Access Program Research Articles

Prospective study of the real impact of fusion centered genomic assays in patient management in a national collaborative group: the GETHI-XX-16 study.

Precision medicine represents a paradigm shift in oncology. Access to genetic testing and targeted therapies is frequently limited. Assays based on DNA sequencing can miss druggable alterations. We aimed to determine the impact of a free access program to RNA tests in patient management. We designed a multicenter prospective observational study within the Spanish National Group for Translational Oncology and Rare and Orphan Tumors (GETTHI). Eligible patients were adults with solid cancers that had progressed on standard therapies. Tumor samples were analyzed using two RNA sequencing assays (Trailblaze PharosTM and Archer FusionPlex Solid TumorTM). A central committee evaluated the actionability of genetic alterations and reported the findings to attending physicians, who made the final clinical management decisions. Between November 2016 and April 2019, 395 patients with 41 different tumors across 30 hospitals were included. Molecular analysis revealed actionable genetic alterations in 57 individuals (14.4%). Targeted therapies were advised for 23 and seven received a matched targeted therapy: two lung cancers (EML4-ALK and CD74-ROS1 fusion), three glioblastomas (EGFR point mutations), one oligodendroglioma (FGFR3-TACC3 fusion) and a prostate cancer (SND1-BRAF fusion). The outcomes included two tumor responses, one disease stabilization, one early withdrawal due to toxicity, one progression, and one unknown. Despite the growing knowledge of cancer biology and its translation to drug development, the overall impact of personalized treatments remains low. Access to comprehensive molecular tests covering properly all known actionable alterations and programs for a wide access to targeted therapies seem to be critical steps.

Tumor Necrosis Alpha (TNF-α) Antagonists Used in Chronic Inflammatory Rheumatic Diseases: Risks and their Minimization Measures.

Tumor necrosis factor alpha (TNF- α) inhibitors are widely employed for the management of chronic inflammatory rheumatism. However, their usage carries significant risks, including site and infusion reactions, serious infections, malignancy, heart failure autoimmune and demyelinating disorders. These risks are comprehensively outlined in risk management plans (RMPs) associated with these molecules. RMP provides information on the safety profile of a medicinal product as well as the measures that will be taken to minimize risks; these are known as risk minimization measures. These measures are divided into routine measures related to elements, such as the summary of product characteristics, labeling, pack size, package leaflet, or legal supply status of the product, while additional measures may include educational programs, including tools for healthcare providers and patients, controlled access or pregnancy prevention programs, among others. Additional measures can consist of one or more interventions that need to be implemented in a sustainable way in a defined target group, while respecting the timing and frequency of any intervention and procedures to reach the target population. An evaluation of the effectiveness of these measures is required to determine whether or not an intervention has been effective. This comprehensive review offers an in-depth exploration of the current treatment, uses, and associated risks of TNF-α inhibitors. Additionally, it provides a detailed account of risk minimization measures and risk management practices while shedding light on their real-world implementation and effectiveness.

Mindfulness improves psychological health and supports health behaviour cognitions: Evidence from a pragmatic RCT of a digital mindfulness-based intervention.

Mindfulness-based interventions can improve psychological health; yet the mechanisms of change are underexplored. This pre-registered remote RCT evaluated a freely accessible digital mindfulness programme aiming to improve well-being, mental health and sleep quality. Health behaviour cognitions were explored as possible mediators. Participants from 91 countries (N = 1247, Mage = 27.03 [9.04]) were randomized to 30 days of mindfulness practice or attention-matched control condition. Measures of well-being, depression, anxiety, stress, sleep quality, barriers self-efficacy, self-regulation and behavioural predictors (e.g., attitudes and behavioural intentions) were taken at baseline, 1-month (post-intervention) and 2-months (follow-up). Linear regression examined intervention effects between and within groups. Longitudinal mediation analyses explored indirect effects through health behaviour cognitions. Three hundred participants completed post-intervention measures. Those receiving mindfulness training reported significantly better well-being (Mdifference = 2.34, 95%CIs .45-4.24, p = .016), lower depression (Mdifference = -1.47, 95%CIs -2.38 to -.56, p = .002) and anxiety symptoms (Mdifference = -.77, 95%CIs -1.51 to -.02, p = .045) than controls. Improvements in well-being and depression were maintained at follow-up. Intervention effects on primary outcomes were mediated by attitudes towards health maintenance and behavioural intentions. Mediating effects of attitudes remained when controlling for prior scores in models of depression and well-being. Digital, self-administered mindfulness practice for 30 days meaningfully improved psychological health, at least partially due to improved attitudes towards health behaviours and stronger behavioural intentions. This trial found that digital mindfulness is a promising and scalable well-being tool for the general population, and highlighted its role in supporting health behaviours.

