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.

As startups no contexto da organização capitalista financeira e as subjetividades empreendedoras / Startups in the context of financial capitalist organization and entrepreneurial subjectivities / Startups en el contexto de la organización capitalista financiera y subjetividades emprendedoras

As startups são empresas que apresentam modelos de negócios marcados pela inovação, rapidez, flexibilidade e alta capacidade de adaptação aos mercados. Atuando em diferentes setores socioeconômicos, elas prometem criar e transformar produtos e serviços. A emergência e disseminação dessas empresas ocorrem em um momento histórico de mudanças iniciadas a partir de 1970 e marcadas pelas crises geradas com o esgotamento do paradigma da sociedade urbano industrial. No Brasil, o número desse modelo de negócio apresentou uma expansão expressiva, alcançando a marca de 13.374 nos últimos cinco anos. Atento a esse cenário, o objetivo desta pesquisa consistiu em compreender como sujeitos, grupos e instituições atribuem sentidos à experiência de trabalho nas chamadas startups. Na parte teórica, as condições sociais e econômicas que possibilitaram a emergência e disseminação das startups são analisadas em uma perspectiva crítica. A parte empírica, por sua vez, apresenta depoimentos de empreendedores relatando o contexto geral de atuação nas startups. Ao final deste artigo, conclui-se que há uma instrumentalização capitalística de componentes subjetivos específicos selecionados e colocados em circulação para fortalecer o modo de produção capitalista financeirizado.(AU)

Startups are companies that have business models characterized by innovation, speed, flexibility, and a high capacity to adapt to markets. Operating in different socioeconomic sectors, they promise to create and transform products and services. The emergence and dissemination of these companies occur at a historical moment of changes that began from 1970 and are marked by the crises generated by the exhaustion of the paradigm of industrial urban society. In Brazil, the number of businesses in this model showed a significant expansion, reaching 13,374 companies in the last five years. Attentive to this scenario, the objective of this research was to understand how subjects, groups, and institutions attribute meanings to the work experience in so-called startups. In the theoretical part, the social and economic conditions that enabled the emergence and dissemination of startups are analyzed in a critical perspective. The empirical part presents entrepreneurs reporting the general context of action in startups. At the end of this article, it is concluded that there is a capitalistic instrumentalization of specific subjective components that are selected and put into circulation to strengthen the financed capitalist production.(AU)

Las startups son empresas que tienen modelos de negocio marcados por la innovación, la velocidad, la flexibilidad y una alta capacidad de adaptación a los mercados. Desde diferentes sectores socioeconómicos, las startups prometen crear y transformar productos y servicios. La aparición y difusión de estas empresas se produce en un momento histórico de cambios que comenzó a partir de 1970 y que está marcado por crisis generadas por el agotamiento del paradigma de la sociedad urbana industrial. En Brasil, estas empresas se expandieron significativamente alcanzando la marca de 13.374 empresas en los últimos cinco años. En este escenario, el objetivo de esta investigación fue entender cómo los sujetos, grupos e instituciones atribuyen significados a la experiencia laboral en las startups. En la parte teórica, se analizan las condiciones sociales y económicas que permitieron el surgimiento y la difusión de las startups en una perspectiva crítica. La parte empírica presenta testimonios de emprendedores que informan sobre el trabajo en startups. La investigación concluye que hay una instrumentalización capitalista de componentes subjetivos específicos que se seleccionan y ponen en circulación para fortalecer el modo de producción capitalista financiero.(AU)

Harmonizing neuropsychological assessment for mild neurocognitive disorders in Europe.

INTRODUCTION: Harmonized neuropsychological assessment for neurocognitive disorders, an international priority for valid and reliable diagnostic procedures, has been achieved only in specific countries or research contexts. METHODS: To harmonize the assessment of mild cognitive impairment in Europe, a workshop (Geneva, May 2018) convened stakeholders, methodologists, academic, and non-academic clinicians and experts from European, US, and Australian harmonization initiatives. RESULTS: With formal presentations and thematic working-groups we defined a standard battery consistent with the U.S. Uniform DataSet, version 3, and homogeneous methodology to obtain consistent normative data across tests and languages. Adaptations consist of including two tests specific to typical Alzheimer's disease and behavioral variant frontotemporal dementia. The methodology for harmonized normative data includes consensus definition of cognitively normal controls, classification of confounding factors (age, sex, and education), and calculation of minimum sample sizes. DISCUSSION: This expert consensus allows harmonizing the diagnosis of neurocognitive disorders across European countries and possibly beyond.

