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Background: Clinical practice guidelines recommend the use of bone-targeting agents for preventing skeletal-related events (SREs) among patients with bone metastases from solid tumors. The anti-RANKL monoclonal antibody denosumab is approved for the prevention of SREs in patients with bone metastases from solid tumors. However, real-world data are lacking on the impact of individual risk factors for SREs, specifically in the context of denosumab discontinuation. Purpose: We aim to identify risk factors associated with SRE incidence following denosumab discontinuation using a machine learning approach to help profile patients at a higher risk of developing SREs following discontinuation of denosumab treatment. Methods: Using the Optum PanTher Electronic Health Record repository, patients diagnosed with incident bone metastases from primary solid tumors between January 1, 2007, and September 1, 2019, were evaluated for inclusion in the study. Eligible patients received ≥ 2 consecutive 120 mg denosumab doses on a 4-week (± 14 days) schedule with a minimum follow-up of ≥ 1 year after the last denosumab dose, or an SRE occurring between days 84 and 365 after denosumab discontinuation. Extreme gradient boosting was used to develop an SRE risk prediction model evaluated on a test dataset. Multiple variables associated with patient demographics, comorbidities, laboratory values, treatments, and denosumab exposures were examined as potential factors for SRE risk using Shapley Additive Explanations (SHAP). Univariate analyses on risk factors with the highest importance from pooled and tumor-specific models were also conducted. Results: A total of 1,414 adult cancer patients (breast: 40%, prostate: 30%, lung: 13%, other: 17%) were eligible, of whom 1,133 (80%) were assigned to model training and 281 (20%) to model evaluation. The median age at inclusion was 67 (range, 19–89) years with a median duration of denosumab treatment of 253 (range, 88–2,726) days; 490 (35%) patients experienced ≥ 1 SRE 83 days after denosumab discontinuation. Meaningful model performance was evaluated by an area under the receiver operating curve score of 77% and an F1 score of 62%; model precision was 60%, with 63% sensitivity and 78% specificity. SHAP identified several significant factors for the tumor-agnostic and tumor-specific models that predicted an increased SRE risk following denosumab discontinuation, including prior SREs, shorter denosumab treatment duration, ≥ 4 clinic visits per month with at least one hospitalization (all-cause) event from the baseline period up to discontinuation of denosumab, younger age at bone metastasis, shorter time to denosumab initiation from bone metastasis, and prostate cancer. Conclusion: This analysis showed a higher cumulative number of SREs, prior SREs relative to denosumab initiation, a higher number of hospital visits, and a shorter denosumab treatment duration as significant factors that are associated with an increased SRE risk after discontinuation of denosumab, in both the tumor-agnostic and tumor-specific models. Our machine learning approach to SRE risk factor identification reinforces treatment guidance on the persistent use of denosumab and has the potential to help clinicians better assess a patient’s need to continue denosumab treatment and improve patient outcomes.

Consumer and community involvement (also referred to as patient and public involvement) in health-related curricula involves actively partnering with people with lived experience of health and social care systems. While health professions education has a long history of interaction with patients or consumers, a shift in the way consumer and community engage in health-related education has created novel opportunities for mutual relationships valuing lived experience expertise and shifting traditional education power relations. Drawing on a mixed methods design, we explored consumer and community involvement practices in the design and delivery of health-related education using the capability, opportunity, motivation and behaviour framework (COM-B). In our results, we describe educator capabilities, opportunities and motivations, including identifying barriers and enablers to consumer and community involvement in health-related education. Educators have varying philosophical reasons and approaches for involving consumers and community. There is a focus on augmenting student learning through inclusion of lived and living experience, and on mutual transformative learning through embedding lived experience and co-creating learning. How these philosophical positionings and motivations shape the degree by which educators involve consumers and community members in health-related curricula is important for further understanding these educational partnerships within universities.

