Search

David MG Halpin,1 Adrian Paul Rabe,2,3 Wei Jie Loke,4,5 Stacy Grieve,6 Patrick Daniele,6 Sanghee Hwang,6 Anna Forsythe6,7 1Respiratory Medicine, University of Exeter Medical School, College of Medicine and Health, University of Exeter, Exeter, Devon, UK; 2Primary Care and Public Health, Imperial College London, London, UK; 3Global Medical Affairs, AstraZeneca, Cambridge, UK; 4Lister Hospital, Stevenage, East and North Hertfordshire NHS Trust, Stevenage, UK; 5Ways Group, London, UK; 6North America Real World Advanced Analytics, Cytel, Inc., Waltham, MA, USA; 7Value and Access, Cytel, Inc., Waltham, MA, USACorrespondence: Anna Forsythe, Value and Access, Cytel, Inc., 1050 Winter Street, Suite 2700, Waltham, MA, 02451, USA, Tel +1-617-661-2011, Email Anna.Forsythe@cytel.comPurpose: There has been concern that asthma and chronic obstructive pulmonary disease [COPD] increase the risk of developing and exacerbating COVID-19. The effect of medications such as inhaled corticosteroids (ICS) and biologics on COVID-19 is unclear. This systematic literature review analyzed the published evidence on epidemiology and the burden of illness of asthma and COPD, and the use of baseline medicines among COVID-19 populations.Patients and Methods: Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, Embase®, MEDLINE® and Cochrane were searched (January 2019–August 2021). The prevalence of asthma or COPD among COVID-19 populations was compared to the country-specific populations. Odds ratios (ORs) were estimated to compare healthcare resource utilization (HCRU) rates, and meta-analyses of outcomes were estimated from age-adjusted ORs (aORs) or hazard ratios (aHRs). Meta-analyses of COVID-19 outcomes were conducted using random effects models for binary outcomes.Results: Given the number and heterogeneity of studies, only 183 high-quality studies were analyzed, which reported hospitalization, intensive care unit (ICU) admissions, ventilation/intubation, or mortality. Asthma patients were not at increased risk for COVID-19–related hospitalization (OR = 1.05, 95% CI: 0.92 to 1.20), ICU admission (OR = 1.21, 95% CI: 0.99 to 1.1.48), ventilation/intubation (OR = 1.24, 95% CI: 0.95 to 1.62), or mortality (OR = 0.85, 95% CI: 0.75 to 0.96). Accounting for confounding variables, COPD patients were at higher risk of hospitalization (aOR = 1.45, 95% CI: 1.30 to 1.61), ICU admission (aOR = 1.28, 95% CI: 1.08 to 1.51), and mortality (aOR = 1.41, 95% CI: 1.37 to 1.65). Sixty-five studies reported outcomes associated with ICS or biologic use. There was limited evidence that ICS or biologics significantly impacted the risk of SARS-CoV-2 infection, HCRU, or mortality in asthma or COPD patients.Conclusion: In high-quality studies included, patients with asthma were not at significantly higher odds for adverse COVID-19–related outcomes, while patients with COPD were at higher odds. There was no clear evidence that baseline medication affected outcomes.Registration: PROSPERO (CRD42021233963).Keywords: healthcare resource utilization, mortality, SARS-COV-2, inhaled corticosteroids, biologics

Mihaela Georgiana Musat,1 Christina Soeun Kwon,1 Elizabeth Masters,2 Slaven Sikirica,3 Debduth B Pijush,3 Anna Forsythe4 1Evidence Generation, Purple Squirrel Economics, a Wholly Owned Subsidiary of Cytel, Inc., Waltham, MA, USA; 2Real World Evidence, Pfizer, New York, NY, USA; 3Global Health Economics and Outcomes Research, Pfizer, New York, NY, USA; 4Value and Access, Purple Squirrel Economics, a Wholly Owned Subsidiary of Cytel, Inc., Waltham, MA, USACorrespondence: Mihaela Georgiana MusatPurple Squirrel Economics, a Wholly Owned Subsidiary of Cytel, Inc, 1050 Winter Street, Waltham, MA, 02451, USAEmail mihaela.musat@pshta.comBackground: To date, there has been limited synthesis of RWE studies in high-risk non-muscle invasive bladder cancer (HR-NMIBC). The objective of this research was to conduct a systematic review of published real-world evidence to better understand the real-world burden and treatment patterns in HR-NMIBC.Methods: An SLR was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines with the scope defined by the Population, Intervention Comparators, Outcomes, and Study design (PICOS) criteria. EMBASE, MEDLINE, and Cochrane databases (Jan 2015–Jul 2020) were searched, and relevant congress abstracts (Jan 2018–Jul 2020) identified. The final analysis only included studies that enrolled ≥ 100 patients with HR-NMIBC from the US, Europe, Canada, and Australia.Results: The SLR identified 634 RWE publications in NMIBC, of which 160 studies reported data in HR-NMIBC. The average age of patients in the studies was 71 years, and 79% were males. The rates of BCG intravesical instillations ranged from 3% to 86% (29– 95% for induction and 8– 83% for maintenance treatment). Five-year outcomes were 17– 89% recurrence-free survival (longest survival in patients completing BCG maintenance), 58– 89% progression-free survival, 71– 96% cancer-specific survival (lowest survival in BCG-unresponsive patients), and 28– 90% overall survival (lowest survival in patients who did not receive BCG or instillation therapy).Conclusion: BCG treatment rates and survival outcomes in patients with HR-NMIBC vary in the real world, with better survival seen in patients completing maintenance BCG, responding to treatment, and not progressing to muscle-invasive disease. There is a need to better understand the factors associated with BCG use and discontinuation and for an effective treatment that improves outcomes in HR-NMIBC. Generalization of these results is limited by variations in data collection, reporting, and methodologies used across RWE studies.Keywords: real-world outcomes, high-risk NMIBC

Research has highlighted the connection between involvement and important postsecondary outcomes such as persistence, interpersonal/intrapersonal development, civic engagement, and multicultural competence, among many others. However, for students with minoritized identities of sexuality and gender (MIoSG), engaging in identity-based organizations comes with both risks and benefits, especially in a time of increasingly prevalent anti-queer and anti-trans U.S.-based legislation. Our findings reveal the complexity of student experiences, with a specific focus on STEM students who hold MIoSG, from overall positive involvement experiences to barriers such as danger, inactive clubs, and lack of campus spaces. This focus on MIoSG students within STEM disciplines is important, as students often report STEM spaces as particularly oppressive, therefore having a high need for counter spaces where their identities are supported. These findings could help practitioners rethink how to design campus spaces where students do not have to fear for their physical, emotional, and professional safety.

