Meaningful Change Research Articles

Functional brain connectivity changes associated with day-to-day fluctuations in affective states

Affective neuroscience has traditionally relied on cross-sectional studies to uncover the brain correlates of affects, emotions, and moods. Such findings obfuscate intraindividual variability that may reveal meaningful changing affect states. The few functional magnetic resonance imaging longitudinal studies that have linked changes in brain function to the ebbs and flows of affective states over time have mostly investigated a single individual. In this study, we explored how the functional connectivity of brain areas associated with affective processes can explain within-person fluctuations in self-reported positive and negative affects across several subjects. To do so, we leveraged the Day2day dataset that includes 40 to 50 resting-state functional magnetic resonance imaging scans along self-reported positive and negative affectivity from a sample of six healthy participants. Sparse multivariate mixed-effect linear models could explain 15% and 11% of the within-person variation in positive and negative affective states, respectively. Evaluation of these models’ generalizability to new data demonstrated the ability to predict approximately 5% and 2% of positive and negative affect variation. The functional connectivity of limbic areas, such as the amygdala, hippocampus, and insula, appeared most important to explain the temporal dynamics of affects over days, weeks, and months.

Digital oncology, the dawn of a new era turning the clock back on tumor mass

Evolutionary path of cancer therapeutics which started around eighty-two years ago, following serendipitous discovery of nitrogen mustard [1] has been guided by an accelerated pace of new discoveries, an ever-increasing depth of understanding of intracellular biological processes [2] and application of advances made in other fields of science [3]. Success in any field, especially in cancer medicine, is based on embracing evolution in understanding other scientific fields [4] and its application to the forward move in cancer therapeutics. As such, we have gone through discovery of a diverse group of therapeutics, targeting different sub compartments of growth and proliferation pathways [5] and taking advantage of their synergistic efficacy, in different combinations [6]. Dissection of immune regulatory pathways [7] and their interaction with cancer cell has led to the generation of modern immune therapeutic agents. Single-cell sequencing technology [8] has paved the way for the development of spatial omics [9], which has opened the way on deeper understanding of tumor evolutionary path [10]. This would give us the opportunity to design a new generation of cancer therapeutics [11] intercepting with the forward evolutionary path of tumor mass. Along this path, we face insurmountable barriers in developing meaningful and game changing treatment strategies by directing single changes in a hyper complex biological system [12], manifested by complexities of genome [13], epigenome [14], microRNA network [15], gene regulatory mechanisms [16], and protein-protein interactions [17]. Consequently, we need to search for a solution that enables us to freeze or slow down the forward evolutionary path of tumor mass [18], by making a single change in a game changing variable of cancer cell.

Reliable Change Indices for the Serial Administration of the Concussion Clinical Profiles Screening Tool.

The Concussion Clinical Profiles Screening Tool (CP Screen) self-report concussion symptom inventory is often administered at weekly intervals. However, 1-week reliable change indices (RCIs) for clinical cutoffs and the test-retest reliability of the CP Screen are unknown. To document RCI cutoff scores and 1-week test-retest reliability for each profile and modifier of the CP Screen for men and women. Case series. A large US university. One hundred seventy-three healthy college students. Participants completed 2 administrations of the CP Screen 7 days apart. The CP Screen items yielded 5 clinical profiles and 2 modifiers. Spearman ρ coefficients (rs), intraclass correlation coefficients (ICCs), single measures, and unbiased estimates of reliability (UERs) were used to assess test-retest reliability. Wilcoxon signed-rank tests assessed differences across time. Reliable change index values and cutoff scores are provided at 90%/95% CIs. All analyses were performed for the total sample and separately for men and women. Reliable change index cutoffs for clinically significant change (increase/decrease) at a 90% CI for men were as follows: ocular, vestibular >2/>4; anxiety/mood, cognitive/fatigue, and migraine >3/>3; sleep >4/>6; and neck >2/>2. Reliable change index cutoffs for clinically significant change (increase/decrease) at a 90% CI for women were as follows: anxiety/mood ≥2/≥4; cognitive/fatigue, migraine, ocular, vestibular, and sleep ≥3/≥3; and neck ≥1/≥1. Correlations for the CP Screen ranged from 0.51 (migraine) to 0.79 (anxiety/mood) for the total sample, from 0.48 (migraine) to 0.84 (vestibular) for men, and from 0.51 (migraine) to 0.77 (ocular) for women. Test-retest indices for each profile and modifier were moderate to good for the total sample (ICC, 0.64-0.82; UER, 0.79-0.90), men (ICC, 0.60-0.87; UER, 0.76-0.94), and women (ICC, 0.64-0.80; UER, 0.78-0.89). The CP Screen is reliable and stable across a 1-week interval, and established RCIs for men and women can help identify meaningful change throughout recovery.