Spinocerebellar ataxias (SCA) are rare inherited neurodegenerative disorders characterized by a progressive impairment of gait, balance, limb coordination, and speech. There is currently no composite scale that includes multiple aspects of the SCA experience to assess disease progression and treatment effects. Applying the method of partial least squares (PLS) regression, we developed the Spinocerebellar Ataxia Composite Scale (SCACOMS) from two SCA natural history datasets (NCT01060371, NCT02440763). PLS regression selected items based on their ability to detect clinical decline, with optimized weights based on the items degree of progression. Following model validation, SCACOMS was leveraged to examine disease progression and treatment effects in a 48-week SCA clinical trial cohort (NCT03701399). Items from the Clinical Global Impression-Global Improvement Scale (CGI-I), the Friedreich Ataxia Rating Scale (FARS) - functional stage, and the Modified Functional Scale for the Assessment and Rating of Ataxia (f-SARA) were objectively selected with weightings based on their sensitivity to clinical decline. The resulting SCACOMS exhibited improved sensitivity to disease progression and greater treatment effects (compared to the original scales from which they were derived) in a 48-week clinical trial of a novel therapeutic agent. The trial analyses also provided a SCACOMS-derived estimate of the temporal delay in SCA disease progression. SCACOMS is a useful composite measure, effectively capturing disease progression and highlighting treatment effects in patients with SCA. SCACOMS will be a powerful tool in future studies given its sensitivity to clinical decline and ability to detect a meaningful clinical impact of disease-modifying treatments.

ObjectivesInformed by a social-ecological framework, this study nested undocumented students' individual mental health needs within micro-level campus factors and the macro-level immigration policy context to examine how these are associated with undocumented Latina/o/x college students' use of on-campus mental health services.MethodA large-scale survey was administered to 1,277 undocumented college students attending 4-year public universities in California. Only Latina/o/x respondents were included in this study (N = 1,181). Fifty percent of students attended a UC system (n = 589). On average, students were 21.84 years old (SE = .15), and most were women (75.3%, n = 890).ResultsGreater level of mental health symptoms and perceived mental health need, and greater use of campus-wide resources and undocumented student services predicted greater likelihood of using on-campus mental health services. Greater perceptions of social exclusion due to the immigration policy context predicted lower use of mental health services.ConclusionsResults indicate that a greater use of resources and an inclusive campus environment, as well as efforts to minimize policy-related feelings of social exclusion, may facilitate undocumented students' professional mental health help-seeking. These findings emphasize the need to take multiple and multi-level ecological factors into account when considering mental health service use, particularly in the case of undocumented immigrants and likely other structurally marginalized groups. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Abstract Background Migraine is a disabling disorder that impacts 40 million people in the US. Zavegepant is the first calcitonin gene-related peptide (CGRP) receptor antagonist nasal-spray approved for the acute treatment of migraine with or without aura in adults. This study aimed to evaluate the proportion of patients in various pain and functional disability states over 48-h, for patients treated with zavegepant 10 mg nasal-spray versus placebo. Methods This post-hoc analysis included adult patients with > 1-year history of migraine from BHV3500-301 (NCT04571060): a phase 3 double-blind, randomized, placebo-controlled, single-attack study. Over 48-h, pain severity and functional disability were captured at various timepoints (pre- and post-dosing). The proportion of patients at each pain severity or functional disability state and the time spent in each category was calculated. These were analyzed for patients with complete timepoint data available and using missing not at random (MNAR) imputation for missing timepoints. Predictors of functional disability were assessed using a mixed-effects logistic regression model. Results There were 1,269 patients included in the MNAR imputation analysis, and between 630–641 in the complete-case analysis. As early as 15-min post-dose, a larger proportion of zavegepant patients achieved no/mild pain compared to placebo, despite balanced migraine severity pre-dose. Furthermore, zavegepant patients spent significantly more time (over 2.5-h) in pain freedom compared to placebo. Similarly, a higher proportion of patients with normal function was observed with zavegepant vs placebo, as early as 30-min post-dose. Over 48-h, patients treated with zavegepant spent an average of ~ 3-h longer with normal functioning compared to placebo. Results were similar when analyzing both analytic groups. In a regression model, treatment with zavegepant, lower pain severity, fewer baseline monthly migraine days, and absence of photophobia, phonophobia, and nausea were associated with better functioning (p

In this article, we draw from our collaboration across a diverse cadre of colleagues who have focused on different aspects of teaching, higher education, and carcerality. In particular, our research team, known as STEM-OPS (STEM Opportunities in Prison Settings), studied higher education in prison with a specific focus on science, technology, engineering, and mathematics (STEM) and incarceration. We present interrelated findings from interviews across four people who are formerly incarcerated. Most Higher Education in Prison (HEP) programs are taught by university professors who are experts in content areas (such as science, chemistry, and math) and not pedagogy. As such, we believe teacher educators have an opportunity and an obligation to build professional learning opportunities related to pedagogy to support these instructors' practices.

