Responder Rate Research Articles

Mean global field power is reduced in infantile epileptic spasms syndrome after response to vigabatrin

PurposeInfantile epileptic spasms syndrome (IESS) is associated with abnormal neuronal networks during a critical period of synaptogenesis and brain plasticity. Hypsarrhythmia is a visual EEG biomarker used to diagnose IESS, assess response to treatment, and monitor relapse. Computational EEG biomarkers hold promise in providing unbiased, reliable, and objective criteria for clinical management. We hypothesized that computational and visual EEG biomarkers of IESS would correlate after treatment with vigabatrin and that these responses might differ between responders and non-responders.MethodsA retrospective analysis was conducted at a single center, involving children with IESS at initial diagnosis and following first-line treatment with vigabatrin. Visual EEG biomarkers of hypsarrhythmia were compared with computational EEG biomarkers, including spike and spike fast-oscillation source coherence, spectral power, and mean global field power, using retrospective analysis of EEG recorded at initial diagnosis and after vigabatrin treatment. Responders and non-responders were compared based on the characteristics of their follow-up EEGs.ResultsIn this pilot study, we observed a reduction in the EEG biomarker of hypsarrhythmia/modified hypsarrhythmia from 20/20 (100%) cases at the initial diagnosis to 9/20 (45%) cases after treatment with vigabatrin, indicating a 55% (11/20) responder rate. No significant difference in spike frequency was observed after treatment (p = 0.104). We observed no significant differences after treatment with vigabatrin in the computational EEG biomarkers that we assessed, including spike source coherence at 90% (p = 0.983), spike source coherence lag range (p > 0.999), spike gamma source coherence at 90% (p = 0.177), spike gamma source coherence lag range (p > 0.999), spectral power (0.642), or mean global field power (0.932). However, when follow-up EEGs were compared, there was a significant difference in mean global field power (p = 0.038) between vigabatrin responders and non-responders. In contrast, no such difference was observed for spike source coherence at 90% (p = 0.285), spike course coherence lag range (p = 0.819), spike gamma source coherence at 90% (p = 0.205), spike gamma source coherence lag range (p > 0.999), or spectral power (p = 0.445). Finally, our treated group did not differ significantly from healthy controls at initial diagnosis or follow-up in terms of spectral power (p = 0.420) or mean global field power (0.127).ConclusionIn this pilot study, we show that mean global field power is a computational EEG biomarker that is significantly reduced in IESS after treatment with vigabatrin. Although computational EEG biomarkers of network connectivity using spike source coherence appear to be a promising tool, future studies should further explore their potential for assessing treatment responses in IESS.

Allogenic bone marrow–derived mesenchymal stromal cell–based therapy for patients with chronic low back pain: a prospective, multicentre, randomised placebo controlled trial (RESPINE study)

ObjectivesTo assess the efficacy of a single intradiscal injection of allogeneic bone marrow mesenchymal stromal cells (BM-MSCs) versus a sham placebo in patients with chronic low back pain (LBP).MethodsParticipants were...

Midface Projection Using Biostimulatory Poly-l-Lactic Acid Injectable Implant: A Subgroup Analysis of the Cheek Wrinkle Trial.

Correction of cheek wrinkles using poly-l-lactic acid (PLLA-SCA) was demonstrated in a 12-month study. This analysis assessed change from baseline in lifting effect of PLLA-SCA using a 3D camera to provide additional quantified data. Subjects received PLLA-SCA (reconstituted in 8 mL of sterile water + 1 mL of 2% lidocaine) in both cheeks or no treatment (control). Assessments included the Galderma Cheek Wrinkle Scale (GCWS), aesthetic improvement, and 3D photography. In subjects with severe GCWS at baseline, Canfield software analyzed 3D images for change from baseline in midface volume projection and volume change of both cheeks at Month 9. The primary study showed a statistically significant higher at-rest GCWS responder rate at Month 12 for PLLA-SCA, 71.6%, versus control, 26.1% (p < .0001). In this Month 9 analysis, mean midface volume projection demonstrated a positive volume shift for PLLA-SCA (left: 0.45 mm; right: 0.34 mm; n = 46) versus control (left: 0.25 mm; right: -0.01 mm; n = 21). Midface volume and max projection changes for PLLA-SCA were +4.88 mL/+1.62 mm (left), +2.84 mL/+1.12 mm (right) versus +0.26 mL/+0.34 mm (left), +0.68 mL/+0.37 mm (right) for control. Poly-l-lactic acid-treatment of subjects with severe GCWS had a clinically meaningful lifting effect in both cheeks (positive volume shift, positive volume change, and max projection) in the midface. NCT04124692.