Building a sustainable creative economy: The influence of capital access and government programs

The future of Indonesia's economy lies in the creative economy, contributing to GDP and creating jobs. This research is important to understand the policies, entrepreneurial skills, and impact of the creative industry on cultural heritage. The creative industry in Bojonegoro faces the challenge of limited research in several areas. This study analyzes the relationship between access to capital, cultural heritage, and government programs on the performance and growth of the creative industry. This study uses a quantitative method with SEM-PLS to analyze the complex relationships between constructs in the creative industry in Bojonegoro. Samples were taken purposively from creative industry players, with 127 respondents. Data were collected through questionnaires, interviews, and observations to understand the factors that influence the growth of the creative industry. The variables studied include Government Programs, Cultural Heritage, Access to Capital, Creative Industry Performance, and Creative Industry Growth. Testing is done by ensuring the validity and reliability of the data, and analyzing R-Square and hypotheses using T-statistics to confirm the relationship between variables. In this analysis, the accepted hypothesis shows that access to capital has a significant effect on access to capital with an O value of 0.850, T-statistics 23.307, and P-values 0.000. In addition, access to capital also has a positive effect on the growth of the creative industry with O 0.494, T-statistics 5.213, and P-values 0.000. The performance of the creative industry also has a significant effect on the growth of the creative industry, with O 0.446, T-statistics 4.129, and P-values 0.000. Finally, access to capital through the performance of the creative industry has a positive effect on the growth of the creative industry, with O 0.379, T-statistics 4.117, and P-values 0.000. This study confirms the importance of access to capital in supporting the performance and growth of the creative industry. This study found a significant relationship between access to capital, creative industry performance, and the growth of the creative industry in Indonesia. The hypothesis stating that access to capital has a positive effect is accepted, while the hypothesis related to cultural heritage and government programs is rejected. Policy recommendations are focused on strengthening access to capital and preserving cultural heritage to support sustainable creative industries.

Real-World Evidence of Crizanlizumab Showing Reductions in Vaso-Occlusive Crises and Opioid Usage in Sickle Cell Disease.

Access to crizanlizumab, a disease-modifying therapy for sickle cell disease (SCD), was provided through a managed access program (MAP, NCT03720626). The present analysis evaluated the impact of 12 months of crizanlizumab treatment on vaso-occlusive crises (VOCs), and on the use of opioids for VOC-related pain relief, in patients with SCD from the MAP. From June 2018 to January 2023, 112 patients with a history of recurrent VOCs completed 12 months of crizanlizumab (5 mg/kg) treatment and were monitored for adverse events (AEs). Crizanlizumab led to reductions of 18.0% and 36.2% in the proportions of patients having ≥ 1 home- and ≥ 1 healthcare-managed VOCs. Median absolute changes (interquartile range) from baseline in the rates of home- and healthcare-managed VOCs were -3.0 (-6.0, -1.0) and -2.0 (-4.0, 0), respectively. Data stratified by genotype and prior hydroxyurea use showed similar reductions in VOC rates. A 35.5% reduction in the proportion of patients requiring opioids was noted. AEs were consistent with earlier reports, and no new safety concerns were identified. Crizanlizumab demonstrated potential benefits in attenuating VOC episodes, irrespective of SCD genotype and prior hydroxyurea use, and in lowering opioid usage. The safety of crizanlizumab was consistent with earlier reports. The MAP has been registered at ClinicalTrials.gov with the ID, NCT03720626.

