Access Program Research Articles

Infection and pulmonary vascular diseases consortium: United against a global health challenge.

Leveraging the potential of virtual platforms in the post-COVID-19 era, the Infection and Pulmonary Vascular Diseases Consortium (iPVDc), with the support of the Pulmonary Vascular Research Institute (PVRI), launched a globally accessible educational program to highlight top-notch research on inflammation and infectious diseases affecting the lung vasculature. This innovative virtual series has already successfully brought together distinguished investigators across five continents - Asia, Europe, South and North America, and Africa. Moreover, these open global forums have contributed to a comprehensive understanding of the complex interplay among immunology, inflammation, infection, and cardiopulmonary health, especially concerning pulmonary hypertension and related pulmonary disorders. These enlightening discussions have not only heightened awareness about the impact of various pathogenic microorganisms, including fungi, parasites, and viruses, on the onset and development of pulmonary vascular diseases but have also cast a spotlight on co-infections and neglected illnesses like schistosomiasis - a disease that continues to impose a heavy socioeconomic burden in numerous regions worldwide. Thus, the overall goal of this review article is to present the most recent breakthroughs from infectious PVDs as well as bring to light the scientific and educational insights from the 2023 iPVDc/PVRI virtual symposium series, shaping our understanding of these crucial health issues in this more than ever interconnected world.

The African Initiative for Bioinformatics Online Training in Neurodegenerative Diseases (AI‐BOND): Investing in the next generation of African neuroscientists

AbstractNeurodegenerative disorders, including Alzheimer's disease and AD‐related dementias (AD/ADRD), pose significant challenges to health care systems globally, particularly in Africa. With the advances in medical technology and research capabilities, especially in next‐generation sequencing and imaging, vast amounts of data have been generated from AD/ADRD research. Given that the greatest increase in AD/ADRD prevalence is expected to occur in Africa, it is critical to establish comprehensive bioinformatics training programs to help African scientists leverage existing data and collect additional information to untangle AD/ADRD heterogeneity in African populations. The South Texas Alzheimer's Disease Research Center, with efforts from the National Institutes of Health and the Global Brain Health Institute, has partnered with the Brain Research Africa Initiative to develop the African Initiative on Bioinformatics Online Training in Neurodegenerative Disease (AI‐BOND). AI‐BOND is a comprehensive and accessible training program, the aim of which is to advance biostatistics and bioinformatics expertise in Africa in studying neurodegenerative diseases. This expertise is essential to enable African scientists to utilize the extensive AD/ADRD data and enhance the continent's ability to contribute to global research efforts in this field. The training addresses the gap in analyzing neurodegenerative disease data by providing skills and knowledge in genetic epidemiology, biostatistics, and bioinformatics to African students and researchers. This innovative online training program will last 6 months and provide training in skill sets R, SAS, and Python programing, genome‐wide association studies, genomics, transcriptomics, proteomics, metabolomics, microbiome analysis, and advanced statistical methods. Additional training will include study design and manuscript and grant writing. The first cohort of the AI‐BOND program will graduate in June 2024. The AI‐BOND program is expected to build research computational capacities in Africa that will improve the ability of graduates to conduct and utilize large‐scale studies, with the goal of curbing the growing incidence of neurodegenerative diseases in Africa.Highlights Alzheimer's disease (AD) and AD‐related dementias (ADRD) pose significant health challenges globally, particularly in Africa. The most significant AD/ADRD prevalence increase is predicted to occur in Africa. It is crucial to establish a bioinformatics training capacity in Africa to leverage the vast number of multi‐omics and imaging biomarkers of AD/ADRD data being generated. The African Initiative on Bioinformatics Online Training in Neurodegenerative Disease (AI‐BOND) training addresses the gaps in study design, biostatistics, genetic epidemiology, and bioinformatics related to neurodegenerative diseases in Africa. The success of AI‐BOND is anticipated to help build computational research capacities in Africa.