Community Awareness and Participation for Land and Forest Fire Prevention and Implementation of Lancang Kuning Nusantara System Application in Toba District, North Sumatra Province

This study employs a sociometric analysis of Community Concern and Participation in Implementing the Lancang Kuning Nusantara Application for Forest and Land Fire Prevention in Toba Regency, Indonesia. With a sample of 401 respondents, the study aims to comprehensively understand social interactions and community engagement in this context. Results indicate that the perception score (X(i.1)) and participation score (X(i.2)) are high or significant, reflecting positive community awareness and active involvement in fire prevention activities. However, the acceptability score (X(i.3)) is low or insignificant, suggesting potential dissatisfaction or skepticism regarding the effectiveness or implementation of current programs. Furthermore, standard deviation analysis reveals that variability in respondent ratings is generally within control, with only 2 out of 15 testing points showing high standard deviation, while 13 are within acceptable limits. Nevertheless, the proportion of respondents who rate low (PRMR) exceeds the desired threshold of 10% across all variables, indicating that many respondents have low evaluations. These findings suggest a need for improved communication, education, and potential adjustments to enhance the acceptability and effectiveness of the fire prevention initiatives and the Lancang Kuning Nusantara System application.

Responsive Neurostimulation in Pediatric and Young Adult Patients With Drug-Resistant Focal, Multifocal, and Generalized Epilepsy: A Single-Center Experience

BackgroundResponsive neurostimulation (RNS) is used off-label in pediatric patients with drug-resistant epilepsy (DRE). Our study aims to assess the safety and efficacy of RNS in pediatric and young adult patients with focal, multifocal, and generalized DRE. MethodsAll patients who underwent RNS implantation at Primary Children's Hospital in Salt Lake City, UT, between December 2017 and 2022. ResultsA total of 47 patients were retrospectively identified, of which 32 patients were included in the final analysis. Patients ranged in age from five to 21 years (pediatric n = 22, young adult n = 10) at the time of RNS implantation with focal (20 [63%]), multifocal (8 [25%]), and generalized (4 [12%]) DRE. Operative complications (3 [9%]) and negative side effects (6 [19%]) were minor. At the time of most recent clinic visit (mean 18.6 months, S.D. 13.9), 19 of 32 patients (59%) were responders with ≥50% reduction in seizure frequency (pediatric n = 14, young adult n = 5). The rate of responders increased with prolonged activation of RNS stimulation, reaching 71% (five of seven patients) after 24 months. Antiseizure medication was reduced in five (16%) patients, and seizure rescue medication usage was reduced in 10 (31%) patients. Quality of life improved in 15 (47%) patients. ConclusionsRNS implantation resulted in a sustained reduction in seizure frequency with minimal side effects in a majority of patients. Taken together, our data suggest that RNS is an effective and safe treatment option for focal, multifocal, and potentially generalized DRE in the pediatric and young adult population.

6807 Evaluation of Tobacco Exposure and Teprotumumab Efficacy: Pooled Results from Acute TED Clinical Trials

Abstract Disclosure: S. Ugradar: Consulting Fee; Self; Acelyrin. S.T. Wester: Advisory Board Member; Self; Amgen Inc. Consulting Fee; Self; Immunovant, Lassen. Research Investigator; Self; Amgen Inc, Sling, Immunovant. R. Holt: Employee; Self; Amgen Inc. Stock Owner; Self; Amgen Inc. Q. Fu: Employee; Self; Amgen Inc. Stock Owner; Self; Amgen Inc. G.J. Kahaly: Consulting Fee; Self; Amgen Inc. Research Investigator; Self; Amgen Inc. Introduction: Tobacco exposure is a known risk factor for Thyroid Eye Disease (TED) development and severity. Here, we compare outcomes with teprotumumab in smokers versus non-smokers as reported in pooled clinical trials in patients with acute TED. Methods: Patients ≥18 years old from two placebo-controlled trials and an open-label extension in the US and EU (Phase 2, NCT01868997; OPTIC, NCT03298867; OPTIC-X, NCT03461211) and one placebo-controlled trial in Japan (OPTIC-J, jRCT2031210453) with Graves’ disease and recent onset (≤9 month duration) active TED (Clinical activity score, CAS≥4), were included. Patients received eight infusions of teprotumumab over 21 weeks, with the final study visit at Week 24 (three weeks after final dose). Statistical analyses were conducted to test differences in responder rates for proptosis (≥2mm, primary outcome), diplopia (Bahn-Gorman scale≥1), clinical activity score (CAS, 2-point improvement), and Overall response (proptosis + CAS), as well as proptosis mm change and Graves’ Ophthalmopathy Quality of Life (GO-QOL, range 0-100) score change. Cochran-Mantel-Haenszel tests were conducted to test the difference in responder rate for proptosis, diplopia, CAS, and Overall responder rate between smokers and non-smokers stratified by study (Phase 2, OPTIC, OPTIC-X, and OPTIC-J). Mixed Model for Repeated Measures was conducted to test the difference in the mean change in proptosis and GO-QOL. Results: Baseline characteristics and TED characteristics between teprotumumab-treated smokers (N=32, mean age 51 years, 75% female) and non-smokers (N=116), mean age 49.5 years, 68% female were similar. No significant differences were seen in proptosis (78.1% vs 83.6%, P=.585), diplopia (55.6% vs 70.2%, P=.175), CAS (73.3% vs 59.3%, P=.145), Overall (73.3% vs 76.1%, P=.814) responses and GO-QOL least squares mean (LSM) change (17.3 vs 17.0, P=.927) between smokers and non-smokers. The magnitude of LSM proptosis mm change was similar (-2.82 vs -3.23 mm, P=.19). Conclusion: In this post-hoc assessment, proptosis response rates with teprotumumab were comparable in smokers and non-smokers at Week 24. Teprotumumab produced clinically relevant decreases in proptosis, CAS, Overall response, diplopia, and improvements in quality of life over the study period of 24 weeks in both groups. These improvements were comparable to those seen in the overall teprotumumab-treated patient populations with TED. Smoking is a known risk factor for more severe TED but does not significantly affect response to teprotumumab. Public Presentation: 6/2/2024

