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Occupational therapy practitioners provide sensory-based interventions to support children as they learn academically, develop self-regulation skills, and participate in play and activities of daily living skills alongside their peers. These interventions are used both for children who have a specific sensory-related diagnosis as well as children who do not have a specific diagnosis. This study explored common occupational therapy sensory interventions utilized within the United States school settings along with implementation barriers for sensory intervention services for children ages 3-18 years old. Occupational therapy practitioners completed an electronic survey and a focus group. Results indicated that many occupational therapy practitioners frequently used sensory interventions through indirect services with children in preschool and elementary school. Occupational therapy practitioners must provide interprofessional training for education teams for effective sensory intervention implementation in school-based settings.

Objectives Chart review as the current gold standard for phenotype evaluation cannot support observational research on electronic health records and claims data sources at scale. We aimed to evaluate the ability of structured data to support efficient and interpretable phenotype evaluation as an alternative to chart review. Materials and Methods We developed Knowledge-Enhanced Electronic Profile Review (KEEPER) as a phenotype evaluation tool that extracts patient's structured data elements relevant to a phenotype and presents them in a standardized fashion following clinical reasoning principles. We evaluated its performance (interrater agreement, intermethod agreement, accuracy, and review time) compared to manual chart review for 4 conditions using randomized 2-period, 2-sequence crossover design. Results Case ascertainment with KEEPER was twice as fast compared to manual chart review. 88.1% of the patients were classified concordantly using charts and KEEPER, but agreement varied depending on the condition. Missing data and differences in interpretation accounted for most of the discrepancies. Pairs of clinicians agreed in case ascertainment in 91.2% of the cases when using KEEPER compared to 76.3% when using charts. Patient classification aligned with the gold standard in 88.1% and 86.9% of the cases respectively. Conclusion Structured data can be used for efficient and interpretable phenotype evaluation if they are limited to relevant subset and organized according to the clinical reasoning principles. A system that implements these principles can achieve noninferior performance compared to chart review at a fraction of time. [ABSTRACT FROM AUTHOR]

This article examines how ignorance can be produced by regulatory systems. Using the case of contamination from per- and polyfluoroalkyl substances (PFAS), we identify patterns of institutionalized ignorance in U.S. chemical regulation. Drawing on in-depth interviews and archival research, we develop a chemical regulatory pathway approach to study knowledge and ignorance production through the regulatory framework, the Toxic Substances Control Act (TSCA). Investigating TSCA's operation, we consider why PFAS were relatively recently recognized as a significant public health threat, despite evidence of their risks in the 1960s. The historical context of TSCA's enactment, including the mobilization of the chemical industry, contributed to the institutionalization of organizational practices promoting distinct types of ignorance based on stakeholder position: chemical manufacturers who have discretion over knowledge production and dissemination, regulators who operate under selective ignorance, and communities and consumers who experience nescience, or total surprise. [ABSTRACT FROM AUTHOR]

In the absence of comprehensive environmental regulation, under what conditions can social movement pressure on the private sector generate substantive change? We explore this question in relation to per- and poly-fluoroalkyl substances (PFAS), a class of persistent, bioaccumulative, and toxic chemicals that are widely used in consumer products and industrial processes yet remain largely understudied and weakly regulated. This paper focuses on the strengths and limitations of one high-profile shame campaign by Greenpeace that has called for clothing and outdoor brands to eliminate PFAS from their products. We find that while the campaign appears to have spurred widespread awareness of PFAS in the apparel industry, corporate action remains fragmented and leaves broader environmental and social justice concerns unaddressed. We highlight the urgent need for comprehensive federal regulation for toxic chemicals, increased funding for green chemistry, and collaborative governance of global production networks. [ABSTRACT FROM AUTHOR]

