The foundation for the microbiology laboratory's essential role in diagnostic stewardship: an ASM Laboratory Practices Subcommittee report.

Diagnostic stewardship (DxS) has gained traction in recent years as a cross-disciplinary method to improve the quality of patient care while appropriately managing resources within the healthcare system. Clinical microbiology laboratorians have been highly engaged in DxS efforts to guide best practices with conventional microbiology tests and more recently with molecular infectious disease diagnostics. Laboratories can experience resistance to their role in DxS, especially when the clinical benefits, motivations for interventions, and underlying regulatory requirements are not clearly conveyed to stakeholders. Clinical laboratories must not only ensure ethical practices but also meet obligatory requirements to steward tests responsibly. In this review, we aim to support clinical microbiology laboratorians by providing the background and resources that demonstrate the laboratory's essential role in DxS. The heart of this review is to collate regulatory and accreditation requirements that, in essence, mandate DxS practices as a long-standing, core element of high-quality laboratory testing to deliver the best possible patient care. While examples of the clinical impact of DxS are plentiful in the literature, here, we focus on the operational and regulatory justification for the laboratory's role in stewardship activities.

Should AI models be explainable to clinicians?

In the high-stakes realm of critical care, where daily decisions are crucial and clear communication is paramount, comprehending the rationale behind Artificial Intelligence (AI)-driven decisions appears essential. While AI has the potential to improve decision-making, its complexity can hinder comprehension and adherence to its recommendations. "Explainable AI" (XAI) aims to bridge this gap, enhancing confidence among patients and doctors. It also helps to meet regulatory transparency requirements, offers actionable insights, and promotes fairness and safety. Yet, defining explainability and standardising assessments are ongoing challenges and balancing performance and explainability can be needed, even if XAI is a growing field.

Regulatory compliance of PCDD/F emissions by a municipal solid waste incinerator. A case study in Sant Adrià de Besòs, Catalonia, Spain.

Despite incineration is an important emission source of toxic pollutants, such as heavy metals and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), it is still one of the most widely used methods for the management of municipal solid waste. The current paper summarizes the results of a 20-year follow-up study of the emissions of PCDD/Fs by a municipal solid waste incinerator (MSWI) in Sant Adrià de Besòs (Catalonia, Spain). Samples of ambient air, soils and herbage were periodically collected near the facility and the content of PCDD/Fs was analyzed. In the last (2017) survey, mean levels in soil were 3.60 ng WHO-TEQ/kg (range: 0.40-10.6), being considerably higher than the mean concentrations of PCDD/Fs in soil samples collected near other MSWIs in Catalonia. Moreover, air PCDD/F concentrations were even higher than those found in a previous (2014) survey, as they increased from 0.026 to 0.044 pg WHO-TEQ/m3. Ultimately, the PCDD/F exposure would be associated to a cancer risk (2.5 × 10-6) for the population living in the surrounding area. Globally, this information indicates that the MSWI of Sant Adrià de Besòs could have had a negative impact on the environment and potentially on public health, being an example of a possible inappropriate management for years. The application of Best Available Techniques to minimize the emission of PCDD/Fs and other chemicals is critical.

Fate and Exposure Assessment of Pb Leachate from Hypothetical Breakage Events of Perovskite Photovoltaic Modules.

Emerging lead halide perovskite (LHP) photovoltaics are undergoing intense research and development due to their outstanding efficiency and potential for low manufacturing costs that render them competitive with existing photovoltaic (PV) technologies. While today's efforts are focused on stability and scalability of LHPs, the toxicity of lead (Pb) remains a major challenge to their large-scale commercialization. Here, we present a screening-level, EPA-compliant model of fate and transport of Pb leachate in groundwater, soil, and air, following hypothetical catastrophic breakage of LHP PV modules in conceptual utility-scale sites. We estimated exposure point concentrations of Pb in each medium and found that most of the Pb is sequestered in soil. Exposure point concentrations of Pb from the perovskite film fell well below EPA maximum permissible limits in groundwater and air even upon catastrophic release from PV modules at large scales. Background Pb levels in soil can influence soil regulatory compliance, but the highest observed concentrations of perovskite-derived Pb would not exceed EPA limits under our assumptions. Nonetheless, regulatory limits are not definitive thresholds of safety, and the potential for increased bioavailability of perovskite-derived Pb may warrant additional toxicity assessment to further characterize public health risks.