Cardiac resynchronization therapy guided by interventricular conduction delay: How to choose between biventricular pacing or conduction system pacing.

Biventricular pacing (BIV) is the gold standard for cardiac resynchronization therapy (CRT). Thirty percent of patients do not respond to CRT. Conduction system pacing (CSP) represents a viable alternative. Interventricular conduction delay (IVCD), as electrical desynchrony marker, is a CRT response predictor. The aim of this study was to determine the incidence of CRT responders by selecting the best approach between BIV and CPS based on intraoperative IVCD measurement in patients with HFrEF and LBBB. Ninety-six patients were randomly assigned in a 1:1 ratio to either a standard BIV group(control group, CG) or a group where the CRT approach was determined based on IVCD evaluation(study group, SG). If the right ventricular sensed electrogram (RVs)-left ventricular sensed electrogram (LVs) interval was ≥100 ms, the lead was left in its original position; otherwise, the LV lead was removed, and CSP was performed instead. Clinical, EKG, and echocardiographic features have been assessed pre- and 6 months post-implant. Echocardiographic and clinical responder were evaluated. Thirty-seven percent of patients in the SG underwent CSP, as the operative algorithm. The incidence of CRT responders was significantly higher in the SG (echocardiographic criterion: 92.5% vs. 69.8%, p:.009; clinical criterion 87.5% vs. 62.8%, p:.014). The SG showed a significantly greater difference in EF between pre- and post-implant as well as reduced end-diastolic and systolic volumes. Univariate and multivariate regression analysis indicated that enrollment in the SG was the only factor associated with CRT response. Intraoperative assessment of IVCD could help determine the optimal CRT approach between BIV and CSP, leading to a significant improvement in the rate of CRT responders.

Long-term efficacy and safety of cannabidiol in patients with tuberous sclerosis complex: 3-year results from the cannabidiol expanded access program.

The cannabidiol (CBD) Expanded Access Program provided compassionate access to CBD for patients with treatment-resistant epilepsy, including tuberous sclerosis complex (TSC), at 35 US epilepsy centers. Here, we present the long-term efficacy and safety outcomes for add-on CBD treatment in patients with TSC. Patients received plant-derived, highly purified CBD (Epidiolex® 100 mg/mL, oral solution), increasing from 2 to 10 mg/kg/d to tolerance or maximum of 25-50 mg/kg/d. Efficacy endpoints were percentage change from baseline in median monthly convulsive, focal, and total seizure frequency and ≥ 50%, ≥75%, and 100% responder rates across 12-week visit windows through 144 weeks. Adverse events (AEs) are reported through 233 weeks. Thirty-four patients with confirmed TSC were included. Mean age was 12.4 years (range, 1.8-31.2), and patients were receiving a median of 3 (range, 1-7) antiseizure medications (ASMs) at baseline. Median CBD dose was 25-28 mg/kg/d for 36 weeks and then 20-50 mg/kg/d through 228 weeks. Dose reduction from baseline occurred for most ASMs, except topiramate. Median reduction in the frequency of convulsive, focal, and total seizures was 44%-81%, 51%-87%, and 44%-87%, respectively, through 144 weeks. Responder rates (≥50%, ≥75%, and 100% reduction) were 43%-71%, 14%-58%, and 0%-25% for convulsive seizures; 52%-75%, 35%-60%, and 7%-32% for focal seizures; and 46%-79%, 26%-65%, and 0%-13% for total seizures. A total of 94% of patients experienced ≥1 AE; 47% had serious AEs, considered treatment unrelated by the investigator. Treatment-related AEs (TRAEs) occurred in 71% of patients. The most frequently reported TRAEs were somnolence, diarrhea, and ataxia. Two patients experienced AEs leading to discontinuation. There were no deaths. Long-term add-on CBD use was associated with reduced seizure frequency through 144 weeks. The safety profile was consistent with previous reports. In this study, we evaluated efficacy and safety of cannabidiol (CBD) treatment in patients with tuberous sclerosis complex receiving CBD in addition to other antiseizure treatments in an Expanded Access Program. After starting CBD, 46%-79% of patients had at least 50% reduction and 26%-65% had at least 75% reduction in the number of seizures per month; up to 13% had no seizures through 144 weeks. Safety results were similar to prior studies; sleepiness and diarrhea were common treatment-related side effects. These results show that long-term CBD treatment was associated with fewer seizures and mild/moderate side effects.