Scholarly writing for academic publication follows discipline-specific constraints where alpha-numeric forms of text are common modes of communication. While figures can be integrated into scholarly publications, graphics are required to fit specific style guides depending on the established criteria for the academic journal. When preparing teaching materials, constraints on communication and production can limit thinking and understanding. In this paper, we outline how we incorporate graphic creations called sketchnotes into our academic writing practices. Sketchnotes are one-to-two-page, free-form, image-rich documents focusing on a topic, concept, or presentation. For our purposes, academic writing is defined as not only peer-reviewed publications but also web-published scholarly works, including research outputs and writing relating to and including our teaching materials. With this definition, we hope to open up a model for expanding the landscape of academic writing, which supports our sketchnoting as part of an open educational practice. Our open practices using sketchnotes include peer-reviewed journal publications, open web publications on our blog sites, and the learning objects we have created as alternative readings of course content.

Anna Forsythe, Karen Sandman Purple Squirrel Economics, New York, NY, USACorrespondence: Anna ForsytheManaging Partner and CEO, Purple Squirrel Economics, 4 Lexington Ave, Suite 15K, New York, NY, 10010, USATel +1-646-477-0936Email Annaforsythe@pshta.comAbstract: Acute myeloid leukemia (AML) is conventionally treated with chemotherapy in eligible patients. Potentially curative regimens are associated with significant toxicity, and the major cost drivers in AML historically have been hospitalization and hematopoietic stem cell transplantation. The past several years have seen a dramatic increase in the number of treatment options, including oral therapies and drugs targeted to biological pathways implicated in AML. Major current and future drivers of cost in AML include hospitalization and medical costs, stem cell transplantation for eligible patients, and medication costs. It is likely that hospitalization and medical costs will decline as more AML treatment moves to the outpatient setting. Stem cell transplantation costs may increase, if more patients are eligible for improved procedures, although the overall cost of transplantation could decrease if new procedures reduce the need for hospitalization. Medication costs are likely to increase, with various branded drugs available and in development. From a broader perspective, another driver of cost is the proportion of patients with AML who can undergo treatment. Patients who may previously have been unable to tolerate chemotherapy are more likely to be treated with the range of less intensive, more tolerable options now available. The effectiveness of newer AML treatment options also suggests that, overall, there may be more patients staying alive and on treatment longer than in the past. While certain advances, such as increased use of oral and outpatient therapies, could potentially reduce costs, the overall economic impact of AML is likely to increase as more patients are eligible for novel therapies across several phases from induction to maintenance to relapsed/refractory disease. While these novel therapies have the potential to deliver value in the form of improved efficacy, safety, and convenience, payers will need to determine how to cover a longer, more complex AML treatment pathway.Keywords: AML, leukemia, cost of illness, economic burden

Gabriel Tremblay,1 Qayyim Said,2 Anuja Nidumolu Roy,2 Beilei Cai,2 Shan Ashton Garib,1 Jaclyn Hearnden,1 Anna Forsythe1 1Purple Squirrel Economics, New York, NY, USA; 2Novartis Pharmaceutical Corporation, East Hanover, NJ, USACorrespondence: Gabriel TremblayPurple Squirrel Economics, 4 Lexington Ave, Suite 15K, New York, NY 10010, USATel +1 418 317 5627Email gabrieltremblay@pshta.comBackground: Severe aplastic anemia (SAA) is a rare autoimmune condition resulting in low blood cell counts across lineages. Immunosuppressive therapy (IST) has demonstrated low response, toxicity, and risk of transformation. In a Phase I/II trial, the addition of eltrombopag to first-line IST increased response rates relative to an IST-only historical cohort.Methods: A model was developed to estimate the budget impact of treating SAA with eltrombopag-based therapy from a US private healthcare system perspective. A simulated cohort of newly diagnosed SAA patients based on the total US population received 6 months of IST ± eltrombopag and were followed for 1 year, with mutually exclusive patient cohorts entering in years 1, 2, and 3. The model assessed the budget impact of first-year treatment for each cohort without considering subsequent years. At 6 months, responders in either arm received maintenance therapy (low-dose cyclosporine), and non-responders received 6 months of second-line eltrombopag monotherapy. Costs considered included first-line, maintenance, and second-line therapy, administration, routine care, mortality, and adverse events (AEs). All cost data were reported in 2018 US dollars.Results: The annual incidence of aplastic anemia was 0.000234%, with 83.8% of cases assumed to be SAA. Based on trial data, 94% of patients receiving eltrombopag and IST responded versus 66% of patients receiving IST, with a 0.3% reduction in the annual risk of mortality for the eltrombopag + IST group. Use of first-line eltrombopag in a model SAA population based on the total US population increased overall costs by $50 million over 3 years. First-line drug costs accounted for an increase of $69 million, while improved response produced $19 million in secondary therapy cost savings. Sensitivity analyses confirmed the robustness of the analysis.Conclusion: High response rates combined with reduced rescue medication use and mortality in patients treated with eltrombopag and IST mediated higher medication costs.Keywords: budget impact analysis, costs, eltrombopag, severe aplastic anemia, thrombopoietin receptor agonist, United States