Safety and efficacy of adipose-derived mesenchymal stem cell therapy in elderly Parkinson's disease patients: an intermediate-size expanded access program

ObjectiveThis intermediate-size expanded access program aimed to evaluate safety and clinical efficacy of multiple intravenous infusions of autologous, Hope Biosciences adipose-derived mesenchymal stem cell (HB-adMSC) therapy in elderly patients with Parkinson's disease (PD). MethodsTen eligible participants (aged 76–95 years) received six intravenous infusions each with 200MM autologous HB-adMSCs over 18 weeks, with the end of study (EOS) at week 26. Safety was assessed through adverse events (AEs) and serious adverse events (SAEs). Efficacy was measured through improvements in both motor and non-motor symptoms, utilizing scales including Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) parts I-IV, Parkinson's Disease Questionnaire-39 (PDQ-39), Parkinson's disease Fatigue Scale (PFS-16), Patient Health Questionnaire-9 (PHQ-9), and Visual Analog Scale (VAS). Analysis employed paired t-tests and Minimal Clinically Important Difference (MCID) thresholds for the patient-reported outcomes. ResultsMost AEs (37 out of 46) were mild in severity, with 5 SAEs reported, none attributed to the drug. No deaths occurred. Despite lack of statistical significance across the efficacy endpoints, modest yet clinically meaningful improvements with effect size > 0.3 were observed in several secondary efficacy endpoints (MDS-UPDRS part I & III, PDQ-39, and PHQ-9) at the EOS, nearing or surpassing the established MCID values. ConclusionsThe administration of autologous 200MM HB-adMSCs was found to be safe and well-tolerated in the elderly PD population. Although not achieving statistical significance, modest clinical improvements were noted across multiple secondary endpoints. These findings underscore the safety profile of the treatment in elderly patients and highlight the importance of evaluating clinical relevance alongside statistical measures for meaningful patient outcomes. Further investigation with a larger, randomized, placebo-controlled design is warranted to validate these observations.

Psychiatry Consultation in Primary Care: Examining Treatment Access for Adolescent Depression

PurposeYouth in the United States are experiencing mental health concerns at an unprecedented level. Child Psychiatry Access Programs offer an innovative approach to close the gap between the need for care and insufficient mental health workforce. This study examined whether primary care provider consultation with a Child Psychiatry Access Program, Michigan Clinical Consultation & Care (MC3), was associated with greater access to treatment for adolescents with moderate to severe depression symptoms. MethodsA retrospective chart review was conducted of primary care visits between 2017 and 2021 for adolescent patients with first-time positive scores on the Patient Health Questionnaire-9. Descriptive statistics and logistic regression were used to examine if patients whose primary care provider used MC3 psychiatric consultations had improved access to depression treatment compared to those who did not. ResultsFour hundred seventy nine patients reported Patient Health Questionnaire-9 scores indicating moderate to severe depression symptoms. Compared to non-MC3 consult patients (n = 409), MC3 consult patients (n = 70) had higher odds of being prescribed antidepressant medications (odds ratio [OR], 2.16; 95% confidence interval [CI] [1.11–4.22], p = .05), 4 times higher odds of having a primary care follow-up visit to monitor depression symptoms (OR, 4.56, 95% CI [2.56–8.14], p < .001), and higher odds of accessing mental health therapy (OR, 2.14; 95% CI [1.13–4.05], p = .05). DiscussionUse of MC3 consultations was associated with increased utilization of evidence-based depression treatments including medication, therapy, and follow-up care. Greater adoption of models such as MC3 may increase the capacity for addressing mental health needs in children.

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.

The real-world use and effectiveness of avacopan in routine practice for the treatment of ANCA vasculitis. First experiences in Spain.

ANCA-associated vasculitis (AAV) are chronic diseases with relapses that associate organic damage because of the disease and its treatment. Avacopan is a new treatment indicated for AAV. We present the first experiences with avacopan in Spain as part of an Early Access program. Patients with AAV who started avacopan between June 2022-September 2023 were included. For comparison, a historical cohort of patients diagnosed with AAV around the same time and treated without avacopan was also included. 29 patients treated with avacopan were analyzed. Twelve patients (41.4%) were male, median age was 56 years. Most of patients were ANCA MPO positive (21/29, 72.4%). The most frequently affected organ was the kidney (23/29, 79.31%), with a mean eGFR of 23.2 ml/minMedian follow-up was 456.8 ± 181.7 days with a remission rate of 86.2%. eGFR increased from 23.2 ± 11.2-38.38 ± 18.55 ml/min after 12 months of diagnosis.2 patients had Adverse Events related to avacopan as severe neutropenia and a gastrointestinal affectation , 13 infections were reported and 1 death.Patients treated with avacopan received a significantly lower cumulative dose of prednisone at 6 and 12 months (p-values of 0.02 and <0.01, respectively) compared with historical controls. The evolution of GFR at 1 year of follow-up and the incidence of relapse were similar in both groups. The combination of avacopan in clinical practice presents a good safety profile and provides added value by contributing to the control of AAV activity, increase GFR, and removal of steroids.