Effectiveness and safety of alirocumab and evolocumab for hypercholesterolemia in a population with high cardiovascular risk

Background and aimsThe criteria for the use of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) more restrictive than those approved were established in Catalonia by the Health System (CatSalut) to improve their efficiency, with different LDL-C values from which to start treatment according to risk factors. The aim of the study is to analyse adherence to these criteria and results. MethodsA retrospective study of patients treated with PCSK9i at Vall d’Hebron University Hospital between 2016 and 2021 was performed using data from the Registry of Patients and Treatments and medical records. The degree of agreement with the CatSalut criteria, LDL-C-responders (decrease ≥30%), cardiovascular events and discontinuations were analysed. ResultsA total of 193 patients treated with PCSK9i were followed for a median of 27 months (IQR 23). The median age was 61 (IQR 15); 62.7% were men. Seventy percent of the patients had non-familial hypercholesterolemia. Treatment was for secondary prevention of cardiovascular disease in 82.4% of cases. The median LDL-C decreased from 139 (IQR 52) to 59 (IQR 45) mg/dL. The percentage of LDL-C reduction was 61.0% (IQR 30). In 72.5% of patients, all CatSalut criteria for starting treatment were met. The rate of responders was 85.4%. During follow-up, 19 patients (9.8%) had a cardiovascular event, and 15 (7.7%) discontinued treatment, in two cases due to toxicity. ConclusionPCSK9i were used according to CatSalut criteria in three out of four cases. In this high-risk population, incidence of cardiovascular events was similar to that in clinical trials.

Efficacy of perampanel by etiology in Japanese patients with epilepsy-subpopulation analysis of a prospective post-marketing observational study.

To examine the efficacy and safety of perampanel (PER) in patients with post-stroke epilepsy (PSE), brain tumor-related epilepsy (BTRE), and post-traumatic epilepsy (PTE) using Japanese real-world data. The prospective post-marketing observational study included patients with focal seizures with or without focal to bilateral tonic-clonic seizures who received PER combination therapy. The observation period was 24 or 52 weeks after the initial PER administration. The safety and efficacy analysis included 3716 and 3272 patients, respectively. This post hoc analysis examined responder rate (50% reduction in seizure frequency), seizure-free rate (proportion of patients who achieved seizure-free), and safety in patients included in the post-marketing study who had PSE, BTRE, and PTE in the 4 weeks prior to the last observation. Overall, 402, 272, and 186 patients were included in the PSE, BTRE, and PTE subpopulations, and 2867 controls in the "Other" population (etiologies other than PSE, BTRE, or PTE). Mean modal dose (the most frequently administered dose) values at 52 weeks were 3.38, 3.36, 3.64, and 4.04 mg/day for PSE, BTRE, PTE, and "Other," respectively; PER retention rates were 56.2%, 54.0%, 52.6%, and 59.7%, respectively. Responder rates (% [95% confidence interval]) were 82% (76.3%-86.5%), 78% (70.8%-83.7%), 67% (56.8%-75.6%), and 50% (47.9%-52.7%) for PSE, BTRE, PTE, and "Other," respectively, and seizure-free rates were 71% (64.5%-76.5%), 62% (54.1%-69.0%), 50% (40.6%-60.4%), and 28% (25.8%-30.1%), respectively. Adverse drug reactions tended to occur less frequently in the PSE (14.7%), BTRE (16.5%), and PTE (16.7%) subpopulations than in the "Other" population (26.3%). In real-world clinical conditions, efficacy and tolerability for PER combination therapy were observed at low PER doses for the PSE, BTRE, and PTE subpopulations. To find out how well the medication perampanel works and whether it is safe for people who have epilepsy after having had a stroke, brain tumor, or head injury, we used information from real-life medical situations in Japan. We looked at the data of about 3700 Japanese patients with epilepsy who were treated with perampanel. We found that perampanel was used at lower doses and better at controlling seizures, and had fewer side effects for patients with epilepsy caused by these etiologies than the control group.