Age-based comparison of patients with heart failure treated with sacubitril-valsartan in France: a real-world evaluation

Abstract Background Sacubitril-Valsartan (S/V) was approved in Europe in 2015, for treatment of adults with symptomatic chronic heart failure with reduced left ventricular ejection fraction (HFrEF). In France, S/V had benefited from an early access program (2015-2018) and became available in community pharmacy since October 2018. Purpose Our study aimed to describe characteristics of patients who received S/V in France and to assess real-life mortality in this population regarding age. Methods This non-interventional retrospective study utilized existing claims data from the French National Healthcare Data System (SNDS) allowing long-term follow-up of patients who benefited from at least one reimbursement of S/V. Patient data between April 2012 and December 2020 were extracted from the database. Prespecified subgroup analyses were conducted for subjects aged <75 and ≥75 y to describe characteristics of patients at first reimbursement of S/V. Cardiovascular mortality and all-cause mortality were estimated using Kaplan-Meier method. Results Between 2015 and 2020, 104,910 patients initiated S/V and were followed for an average of 20 months; 42.6% (44,743 patients) were ≥75 y. Mean (SD) age difference between the 2 subgroups was 20.3 years [62.2 (9.6) vs 82.5 (5.2) in patients <75 and ≥75 y respectively]. Patients ≥75 y had a higher prevalence of atrial fibrillation (50.6% vs 31.2%) and chronic renal failure (20.9% vs 10.1%) and were less co-treated with mineralocorticoid-receptor antagonists (21.8% vs 40.5%) and ß-Blockers (64.0% vs 73.8%) compared to those <75 y. Three months after first dispensation, 48.3%, 35.3%, and 16.4% of patients aged ≥75 y received S/V dosages of 24/26mg, 49/51mg, and 97/103mg respectively, compared to 31.4%, 38.2%, and 30.4% for patients aged <75 y. The mean (SD) exposure period was 14.7 (13.6) months in patients ≥75 y vs 19.0 (15.5) months in <75 y patients. As expected, given the age difference, patients ≥75 y had a higher probability of all-cause mortality at 12-month 16.5% vs 6.2% in patients <75 y. Furthermore, 12-month cardiovascular mortality – evaluated during the early access program period (2015-2017) – in patients ≥75 y was 11.0% vs 4.8% in patients <75 y. Figures 1 and 2 show survival curves for cardiovascular mortality and all-cause mortality of these 2 subgroups. Of interest, cardiovascular mortality rate at 12 months was 7% in this study, compared to 6% in PARADIGM-HF, and all-cause mortality at 12-month was higher (10,6% vs 7%), likely due to the profile of the patients, who were older and have more comorbidities in real life. Finally, very few patients were hospitalized for reasons related to angioedema, 16/44,743 in ≥75 y patients and 26/60,167 in those <75 y. Conclusion This is the first French real-world study providing exhaustive nationwide data on S/V mortality over a period of almost 6 years in a very large population of elderly with a mean age of 70.9 y vs 63.8 y in PARADIGM-HF.Figure 1Figure 2

Transition of patients with familial chylomicronaemia syndrome from volanesorsen to olezarsen: safety and pharmacokinetic results