Experience with Iptacopan in Patients with Recurrent Complement 3 Glomerulopathy (C3G): Early Access Program Data

Experience with Iptacopan in Patients with Recurrent Complement 3 Glomerulopathy (C3G): Early Access Program Data

Cost effectiveness of a vascular access education and training program for hospitalized emergency department patients.

Education and training in vascular access is a critical component to delivering quality vascular access care. Given that organizations must invest resources to implement and sustain high-quality vascular access programming, we aimed to demonstrate the cost effectiveness of a program (Operation STICK (OSTICK)) in the emergency department (ED). This was an observational cohort study conducted at a tertiary care academic center with 120,000 ED visits. Consecutive hospitalized adults with ultrasound-guided (DIVA) and traditionally-placed (non-DIVA) peripheral intravenous catheters (PIVC) in the ED were included in the analysis. Two groups (OSTICK and non-OSTICK) were compared in the analysis: OSTICK PIVCs were inserted by clinicians with formal, standardized training in peripheral venous access while non-OSTICK PIVCs were inserted by staff with basic departmental training in PIVC care. Cost factors included number of procedures, wait time to establish a PIVC, complications, and training. Effect was complication-free PIVC functionality. Multiple linear regressions were used to estimate incremental cost (ΔC), incremental effect (ΔE), and incremental net benefit (INB) of the OSTICK program. From 10/1/2022 thru 3/31/2023, 21,259 PIVCs including 1681 OSTICK and 19,578 non-OSTICK PIVCs were included in the analysis. Average age was 64.8 and 53.7% were female. The estimate of incremental cost (ΔC) for each patient was -$83.175 (95% CI: -$103.953 to -$62.398; p<0.001), indicating that the OSTICK group saves money compared to the non-OSTICK group. The OSTICK group is also more effective at increasing the proportion of catheter dwell time relative to hospital length of stay (ΔE), with an estimate of 0.037 (95% CI: 0.016 to 0.059; p<0.001), compared to those in the non-OSTICK group. The estimated incremental cost-effectiveness ratio (ICER) for the OSTICK group compared with the non-OSTICK group was -$221.964 (95% CI: -$177.400 to -$381.716) per ten percentage points of PIVC dwell time to hospital length of stay increase. Strategic investment in vascular access education and training can yield impressive financial returns while simultaneously enhancing vascular access outcomes. It is imperative for organizations to recognize the significant impact of such initiatives and prioritize the implementation of comprehensive programs.

Seroconversion Toxoplasmosis as a predictor for gestational diabetes mellitus among pregnant ladies in Iraq

Background. Toxoplasma gondii (T.g.) can reach many host organs including the pancreas and pancreatic tissue may be directly attacked and compromised by the organisms. Aim. This study aimed to evaluate the risk of toxoplasmosis infestation as a predictor of gestational diabetes mellitus (GDM) among pregnant ladies in Thi-Qar, Southern Iraq. Methodology. A case-control study was conducted on 151 pregnant ladies classified (61) with GDM and (89) healthy pregnant ladies attending a tertiary Endocrine Center. All patient data were gathered from direct interviews and the digital records of the tertiary center, which used an internal network system and Microsoft Access program. Each pregnant woman was diagnosed with new GDM according to the American Diabetes Association (ADA) definition criteria. Results. The mean ages of the whole participants were 28 ±6 years old and more than half of them were in the second decade of life, their mean weight was 75.38±13.29) kg and their body mass index was 29.82 ± 5.23 (Kg/m2). Family history of DM, history of toxoplasmosis infestation, and positive serological test of IgG for toxoplasmosis was significantly predominant among women with GDM rather than those without (p-value= 0.007, 0.002, 0.004 respectively). Conclusions. The second decade of age is the independent risk factor for developing new GDM, while toxoplasmosis infestation and positive IGG were additive-dependent risk factors for developing new GDM in collaboration with other patients' profiles. Pregnant women with GDM were significantly older, heavier in body weight, and obese than those without GDM making them at higher risk factors for getting hyperglycemia.