Effect of add-on naldemedine treatment in patients with cancer and opioid-induced constipation insufficiently responding to magnesium oxide: a pooled, subgroup analysis of two randomized controlled trials.

To evaluate the additive effect of naldemedine tosylate (naldemedine) on opioid-induced constipation in cancer patients insufficiently responding to magnesium oxide treatment. We combined two randomized, double-blind, placebo-controlled, phase IIb and III trials of naldemedine and conducted a post hoc subgroup analysis. We evaluated the effect and safety of naldemedine in 116 patients who received naldemedine in addition to magnesium oxide (naldemedine group) and 117 patients who received placebo in addition to magnesium oxide (placebo group). Both groups included patients insufficiently responding to magnesium oxide for opioid-induced constipation. Effect was assessed using spontaneous bowel movement responder rate, complete spontaneous bowel movement responder rate, changes in spontaneous bowel movements and complete spontaneous bowel movements. Safety was also assessed. During the 2-week treatment period, the responder rates for spontaneous bowel movement and complete spontaneous bowel movement were 73.3 and 43.1% in naldemedine group, respectively, which were significantly higher (P<0.0001) than 41.9 and 14.5% in placebo group, respectively. Median time to first spontaneous bowel movement and first complete spontaneous bowel movement was significantly shorter (P<0.0001) in the naldemedine group (4.0 and 21.3h, respectively) than in the placebo group (27.7 and 211.7h, respectively). The incidence of adverse events and diarrhoea was significantly higher (P<0.05) in the naldemedine group than in the placebo group, while the incidence of serious adverse events and severe diarrhoea was not significantly different between the naldemedine and placebo groups. The study suggested the addition of naldemedine as an effective treatment option for opioid-induced constipation in cancer patients insufficiently responding to magnesium oxide treatment.

Long-term duration and safety of Radiesse (+) for the treatment of jawline.

Calcium hydroxyapatite (CaHA)-carboxymethylcellulose (CMC)+ has unique properties that make it optimal for lifting, contouring, and defining the jawline. This long-term follow-up of a randomized, multicenter, rater-blinded trial reports efficacy and safety of CaHA-CMC(+) through 48 and up to 60 weeks post-treatment. Eligible patients were randomized (2:1) to the treatment or the control/delayed treatment group to receive CaHA-CMC(+) injections in both jawlines. While touch-ups were permitted 4 weeks post-treatment for both groups, only the treatment group was eligible for optional retreatment after 48 weeks. The primary outcome was ≥1-point improvement on both jawlines on the Merz Jawline Assessment Scale (MJAS); secondary endpoints included the Subject Global Aesthetic Improvement Scale (SGAIS) among others. Post hoc analysis included pooling up to 48-week data from the combined treatment and control/delayed groups and 60-week data for the treatment group. Overall, 175 received treatment. MJAS responder rates were 77.9%, 78.7%, and 62.9% at 12, 24, and 48 weeks post-treatment, respectively. Responder rate on the MJAS at 60 weeks was 74.6% for those who received retreatment and 43.5% for those patients who received only the initial and touchup treatments. SGAIS scores demonstrated 93.4%, 85.6%, and 68.5% of patients rated themselves very much improved after 12, 24, and 48 weeks, respectively. Adverse events consisted of procedure or CaHA-CMC(+)-related events that were mostly resolved and overwhelmingly mild. CaHA-CMC(+) produced clinically meaningful and long-lasting improvements in jawline contour and was well tolerated in patients through 60 weeks. ClinicalTrials.gov Identifier: NCT03583359.