Anna Forsythe,1 Christina S Kwon,1 Timothy Bell,2 T Alexander Smith,3 Bhakti Arondekar4 1Purple Squirrel Economics, New York, NY, USA; 2Pfizer Inc, New York, NY, USA; 3Pfizer Ltd, Walton Oaks, UK; 4Pfizer Inc, Collegeville, PA, USA Background: AML is a rapidly progressing bone marrow cancer, with poor survival rates compared to other types of leukemia. IC and NIC as well as BSC treatment options are available; however, there is scant published literature on the impact of disease and treatment on the HRQoL in patients receiving NIC.Aim: This study determined the HRQoL among NIC AML patients.Materials and methods: Embase, Medline, Cochrane database, and conference abstracts were searched using the prespecified PICOS criteria from January 2000 to November 2017 for studies reporting HRQoL and patient preference utilities in NIC AML. Studies on patients with RAEB-t MDS, randomized clinical trials (RCTs), prospective observational studies, and patient surveys were included, while systematic reviews and meta-analyses were used for bibliographic searching.Results: Thirteen records from 12 original studies were identified. These included five records from four RCTs, three prospective studies, four patient survey studies, and one cost-effectiveness analysis. At baseline, NIC AML patients had poor HRQoL scores especially in fatigue (33) and GHS (50) on a 0–100 scale, with higher scores indicating better health. Low baseline HRQoL scores, especially PF and fatigue (

Anna Forsythe,1 David Chandiwana,2 Janina Barth,3 Marroon Thabane,4 Johan Baeck,2 Gabriel Tremblay1 1Purple Squirrel Economics, New York, NY, 2Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 3Novartis Pharma GmbH, Nuremberg, Germany; 4Novartis Pharmaceuticals Incorporated, Dorval, QC, Canada Background: Several recent randomized controlled trials (RCTs) in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) metastatic breast cancer (MBC) have demonstrated significant improvements in progression-free survival (PFS); however, few have reported improvement in overall survival (OS). The surrogacy of PFS or time to progression (TTP) for OS has not been formally investigated in HR+, HER2– MBC.Methods: A systematic literature review of RCTs in HR+, HER2– MBC was conducted to identify studies that reported both median PFS/TTP and OS. The correlation between PFS/TTP and OS was evaluated using Pearson’s product–moment correlation and Spearman’s rank correlation. Subgroup analyses were performed to explore possible reasons for heterogeneity. Errors-in-variables weighted least squares regression (LSR) was used to model incremental OS months as a function of incremental PFS/TTP months. An exploratory analysis investigated the impact of three covariates (chemotherapy vs hormonal/targeted therapy, PFS vs TTP, and first-line therapy vs second-line therapy or greater) on OS prediction. The lower 95% prediction band was used to determine the minimum incremental PFS/TTP months required to predict OS benefit (surrogate threshold effect [STE]).Results: Forty studies were identified. There was a statistically significant correlation between median PFS/TTP and OS (Pearson =0.741, P=0.000; Spearman =0.650, P=0.000). These results proved consistent for chemotherapy and hormonal/targeted therapy. Univariate LSR analysis yielded an R2 of 0.354 with 1 incremental PFS/TTP month corresponding to 1.13 incremental OS months. Controlling the type of treatment (chemotherapy vs hormonal/targeted therapy), line of therapy (first vs subsequent), and progression measure (PFS vs TTP) led to an improved R2 of 0.569 with 1 PFS/TTP month corresponding to 0.78 OS months. The STE for OS benefit was 5–6 months of incremental PFS/TTP.Conclusion: We demonstrated a significant association between PFS/TTP and OS, which may justify the use of PFS/TTP as a surrogate for OS benefit in HR+, HER2– MBC. Keywords: breast cancer, overall survival, progression-free survival, time to progression, correlation analysis, surrogate endpoint

Gabriel Tremblay,1 David Chandiwana,2 Mike Dolph,1 Jaclyn Hearnden,1 Anna Forsythe,1 Mauricio Monaco2 1Purple Squirrel Economics, New York, NY, USA; 2Novartis Pharmaceutical Corporation, East Hanover, NJ, USA Background: Ribociclib (RIBO) and palbociclib (PALBO), combined with letrozole (LET), have been evaluated as treatments for hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in separate Phase III randomized controlled trials (RCTs), but not head-to-head. Population differences can lead to biased results by classical indirect treatment comparison (ITC). Matching-adjusted indirect comparison (MAIC) aims to correct these differences. We compared RIBO and PALBO in hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer using MAIC. Methods: Patient-level data were available for RIBO (MONALEESA-2), while only published summary data were available for PALBO (PALOMA-2). Weights were assigned to MONALEESA-2 patient data such that mean baseline characteristics matched those reported for PALOMA-2; the resulting matched cohort was used in comparisons. Limited by the results reported in PALOMA-2, progression-free survival (PFS) was the primary comparison. Cox regression models were used to calculate adjusted hazard ratios (HRs) for PFS, before indirect treatment comparison (ITC) was performed with 95% confidence intervals. An exploratory analysis was performed similarly for overall survival using earlier PALBO data (PALOMA-1). Grade 3/4 adverse events were also compared. Results: Racial characteristics, prior chemotherapy setting, and the extent of metastasis were the most imbalanced baseline characteristics. The unadjusted PFS HRs were 0.556 (0.429, 0.721) for RIBO+LET versus LET alone and 0.580 (0.460, 0.720) for PALBO+LET versus LET alone. MAIC adjustment resulted in an HR of 0.524 (0.406, 0.676) for RIBO+LET versus LET. PFS ITC using unadjusted trial data produced an HR of 0.959 (0.681, 1.350) for RIBO versus PALBO, or 0.904 (0.644, 1.268) with MAIC. Unadjusted overall survival HR of RIBO versus PALBO was 0.918 (0.492, 1.710); while exploratory MAIC was 0.839 (0.440, 1.598). ITC of grade 3/4 adverse events yielded a risk ratio of 0.806 (0.604, 1.076). Conclusion: MAIC was performed for RIBO and PALBO in the absence of a head-to-head trial: though not statistically significant, the results favored RIBO. Keywords: breast cancer, indirect treatment comparison, matching-adjusted indirect treatment comparison, ribociclib, palbociclib