The Trump administration has undertaken an assault on the Environmental Protection Agency (EPA), an agency critical to environmental health. This assault has precedents in the administrations of Ronald Reagan and George W. Bush. The early Reagan administration (1981-1983) launched an overt attack on the EPA, combining deregulation with budget and staff cuts, whereas the George W. Bush administration (2001-2008) adopted a subtler approach, undermining science-based policy. The current administration combines both these strategies and operates in a political context more favorable to its designs on the EPA. The Republican Party has shifted right and now controls the executive branch and both chambers of Congress. Wealthy donors, think tanks, and fossil fuel and chemical industries have become more influential in pushing deregulation. Among the public, political polarization has increased, the environment has become a partisan issue, and science and the mainstream media are distrusted. For these reasons, the effects of today's ongoing regulatory delays, rollbacks, and staff cuts may well surpass those of the administrations of Reagan and Bush, whose impacts on environmental health were considerable. [ABSTRACT FROM AUTHOR]

Concern about the toxicity and exposure of per- and polyfluoroalkyl substances (PFASs) is growing among scientists, regulators, and residents of contaminated communities. In 2016, the United States Food and Drug Administration (FDA) removed three food contact substances (FCSs) containing perfluorinated chemicals from the list of approved FCSs due to concerns regarding chemical safety. To investigate the significance and limitations of the FDA's regulatory action for environmental health research, advocacy, and regulation, we conducted a media analysis and qualitative interviews with a range of involved stakeholders. We find that the FDA's regulatory action represents a potential shift from chemical-by-chemical regulation toward class-based regulation, where groups of chemicals can be identified as sharing properties and risks, and are thus evaluated and regulated together. The FDA decision sets an important precedent of using a petition process to delist chemicals based on a safety standard. However, the narrow reach of this action also highlights the need for more comprehensive, precautionary chemical regulation capable of thoroughly evaluating classes of chemicals, and raises important questions about how classes of chemicals are delimited in environmental health science and regulation. [ABSTRACT FROM AUTHOR]

Background: As breast cancer rates increase globally, there is growing scientific consensus that greater understanding of the causes of breast cancer is needed to better prevent its occurrence. Genetics accounts for a small percentage of cases, thus environmental factors and epigenetics are increasingly suspect in breast cancer etiology. Within the breast cancer and environmental breast cancer social movements, there are longstanding calls for research and policy aimed toward the prevention of breast cancer. To better understand the opportunities and barriers to addressing environmental contributors to breast cancer, this article investigates both outcomes and perceptions of stakeholders involved in the Interagency Breast Cancer and Environment Research Coordinating Committee (IBCERCC). The IBCERCC was mandated by the 2008 U.S. Breast Cancer and Environmental Research Act, a law representing years of advocate and researcher efforts to produce national strategies and federal funding for breast cancer prevention research.Methods: To understand the meaning and impact of the IBCERCC advisory committee and final report, Prioritizing Prevention, I draw on fifteen confidential semi-structured interviews with members of the twenty-five person IBCERCC, in addition to six confidential semi-structured interviews with key breast cancer funders, advocates, and researchers affiliated with national reports on environmental contributors to cancer. I examine media coverage, congressional hearing transcripts, and official responses to the release of the IBCERCC report by governmental and non-governmental organizations.Results: Interviews and publicly available documents reveal a set of direct and indirect outcomes of the 2013 IBCERCC report. Interviewees in government positions perceived the 2014 renewal of the Breast Cancer and the Environment Research Program to result from IBCERCC efforts, notable in the context of declining U.S. federal research funding. Interviews also revealed a suite of potential barriers to the implementation of report recommendations including: distinct interpretations of the federal mandate, disparate assessments of scientific evidence, government funding crises, and lack of specificity around responsibility for implementation of report findings.Conclusion: This article examines efforts to shift institutional research and funding priorities in cancer research towards prevention. Social science research can support efforts to shift institutional priorities by identifying broader social contexts and underlying values typically unnamed in scientific discourse. [ABSTRACT FROM AUTHOR]