Immersive learning in a block teaching model: A case study of academic reform through principles, policies and practice

Universities across the globe are considering how to effect meaningful change in their higher education (HE) delivery in the face of the COVID-19 pandemic and shifting student learning preferences. This paper reports on a descriptive case- study of whole-of-institution curriculum reform at one regional Australian university, where more traditional 13-week semesters have been replaced with a 6-week immersive block model known as the Southern Cross Model. Based on a synthesis of literature in best practice HE pedagogy and principles, the case study draws on both a review of policy and staff interviews (N = 5) to outline the key changes necessary for successful HE transformation. Analysis revealed themes related to the vital roles of leadership, capacity building, monitoring the transition, staff adoption, and adequate technical systems in implementing a radical, multifaceted institutional transformation. Implications for practice at institutions considering reforming their curriculum model are also discussed. The findings from this case study indicate that an institutional transformation to an immersive block model requires both a considered change in institutional policy and process, as well as the appropriate resourcing of roles, governance committees, technical solutions, and, importantly, communities of practice.

Longitudinal health outcomes in caregivers of military members with traumatic brain injury.

To examine longitudinal change in health-related quality of life (HRQOL) in caregivers of service members/veterans with traumatic brain injury and factors associated with clinically elevated symptoms. Caregivers (N = 220) completed nine HRQOL outcome measures and 10 risk factor measures at a baseline evaluation and follow-up evaluation 3 years later. Caregiver's responses on the nine HRQOL outcome measures were classified into four clinical change categories based on the presence/absence of clinically elevated T-scores (≥ 60 T) at baseline and follow-up: (a) Persistent (baseline ≥ 60T + follow-up ≥ 60 T), (b) Developed (baseline < 60 T + follow-up ≥ 60 T), (c) Improved (baseline ≥ 60 T + follow-up < 60 T), and (d) Asymptomatic (baseline < 60 T + follow-up < 60 T). A clinical change composite score was calculated by summing the number of Persistent or Developed HRQOL outcome measures and used to create three clinical change groups: (a) No Symptoms (n = 69, zero measures), (b) Some Symptoms (n = 88, one to three measures), and (c) Numerous Symptoms (n = 63, four to nine measures). Of the nine HRQOL outcome measures, Bodily Pain, Perceived Stress, Sleep-Related Impairment, and Fatigue were most frequently classified as Persistent or Developed from baseline to follow-up in the entire sample. A linear relationship was found between the vast majority of risk factors across the three clinical change groups at baseline and follow-up (Numerous > Some > None). The risk factors were correlated with the number of elevated HRQOL symptoms at baseline and follow-up. Most Asymptomatic or Persistent caregivers did not have meaningful change (≥ 1 SD) in HRQOL scores. A sizable proportion of Developed or Improved caregivers had either meaningful or no change in HRQOL scores. There is a need for ongoing clinical services for military caregivers. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Recreational use of psychedelics at music festivals: Motivation, nature of experiences and learnings