Electrodiagnostic assessment of the autonomic nervous system: A consensus statement endorsed by the American Autonomic Society, American Academy of Neurology, and the International Federation of Clinical Neurophysiology.

Evaluation of disorders of the autonomic nervous system is both an art and a science, calling upon the physician's most astute clinical skills as well as knowledge of autonomic neurology and physiology. Over the last three decades, the development of noninvasive clinical tests that assess the function of autonomic nerves, the validation and standardization of these tests, and the growth of a large body of literature characterizing test results in patients with autonomic disorders have equipped clinical practice further with a valuable set of objective tools to assist diagnosis and prognosis. This review, based on current evidence, outlines an international expert consensus set of recommendations to guide clinical electrodiagnostic autonomic testing. Grading and localization of autonomic deficits incorporates scores from sympathetic cardiovascular adrenergic, parasympathetic cardiovagal, and sudomotor testing, as no single test alone is sufficient to diagnose the degree or distribution of autonomic failure. The composite autonomic severity score (CASS) is a useful score of autonomic failure that is normalized for age and gender. Valid indications for autonomic testing include generalized autonomic failure, regional or selective system syndromes of autonomic impairment, peripheral autonomic neuropathy and ganglionopathy, small fiber neuropathy, orthostatic hypotension, orthostatic intolerance, syncope, neurodegenerative disorders, autonomic hyperactivity, and anhidrosis.

Principles of Harm Reduction for Young People Who Use Drugs.

In summarizing the proceedings of a longitudinal meeting of experts on substance use disorders among adolescents and young adults, we review 2 principles of care related to harm reduction for young adults with substance use disorders. The first is that harm reduction services are critical to keeping young adults alive and healthy and can offer opportunities for future engagement in treatment. Such services therefore should be offered at every opportunity, regardless of an individual's interest or ability to minimize use of substances. The second is that all evidence-based harm reduction strategies available to older adults should be available to young adults and that whenever possible, harm reduction programs should be tailored to young adults and be developmentally appropriate.

Does improving the skills of researchers and decision-makers in health policy and systems research lead to enhanced evidence-based decision making in Nigeria?-A short term evaluation.

INTRODUCTION: Health care decision makers require capacity to demand and use research evidence for effective decision making. Capacity to undertake health policy and systems research (HPSR) and teaching is low in developing countries. Strengthening the capacity of producers and users of research is a more sustainable strategy for developing the field of HPSR in Africa, than relying on training in high-income countries. METHODS: Data were collected from 118 participants who had received the capacity building, using a pre-tested questionnaire. Respondents included health research scientists from institutions (producers) and decision makers (users) in the public health sector, in Anambra and Enugu states, southeast Nigeria. Data were collected on participants' progress with proposed group activities in their short- term goals; effects of these activities on evidence-informed decision making and constraints to implementing activities. Univariate analysis was done using SPSS version 16. FINDINGS: All prioritised activities were carried out. However, responses were low. Highest response for an activity amongst producers was 39.1%, and 44.4% for users. Some of the activities implemented positively influenced changes in practice; like modification of existing policies and programme plans. There was a wide range of responses between producers of evidence (0.0-39.1%) and users (2.7-44.4%) across both study states. Lack of authority to implement activities was the major constraint (42-9-100.0% across activities), followed by financial constraints (70.6%). CONCLUSION: Capacity building intervention improved skills of a critical mass of research scientists, policymakers and practitioners, towards evidence-based decision making. Participants committed to undertake proposed activities but faced a number of constraints. These need to be addressed, especially the decision space and authority, improving funding to implement activities that influence Getting Research into Policy & Practice (GRIPP). Being at different stages of planning and implementing proposed activities; participants require continuous technical and financial support to successfully implement activities and engage meaningfully within and across professional boundaries and roles, in order to achieve short-, medium- and long- term goals.

Why Nurses Are Essential to Research on Birth Outcomes in the United States.

In a consensus study on birth settings in the United States, the National Academy of Sciences, Engineering, and Medicine concluded that childbirth outcomes are influenced by quality of care, access to services, and choices of women within the maternity health care system. The United States has one of the highest rates of maternal mortality among the most developed nations in the world, and outcomes are marked by disparities among racial and ethnic groups of women. However, recommendations for improving birth outcomes are limited by the lack of an evidence base related to the physical and psychological safety of women during childbirth. Nurses who care for pregnant women and their infants are dedicated to ensuring that safe, high-quality care is provided during every encounter. Therefore, they are uniquely positioned to conduct the research on the fundamental elements of safety, quality, and inequities in health care that is needed to improve the maternity care system and outcomes for women and infants.