Engagement with science is a prominent feature for many social movements, yet the dimensions of that scientific engagement and bidirectional relationships between science and advocacy are incompletely theorized in social movement scholarship. While social movement scholarship has previously demonstrated the importance of external political and economic factors for social movement processes and efficacy, we show that the emergence and success of environmental health activism is also dependent on dynamic relationships between scientific evidence and lay demands for particular types of knowledge production and application. Despite decades of industrial production and widespread contamination, per- and polyfluoroalkyl substances (PFAS) were a politically obscure class of chemicals until a recent spike in attention from activist, regulatory, and scientific circles. Drawing from in-depth interviews with activists of PFAS-impacted communities, we develop the scientific opportunity concept to examine how activists create and mobilize scientific factors to support their goals, and how scientific factors, in turn, support the emergence of further activism. Dimensions of scientific opportunity include availability of funding streams, openness and receptivity of institutionalized scientific spaces, presence of collaborative or community-led research, methodological and technological advancements aligned with activist demands, availability of relevant scientific findings and datasets, and presence of prominent scientific allies. We conclude by discussing the relevance of our concept to a wide range of social movements addressing science and technology. [ABSTRACT FROM AUTHOR]

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce the risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM). However, their effectiveness relative to each other and other second-line antihyperglycemic agents is unknown, without any major ongoing head-to-head clinical trials., Objectives: The aim of this study was to compare the cardiovascular effectiveness of SGLT2is, GLP-1 RAs, dipeptidyl peptidase-4 inhibitors (DPP4is), and clinical sulfonylureas (SUs) as second-line antihyperglycemic agents in T2DM., Methods: Across the LEGEND-T2DM (Large-Scale Evidence Generation and Evaluation Across a Network of Databases for Type 2 Diabetes Mellitus) network, 10 federated international data sources were included, spanning 1992 to 2021. In total, 1,492,855 patients with T2DM and cardiovascular disease (CVD) on metformin monotherapy were identified who initiated 1 of 4 second-line agents (SGLT2is, GLP-1 RAs, DPP4is, or SUs). Large-scale propensity score models were used to conduct an active-comparator target trial emulation for pairwise comparisons. After evaluating empirical equipoise and population generalizability, on-treatment Cox proportional hazards models were fit for 3-point MACE (myocardial infarction, stroke, and death) and 4-point MACE (3-point MACE plus heart failure hospitalization) risk and HR estimates were combined using random-effects meta-analysis., Results: Over 5.2 million patient-years of follow-up and 489 million patient-days of time at risk, patients experienced 25,982 3-point MACE and 41,447 4-point MACE. SGLT2is and GLP-1 RAs were associated with lower 3-point MACE risk than DPP4is (HR: 0.89 [95% CI: 0.79-1.00] and 0.83 [95% CI: 0.70-0.98]) and SUs (HR: 0.76 [95% CI: 0.65-0.89] and 0.72 [95% CI: 0.58-0.88]). DPP4is were associated with lower 3-point MACE risk than SUs (HR: 0.87; 95% CI: 0.79-0.95). The pattern for 3-point MACE was also observed for the 4-point MACE outcome. There were no significant differences between SGLT2is and GLP-1 RAs for 3-point or 4-point MACE (HR: 1.06 [95% CI: 0.96-1.17] and 1.05 [95% CI: 0.97-1.13])., Conclusions: In patients with T2DM and CVD, comparable cardiovascular risk reduction was found with SGLT2is and GLP-1 RAs, with both agents more effective than DPP4is, which in turn were more effective than SUs. These findings suggest that the use of SGLT2is and GLP-1 RAs should be prioritized as second-line agents in those with established CVD., Competing Interests: Funding Support and Author Disclosures This study was partially funded through National Institutes of Health grants R01 HL167858, K23 HL153775, R01 LM006910, R01 HG006139, and R01 HL169954 and the U.S. Department of Veterans Affairs under the research priority to “Put VA Data to Work for Veterans” (VA ORD 22-D4V). The funders had no role in the design and conduct of the protocol; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Dr Khera is an associate editor at JAMA; and has received support from the National Heart, Lung, and Blood Institute of the National Institutes of Health (awards R01 HL167858 and K23 HL153775) and the Doris Duke Charitable Foundation (award 2022060); has received research support, through Yale University, from Bristol Myers Squibb, Novo Nordisk, and BridgeBio; is a coinventor of U.S. provisional patent applications WO2023230345A1, US20220336048A1, 63/346,610, 63/428,569, 63/484,426, 63/508,315, 63/580,137, 63/606,203, 63/619,241, and 63/562,335, unrelated to the present work; and is a cofounder of Evidence2Health and Ensight-AI, precision health platforms to improve evidence-based cardiovascular care and cardiovascular diagnostics. Dr DuVall has received grants from Alnylam Pharmaceuticals, AstraZeneca Pharmaceuticals, Biodesix, Celgene, Cerner Enviza, GlaxoSmithKline, Janssen Pharmaceuticals, Novartis International, and Parexel International through the University of Utah or the Western Institute for Veteran Research (outside the submitted work). Dr Man has received support from the C.W. Maplethorpe Fellowship, the National Institute of Health Research, European Commission Framework Horizon 2020, the Hong Kong Research Grant Council, and the Innovation and Technology Commission of the Hong Kong Special Administration Region Government outside the submitted work). Dr Morales is supported by a Wellcome Trust Clinical Research Fellowship (214588/Z/18/Z). In the past 3 years, Dr Krumholz has received expenses and/or personal fees from UnitedHealth, Element Science, Aetna, Reality Labs, Tesseract/4Catalyst, F-Prime, the Siegfried and Jensen Law Firm, the Arnold and Porter Law Firm, and the Martin/Baughman Law Firm; is a cofounder of Refactor Health, HugoHealth, and Ensight-AI; and is associated with contracts, through Yale New Haven Hospital, from the Centers for Medicare and Medicaid Services and, through Yale University, from Johnson & Johnson. Dr You is chief technology officer of PHI Digital Healthcare. Dr Ross has received research support through Yale University from Johnson & Johnson to develop methods of clinical trial data sharing, from the Food and Drug Administration for the Yale-Mayo Clinic Center for Excellence in Regulatory Science and Innovation program (grant U01 FD005938), from the Agency for Healthcare Research and Quality (grant R01 HS022882), and from Arnold Ventures; has received research support from the Medical Device Innovation Consortium as part of the National Evaluation System for Health Technology and from the National Heart, Lung, and Blood Institute of the National Institutes of Health (grants R01 HS025164 and R01 HL144644); and was an expert witness at the request of the relator’s attorneys, the Greene Law Firm, in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled September 2022. Dr Thangaraj is a coinventor on provisional patent 63/606,203, unrelated to the present work, and is funded by grant 5T32 HL155000-03. Ms Blacketer, Dr Ostropolets, and Dr Ryan are employees of Johnson & Johnson. Dr Schuemie is an employee and shareholder of Johnson & Johnson. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. All rights reserved.)

