Trial Of Therapy Research Articles

1646P A multicohort phase II trial of androgen deprivation therapy (ADT), docetaxel (DOCE) and nivolumab (NIVO) in patients (pts) with newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC) enriched for inflamed tumours and DNA damage repair (DDR) alterations: Cohort 3 results

1646P A multicohort phase II trial of androgen deprivation therapy (ADT), docetaxel (DOCE) and nivolumab (NIVO) in patients (pts) with newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC) enriched for inflamed tumours and DNA damage repair (DDR) alterations: Cohort 3 results

455P Phase II trial of hippocampus-avoidance whole-brain radiation therapy with simultaneous integrated boost for multiple brain metastases in non-small cell lung cancer

455P Phase II trial of hippocampus-avoidance whole-brain radiation therapy with simultaneous integrated boost for multiple brain metastases in non-small cell lung cancer

Validation of Breast Idea Volume Estimator Application in Transfeminine People.

Accurate estimation of breast volume is important as researchers aim to achieve optimal feminization for transfeminine people. The Breast Idea Volume Estimator (BIVE) application allows estimation of breast volume using two-dimensional (2D) photographs but has not been validated in the chests of people who have undergone testosterone-mediated puberty. To estimate breast volume, clinical photographs and 3D scans were collected at baseline and 6 months, as a prespecified secondary outcome of a randomized clinical trial of antiandrogen therapy in transfeminine people commencing hormone therapy. BIVE was used to estimate breast volume by two independent researchers and compared with the gold standard of 3D scan calculated volume at different timepoints. Statistical analysis was performed, including the mean absolute difference, standard error of measurement, and intraclass correlation, to determine accuracy, precision, and interrater agreement. Clinical photography and 3D scans were collected from 82 breasts of 41 participants. The median (interquartile range) age of participants was 25 (22-28) years, and the median (interquartile range) body mass index was 24.6 (21.2-28.9) kg/m2. The BIVE sagittal and transverse algorithms demonstrated robust performance, with mean absolute difference less than 20 mL and intraclass correlation greater than 0.87 indicating clinical reliability with high interrater agreement. BIVE provided an accurate, precise, and reliable measure of breast volume in the chests of people who have undergone testosterone-mediated puberty, compared with the gold standard of 3D scan.

Age and Sex Affects the Frequency and Mutation Type of FGFR2 Alterations in Cholangiocarcinoma

PURPOSE FGFR2 alterations are infrequent but currently represent the most common targetable mutation in cholangiocarcinoma. We performed a large-scale genomic analysis to assess associations between FGFR2 and other driver gene alterations in cholangiocarcinoma with patient demographics. METHODS Clinical and molecular data for patients with intrahepatic cholangiocarcinoma were abstracted from the Foundation Medicine (FMI) and Genomics, Evidence, Neoplasia, Information, Exchange (GENIE) genomic databases. The Chi-squared test was used to assess the association between sex and alterations in driver genes. FGFR2 fusion partners were analyzed using descriptive statistics. RESULTS Across both FMI (N = 7,859) and GENIE (N = 1,395) cohorts, FGFR2 rearrangements were more frequent in female than male patients with cholangiocarcinoma (odds ratio, 1.69 and 2.45). By contrast, FGFR2 missense mutations, TP53 mutations, and KRAS mutations were not associated with sex. Stratifying patients by age groups showed that FGFR2 rearrangements were specifically enriched in younger ages (<45 years). Although the most common FGFR2 fusion partners were shared across both sexes, a subset of fusion partners was recurrent and uniquely associated with female or male patients. CONCLUSION FGFR2 rearrangements but not other driver alterations in cholangiocarcinoma are concentrated in young female patients, where the prevalence reached nearly 20% across two large patient cohorts. These results suggest that the molecular basis of FGFR2 rearrangements may be distinct between sexes. These results indicate the importance of genetic testing in cholangiocarcinoma, particularly for younger patients, and suggest that patient recruitment strategies in trials for FGFR2-targeting therapies should seek to reduce barriers to enhance the enrollment of young female patients.