Preventive Medications in Pediatric Migraine

Pediatric migraine substantially impacts quality of life and academic performance among children and adolescents. Understanding the efficacy and safety of pharmacological interventions for migraine prophylaxis in this population is crucial for developing effective treatment strategies. To conduct a comprehensive network meta-analysis to evaluate the efficacy and safety associated with pharmacological treatments for pediatric migraine prophylaxis among pediatric patients with a migraine diagnosis and assess interventions involving various oral pharmacological interventions compared with each other and placebo. PubMed, Embase, and SCOPUS were searched for publications up to September 2023. Search terms and indexing were chosen to encompass relevant studies, focusing on randomized clinical trials in pediatric migraine prophylaxis. Inclusion criteria targeted randomized clinical trials involving pediatric patients with migraine. Studies were selected based on their examination of oral pharmacological interventions. The search yielded an initial 9162 citations. Data extraction adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. Five investigators independently extracted study data into a spreadsheet in duplicate. Study-level estimates were calculated, employing a random-effects model for primary and secondary outcomes due to identified heterogeneity. Data analysis was conducted from December 2023 to March 2024. The primary outcome was migraine frequency (number of attacks per month). Secondary outcomes included a 50% or greater responder rate, headache duration, headache intensity, and disability (assessed by pediatrics migraine-specific disability tool). Adverse events were also evaluated. The analysis incorporated 45 trials with 3771 participants. Compared with placebo, pregabalin (ratio of means [RoM], 0.38; 95% CI, 0.18-0.79) and topiramate with vitamin D3 (RoM, 0.44; 95% CI, 0.30-0.65) were associated with reduction in migraine frequency. Flunarizine (RoM, 0.46; 95% CI, 0.26-0.81), levetiracetam (RoM, 0.47; 95% CI, 0.30-0.72), riboflavin (RoM, 0.50; 95% CI, 0.32-0.77), cinnarizine (RoM, 0.64; 95% CI, 0.46-0.88), topiramate (RoM, 0.70; 95% CI, 0.55-0.89), and amitriptyline (RoM, 0.73; 95% CI, 0.54-0.97) were also associated with reduction in migraine frequency, but these findings were drawn from individual studies. For the 50% or greater responder rate, flunarizine and α-lipoic acid (risk ratio [RR], 8.73; 95% CI, 2.44-31.20), flunarizine (RR, 4.00; 95% CI, 1.38-11.55), pregabalin (RR, 1.88; 95% CI, 1.13-3.14), and cinnarizine (RR, 1.46; 95% CI, 1.04-2.05) were associated with significantly greater effectiveness than placebo. Compared with placebo, propranolol and cinnarizine (RoM, 0.45; 95% CI, 0.28-0.72), pregabalin (RoM, 0.57; 95% CI, 0.33-0.96), valproate (RoM, 0.60; 95% CI, 0.49-0.72), levetiracetam (RoM, 0.62; 95% CI, 0.50-0.77), and cinnarizine (RoM, 0.64; 95% CI, 0.54-0.76) were significantly associated with reduction in headache intensity. However, no treatments were associated with significant improvements in quality of life or reduction of the duration of migraine attacks. Adverse events were higher with amitriptyline (RR, 3.81; 95% CI, 1.41-10.32), topiramate (RR, 4.34; 95% CI, 1.60-11.75), and valproate (RR, 5.93; 95% CI, 1.93-18.23) compared with placebo. In this network meta-analysis of randomized clinical trials, topiramate and pregabalin were associated with reduction in headache frequency and intensity. Although there were also other drugs that showed statistically significant results (flunarizine, riboflavin, amitriptyline, and cinnarizine), more studies were required for a robust conclusion. None of the drugs were associated with improved quality of life or attack duration, underscoring the need for further research to develop more comprehensive treatment strategies and explore the potential of combination therapies, especially those involving vitamins. Future studies should focus on validating these findings and expanding the treatment landscape for pediatric migraine management.

Effectiveness of Changing Drug Classes in Patients With Refractory Laryngopharyngeal Reflux Disease.

To investigate the effectiveness of drug class changes in patients with refractory laryngopharyngeal reflux disease (LPRD). Retrospective case series with prospective data. Multicenter study. The data of patients treated for a refractory LPRD from September 2017 to December 2023 were collected. The effectiveness of drug class changes was assessed through the reflux symptom score (RSS) change. Signs were evaluated with the Reflux Sign Assessment. The RSS reduction was used to categorize the therapeutic responses as mild (20%-40% RSS reduction), moderate (40.1%-60% RSS reduction), high (60.1%-80%), and complete (>80%). Among the 334 medical records, 74 (22.2%) patients had refractory LPRD defined as no RSS change in the pre- to 3-month posttreatment. The mean age was 52.6 ± 15.5 years. Changing drug class was associated with significant 3- to 6-month posttreatment reductions of RSS and RSA. Thirty patients (39%) did not experience symptom reduction after changing drugs. Changing alginate to magaldrate and magaldrate to alginate was associated with the highest responder rate (76.9%). Changing PPI and alginate/magaldrate molecules led to a response rate of 62.5%. In patients initially treated with a combination of PPI and alginate or magaldrate, changing PPI without changing alginate/magaldrate led to a 37.5% response rate. The baseline RSS was predictive of the 3- and 6-month RSS (therapeutic response). Changing drug class, especially alginate-to-magaldrate, may be an effective therapeutic approach for patients with a refractory LPRD.

Exploring early- and mid-career academic work wellbeing challenges through a diversity and inclusion lens