Objectives: Chart review as the current gold standard for phenotype evaluation cannot support observational research on electronic health records and claims data sources at scale. We aimed to evaluate the ability of structured data to support efficient and interpretable phenotype evaluation as an alternative to chart review., Materials and Methods: We developed Knowledge-Enhanced Electronic Profile Review (KEEPER) as a phenotype evaluation tool that extracts patient's structured data elements relevant to a phenotype and presents them in a standardized fashion following clinical reasoning principles. We evaluated its performance (interrater agreement, intermethod agreement, accuracy, and review time) compared to manual chart review for 4 conditions using randomized 2-period, 2-sequence crossover design., Results: Case ascertainment with KEEPER was twice as fast compared to manual chart review. 88.1% of the patients were classified concordantly using charts and KEEPER, but agreement varied depending on the condition. Missing data and differences in interpretation accounted for most of the discrepancies. Pairs of clinicians agreed in case ascertainment in 91.2% of the cases when using KEEPER compared to 76.3% when using charts. Patient classification aligned with the gold standard in 88.1% and 86.9% of the cases respectively., Conclusion: Structured data can be used for efficient and interpretable phenotype evaluation if they are limited to relevant subset and organized according to the clinical reasoning principles. A system that implements these principles can achieve noninferior performance compared to chart review at a fraction of time., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Type 2 diabetes mellitus is a complex and under-treated disorder closely intertwined with obesity. Adolescents with severe obesity and type 2 diabetes have a more aggressive disease compared to adults, with a rapid decline in pancreatic β cell function and increased incidence of comorbidities. Given the relative paucity of pharmacotherapies, bariatric surgery has become increasingly used as a therapeutic option. However, subsets of this population have sub-optimal outcomes with either inadequate weight loss or little improvement in disease. Predicting which patients will benefit from surgery is a difficult task and detailed physiological characteristics of patients who do not respond to treatment are generally unknown. Identifying physiological predictors of surgical response therefore has the potential to reveal both novel phenotypes of disease as well as therapeutic targets. We leverage data assimilation paired with mechanistic models of glucose metabolism to estimate pre-operative physiological states of bariatric surgery patients, thereby identifying latent phenotypes of impaired glucose metabolism. Specifically, maximal insulin secretion capacity, σ, and insulin sensitivity, S I , differentiate aberrations in glucose metabolism underlying an individual's disease. Using multivariable logistic regression, we combine clinical data with data assimilation to predict post-operative glycemic outcomes at 12 months. Models using data assimilation sans insulin had comparable performance to models using oral glucose tolerance test glucose and insulin. Our best performing models used data assimilation and had an area under the receiver operating characteristic curve of 0.77 (95% confidence interval 0.7665, 0.7734) and mean average precision of 0.6258 (0.6206, 0.6311). We show that data assimilation extracts knowledge from mechanistic models of glucose metabolism to infer future glycemic states from limited clinical data. This method can provide a pathway to predict long-term, post-surgical glycemic states by estimating the contributions of insulin resistance and limitations of insulin secretion to pre-operative glucose metabolism., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling Editor CDB declared a past co-authorship with authors DA and GH., (Copyright © 2022 Richter, Albert, Zhang, Ostropolets, Zitsman, Fennoy, Albers and Hripcsak.)