Anna Forsythe,1 David Chandiwana,2 Janina Barth,3 Marroon Thabane,4 Johan Baeck,5 Anastasiya Shor,1 Gabriel Tremblay6 1Health Technology Assessment Evidence, Purple Squirrel Economics, New York, NY, USA; 2Global Value and Access, Novartis Pharmaceutical Corporation, East Hanover, NJ, USA; 3German Market Access, Novartis Pharma GmbH, Nuremberg, Germany; 4Health Policy and Patient Access, Novartis Pharmaceuticals Incorporated, Dorval, QC, Canada; 5Global Medical Affairs (Oncology Business Unit), Novartis Pharmaceutical Corporation, East Hanover, NJ, USA; 6Health Economics, Purple Squirrel Economics, New York, NY, USA Background: Hormone receptor-positive (HR+), human epidermal growth factor receptor 2- negative (HER2−), metastatic breast cancer (MBC) accounts for 73% of all MBCs. Endocrine therapy (ET) is the basis of first-line (1L) therapy for patients with HR+/HER2− MBC. Novel therapies have demonstrated improvements in progression-free survival (PFS) compared to ET. The clinical relevance of PFS is being debated, as there is no proven direct correlation with overall survival (OS) benefit to date. We reviewed studies of HR+/HER2− MBC to assess PFS and other factors that influence OS and treatment response, and health-related quality of life (HRQoL). Methods: The Embase®, Medline®, and Cochrane databases were systematically searched to identify studies in adult women with HR+/HER2− MBC, published between January 2006 and January 2017, and written in English. Phase II and III randomized controlled trials (RCTs), observational, and retrospective studies were included. Results: Seventy-nine RCTs were identified: 58 (73%) in the 1L+ setting and 21 (27%) in second-line or greater settings. PFS hazard ratios (HRs) were reported in 61 (77%) studies; 31 (39%) reported significant PFS improvements. OS was reported in 44 (41%) studies; 12 (15%) reported significant OS improvements. Significant improvements in both PFS and OS were reported in only 6 (8%) studies (1 Phase II; 5 Phase III). Patients with HER2− MBC received, on average, ≥5 lines of therapy, with no consistent treatment pathway. Baseline characteristics, prior therapies, and the type and number of post-progression therapies significantly impacted OS. PFS, response rates, and HRQoL decreased with each line of therapy (EuroQol 5 Dimensions: 0.78 1L vs. 0.70 post-progression). Conclusion: Few RCTs in HR+/HER2− MBC have demonstrated significant improvements in OS. Factors other than choice of 1L therapy impact OS, including post-progression therapies, which cannot be controlled in RCTs. This study emphasizes the importance of PFS improvement in 1L treatment of HR+/HER2− MBC. Keywords: breast cancer, overall survival, progression-free survival, health-related quality of life, systematic literature review

Anna Forsythe,1 Patricia S Brandt,2 Mike Dolph,1 Sachin Patel,3 Adrian Paul J Rabe,1 Gabriel Tremblay1 1Purple Squirrel Economics, New York, NY, 2Novartis Pharmaceuticals, East Hanover, NJ, USA; 3Novartis Pharmaceuticals UK Limited, Frimley, Camberley, Surrey, UK Background: Cost-utility analyses for acute myeloid leukemia (AML) require health state utility values (HSUVs) in order to calculate quality-adjusted life-years (QALYs) for each health state. Aim: This study reviewed AML-related HSUVs that could be used in economic evaluation studies. Materials and methods: EMBASE, MEDLINE, and Cochrane databases were searched from January 2000 to November 2016 for relevant studies that reported quality of life (QoL) and HSUVs in AML. Identified relevant European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 values were mapped to HSUVs. HSUVs for each health state in the AML treatment pathway were then collated. Results: Ten relevant studies were identified. Six were cost-effectiveness analyses utilizing HSUVs for calculation of QALYs, one was an effectiveness analysis (incremental QALY), and two were QoL studies reporting AML-specific utilities. An additional study reported QoL for patients undergoing stem cell transplantation (SCT). Since no study reported HSUVs for relapse, values from a study of secondary AML patients who failed prior treatment for myelodysplastic syndrome were used. Where multiple HSUVs were available, collected values were given priority over assumed values. AML treatment (induction, consolidation, or SCT) was associated with decreased HSUV, while post-treatment complete remission led to increased HSUV. Conclusion: There are some methodologically robust HSUVs that can be directly used in economic evaluations for AML. Careful interpretation is advised considering significant differences in methodologies and patient population (inclusion, size). We need to develop HSUVs with larger-sized studies, making greater use of condition-specific data. Keywords: acute myeloid leukemia, EQ-5D, health-related quality of life, utility, systematic review, economic analysis, QALY

Small intestinal neuroendocrine tumors, siNETs, are a group of rare cancers that arise from neuroendocrine cells in the lining of the jejunum and ileum, which are either classified as tumors, siNETs, or small intestinal neuroendocrine carcinomas, siNECs. Current treatment strategies for low-grade tumors include surgical resection, peptide radionucleotide receptor therapy, and somatostatin analogues, while high-grade and recurrent tumors may receive cytotoxic chemotherapy. These limited treatment options are linked to the lack of representative models that can both reflect the biology of the tumor and are amenable to mid-to-high throughput experimentation. Cell line generation is challenging considering the indolent nature of primary lesions, although some attempts have been successful using a variety of methods and include the primary P-STS line and those derived from metastatic lesions, including GOT1, CNDT2.5, and HC45. Patient-derived modeling, including organoids and xenografting, have allowed for multicellular and 3D representations of the original tumor. These specific models allow for multicellular populations derived from the tumor, providing better tumor representation for use in drug screening and in vitro assays. Currently, there are limited, although increasing, published models of siNETs implanted as xenografts in mice and zebrafish. As these cellular and animal models provide insights into siNET biology, theragnostic modeling has provided key information on the clinical progression and treatment of this disease. Significant strides toward more representative models have been made throughout the last decade. In this review, details of these attempts as well as future directions and strategies for more robust models will be addressed.