Sex Disparities in Mortality After Endovascular Therapy in Large Core Infarcts

Background In recent large core endovascular therapy (EVT) trials of large vessel occlusion acute ischemic stroke (AIS), treatment was associated with reduced rates of mortality. Because post‐AIS mortality can be influenced by societal and biological factors that differ between women and men, we investigate sex‐based differences in mortality outcomes following EVT in large core AIS. Methods From our prospectively collected multicenter registry across 4 comprehensive stroke centers in the Greater Houston area, we identified patients from 2017 to 2022 with large vessel occlusion AIS and large infarct core. Large infarct core was defined by computed tomography perfusion exceeding 70 mL (by regional cerebral blood flow measurements using automated postprocessing) or computed tomography Alberta Stroke Program Early CT [Computed Tomography] Score<6. The primary outcome of this study was the likelihood of mortality at 90 days, determined through multivariable logistic regression adjusted for EVT, sex, and EVT/sex interaction term. Secondary outcomes included 90‐day disability outcomes and intracerebral hemorrhage. Results Among 190 patients who met inclusion criteria, 50% were female and 45.3% received EVT. Demographic differences between the sexes were largely balanced apart from the older age of presentation for women compared with men (75 versus 67, women versus men; P <0.01). In univariable analysis, women who did not receive EVT had greater mortality (27.4% difference; P <0.001) compared with men, with comparable rates in EVT‐treated cohorts. In multivariable analysis, non‐EVT management was strongly associated with mortality in women compared with men at discharge (odds ratio [OR] 5.81, 95% CI [1.96–17.23]) and 90‐days (OR 6.77, 95% CI [2.09–21.94]). In the secondary analysis, which additionally adjusted the model for age and National Institutes of Health Stroke Scale score, these findings were unchanged. The sex/EVT interaction term showed significant interaction for mortality both at discharge and 90 days ( P <0.01). Conclusion EVT in large core AIS populations may disparately reduce mortality in women compared to men.

Plasma Brain-Derived Tau in Prognosis of Large Vessel Occlusion Ischemic Stroke.

Large vessel occlusion acute ischemic stroke prognosis improved following the 2015 endovascular therapy (EVT) trials. Blood-based biomarkers may improve outcome prediction. We aimed to assess plasma brain-derived tau (BD-Tau) performance in predicting post-EVT large vessel occlusion acute ischemic stroke outcomes. We included 2 temporally independent prospective cohorts of anterior circulation in patients with large vessel occlusion acute ischemic stroke who successfully recanalized post-EVT. We measured plasma BD-Tau, GFAP (glial-fibrillary-acidic-protein), NfL (neurofilament-light-chain), and total-Tau upon admission, immediately, 24 hours, and 72 hours post-EVT. Twenty-four-hour neuroimaging and 90-day functional outcomes were independently assessed using the Alberta Stroke Program Early Computed Tomography Score (good outcome: >7 or unchanged) and the modified Rankin Scale (favorable outcome <3 or unchanged), respectively. Based on the first cohort (derivation), we built a multivariable logistic regression model to predict a 90-day functional outcome. Model results were evaluated using the second cohort (evaluation). In the derivation cohort (n=78, mean age=72.9 years, 50% women), 62% of patients had a good 24-hour neuroimaging outcome, and 45% had a favorable 90-day functional outcome. GFAP admission-to-EVT rate-of-change was the best predictor for early neuroimaging outcome but not for 90-day functional outcome. At admission, BD-Tau levels presented the highest discriminative performance for 90-day functional outcomes (area under the curve, 0.76 [95% CI, 0.65-0.87]; P<0.001). The model incorporating age, admission BD-Tau, and 24-hour Alberta Stroke Program Early Computed Tomography Score achieved excellent discrimination of 90-day functional outcome (area under the curve, 0.89 [95% CI, 0.82-0.97]; P<0.001). The score's predictive performance was maintained in the evaluation cohort (n=66; area under the curve, 0.82 [95% CI, 0.71-0.92]; P<0.001). Admission plasma BD-Tau accurately predicted 90-day functional outcomes in patients with large vessel occlusion acute ischemic stroke after successful EVT. The proposed model may predict functional outcomes using objective measures, minimizing human-related biases and serving as a simplified prognostic tool for AIS.

