Improving Statewide Post-Operative Sepsis Performance Measurement Using Hospital Risk Adjustment Within a Surgical Collaborative.

Background: The Georgia Quality Improvement Program (GQIP) surgical collaborative participating hospitals have shown consistently poor performance in the post-operative sepsis category of National Surgical Quality Improvement Program data as compared with national benchmarks. We aimed to compare crude versus risk-adjusted post-operative sepsis rankings to determine high and low performers amongst GQIP hospitals. Patients and Methods: The cohort included intra-abdominal general surgery patients across 10 collaborative hospitals from 2015 to 2020. The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) sepsis definition was used among all hospitals for case abstraction and NSQIP data were utilized to train and validate a multivariable risk-adjustment model with post-operative sepsis as the outcome. This model was used to rank GQIP hospitals by risk-adjusted post-operative sepsis rates. Rankings between crude and risk-adjusted post-operative sepsis rankings were compared ordinally and for changes in tertile. Results: The study included 20,314 patients with 595 cases of post-operative sepsis. Crude 30-day post-operative sepsis risk among hospitals ranged from 0.81 to 5.11. When applying the risk-adjustment model which included: age, American Society of Anesthesiology class, case complexity, pre-operative pneumonia/urinary tract infection/surgical site infection, admission status, and wound class, nine of 10 hospitals were re-ranked and four hospitals changed performance tertiles. Conclusions: Inter-collaborative risk-adjusted post-operative sepsis rankings are important to present. These metrics benchmark collaborating hospitals, which facilitates best practice exchange from high to low performers.

A science-based agenda for health-protective chemical assessments and decisions: overview and consensus statement.

The manufacture and production of industrial chemicals continues to increase, with hundreds of thousands of chemicals and chemical mixtures used worldwide, leading to widespread population exposures and resultant health impacts. Low-wealth communities and communities of color often bear disproportionate burdens of exposure and impact; all compounded by regulatory delays to the detriment of public health. Multiple authoritative bodies and scientific consensus groups have called for actions to prevent harmful exposures via improved policy approaches. We worked across multiple disciplines to develop consensus recommendations for health-protective, scientific approaches to reduce harmful chemical exposures, which can be applied to current US policies governing industrial chemicals and environmental pollutants. This consensus identifies five principles and scientific recommendations for improving how agencies like the US Environmental Protection Agency (EPA) approach and conduct hazard and risk assessment and risk management analyses: (1) the financial burden of data generation for any given chemical on (or to be introduced to) the market should be on the chemical producers that benefit from their production and use; (2) lack of data does not equate to lack of hazard, exposure, or risk; (3) populations at greater risk, including those that are more susceptible or more highly exposed, must be better identified and protected to account for their real-world risks; (4) hazard and risk assessments should not assume existence of a "safe" or "no-risk" level of chemical exposure in the diverse general population; and (5) hazard and risk assessments must evaluate and account for financial conflicts of interest in the body of evidence. While many of these recommendations focus specifically on the EPA, they are general principles for environmental health that could be adopted by any agency or entity engaged in exposure, hazard, and risk assessment. We also detail recommendations for four priority areas in companion papers (exposure assessment methods, human variability assessment, methods for quantifying non-cancer health outcomes, and a framework for defining chemical classes). These recommendations constitute key steps for improved evidence-based environmental health decision-making and public health protection.

Georgia Quality Improvement Programs Multi-Institutional Collection of Postoperative Opioid Data Using ACS-NSQIP Abstraction.

