Switching Effect Research Articles

The Importance of Early Intervention in Multiple Sclerosis

A satellite symposium titled ‘Transforming MS Care: Early Intervention and Sustained Safety’ held at the 40th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) discussed current challenges and future advances in the management of multiple sclerosis (MS). The symposium discussed the importance of early intervention with disease-modifying therapy (DMT) in people with MS. The session explored the effects of DMT switching in patients with MS, and discussed data on the persistence, patient satisfaction, and long-term safety associated with DMTs. The DAYBREAK OLE trial investigating once-daily ozanimod showed that early treatment with high-efficacy DMT is essential to improve disability outcomes, preserve cognition, and delay MS disease progression.

P1188 Real-world quality of life experience of subcutaneous infliximab use in children with Inflammatory Bowel Disease (IBD) at a tertiary paediatric centre

Abstract Background Subcutaneous infliximab (SC-IFX) use offers relative pharmacokinetic stability and efficacy and safety profiles comparable to intravenous-infliximab (IV-IFX) in adult patients with IBD (1-4). Regular hospital admissions for infusions have an impact Quality of Life (QoL), impacting work and school commitments as well as increasing financial burden. Aim to assess tolerability and QoL in patients switched from IV to SC infliximab collected 12 weeks after the switch. Methods A prospectively identified cohort of 33 children with IBD commenced 120mg fortnightly SC-IFX dosing between February to July 2024 in an Australian tertiary paediatric IBD service. QoL and medication tolerability questionnaires (SIAQ and Costs For Patient’s questionnaire) included assessment of tolerability, convenience, satisfaction along with data about travel time and costs were completed at week 12. Assessment of disease activity, inflammatory biomarkers and therapeutic drug monitoring occurred 4 weekly for the first 12 weeks. Results 31(94%) patients completed the 12-week study treatment period. 21 patients (68%) responded to the QOL questionnaires. Satisfaction with SC treatment was 20 (95%) across respondents, only 1 patient reporting ‘somewhat dissatisfied’ experience. 18 (85%) described ease of administration, with 3 (14%) finding injections "not easy". Respondents described financial impacts to be greatest, followed by time-commitment for attendance, loss of school and work time for attendance for infusions. Nearly 2/3 caregivers required formal leave from employment to facilitate infusion attendance, and 1/3 of patients required full day off school. 100% described a definite or probable willingness to continue SC injections beyond the 12-week period. Conclusion We describe the largest cohort of children with IBD prescribed SC-IFX with short-term follow-up. There was high treatment persistence with the drug. QOL data demonstrates high patient satisfaction, with positive impacts on patient quality-of-life with treatment described. Our real-world experience of paediatric SC-IFX use suggests this well tolerated and preferable alternative to IV-IFX dosing in children in with IBD. Further large-cohort and long-term paediatric data is required. References 1)Schreiber S, Ben-Horin S, Leszczyszyn J et al. Randomized Controlled Trial: Subcutaneous vs Intravenous Infliximab CT-P13 Maintenance in Inflammatory Bowel Disease. Gastroenterology 2021; 160: 2340-53. 2)Buisson A, Nachury M, Bazoge M et al. Long-term effectiveness and acceptability of switching from intravenous to subcutaneous infliximab in patients with inflammatory bowel disease treated with intensified doses: The REMSWITCH-LT study. Aliment Pharmacol Ther 2024; 59: 526-34. 3)Gianolio L, Armstrong K, Swann E et al. Effectiveness of Switching to Subcutaneous Infliximab in Pediatric Inflammatory Bowel Disease Patients on Intravenous Maintenance Therapy. J Pediatr Gastroenterol Nutr 2023; 77: 235-9. 4)Gianolio L, Armstrong K, Swann E et al. OC5 Effectiveness and safety of switching to subcutaneous infliximab in paediatric inflammatory bowel disease patients on established intravenous biosimilar infliximab maintenance therapy: real world data from a regional cohort. Frontline Gastroenterology 2024; 15: A4-A.