Mavacamten-Associated Temporal Changes in Left Atrial Function in Obstructive HCM: Insights From the VALOR-HCM Trial

BackgroundIn severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM), the VALOR-HCM (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Who Are Eligible for Septal Reduction Therapy) trial showed that mavacamten reduced the eligibility for septal reduction therapy with sustained improvement in left ventricular outflow tract gradients. Mavacamten also resulted in favorable cardiac remodeling, including improvement in biomarkers (eg, N-terminal pro–B-type natriuretic peptide and troponin T). However, the impact of mavacamten on left atrial (LA) function is unknown. ObjectivesThe aim of this study was to assess serial changes in LA strain measures in patients enrolled in the VALOR-HCM trial. MethodsVALOR-HCM included 112 symptomatic patients with obstructive HCM (mean age 60 years; 51% male). Patients assigned to receive mavacamten at baseline (n = 56) continued therapy for 56 weeks and those assigned to placebo transitioned to mavacamten (n = 52) from week 16 to week 56. Echocardiographic LA strain (reservoir, conduit, and contraction) was measured by using a vendor-neutral postprocessing software. ResultsAt baseline, the mean LA volume index (LAVI) and LA strain values (conduit, contraction, and reservoir) were 41.3 ± 16.5 mL/m2, −11.8% ± 6.5%, −8.7% ± 5.0%, and 20.5% ± 8.7%, respectively (all worse than reported normal). LAVI significantly improved by −5.6 ± 9.7 mL/m2 from baseline to week 56 (P < 0.001). There was a significant (P < 0.05) improvement in absolute LA strain values from baseline to week 56 (conduit [−1.7% ± 6%], contraction [−1.2% ± 4.5%], and reservoir [2.8% ± 7.7%]). Patients originally receiving placebo had no differences in LA measurements up to week 16. There was no significant improvement in LA strain values (conduit [−0.9% ± 3.8%], contraction [−0.4% ± 3.4%], and reservoir [1.4% ± 6.1%]; all; P = NS) from baseline to week 56 in patients with history of atrial fibrillation. ConclusionsIn VALOR-HCM, mavacamten resulted in an improvement in LAVI and LA strain at week 56, suggesting sustained favorable LA remodeling and improved function, except in the atrial fibrillation subgroup. Whether the advantageous LA remodeling associated with long-term treatment with mavacamten results in a favorable impact on the observed high burden of atrial tachyarrhythmias in HCM remains to be proven. (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Who Are Eligible for Septal Reduction Therapy [VALOR-HCM]; NCT04349072)

Expression and prognostic value of cell-cycle-associated genes in lung squamous cell carcinoma.

Lung cancer continues to be a prevalent cause of cancer-related deaths worldwide, with lung squamous carcinoma (LUSC) being a significant subtype characterized by comparatively low survival rates. Extensive molecular studies on LUSC have been conducted; however, the clinical importance of cell-cycle-associated genes has rarely been examined. This study aimed to investigate the relationship between these genes and LUSC. The expression trends of genes related to the cell cycle in a group of patients with LUSC were analyzed. Clinical information and mRNA expression data were obtained from The Cancer Genome Atlas via cBioportal. Multiple analyses have been performed to investigate the association between these genes and LUSC. Three clusters were identified based on the mRNA expression of 124 cell cycle-associated genes. Cluster 3 exhibited the worst prognosis. A comparative analysis showed that nine expressed genes differed distinctly among all the clusters. Among these nine genes, elevated expression of CDK4 was strongly associated with positive prognosis. Furthermore, the expression of ANAPC11, ANAPC5, and ORC4 correlated with the advancement of LUSC pathological stages. Gene expression profiles associated with the cell cycle across various LUSC subtypes were identified, highlighting that specific genes are related to prognosis and disease stages. Based on these results, new prognostic strategies, patient stratification, and targeted therapy trials have been conducted for LUSC.

Off-Protocol Radiation Therapy in Phase 3 Metastatic Solid Tumor Trials.

Increasing data suggest that radiation therapy, particularly ablative radiation therapy, alters the natural history of metastatic disease. For patients with metastatic disease enrolled in prospective trials testing systemic therapy, the use of off-protocol radiation therapy to improve clinical symptoms or extend the duration of study systemic therapy may influence study endpoints. We sought to evaluate how often off-protocol radiation therapy was permitted among systemic therapy phase 3 trials, how often off-protocol radiation therapy is used, and whether off-protocol radiation therapy correlated with study outcomes. Two-arm, superiority-design, phase 3 randomized trials testing systemic therapy were screened from ClinicalTrials.gov. Protocol availability was required to assess the trial approach to off-protocol radiation therapy if not described in the manuscript. Adjusted odds ratios with 95% CI were calculated by logistic regression. A total of 112 trials enrolling 80,134 patients were included, with publication dates between 2010 and 2019. Of these, off-protocol radiation therapy was allowed, not discussed, or prohibited during study systemic therapy in 52% (N =58), 25% (N = 28), and 23% (N = 26) of trials, respectively. However, only 2% (2 of 112) of trials reported off-protocol radiation therapy utilization rates, although no data were reported on the use of ablative off-protocol radiation therapy. No trials evaluated or adjusted for the potential influence of off-protocol radiation therapy on study endpoints. Among the subset of open-label studies, trials permissive toward off-protocol radiation therapy were more likely to meet their primary endpoint (adjusted odds ratio, 4.50; 95% CI, 1.23-20.23; P = .04). Although most trials allowed off-protocol radiation therapy during the receipt of the study systemic therapy, the influence of off-protocol radiation therapy, especially ablative radiation therapy, on study outcomes is underevaluated among phase 3 systemic therapy trials.