Outcome Measures And Analysis Of Memory Movers- An Exercise Programme For The Brain, Body And Mind

Abstract Background Memory Movers is a six-week early intervention specialist programme designed for implementation in community settings to meet key healthcare needs for individuals experiencing memory difficulties/dementia and their family carers. This programme provides individuals with the knowledge, skills and education to care for their overall health and well-being. It supports mental health and well-being by utilising cognitive stimulation exercises in conjunction with physical health exercises and providing information and basic exercises in mental health. Methods The Specialist Mental Health Service for Older People collaborated with an Acute Hospital, local Council, and Sports and Wellbeing Partnership in designing a suitable, accessible programme to promote Mental Health and well-being in the community. The programme incorporates the following aspects of health: Memory, Movement, and Mental Health. Results Pre- and post-assessments were undertaken with results highlighting the following: The Life Satisfaction Scale improved by 6%; the Mood Rating Scale improved by 19% and the overall rating of experiencing feelings of anxiety was reduced by 14% within the final week. There was also a 101% increase in the average engagement in physical activity. A range of positive comments received from attendees were recorded on feedback questionnaires. Conclusion Findings highlighted that remaining active supports both physical and mental health. According to the HSE (2020), physical exercise can cause chemical changes in the brain, which can help improve mood. Cognitive stimulation is beneficial to brain health and cognition (Schulz 2015). These contribute to the overall well-being of individuals, promoting cognitive functioning and movement, as well as overall mental health and well-being. This programme also provides opportunities for social connection and integration with services.

Family and Staff Cooperation in Early Childhood Special Education

Introduction: Early childhood is a critical period for supporting children's development. The role of families and the staff responsible for the services is crucial in supports to be provided in the development of children with special needs. In this study, stakeholders' cooperation processes were examined in the context of family-staff and staff-staff cooperation. Method: The participants are 12 staff and seven parents at a special education center. The data of the study, which was conducted in the phenomenological design of qualitative research methods, were obtained with the semi-structured interview technique and analyzed with content analysis. Findings: Findings were discussed under the titles cooperation experiences, family participation and needs, early childhood special education, staff, institution features, opinion and suggestions. Six main themes and 18 subthemes were reached. Discussion: The findings of the study were consistent with the findings of the studies examining the cooperation process in special education services in the literature. Physical features of the institution, its operation in accordance with legal regulations and the staff's efficiency are effective in meeting families' needs of information and social support. Families need cooperation with staff expert in different fields in the process of starting education of children with special needs after early diagnosis and evaluation. The role of families and the directors and staff of the special education institutions are critical in maintaining the cooperation. Parents' needs such as information, social and psychological support must be met in line with the family participation. Family participation should be supported through accessible digital-based cooperation programs, professional skills of staff must be developed, and the physical features of institutions must be improved.

Real-Life Experience with Entrectinib in Neurotrophic Tyrosine Receptor Kinase Fusion-Positive Solid Tumors: A Multicenter Retrospective Trial.

