Responder Rate Research Articles

Hyaluronic Acid Filler VYC-25L for Jawline Restoration Yields High Satisfaction, Improved Jawline Measurements, and Sustained Effectiveness Across Skin Types, Age, and Gender for up to 12 Months.

A randomized study was previously reported to demonstrate the safety and efficacy of hyaluronic acid filler VYC-25L for restoring jawline definition. Evaluate patient-reported outcomes (PROs), objective changes in jawline profile, and safety and effectiveness measures by Fitzpatrick Skin Phototype (FST), gender, and age following VYC-25L treatment. Adults were randomized to receive VYC-25L (n=157) or no treatment (control; n=49) for 6 months. PROs were assessed by FACE-Q Satisfaction with Lower Face and Jawline, FACE-Q Appraisal of Lines: Marionette, and participant satisfaction with treatment questionnaires. Changes in jawline profile linear depth and volume were calculated using 3D digital image analysis. Responder rates, PROs, and injection site responses (ISRs) were assessed by FST, gender, and age. At month 6, >70% of treated participants responded "somewhat/very satisfied" to FACE-Q Satisfaction with Lower Face and Jawline questions, and ≥78% of treated participants responded "satisfied/definitely satisfied" with treatment overall. For participants treated in the marionette lines, the FACE-Q Appraisal of Lines: Marionette questionnaire mean score improved by 32.6 (baseline to month 6). Mean change in linear depth in the prejowl sulcus in the treatment vs control groups was 4.6 mm vs 2.5 mm, respectively, and for jawline volume was 6.0 cc and -2.6 cc, respectively, (baseline to month 6). Subanalyses showed similar outcomes by FST, gender, and age except for a numerically higher ISR incidence in females vs males. Treatment with VYC-25L to improve jawline definition yielded high patient satisfaction, objective improvements in jawline profile, and comparable effectiveness across various demographics.

Perampanel for the treatment of Asian people with epilepsy: Real-world evidence from the PERMIT extension study

This post-hoc analysis of the PERMIT Extension study compared the effectiveness and safety/tolerability of perampanel (PER) between Asian and non-Asian participants. Retention rates, adverse events (AEs), seizure frequency, responder rate (≥50% seizure frequency reduction), and seizure freedom rate (no seizures since at least the prior visit) were assessed. Retention was assessed after 3, 6 and 12 months. Effectiveness assessments were evaluated at 3, 6 and 12 months and the last visit by seizure type (total, focal and generalised). PERMIT Extension included 730 Asian and 1662 non-Asian individuals. Significant differences in demographic/baseline characteristics were reported for the Asian versus non-Asian subgroups including higher median age at epilepsy onset, longer median duration of epilepsy, higher mean number of previous and concomitant ASMs and lower mean monthly seizure frequency (total, focal and generalised). Retention rates were similar between the two subgroups at 3 and 12 months, but significantly lower in the Asian versus non-Asian subgroup at 6 months (65.6% vs. 71.8%; p = 0.004). At last visit, seizure freedom rate was significantly higher in the Asian versus non-Asian for total (35.9% vs. 25.4%; p = 0.001) and focal seizures (32.4% vs. 18.9%; p = 0.001) as was responder rate for both total (63.9% vs. 52.3%; p = 0.001) and focal seizures (62.2% vs. 44.7%; p < 0.001). Seizure freedom and responder rates for generalised seizures were similar between the two subgroups at the last visit. Rates of AEs were similar between the two subgroups (Asian, 47.6%; non-Asian, 45.4%). PER was effective and generally well-tolerated in Asian and non-Asian individuals.

Adjunctive cenobamate in people with focal onset seizures: Insights from the Italian Expanded Access Program.

This study was undertaken to assess the effectiveness/tolerability of adjunctive cenobamate, variations in the load of concomitant antiseizure medications (ASMs) and predictors of clinical response in people with focal epilepsy. This was a retrospective study at 21 centers participating in the Italian Expanded Access Program. Effectiveness outcomes included retention and responder rates (≥50% and 100% reduction in baseline seizure frequency). Tolerability/safety outcomes included the rate of treatment discontinuation due to adverse events (AEs) and their incidence. Total drug load was quantified as the number of concomitant ASMs and total defined daily dose (DDD). Concomitant ASMs were also classified according to their mechanism of action and pharmacokinetic interactions to perform explorative subgroup analyses. A total of 236 subjects with a median age of 38 (Q1-Q3 = 27-49) years were included. At 12 months, cenobamate retention rate was 78.8% and responders were 57.5%. The seizure freedom rates during the preceding 3 months were 9.8%, 12.2%, 16.3%, and 14.0% at 3, 6, 9, and 12 months. A higher percentage of responders was observed among subjects treated with clobazam, although the difference was not statistically significant. A total of 223 AEs were recorded in 133 of 236 participants, leading to cenobamate discontinuation in 8.5% cases. At 12 months, a reduction of one or two concomitant ASMs occurred in 42.6% and 4.3% of the subjects. The median total DDD of all concomitant ASMs decreased from 3.34 (Q1-Q3 = 2.50-4.47) at baseline to 2.50 (Q1-Q3 = 1.67-3.50) at 12 months (p < .001, median percentage reduction = 22.2%). The highest rates of cotreatment withdrawal and reductions in the DDD were observed for sodium channel blockers and γ-aminobutyric acidergic modulators (above all for those linked to pharmacokinetic interactions), and perampanel. Adjunctive cenobamate was associated with a reduction in seizure frequency and in the burden of concomitant ASMs in adults with difficult-to-treat focal epilepsy. The type of ASM associated did not influence effectiveness except for a favorable trend with clobazam.