Abstract Background The uptake of research findings into clinical practice is critical to providing health care that improves health outcomes for patients. This study explored how Patient-Centered Outcomes Research Institute (PCORI) awardees perceive the relationship between engagement of patients and other partners in research and three uses, or applications, of patient-centered comparative clinical effectiveness research (CER) study findings, which may lead to uptake in clinical practice: (1) Integration into clinical practice guidelines, recognized point-of-care decision tools, or documents that may inform policy; (2) Implementation beyond the study, including at sites outside of the study setting or patient populations; and (3) Active dissemination of findings to specific audiences by parties external to the study team. Methods This exploratory qualitative study examined awardee and partner perceptions of what led to each use of study findings and how engaged partners contributed. We purposively selected PCORI-funded research projects with documentation of each use and conducted virtual interviews with 42 individuals (15 PIs or project leads, 2 research team members, and 25 partners) from 17 projects. We conducted thematic analysis of individual projects or project sets, across projects within each use case, and across the three uses. Results Participants described three primary activities in which engaged partners made contributions before, during and after CER studies that facilitated the use of study findings: (1) generating relevant study findings, (2) distributing study findings strategically, and (3) making connections to people or organizations outside the study team. In addition, engagement continued to facilitate the use of study findings during subsequent PCORI-funded implementation and dissemination-specific projects, with partners adapting interventions and creating and tailoring dissemination messages and products. Finally, participants described attributes of teams’ engagement approaches that may have supported partner contributions, including early and ongoing engagement, leveraging partners’ connections and understanding of community needs, and using multiple engagement approaches. Conclusion This study identified examples of how engagement can help facilitate the use of CER study findings, especially when engagement contributions occur in meaningful ways. Findings from this study suggest a framework for future research on the relationship between engagement in research and uptake of study findings into clinical practice.

Introduction: A valid, longitudinal approach is critical for service planning in healthcare and to understand career choice in medical graduates. Methods: We quantitatively analysed self-reported influences underlying career choice in a national cohort of medical graduates over the first five years of their careers. Participants rated career influences on importance across 26 items using a 5-point Likert scale (1=not at all, 5=a great deal). Results: We included 659 New Zealand medical graduates (mean 25.4 years old, 376 F, 283 M) from the University of Auckland and the University of Otago, graduating in 2012 and 2013 (85% response rate). Responses were linked longitudinally over their post-graduate years 1, 3 and 5, and underwent principal component analyses. At graduation the factor rated as the most important in career choice had a mean (SD) item score of 3.9 (0.7) and comprised: Medical School Experiences; Specialty Experience; Mentors; and Self-Appraisal – consistent with graduates securing initial employment. Factors which explained the most variance in career choice over the five years after graduation indicated that the costs of medical school and further training were consistently rated as the least important in career choices, while flexibility in working hours were consistently rated as the most important. Factors remained relatively stable over time, showing variation in scores of only a median of 0.5 Likert points, indicating further opportunities for career choice research. Conclusion: Our results regarding costs of medical training are reassuring, and suggest that greater flexibility in working hours may attract graduates to underserved specialties.

Andrew G Gianoukakis,1 Natalia M Flores,2 Corey L Pelletier,3 Anna Forsythe,3 Gregory R Wolfe,2 Matthew H Taylor41Division of Endocrinology and Metabolism, Harbor-UCLA Medical Center, The University of California, Los Angeles, 2Health Outcomes Research, Kantar Health, Foster City, CA, 3Global Value and Access, Eisai, Inc., Woodcliff Lakes, NJ, 4Division of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR, USABackground: Patients with differentiated thyroid cancer (DTC) often respond well to treatment but some become refractory to radioactive iodine (RAI) treatment, and treatment options are limited. Despite the humanistic and economic burden RAI refractory disease imposes on patients, published research concerning treatment patterns and health care resource utilization is sparse.Methods: Data were collected from an online retrospective chart review study in the US and five European Union (EU) countries (France, Germany, Italy, Spain, and UK) with physicians recruited from an online panel. Physicians (N=211) provided demographics, disease history, treatment information, and health care resource utilization for one to four of their patients with radioactive iodine refractory differentiated thyroid cancer (RR-DTC).Results: The majority of the patients with RR-DTC (N=623) were female (56%), and their mean age was 58.2 years. In this sample, 63.2% had papillary thyroid cancer and 57.0% were in Stage IV when deemed RAI refractory. Patients with RR-DTC experienced regional recurrence in the thyroid bed/central neck area (25.3%) and had distant metastatic disease (53.6%). At the time data were collected, 50.7% were receiving systemic treatment. Of those, 78.5% were on first-line treatment and 62.7% were receiving multikinase inhibitors. Regional differences for prescribed treatments were observed; the US was more likely to have patients receiving multikinase inhibitors (79.2%) compared with UK (41.2%) and Italy (17.1%). Additional details regarding treatment patterns and resource utilization are discussed.Conclusion: The current study aimed to obtain a greater understanding of RR-DTC treatment globally. These results can assist in the development and implementation of treatment guidelines and ultimately enhance the care of patients with RR-DTC.Keywords: thyroid cancer, disease burden, therapy options, cost of illness

There is a mountain of evidence demonstrating that students with marginalized, i.e. purposefully socially excluded, identities experience significantly worse academic and social outcomes in STEM disciplines. However, there has been less attention on how white women, who experience sexism due to their gender but are privileged due to their race, simultaneously contribute to and play a role in dismantling systemic racism. In this study, I used constructivist grounded theory to explore the process through which white women in STEM commit to racial justice both within and outside of their disciplines. Interviews with 36 white women in STEM across a range of disciplines helped build an emergent model that illustrated how participants advanced through three stages to move toward actionable anti-racist commitment. However, many participants struggled to connect STEM with their anti-racist practice, as many STEM disciplines lacked anti-racism curriculum and/or the ability to practice anti-racism within STEM. This model helps illustrate the complex process in which white women in STEM become committed to racial justice. Within STEM specifically, this research has direct implications for the importance of adding social contexts and anti-racist material directly into STEM curricula to foster anti-racist practices for future STEM professionals.

While decades of scholarship show the oppression of women by the enforcement of patriarchal gender norms, little research has explored the ways in which masculinity receives preferential treatment over femininity, independent of a man/woman binary. This exploration is needed to understand why femininity is devalued within the heteropatriarchal masculine social context under which much of current Western society was formed. In response to this anti-femininity sentiment, an emerging area of study called critical femininity was developed to add unique insights into the way in which femininity is embodied and rejected across genders. In this paper, critical femininity is used to explore how masculine-identifying science, technology, engineering, and mathematics (STEM) students holding minoritized identities of sexuality and/or gender (MIoSG) experience and navigate their campus environments that are steeped in anti-femininity. Only by documenting complex understandings of how men and masculine-identifying STEM individuals (who are the majority of STEM learners and faculty) learn, enact, and reproduce anti-femininity can educators begin to resist and alter harmful patriarchal STEM environments.