Gemcitabine, carboplatin, and Epstein–Barr virus-specific autologous cytotoxic T lymphocytes for recurrent or metastatic nasopharyngeal carcinoma: VANCE, an international randomized phase III trial

Epstein-Barr virus-specific cytotoxic T lymphocyte (EBV-CTL) is an autologous adoptive T-cell immunotherapy generated from the blood of individuals and manufactured without genetic modification. In a previous phase II trial of locally recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) patients, first-line gemcitabine and carboplatin (GC) and EBV-CTL combination demonstrated objective antitumor EBV-CTL activity and a favorable safety profile. The present study explored whether this combined first-line chemo-immunotherapy strategy would produce superior clinical efficacy and better quality of life compared with conventional chemotherapy treatment. This multicenter, randomized, phase III trial evaluated the efficacy and safety of GC followed by EBV-CTL versus GC alone as first-line treatment of R/M NPC patients. Thirty clinical sites in Singapore, Malaysia, Taiwan, Thailand, and the USA were included. Subjects were randomized to first-line GC (four cycles) and EBV-CTL (six cycles) or GC (six cycles) in a 1 : 1 ratio. The primary outcome was overall survival (OS) and secondary outcomes included progression-free survival, objective response rate, clinical benefit rate, quality of life, and safety. gov identifier: NCT02578641. A total of 330 subjects with NPC were enrolled. Most subjects in both treatment arms received four or more cycles of chemotherapy and most subjects in the GC+ EBV-CTL group received two or more infusions of EBV-CTL. The central Good Manufacturing Practices (GMP) facility produced sufficient EBV-CTL for 94% of GC+ EBV-CTL subjects. The median OS was 25.0 months in the GC+ EBV-CTL group and 24.9 months in the GC group (hazard ratio= 1.19; 95% confidence interval 0.91-1.56; P= 0.194). Only one subject experienced a grade 2 serious adverse event related to EBV-CTL. GC+ EBV-CTL in subjects with R/M NPC demonstrated a favorable safety profile but no overall improvement in OS versus chemotherapy. This is the largest adoptive T-cell therapy trial reported in solid tumors to date.

2129: Phase 2 Trial of Stereotactic MRI-guided Adaptive Radiation Therapy in One Fraction (SMART ONE)

2129: Phase 2 Trial of Stereotactic MRI-guided Adaptive Radiation Therapy in One Fraction (SMART ONE)

Single pre-operative radiation therapy (SPORT-CK) trial for low-risk breast cancer: Early results of a phase 2 study

Background and purposePreoperative partial breast irradiation (PBI) is a novel technique that can be used in patients with early-stage breast cancer with the goal of limiting the irradiated breast volume, toxicity and number of fractions. The aim of this trial is to assess the toxicity, surgical, oncologic and cosmetic outcomes of preoperative PBI. Materials and MethodsIn this single-arm phase II trial, we enrolled women ≥ 60 years, with unifocal low-risk breast invasive ductal carcinoma (cT1N0, grade 1–2, ER+, Her2-). Patients were treated with a single fraction of 20 Gy of preoperative PBI using volumetric modulated arc therapy (VMAT). Patients then underwent breast-conserving surgery (BCS) +/- sentinel lymph node biopsy within 72 h of radiation. Primary outcomes were rate of surgical complications and early toxicity. Secondary outcomes were cosmesis at 12 months, chronic toxicity and ipsilateral breast tumor recurrence. ResultsTwenty-five patients were recruited with a median age of 67 years, and a median follow-up of 60 months. Sentinel biopsy was positive in 1 out of 24 patients (4 %). Two patients received adjuvant RT for close margins or positive lymph nodes. Within the first 90 days, none of the patients had surgical complications; almost all had grade 0 to 1 acute and late RTOG skin toxicity. The cosmetic outcome was rated between good and excellent in all cases by physicians and patients, except for one patient who self-rated her cosmesis as fair as of the third year. There were no recurrences. ConclusionPreoperative single-fraction PBI is a safe and feasible treatment for elderly patients with low-risk early-stage breast cancer, with no surgical complications, very low rates of acute and late radiation toxicity, and excellent cosmetic outcomes. Randomized controlled trials are needed to compare preoperative to adjuvant PBI in this patient population.