Neurotrophic tyrosine receptor kinase (NTRK) gene fusions represent rare somatic mutations in many types of cancer and have enabled the use of promising targeted therapies. In clinical studies, increased response rates to tropomyosin receptor kinase inhibitors have been demonstrated in NTRK fusion-positive cancer types; however, real-world experiences on these targeted agents are scarce. We evaluated the clinical characteristics and treatment responses of NTRK fusion-positive patients who received entrectinib treatment within the scope of an early access program in Turkey. This multicenter, retrospective analysis involved 17 patients with solid tumors harboring NTRK fusions or rearrangements from 14 oncology centers between June 2019 and 31 March 2024. Demographic and clinical data were obtained via retrospective review of medical records with a cutoff date of 31 March 2024. The median age at diagnosis of the patients in our study was 42 [interquartile range (IQR) 33-60] years. Nine different types of solid tumors were diagnosed in these patients. The most common NTRK gene rearrangements involved NTRK1 (n=8), followed by NTRK3 (n=7). The median duration of entrectinib usage was 6.9 (IQR 3.1-16.1) months. Dose reductions due to side effects were performed in four patients: two due to leukopenia, one due to visual disturbance, and one due to troponin elevation. Leukopenia was the most commonly observed side effect. The objective response rate (ORR) was 35.3% (95% confidence interval (CI) 14.2-62.7), with complete response (CR) achieved in four patients. The duration of response (DOR) in patients who responded after initiating entrectinib was 9.8 (95% CI 0-30.7) months, the median overall survival (mOS) in all patients was 20.8 (95% CI 0-48.5) months, and the time-to-treatment failure (TTF) was 6.4 (95% CI 0-13.5) months. In this retrospective study, we aimed to obtain real-world data concerning the use of entrectinib in patients with solid tumors harboring NTRK fusion genes. Although our findings are partially similar to the results of clinical studies, prospective studies in larger patient groups with more diverse tumor types and different demographic characteristics are needed to confirm the findings.

A Pilot Study in Adapting the Chronic Care Model to Address Shortage of Child and Adolescent Psychiatry.

There is a nationwide shortage of child and adolescent psychiatrists. This, combined with the mental health crisis caused by the coronavirus 2019 pandemic has lead to low access to care for many individuals. Child Psychiatry Access Programs have been developed to address this need, but we believe they are not sufficient to care for complex cases. We propose that the Chronic Care Model can address these issues by providing, more longitudinal and and faster access to mental health care for patients. Our pilot study had 50 children and adolescent participants in our clinic model, which included the use of trainees supervised by an attending. We found that the mean wait time to appointment with a child and adolescent psychiatrist was 13.54 ± 14.8days, which is significantly shorter by that reported by other studies. We believe our model clinic may be helpful in a variety of settings and want to share it with other psychiatrists.

Abstract A125: A nationwide initiative to expand access to lung cancer screening: Results and impact of the Color/American Cancer Society Lung Screening Access Program

Abstract Lung cancer is a leading health challenge in the United States – it is the third most common cancer and disproportionately impacts people of color. Early detection of lung cancer is possible through routine screenings using low-dose lung CT scans. Despite the efficacy of screening, 80-85% of people eligible for screening are not up-to-date. The underutilization of regular screening has often been attributed to gaps in primary care and insufficient support following an abnormal result. In an effort to improve access, Color and the American Cancer Society (ACS), launched a nationwide initiative to make lung cancer screening readily accessible and free across all 50 states based on ACS guidelines. The program simplifies the screening process by managing all logistical steps from physician orders to finding and booking appointments at local clinics to assisting with next steps if abnormalities are detected.Since the program launched in November 2023, 74 people completed the online health risk assessment. On average participants were 54 years of age (range: 18-81 years), 64% (n=41) female, and 65% (n=48) White. 28% (n=19) respondents currently smoked, 50% (n=34) had a former history of smoking, and average smoking history was 23.0 pack years (range: 0.1 - 66 pack years). While the program primarily supports individuals who meet ACS lung screening guidelines, all participants can speak with a clinician about screening.Of those who completed the health risk assessment, 45.6% (n=31) met ACS eligibility criteria for lung screening. Eligible participants were on average 62 years of age (range: 51 - 77 years), 74% (n=23) were female, and 87% (n=27) were White. Eligible participants resided in 21 states, with Georgia and Ohio having the highest number of eligible individuals.To date, 9 people have completed a lung CT and 3 are in progress of scheduling. On average, appointments were scheduled within 25 days from the initial referral submission (range: 8-55 days) and all appointments were within 17 miles from the individual’s preferred location (average: 6.8 miles, range: 0.5-17 miles).3 participants had a change in their lung screening plan based on their result, with 2 participants having Lung-RADS 3 category nodules (follow-up in 6 months) and 1 having Lung-RADS 4A nodules (follow-up in 6 months). Other findings included an ascending aortic aneurysm (4.2 cm), a hiatal hernia, an indeterminate adrenal nodule, and mild coronary artery calcification, some of which required additional follow-up care with a PCP or cardiologist within 3-12 months. No participants were recommended to have immediate diagnostic testing for lung cancer based on their results. The Color/ACS Lung Screening Access Program demonstrates the impact that a virtual lung cancer screening program has on closing screening gaps. It underscores the critical role of supporting patients not only in undergoing cancer screening, but also in navigating the complexities of follow-up care, thereby enhancing the overall efficacy of lung cancer prevention and early detection strategies. Citation Format: Deanna Brockman, Jennifer Fung, Ashly Emig, Gabrielle Hands, Wendy McKennon, Jennifer Cho, Robert Smith, William Dahut, Alicia Zhou, Keegan Duchicela. A nationwide initiative to expand access to lung cancer screening: Results and impact of the Color/American Cancer Society Lung Screening Access Program [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A125.