Periodontal disease and its impact on general health in Latin America: LAOHA Consensus Meeting Report.

Periodontal diseases are considered a worldwide public health problem, owing to their high prevalence in developed and developing countries. Periodontitis may lead to tooth loss, which can impact oral health-related quality of life. Gingivitis and periodontitis have been extensively studied regarding their etiopathogenesis, epidemiology, prevention and treatment outcomes. However, most of these aspects are studied and discussed globally, which may hamper a clear interpretation of the findings and the design of effective plans of action for specific regions or populations. For example, in Latin America, epidemiological data about the distribution of periodontal diseases is still scarce, mainly when it comes to nationwide representative samples. This Consensus aimed to address the following topics related to periodontal diseases in Latin America: a) The impact of the global burden of periodontal diseases on health: a global reality; b) Periodontal diseases in Latin America; c) Strategies for the prevention of periodontal diseases in Latin America; d) Problems associated with diagnosis of periodontal conditions and possible solutions for Latin America; e) Treatment of Periodontitis. This consensus will help to increase awareness about diagnosis, prevention and treatment of periodontal diseases, in the context of Latin American countries.

The Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD): The development and reliability testing of a novel clinical outcome measurement instrument for the severity of atopic dermatitis.

BACKGROUND: An Investigator Global Assessment (IGA) is recommended by health agencies for drug registration in atopic dermatitis (AD). Current IGA scales lack standardization. OBJECTIVES: To develop an IGA scale, training module, and clinical certification examination for use in AD trials; establish content validity; and assess reliability. METHODS: Expert dermatologists participated in the development of the validated IGA for AD (vIGA-ADTM). Reliability (interrater and intrarater) was assessed by 2 web-based surveys. Clinical certification for investigators consisted of a training module and examination. RESULTS: Expert consensus was achieved around a 5-point IGA scale including morphologic descriptions, and content validity was established. Survey 1 showed strong interrater reliability (Kendall's coefficient of concordance W [Kendall's W], 0.809; intraclass correlation [ICC], 0.817) and excellent agreement (weighted kappa, 0.857). Survey 2, completed 5 months after training of dermatologists, showed improvements in scale reliability (Kendall's W, 0.819; ICC, 0.852; weighted kappa, 0.889). In this study, 627 investigators completed vIGA-AD training and certification. LIMITATIONS: Ratings were assessed on photographs. CONCLUSION: A validated IGA scale and training module were developed with the intent of harmonizing assessment of disease severity in AD trials. Strong reliability and excellent agreement between assessments were observed.

Summary of a workshop on preclinical and translational safety assessment of CD3 bispecifics.

Currently, there is a multitude of CD3 bispecifics with different molecular designs and binding properties in preclinical and clinical development for the treatment of liquid or solid tumors. The key safety concerns with CD3 bispecifics are excessive release of cytokines, which may translate to potentially life-threating cytokine release syndrome (CRS), target organ toxicity due to redirection of T-cells to normal tissues expressing the tumor-associated antigen (TAA) (off-tumor/on-target cytotoxicity), and, in some instances, neurotoxicity. Another key challenge is to arrive at a safe clinical starting dose and an efficient escalating strategy that allows patients in early dose cohorts the potential for clinical benefit in Phase 1 trials. To expand the therapeutic index and bring more treatment options to patients, there are intense efforts to overcome these challenges through improvements in molecular design, preclinical safety assessment strategies, and clinical management practices. A recent workshop at the U.S. Food and Drug Administration (FDA) with industry, academic, and regulatory agency representation was held to discuss the challenges and explore where such improvements to the development of CD3 bispecifics can be implemented. Here, the content of the presentations and the discussion that occurred during this workshop are summarized.

Periodontal disease and its impact on general health in Latin America: LAOHA Consensus Meeting Report

Abstract: Periodontal diseases are considered a worldwide public health problem, owing to their high prevalence in developed and developing countries. Periodontitis may lead to tooth loss, which can impact oral health-related quality of life. Gingivitis and periodontitis have been extensively studied regarding their etiopathogenesis, epidemiology, prevention and treatment outcomes. However, most of these aspects are studied and discussed globally, which may hamper a clear interpretation of the findings and the design of effective plans of action for specific regions or populations. For example, in Latin America, epidemiological data about the distribution of periodontal diseases is still scarce, mainly when it comes to nationwide representative samples. This Consensus aimed to address the following topics related to periodontal diseases in Latin America: a) The impact of the global burden of periodontal diseases on health: a global reality; b) Periodontal diseases in Latin America; c) Strategies for the prevention of periodontal diseases in Latin America; d) Problems associated with diagnosis of periodontal conditions and possible solutions for Latin America; e) Treatment of Periodontitis. This consensus will help to increase awareness about diagnosis, prevention and treatment of periodontal diseases, in the context of Latin American countries.