AbstractThe present research study investigated the phenomenon of recreational use of psychedelics at music festivals, analysing whether the resulting experiences could possibly be recognized as valuable in terms of preventive mental health strategies. Quantitative (online survey) and qualitative (interviews) research methods have been combined to illuminate 3 main topics: motivation for the setting choice; the nature of the resulting experiences &amp; their influence on people's lives; learnings from psychedelic experiences at music festivals (PEMF).Among other findings, motivation evolved around fun, enhancing the sensory exploration of the world, and deepening the connection to its diverse parts through engagement with art, nature and other beings. Factors, distinguishing music festivals from other settings, were significant for the setting choice (non-controllability of the environment, community &amp; connection aspect, diversity &amp; richness of the surroundings, pharmacological specifics). Remarkably, the non-controllability of the environment, otherwise avoided in the psychedelic research, contributed to the life-changing effects of PEMF. Exploration of their nature showed that, mostly rooted in poly-drug use, the enjoyable were clearly dominating over the challenging ones. The mystical PEMF appeared to be surprisingly common. Participants shared the related life-changing effects, centred around changed perception (increased empathy, awareness, acceptance; new perspectives, etc.) and changed behaviours (increased mindfulness in all life areas; making different life choices; changed approach to relationships, etc.). Except for post MDMA recovery, a positive impact of PEMF on mental health and the emotional state of the participants was reported, referring to increased levels of happiness, compassion, awe, trust and to emotional balance. This study showed the potential value of PEMF in terms of preventive mental health strategies in various forms. Acknowledging these findings as well as the existence of potential risks for triggering psychiatric conditions, de-stigmatization of recreational use could help introduce meaningful changes, including substance testing availability, prioritization of education as well as mandatory welfare and harm reduction services on-site.

A Theoretical Foundation to Inform the Implementation of Precision Education and Assessment.

Precision education (PE) uses personalized educational interventions to empower trainees and improve learning outcomes. While PE has the potential to represent a paradigm shift in medical education, a theoretical foundation to guide the effective implementation of PE strategies has not yet been described. Here, the authors introduce a theoretical foundation for the implementation of PE, integrating key learning theories with the digital tools that allow them to be operationalized. Specifically, the authors describe how the master adaptive learner (MAL) model, transformative learning theory, and self-determination theory can be harnessed in conjunction with nudge strategies and audit and feedback dashboards to drive learning and meaningful behavior change. The authors also provide practical examples of these theories and tools in action by describing precision interventions already in use at one academic medical center, concretizing PE's potential in the current clinical environment. These examples illustrate how a firm theoretical grounding allows educators to most effectively tailor PE interventions to fit individual learners' needs and goals, facilitating efficient learning and ultimately improving patient and health system outcomes.

Physician and Professional Caregiver Perspectives on Meaningful Change to Agitation Behaviors in Alzheimer's Dementia: Insights from Qualitative Interviews

Physician and Professional Caregiver Perspectives on Meaningful Change to Agitation Behaviors in Alzheimer's Dementia: Insights from Qualitative Interviews

Image Comparison Based On Local Pixel Clustering

Image comparison is a fundamental step for monitoring images and has wide applications in many disciplines of sciences, including satellite imaging, medical research, quality control and so forth. This problem, however, is complicated because (i) the observed images often contain noise, (ii) the image intensity functions are discontinuous and have spatial structures. In the literature, a vast majority of the methods are intensity-based. However, such an approach is often questionable in real life situations where small changes in the background may not indicate an actual meaningful change in the images as long as the boundaries of the image objects remain the same. In this article, we propose a flexible and effective image comparison method based on local pixel clustering and construct a test statistic based on the Variation of Information metric. This is a feature based image comparison technique where edges or the jump points are considered as the primary features. Numerical examples and statistical properties show that the proposed image comparison method performs well in various real life scenarios.

The Political Economy of Digital Health Equity: Structural Analysis.

Digital technologies have produced many innovations in care delivery and enabled continuity of care for many people when in-person care was impossible. However, a growing body of research suggests that digital health can also exacerbate health inequities for those excluded from its benefits for reasons of cost, digital literacy, and structural discrimination related to characteristics such as age, race, ethnicity, and socioeconomic status. In this paper, we draw on a political economy perspective to examine structural barriers to progress in advancing digital health equity at the policy level. Considering the incentive structures and investments of powerful actors in the field, we outline how characteristics of neoliberal capitalism in Western contexts produce and sustain digital health inequities by describing 6 structural challenges to the effort to promote health equity through digital health, as follows: (1) the revenue-first incentives of technology corporations, (2) the influence of venture capital, (3) inequitable access to the internet and digital devices, (4) underinvestment in digital health literacy, (5) uncertainty about future reimbursement of digital health, and (6) justified mistrust of digital health. Building on these important challenges, we propose future immediate and long-term directions for work to support meaningful change for digital health equity.