Abstract Background Familial chylomicronaemia syndrome (FCS) is a rare genetic disorder of lipoprotein lipase deficiency resulting in severe hypertriglyceridaemia and pancreatitis risk. Volanesorsen is a weekly-injected antisense oligonucleotide (ASO) designed to degrade APOC3 mRNA that is approved as an adjunct to diet to treat FCS in the EU, UK, and Brazil. Olezarsen is an investigational monthly-injected ASO-GalNAC3 conjugate also designed to degrade APOC3 mRNA, but directed to hepatocytes, resulting in more potency and less systemic exposure and making it a potential alternative to volanesorsen for FCS. Purpose This interim analysis of an open-label phase 3 trial evaluated olezarsen safety and pharmacokinetics in patients (pts) with FCS previously treated with volanesorsen. Methods Adults with FCS with prior volanesorsen treatment, or actively participating in an expanded access programme (US and Canada), started olezarsen 80 mg by subcutaneous injection every 4 weeks after a minimum washout of 6 weeks. Historical volanesorsen laboratory and safety data were unavailable. The primary objective was to assess safety from changes vs baseline in platelet count, liver enzymes, and renal function; bleeding events; and adverse events. Pharmacokinetic measurements included plasma volanesorsen and olezarsen concentrations. Immunogenicity was assessed by measuring anti-drug antibodies (Abs). Results Of 24 pts enrolled, the majority were female (n=13; 54.2%) and White (n=21; 87.5%), with mean age of 49.1 years; 20 (83.3%) had genetically and 4 (16.7%) clinically validated FCS, all had history of acute pancreatitis (or symptoms suggestive of pancreatitis requiring hospitalisation or emergency room/urgent care visit; mean, 3.4 episodes within 5 years) and 5 (20.8%) of thrombocytopaenia. Time since last volanesorsen dose was 42—1118 days. Baseline fasting triglyceride (median [interquartile range (IQR)], 18.6 [9.6,34.0] mmol/L [1648 (852,3007) mg/dL]; mean [standard deviation (SD)], 25.5 [20.5] mmol/L [2256 (1812) mg/dL]) and apolipoprotein C-III (median [IQR], 0.2 [0.1,0.4] g/L [16.1 (12.4,39.0) mg/dL]; mean [SD], 0.3 [0.2] g/L [25.9 (19.5) mg/dL]) levels were elevated. During a mean (SD) of 329 (95) days of olezarsen 80 mg treatment, no pts experienced hepatic failure, renal impairment, major bleeding events, or platelet count below the prespecified threshold of 50,000 mm³ (Table 1). Olezarsen levels at trough were elevated during the first 3 months, mainly due to residual volanesorsen levels in pts with washout <90 days (Figure 1). Eleven (45.8%) pts had treatment-emergent anti-olezarsen Abs, of whom 5 (20.8%) had anti-volanesorsen Abs, with no impact on safety or efficacy; pts with vs without anti-drug Abs had higher olezarsen trough levels (mean, 4.4–7.8 ng/mL vs 1.1 ng/mL). Conclusions In this interim analysis, olezarsen was safe and well tolerated in pts with FCS previously treated with volanesorsen after a minimum washout of 6 weeks.

Long-term safety of mepolizumab for up to ∼10 years in patients with severe asthma: open-label extension study

Objectives Long-term safety monitoring of mepolizumab is necessary to support real-world use for the treatment of severe asthma. This Long-Term Access Program assessed the safety and benefit:risk of mepolizumab in pediatric, adolescent, and adult patients with severe asthma. Materials and methods This was a multicenter, Phase IIIb safety, open-label extension study of multiple prior studies assessing mepolizumab in addition to standard of care (Aug 2015 − Aug 2022). Adults/adolescents (≥12 years of age) received mepolizumab 100 mg subcutaneously (SC) every 4 weeks until mepolizumab was commercialized. Pediatric patients (6–11 years of age) received mepolizumab 40 mg or 100 mg SC (bodyweight <40 or ≥40 kg, respectively) every 4 weeks. Safety was assessed every 4 weeks and benefit:risk every 12 weeks. Results Of the 514 patients enrolled, 57% were female and the mean age was 51.1 (standard deviation: 14.9) years; 24 (5%) patients were 6–17 years of age. Total cumulative mepolizumab exposure across all mepolizumab studies included in this analysis was 1500.59 patient-years; median exposure was 2.03 (range, 0.08 to 9.97) years. Overall, 37 (7%) patients experienced on-treatment serious adverse events (SAEs): 34/502 (7%) in the 100 mg SC group and 3/7 (43%) in the 40 mg SC pediatric group. Two patients experienced SAEs considered to be treatment-related by the investigator. Infections were the most common SAEs of special interest (9 [2%] patients). Physician-assessed benefit:risk of mepolizumab supported continued treatment over the study period. Conclusions This long-term safety analysis of mepolizumab was consistent with previous reports, with no emerging safety concerns; most patients had a favorable benefit:risk up to ∼10 years. Clinical trial identifier NCT00244686 (GSK ID 201956)