Efficacy and safety of simultaneous combined Zephyr and Spiration valve therapy in patients with advanced pulmonary emphysema

BackgroundEndoscopic lung volume reduction with valves is a minimally invasive treatment strategy for patients with severe pulmonary emphysema. Two valve systems are currently available: Zephyr and Spiration valves. As these can be implanted simultaneously in the same procedure, the question arose as to the effect on lung function, exercise capacity and subjective disease perception after combined valve treatment. MethodsWe conducted a retrospective analysis of 108 patients with combined, simultaneous treatment of Zephyr and Spiration valves. The decision on which and how many valves to implant was based on the individual patient anatomy. Effects on lung function, exercise capacity and atelectasis formation as well as complications were evaluated 90- and 180-days post-treatment (90d-FU and 180d-FU). ResultsAt 90d-FU (n = 90), the mean change was 86.7 ± 183.7 mL for FEV1 and -645.3 ± 1276.5 mL for RV, with responder rates of 39.8 % and 46.5 %, respectively. Complete atelectasis occurred in 16.7 % and partial atelectasis in 25.5 % of patients. Six-minute walking distance increased by 27.00 m [-1.50 – 68.50m]. The rates of pneumothorax (10.2 %) 6 months after treatment were not higher than in randomized controlled trials (RCTs). Likely due to the inclusion of high-risk patients, there was a higher incidence of severe COPD exacerbation (21.3 %) and pneumonia (12.0 %) compared to RCTs. ConclusionsThe combined implantation of Zephyr and Spiration valves resulted in significant clinical and functional improvements with an acceptable risk profile. Therefore, the ability to combine both valve types in severe emphysema could be a promising option in endoscopic lung volume reduction.

Education quality of public and private universities in Bangladesh: Comparative perspective

The quality of a nation's higher education system significantly influences its socioeconomic progress. Universities have immense capacity to promote economic well-being in underdeveloped nations. This study examines the relative quality of education at both private and public universities in Bangladesh. The study used a quantitative research method, with a total of 220 respondents participating in a cross-sectional survey. Data was collected physically via a face-to-face interview and online using a standardized Google form. The cross-sectional survey respondents found both offline and online methods convenient. Data were analyzed using Excel and SPSS. The study used statistical data to analyze crucial elements that influence the quality of education. Results reveal considerable disparities in educational quality evaluations between public and private universities. Both kinds of universities have reasonable teacher-student ratios, but private universities do better. 45% of public university respondents rate library facilities highly, compared to 22% at private universities. Research facilities prefer public universities, with 44% of respondents evaluating them highly, compared to just 14% for private universities. The quality of ICT facilities is seen as superior at private universities, with 57% of participants rating them highly, in contrast to a mere 11% in public universities. Private universities perceive international collaboration as more effective, with 67% of respondents rating it as high, compared to 38% in public universities. This investigation emphasizes the strengths and weaknesses of both public and private universities in Bangladesh, offering valuable insights for educational administrators and policymakers who are endeavoring to improve the quality of education in both sectors.

Dupilumab Efficacy in Children With Type 2 Asthma Receiving High- to Medium-Dose Inhaled Corticosteroid (VOYAGE)