ISO 15189 is a sufficient instrument to guarantee high-quality manufacture of laboratory developed tests for in-house-use conform requirements of the European In-Vitro-Diagnostics Regulation.

The EU In-Vitro Diagnostic Device Regulation (IVDR) aims for transparent risk-and purpose-based validation of diagnostic devices, traceability of results to uniquely identified devices, and post-market surveillance. The IVDR regulates design, manufacture and putting into use of devices, but not medical services using these devices. In the absence of suitable commercial devices, the laboratory can resort to laboratory-developed tests (LDT) for in-house use. Documentary obligations (IVDR Art 5.5), the performance and safety specifications of ANNEX I, and development and manufacture under an ISO 15189-equivalent quality system apply. LDTs serve specific clinical needs, often for low volume niche applications, or correspond to the translational phase of new tests and treatments, often extremely relevant for patient care. As some commercial tests may disappear with the IVDR roll-out, many will require urgent LDT replacement. The workload will also depend on which modifications to commercial tests turns them into an LDT, and on how national legislators and competent authorities (CA) will handle new competences and responsibilities. We discuss appropriate interpretation of ISO 15189 to cover IVDR requirements. Selected cases illustrate LDT implementation covering medical needs with commensurate management of risk emanating from intended use and/or design of devices. Unintended collateral damage of the IVDR comprises loss of non-profitable niche applications, increases of costs and wasted resources, and migration of innovative research to more cost-efficient environments. Taking into account local specifics, the legislative framework should reduce the burden on and associated opportunity costs for the health care system, by making diligent use of existing frameworks.

Potency Assays: The 'Bugaboo' of Stem Cell Therapy.

Substantially manipulated cell-based products for human use are considered medicines and therefore regulatory authorities require extensive characterisation in terms of identity, purity and potency. The latter critical quality attribute is probably the most challenging to identify and measure, requiring provision that potency assays should reflect the intended mechanism of action and demonstrate the drugs' biological effect. However, in most cases, the mechanisms involved are not fully understood, making the definition and validation of suitable potency tests difficult, a 'bugaboo' quest to be feared. Although it is evident that much work is still needed in the scientific arena, the present chapter focuses on strategies currently used by developers of cell- and gene-based therapies to demonstrate potency of innovative medicines, the regulatory framework and need for standardisation seeking to demystify critical factors to consider when designing a potency assay.

Scoping review: Positive and negative impact of technology on clinicians.

BACKGROUND: Unnecessary electronic health record (EHRs) documentation burden and usability issues have negatively impacted clinician well-being (e.g., burnout and moral distress). PURPOSE: This scoping review was conducted by members from three expert panels of the American Academy of Nurses to generate consensus on the evidence of both positive and negative impact of EHRs on clinicians. METHODS: The scoping review was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Extension for Scoping Reviews guidelines. RESULTS: The scoping review captured 1,886 publications screened against title and abstract 1,431 excluded, examined 448 in a full-text review, excluded 347 with 101 studies informing the final review. DISCUSSION: Findings suggest few studies that have explored the positive impact of EHRs and more studies that have explored the clinician's satisfaction and work burden. Significant gaps were identified in associating distress to use of EHRs and minimal studies on EHRs' impact on nurses. CONCLUSION: Examined the evidence of HIT's positive and negative impacts on clinician's practice, clinicians work environment, and if psychological impact differed among clinicians.

Accommodating clinical trials and other externally manufactured cellular therapy products: challenges, lessons learned and creative solutions.

