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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.

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.

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.

Prior research has established that undocumented immigrant experiences are dynamic, reflecting the complex web of immigration-related policies that create legal vulnerability. As such, undocumented college students' experiences must be situated in their current policy context. Drawing on descriptive analyses of a survey of 1,277 undocumented 4-year college students in California, we examine how undocumented students are faring in a relatively inclusive policy context. Results demonstrate the heterogeneity of undocumented student experiences and unpack the challenges they confront while also demonstrating the ways they thrive. We document how respondents are performing across a variety of academic, well-being, and civic and political engagement outcomes. We also show that undocumented students' perceptions of legal vulnerability are complex and varied, taking into account family-level legal vulnerability and individual protections. Further, students perceive campuses as fairly welcoming spaces, with some differences arising across the two university systems. Ultimately, we argue that undocumented college students' experiences merit more nuanced and contextualized analysis.

DNA barcoding is a promising technology for the simultaneous analysis of genetic and phenotypic heterogeneity. Here, the authors combine DNA barcoding and single-cell RNA-seq to study heterogeneity, progression and response to therapy in B-cell acute lymphoblastic leukaemia patient-derived xenografts.