OBJECTIVES/SPECIFIC AIMS: This study seeks to understand the relationship between opioid prescribing and patient satisfaction among non-surgical, hospitalized patients. As part of this study, we qualitatively examined challenges in delivering safe and patient-centered care through voices of physicians’, and nurses.’ METHODS/STUDY POPULATION: We collected data through in-person interviews using semi-structured guides tailored to the informant roles. Study participants came from 1 healthcare system located in a mid-Western state. Each interview lasted 30–45 minutes, was audio-recorded with consent, and transcribed for analysis. Two researchers each coded 17 transcripts for discussions around patient-centeredness (including patient satisfaction, patient experiences), and patient safety for hospitalized patients experiencing pain. Analysis followed a general inductive approach, where researchers identified themes related to the research questions using an open coding technique. They discussed and reached consensus on all codes, and extracted several preliminary themes. The analysis was supported by NVivo software. RESULTS/ANTICIPATED RESULTS: The following themes emerged: (1) complex decision-making process to prescribe opioids for hospitalized patients; (2) the role of objective findings in prescribing decisions; (3) bargaining process in prescribing opioids; (4) balancing patient-centeredness and patient safety for selected populations; (5) opioids are the predominant medications for pain care. DISCUSSION/SIGNIFICANCE OF IMPACT: Clinicians’ decision to prescribe opioids for nonsurgical hospitalized patients is based on multiple factors, including patient’s condition, patient’s preference for pain medications, or standard hospital’s pain care regimen. Interventions that improve clinicians’ ability to prescribe opioids may be needed to improve delivery of patient-centered and safe pain care.

Higher education institutions promote interfaculty collaborations in research and education projects, but few studies have examined the challenges of such collaborations. This case study investigates how a heterogeneous interfaculty group worked in a community of practice for two years curating an educational e-resource to support the professional learning of academic leaders of student international mobility experiences in their university. Focusing on the "journey" of working within this community of practice rather than the "destination" (the e-resource they produced), the study explores how the different members of the group negotiated the tensions and uncertainty associated with an interdisciplinary collaboration. Data in the form of reflexive 'critical incident' narratives written by all seven authors reveal the challenges of sustaining a 'dialogue across difference' in this cross-disciplinary collaboration. The study supports existing research that argues interfaculty collaborations are potentially rich and generative, but shows why success should not be taken for granted.

Abstract Background Burden of dementia is expected to substantially increase. Early dementia is underdiagnosed in primary care. Given the benefits of active management of dementia, earlier detection in primary care is imperative. The aim of this study was to understand primary care provider (PCP) perceptions of implementing a cognitive assessment toolkit in primary care. Methods PCPs in a large health system in the US were recruited to a qualitative study utilizing semi-structured interviews. Interviews captured provider perceptions of options for implementing a cognitive assessment toolkit derived from the Gerontological Society of America (GSA) KAER (Kickstart, Assess, Evaluate, Refer) toolkit, including a workflow and adapted clinical tools. A content analysis approach distinguished themes and exemplary quotes. Results Ten PCPs were interviewed. They found the toolkit useful, felt the term Kickstart was not specific to dementia care, and stressed that addressing cognitive evaluation would need to be easy to implement in a clinical workflow. Finally, providers knew many resources for referral but were unsure how to help patients navigate options. Conclusions Providers stressed simplicity, ease, and efficiency for implementation of a cognitive assessment toolkit. Incorporating these findings into the development of clinical tools and workflows may increase cognitive evaluations conducted by PCPs.

The global market for End of Life Lithium-Ion Batteries is growing exponentially to satisfy the needs of electric mobility and clean energy technologies. Reusing or repurposing these batteries could ensure sustainability and keep the excessive demands of raw materials in check. However, a strong commitment and trust from the various stakeholders is necessary to build such circular industrial systems. In this paper, a thorough analysis of practices and regulations allowed us to highlight the actors and processes involved in the life cycle of repurposed Lithium-Ion Batteries (LIBs). This led us to propose a conceptual framework describing a generic organization for LIB repurposing. LIB State of Health and diagnosis estimations, which can be carried out with data from LIB passports, are also underlined as essential for the functioning of the organization. This was discussed and implemented on a real case of LIBs used as a power source for electric heaters after their first life in a mobility application.