Stereotactic ultrahypofractionated MR-guided radiotherapy for localized prostate cancer – Acute toxicity and patient-reported outcomes in the prospective, multicenter SMILE phase II trial

BackgroundDue to superior image quality and daily adaptive planning, MR-guided stereotactic body radiation therapy (MRgSBRT) has the potential to further widen the therapeutic window in radiotherapy of localized prostate cancer. This study reports on acute toxicity rates and patient-reported outcomes after MR-guided adaptive ultrahypofractionated radiotherapy for localized prostate cancer within the prospective, multicenter phase II SMILE trial. Materials and methodsA total of 69 patients with localized prostate cancer underwent MRgSBRT with daily online plan adaptation. Inclusion criteria comprised a tumor stage ≤ T3a, serum PSA value ≤ 20 ng/ml, ISUP Grade group ≤ 4. A dose of 37.5 Gy was prescribed to the PTV in five fractions on alternating days with an optional simultaneous boost of 40 Gy to the dominant intraprostatic lesion defined by multiparametric MRI. Acute genitourinary (GU-) and gastrointestinal (GI-) toxicity, as defined by CTCAE v. 5.0 and RTOG as well as patient-reported outcomes according to EORTC QLQ-C30 and -PR25 scores were analyzed at completion of radiotherapy, 6 and 12 weeks after radiotherapy and compared to baseline symptoms. ResultsThere were no toxicity-related treatment discontinuations. At the 12-week follow-up visit, no grade 3 + toxicities were reported according to CTCAE. Up until the 12-week visit, in total 16 patients (23 %) experienced a grade 2 GU or GI toxicity. Toxicity rates peaked at the end of radiation therapy and subsided within the 12-week follow-up period. At the 12-week follow-up visit, no residual grade 2 GU toxicities were reported and 1 patient (1 %) had residual grade 2 enteritic symptoms. With exception to a significant improvement in the emotional functioning score following MRgSBRT, no clinically meaningful changes in the global health status nor in relevant subscores were reported. ConclusionDaily online-adaptive MRgSBRT for localized prostate cancer resulted in an excellent overall toxicity profile without any major negative impact on quality of life.

Longitudinal Risk Phenotyping in Incident Systemic Sclerosis-associated Pulmonary Arterial Hypertension (SSc-PAH): An Unsupervised Cluster Analysis of the PHAROS Registry

Background: Systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) is characterized by pulmonary arterial remodeling resulting in right ventricular failure and death if untreated. Despite therapeutic advances, there is survival variability within the SSc-PAH population. The aim of this study was to delineate high-risk subgroups of SSc-PAH using readily available clinical parameters. Methods: We analyzed data from the PHAROS database, a prospective observational registry of incident SSc-PAH patients. Latent class modeling was performed based on trends in 6MWD over time. We compared survival between the clusters regarding baseline clinical parameters and changes in these parameters over time. Results: We identified four unique groups within 103 patients meeting our inclusion criteria, based on trajectories of 6MWD. Patients in Cluster 4 exhibited a decline in 6MWD over time and had the worst prognosis with a median survival of 3 years. Patients in Cluster 3, with the lowest baseline 6MWD, were associated with lower median survival (5 years) when compared to Clusters 1 and 2 (&gt; 9 and 7 years, respectively), despite an improvement in 6MWD over time. There were no meaningful changes in SF-36 and WHO functional class between the clusters, but BNP trended higher over time in the higher-risk clusters. Conclusion: We identified high-risk subsets of SSc-PAH characterized by significantly worse survival. Incident SSc-PAH patients with a decline in 6MWD over time or low baseline 6MWD had worse survival when compared to SSc-PAH patients who demonstrated relatively stable or mild reduction in 6MWD over time.