BACKGROUND AIMS: The Division of Transfusion Medicine and Cellular Therapy at New York-Presbyterian/Columbia University Irving Medical Center (NYPH-CUIMC) comprises the immunohematology laboratory and blood bank (transfusion service), hemotherapy/apheresis and the cellular therapy laboratory (CTL). The CTL processes and stores hematopoietic progenitor cells for bone marrow transplantation from all currently acceptable sources, including bone marrow, peripheral blood and umbilical cord blood. The laboratory provides services for the pediatric and adult blood and marrow transplant programs at both NYPH-CUIMC and the Morgan Stanley Children's Hospital of New York-Presbyterian. The laboratory processes and stores approximately 200 cellular therapy products per year, and the division participates in numerous clinical trials within the institution and with external pharmaceutical manufacturing facilities. As a licensed tissue bank, commercial chimeric antigen receptor T-cell products and other cellular-based therapies that are approved by the US Food and Drug Administration (FDA) are routed through the CTL for storage, processing, coordination of transportation, chain of custody and, eventually, thaw and distribution. Currently, we are distributing four such products from Kite Pharma, Novartis and Bristol Meyers Squid. In comparison to the amount of work, we employ a small staff of only four full-time clinical laboratory technologists, one technical specialist, one quality and operations manager and one medical director. In recent years, the growing use of the hematology/oncology service and the introduction of new immunotherapies have put significant pressure on our division to accommodate and scale up operations. Accompanying this growth is a mounting administrative burden and upsurge in regulatory and protocol-specific oversight. The purpose of this article is to share lessons learned and creative solutions to help better accommodate the surge in development of novel cellular therapies. METHODS: To handle this increase in demand, the CTL worked to standardize administrative procedures, implement comprehensive document control solutions, digitize data collection and implement lean design concepts to increase effectiveness and mitigate risk. RESULTS: Distribution of a standard operating procedure for clinical trial management improved the "on-boarding" process and allowed the laboratory to have more influence in the decision-making process. Implementation of digital workflows and a comprehensive document control system allowed for improved organization of critical documents and proved to be flexible enough to accommodate various protocol-specific requirements. Introduction of visual ques and reorganization of the workspace facilitated better organization, mitigated risk and assisted the laboratory in maintaining regulatory compliance. CONCLUSIONS: Better-defined, structured and controlled laboratory processes helped laboratory management implement new clinical trials and track critical data. Implementing digital solutions using widely available tools like Microsoft SharePoint has proven to be a very secure, low-cost and flexible solution to keeping us "up-to-date" and inspection-ready.

Drivers of Spatiotemporal Variability in Drinking Water Quality in the United States.

Approximately 10% of community water systems in the United States experience a health-based violation of drinking water quality; however, recently allocated funds for improving United States water infrastructure ($50 billion) provide an opportunity to address these issues. The objective of this study was to examine environmental, operational, and sociodemographic drivers of spatiotemporal variability in drinking water quality violations using geospatial analysis and data analytics. Random forest modeling was used to evaluate drivers of these violations, including environmental (e.g., landcover, climate, geology), operational (e.g., water source, system size), and sociodemographic (social vulnerability, rurality) drivers. Results of random forest modeling show that drivers of violations vary by violation type. For example, arsenic and radionuclide violations are found mostly in the Southwest and Southcentral United States related to semiarid climate, whereas disinfection byproduct rule violations are found primarily in Southcentral United States related to system operations. Health-based violations are found primarily in small systems in rural and suburban settings. Understanding the drivers of water quality violations can help develop optimal approaches for addressing these issues to increase compliance in community water systems, particularly small systems in rural areas across the United States.

Costs associated with United States pharmacopeia compliant infusion clinics.