Patient and provider costs of the new BPaL regimen for drug-resistant tuberculosis treatment in South Africa: A cost-effectiveness analysis.

Drug-resistant (DR) tuberculosis (TB) is typically characterized by resistance to a single or combination of first- and/or second-line anti-TB agents and commonly includes rifampicin-resistant (RR)-TB, multidrug-resistant (MDR)-TB, pre-extensively drug-resistant (pre-XDR)-TB and XDR-TB. Historically, all variations of DR-TB required treatment with second-line drugs which are less effective and more toxic than first-line options, have a longer treatment duration and are more expensive to both patients and providers. The World Health Organization (WHO) now recommends a new second-line 3-drug 6-month all-oral regimen consisting of bedaquiline, pretomanid, and linezolid referred to as BPaL. We estimate patient and provider costs of DR-TB treatment with BPaL compared to the current standard of care in South Africa. In coordination with South Africa's BPaL clinical access programme (CAP) we conducted an economic evaluation of A) patient costs through a cross-sectional patient cost survey and B) provider costs through a bottom-up costing analysis consisting of a retrospective medical record review (patient resource-use) and top-down financial record review (fixed/shared costs such as overhead). Across both costing perspectives, we compare costs of 1) BPaL, to current standard of care options including the 2) 9-11-month standard short oral regimen (SSOR) and 3) 18-21-month standard long oral regimen (SLOR). Eligible patients included those ≥14 years old with confirmed sputum pulmonary RR/MDR-TB, pre-XDR or XDR-TB. All costs are reported in 2022 United States Dollar (US$). A total of 72 patients were enrolled and completed the patient cost survey (41.7% on BPaL, 16.7% on the SSOR and 41.7% on the SLOR). Mean on-treatment patient costs were lowest among those on BPaL ($56.6) and increased four-fold among those on the SSOR ($228.1) and SLOR ($224.7). Direct medical patient costs were negligible across all treatment regimens, while direct non-medical patient and guardian costs for travel, food and nutritional supplementation accounted for the largest proportion of total costs ($54.6, $227.8 and $224.3 for BPaL, the SSOR and SLOR respectively). In assessing provider costs, a total of 112 medical records were reviewed (37.5%, 41.1% and 21.4% on BPaL, the SSOR and SLOR respectively). Total provider costs for producing a favorable treatment outcome (cured/completed treatment) were similar among those on BPaL ($4,948.7 per patient) and the SSOR ($4,905.6 per patient) with costs increasing substantially among those on the SLOR ($8,919.9 per patient). Based on incremental cost-effectiveness ratios (ICERs), at even the lowest willingness to pay (WTP) threshold, treatment with the new BPaL regimen was more cost-effective than current standard of care treatment options (ICER: $311.4 < WTP: $3,341). When using the newly recommended BPaL regimen, cost to patients decreased by 75% compared to current standard of care treatment options in South Africa. Due in part to higher resource-use within the BPaL CAP offsetting the shorter treatment duration, cost of treatment provision through BPaL and the 9-11-month SSOR were similar. However, when considering cost and treatment outcomes, BPaL was more cost-effective than other standard of care regimens currently available for DR-TB in South Africa.

The establishment and potential spread of Osmia cornuta (Hymenoptera: Megachilidae) in North America.