Meaningful within-patient change for clinical outcome assessments: model-based approach versus cumulative distribution functions

ABSTRACT Objectives The FDA recommends the use of anchor-based methods and empirical cumulative distribution function (eCDF) curves to establish a meaningful within-patient change (MWPC) for a clinical outcome assessment (COA). In practice, the estimates obtained from model-based methods and eCDF curves may not closely align, although an anchor is used with both. To help interpret their results, we investigated and compared these approaches. Methods Both repeated measures model (RMM) and eCDF approaches were used to estimate an MWPC on a target COA. We used both real-life (ClinicalTrials.gov: NCT02697773) and simulated data sets that included 688 patients with up to six visits per patient, target COA (range 0 to 10), and an anchor measure on patient global assessment of osteoarthritis from 1 (very good) to 5 (very poor). Ninety-five percent confidence intervals for the MWPC were calculated by the bootstrap method. Results The distribution of the COA score changes affected the degree of concordance between RMM and eCDF estimates. The COA score changes from simulated normally distributed data led to greater concordance between the two approaches than did COA score changes from the actual clinical data. The confidence intervals of MWPC estimate based on eCDF methods were much wider than that by RMM methods, and the point estimate of eCDF methods varied noticeably across visits. Conclusions Our data explored the differences of model-based methods over eCDF approaches, finding that the former integrates more information across a diverse range of COA and anchor scores and provides more precise estimates for the MWPC.

Evaluation of a remote hybrid staffing model for investigational drug service pharmacists.

This project compared the time to complete investigational prescription drug order verification by investigational drug service (IDS) pharmacists in an onsite vs offsite (hybrid) staffing model, evaluating the impact of remote work on verification time. Parenteral IDS drug orders from August 2019 through June 2022 were analyzed. Electronic medical records were timestamped for each order, first verification, second verification, and medication administration. The project was divided into four 6-month time periods to allow for 2 independent comparisons of onsite vs hybrid staffing models. A survey was given retrospectively to IDS pharmacists for the last hybrid timeframe to assess work satisfaction and burnout. A total of 4,398 orders were evaluated. The time from order entry to first verification was 14 minutes (n = 1,248) during the first onsite time period compared to 13 minutes (n = 1,042) during the first hybrid period (P = 0.003). The time for order verification was similar between the second onsite and hybrid periods (12 minutes [n = 1,041] vs 10 minutes [n = 1,067], respectively; P < 0.0001). The staff satisfaction survey for the hybrid model showed high levels of job satisfaction and no self-reported burnout. The remote hybrid staffing model did not result in a meaningful change in the time from order placement to medication administration within the IDS pharmacy. Hybrid staffing also resulted in greater job satisfaction among IDS pharmacists. This study highlights the benefits of implementing remote work practices in the pharmacy practice setting.

A Need for Standardized Approaches to Manage Sustainability Strategically

This study aims to explore the challenges and opportunities associated with measuring and assessing sustainability impacts and investigate digitalization’s role in addressing these challenges. The study gathers stakeholders’ perspectives on strategically managing sustainability and employs a qualitative research approach, utilizing semi-structured face-to-face interviews with seven industry participants. The findings reveal that the measurement and assessment of sustainability impacts pose significant challenges due to the lack of standardized approaches and the diversity of evaluation methods. Companies have started to address these challenges by applying digitalization to standardize and streamline sustainability measures. Digital platforms and technologies are being developed to collect, analyze, and report sustainability data, providing a foundation for reliable and comprehensive sustainability reporting. This study contributes to the existing literature by highlighting the need for standardized approaches and digital platforms for measuring and assessing sustainability impacts. The findings emphasize the importance of integrating sustainability into corporate strategies, as well as the role of digitalization in enabling companies to focus strategically on the most important societal goals. The study also underscores the need for clear definitional parameters and accurate measurement of sustainability performance. Overall, this research highlights the potential of digitalization in driving meaningful change and promoting sustainability in economic, environmental, and social domains.

Prolonged acid reflux monitoring using acid exposure time and DeMeester score: two days are not enough.

