharides and polyols (FODMAPs) has a significant and non-unidirectional impact on irritable bowel syndrome (IBS) symptoms. Food volume, nutritive and chemical composition, and its malabsorption are associated with symptom generation in DGBIs. Further multicenter, randomized-controlled clinical trials are needed to clarify the underlying pathophysiology.