Protocol for a randomized clinical trial of strength at home parents: A trauma informed parenting intervention for veterans

BackgroundPost-traumatic stress disorder (PTSD) is highly prevalent in veterans and associated with impairments in family functioning, including parenting. There is a bidirectional relationship between PTSD and familial functioning such that impaired functioning is related to increases in trauma-related symptoms, and vice versa. Despite this known bidirectional association, there is currently no trauma-informed parenting intervention available for veterans within the Department of Veterans Affairs (VA). Strength at Home – Parents (SAHP) is an 8-session telehealth delivered psychotherapy group that aims to improve parenting behaviors and overall parent-child and family functioning among U.S. military veterans with PTSD symptoms. This paper describes the methods of an individually randomized group therapy trial to test the efficacy of SAHP compared to a VA treatment as usual control condition.Methods are reported using SPIRIT guidelines. MethodsOne hundred and ninety veterans with elevated PTSD symptoms and parent-child functioning problems will be randomly assigned to the SAHP intervention or a treatment-as-usual control group. Outcomes are measured at 4 timepoints including baseline. The primary outcome is parenting stress. We will also examine changes in parenting behaviors, whether treatment gains are maintained over time, and will conduct an exploratory analysis to examine results separately by gender. Secondary outcomes include symptoms of PTSD and depression, family functioning, and child psychosocial functioning. ConclusionStudy findings will determine the efficacy of SAHP, an intervention developed for ease of use and implementation within the VA to improve parenting stress and parenting behaviors in veterans with elevated PTSD symptoms and parenting difficulties.

Comparative efficacy, safety, and tolerability of pharmacotherapies for acute mania in adults: a systematic review and network meta-analysis of randomized controlled trials.

The aim of this study was to provide evidence-based recommendations regarding the efficacy, safety, and tolerability of currently used pharmacological treatments for adults with acute bipolar mania. To achieve this, we conducted a systematic review and network meta-analysis (NMA) using R software and related packages. We searched primary clinical databases until February 2023 for reports of randomized controlled trials of drug treatments and adjunctive therapies for adults with acute bipolar mania, with outcomes including efficacy (mean change from baseline to endpoint in mania rating scores), safety (clinically significant adverse events from baseline to end of treatment), and tolerability (the proportion of patients who completed the whole trial to the planned endpoint). A total of 113 studies were included in our analysis, in which 23,491 participants (50.38% males; mean age = 38.6 years; mean study duration = 3.39 weeks; mean manic baseline score = 29.37) were randomly allocated to one of 51 monotherapies, adjunctive treatments, or placebo. Our results showed that tamoxifen (mean difference, -22.31 [-25.97, -18.63], N = 2, n1 = 43, n2 = 39) and tamoxifen+ lithium or valproate (LIT/VAL) (-16.37 [-22.55, -10.25], N = 1, n1 = 20, n2 = 20) had the best and second-best clinical efficacy in adults with acute bipolar mania over the placebo. Furthermore, olanzapine, paliperidone, quetiapine, ziprasidone, risperidone, divalproex, and haloperidol were significantly better tolerated than placebo. Combination therapies of antipsychotics and LIT/VAL appeared to be more effective than their corresponding monotherapies. While pharmacotherapies were associated with specific common adverse events, we found no evidence of increased incidence of headache or depression events compared to the placebo. Overall, our NMAs provided important insights into the effectiveness, safety, and tolerability of pharmacological treatments for acute bipolar mania and can help guide treatment decisions for clinicians.