BACKGROUND: Excessive postoperative opioid prescribing contributes to opioid misuse throughout the US. The Georgia Quality Improvement Program (GQIP) is a collaboration of ACS-NSQIP participating hospitals. GQIP aimed to develop a multi-institutional opioid data collection platform as well as understand our current opioid-sparing strategy (OSS) usage and postoperative opioid prescribing patterns. METHODS: This study was initiated 7/2019, when 4 custom NSQIP variables were developed to capture OSS usage and postoperative opioid oral morphine equivalents (OMEs). After pilot collection, our discharge opioid variable required optimization for adequate data capture and was expanded from a free text option to 4 drop-down selection variables. Data collection then continued from 2/2020-5/2021. Logistic regression was used to determine associations with OSS usage. Average OMEs were calculated for common general surgery procedures and compared to national guidelines. RESULTS: After variable optimization, the percentage where a total discharge prescription OME could be calculated increased from 26% to 70% (P < .001). The study included 820 patients over 10 operations. There was a significant variation in OSS usage between GQIP centers. Laparoscopic cases had higher odds of OSS use (1.92 (1.38-2.66)) while OSS use had lower odds in black patients on univariate analysis (.69 (.51-.94)). On average 7 out of the 10 cases had higher OMEs prescribed compared to national guidelines recommendations. CONCLUSION: Developing a multi-institutional opioid data collection platform through ACS-NSQIP is feasible. Preselected drop-down boxes outperform free text variables. GQIP future quality improvement targets include variation in OSS use and opioid overprescribing.

Proposed Key Characteristics of Female Reproductive Toxicants as an Approach for Organizing and Evaluating Mechanistic Data in Hazard Assessment.

BACKGROUND: Identification of female reproductive toxicants is currently based largely on integrated epidemiological and in vivo toxicology data and, to a lesser degree, on mechanistic data. A uniform approach to systematically search, organize, integrate, and evaluate mechanistic evidence of female reproductive toxicity from various data types is lacking. OBJECTIVE: We sought to apply a key characteristics approach similar to that pioneered for carcinogen hazard identification to female reproductive toxicant hazard identification. METHODS: A working group of international experts was convened to discuss mechanisms associated with chemical-induced female reproductive toxicity and identified 10 key characteristics of chemicals that cause female reproductive toxicity: 1) alters hormone receptor signaling; alters reproductive hormone production, secretion, or metabolism; 2) chemical or metabolite is genotoxic; 3) induces epigenetic alterations; 4) causes mitochondrial dysfunction; 5) induces oxidative stress; 6) alters immune function; 7) alters cell signal transduction; 8) alters direct cell­cell interactions; 9) alters survival, proliferation, cell death, or metabolic pathways; and 10) alters microtubules and associated structures. As proof of principle, cyclophosphamide and diethylstilbestrol (DES), for which both human and animal studies have demonstrated female reproductive toxicity, display at least 5 and 3 key characteristics, respectively. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), for which the epidemiological evidence is mixed, exhibits 5 key characteristics. DISCUSSION: Future efforts should focus on evaluating the proposed key characteristics against additional known and suspected female reproductive toxicants. Chemicals that exhibit one or more of the key characteristics could be prioritized for additional evaluation and testing. A key characteristics approach has the potential to integrate with pathway-based toxicity testing to improve prediction of female reproductive toxicity in chemicals and potentially prevent some toxicants from entering common use. https://doi.org/10.1289/EHP4971.

How much green does it take to be orange? Determining the cost associated with trauma center readiness.

BACKGROUND: Readiness costs are real expenses incurred by trauma centers to maintain essential infrastructure to provide emergent services on a 24/7 basis. Although the components for readiness are well described in the American College of Surgeons' Resources for Optimal Care of the Injured Patient, the cost associated with each component is not well defined. We hypothesized that meeting the requirements of the 2014 Resources for Optimal Care of the Injured Patient would result in significant costs for trauma centers. METHODS: The state trauma commission in conjunction with trauma medical directors, program managers, and financial officers of each trauma center standardized definitions for each component of trauma center readiness cost and developed a survey tool for reporting. Readiness costs were grouped into four categories: administrative/program support staff, clinical medical staff, in-house operating room, and education/outreach. To verify consistent cost reporting, a financial auditor analyzed all data. Trauma center outliers were further evaluated to validate variances. All level I/level II trauma centers (n = 16) completed the survey on 2016 data. RESULTS: Average annual readiness cost is US $10,078,506 for a level I trauma center and US $4,925,103 for level IIs. Clinical medical staff was the costliest component representing 55% of costs for level Is and 64% for level IIs. Although education/outreach is mandated, levels I and II trauma centers only spend approximately US $100,000 annually on this category (1%-2%), demonstrating a lack of resources. CONCLUSION: This study defines the cost associated with each component of readiness as defined in the Resources for Optimal Care of the Injured Patient manual. Average readiness cost for a level I trauma center is US $10,078,506 and US $4,925,103 for a level II. The significant cost of trauma center readiness highlights the need for additional trauma center funding to meet the requirements set forth by the American College of Surgeons. LEVEL OF EVIDENCE: Economic and value-based evaluations, level III.