Impact of BCR::ABL1 single nucleotide variants on asciminib efficacy

Asciminib is a potent and selective inhibitor of BCR::ABL1, with potential to avoid toxicity resulting from off-target kinase inhibition. Forty-nine patients treated with asciminib under a managed access program in the UK were evaluated for toxicity and response. Intolerance, rather than resistance (65% vs. 35%), was the most common reason for cessation of the last-line of treatment but asciminib was well tolerated, with most patients (29, 59%) remaining on treatment at a median of 14 months follow-up, and only 6 (12%) stopping for intolerance. Of 44 patients assessable for response, 29 (66%) achieved a complete cytogenetic response (CCyR) or better, with poorer responses seen in those stopping their last-line of therapy for resistance. Fewer patients with a prior history of a non-T315I-BCR::ABL1 single nucleotide variant (BSNV), or a non-T315I-BSNV detectable at baseline achieved CCyR. Serial tracking of BSNV by next generation sequencing demonstrated clonal expansion of BSNV-harbouring populations, which in some settings was associated with resistance (E459K, F317L, F359I), while in others was seen in the context of ongoing response, often with intensified dosing (T315I, I502F). These data suggest that asciminib exerts selective pressure on some BSNV-harbouring populations in vivo, some of which may respond to intensified dosing.

A longitudinal health promotion program for autistic children and their caregivers: Impact of an urban community-based program.

Autistic children, as well as their primary caregivers (e.g., parents), experience greater health disparities when compared with the general population. Despite this reality, there has been relatively little priority placed on promoting positive trajectories of health in either of these underserved populations. The primary purpose of this study was to examine the impact of participation in a 12-month, longitudinal health promotion program designed for both autistic children and their parent. A total of 27 families participated in the intervention, including 29 autistic children (83% male, M = 8.28 ± 3.60 years) and 27 parents (93% female, M = 40.04 ± 7.95). Families attended in-person health promotion programming for 90 min per week. Children and parents were evaluated at four time points across the program, including baseline (0-months), 4-months, 8-months, and 12-months. Children were measured on fundamental motor competence, physical fitness, body composition, and proxy-reported physical activity. Parents were measured on body composition, physical fitness, and self-reported physical activity. Significant improvements were observed for autistic children in motor competence (p < 0.001) and grip strength (p = 0.006), and for parents in body mass index (p = 0.004) and aerobic capacity (p = 0.003) across the 12-month intervention. Differing trajectories of improvement were noted between urban- and suburban-dwelling families on multiple outcomes. The knowledge acquired from this research may offer initial support for the need to bolster opportunities for accessible and ongoing health promotion programs for both autistic children and their parents.

Qualitative focus group study of interprofessional healthcare providers to inform the development of a virtual psychoeducational training program for the treatment of childhood interpersonal trauma

ABSTRACT The shortage of adequately trained healthcare providers (HCPs) able to treat adults who have experienced childhood interpersonal trauma (CIT) is a pressing concern. This study explored HCPs’ training needs for a trauma-focused psychoeducational group intervention and the potential barriers and facilitators to accessing such training. Three 1-hour focus group sessions were conducted with HCPs (n = 17) from two urban and one rural community healthcare organization serving diverse populations in Ontario, Canada, including under-housed people, women struggling with mental health and addiction, and LGBTQ+ populations. On average, participants had 2.4 years in their current role and 18.1 years of mental health field experience. Thematic analysis revealed key findings: a strong clinical need for trauma services, accessible training programs, and broadly applicable interventions relevant for diverse populations. Notably, participants emphasized the clinical advantages and increased accessibility of a virtual training programs focused on psychoeducational treatment interventions, particularly within community-based healthcare settings. This study highlights the potential of a virtual psychoeducational training programs for HCPs to address this critical gap in healthcare provision for individual with CIT. It also underscores the need to move beyond training program development and focus on implementation and sustainability of interventions in clinical practice.