P0985 Real-world experience of subcutaneous infliximab use in children with inflammatory bowel disease (IBD) at a tertiary paediatric centre

Abstract Background Subcutaneous infliximab (SC-IFX) offers comparable efficacy and safety profiles to intravenous infliximab (IV-IFX) use in patients with inflammatory bowel disease (IBD), with relative pharmacokinetic stability demonstrated 1, 2. Minimal experience with SC-IFX use in paediatric IBD has been described3, 4. We aimed to assess the clinical tolerability of SC-IFX use in children with IBD requiring anti-tumour-necrosis factor (anti-TNF) treatment. Methods A prospectively identified cohort of children with IBD commenced 120mg fortnightly SC-IFX dosing between February to July 2024 in an Australian tertiary paediatric centre. Treatment followed switch from stable intravenous infliximab (IV-IFX) biosimilar maintenance dosing, or as part of induction treatment. Baseline and four-weekly biochemical and clinical disease activity assessments were undertaken over a 12 week period of follow-up. Results Thirty-one of thirty-three patients completed the 12-week period of treatment follow-up. Median age was 15 years (IQR 14-16.5 years) and 76% (25/33) were male. Twenty-seven patients (82%) had a Crohn’s disease diagnosis. SC-IFX was prescribed as part of induction dosing in 18% (6/33). Biochemical parameters are outlined in Table 1. Median infliximab level increased by 10mg/L to 17.6mg/L at week 12, with a statistically significant increase between baseline level and all other timepoints over the follow-up period (Figure 1). Sixteen patients (48%) had a serum infliximab level greater than 20mg/L at 12 week follow-up. There was no statistically significant change in clinical disease activity indices (Paediatric Crohn’s Disease Activity Index [PCDAI] or Paediatric Ulcerative Colitis Activity Index [PUCAI]) assessed across study timepoints. No correlation between patient characteristics, including demographics, immunomodulator use and previous (if any) IV-IFX regimen, and biochemical markers at baseline or week 12 was seen. High tolerability and treatment persistence were observed in our patient group without any safety concerns. Conclusion We describe the largest cohort of children with IBD prescribed SC-IFX with short-term follow-up. Serum infliximab level increased by 10mg/L over the study period, without significant change in faecal calprotectin and clinical disease activity indices. We observed high treatment persistence in our patient group. Our real-world experience suggests paediatric SC-IFX use may be a reasonable alternative to IV-IFX dosing in children in with IBD. Further large-cohort studies and long-term paediatric data is required. References 1)Schreiber S, Ben-Horin S, Leszczyszyn J et al. Randomized Controlled Trial: Subcutaneous vs Intravenous Infliximab CT-P13 Maintenance in Inflammatory Bowel Disease. Gastroenterology 2021; 160: 2340-53. 2)Buisson A, Nachury M, Bazoge M et al. Long-term effectiveness and acceptability of switching from intravenous to subcutaneous infliximab in patients with inflammatory bowel disease treated with intensified doses: The REMSWITCH-LT study. Aliment Pharmacol Ther 2024; 59: 526-34. 3)Gianolio L, Armstrong K, Swann E et al. Effectiveness of Switching to Subcutaneous Infliximab in Pediatric Inflammatory Bowel Disease Patients on Intravenous Maintenance Therapy. J Pediatr Gastroenterol Nutr 2023; 77: 235-9. 4)Gianolio L, Armstrong K, Swann E et al. OC5 Effectiveness and safety of switching to subcutaneous infliximab in paediatric inflammatory bowel disease patients on established intravenous biosimilar infliximab maintenance therapy: real world data from a regional cohort. Frontline Gastroenterology 2024; 15: A4-A.

P1082 Is mutiple switching between infliximab biosimilars safe in iInflammatory Bowel Disease?