An Integrated Approach Using Publicly Available Resources for Identifying and Characterizing Chemicals of Potential Toxicity Concern: Proof-of-Concept With Chemicals That Affect Cancer Pathways.

We developed an integrated, modular approach to predicting chemical toxicity relying on in vitro assay data, linkage of molecular targets to disease categories, and software for ranking chemical activity and examining structural features (chemotypes). We evaluate our approach in a proof-of-concept exercise to identify and prioritize chemicals of potential carcinogenicity concern. We identified 137 cancer pathway-related assays from a subset of U.S. EPA's ToxCast platforms. We mapped these assays to key characteristics of carcinogens and found they collectively assess 5 of 10 characteristics. We ranked all 1061 chemicals screened in Phases I and II of ToxCast by their activity in the selected cancer pathway-related assays using Toxicological Prioritization Index software. More chemicals used as biologically active agents (eg, pharmaceuticals) ranked in the upper 50% versus lower 50%. Twenty-three chemotypes are enriched in the top 5% (n = 54) of chemicals; these features may be important for their activity in cancer pathway-related assays. The biological coverage of the ToxCast assays related to cancer pathways is limited and short-term assays may not capture the biology of some key characteristics. Metabolism is also minimal in the assays. The ability of our approach to identify chemicals with cancer hazard is limited with the current input data, but we expect that our approach can be applied with future iterations of ToxCast and other data for improved chemical prioritization and characterization. The novel approach and proof-of-concept exercise described here for ranking chemicals for potential carcinogenicity concern is modular, adaptable, and amenable to evolving data streams.

Screening for Chemical Contributions to Breast Cancer Risk: A Case Study for Chemical Safety Evaluation.

BACKGROUND: Current approaches to chemical screening, prioritization, and assessment are being reenvisioned, driven by innovations in chemical safety testing, new chemical regulations, and demand for information on human and environmental impacts of chemicals. To conceptualize these changes through the lens of a prevalent disease, the Breast Cancer and Chemicals Policy project convened an interdisciplinary expert panel to investigate methods for identifying chemicals that may increase breast cancer risk. METHODS: Based on a review of current evidence, the panel identified key biological processes whose perturbation may alter breast cancer risk. We identified corresponding assays to develop the Hazard Identification Approach for Breast Carcinogens (HIA-BC), a method for detecting chemicals that may raise breast cancer risk. Finally, we conducted a literature-based pilot test of the HIA-BC. RESULTS: The HIA-BC identifies assays capable of detecting alterations to biological processes relevant to breast cancer, including cellular and molecular events, tissue changes, and factors that alter susceptibility. In the pilot test of the HIA-BC, chemicals associated with breast cancer all demonstrated genotoxic or endocrine activity, but not necessarily both. Significant data gaps persist. CONCLUSIONS: This approach could inform the development of toxicity testing that targets mechanisms relevant to breast cancer, providing a basis for identifying safer chemicals. The study identified important end points not currently evaluated by federal testing programs, including altered mammary gland development, Her2 activation, progesterone receptor activity, prolactin effects, and aspects of estrogen receptor ß activity. This approach could be extended to identify the biological processes and screening methods relevant for other common diseases.

Seafood contamination after the BP Gulf oil spill and risks to vulnerable populations: a critique of the FDA risk assessment.