In phase 3 VOYAGE (NCT02948959), dupilumab showed clinical efficacy with an acceptable safety profile in children (6-11 years) with uncontrolled, moderate-to-severe type 2 asthma (blood eosinophils ≥150 cells/μL or fractional exhaled nitric oxide ≥20 ppb). We analyzed dupilumab's efficacy in children with type 2 asthma by high- or medium-dose inhaled corticosteroids (ICS) at baseline. Children were randomized to receive add-on dupilumab 100/200 mg (by body-weight ≤30 kg/>30 kg) every 2 weeks or placebo for 52 weeks and stratified by high- or medium-dose ICS at baseline. Endpoints were annualized severe exacerbation rate, changes from baseline in percent-predicted forced expiratory volume in 1 second (ppFEV1) and 7-item Asthma Control Questionnaire - Interviewer Administered (ACQ-7-IA) score, proportions of ACQ-7-IA responders (improvement ≥0.5), and biomarker changes. In children receiving high- (n = 152) or medium- (n = 195) dose ICS at baseline, dupilumab versus placebo reduced severe exacerbation rates by 63% (P < .001) and 59% (P = .003), respectively. At week 52, dupilumab improved ppFEV1 by least squares mean difference versus placebo of 5.7 percentage points (P = .02) and 9.35 points (P < .001), and reduced ACQ-7-IA scores by 0.53 points (P < .001) and 0.40 points (P < .001), respectively. No significant treatment interactions between ICS subgroups were detected at week 52. Significant improvements were observed in ACQ-7-IA responder rates and most type 2 biomarker levels. Dupilumab reduced severe exacerbation rates and improved lung function and asthma control in children with uncontrolled, moderate-to-severe type 2 asthma, regardless of ICS dose at baseline.

Treatment simplification to optimize cenobamate effectiveness and tolerability: A real-world retrospective study in Spain.

This study aimed to explore the impact of co-antiseizure medication (co-ASM) optimization on the effectiveness and tolerability of adjunctive cenobamate (CNB) in patients with drug-resistant epilepsy in a real-world setting. This unicentric, retrospective, observational study included adults with focal-onset seizures who had received ≥2 previous ASMs. The main effectiveness endpoints included responder rates and seizure frequency reduction at 3, 6, and 12-month visits. The number of co-ASMs and defined daily dose (DDD) were analyzed at every visit. Safety endpoints included adverse drug reactions (ADRs). Thirty-four patients with a median epilepsy duration of 22 years and a median of 15.5 seizures/month were analyzed. The median number of prior ASMs was 12, and the mean number of co-ASMs was 2.9 (SD 1). There was a reduction in seizure frequency/month from baseline to the last visit (p < 0.0001). Between baseline and the end of the study, the mean number of co-ASMs in the per-protocol (PP) population was reduced from 2.9 to 1.6 (p < 0.0001), and DDD was reduced from 3.6 to 1.4 (p < 0.0001). Sodium channel blockers (carbamazepine and lacosamide) and GABAergic drugs (clobazam) were the agents with the most significant reductions in DDD after 12 months. The percentage of patients in the PP population with ≥3 co-ASMs was reduced from 61.8% at baseline to 14.3% at 12 months; 1 patient was receiving CNB as monotherapy at the last visit. At the last visit, 85.7% of the PP population were ≥50% responders, and 33.3% were seizure-free. The percentage of patients with ADRs in the PP population was 71.9% at 3 months and 52.3% at 12 months. Following rational polytherapy, optimization of co-ASM management during CNB treatment allowed high seizure freedom rates despite meaningful reductions in co-medication, while also achieving both good tolerability and patient satisfaction scores in a highly drug-resistant population. Many patients with epilepsy still have seizures, even after being treated with several different epilepsy drugs. In this study of 34 patients from a Spanish clinic, we show that the epilepsy drug cenobamate can reduce the number of seizures in these patients, even after many other epilepsy drugs have failed. We also show that patients treated with cenobamate can reduce the dose or even stop taking certain other epilepsy drugs. This allows them to simplify their treatment and reduce adverse effects while still keeping control of their epilepsy.

RECIST 1.1, mRECIST, and Choi criteria for evaluating treatment response and survival outcomes in hepatocellular carcinoma patients treated with atezolizumab plus bevacizumab.

We aimed to compare the early responder rates, defined as complete or partial responders, using response evaluation criteria in solid tumors (RECIST) 1.1, modified RECIST (mRECIST), and Choi criteria in advanced HCC patients treated with atezolizumab-bevacizumab (atezo-bev), and to correlate them with progression-free survival (PFS) and overall survival (OS). This retrospective study included advanced HCC patients treated with ≥ 3 cycles of atezo-bev. Two reviewers assessed responses using RECIST 1.1, mRECIST, and Choi criteria at 1st follow-up imaging. Kaplan-Meier curves with log-rank tests evaluated and compared PFS and OS. Cox proportional hazard models identified survival outcome predictors. Kappa statistics assessed inter-reader agreement. We evaluated 77 patients (65 men; mean age, 62.8 ± 12.3 years). Choi's criteria revealed the highest early responders rate (53.2%), exceeding mRECIST (32.5-33.8%) and RECIST 1.1 (24.7-26.0%), with an excellent agreement in all criteria (κ, 0.85-0.95). Across criteria, a consistent number of patients progressed (23-26) and was associated with significantly poor OS (ps ≤ 0.049). Responders by any criteria showed longer PFS (ps ≤ 0.009), and 1-year OS (ps ≤ 0.01). Choi criteria linked to significantly better OS without landmark (p = 0.003), with 1-year OS rates at 76.9% for responders vs 38.1% for non-responders. Cox analysis identified responders by Choi criteria as a significant OS predictor. Choi criteria identified more early responders than RECIST 1.1 and mRECIST, significantly correlating with improved OS. Choi criteria could be considered as a formal response assessment criterion for the emerging atezo-bev systemic treatment. For atezo-bev treatment of advanced HCC, more comprehensive response criteria, such as Choi criteria, could be effective in identifying early responders and predicting survival outcomes along with RECIST 1.1 and mRECIST. Choi criteria identified a higher rate of early responders compared to mRECIST and RECIST1.1 following atezo-bev treatment. Responders by all criteria had longer PFS and 1-year OS, and only those by Choi criteria experienced longer OS without landmark time. Choi criteria, with RECIST 1.1 and mRECIST, is an effective response assessment tool for atezo-bev treatment.