Embryonic stem cells (ESC) are excellent cell culture systems for elucidating developmental signals that may be part of the stem cell niche. Although stem cells are traditionally induced using predominately soluble signals, the mechanical environment of the niche can also play a role in directing cells towards differential cell lineages. Interested in diverging vascular fates, we set out to examine to what extent mechanical signaling played a role in endothelial cell and/or smooth muscle fate. Using chemically-defined staged vascular differentiation methods, vascular progenitor cells (VPC) fate was examined on single stiffness polyacrylamide hydrogels of 10 kPa, 40 kPa and >0.1 GPa. Emergence of vascular cell populations aligned with corresponding hydrogel stiffness: EC-lineages favoring the softer material and SMC lineages favoring the stiffest material. Statistical significance was observed on both cell lines on almost all days. Transcriptome analysis indicated that the populations on the varying stiffness emerge in distinct categories. Lastly, blocking studies show that αvβ1, and not αvβ6, activation mediates stiffness-directed vascular differentiation. Overall, these studies indicate that softer materials direct VPCs into a more EC-like fate compared to stiffer materials. STATEMENT OF SIGNIFICANCE: Although stem cells are traditionally induced using predominately soluble signals, the mechanical environment of the niche also plays a role in directing cell fate. Several studies have examined the stiffness-induced cell fate from mesenchymal stem cells (MSCs) and undifferentiated embryonic stem cells (ESCs). This is the first study that rigorously examines the role of matrix stiffness in diverging vascular fates from a purified population of vascular progenitor cells (VPCs). We show that the emergence of endothelial cell (EC) versus smooth muscle cell (SMC) populations corresponds with hydrogel stiffness: EC-lineages favoring the softness material and SMC lineages favoring the stiffest material, and that αvβ1 activation mediates this stiffness-directed vascular differentiation.

Background: Migraine is a disabling disorder that impacts 40 million people in the US. Zavegepant is the first calcitonin gene-related peptide (CGRP) receptor antagonist nasal-spray approved for the acute treatment of migraine with or without aura in adults. This study aimed to evaluate the proportion of patients in various pain and functional disability states over 48-h, for patients treated with zavegepant 10 mg nasal-spray versus placebo. Methods: This post-hoc analysis included adult patients with > 1-year history of migraine from BHV3500-301 (NCT04571060): a phase 3 double-blind, randomized, placebo-controlled, single-attack study. Over 48-h, pain severity and functional disability were captured at various timepoints (pre- and post-dosing). The proportion of patients at each pain severity or functional disability state and the time spent in each category was calculated. These were analyzed for patients with complete timepoint data available and using missing not at random (MNAR) imputation for missing timepoints. Predictors of functional disability were assessed using a mixed-effects logistic regression model. Results: There were 1,269 patients included in the MNAR imputation analysis, and between 630–641 in the complete-case analysis. As early as 15-min post-dose, a larger proportion of zavegepant patients achieved no/mild pain compared to placebo, despite balanced migraine severity pre-dose. Furthermore, zavegepant patients spent significantly more time (over 2.5-h) in pain freedom compared to placebo. Similarly, a higher proportion of patients with normal function was observed with zavegepant vs placebo, as early as 30-min post-dose. Over 48-h, patients treated with zavegepant spent an average of ~ 3-h longer with normal functioning compared to placebo. Results were similar when analyzing both analytic groups. In a regression model, treatment with zavegepant, lower pain severity, fewer baseline monthly migraine days, and absence of photophobia, phonophobia, and nausea were associated with better functioning (p < 0.05) over 48-h. Conclusion: This post-hoc analysis demonstrates the benefit of zavegepant nasal spray over placebo on two patient-centric endpoints: time spent with pain freedom and normal functioning over 48-h post-dose. These data support the use of zavegepant for providing rapid and sustained freedom from migraine pain and freedom from migraine related disability, particularly for those who would benefit from the nasal CGRP formulation. [ABSTRACT FROM AUTHOR]

Traumatic spinal cord injury (TSCI) is a significant public health challenge that has an adverse impact on functional independence, quality of life, and life expectancy. Management of people’s chronic conditions is a key aspect of contemporary medical practice. Our study was an open label, single arm, prospective pilot study to evaluate the feasibility of treating people with TSCI. The study intervention was treatment with oral selenium and vitamin E. Participants were 18 years or older and experienced a TSCI at least one year prior to enrollment. Daily doses of 50 mcg of selenium and 400 IU of vitamin E were administered. Participants had radiologic (MRI tractography) and clinical (ASIA) assessments prior to initiating treatment, and these assessments were repeated after one year of treatment. Four subjects completed the full twelve-month study. Adherence, based on pill counts, was approximately 75% in all subjects. There were no adverse events related to study medications. During the treatment period, subjects reported improvement in certain symptoms. There was no significant difference in ASIA scores before and after the intervention. Combination treatment with vitamin E and selenium has been demonstrated as safe for TSCI patients. It is possible to use DTI values to locate the epicenter of a lesion as well as gauge the extent of injury. MRI tractography may serve as a meaningful surrogate endpoint. The results of this study suggest that it is feasible to conduct a larger long-term clinical trial to evaluate the efficacy of combination treatment of TSCI.