As the prevalence of obesity-induced type 2 diabetes mellitus (T2DM) and nonalcoholic steatohepatitis (NASH) continue to increase, the need for pharmacologic therapies becomes urgent. However, endeavors to identify and develop novel therapeutic strategies for these chronic conditions are balanced by the need for safety, impeding clinical translation. One shared pathology of these two diseases is a maladaptive reactivation of the Notch signaling pathway in liver. Notch antagonism with γ-secretase inhibitors effectively suppresses hepatic glucose production and reduces liver fibrosis in NASH, but its extrahepatic side effects, particularly goblet cell metaplasia, limit therapeutic utility. To overcome this barrier, we developed a nanoparticle-mediated delivery system to target γ-secretase inhibitor to liver (GSI NPs). GSI NP application reduced hepatic glucose production in diet-induced obese mice and reduced hepatic fibrosis and inflammation in mice fed a NASH-provoking diet, without apparent gastrointestinal toxicity. By changing the delivery method, these results provide proof-of-concept for the repurposing of a previously intolerable medication to address unmet needs in the clinical landscape for obesity-induced T2DM and NASH.

We report here on a multifaceted body of research on per- and polyfluoroalkyl substances (PFAS), chemicals that have become a well-known group of 'emerging contaminants' in recent years. Our PFAS Project team of over 10 researchers - faculty, postdocs, graduate students, and undergraduates - has been working since 2015 to study the extent and health effects of PFAS contamination through a broad model of engaged public sociology. Our model of research combines organic public sociology with elements of community-based participatory research, a related but distinct research form most widely used in the environmental health sciences. Based on long-term, place-based relationships, our engaged public sociology has led to numerous academic, regulatory, and social movement effects. We argue that this form of engaged, intervention-oriented public sociology is appropriate and beneficial for research in many areas of environmental sociology given the social and ecological stakes in the current moment. Engaged public sociology involves collaborative, reflexive research with broadly-conceived communities or publics. It facilitates the creation of previously undone science by addressing research topics of interest to community members, and allows researchers to directly contribute to environmental and social justice movements by acting as reflexive, observant participants.