Mason bees, subgenus Osmia Panzer (Hymenoptera: Megachilidae), are economically and ecologically significant pollinators. In eastern North America, the rapid spread of 2 non-native species from Asia, Osmia cornifrons Radoszkowski and Osmia taurus Smith, has coincided with declines in native Osmia populations, raising concern about the effects of further exotic arrivals. Here we investigate the recent establishment in British Columbia, Canada of the European orchard bee, Osmia cornuta Latreille, previously thought to be limited to Europe and its periphery. We document O. cornuta records ranging more than 170 km, including sightings of live adults and the discovery of a multigenerational nest with hundreds of cocoons. We tested whether these cocoons could be discriminated from other Osmia species by training a machine learning classifier on features extracted from images. The best performing model could not reliably discriminate cocoons by species, raising the possibility O. cornuta could be inadvertently intermingled in future commercial shipments. Recent occurrence records of O. cornifrons and O. taurus were spatially isolated, suggesting ongoing anthropogenic dispersal of these species. We predicted the suitability of North American habitats for O. cornuta by estimating its native climate niche. This analysis indicated broad regions of the Pacific Northwest and eastern North America contain potentially suitable habitat. Our findings document the establishment of O. cornuta in North America and the potential for its expansion. Our study demonstrates the utility of accessible biodiversity data archives and public observation programs in tracking non-native species spread and highlights the need for future monitoring of exotic Osmia.

Global initiatives and challenges in integrating artificial intelligence literacy in elementary education: Mapping policies and empirical literature

AbstractArtificial intelligence (AI) has permeated most facets of life in the 21st century and has rapidly transformed various aspects of modern society. From entertainment to education, these advanced technologies have achieved a high level of competency in skills that once necessitated human involvement. Given AI's potential impact, ensuring students are literate in AI will support the careful integration of these advanced technologies to achieve sustainable development goals. This review hence examines the avenues for integrating AI literacy into elementary education by analyzing current global initiatives focused on implementing AI literacy education. The purpose is to support innovations within the educational framework to develop a universally accessible AI literacy education program. In line with this purpose, this study explores worldwide AI literacy initiatives that use hands‐on activities, collaborative learning, and project‐based learning to introduce AI fundamentals to diverse learners. Limitations on the provision of AI literacy education are also discussed, including professional development, openness to AI tools, and other challenges. This review aims to inform global efforts to support universal access to AI literacy education, which can ensure equitable outcomes for all learners, emphasizing the need for collaborative efforts to support the development and delivery of quality AI literacy education.

Bridging Gaps in STEM Education: The Case for Dedicated Learning Centres in South African Townships and Rural Areas

This article explores the critical need for improved Mathematics, Science, Engineering and Technology (STEM) education in South African townships and rural areas, where persistent challenges in teaching methods and resource accessibility have hindered the development of these crucial subjects. The perception of Mathematics and Science as complex subjects, coupled with societal pressures to prioritise less ‘challenging’ subjects, has resulted in a quantity-over-quality approach to education. This article argues for establishing dedicated Mathematics, Science, Engineering, and technology centres in these underserved regions, drawing upon global research findings that underscore the importance of continuous improvement in STEM subjects for individual and national advancement. The proposed centres aim to address educational disparities by providing innovative teaching methods, resource access, and mentorship programs. These proposed centres intend to rectify educational disparities by offering innovative teaching methods, improved resource access, and mentorship programs. Through examining successful case studies and potential challenges, this article calls for a comprehensive approach to reshape the STEM education landscape in South African townships and rural areas, contributing to a more equitable and robust educational system.

P3.12E.04 Long-Term Outcomes with Sotorasib in KRAS G12c-Mutated Advanced NSCLC from the Global Expanded Access Program (EAP) Study-436

P3.12E.04 Long-Term Outcomes with Sotorasib in KRAS G12c-Mutated Advanced NSCLC from the Global Expanded Access Program (EAP) Study-436

Clinicians' priorities for exercise programming for people receiving peritoneal dialysis: Qualitative content analysis from an international survey.