The Influence of Work Discipline and Workload on Employee Performance

This study was done by selecting a sample of 40 respondents from the population. This study investigates the use of SPSS 22 software for Windows operating systems. The research findings are as follows: A study was conducted to assess the work discipline of employees at a bank in Bandung. The data processing revealed that the average rating of respondents' responses was 2.98, which falls within the "Good enough" threshold. The workload of staff at a bank in Bandung was assessed by analyzing data processing results from respondents. The average score received was 3.00, which falls within the "Good enough" requirements for the test findings. The data processing findings from respondents at one of the banks in Bandung provided an overview of employee performance. The average score received was 3.28, which falls within the "Quite good" requirement for test results. The impact of work discipline and workload on employee performance at a bank in Bandung is as follows: the direct influence of work discipline on employee performance is 28.40%, and the indirect influence through work discipline is 17.44%. Therefore, the total influence of work discipline on employee performance is 46.95%. The impact of workload on employee performance at a bank in Bandung is directly influenced by work discipline, accounting for 17.44% of the total influence. Additionally, there is an indirect influence of 29.53% through workload, resulting in a total influence of work discipline on employee performance of 76.8% at this particular bank in Bandung. The impact of work discipline on employee performance at a bank in Bandung is measured at 0.546 or 54.6%, indicating a reasonably good correlation. Similarly, the influence of workload on employee performance at the same bank in Bandung is measured at 0.352 or 35.2%. The criteria are highly stringent, and the correlation between work discipline and workload is 0.892 or 89.2%, indicating a strong association. When considered jointly or concurrently, these factors have a combined total influence of 76.48%, with work discipline accounting for 46.95% and workload accounting for 29.53%. Hence, the overall impact amounts to 76.8%. The results indicate that the impact of these two variables falls within the very significant range, while the remaining elements, which have not been examined, also influence employee performance by 23.2%.

Responsive neurostimulation in pediatric epilepsy: a systematic review and individual patient meta-analysis supplemented by a single institution case series in 105 aggregated patients.

To assess responsive neurostimulation (RNS) efficacy in pediatric patients with drug-resistant epilepsy, comparing response (≥ 50% reduction in seizure frequency) rates between patients with two or fewer seizure foci and those with multifocal or generalized epilepsy. This study seeks to address the gap in knowledge regarding RNS effectiveness in pediatric populations. A systematic review and meta-analysis included data from PubMed, Embase, and Web of Science through November 2023, including 17 retrospective studies and a case series of 24 patients from our practice for a total of 105 aggregated patients. The inclusion criteria of patients were age 18 and diagnosis of DRE. Exclusion criteria were nonhuman subjects and cases where RNS was not utilized to treat DRE. Study inclusion criteria were detailing the use of RNS and comparing patients with 2 foci with other focalities. Study exclusion criteria were failure to specify RNS lead placement or type of epilepsy. The risk of bias was assessed using the ROBINS-I tool for all non-randomized studies. Effect sizes and variances were aggregated to provide a comprehensive measure of RNS efficacy, and heterogeneity among the studies was assessed using I2 statistics and Cochran's Q test to evaluate the consistency of the findings. Statistical analyses were conducted using IBM SPSS. We analyzed demographics, epilepsy history, treatment outcomes, and RNS details using descriptive and inferential statistics, including Wilcoxon-Mann-Whitney, Fisher's exact, and chi-squared tests. This systematic review was not registered. Seventeen retrospective studies and a single-institution case series, encompassing 105 pediatric patients, were analyzed. Effect sizes and confidence intervals were calculated to quantify treatment effects. Analyses revealed that RNS reduces seizure frequency across a spectrum of pediatric epilepsy syndromes, irrespective of the seizures' focal, multifocal, or generalized origins. The effectiveness of RNS was not influenced by the patient's sex, age at epilepsy onset, or presence of neurological and psychiatric comorbidities. Prior vagus nerve stimulation surgery and the presence of an epileptic syndrome were factors associated with a lower likelihood of near-complete seizure remission with RNS, underscoring the complexities of treating patients with generalized epilepsies or previous interventional failures. The necessity of further research into individualized surgical strategies for patients was underscored by the mixed results of comparisons of electrode characteristics with responder rates. Limitations of our study include its reliance on retrospective studies, which introduces potential bias and limits the ability to infer causality. RNS is a safe and effective treatment in pediatric patients with DRE across demographic, comorbidity, and focality variability. FDA age and focality restrictions, along with patient and physician hesitancy, may be limiting the potential for effective treatment of pediatric DRE with RNS. Prospective randomized trials are recommended to validate these findings.