Wireless pH monitoring allows for a definitive GERD diagnosis, which is essential for optimal medical or surgical management of the patient. However, there is no guideline recommendation on whether prolonged pH testing (72 or 96h) provides additional benefit when compared to the standard 48-h testing. We aimed to assess whether prolonged pH monitoring diagnoses more patients with GERD, as well as compare the DeMeester score to acid exposure time as diagnostic criteria for GERD. This was a retrospective analysis of consecutive adult patients who underwent wireless esophageal pH monitoring between August 2018 and July 2021. The primary outcome was the additional diagnoses of GERD (predominant acid exposure pattern) in patients who underwent 48-h versus 96-h pH monitoring. Secondary outcomes included comparison of the DeMeester score to acid exposure time and internal agreement between the first and second 48-h blocks of a prolonged96-hpH study. When comparing 48-h versus 96-h pH testing, the prolonged monitoring group was more likely to have a predominant reflux pattern and thus be diagnosed with definitive GERD by elevated DeMeester score (58.8% vs. 40.8%, p = 0.003) or acid exposure time > 6% (44.7% vs. 32.4%, p = 0.039). For patients who underwent prolonged testing, the results of monitoring beyond 48h led to a clinically meaningful change in study interpretation in 24.8% of patients. The study data from Days 3 to 4 yielded only a 56.6% agreement with the first 2days. In patients undergoing extended pH monitoring, almost half were found to have an abnormal pH study after a normal study on Day 1. An additional 25% of patients had a change in study interpretation by extending the study beyond 48h. Our findings suggest only 48h of pH monitoring will miss a diagnosis of GERD in a clinically important number of patients.

"Nothing without connection"-Participant perspectives and experiences of mentorship in capacity building in Timor-Leste.

The literature on mentorship approaches to capacity building in global health is limited. Likewise, there are few qualitative studies that describe mentorship in capacity building in global health from the perspective of the mentors and mentees. This qualitative study examined the perspectives and experiences of participants involved in a program of health capacity building in Timor-Leste that was based on a side-by-side, in-country mentorship approach. Semi-structured interviews were conducted with 23 participants (including Timorese and expatriate mentors, and local Timorese colleagues) from across a range of professional health disciplines, followed by a series of member checking workshops. Findings were reviewed using inductive thematic analysis. Participants were included in review and refinement of themes. Four major themes were identified: the importance of trust and connection within the mentoring relationship; the side-by-side nature of the relationship (akompaña); mentoring in the context of external environmental challenges; and the need for the mentoring relationship to be dynamic and evolving, and aligned to a shared vision and goals. The importance of accompaniment (akompaña) as a key element of the mentoring relationship requires further exploration and study. Many activities in global health capacity building remain focused on provision of training, supervision, and supportive supervision of competent task performance. Viewed through a decolonising lens, there is an imperative for global health actors to align with local priorities and goals, and work alongside individuals supporting them in their vision to become independent leaders of their professions. We propose that placing mentoring relationships at the centre of human resource capacity building programs encourages deep learning, and is more likely to lead to long term, meaningful and sustainable change.

Arterial Spin-Labeling and DSC Perfusion Metrics Improve Agreement in Neuroradiologists' Clinical Interpretations of Posttreatment High-Grade Glioma Surveillance MR Imaging-An Institutional Experience.