Exercise and physical activity have been shown to improve health outcomes among people receiving peritoneal dialysis (PD), however, little is known about PD clinicians' perceptions and practices regarding exercise counselling. To inform exercise program design and implementation, we distributed a cross-sectional online questionnaire to PD clinicians between July and December 2021 through professional nephrology societies and networks. As part of this survey, participants were asked, "What are the most important aspects you would like to see incorporated in an exercise program for PD patients?" Six hundred and nine respondents provided 1249 unique perspectives. Responses were coded using summative content analysis and grouped into themes. The overarching theme identified was the need for individualized and accessible programming. Under this umbrella, the four main sub-themes identified were: promotion of specific exercises, overcoming common barriers to exercise, perceived cornerstones of exercise prescriptions, and program design to address patient-relevant outcomes. Overall, PD clinicians believed that PD does not preclude exercise participation and recognized the potential for exercise to improve physical, mental, and social well-being. The involvement of exercise professionals was valued in PD clinical programs. However, additional education for practitioners and patients regarding safety and the benefits of exercise is required to assist in widespread implementation and acceptance of exercise programming in the PD population.

Recognizing the Unseen: Enhancing Family Caregiver Education in Morocco's Cancer Care.

During my thesis, I had the opportunity to work closely with family caregivers of cancer patients. This allowed me to meet these individuals and hear their stories filled with suffering. A large part of their complaints centered on the lack of information and training necessary to properly care for their ill relatives. Often, they find themselves responsible for a patient at home without possessing the required skills, sometimes knowing only the dosage of treatments to administer. This lack of training can lead to serious complications, such as bedsores in immobile patients or urinary infections. This experience underscores the critical need for comprehensive caregiver education in Morocco, a country where family caregivers play a crucial role in oncology care, especially in home-based support.To achieve this, the government, health care professionals, and NGOs must collaborate to develop accessible educational programs that equip caregivers with the necessary skills and knowledge.

Type 1 spinal muscular atrophy treated with nusinersen in Norway, a five-year follow-up

BackgroundNew treatments for 5q spinal muscular atrophy (SMA) have led to changes in the disease phenotype. Questions about long-term efficacy, however, persist. We present the results from five-year follow-up of the first ten Norwegian patients with SMA type1 treated with nusinersen. Methods– Ten patients referred to the expanded access program were included. Standardized assessments with Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND), the Hammersmith Infant Neurological Examination (HINE-2), compound muscle action potential (CMAP) examination and cerebrospinal fluid analysis of neurofilament light chain (cNfL) were performed. ResultAge at baseline ranged from three months to 11 years and eight months. Nine patients were alive and continued to receive treatment at 62 months of follow-up. CHOP INTEND scores increased significantly up to 38 months. Any further increase from 38 to 50 months was not statistically significant, and scores remained almost unchanged from 50 to 62 months. HINE-2 scores increased but the difference from baseline never reached statistical significance.The youngest patients showed the best motor outcome. The changes in CMAP scores were not statistically significant. cNfL values were significantly reduced after 18 months compared with baseline; the largest difference occurred between baseline and 6 months. There was a significant negative correlation between log cNfL and CHOP INTEND (p = 0.042). Bulbar and respiratory function did not improve during the observation period. ConclusionOur findings support previously reported results on efficacy and safety of nusinersen. All patients have shown improvement in motor function. The need of respiratory and nutritional support did not improve.

Perspective: Expanding Pediatric Mental Health Care Access Programs Into Hospital Settings.

Perspective: Expanding Pediatric Mental Health Care Access Programs Into Hospital Settings.

Spesolimab, the first-in-class anti-IL-36R antibody: From bench to clinic.