The Influence of Technology Literacy and the Use of Artificial Intelligence (AI) By Hasanuddin University Students on the Change of Habits in Completing Academic Tasks

With the rapid advancement of technology and the integration of artificial intelligence in various aspects of life, students' approach to academic tasks is evolving. This study aims to analyze the effect of using AI on changes in habits in completing academic assignments. The type of research used is descriptive quantitative with multiple Linear Regression method. In this study, the sample was drawn with cluster random sampling of 400 people who had used AI which was divided into 16 faculties at Hasanuddin University. The data collection method in this study uses a questionnaire distributed online via kuesio.id which contains statements, interviews and documentation by searching the internet. In testing data analysis techniques, namely validity and reliability tests calculated using the SPSS (Statistical Product and Service Solutions) program with Cronbach Alpha (α) above 0.60, so the overall statement is declared reliable. The results of this study indicate that the literacy level of Hasanuddin University students is categorized as good with a respondent achievement rate (TCR) of 78.3% and the use of AI that is often used from the 15 applications listed by researchers, namely ChatGPT by 26.7%, Perplexity 12.7%, and Grammarly 12.6%. The results of data analysis show that there is a positive correlation between technological literacy and the ability to use AI with changes in habits in completing academic tasks. Students who have high literacy and are skilled in utilizing AI tend to be more efficient and effective in completing their tasks.

A Review of Current Data on Duration of Effect in Glabellar Lines After Treatment With AbobotulinumtoxinA 50 U.

AbobotulinumtoxinA has become well established as a treatment option for moderate to severe glabellar lines since its first aesthetic approval in 2009. Pivotal trials leading to regulatory approval showed that abobotulinumtoxinA treatment was associated with high responder rates when defined as achievement of none or mild glabellar lines (0 or 1 on the glabellar line severity scale) and a duration of action of up to 5 months. More recently, the goals for treatment of glabellar lines have shifted toward not only achieving a decrease in glabellar line severity but also ensuring that patients are satisfied with their experience. Patients seek an improvement in the appearance of their glabellar lines while maintaining a "natural look," fast onset of effect, and long duration of response. Trial designs have evolved to meet these new targets, including expanding the definition of responders to those having at least 1-grade improvement in the glabellar line severity scale score from baseline coupled with the use of subject satisfaction and psychological well-being questionnaires. The findings demonstrate that abobotulinumtoxinA remains a well-tolerated and consistently effective treatment option associated with a rapid onset of effect, duration of efficacy lasting up to 6 months, and high, long-lasting levels of patient satisfaction.

Acute and Preventive Treatment of COVID-19-Related Headache: A Series of 100 Patients.

To describe the need and effectiveness of acute and preventive medications in a series of 100 consecutive patients referred due to COVID-19-related headaches. Patients were aged 48.0 (standard deviation (SD): 12.4), 84% were female, and 56% had a prior history of headache. The most common headache phenotype was holocranial (63%), frontal (48%), pressing (75%), of moderate intensity (7 out of 10), and accompanied by photophobia (58%). Acute medication was required by 93%, with paracetamol (46%) being the most frequently used drug, followed by ibuprofen (44%). The drugs with the highest proportion of a 2 h pain-freedom response were dexketoprofen (58.8%), triptans (57.7%), and ibuprofen (54.3%). Preventive treatment was required by 75% of patients. The most frequently used drugs were amitriptyline (66%), anesthetic blockades (18%), and onabotulinumtoxinA (11%). The drugs with the highest 50% responder rate were amitriptyline (45.5%), mirtazapine (50%), and anesthetic blockades (38.9%). The highest 75% responder rate was experienced following onabotulinumtoxinA (18.2%). In conclusion, most patients required acute medication, with triptans and non-steroidal anti-inflammatory drugs achieving the best responses. Three-quarters of patients required preventive medication. The most frequently used drug was amitriptyline, which obtained the best results. In some treatment-resistant patients, anesthetic blockades and onabotulinumtoxinA were also beneficial.