BackgroundEarly- to mid-career academics (EMCAs) represent a core component of the Australian higher education workforce. These academics experience major challenges to their wellbeing, driving a strong desire to leave academia.ObjectivesDetermine (1) EMCA awareness of, and engagement with, previous University- and Faculty-level diversity and inclusion events/initiatives and (2) opportunities and solutions to address previously reported diversity and inclusion issues experienced in the workplace.Methods114 EMCAs in medicine, dentistry and health sciences completed an electronic cross-sectional survey. The survey contained a list of University- and Faculty-provided diversity and inclusion initiatives and sought respondent ratings of interest, awareness (knowing/hearing about) and engagement (attending/applying/participating). Two in-person focus groups comprising participants who opted in during the survey or who responded to broader advertising were conducted. Both groups explored opportunities and solutions to address diversity and inclusion issues reported in an earlier organisation-wide survey.ResultsWhilst early- and mid-career academics reported high interest in diversity and inclusion events, they also reported limited awareness and engagement with these events, feeling unsupported to engage or perceiving consequences for workload. Focus groups identified five themes related to opportunities and solutions to address diversity and inclusion issues experienced in the workplace (1) enhanced relational support for career progression, (2) clear and transparent processes for efficient working, (3) reducing structural barriers to create opportunity, (4) improved financial renumeration, and (5) improved transitions and pathways.ConclusionEarly- and mid-career academics often felt unable to engage with activities outside of their immediate work responsibilities, such as events about diversity and inclusion, due to feelings of high workload. A systems approach to deploying targeted strategies to address these wellbeing challenges is recommended to sustain and retain this critical workforce.

Cenobamate's Efficacy for Seizure Treatment in Tuberous Sclerosis Complex

BackgroundEpilepsy is prevalent, and seizure control is challenging in patients with tuberous sclerosis complex (TSC). Cenobamate (CBM) has proven efficacy in several studies; however, its benefit in the TSC population is not known. MethodsWe performed a retrospective review of patients with TSC who received adjunctive CBM for seizure treatments. We assessed treatment efficacy by comparing seizure frequencies three months before CBM (baseline) and those at 3-, 6-, 12-, and 18- month follow-ups. ResultsWe identified 70 patients with TSC receiving CBM and excluded 16 with insufficient data. Fifty-four patients aged 2 to 39 years, with an average baseline seizure of 66.1 ± 88.9 per month, were analyzed. Treatment retention rates at 3, 6, 12, and 18 months were 94.4%, 79.6%, 66.7%, 44.4%, and responder rates (proportions of patients who remained on treatment and had ≥50% seizure reduction) were 38.1%, 51.7%, 53.1%, and 59.1%, respectively. Seizure-free rates at these respective follow-ups were 7.1%, 13.8%, 6.3%, and 9.1%. For patients experiencing reduced seizures, the mean percentage of change ranged from 61.5% to 74.6%. Side effects were common (64.8%), particularly sedation (42.6%), behavioral disturbance (24.1%), and gastrointestinal disturbance (22.2%). ConclusionsMost patients in this study showed seizure reduction; however, the overall responder and seizure-free rates were lower than the literature, likely due to the unique underlying epileptogenesis in TSC and the challenges of tolerating CBM. The lower treatment retention rates signal areas for improvement in concurrent medication adjustment practices.

The Suboptimal QLV Ratio May Indicate the Need for a Left Bundle Branch Area Pacing-Optimized Cardiac Resynchronization Therapy Upgrade.

Background: The QLV ratio (QLV/baseline QRS width) is an established intraoperative-measurable parameter during cardiac resynchronization therapy (CRT) device implantation, potentially predicting the efficacy of electrical resynchronization. Methods: Left bundle branch area pacing-optimized CRT (LOT-CRT) is a novel approach with the potential to improve both responder rate and responder level in the CRT candidate patient group, even when an optimal electro-anatomical left ventricular lead position is not achievable. In our observational study, 72 CRT-defibrillator candidate patients with a QRS duration of 160 ± 12 ms were consecutively implanted. Using a QLV-ratio-based implant strategy, 40 patients received a biventricular CRT device (Biv-CRT) with an optimal QLV ratio (≥70%). Twenty-eight patients with a suboptimal QLV ratio (<70%) were upgraded intraoperatively to a LOT-CRT system. Patients were followed for 12 months. Results: The postoperative results showed a significantly greater reduction in QRS width in the LOT-CRT patient group compared to the Biv-CRT patients (40.4 ± 14 ms vs. 32 ± 13 ms; p = 0.024). At 12 months, the LOT-CRT group also demonstrated a significantly greater improvement in left ventricular ejection fraction (14.9 ± 8% vs. 10.3 ± 7.4%; p = 0.001), and New York Heart Association functional class (1.2 ± 0.5 vs. 0.8 ± 0.4; p = 0.031), and a significant decrease in NT-pro-BNP levels (1863± 380 pg/mL vs. 1238 ± 412 pg/mL; p = 0.012). Notably, the LOT-CRT patients showed results comparable to Biv-CRT patients with a super-optimal QLV ratio (>80%) in terms of QRS width reduction and LVEF improvement. Conclusions: Our single-center study demonstrated the feasibility of a QLV-ratio-based implantation strategy during CRT implantation. Patients with a LOT-CRT system showed significant improvements, whereas Biv-CRT patients with a super-optimal QLV ratio may not be expected to benefit from an additional LOT-CRT upgrade.

