International approaches to contamination management: Introduction to the RemTech Europe 2021 Special Series.

Soil is a nonrenewable resource, and groundwater is a critical source of drinking water. Effective soil and water protection, assessment and, if affected, recovery from contamination are priorities around the world; eco-friendly interventions in line with the United Nations Sustainable Development Goals are favored objectives. These issues were discussed during the sixth RemTech Europe conference (https://www.remtechexpo.com/it/remtech-europe/remtech-europe), which focused on sustainable technologies for land and water remediation; environmental protection; and the rehabilitation, regeneration, and sustainable development of contaminated sites, encouraging diverse stakeholders to share cutting-edge technologies, case studies, and innovation. Effective, practical, and sustainable management of remediation is only possible if the projects are completed, which is supported when the participants start the remediation planning with this end in mind. Several strategies to support and achieve the finalization of sustainable remediation processes were discussed at the conference. Addressing these gaps were among the goals of the papers included in this special series, which were selected from the RemTech EU conference presentations. The papers include risk management plan case studies, bioremediation tools, and preventive measures for minimizing disaster impacts. Moreover, the use of common and shared international best practices for effective and sustainable contaminated site management, with policy alignment among the remediation stakeholders in different countries, was also reported. Finally, many regulatory gaps, for example, the lack of practical end-of-waste criteria for contaminated soils, were also discussed. Integr Environ Assess Manag 2023;19:910-912. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Ecological risk assessment for contaminated sites in Italy: Guidelines and path forward.

Ecological risk assessment (ERA) is defined as an iterative process that evaluates the likelihood of adverse ecological effects resulting from exposure to one or more stressors. Although ERA is recognized as a valuable procedure to better address efforts and strategies for site remediation, in Europe a common framework for the implementation of ERA in the management of contaminated sites is lacking. In Italy, there are no legally binding provisions regulating the direct assessment of potential likelihood of ecological risks. In this context, the main objective of this article was to develop a guideline to facilitate ERA application in support of an effective and sustainable management of contaminated sites in Italy and to facilitate a multistakeholder dialogue. The work was based on a critical review of existing ERA guidelines in the international context, as well as other regulatory documents and technical approaches dealing with the evaluation of ecological effects of chemical contaminants in different environmental compartments. Approaches and tools available in these documents were then used to prepare a proposed guideline for the Italian context; the proposed ERA guideline is meant to represent a flexible but robust approach that can be useful in evaluating existing data (e.g., from past investigations) as well as in the planning of site-specific investigations. To facilitate the direct application of the ERA procedure, the guideline was prepared including several templates of summary tables, checklists, and examples. The proposed ERA guideline could facilitate the decision-making process for contaminated sites with ecological values, although its application would necessarily require, at least in the initial phase, testing of its suitability to the Italian context and setting-up of a close dialogue and collaboration with local authorities and other stakeholders. Integr Environ Assess Manag 2023;19:913-919. © 2022 SETAC.

Tumorigenicity Assessment of Human Cancer Cell Lines Xenografted on Immunodeficient Mice as Positive Controls of Tumorigenicity Testing.

Recent advances in human pluripotent stem cell (hPSC)-derived cell therapies and genome editing technologies such as CRISPR/Cas9 make regenerative medicines promising for curing diseases previously thought to be incurable. However, the possibility of off-target effects during genome editing and the nature of hPSCs, which can differentiate into any cell type and infinitely proliferate, inevitably raises concerns about tumorigenicity. Tumorigenicity acts as a major obstacle to the application of hPSC-derived and gene therapy products in clinical practice. Thus, regulatory authorities demand mandatory tumorigenicity testing as a key pre-clinical safety step for the products. In the tumorigenicity testing, regulatory guidelines request to include human cancer cell line injected positive control group (PC) animals, which must form tumors. As the validity of the whole test is determined by the tumor-forming rates (typically above 90%) of PC animals, establishing the stable tumorigenic condition of PC animals is critical for successful testing. We conducted several studies to establish the proper positive control conditions, including dose, administration routes, and the selection of cell lines, in compliance with Good Laboratory Practice (GLP) regulations and/or guidelines, which are essential for pre-clinical safety tests of therapeutic materials. We expect that our findings provide insights and practical information to create a successful tumorigenicity test and its guidelines.

An assessment of intervention thresholds for very high fracture risk applied to the NOGG guidelines : A report for the National Osteoporosis Guideline Group (NOGG).