Retrospective evaluation of the short-term response of human intravenous immunoglobulin therapy in the management of canine immune-mediated thrombocytopenia (2010-2015): 27 cases.

To describe the short-term response, early prognostic markers, and survival after treatment of canine immune-mediated thrombocytopenia (ITP) with human intravenous immunoglobulin (hIVIG) and methylprednisolone. Retrospective cohort study. Private referral veterinary medical center. Twenty-seven client-owned dogs with primary or secondary ITP. All dogs received 2mg/kg IV methylprednisolone once daily and a single infusion of 5% hIVIG administered over 6-12hours. A substantial increase in platelet count within 60±12hours post-hIVIG infusion (T60) was observed in 19 of the 27 (70%) dogs with ITP (responders). Thirty-four variables, including serum immunoglobulin (Ig) G concentration 24±12hours post-hIVIG infusion (T24IgG) and increase in serum IgG concentration 24±12hours post-hIVIG infusion (T24ΔIgG), were compared between responders and nonresponders at 5 different time points. Mortality rates of responders and nonresponders were evaluated 14days post-hIVIG infusion. Serum T24IgG and serum T24ΔIgG were both significantly higher at T60 in responders. All responders were alive 14days post-hIVIG infusion, and their mortality rate was significantly lower compared with nonresponders. Responder dogs had an excellent 14-day survival rate. Serum T24IgG and serum T24ΔIgG concentrations accurately predicted response status at 60hours post-hIVIG infusion.

Efficacy and safety of atogepant, a small molecule CGRP receptor antagonist, for the preventive treatment of migraine: a systematic review and meta-analysis

BackgroundMigraine is one of the most common diseases worldwide while current treatment options are not ideal. New therapeutic classes of migraine, the calcitonin gene-related peptide (CGRP) antagonists, have been developed and shown considerable effectiveness and safety. The present study aimed to systematically evaluate the efficacy and safety of atogepant, a CGRP antagonist, for migraine prophylaxis from the results of randomized controlled trials (RCTs).MethodsThe Cochrane Library, Embase, PubMed and https://www.clinicaltrials.gov/ were searched for RCTs that compared atogepant with placebo for migraine prophylaxis from inception of the databases to Feb 1, 2024. Outcome data involving efficacy and safety were combined and analyzed using Review Manager Software version 5.3 (RevMan 5.3). For each outcome, risk ratios (RRs) or standardized mean difference (SMD) were calculated.Results4 RCTs with a total of 2813 subjects met our inclusion criteria. The overall effect estimate showed that atogepant was significantly superior to placebo in terms of the reduction of monthly migraine (SMD − 0.40, 95% CI -0.46 to -0.34) or headache (SMD − 0.39, 95% CI -0.46 to -0.33) days, the reduction of acute medication use days (SMD − 0.45, 95% CI -0.51 to -0.39) and 50% responder rate (RR 1.66, 95% CI 1.46 to 1.89), while no dose-related improvements were found between different dosage groups. For the safety, significant number of patients experienced treatment-emergent adverse events (TEAEs) with atogepant than with placebo (RR 1.10, 95% CI 1.02–1.21) while there was no obvious difference between the five dosage groups. Most TEAEs involved constipation (RR 2.55, 95% CI 1.91–3.41), nausea (RR 2.19, 95% CI 1.67–2.87) and urinary tract infection (RR 1.49, 95% CI 1.05–2.11). In addition, a high dosage of atogepant may also increase the risk of treatment-related TEAEs (RR 1.64, 95% CI 1.02–2.63) and fatigue (RR 3.07, 95% CI 1.13–8.35).ConclusionsThis meta-analysis suggests that atogepant is effective and tolerable for migraine prophylaxis including episodic or chronic migraine compared with placebo. It is critical to weigh the benefits of different doses against the risk of adverse events in clinical application of atogepant. Longer and multi-dose trials with larger sample sizes are required to verify the current findings.

Proposing a more conservative Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Effort Index cutoff score for forensic inpatient populations.

The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Effort Index (EI) may be unreliable at its standard recommended cutoff score when used with forensic psychiatric inpatient populations given high rates of genuine cognitive impairment. The present study sought to (a) examine the rate of invalid performance on the RBANS EI using the standard cutoff among incompetent to stand trial (IST) inpatients and (b) investigate the psychometric properties of the RBANS EI at various cutoff scores. This study was conducted using archival assessment data collected at a large forensic psychiatric hospital. Across the entire sample (N = 238, 79% male, Mage = 45 years, 24% primary Spanish-speaking), 79% were diagnosed with a schizophrenia spectrum disorder. Experiment 1 of the study (n = 165) contained IST patients who were classified as having a valid presentation. Experiment 2 contained a valid (n = 46) and invalid (n = 27) presentation group comprised of postadjudication and IST inpatients, respectively. In Experiment 1, over one third (36.4%) of the valid presentation sample scored above the standard recommended EI cutoff. In Experiment 2, applying the standard recommended cutoff score of > 3 was associated with a false positive rate of over 20%. Obtaining < 10% false positive errors was achieved at a cutoff score of > 5. At this cutoff score, the estimated local base rate of invalid responding among IST patients was 28%. Clinical and forensic implications and recommendations for adopting this more conservative RBANS EI cutoff score are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Twelve-month results from a randomized controlled trial comparing differential target multiplexed spinal cord stimulation and conventional spinal cord stimulation in subjects with chronic refractory axial low back pain not eligible for spine surgery