PURPOSE: As costs continue to rise in oncology, a strategy that has been implemented to limit these costs is use of alternative sites of care. However, there are differences in regulatory standards between common sites of care such as freestanding infusion clinics and hospital outpatient departments. The costs associated with United States Pharmacopeia compliance were evaluated in order to better understand the cost of universally compliant hospital outpatient departments. METHODS: Annual operational costs associated with United States Pharmacopeia compliance were estimated for a 30-chair infusion clinic with United States Pharmacopeia <797> and <800> pharmacy cleanrooms for non-hazardous and hazardous drugs, respectively. Annual United States Pharmacopeia compliance costs included: competency assessments, personal protective equipment, closed system transfer devices, labels, cleaning supplies, and environmental monitoring. One-time costs included initial cleanroom construction and renovations. Published information and benchmarks provided baseline assumptions for patient volume, staffing, and unit costs. If no published data was available, prices were estimated based on a similarly sized clinic. RESULTS: Recurring annual costs for a 30-chair fully compliant infusion clinic were calculated to be $785,207. One-time costs associated with initial construction and renovations were estimated to be $1,365,207-$1,535,207 and $965,207-$1,005,207, respectively. CONCLUSIONS: Costs associated with increased operational oversight and regulatory standards are a major contributing factor to the facility fee of hospital outpatient departments. Ultimately, all sites of care share in the goal to provide optimal patient care while considering all aspects of patient care, including cost. Therefore, a move towards consistent regulatory standards across all settings would aid in preventing discrepancies in care.

Quality assessment of cold chain storage facilities for regulatory and quality management compliance in a developing country context.

BACKGROUND: Supply chain management is essential for cold chain medicines since they are temperature-controlled and must be maintained within a specific temperature range to ensure product integrity and quality. In Nigeria, guidelines that address drug distribution do not adequately address the issue of cold chain management in addition to challenges in implementation. Given the chaotic medicines distribution system, this study examined the quality of practice of supply chain management of cold chain products in line with the World Health Organisation's Expert Committee report on Specifications for Pharmaceutical Preparations. METHODS: The study was set in Abuja Nigeria and descriptive survey was used to explore cold chain supply management. A checklist developed from regulatory requirements stipulated by the World Health Organisation covering documentations, storage and distribution guidelines was used to assess supply chain management of cold chain medicines across various facilities. Data were analysed using IBM Statistical Package for the Social Sciences (SPSS) version 25. RESULTS: The results from this study showed that most of the storage facilities assessed (66.7%) did not meet up to the required standards of quality management for cold chain products. In addition, 50.4% of retail and hospital pharmacy facilities performed poorly in cold chain management practices. Many of aspects of quality management guidelines and regulations were not met by the facilities. Most facilities (66.7%) do not have their equipment calibrated, 43.6% of the hospital and retail pharmacies assessed do not have an automated system to cater for power failure while 37.6% do not perform a temperature check on cold chain products before receiving from suppliers. CONCLUSION: The study has shown that the levels of the supply chain assessed for quality management and regulatory compliance performed poorly. There was limited availability and use of validated quality monitoring systems for cold chain medicines in these facilities.

Assessment of Automated Flow Cytometry Data Analysis Tools within Cell and Gene Therapy Manufacturing.

Flow cytometry is widely used within the manufacturing of cell and gene therapies to measure and characterise cells. Conventional manual data analysis relies heavily on operator judgement, presenting a major source of variation that can adversely impact the quality and predictive potential of therapies given to patients. Computational tools have the capacity to minimise operator variation and bias in flow cytometry data analysis; however, in many cases, confidence in these technologies has yet to be fully established mirrored by aspects of regulatory concern. Here, we employed synthetic flow cytometry datasets containing controlled population characteristics of separation, and normal/skew distributions to investigate the accuracy and reproducibility of six cell population identification tools, each of which implement different unsupervised clustering algorithms: Flock2, flowMeans, FlowSOM, PhenoGraph, SPADE3 and SWIFT (density-based, k-means, self-organising map, k-nearest neighbour, deterministic k-means, and model-based clustering, respectively). We found that outputs from software analysing the same reference synthetic dataset vary considerably and accuracy deteriorates as the cluster separation index falls below zero. Consequently, as clusters begin to merge, the flowMeans and Flock2 software platforms struggle to identify target clusters more than other platforms. Moreover, the presence of skewed cell populations resulted in poor performance from SWIFT, though FlowSOM, PhenoGraph and SPADE3 were relatively unaffected in comparison. These findings illustrate how novel flow cytometry synthetic datasets can be utilised to validate a range of automated cell identification methods, leading to enhanced confidence in the data quality of automated cell characterisations and enumerations.