Abstract Background A biosimilar biological drug is a biologic that has similar efficacy and safety to the original product.The goal of biosimilar therapy is to provide a cost-effective option that is as effective and safe as the original product.The introduction of biosimilars into clinical practice has raised several clinical concerns, such as disease activation and the development of immunogenicity(1,2).There are very few studies evaluating the effect of multiple switches between biosimilars on patients with inflammatory bowel disease (IBD). In this study, we aimed to evaluate the safety and efficacy of multiple switches between biosimilars in patients with IBD receiving Infliximab (IFX) Patients used the biosimilar available at the hospital pharmacy,because obtaining medication from an outside pharmacy was more difficult based on the patient’s preference. Methods The data of 147 patients who were followed at the IBD outpatient clinic of Gazi University Hospital and received IFX treatment were retrospectively reviewed from the hospital information system. 70 patients were excluded from the study due to discontinuation of follow-up, short follow-up duration, or receiving a low number of infliximab doses. A total of 77 patients were included in the study. In Turkey, three commercial IFX preparations are available, one of which is the original product: REMICADE® (Janssen Biotech, Inc., Horsham, PA, USA), REMSIMA™ (Celltron, Inc., Incheon, Korea), and IXIFI® (Pfizer, USA). The commercial formulation used by the patients, the number of biosimilar switches, disease duration, and the presence of disease activation during switches were evaluated. Results Of the 77 patients included in the study, 37.7% (n=29) had ulcerative colitis (UC) and 62.3% (n=48) had Crohn’s disease (CD). The average age at diagnosis was 35±14.58 years. Thirty-seven patients had used the same preparation continuously, while 40 patients used different biosimilars. The number of switches ranged from a minimum of 1 to a maximum of 6 times. After switching to biosimilars, only one patient experienced disease activation. There was no statistically significant difference between the patients who had switches and those who did not regarding primary non-response and secondary non-response (p=0.419 and p=0.314, respectively). Conclusion In this study, the safety and efficacy of multiple switches between biosimilars in IBD patients receiving IFX were evaluated. Our findings indicate that biosimilars have similar efficacy and safety profiles when compared to the original infliximab products. Our results are consistent with the studies in literature(3,4) . However, long-term effects of switching between biosimilars and original products should be evaluated in more comprehensive studies.

P1014 Anti-TNF-alpha biosimilar cross and reverse-switching in pediatric IBD: Preliminary real-world data from the SIGENP IBD Working Group

Abstract Background Due to the increasing number of pediatric IBD patients receiving anti-TNF-alpha, multiple switching between biosimilars has become part of everyday clinical practice, although it is not yet officially recommended. A multicenter, nationwide retrospective study to determine the safety and effectiveness of multiple switching is currently underway within the IBD Working Group of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP). Methods Data from all pediatric IBD patients on anti-TNF-alpha treatment (IFX, ADA) who made one or more switches from one biosimilar to another (cross-switch) or from one biosimilar to the originator (reverse-switch) from 2013 to present have been collected. Safety was the primary study objective. These data are preliminary as data collection is still ongoing in additional centers. Results To date, three centers have collected data on 89 patients who underwent at least one cross- or reverse-switch 13.7 months (7-23.5) after starting biologic therapy: 51 with IFX (significantly more for UC and IBDU patients than CD patients, p<0.01) and 38 with ADA (significantly more in CD than in UC/IBDU patients, p<0.01). Twenty-one (23.6%) patients were switched twice, four (4.5%) three times, at 5.2 months (2-14.7) and 16.4 months (5.1-18.7), respectively since the previous switch. 84 were cross-switches and 5 were reverse-switches. The switch was non-medical in most cases (n=86, 89%) and medical in the remaining cases (due to adverse events). The median follow-up time was 3.6 years (2.2–6.4) from the start of biologic therapy. An acute infusion reaction occurred in 6/89 (6.7%), 1/21 (4.8%) and 1/4 (25%) patients after the first, second and third switches, respectively. Multiple switching was associated with a relapse in 2/89 (2.2%) and 2/21 (9.5%) after the first and second switching, respectively. No between-group differences in reactions or flares were noted between IFX and ADA. Conclusion Multiple switching biosimilars are a reality in the current practice in pediatric IBD. This practice does not appear to have any effect on the course of the disease, but further data are pending. References de Ridder L, Assa A, Bronsky J, et al. Use of biosimilars in pediatric inflammatory bowel disease: an updated position statement of the pediatric IBD Porto Group of ESPGHAN. J Pediatr Gastroenterol Nutr. 2019;68:144–153. doi:10.1097/MPG.0000000000002141 Mysler, E., Azevedo, V.F., Danese, S. et al. Biosimilar-to-biosimilar switching: what is the rationale and current experience?. Drugs 81, 1859–1879 (2021). https://doi.org/10.1007/s40265-021-01610-1 Cohen, H.P., Hachaichi, S., Bodenmueller, W. et al. Switching from one biosimilar to another biosimilar of the same reference biologic: a systematic review of studies. BioDrugs 36, 625–637 (2022). https://doi.org/10.1007/s40259-022-00546-6 Dipasquale V, Pellegrino S, Ventimiglia M, Cucinotta U, Citrano M, Graziano F, Cappello M, Busacca A, Orlando A, Accomando S, Romano C; Sicilian Network for Inflammatory Bowel Disease. Real-life experience of infliximab biosimilar in pediatric-onset inflammatory bowel disease: data from the Sicilian Network for Inflammatory Bowel Disease. Eur J Gastroenterol Hepatol. 2022 Oct 1;34(10):1007-1014. doi: 10.1097/MEG.0000000000002408 Dipasquale V, Pellegrino S, Ventimiglia M, Citrano M, Graziano F, Cappello M, Busacca A, Orlando A, Accomando S, Romano R; Sicilian Network for Inflammatory Bowel Disease. Adalimumab biosimilar in pediatric inflammatory bowel disease: a retrospective study from the Sicilian Network for Inflammatory Bowel Disease (SN-IBD). Healthcare (Basel). 2024 Feb 4;12(3):404. doi: 10.3390/healthcare12030404 Dipasquale V, Cicala G, Spina E, Romano C. Biosimilars in Pediatric Inflammatory Bowel Diseases: A Systematic Review and Real Life-Based Evidence. Front Pharmacol. 2022 Mar 17;13:846151. doi: 10.3389/fphar.2022.846151