BackgroundSuccessful treatments for intractable chronic low back pain (CLBP) in patients who are not eligible for surgical interventions are scarce. The superior efficacy of differential target multiplexed spinal cord stimulation (DTM SCS) to conventional SCS (Conv-SCS) on the treatment of CLBP in patients with persistent spinal pain syndrome (PSPS) who have failed surgical interventions (PSPS-T2) motivated the evaluation of DTM SCS versus Conv-SCS on PSPS patients who are non-surgical candidates (PSPS-T1). MethodsThis is a prospective, open label, crossover, post-market randomized controlled trial in 20 centers across the United States. Eligible patients were randomized to either DTM SCS or Conv-SCS in a 1:1 ratio. Primary endpoint was CLBP responder rate (percentage of subjects with ≥50% CLBP relief) at 3-month in randomized subjects who completed trialing (modified intention-to-treat population). Patients were followed up to 12 months. Secondary endpoints included change of CLBP and leg pain, responder rates, changes in disability, quality of life, patient satisfaction and global impression of change, and safety profile. An optional crossover was available at 6-month to all patients. Results121 PSPS-T1 subjects with CLBP and leg pain mostly associated with degenerative disc disease and radiculopathy and who were not eligible for spine surgery were randomized. CLBP responder rate with DTM SCS (93.5%) was superior to Conv-SCS (36.4%) at the primary endpoint. Superior CLBP responder rates (88.1-90.5%) were obtained with DTM SCS at all other timepoints. Mean CLBP reduction with DTM SCS (6.52 cm) was superior to that with Conv-SCS (3.01 cm) at the primary endpoint. Similar CLBP reductions (6.23-6.43 cm) were obtained with DTM SCS at other timepoints. DTM SCS provided significantly better leg pain reduction and responder rate, improvement of disability and quality of life, and better patient satisfaction and global impression of change. 90.9% of Conv-SCS subjects who crossed over were CLBP responders at completion of the study. Similar safety profiles were observed between the two groups. ConclusionDTM SCS for chronic CLBP in non-surgical candidates is superior to Conv-SCS. Improvements were sustained and provided significant benefits on the management of these patients.

Recombinant human nerve growth factor (cenegermin) for moderate-to-severe dry eye: phase II, randomized, vehicle-controlled, dose-ranging trial

BackgroundDry eye disease (DED) includes neurosensory abnormalities as part of its multifactorial etiology. Nerve growth factor is important for maintaining corneal nerve integrity and wound healing. Cenegermin (recombinant human nerve growth factor) is a topical biologic that promotes corneal healing in patients with neurotrophic keratitis. The purpose of this study was to evaluate efficacy and safety of cenegermin in moderate-to-severe DED and identify an optimal dosing strategy.MethodsThis was a phase II, multicenter, randomized, double-masked, vehicle-controlled, dose-ranging clinical trial in patients with moderate-to-severe DED, including Sjögren’s DED (NCT03982368). Patients received 1 drop of cenegermin 3 times daily (t.i.d.; 20 mcg/mL), cenegermin 2 times daily (b.i.d.; 20 mcg/mL) and vehicle once daily, or vehicle t.i.d. for 4 weeks. Follow-up continued for 12 additional weeks. The primary endpoint was change in Schirmer I score from baseline to week 4. Other key endpoints included rate of responders (Schirmer I test > 10 mm/5 min) after treatment and change in Symptoms Assessment iN Dry Eye (SANDE) scores from baseline to end of follow-up. A 1-sided test (α = 0.025) was used to evaluate statistical significance.ResultsAt week 4, mean changes in Schirmer I scores were not statistically significantly different in either cenegermin group versus vehicle (cenegermin vs vehicle [treatment difference; 95% CI]: t.i.d., 2.60 mm and b.i.d., 3.99 mm vs 1.68 mm [t.i.d.: 0.93; −1.47 to 3.32, P = 0.078; b.i.d.: 2.31; −0.08 to 4.70, P = 0.066]). More patients responded to treatment with cenegermin t.i.d. and b.i.d. versus vehicle (t.i.d.: 25.9% [21/81, P = 0.028]; b.i.d.: 29.3% [24/82, P = 0.007] vs 11.9% [10/84]), with statistical significance (set at P < 0.025) observed in the b.i.d. group. Only cenegermin t.i.d. yielded statistically significant (P < 0.025) reductions in SANDE scores versus vehicle, which were sustained up to the end of follow-up (P value range, 0.002–0.008). Eye pain, primarily mild and transient, was the most frequently observed treatment-emergent adverse event with cenegermin. Similar results were observed in patients with Sjögren’s DED.ConclusionsCenegermin was well tolerated and although this study did not meet its primary endpoint, significant improvement in patient-reported symptoms of dry eye was observed through follow-up. Larger studies evaluating cenegermin in patients with DED are warranted.Trial registrationNCT03982368; registered May 23, 2019.