BACKGROUND: The BP oil spill of 2010 resulted in contamination of one of the most productive fisheries in the United States by polycyclic aromatic hydrocarbons (PAHs). PAHs, which can accumulate in seafood, are known carcinogens and developmental toxicants. In response to the oil spill, the U.S. Food and Drug Administration (FDA) developed risk criteria and established thresholds for allowable levels [levels of concern (LOCs)] of PAH contaminants in Gulf Coast seafood. OBJECTIVES: We evaluated the degree to which the FDA's risk criteria adequately protect vulnerable Gulf Coast populations from cancer risk associated with PAHs in seafood. DISCUSSION: The FDA LOCs significantly underestimate risk from seafood contaminants among sensitive Gulf Coast populations by failing to a) account for the increased vulnerability of the developing fetus and child; b) use appropriate seafood consumption rates; c) include all relevant health end points; and d) incorporate health-protective estimates of exposure duration and acceptable risk. For benzo[a]pyrene and naphthalene, revised LOCs are between two and four orders of magnitude below the level set by the FDA. Comparison of measured levels of PAHs in Gulf seafood with the revised LOCs revealed that up to 53% of Gulf shrimp samples were above LOCs for pregnant women who are high-end seafood consumers. CONCLUSIONS: FDA risk assessment methods should be updated to better reflect current risk assessment practices and to protect vulnerable populations such as pregnant women and children.

Health effects of common home, lawn, and garden pesticides.

Children encounter pesticide products and their residues where they live and play and in the food supply. Pesticide exposure affects pediatric health both acutely and chronically; effects range from mild and subtle to severe. Pediatricians play an important role in identifying and reducing significant pesticide exposure in their patients by taking an exposure history to clarify the extent and types of exposures that may have occurred during acute care and preventive care visits. Developing knowledge about the toxicity of various chemicals, identifying reliable resources for pesticide information, and providing a common-sense approach toward recommending the safest practical alternatives is necessary.

Transgenerational exposures: persistent chemical pollutants in the environment and breast milk.

Persistent organic pollutants (POPs) are anthropogenic chemicals that are poorly biodegradable and have the potential for adverse human health effects. Although national regulations and an international treaty have resulted in the gradual decline of many POPs in human blood and breast milk, the levels of other POPs continue to rise. Children and developing fetuses are sensitive to health effects from these substances. This article reviews the health risks posed by the POPs that have been largely banned or regulated and the potential for health effects from a variety of other chemicals in widespread use today.

The ethics of industry experimentation using employees: the case of taste-testing pesticide-treated tobacco.

In the United States, companies that use their own funds to test consumer products on their employees are subject to few regulations. Using previously undisclosed tobacco industry documents, we reviewed the history of that industry's efforts to create internal guidelines on the conditions to be met before employee taste testers could evaluate cigarettes made from tobacco treated with experimental pesticides. This history highlights 2 potential ethical issues raised by unregulated industrial research: conflict of interest and lack of informed consent. To ensure compliance with accepted ethical standards, an independent federal office should be established to oversee industrial research involving humans exposed to experimental or increased quantities of ingested, inhaled, or absorbed chemical agents.

The tobacco industry and pesticide regulations: case studies from tobacco industry archives.

Tobacco is a heavily pesticide-dependent crop. Because pesticides involve human safety and health issues, they are regulated nationally and internationally; however, little is known about how tobacco companies respond to regulatory pressures regarding pesticides. In this study we analyzed internal tobacco industry documents to describe industry activities aimed at influencing pesticide regulations. We used a case study approach based on examination of approximately 2,000 internal company documents and 3,885 pages of U.S. Environmental Protection Agency documents obtained through Freedom of Information Act requests. The cases involved methoprene, the ethylene bisdithiocarbamates, and phosphine. We show how the tobacco industry successfully altered the outcome in two cases by hiring ex-agency scientists to write reports favorable to industry positions regarding pesticide regulations for national (U.S. Environmental Protection Agency) and international (World Health Organization) regulatory bodies. We also show how the industry worked to forestall tobacco pesticide regulation by attempting to self-regulate in Europe, and how Philip Morris encouraged a pesticide manufacturer to apply for higher tolerance levels in Malaysia and Europe while keeping tobacco industry interest a secret from government regulators. This study suggests that the tobacco industry is able to exert considerable influence over the pesticide regulatory process and that increased scrutiny of this process and protection of the public interest in pesticide regulation may be warranted.