Current models of best practice in science education advocate for students to learn science by engaging in applied contexts that integrate the various science disciplines. Permaculture offers one such integrated context for elementary science. Although permaculture is relatively new in PK-12 education, the broader practice of school gardening has an established history of supporting student engagement in and conceptual understanding of science. However, many elementary teachers report feeling unprepared to implement garden-based lessons. This article examines preservice teacher (PST) ideas about permaculture and views toward teaching permaculture that emerged within an elementary science methods course. The course's pilot instructional intervention on permaculture included four components: background permaculture readings and videos, guided discussion, food forest design activity, and lesson plan analysis activity. We designed these components to engage preservice teachers both as current learners and future teachers of permaculture. Data was collected from pre/post-tests, the lesson analysis activity, and the PST daily endof-class reflections. After the permaculture intervention, PSTs self-reported higher levels of knowledge of permaculture topics and ways to use permaculture in their classrooms. They also effectively connected permaculture-based lesson plans to a variety of elementary learning standards. The PSTs positively viewed permaculture-based lessons as providing active, real-life learning experiences that support environmental consciousness, but viewed the cost and time required as barriers to implementing permaculture in their classrooms. Collectively, they positioned the developmental appropriateness and spatial resources required of the lessons as both advantages and disadvantages. Implications for teacher preparation and development are discussed.

The purpose of this qualitative case study was to explore and document the complexity of elementary level teacher candidates' (TC) visions of linguistically responsive literacy instruction while reflecting on and discussing exemplary teachers' video cases in a semester-long video club. The following questions guided this study: What do TC notice and reflect on while engaging in a language and literacy-focused video club? In what ways does participating in a video club inform TC visions of being linguistically responsive literacy teachers? Findings illustrate that as TC engaged in video clubs with their peers, they noticed and reflected on scaffolded instruction (visual and physical supports), student engagement (providing engaging and socially interactive instruction), the importance of building relationships, and equitable and inclusive resources and classroom organization. The process of individually and collectively observing a video case, writing a reflection on that case then discussing it with others provided numerous and repeated opportunities for TC to identify, consider and reconsider specific literacy practices that support language learners. Each case highlighted ways in which TC revealed the vision they have for themselves as teachers, for students, and for their teaching practice. As TC solicited their past lived experiences and present experiences in response to the video cases, they were subtly shaping their visions of their future teaching.

With constantly changing political landscapes affecting the ability of college students with minoritized identities of sexuality and/or gender (MIoSG; Vaccaro et al., 2015) to thrive on campus, higher educators need to understand student reported stressors to design more inclusive learning environments. Building from minority stress theory and using data from a grounded theory study with 56 collegiate STEM students with MIoSG, this paper documents stressors that students reported as contributing to diminished wellbeing. We used constant comparative grounded theory analysis to identify stressors shared by all participants, which included lack of belonging and invisibility in competitive STEM cultures as well as exclusionary interactions with STEM peers. Recommendations include the design and delivery of holistic education and support services on campus.

Beth A Fordham,1 Cicely Kerr,1 Hayley M de Freitas,1 Andrew J Lloyd,1 Karissa Johnston,2 Corey L Pelletier,3 Gabriel Tremblay,3 Anna Forsythe,3 Bryan McIver,4 Ezra EW Cohen5 1ICON Patient Reported Outcomes, Oxford, UK; 2ICON Epidemiology, Toronto, ON, Canada; 3Eisai Inc., NJ, 4Moffitt Cancer Center, FL, 5University of California San Diego Moores Cancer Center, La Jolla, CA, USA Purpose: The aim of this study was to elicit utilities for radioactive iodine-refractory differentiated thyroid cancer (RR-DTC) and evaluate the impact of treatment response and toxicities on quality of life.Patients and methods: RR-DTC health states were developed based on data from a previous qualitative study and iterative review by clinical experts. Following piloting, health states underwent valuation by 100 members of the UK public during time trade-off interviews. Mean utilities and descriptive distribution statistics were calculated, and a logistic regression analysis was conducted.Results: The demographic characteristics of the study sample were generally reflective of the UK population. Clear differentiation in valuation between health states was observed. No response/stable disease had an adjusted utility value of 0.87, with a corresponding gain of +0.04 following a treatment response and a decline of –0.35 for disease progression. Adverse events were associated with utility decrements between –0.47 (grade III diarrhea) and –0.05 (grade I/II alopecia).Conclusion: The trade-off interviews derived utility weights show clear differentiation between RR-DTC health states in response to treatment. The values reported in this study are suitable for cost-effectiveness evaluations for new treatments in RR-DTC. Keywords: differentiated thyroid cancer, radioactive iodine-refractory, health-related quality of life, health utility, vignette

Shaloo Gupta,1 Lance Richard,2 Anna Forsythe3 1Kantar Health, Princeton, NJ, USA; 2Eisai Europe Ltd, Hatfield, UK; 3Eisai Inc., Woodcliff Lake, NJ, USA Objectives: This study evaluated the association of body mass index (BMI) with health-related quality of life (HRQoL), health utilities, health care resource utilization, productivity, activity impairment, and the associated costs. Methods: Results were from the 2013 EU5 (France, Germany, Italy, Spain, UK) National Health and Wellness Survey, a nationally representative, online survey of respondents aged ≥18 years. Analyses focused on normal weight (BMI ≥18.5 kg/m2 and BMI