A rare case of adult rhabdomyosarcoma with adnexal metastasis responding tonon-conventional chemotherapy

Rhabdomyosarcoma (RMS) is a pediatric soft tissue sarcoma having a rare incidence among adults. It is a highly chemo-radiosensitivetumor among the pediatric population but has poor biology in adults with dismal outcomes. Due to the rarity of adult RMS, there areno well-defined treatment guidelines for adult RMS and are mostly managed with pediatric-defined protocols but lack similar response.Here, we present the case of an adult female with extremely atypical metastatic site RMS which showed an extraordinary response tonon-pediatric protocol, rather than adult sarcoma-based protocol. This might give an idea to have more research and trials in the futureto implement adult sarcoma-based therapy among adult RMS cases.

A parallel-arm, randomized trial of Behavioral Activation Therapy for anhedonia versus mindfulness-based cognitive therapy for adults with anhedonia

BackgroundAnhedonia, deficits in motivation and pleasure, is a transdiagnostic symptom of psychopathology and negative prognostic marker. MethodsIn this randomized, parallel-arm clinical trial, a novel intervention, Behavioral Activation Treatment for Anhedonia (BATA), was compared to an individually administered Mindfulness-Based Cognitive Therapy (MBCT) in a transdiagnostic cohort of adults with clinically significant anhedonia (ClinicalTrials.gov Identifiers NCT02874534 and NCT04036136). Participants received 8–15 individual psychotherapy sessions, once weekly, with either BATA (n = 61) or MBCT (n = 55) and completed repeated self-report assessment of anhedonia and other internalizing symptoms. ResultsIndicators of treatment feasibility were similar across conditions, though MBCT showed a trend towards greater attrition rates than BATA, with an adjusted odd's ratio of 2.04 [0.88, 4.73]. Treatment effects on the primary clinical endpoint of anhedonia symptoms did not significantly differ, with a 14-week estimated difference on the Snaith Hamilton Pleasure Scale (SHAPS) of −0.20 [-2.25, 1.84] points in BATA compared to MBCT (z = 0.19, p = 0.845, d = 0.05). The expected 14-week change in SHAPS scores across conditions was −7.18 [-8.22, −6.15] points (z = 13.6, p < 0.001, d = 1.69). There were no significant differences in the proportion of participants demonstrating reliable and clinically significant improvements in SHAPS scores, or in the magnitude of internalizing symptom reductions. LimitationsLimitations included a modest sample size, lack of longer-term follow up data, and non-preregistered analytic plan. DiscussionThere was no evidence to support superior clinical efficacy of BATA over MBCT in a transdiagnostic cohort of adults with elevated anhedonia. Both interventions reduced anhedonia symptoms to a comparable magnitude of other existing treatments.

Randomized Clinical Trial of Electrostimulation Therapies as an Adjuvant for the Treatment of Temporomandibular Disorders.

We carried out a comparison of the neuromuscular and clinical effects produced by electrostimulation therapies, as an adjuvant to the use of occlusal splints (removable muscle relaxation apparatus) in patients with temporomandibular disorders In this simple randomized clinical trial, 91 patients were randomly divided into three groups. Group A (GA) received transcutaneous electrostimulation therapy and an occlusal splint, Group B (GB) received percutaneous electrostimulation therapy and an occlusal splint, and Group C (GC) received an occlusal splint. The neuromuscular activity, as well as the signs and symptoms of each patient, were evaluated every week throughout the treatment (T0 = baseline; T1 = 7 days; T2 = 14 days; T3 = 21 days; T4 = 28 days; and T5 = 35 days). Pain was measured with a visual analog scale, and neuromuscular electrical activity was determined by the root mean square of the masseter muscles through the use of a UNAM-CINVESTAV 1.2 electromyograph. Comparisons were made using ANOVA for repeated measures (p-value = 0.05). The comparison between the groups determined that muscle fatigue (p-value = 0.001), joint pain (p-value = 0.009), and muscle pain (p-value = 0.003) decreased to a greater extent, and in the short term for the group treated with transcutaneous electrostimulation therapy as an adjuvant to the use of the occlusal splint. The comparison between the groups determined that muscle fatigue (p-value = 0.001), joint pain (p-value = 0.009), and muscle pain (p-value = 0.003) decreased to a greater extent and in a shorter term in the GA (calculation therapy, transcutaneous electrostimulation) and GB (occlusal splint). Transcutaneous electrostimulation is a feasible and faster alternative that was accepted by most of the patients for treating temporomandibular disorders.

Exploring Analysis Approaches for Using the Dopamine Transporter Striatal Binding Ratio in Early- to Mid-Stage Parkinson's Disease Modification Trials.