MR perfusion has shown value in the evaluation of posttreatment high-grade gliomas, but few studies have shown its impact on the consistency and confidence of neuroradiologists' interpretation in routine clinical practice. We evaluated the impact of adding MR perfusion metrics to conventional contrast-enhanced MR imaging in posttreatment high-grade glioma surveillance imaging. This retrospective study included 45 adults with high-grade gliomas who had posttreatment perfusion MR imaging. Four neuroradiologists assigned Brain Tumor Reporting and Data System scores for each examination on the basis of the interpretation of contrast-enhanced MR imaging and then after the addition of arterial spin-labeling-CBF, DSC-relative CBV, and DSC-fractional tumor burden. Interrater agreement and rater agreement with a multidisciplinary consensus group were assessed with κ statistics. Raters used a 5-point Likert scale to report confidence scores. The frequency of clinically meaningful score changes resulting from the addition of each perfusion metric was determined. Interrater agreement was moderate for contrast-enhanced MR imaging alone (κ = 0.63) and higher with perfusion metrics (arterial spin-labeling-CBF, κ = 0.67; DSC-relative CBV, κ = 0.66; DSC-fractional tumor burden, κ = 0.70). Agreement between raters and consensus was highest with DSC-fractional tumor burden (κ = 0.66-0.80). Confidence scores were highest with DSC-fractional tumor burden. Across all raters, the addition of perfusion resulted in clinically meaningful interpretation changes in 2%-20% of patients compared with contrast-enhanced MR imaging alone. Adding perfusion to contrast-enhanced MR imaging improved interrater agreement, rater agreement with consensus, and rater confidence in the interpretation of posttreatment high-grade glioma MR imaging, with the highest agreement and confidence scores seen with DSC-fractional tumor burden. Perfusion MR imaging also resulted in interpretation changes that could change therapeutic management in up to 20% of patients.

Deucravacitinib in moderate-to-severe plaque psoriasis: Pooled safety and tolerability over 52 weeks from two phase 3 trials (POETYK PSO-1 and PSO-2).

Two phase 3 trials, POETYK PSO-1 and PSO-2, previously established the efficacy and overall safety of deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, in plaque psoriasis. To further assess the safety of deucravacitinib over 52 weeks in the pooled population from these two trials. Pooled safety data were evaluated from PSO-1 and PSO-2 in which patients with moderate-to-severe plaque psoriasis were randomized 1:2:1 to receive oral placebo, deucravacitinib or apremilast. A total of 1683 patients were included in the pooled analysis. Adverse event (AE) incidence rates were similar in each treatment group, serious AEs were low and balanced across groups, and discontinuation rates were lower with deucravacitinib versus placebo or apremilast. No new safety signals emerged with longer deucravacitinib treatment. Exposure-adjusted incidence rates of AEs of interest with placebo, deucravacitinib and apremilast, respectively, were as follows: serious infections (0.8/100 person-years [PY], 1.7/100 PY, and 1.8/100 PY), major adverse cardiovascular events (1.2/100 PY, 0.3/100 PY, and 0.9/100 PY), venous thromboembolic events (0, 0.2/100 PY, and 0), malignancies (0, 1.0/100 PY and 0.9/100 PY), herpes zoster (0.4/100 PY, 0.8/100 PY, and 0), acne (0.4/100 PY, 2.9/100 PY, and 0) and folliculitis (0, 2.8/100 PY, and 0.9/100 PY). No clinically meaningful changes from baseline in mean levels, or shifts from baseline to CTCAE grade ≥3 abnormalities, were reported in laboratory parameters with deucravacitinib. Deucravacitinib was well-tolerated with acceptable safety over 52 weeks in patients with psoriasis.

A work in progress: inclusion for students with developmental disabilities from the perspectives of principals and teachers

ABSTRACT Legislatively and practically, school districts around the world have transitioned to more inclusive service delivery for students with disabilities. Despite consistent and meaningful changes across the spectrum of disability, students with Developmental Disabilities (DD) remain segregated in self-contained classrooms at a high rate. Within a Canadian context numbers vary: some provinces are fully inclusive and others continue to segregate students with disabilities. In Canada’s most populous province, Ontario, the number of students with Developmental Disabilities (DD) in segregated settings remains consistently high (Bennett, S., D. Dworet, T. Gallagher, and M. Somma. 2019. Special Education in Ontario Schools. 8th ed. St. David's ON: Highland Press). Despite these concerning numbers, individual school districts are trying to shift practices to more fully inclusive service delivery. This paper examines one Ontario school district that transitioned to full inclusive education for students with disabilities. Utilising 10 principal and 21 teacher interviews, this paper examines the perceptions of these stakeholders as they reflect on their transition to inclusion and their experiences. Implications discuss the participants’ perceived successes and challenges, and recommendations provide insights to assist school districts in shifting embedded practices of segregation towards full inclusion for all students.