Safety and efficacy of HK-660S in patients with primary sclerosing cholangitis: A randomized double-blind phase 2a trial.

A clinical unmet need persists for medications capable of modulating the progression of primary sclerosing cholangitis (PSC). This study aimed to assess the clinical feasibility of HK-660S (beta-lapachone) in PSC. In this multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 2 trial, participants were assigned in a 2:1 ratio to receive either 100 mg of HK-660S or a placebo twice daily for 12 weeks. The primary outcomes were the reduction in serum alkaline phosphatase (ALP) levels and the percentage of participants showing improvements in PSC severity, as determined by magnetic resonance cholangiopancreatography (MRCP) with the Anali score. Secondary endpoints included changes in liver stiffness and adverse events. The analysis included 21 patients, 15 receiving HK-660S, and six receiving a placebo. Improvements in the Anali score were observed in 13.3% of the HK-660S group, with no improvements in the placebo group. HK-660S treatment resulted in a 15.2% reduction in mean ALP levels, compared to a 6.6% reduction in the placebo group. A stratified ad-hoc analysis based on baseline ALP levels showed a statistically significant response in the HK-660S group among those with ALP levels greater than twice the upper limit of normal, with a 50% responder rate (p = 0.05). Additionally, 26.7% of the HK-660S group showed improvements in the enhanced liver fibrosis score, with no improvements in the placebo group. HK-660S was generally well-tolerated. HK-660S is well-tolerated among patients with PSC and may improve bile duct strictures, decrease serum ALP levels, and reduce liver fibrosis. (cris.nih.go.kr, Number KCT0006590).

Calcitonin Gene-Related Peptide Monoclonal Antibodies: Key Lessons from Real-World Evidence.

The advent of monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway has transformed the management of migraine, offering newfound optimism for clinicians and individuals with episodic migraine (EM) and chronic migraine (CM). While randomized controlled trials (RCTs) have provided crucial insights into the effectiveness and safety profiles of these treatments, their translation into real-world clinical practice remains a challenge. This review aims to conduct a comprehensive assessment of real-world studies, offering valuable insights tailored for practical application in clinical settings. We conducted a comprehensive literature search in PubMed, SCOPUS, and MEDLINE for real-life studies on erenumab, fremanezumab, and galcanezumab. Abstracts underwent rigorous screening by two reviewers for relevance. Data extraction from selected articles was performed using a standardized form, with verification by a second reviewer. Data synthesis was narrative, following PRISMA guidelines. Our search included 61 pertinent studies conducted between 2019 and 1 March 2024. Real-world study designs demonstrated notable variability in the selection and inclusion of migraine patients, influenced by factors such as attack frequency, data collection criteria, and primary/secondary objectives. Key findings commonly reported considerable improvements in efficacy outcomes (migraine frequency, analgesic use, pain severity, and disability), high responder rates, and optimal safety and tolerability profiles. Real-world evidence underscores the role of anti-CGRP mAbs as targeted therapies for both CM and EM patients. The overall results indicate that the effectiveness and tolerability of anti-CGRP mAbs in real-world applications may exceed those observed in RCTs, an extraordinary finding in clinical neurology.

Differential analysis of the impact of lesions’ location on clinical and radiological outcomes after the implantation of a novel aragonite-based scaffold to treat knee cartilage defects

Abstract Purpose There is limited comparative evidence on patient outcomes following cartilage repair in various knee compartments. The aim of this study was to compare clinical and imaging outcomes after treating cartilage defects in femoral condyles and trochlea with either an aragonite-based scaffold or surgical standard of care (SSoC, i.e., debridement/microfractures) in a large multicentre randomized controlled trial. Methods 247 patients with up to three knee joint surface lesions (ICRS grade IIIa or above) in the femoral condyles, trochlea or both (“mixed”), were enrolled and randomized to surgery with either a cell-free aragonite scaffold or SSoC. Patients were followed for up to 48 months by analysing subjective scores (KOOS and IKDC), radiological outcomes (defect filling on MRI), as well as treatment failure rates and adverse events. A differential analysis of outcomes for condylar, trochlear and mixed lesions was performed. Results The scaffold group significantly outperformed the SSoC group regardless of lesion location with statistically significantly better KOOS Overall scores at 24 months (all p ≤ 0.0009) and 48 months (all p ≤ 0.02). Similar results were observed for KOOS subscales and IKDC scores. For KOOS responder rates, superiority of the implant group was demonstrated at 24, 36, and 48 months (all p ≤ 0.004). Higher defect filling on MRI for implants was observed for all locations. Lower treatment failure rates for the implant were observed in condylar and mixed lesions. Conclusion The aragonite-based scaffold was safe and effective regardless of the defect location, providing superior clinical and radiological outcomes compared to SSoC up to four years follow-up. Level of evidence I – Randomized controlled trial.