System for Storage, Dispensing, and Tracking Expiration of Electrocardiography Electrodes.

Electrocardiography electrodes have expiration dates that are foreshortened once the manufacturer's packaging is opened. A system is described for storing and dispensing these perishable electrodes while tracking their new expiration date for safety and regulatory purposes.

Treatment of Legacy Nitrogen as a Compliance Option to Meet Chesapeake Bay TMDL Requirements.

In efforts to combat eutrophication, the U.S. Environmental Protection Agency has established aggressive nitrogen, phosphorus, and sediment reduction goals for states and regulated dischargers within the Chesapeake Bay watershed. Chesapeake Bay jurisdictions are struggling to meet the nutrient (N, P) reduction goals. This paper evaluates the efficacy of removing legacy N from groundwater as a compliance strategy for three potential classes of "buyers" of N reductions in the Chesapeake Bay watershed: permitted point sources, permitted municipal stormwater systems (called MS4s), and state nonpoint source (NPS) managers. We compare denitrifying spring bioreactors with conventional agricultural and urban NPS removal technologies using evaluative criteria important to each of these buyers. Results indicate that spring bioreactors compare favorably to other N removal technologies based on cost effectiveness, administrative costs, and certainty of N removal performance. Most conventional NPS technologies provide greater ancillary benefits. On balance, denitrifying spring bioreactors add a valuable compliance option to those tasked with achieving Bay N reduction goals.

National trends in drinking water quality violations.

Ensuring safe water supply for communities across the United States is a growing challenge in the face of aging infrastructure, impaired source water, and strained community finances. In the aftermath of the Flint lead crisis, there is an urgent need to assess the current state of US drinking water. However, no nationwide assessment has yet been conducted on trends in drinking water quality violations across several decades. Efforts to reduce violations are of national concern given that, in 2015, nearly 21 million people relied on community water systems that violated health-based quality standards. In this paper, we evaluate spatial and temporal patterns in health-related violations of the Safe Drinking Water Act using a panel dataset of 17,900 community water systems over the period 1982-2015. We also identify vulnerability factors of communities and water systems through probit regression. Increasing time trends and violation hot spots are detected in several states, particularly in the Southwest region. Repeat violations are prevalent in locations of violation hot spots, indicating that water systems in these regions struggle with recurring issues. In terms of vulnerability factors, we find that violation incidence in rural areas is substantially higher than in urbanized areas. Meanwhile, private ownership and purchased water source are associated with compliance. These findings indicate the types of underperforming systems that might benefit from assistance in achieving consistent compliance. We discuss why certain violations might be clustered in some regions and strategies for improving national drinking water quality.

University Stormwater Management within Urban Environmental Regulatory Regimes: Barriers to Progressivity or Opportunities to Innovate?

U.S. public university campuses are held directly responsible for compliance with many of the same federal- and state-level environmental regulations as cities, including stormwater management. While operating as 'cities within cities' in many respects, campuses face unique constraints in achieving stormwater regulatory compliance. To compare the abilities of campuses to comply with stormwater regulations to municipalities, we conduct mixed-methods research using primary data from five University of California (UC) campuses. Public universities constituted over 20% of California's "nontraditional" permittees under the municipal separate storm sewer system (MS4) regulation regime in 2013. We utilize semi-structured interviews with campus and regulatory officials, a survey of campus students and staff around support and willingness to pay for innovative stormwater management, and content analysis of campus stormwater management documents to examine challenges to public university stormwater compliance. We find that, despite their progressive environmental practices in other areas like energy and water conservation, even as compared to cities, stormwater management practices on the evaluated campuses are constrained by several factors: infrastructure financing limitations, lack of transparent and coordinated decision-making, a lack of campus resident involvement, and regulatory inflexibility. Our study provides new insights, both for understanding campuses as sustainable 'cities within cities' and more broadly for urban environmental compliance regimes globally.

Deterrence approach on the compliance with electronic medical records privacy policy: the moderating role of computer monitoring.