The National Osteoporosis Guideline Group (NOGG) has developed intervention thresholds based on FRAX® to characterise patients at high and very high risk of fracture. INTRODUCTION: Guidelines for the assessment of fracture risk have begun to categorise patients eligible for treatment into high and very high risk of fracture to inform choice of therapeutic approach. The aim of the present study was to develop intervention thresholds based on the hybrid assessment model of NOGG. METHODS: We examined the impact of intervention thresholds in a simulated cross-sectional cohort of women age 50 years or more from the UK with the distribution of baseline characteristics based on that in the FRAX cohorts. The prevalence of very high risk using the hybrid model was compared with age-dependent thresholds used by the International Osteoporosis Foundation and the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (IOF/ESCEO). The appropriateness of thresholds was tested based on the populations treated with anabolic agents. RESULTS: With an upper intervention threshold using the IOF/ESCEO criteria, 56% of women age 50 years or more would be characterised at very high risk. This compares with 36% using the IOF/ESCEO criteria and an age-specific intervention threshold over all ages. With an upper intervention threshold of 1.6 times the pre-existing intervention threshold, 10% of women age 50 years or more would be characterised at very high risk. The data from phase 3 studies indicate that most trial participants exposed to romosozumab or teriparatide would fall into the very high-risk category. CONCLUSIONS: Proposals for FRAX-based criteria for very high risk for the NOGG hybrid model categorise a small proportion of women age 50 years or more (10%) in this highest risk stratum. The level of risk identified was comparable to that of women enrolled in trials of anabolic agents.

A framework to benchmark the quality of clinical assessment in a South African undergraduate medical programme.

BACKGROUND: The outcome of the undergraduate medical programme is to produce clinically competent health care providers relevant for the South African context. Educational institutions find it hard to ensure the quality of assessments where competency must be assessed. This study aimed to compile an assessment framework that can be used to benchmark current assessment practices in the clinical phase of the undergraduate medical programme where competency must be certified. METHODS: In this observational, descriptive study, qualitative data were gathered using the steps described by the World Health Organization for rapid reviews. Literature was searched, screened and selected before data were analysed and a framework was constructed. RESULTS: Twenty-five official documents were included in the study. The framework addressed the three components of quality assessment, namely, accreditation, assessment and quality assurance. Assessors should attend to the principles of assessment, namely, validity, reliability, fairness, feasibility, educational effect and acceptability, but realise that no assessment meets all these criteria. The first step to ensure quality assessment is to identify a clear outcome. Assessment should be planned and aligned with this outcome. CONCLUSION: It is clear that clinical assessment is multidimensional and that no assessment is perfect. Programme accreditation, assessment practices and psychometrics can assist to improve the quality of assessment but cannot judge clinical competence. Using experienced assessors with a variety of assessment methods on a continuous basis is the proposed way to assess clinical competence. An assessment framework can assist to improve assessment, but it cannot guarantee quality assessment.

A systematic review of intervention thresholds based on FRAX : A report prepared for the National Osteoporosis Guideline Group and the International Osteoporosis Foundation.

UNLABELLED: This systematic review identified assessment guidelines for osteoporosis that incorporate FRAX. The rationale for intervention thresholds is given in a minority of papers. Intervention thresholds (fixed or age-dependent) need to be country-specific. INTRODUCTION: In most assessment guidelines, treatment for osteoporosis is recommended in individuals with prior fragility fractures, especially fractures at spine and hip. However, for those without prior fractures, the intervention thresholds can be derived using different methods. The aim of this report was to undertake a systematic review of the available information on the use of FRAX® in assessment guidelines, in particular the setting of thresholds and their validation. METHODS: We identified 120 guidelines or academic papers that incorporated FRAX of which 38 provided no clear statement on how the fracture probabilities derived are to be used in decision-making in clinical practice. The remainder recommended a fixed intervention threshold (n = 58), most commonly as a component of more complex guidance (e.g. bone mineral density (BMD) thresholds) or an age-dependent threshold (n = 22). Two guidelines have adopted both age-dependent and fixed thresholds. RESULTS: Fixed probability thresholds have ranged from 4 to 20 % for a major fracture and 1.3-5 % for hip fracture. More than one half (39) of the 58 publications identified utilised a threshold probability of 20 % for a major osteoporotic fracture, many of which also mention a hip fracture probability of 3 % as an alternative intervention threshold. In nearly all instances, no rationale is provided other than that this was the threshold used by the National Osteoporosis Foundation of the USA. Where undertaken, fixed probability thresholds have been determined from tests of discrimination (Hong Kong), health economic assessment (USA, Switzerland), to match the prevalence of osteoporosis (China) or to align with pre-existing guidelines or reimbursement criteria (Japan, Poland). Age-dependent intervention thresholds, first developed by the National Osteoporosis Guideline Group (NOGG), are based on the rationale that if a woman with a prior fragility fracture is eligible for treatment, then, at any given age, a man or woman with the same fracture probability but in the absence of a previous fracture (i.e. at the 'fracture threshold') should also be eligible. Under current NOGG guidelines, based on age-dependent probability thresholds, inequalities in access to therapy arise especially at older ages (≥70 years) depending on the presence or absence of a prior fracture. An alternative threshold using a hybrid model reduces this disparity. CONCLUSION: The use of FRAX (fixed or age-dependent thresholds) as the gateway to assessment identifies individuals at high risk more effectively than the use of BMD. However, the setting of intervention thresholds needs to be country-specific.