The dopamine transporter striatal binding ratio (DAT SBR) has been used as an outcome measure in Parkinson's disease (PD) trials of potential disease-modifying therapies; however, both patient characteristics and analysis approach potentially complicate its interpretation. The aim was to explore how well DAT SBR reflects PD motor severity across different striatal subregions and the relationship to disease duration, and side of onset. DAT SBR for the anterior and posterior putamen and caudate in both hemispheres was obtained using validated automated quantitative software on baseline scans of 132 patients recruited for the Exenatide PD2 and PD3 trials. Associations between mean and lateralized SBR subregions (posterior and anterior putamen and caudate) and summed and lateralized motor characteristics were explored using regression analysis. Analyses were repeated considering disease duration and limiting analysis to the less-affected hemisphere. Lateralized bradykinesia was most consistently associated with the loss of DAT uptake in the contralateral anterior putamen. There was much higher variance in the posterior putamen, and in all regions in those with longer duration disease, although bradykinesia remained robustly associated with anterior putaminal DAT uptake even in longer-duration patients. Restricting analyses to the less-affected side did not usefully reduce the variance compared to the overall cohort. These data suggest that DAT SBR could be a useful biomarker in disease-modifying trials, but a focus on anterior striatal subregions and incorporating disease duration into analyses may improve its utility.

Virtual reality exposure therapy for social anxiety disorders: a meta-analysis and meta-regression of randomized controlled trials.

Virtual reality exposure therapy offers a unique opportunity to treat social anxiety disorder. This meta-analysis aims to evaluate the effectiveness of virtual reality exposure therapy compared to waitlist comparators or other interventions for individuals with social anxiety disorder in alleviating anxiety symptoms. A three-step comprehensive search for the randomized controlled trials of virtual reality exposure therapy was conducted from inception to 7 December 2023. The overall effect was measured using Hedges' g and determined using t-statistics at a significance level of p < 0.05. Sensitivity, subgroup, and meta-regression analyses were carried out. A total of 17 randomized control trials were retrieved from nine electronic databases. Virtual reality exposure therapy has greater efficacy than waitlist comparators in reducing anxiety symptoms at post-intervention and follow-up assessment. Virtual reality exposure therapy demonstrates a similar effect to other interventions at post-intervention and follow-up assessment. We observed a greater effect for participants with symptomatic social anxiety when we combined the intervention with cognitive behavioral therapy compared to its counterpart. Meta-regression analyses found no significant covariate. Overall, virtual reality exposure therapy can provide supplementary therapy for improving anxiety symptoms. Additional high-quality and large-scale trials with long-term follow-up are needed.

Defibrillation of Atrial Fibrillation is not Associated with Increased Risk of Ventricular Fibrillation – The VCD-Trial (Clinical Trial of Electrical Therapy for Atrial Fibrillation using R-wave Guided Cardioversion Versus Defibrillation)

Background: Because of a possible risk of induction of Ventricular Fibrillation (VF) by defibrillation of atrial fibrillation (AF) postulated by LOWN and coworkers, synchronized cardioversion is used worldwide. This prospective, randomized study assessed the efficacy and safety between R-wave controlled cardioversion and defibrillation of AF at 2 study centers in Cologne, Germany. Hypothesis: Defibrillation is not significantly different from cardioversion primarily in the occurrence of VF or sustained Ventricular Tachycardia (VT) and secondarily in restoring sinus rhythm, inducing non-sustained VT, asystole, or bradycardia. Methods: 146 patients at an outpatient practice and 122 at the university hospital were randomized to cardioversion (n = 140) or defibrillation (n = 124). Results: Cardioversion was successful in 92.1% of cases and defibrillation in 87.1%. The difference in efficacy was not statistically significant. In n = 1 patients receiving defibrillation, VF occurred after the first shock (200J) and immediate defibrillation (200J) restored sinus rhythm. In the n = 1 case, asystole occurred during cardioversion which terminated spontaneously. In n = 1 patients cardioverted and n = 2 who were defibrillated, sinus bradycardia occurred requiring Atropine in two cases. There were no thromboembolic events within 10 days. N = 9 patients reverted to AF within two hours. No patients died. Conclusion: Electrical conversion of AF can be performed with similar results and low risk with both R-wave-triggered cardioversion and defibrillation. In particular, defibrillation with higher energies (&gt; 100J) can be performed as effectively and safely without a statistically significant increased risk of VF or VT. There was no difference in efficacy and risk between electrotherapy performed in the outpatient and inpatient settings.