SOD1 gene screening in ALS – frequency of mutations, patients’ attitudes to genetic information and transition to tofersen treatment in a multi-center program

Objective: To report the frequency of pathogenic SOD1 gene variants in a screening program in amyotrophic lateral sclerosis (ALS), and the clinical practice of transition to an expanded access program (EAP) of tofersen treatment. Methods: From October 2021 to February 2024, at 11 ALS centers in Germany genetic testing for SOD1, FUS, TARDBP, and C9orf72 was performed. Patients were offered to opt for notification either about all genetic variants or SOD1 variants relevant for tofersen therapy. The transition to the EAP with tofersen was assessed. Results: 1935 patients were screened (94.7% sporadic ALS). 48.8% (n = 928) opted for notification of treatment-relevant information. Genetic variants were found as follows: SOD1 (likely) pathogenic variants (class 4/5) 1.8% (n = 34), variants of unknown significance (class 3) 0.8% (n = 16), FUS (class 4/5) 0.9% (n = 17), TARDBP (class 4/5) 1.3% (n = 25), C9orf72 hexanucleotide repeat expansion 7.0% (n = 135). In SOD1-ALS (encompassing class 3–5 variants, n = 50), 68.0% (n = 34) reported a negative family history. 74.0% (n = 37) of SOD1-ALS patients – which represent 1.9% of all participants of the screening program – were transitioned to tofersen. Median duration from start of genetic testing to treatment was 94 days (57 to 295 days). Eight patients declined treatment whereas five individuals died before initiation of therapy. Conclusion: The finding of SOD1 variants in patients with a negative family history underscores the need for a broad genetic screening in ALS. In SOD1-ALS, the treatment option with tofersen was mostly utilized. The wide range in the transition time to tofersen calls for a SOD1-ALS management program.

Psilocybin-Assisted Therapy for Brain Cancer Related Existential Distress: A Case-Report.

Introduction: Psilocybin-assisted therapy (PAT) has gained traction in palliative care as a treatment for existential distress in the last decade. Patients with brain cancer have been excluded from studies, yet they stand to benefit as much as other patients with cancer-related psychological distress. Case description: In this report, we discuss the case of a patient with end-of-life distress secondary to stage 4 astrocytoma that received PAT through Health Canada's Special Access Program. The patient had a positive response to PAT without adverse events. Discussion: Standard treatment for existential distress is often inefficacious and PAT is rarely available, especially for patients with brain cancer. We highlight the importance of making PAT more available as many patients with unresolved existential distress resort to medical assistance in dying without ever knowing of the existence of PAT. Conclusion: PAT was effective in partially alleviating the patient's existential distress. Access to PAT needs to be expanded urgently.

Impact of a guaranteed access program to imatinib on the survival of patients with chronic myeloid leukemia.

This work aimed to evaluate the impact of a guaranteed access program to imatinib on the survival of patients with Chronic Myeloid Leukemia. We carried out a retrospective, observational, and analytical study of the database of patients diagnosed with Chronic Myeloid Leukemia of the Instituto Nacional de Cancerología and the Hospital General de México Dr. Eduardo to assess overall survival based on guaranteed access or not to imatinib. With an average follow-up of 99months, all patients' estimated 20-year overall survival was 72% (95% CI, 76-67). A significant difference was found in the 20-year survival probability in favor of patients with guaranteed access 76% (95% CI, 81-71) vs. 61% (95% CI, 69-52) (p < 0.001), in addition to those in which they had better attachment 81.2% (95% CI, 85-76) vs. 44.9% (95% CI, 52-37) (p < 0.001). CML is the most frequent chronic leukemia in Mexico. It mainly affects the economically active population (mean age 40), and the prognosis in our country has improved, emulating developed countries; however, the results depend on access to treatment and proper monitoring.