P0673 Proactive switching to subcutaneous vedolizumab in Inflammatory bowel disease correlates with raised trough levels and confers a clinical benefit: a real-world experience

Abstract Background Vedolizumab is a gut-selective monoclonal antibody that is well-recognised for managing moderate and severe Crohn’s disease (CD) and Ulcerative Colitis (UC) [1]. Subcutaneous (SC) vedolizumab has been shown to be an effective and well-tolerated alternative to the intravenous (IV) form [2,3]. However, there remains a lack of data on real-world outcomes. This study evaluates the effectiveness and safety outcomes of switching from IV to SC vedolizumab in CD and UC. Methods We collected retrospective data from the electronic patient records at West Middlesex Hospital for all adults currently receiving vedolizumab for CD and UC between December 2017 and September 2024. This included patients’ demographics, disease epidemiology, current and previous biologic treatment, vedolizumab serum concentrations, and faecal calprotectin (FCP) levels. The primary endpoints were FCP and serum vedolizumab levels pre- and post-switch. The secondary endpoints were the development of adverse events and the need for rescue therapy post-switch. Results We included 105 patients with a median age of 59. Of these, 54.28% are males (n=57). 43 patients (40.95%) were switched to maintenance SC. Most patients were on the standard 8-weekly dosing regimen of intravenous vedolizumab pre-switch (88.37%, n=38), while the rest (n=5, 11.62%) were on an escalated 4-weekly regimen. More than half (n=23, 53.48%) of the patients were switched on a clinical basis, while the remainder (n=20, 46.51%) were switched due to patient preference. All the patients in the former group had low vedolizumab levels (< 15 mg/dl), and almost half (n=11) had associated active disease. In the low-level group switched to SC, UC constituted 52.17% (n=12) and CD was 47.82% (n=11). Ten patients (43.47%) had previously received anti-TNF-alpha. The median (IQR = Q3-Q1) pre-switch vedolizumab serum concentration level was 10 (5.5) mg/L, which almost tripled to 29.3 (15.6) mg/L after switching (12 to 52 weeks post-switch). The median faecal calprotectin (FCP) levels dropped from 357 (820) µg/g to 259 (493.5) µg/g post-switching to SC. The patients who remained on IV had a median vedolizumab level of 14.6 (11) mg/L and FCP of 263.5 (653.5) µg/g. None of the patients who were switched because of low levels sustained adverse effects compared to 5 patients (8.06%) in the IV group (mucocutaneous (n=2), joint (n=1) and fatigue (n=1) symptoms). Over the one-year follow-up period, one patient (4.34%) required rescue steroid therapy, compared to three (4.83%) in the IV group. Conclusion Implementing proactive subcutaneous switching of vedolizumab in a real-world setting correlates with higher levels confers improved clinical response, and has a good safety profile, reflecting clinical trial results.