SIGN Guidelines for Scotland: BMD Versus FRAX Versus QFracture.

Scottish Intercollegiate Guidelines Network (SIGN) recently issued guidance on the management of osteoporosis and the prevention of fragility fractures. The aim of this paper was to critically review the guidance. The SIGN guidance utilises risk factors for fracture as an initial step for assessment, but recommends treatment only in individuals with a T-score of -2.5. There are many problems with the sole use of BMD as the sole gateway to treatment. Moreover, the assessment tools to determine risk (FRAX or QFracture) are not designed to detect osteoporosis but rather fracture risk. Whereas SIGN assumes that FRAX overestimates fracture probability, there are compelling reasons to believe that the disparity is related to the inadequate calibration of QFracture. The disparities make the use of a single threshold for BMD testing problematic. The SIGN guidance for men at high risk of fracture provides a set of confused and inconsistent recommendations that are in direct conflict with regulatory authorizations and is likely to increase further the large treatment gap in men. For women, the number of women eligible for treatment (i.e. with osteoporosis) is 81,700 with the use of FRAX but only 12,300 with QFracture representing 8.2 and 1.2 % of the total population at risk, respectively. We conclude that serious problems with the SIGN guidance preclude its implementation.

Desarrollo y validación del instrumento meduc-rx32, para la evaluación de docentes de programas de la especialidad de postítulo en radiología / Development and validation of the meduc-Rrx32 questionnaire, to evaluate teachers of postgraduate radiology programs

El objetivo de este estudio es desarrollar y validar una pauta para la evaluación del proceso de enseñanza clínica en radiología; Medicina Universidad Católica, Radiología 32 ítems (MEDUC-RX32). Se utilizó metodología mixta para el desarrollo del instrumento: dos entrevistas grupales (residentes y docentes) y una individual a un jefe de programa de radiología. Utilizando técnica Delfi modificada para lograr acuerdo, un panel de validez nacional evaluó la importancia de cada ítem. El panel Delfi refinó el instrumento de 88 a 32 ítems luego de dos rondas. La pauta final fue piloteada en 55 residentes del programa. El instrumento definitivo presenta alta confiabilidad (coeficiente alfa de Cronbach de 0,957). El promedio de las evaluaciones del desempeño de los docentes fue de 6,23 mas menos 0,8 (escala Likert 0 a 7) constituyéndose en una pauta válida y confiable para la evaluación de docentes de programas de la especialidad de radiología en países de habla hispana.

The objective of this study is to develop and validate a guideline for the evaluation of the clinical teaching process in radiology; Catholic University Medical School, Radiology 32 items (MEDUC-RX32). A mixed methodology was used for the development of the questionnaire; two interview groups (residents and faculty) and one individual to a radiology program head. Using a modified Delphi technique to reach an agreement, a national validity panel assessed the importance of each item. The Delphi panel refined the questionnaire from 88 to 32 items after two rounds. The final guideline was perfomed in 55 residents of the program. The final instrument shows high reliability (Cronbach's alpha coefficient of 0.957). The average performance evaluations of teachers was 6.23 ± 0.8 (Likert scale 0 to 7) becoming a valid and reliable guideline for teacher evaluation of programs in the specialty of radiology, in Spanish speaking countries.