Inflammatory diseases that are driven by several pro-inflammatory cytokines has resulted in in the development of targeted therapies across different disease settings. Interleukin (IL)-36 cytokines have been implicated in several inflammatory diseases. In this review we describe the scientific evidence surrounding the use of the IL-36 receptor (IL-36R)-targeting antibody, spesolimab, in IL-36-mediated skin diseases: generalized pustular psoriasis (GPP), palmoplantar pustulosis (PPP), hidradenitis suppurativa, and Netherton syndrome (NS). Spesolimab, a high affinity, specific, humanized, antagonistic immunoglobulin G1 antibody, targets the IL-36R at a binding site distinct from its agonists, IL-36α/β/γ, and at least one endogenous antagonist, IL-36R antagonist. Invitro and invivo data for spesolimab show effective inhibition of IL-36R-mediated signaling pathways, and six Phase I studies in healthy volunteers presented a favorable safety and pharmacokinetic (PK) profile, leading to the development of a clinical trial program to evaluate spesolimab in the treatment of IL-36R-mediated diseases. Six studies (including an expanded access program) have evaluated the efficacy, safety, PKs, and pharmacogenomics of spesolimab in patients with GPP flares. Spesolimab treatment of GPP flares resulted in rapid and sustained improvements in pustular and skin clearance, and clinically significant improvements in patient-reported symptoms and quality of life. Spesolimab also significantly reduces the risk of GPP flares and flare occurrence, preventing disease worsening and has a favorable safety profile. There have been three trials of spesolimab in PPP; further evaluation is needed to better define those patients who might benefit from the treatment. A trial of spesolimab in NS is ongoing, while other spesolimab trials suggest that IL-36 may only play a secondary role in the pathogenesis of atopic dermatitis. In conclusion, research into spesolimab has provided much needed insight into the role of IL-36 in the human immune system and the mechanism behind IL-36-mediated inflammatory diseases. Spesolimab provides an efficacious targeted treatment for GPP, a disease with a high unmet medical need.

Assessing the Responsiveness of Moulay Ismail University to Teachers' Continuous Professional Development Needs: A Mixed-Methods Analysis

This study investigates the responsiveness of Moulay Ismail University (UMI) to the continuous professional development (CPD) needs of its teaching staff. The study integrates both quantitative and qualitative methods to gain a comprehensive understanding of teachers' perspectives. The quantitative phase involved administering a structured questionnaire to 214 teachers, focusing on their perceptions of the university's CPD offerings, including availability, relevance, accessibility, and institutional support. Descriptive statistics were used to analyze this data, revealing a predominantly negative attitude among teachers towards their university's ability to meet their CPD needs. The qualitative phase involved semi-structured interviews with 21 teachers. These interviews provided deeper insights into teachers' barriers, such as the lack of relevant CPD activities, the irrelevance between CPD content and pedagogical needs, and the overwhelming workload that limits their capacity for professional growth. Thematic analysis of the interview transcripts identified key themes that aligned with the quantitative findings, offering a more nuanced perspective on the challenges associated with CPD at the UMI. The study concludes that the teachers at the UMI perceive the institution as largely unresponsive to their CPD needs. This sentiment echoes broader concerns within the literature about the neglect of university teachers' professional development in Morocco. The findings underscore the need for more relevant and accessible CPD programs tailored to the specific needs of faculty and institutional reforms that alleviate the workload pressures that hinder professional growth.

US suspension policy from the African Growth and Opportunity Act (AGOA): An estimation of the missing exports from sub‐Saharan Africa

AbstractThe African Growth and Opportunity Act (AGOA) is a unilateral duty‐free access program granted by the United States (US) to exports from sub‐Saharan African (SSA) countries. However, provisions of the AGOA text specify that countries can be suspended from the program in case of political turmoil and human rights violations that threaten democracy and the rule of law. This paper constructs a two‐step framework combining matching techniques and gravity regression to quantify the loss of exports due to AGOA suspensions using high‐disaggregated data of exports (10‐digit HTS level) from Africa to the US during 2001–2020. The AGOA suspension resulted in a 54% decline in SSA countries' exports to the US. Estimations suggest that, since 2004, the US suspension policy led to a reduction in exports from suspended countries of approximately 691 million USD on average per year. Over the 17 years (2004–2020), the suspended countries lost a total of 11.7 billion USD in the value of their exports to the US.