Continuously focus tunable 2D/3D switchable cylindrical liquid crystal microlens arrays for autostereoscopic displays.

Cylindrical microlens arrays are important optical elements for autostereoscopic display. Conventional fixed focal length cylindrical microlens arrays do not allow switching between 2D mode and 3D mode when constructing a 3D viewing zone. In contrast, cylindrical liquid crystal microlens arrays with zoom characteristics allow switching between 2D and 3D states, as well as adjusting the width of the sub-viewing zone. Therefore, based on the quantitative analysis of the geometrical structure of the viewing zone in different states, this paper proposes a continuous zoom type cylindrical liquid crystal microlens array structure, which is a liquid crystal cell composed of an array of plano-concave glass substrates and planar glass substrates. Theory and experiments show that it is close to a favorable parabolic phase profile at different driving voltages, and at the same time, it can realize a zoom range of 1.6mm-36 mm at a smaller driving voltage. The wide zoom range and excellent zoom effect make this structure particularly suitable for autostereoscopic display, and this characteristic can achieve the effect of switching between 2D and 3D by adjusting the shape of the central viewing zone.

Long-term effect and reasons for switching and combining device-aided therapies in Parkinson's Disease.

In the advanced stages of Parkinson's disease (PD), when standard drug adjustments fail to sufficiently improve patients' quality of life, device-aided therapies (DATs) such as deep brain stimulation (DBS), continuous subcutaneous apomorphine infusion (CSAI), levodopa-carbidopa intestinal gel infusion (LCIG), levodopa-carbidopa-entacapone intestinal gel infusion, or continuous subcutaneous foslevodoa-foscarbidopa infusion are beneficial in the long run. However, sometimes patients need to switch or combine DATs due to either adverse events or loss of efficacy. The aim of this article was to summarise the existing data on the long-term efficacy and adverse events of DATs, and to review the data on the rationale and efficacy for switching or combining DATs in advanced PD. A total of 50 studies on the long-term efficacy of DBS (N = 28), LCIG (N = 12), CSAI (N = 10) and 13 studies on switching and combining DATs were included in this review. Although the DATs show a favourable long-term effect on the main motor and non-motor symptoms of PD they all feature specific adverse events that need to be considered when deciding which DAT to offer to a particular patient. Occasionally, switching or combining DATs is recommended, e.g. if the first DAT shows inadequate symptom control, or due to adverse events. The choice of the second DAT depends above all on the main problems of the first DAT being correctly recognised. DATs are a safe and long-term effective option for the treatment of advanced PD. Switching and/or combining DATs is recommended for patients in whom the first treatment option is not optimal. Future studies are warranted to address the unresolved issues related to long-term efficacy, side effect profile and switching and combination of DATs in multicentric studies and using advanced analytical approaches such as machine learning.

Controllability analysis for impulsive multi-agent systems with switching effects

Controllability analysis for impulsive multi-agent systems with switching effects

Time to Change: The Effect of Mask Switching on Continuous Positive Airway Pressure Adherence

Time to Change: The Effect of Mask Switching on Continuous Positive Airway Pressure Adherence

Cardiometabolic effect of switching from an efavirenz-based therapy to a dolutegravir-based therapy on clinical and virological outcomes among people living with HIV at the Yaoundé Central Hospital

Cardiometabolic effect of switching from an efavirenz-based therapy to a dolutegravir-based therapy on clinical and virological outcomes among people living with HIV at the Yaoundé Central Hospital

P0745 Effectiveness of Switching to Subcutaneous Infliximab in Inflammatory Bowel Disease Patients with Inadequate Biochemical Response during Intravenous Administration

P0745 Effectiveness of Switching to Subcutaneous Infliximab in Inflammatory Bowel Disease Patients with Inadequate Biochemical Response during Intravenous Administration

Impact of grain boundaries on the electronic properties and Schottky barrier height in MoS2@Au heterojunctions.