BACKGROUND: This study explored the possible antecedents that will motivate hospital employees' compliance with privacy policy related to electronic medical records (EMR) from a deterrence perspective. Further, we also investigated the moderating effect of computer monitoring on relationships among the antecedents and the level of hospital employees' compliance intention. METHODS: Data was collected from a large Taiwanese medical center using survey methodology. A total of 303 responses was analyzed via hierarchical regression analysis. RESULTS: The results revealed that sanction severity and sanction certainty significantly predict hospital employees' compliance intention, respectively. Further, our study found external computer monitoring significantly moderates the relationship between sanction certainty and compliance intention. CONCLUSIONS: Based on our findings, the study suggests that healthcare facilities should take proactive countermeasures, such as computer monitoring, to better protect the privacy of EMR in addition to stated privacy policy. However, the extent of computer monitoring should be kept to minimum requirements as stated by relevant regulations.

Quality of drug stores: Storage practices & Regulatory compliance in Karachi, Pakistan.

OBJECTIVE: To assess and evaluate the drug storage quality and regulatory compliance among privately operated drug stores of Karachi Pakistan. METHODS: A cross-sectional survey of drug stores located in Karachi was conducted from May to December 2013. A total of 1003 drug stores that were involved in the sales, purchase and dispensing of pharmaceutical products were approached by non-probability purposive sampling technique, and the information was collected using a close ended, structured questionnaire. RESULTS: Out of 1003 drug stores inspected only 4.1%(n=41) were found compliant to regulatory requirements. Most of the stores 74.9%(n=752) were selling general items along with the drugs. Only 12%(n=124) stores were having qualified person working on the store, out of which 33% were pharmacist. 47.4%(n=400) of the stores had drug sales license displayed in the premises and 33.4%(n=282) of the stores had expired drug sales license. 11.4%(n=94) stores were found selling vaccines without proper refrigerator and only 11.7% stores had the power backup for the refrigerator. Only 40.2%(n=403) of stores were protected from direct sunlight and 5.4%(n=54) having air conditioning in the premises. CONCLUSION: The regulatory compliance of majority of the drug stores operated privately in different areas of Karachi is below standard. Only a few drugs stores have adequate facilities to protect the drugs from extreme temperature, sunlight and provision of refrigeration. Very few of the drug stores carry out drug sales under the supervision of qualified pharmacist. There is a dire need to improve the storage practices in the drug stores by complying with the regulatory standards/laws as specified by the Drug Regulatory Authority of Pakistan.

Effects of abiotic stress and crop management on cereal grain composition: implications for food quality and safety.

The effects of abiotic stresses and crop management on cereal grain composition are reviewed, focusing on phytochemicals, vitamins, fibre, protein, free amino acids, sugars, and oils. These effects are discussed in the context of nutritional and processing quality and the potential for formation of processing contaminants, such as acrylamide, furan, hydroxymethylfurfuryl, and trans fatty acids. The implications of climate change for cereal grain quality and food safety are considered. It is concluded that the identification of specific environmental stresses that affect grain composition in ways that have implications for food quality and safety and how these stresses interact with genetic factors and will be affected by climate change needs more investigation. Plant researchers and breeders are encouraged to address the issue of processing contaminants or risk appearing out of touch with major end-users in the food industry, and not to overlook the effects of environmental stresses and crop management on crop composition, quality, and safety as they strive to increase yield.

Assessment of public perception and environmental compliance at a pulp and paper facility: a Canadian case study.

Communities across Canada rely heavily on natural resources for their livelihoods. One such community in Pictou County, Nova Scotia, has both benefited and suffered, because of its proximity to a pulp and paper mill (currently owned by Northern Pulp). Since production began in 1967, there have been increasing impacts to the local environment and human health. Environmental reports funded by the mill were reviewed and compared against provincial and federal regulatory compliance standards. Reports contrasted starkly to societal perceptions of local impacts and independent studies. Most environmental monitoring reports funded by the mill indicate some levels of compliance in atmospheric and effluent emissions, but when compliance targets were not met, there was a lack of regulatory enforcement. After decades of local pollution impacts and lack of environmental compliance, corporate social responsibility initiatives need implementing for the mill to maintain its social licence to operate.