OBJECTIVES: The primary objective of this study was to evaluate the prescription patterns and appropriateness of the use of gastroprotectant medication in cats. METHODS: Pharmacy dispensation logs from an academic tertiary referral center were reviewed between 1 January 2018 and 31 December 2018. Cats that were administered proton pump inhibitors (PPIs), histamine-2 receptor antagonists (H2RAs), sucralfate, misoprostol, antacids or a combination were included. Data regarding medication, dosage, formulation, duration of administration, completeness of discharge instructions and clinical rationales for administration were obtained from medical records. The appropriateness of gastroprotectant use was assessed according to the American College of Veterinary Internal Medicine consensus statement guidelines. RESULTS: Of the 110 cases, 67 (60.9%) were prescribed a gastroprotectant medication without an appropriate indication. The most common reason for prescription was acute kidney injury in 26/67 (38.8%). PPIs were the most common gastroprotectant medication administered in 95/110 (86.3%) cats, followed by sucralfate in 18/110 (16.4%) and H2RAs in 11/110 (10%). Of the 35 cases in which gastroprotectant therapy was indicated, the medication chosen or dosage administered was considered suboptimal in 16 (45.7%). Instructions regarding the duration of administration, potential adverse effects and timing of administration in relation to meals or other medications were inconsistently provided in discharge instructions to pet owners. Of the 29 cases discharged with omeprazole, only 13 (44.8%) instructions included a duration of administration, while 6 (20.7%) recommended continuing gastroprotectants indefinitely until further notice, 16 (55.2%) discussed the timing of the administration in relation to a meal and six (20.7%) mentioned potential adverse effects; none advised tapering of omeprazole before discontinuation. CONCLUSIONS AND RELEVANCE: When prescribed, gastroprotectant medications were frequently prescribed injudiciously to cats in this referral population over a 12-month period. Discharge instructions to pet owners also often lacked information and recommendations regarding optimal administration, potential adverse effects, and tapering or discontinuation of the medications.

Since 2011, the Global Energy and Water cycle Exchanges (GEWEX) Water Vapor Assessment (G-VAP) has provided performance analyses for state-of-the-art reanalysis and satellite water vapour products to the GEWEX Data and Analysis Panel (GDAP) and the user community in general. A significant component of the work undertaken by G-VAP is to characterise the quality and uncertainty of these water vapour records to (i) ensure full exploitation and (ii) avoid incorrect use or interpretation of results. This study presents results from the second phase of G-VAP, where we have extended and expanded our analysis of total column water vapour (TCWV) from phase 1, in conjunction with updating the G-VAP archive. For version 2 of the archive, we consider 28 freely available and mature satellite and reanalysis data products, remapped to a regular longitude–latitude grid of 2° × 2° and on monthly time steps between January 1979 and December 2019. We first analysed all records for a “common” short period of 5 years (2005–2009), focusing on variability (spatial and seasonal) and deviation from the ensemble mean. We observed that clear-sky daytime-only satellite products were generally drier than the ensemble mean, and seasonal variability/disparity in several regions up to 12 kg m−2 related to original spatial resolution and temporal sampling. For 11 of the 28 data records, further analysis was undertaken between 1988–2014. Within this “long period”, key results show (i) trends between −1.18 ± 0.68 to 3.82 ± 3.94 kg m−2 per decade and −0.39 ± 0.27 to 1.24 ± 0.85 kg m−2 per decade were found over ice-free global oceans and land surfaces, respectively, and (ii) regression coefficients of TCWV against surface temperatures of 6.17 ± 0.24 to 27.02 ± 0.51 % K−1 over oceans (using sea surface temperature) and 3.00 ± 0.17 to 7.77 ± 0.16 % K−1 over land (using surface air temperature). It is important to note that trends estimated within G-VAP are used to identify issues in the data records rather than analyse climate change. Additionally, breakpoints have been identified and characterised for both land and ocean surfaces within this period. Finally, we present a spatial analysis of correlations to six climate indices within the long period, highlighting regional areas of significant positive and negative correlation and the level of agreement among records.

Abstract Cronobacter sakazakii clonal complex 4 (CC4) is strongly associated with neonatal meningitis. However, C. sakazakii CC4‐specific pathogenicity traits have not been determined. In this study, the comparative genomic analysis of 144 genomes of C. sakazakii CC4 strains and 376 non‐CC4 C. sakazakii strains was undertaken. Twenty‐four CC4 strains were previously undescribed clinical and nonclinical strains that had been collected from various regions in China (2006–2017). The remaining genomes were of multiple sequence types of C. sakazakii strains, which had been isolated worldwide (1973–2021). The pan‐genome of C. sakazakii comprised 32,332 genes, of which 2.58% (832 genes) constituted the core genome. More C. sakazakii CC4 strains have a complete cusABCFR efflux system with a significant difference compared with non‐CC4 strains, and the ibeB‐homologous cusC gene in the cusABCFR efflux system is probably associated with the invasion of human brain microvascular endothelial cells (BMEC). In addition, the isolates with K2:CA2 capsule or type IV pili‐associated genes associated with neonatal meningitis were statistically more present in CC4 strains than non‐CC4 strains (p

Introduction: Articular cartilage injuries of the knee are a complex and challenging clinical pathology. Objectives: The purpose of this study was to establish consensus statements via a Delphi process on the management of failed knee cartilage surgery. Methods: A consensus process on knee cartilage injuries utilizing a modified Delphi technique was conducted. Seventy-nine surgeons across 17 countries participated in these consensus statements. Eleven questions were generated on the management of failed knee cartilage surgery, with 3 rounds of questionnaires and final voting occurring. Consensus was defined as achieving 80% to 89% agreement, whereas strong consensus was defined as 90% to 99% agreement, and unanimous consensus was defined as 100% agreement with a proposed statement. Results: Of the 11 total questions and consensus statements on the management of failed knee cartilage surgery developed from 3 rounds of voting, 0 achieved unanimous consensus, 10 achieved strong consensus, and 1 achieved consensus. Conclusions: The statements that achieved strong consensus related to revision cartilage indications, contraindications, lesion size, prior procedures, unipolar/bipolar lesions, and salvage procedures. The statement that did not achieve strong consensus was related to the management of a failed osteochondral autograft/allograft.

Applications of Unmanned Aerial Vehicles (UAVs) in construction have been increased in recent years mainly for purposes of automatically collecting field data. In the market, there is a growing opportunity for using UAVs in material handling. On the other side, vertical transportation in construction sites is a crucial challenge that leads to a drop in productivity efficiency. This paper presents a proof of concept for automating the lifting procedure of lightweight instruments and materials in construction sites. To do so, a platform is developed that could automatically manage material/instrument handling requests via an autopilot drone. The aircraft position is tracked with an onboard GPS module which is not accurate in urban areas. So inaccurate GPS signals could deviate the drone from the predefined path. To tackle this problem, a machine vision algorithm is utilized to calibrate the real-time position of the aircraft. A self-supervised learning algorithm is integrated into the system to handling collision avoidance during the flight. Finally, the developed methods are tested with an UAV in a real world environment to demonstrate the potentials of hiring autopilot drones in construction.