Using density functional theory (DFT) calculations we thoroughly explored the influence of grain boundaries (GBs) in monolayer MoS2 composed of S-polar (S5|7), Mo-polar (Mo5|7), and (4|8) edge dislocation, as well as an edge dislocation-double S vacancy complex (S4|6), and a dislocation-double S interstitial complex (S6|8), respectively, on the electronic properties of MoS2 and the Schottky barrier height (SBH) in MoS2@Au heterojunctions. Our findings demonstrate that GBs formed by edge dislocations can significantly reduce the SBH in defect-free MoS2, with the strongest effect for zigzag (4|8) GBs (-20% reduction) and the weakest for armchair (5|7) GBs (-10% reduction). In addition, a larger tilt angle in the GBs leads to a more pronounced decrease in the SBH, suggesting that the modulation of SBH in the MoS2@Au heterostructure and analogous systems can be accomplished by GB engineering. Our findings also suggest that planar defects with high mobility in MoS2 may contribute to the memory switching effect observed in MoS2-based memtransistors and the reduction caused by the presence of planar defects can partially contribute to the discrepancy observed between experimental measurements and theoretical SBH predictions at the MoS2@Au heterojunction.

A Review on Ferry Electrification: A Path towards Sustainable Maritime Transport

This paper reviews research and development efforts for ferries' electrification, focusing on energy supply grids, communication networks, charging systems, and energy storage. It analyzes energy storage technologies, battery charging requirements, shore side infrastructure design, power system architecture, and alternative battery charging stations[1]. The study evaluates the effectiveness of using an electric/hybrid ferry boat for tourist transportation in a real case. The optimal system configuration depends on engine power, energy storage, photovoltaic system sizes, and percentage of hybrid or pure electric usage. The analysis can be replicated to other cases, showing the potential of new technologies for sustainable boating and improving passenger service, especially in terms of comfort[15]. One of the most important steps in lowering greenhouse gas emissions and the marine industry's reliance on fossil fuels is the electrification of ships. This analysis examines the technical developments, difficulties, and environmental effects of switching from conventional fossil fuel-powered ships to electric and hybrid ships. The future of fully electric ships, legislative efforts, and how these advancements relate to international sustainability goals are also covered in the study.

Effectiveness of switching strategies in CGRP monoclonal antibody therapy for migraine: A retrospective cohort study.

To evaluate the effectiveness of first switching between monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) or its receptor in the treatment of migraine. Although mAbs targeting CGRP or its receptor have emerged as a leading treatment for migraine prevention, a proportion of patients do not respond. While switching between these antibodies is a common clinical practice in such cases, the effectiveness remains a subject of study. We conducted a retrospective cohort study at a tertiary headache center, analyzing data from clinical records of patients treated with anti-CGRP mAbs from January 2020 to March 2024. Baseline was defined as the monthly headache days (MHDs) in the 3 months prior to the start of the second mAb. The primary endpoint was the change in MHDs at month 3 and month 6 following the switch. Additionally, we evaluated response rates in both periods. Subgroup analyses were conducted based on changes in mechanism of action. Finally, we assessed the influence of the number of doses of the first mAb and the inter-treatment interval. Out of 1244 initially identified patients, 185 were included in the month-3 analysis and 123 in the month-6 evaluation. The median MHDs decreased from 27.0 (interquartile range [IQR] 16.1, 30.0; range 5.0, 30.7) at baseline to 21.0 (IQR 10.0, 30.0; range 0.0, 30.0; p < 0.001) at month 3, and to 20.0 (IQR 10.0, 30.0; range 0.0, 31.0; p < 0.001) at month 6. Subgroup analyses revealed no significant differences in MHDs between maintaining the same target or changing it (baseline: 28.0 [IQR 16.2, 30.0; range 5.0, 31.0] vs. 27.0 [IQR 6.0, 31.0; range 6.0, 31.0]; month 3: 23.0 [IQR 10.0, 30.0; range 0.0, 31.0] vs. 19.0 [IQR 11.0, 30.0; range 1.0, 31.0], p = 0.144; month 6: 24.0 [IQR 11.0, 30.0; range 0.0, 31.0] vs. 17.0 [IQR 10.0, 30.0; range 3.0, 31.0], p = 0.170). There was no association between a ≥50% reduction in MHDs and the number of previous doses of the first mAb (odds ratio [OR] 1.0; 95% confidence interval [CI] 1.0, 1.1; p = 0.189) or the inter-treatment interval (OR 1.0; 95% CI 0.9, 1.1; p = 0.914). Switching between anti-CGRP mAbs resulted in a reduction in MHDs, with no significant differences based on the mechanism of action. Factors such as the number of doses of the first mAb and the inter-treatment interval did not appear to predict a ≥50% reduction in MHDs at month 3. Our findings support the viability of switching as an effective treatment option for patients with migraine who do not respond to initial mAb therapy.