Safe and Effective Restoration of Jawline Definition With Hyaluronic Acid Injectable Gel VYC-25L: Results From a Randomized Controlled Study.

A well-defined jawline improves overall facial aesthetics, thus motivating patients to seek jawline augmentation. This study will evaluate the safety and effectiveness of the hyaluronic acid injectable gel VYC-25L for restoring jawline definition. A US multicenter, evaluator-blinded study randomized adults with grade 2 (moderate) or 3 (severe) Allergan Loss of Jawline Definition Scale (ALJDS) scores. Participants were randomized to VYC-25L treatment group or control group at study onset, with 12 months follow-up. The control group had the option to receive treatment after 6 months (primary endpoint completion). Effectiveness measures included month 6 ALJDS responders rate (proportion of participants with ≥1-grade improvement from baseline on both sides), FACE-Q Satisfaction With Lower Face and Jawline scores, and Global Aesthetic Improvement Scale (GAIS) responders (improved/much improved) as assessed by the investigator and participants. Injection site responses (ISRs) and adverse events (AEs) were monitored. At month 6, ALJDS responder rates were 69.0% versus 38.0% in the VYC-25L treatment (n = 157) and control (n = 49) groups, respectively (p = .0001). In the VYC-25L treatment group, FACE-Q scores improved by a mean of 45.9 points versus baseline at month 6 (p < .0001). Furthermore, 88.4% and 89.0% of participants in the VYC-25L treatment group were GAIS responders on month 6 by participant- and investigator-assessment, respectively. Most ISRs were mild or moderate and resolved within 2 weeks. Most treatment-related AEs were mild and resolved within a week. VYC-25L safely and effectively restores jawline definition through 1 year.

Vitamin D deficiency and effect of treatment on seizure frequency and quality of life parameters in patients with drug-resistant epilepsy: A randomized clinical trial.

This study was undertaken to assess the effect of treatment of vitamin D deficiency in drug-resistant epilepsy. We conducted a multicenter, double-blind, placebo-controlled, randomized clinical trial, including patients aged ≥15 years with drug-resistant focal or generalized epilepsy. Patients with 25-hydroxyvitamin D (25[OH]D) < 30 ng/mL were randomized to an experimental group (EG) receiving vitamin D3 (cholecalciferol, 100 000 IU, five doses in 3 months) or a control group (CG) receiving matched placebo. During the open-label study, EG patients received 100 000 IU/month for 6 months, whereas CG patients received five doses in 3 months then 1/month for 3 months. Monitoring included seizure frequency (SF), 25(OH)D, calcium, albumin, creatinine assays, and standardized scales for fatigue, anxiety-depression, and quality of life (Modified Fatigue Impact Scale [M-FIS], Hospital Anxiety and Depression Scale, Quality of Life in Epilepsy [QOLIE-31]) at 3, 6, and 12 months. The primary efficacy outcome was the percentage of SF reduction compared to the reference period and CG at 3 months. Secondary outcomes were SF and bilateral tonic-clonic seizure (BTCS) reduction, scale score changes, and correlations with 25(OH)D during the follow-up. Eighty-eight patients were enrolled in the study (56 females, aged 17-74 years), with median baseline SF per 3 months = 16.5 and ≥2 antiseizure medications in 88.6%. In 75 patients (85%), 25(OH)D was <30 ng/mL; 40 of them were randomly assigned to EG and 34 to CG. After the 3-month blinded period, SF reduction did not significantly differ between groups. However, during the open-label period, SF significantly decreased (30% median SF reduction, 33% responder rate at 12 months). BTCSs were reduced by 52%. M-FIS and QOLIE-31 scores were significantly improved at the whole group level. SF reduction correlated with 25(OH)D > 30 ng/mL for >6 months. Despite no proven effect after the 3-month blinded period, the open-label study suggests that long-term vitamin D3 supplementation with optimal 25(OH)D may reduce SF and BTCSs, with a positive effect on fatigue and quality of life. These findings need to be confirmed by further long-term studies. ClinicalTrials.gov identifier: NCT03475225 (03-22-2018).