This article aims to generate novel insights by examining gender dynamics within aquaculture and small-scale fisheries, employing a gendered agrifood systems conceptual framework to comprehensively analyze gender equality and women’s empowerment in aquatic food systems. To do this, it evaluates 202 articles using a scoping review methodology. Though additional literature from 19 articles was pulled in to provide the context. The findings are that aquatic foods value chains and food environment are negatively impacted by gender disparities in terms of women’s agency, access to and control over resources, gendered social norms, and policies and governance. This hampers the ability of women to engage in and benefit from aquatic food systems. This results in gendered disparities in dietary outcomes, low achievements in relation to gender equality and women’s empowerment, and less adaptive capacity in relation to developing resilient livelihoods. The article acknowledges the importance of developing and leveraging women’s agency and bargaining power, strengthening their access to and control over key aquatic food systems resources, tackling harmful gender norms, developing gender-sensitive data collection and analysis to inform evidence-based policymaking, and implementing gender-responsive and gender-transformative policies and strategies to create an enabling environment for these interventions to succeed. Investment in multi-level, and multi-layered, gender-responsive and gender-transformative approaches are needed to co-develop – with women and their organizations – positive, gender-equitable norms to strengthen women’s agency and decision-making at a variety of levels, ranging from individual to policy level.

Advanced practice providers (APPs) have become essential to trauma teams in the United States during the last few decades. The optimal utilization of APPs is not yet known and is likely highly variable secondary to many factors. We discuss three aspects of the multidisciplinary approach to caring for trauma patients. First, a review of the literature demonstrates that APPs in trauma improve quality of care, patient throughput, and decrease cost. We then report on models of APP utilization by comparing five trauma centers across the country, concluding that utilization remains highly variable due to several system and provider factors. The final portion of this review highlights current billing and coding practices in integrated teams considering recent changes to Centers for Medicare and Medicaid rules in 2024.

Background: Management of long head of the biceps tendon (LHBT) pathology is accomplished through a biceps tenotomy or tenodesis. While both modalities provide beneficial outcomes, a biceps tenodesis may confer improved cosmesis, functional outcomes, and decreased muscle cramping postoperatively. Many procedural considerations are undertaken prior to a tenodesis, such as the surgical approach and fixation device. While similar clinical outcomes are achieved between an open subpectoral and arthroscopic suprapectoral biceps tenodesis (ASPBT) with interference screw (IS) fixation, the latter technique offers a minimally invasive modality. Indications: The primary indications for an ASPBT include superior labrum anterior posterior (SLAP) tears, LHBT tears, biceps instability, bicipital tunnel disease, biceps pulley lesions, and biceps tenosynovitis. Contraindications to the arthroscopic approach include a distal lesion of the biceps tendon below the pectoralis major tendon (PMT). The IS may be used to create a biomechanically stiffer construct. Technique Description: With the arthroscope in the lateral portal, the distal aspect of the bicipital groove proximal to the superior border of the PMT is identified and opened. The LHBT is subsequently mobilized and released. An anterosuperolateral portal is localized with a spinal needle positioned perpendicular to the bicipital tunnel, 1.5 cm proximal to the superior border of the PMT. The biceps is then removed ex vivo and whip-stitches are sewn beginning 1 cm proximal to the myotendinous junction of the LHBT. After firmly associating the LHBT with the tip of the IS, a guidewire is placed 1.5 cm superior to the superior border of the PMT, perpendicular to the humerus, and a reamer is used to prepare a 6-, 7-, or 8-mm diameter socket. The tendon is inserted through the accessory portal into the tunnel, followed by screw fixation. Suture tails are tied with 5 alternating half hitches, each secured via an arthroscopic knot pusher. Results: ASPBT with IS fixation provides significant pain relief, improves range of motion (ROM), and enhances quality of life. Discussion: ASPBT with IS fixation provides significant improvements in patient-reported and functional outcomes and thus can be an acceptable treatment for LHBT pathology. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

We conduct a discrete choice experiment across 771 U.S. households to estimate willingness to pay (WTP) values for autonomous and human grocery delivery. We estimate that urban households, on average, are willing to pay about $6.70 for same-day human delivery to the household’s doorstep. This value drops by about $1.90 for autonomous delivery, by $2.30 per day of delivery delay, and by $3.10 or $7.90 for delivery to curbside or neighborhood locker locations, respectively. Households located 20 min or more from the nearest major grocery store are willing to pay $3 more for delivery than other households and are more willing to accept delivery delay and curbside or locker delivery locations, while households below the poverty line are less sensitive to delivery delay. Using a latent class logit model, we identify three distinct types of consumers: (1) Delivery Compromisers, representing 45% of weighted respondents, prefer delivery but are sensitive to timing, location, and automation; (2) Delivery Indifferent consumers (39%) have no statistically significant WTP for delivery over in-person shopping; and (3) Delivery Enthusiasts (16%) have high WTP for delivery. Simulation results suggest that if autonomous delivery were able to provide rapid delivery at low cost, it could potentially capture a majority of shopping choices for the Enthusiast groups and a substantial share of choices for Compromisers.

Abstract Open science skills are increasingly important for a career in ecology and evolutionary biology (EEB) as efforts to make data and analyses publicly available continue to become more commonplace. While learning core concepts in EEB, students are also expected to gain skills in conducting open science to prepare for future careers. Core open science skills like programming, data sharing, and practices that promote reproducibility can be taught to undergraduate students alongside core concepts in EEB. Yet, these skills are not always taught in biology undergraduate programs, and a major challenge in developing open science skills and learning EEB concepts simultaneously is the high cognitive load associated with learning multiple disparate concepts at the same time. One solution is to provide students with easily digestible, scaffolded, pre‐formatted code in the form of vignettes and interactive tutorials. Here, we present six open source teaching tutorials for undergraduate students in EEB. These tutorials teach fundamental ecological concepts, data literacy, programming (using R software), and analysis skills using publicly available datasets while introducing students to open science concepts and tools. Spanning a variety of EEB topics and skill levels, these tutorials serve as examples and resources for educators to integrate open science tools, programming, and data literacy into teaching EEB at the undergraduate level.