Assessing healthcare cost changes associated with transitioning away from cigarette smoking using healthcare claims data: an exploratory study among adult male patients with COPD

Abstract Background The assessment of potential health effects of switching from cigarette smoking to non-combustible tobacco products has important implications for public health and regulatory decisions. Robust epidemiological evidence requires long-term follow-up of a large number of individuals. Real-world evidence derived from health records has the potential to help fill the gap in the interim. To our knowledge, this is the first study using individual-level healthcare claims data to assess the potential impact of transitioning from cigarette smoking to smokeless tobacco on short-term direct healthcare costs. Methods We conducted a retrospective cohort study of adult male patients with COPD who smoked cigarettes at baseline using the MarketScan® Databases. We compared changes in direct healthcare costs between the 12-month periods before (baseline) and after the index date (follow-up) across three cohorts: continued smoking (CS), quit all tobacco (QT), or switched to smokeless tobacco (SW), using a non-linear difference-in-differences model with average marginal effects. Results A total of 23,427 COPD patients were included (CS: 11,167; QT: 12,013; SW: 247). At baseline, the QT cohort had the highest total average healthcare costs ($43,771), followed by SW ($38,419), and CS ($27,149). The unadjusted difference-in-differences model revealed no statistically significant differences in total healthcare cost changes when comparing the QT or SW cohorts to the CS cohort (-$1,532 [95% CI: -$3,671, $608] for the QT cohort, and -$452 [95% CI: -$15,415, $14,511] for the SW cohort). After adjusting for Deyo-Charlson Comorbidity Index and COPD exacerbation, assuming patients had two comorbidities and exacerbations, the QT cohort had greater reduction in total healthcare costs compared to the CS cohort (-$2,910 dollars [95% CI: -$4,485, $-1,335]). The same trend was observed for the SW cohort, although the estimate was not statistically significant (-$5,312 [95%CI: -$11,067, $442], p = 0.08). Conclusions This study demonstrated the feasibility of using administrative claims to conduct real-world evidence studies on the harm-reduction potential of non-combustible tobacco products and found evidence suggesting reductions in direct healthcare costs after quitting tobacco or switching to smokeless tobacco among patients with COPD. Based on the learnings and limitations identified during the study, we propose concrete recommendations to improve future observational studies by integrating additional real-world healthcare data from multiple data sources.

Density Functional Theory Insights into Conduction Mechanisms in Perovskite-Type RCoO3 Nanofibers for Future Resistive Random-Access Memory Applications.

In the era of artificial intelligence and Internet of Things, data storage has an important impact on the future development direction of data analysis. Resistive random-access memory (RRAM) devices are the research hotspot in the era of artificial intelligence and Internet of Things. Perovskite-type rare-earth metal oxides are common functional materials and considered promising candidates for RRAM devices because their interesting electronic properties depend on the interaction between oxygen ions, transition metals, and rare-earth metals. LaCoO3, NdCoO3, and SmCoO3 are typical rare-earth cobaltates (RCoO3). These perovskite materials were fabricated by electrospinning and the calcination method. The aim of this study was to investigate the resistive switching effect in the RCoO3 structure. The oxygen vacancies in RCoO3 are helpful to form conductive filaments, which dominates the resistance transition mechanism of Pt/RCoO3/Pt. The electronic properties of RCoO3 were investigated, including the barrier height and the shape of the conductive filaments. This study confirmed the potential application of LaCoO3, NdCoO3, and SmCoO3 in memory storage devices.

CA1 ensembles expressing immediate-early genes are driven by context switch, shrink with sustained presence, and show no effect of change of task demands.

The hippocampus (HPC) is essential for navigation and memory, tracking environmental continuity and change, including navigation relative to moving targets. CA1 ensembles expressing immediate-early gene (IEG) Arc and Homer1a RNA are contextually specific. While IEG expression correlates with HPC-dependent task demands, the effects of behavioral demands on IEG-expressing ensembles remain unclear. In three experiments, we investigated the effects of context switch, sustained presence, and task demands on dorso-proximal CA1 IEG+ ensembles in rats. Experiment 1 showed that the size of IEG+ (Arc, Homer1a RNA) ensembles dropped to baseline during uninterrupted 30-minute exploration, reflecting familiarization, unless a context switch was present. Context-specificity of the ensembles depended on both environment identity and timing of the context switch. Experiment 2 found no effect of HPC-dependent mobile robot avoidance or HPC-independent avoidance of a stationary robot on IEG+ ensembles beyond mere exploration. Experiment 3 replicated these findings for c-Fos protein. The data suggest that IEG+ ensembles are driven by a context switch and shrink over time during sustained presence in the same environment. We found no evidence of task demands or their change affecting the size, stability over time, or task-specificity of IEG+ ensembles. These results shed light on the temporal dynamics of CA1 IEG+ ensembles, and their control by contextual and behavioral factors.

Long-Term Clinical and Economic Effects of Switching to Once-Weekly Semaglutide from Other GLP-1 RAs Among Patients with Type2 Diabetes in China: A Modeling Projection Study.

Previous studies, using clinical trial data, demonstrated that once-weekly (OW) semaglutide is dominant versus other glucagon-like peptide1 receptor agonists (GLP-1 RAs) in China. This study aims to evaluate the long-term clinical and economic effects of switching to OW semaglutide from other GLP-1 RAs among patients with type2 diabetes mellitus (T2DM) in China. The Institute of Health Economics Diabetes Cohort Model (IHE-DCM) was used to project life expectancy, quality-adjusted life years (QALYs), and total direct medical cost over 40years from a Chinese healthcare system perspective. Baseline characteristics, clinical effectiveness, and the treatment dose of OW semaglutide were derived from previously real-world studies. Patients were assumed to switch to semaglutide or continue previous GLP-1 RAs for 3years and change to intensive therapy. Drug prices were based on the median bidding price in January 2024 in China. Costs of other GLP-1 RAs were calculated on the basis of their market share in China. All costs were accounted as 2023 Chinese yuan (CNY). A discount of 5% was applied. One-way sensitivity analyses and probabilistic sensitivity analyses were used to test the robustness of the base-case result. The results show that switching to OW semaglutide from other GLP-1 RAs among patients with T2DM in China can improve life expectancy by 0.02years and afford an additional 0.12 QALYs per patient. Meanwhile, switching to OW semaglutide is associated with decreased total lifetime direct medical costs of 4204 CNY per patient, mainly resulting from savings in microvascular costs (2214 CNY) and macrovascular costs (1228 CNY). Sensitivity analyses show the robustness of modeling projection findings. Based on real-world data from China, this modeling projection study demonstrates that switching to OW semaglutide from other GLP-1 RAs can have better clinical and economic effects for patients with T2DM in China, indicating it as a dominant treatment choice.

ON THE STABILITY BY THE NONLINEAR NON-STATIONARY HYBRID APPROXIMATION

The paper investigates the effect of non-stationary perturbations on the stability of nonlinear nonautonomous systems with switching and impulsive effects. Sufficient conditions have been obtained to guarantee the asymptotic stability of a given equilibrium position of the initial system, and restrictions have been established under which the asymptotic stability is preserved under perturbations acting on the system. Note that the non-stationarities present both in the system itself and in perturbations can be described by unbounded functions with respect to time, as well as functions arbitrarily close to zero. It is assumed that the basic system is homogeneous in terms of the state vector. To find the required results, the second Lyapunov method is used in combination with the theory of differential inequalities.