Eligibility and Radiologic Assessment in Adjuvant Clinical Trials in Bladder Cancer.

Objective: To harmonize eligibility criteria and radiographic disease assessments in clinical trials of adjuvant therapy for muscle-invasive bladder cancer (MIBC). Methods: National experts in bladder cancer clinical trial research, including medical and urologic oncologists, radiologists, biostatisticians, and patient advocates, convened at a public workshop on November 28, 2017, to discuss eligibility, radiographic entry criteria, and assessment of disease recurrence in adjuvant clinical trials in patients with MIBC. Results: The key workshop conclusions for adjuvant MIBC clinical trials included the following points: (1) patients with urothelial carcinoma with divergent histologic differentiation should be allowed to enroll; (2) neoadjuvant chemotherapy is defined as at least 3 cycles of neoadjuvant cisplatin-based combination chemotherapy; (3) patients with muscle-invasive, upper-tract urothelial carcinoma should be included in adjuvant trials of MIBC; (4) patients with severe renal insufficiency can enroll into trials using agents that are not renally excreted; (5) patients with microscopic surgical margins can be included; (6) patients should undergo a standard bilateral lymph node dissection prior to enrollment; (7) computed tomographic (CT) imaging should be performed within 4 weeks prior to enrollment. For patients with renal insufficiency who cannot undergo CT imaging with contrast, noncontrast chest CT and magnetic resonance imaging of the abdomen and pelvis with gadolinium should be done; (8) biopsy of indeterminate lesions to evaluate for malignant disease should be done when feasible; (9) a uniform approach to evaluate indeterminate radiographic lesions when biopsy is not feasible should be included in any trial design; (10) a uniform approach to determining the date of recurrence is important in interpreting adjuvant trial results; and (11) new high-grade, upper-tract primary tumors and new MIBC tumors should be considered recurrence events. Conclusions and Relevance: A uniform approach to eligibility criteria, definitions of no evidence of disease, and definitions of disease recurrence may lead to more consistent interpretations of adjuvant trial results in MIBC.

Global Consensus Frameworks, Standards, Guidelines, and Tools: Their Implications in International Development Policy and Practice.

In the present world, International Consensus Frameworks, commonly called global frameworks or global agendas, guide international development policies and practices. They guide the development of all countries and influence the development initiatives by their respective governments. Recent global frameworks, adopted mostly post-2015, include both a group of over-arching frameworks (eg, the Sendai Framework for Disaster Risk Reduction [SFDRR]) and a group of frameworks addressing specific issues (eg, the Dhaka Declaration on Disability and Disaster Risk Management). These global frameworks serve twin purposes: first, to set a global development standard, and second, to set policies and approaches to achieve these standards. A companion group of professional standards, guidelines, and tools (ie, Sphere's Humanitarian Charter and Minimum Standards) guide the implementation and operationalization of these frameworks on the ground.This paper gathers these global frameworks and core professional guidelines in one place, presents an analytical review of their essential features, and highlights the commonalities and differences between and among these frameworks. The aim of this paper is to facilitate understanding of these frameworks and to help in designing development and resilience policy, planning, and implementation, at international and national levels, where these frameworks complement and contribute to each other.This Special Report describes an important and evolving aspect of the discipline and provides core information necessary to progress the science. Additionally, the report will help governments and policy makers to define their priorities and to design policies/strategies/programs to reflect the global commitments. Development practitioners can pre-empt the focus of the international community and the assistance coming from donors to the priority sectors, as identified in the global agenda. This would then help governments and stakeholders to develop and design a realistic plan and program and prepare the instruments and mechanisms to deliver the goals.

Repeating Vertebral Fracture Assessment: 2019 ISCD Official Position.

Vertebral fracture (VF) is the most common type of osteoporotic fracture. VFs are associated with a decline in quality of life and high morbidity and mortality. The presence of a VF is a significant risk factor for developing another fracture; however, most VFs are not clinically recognized and diagnosed. Vertebral fracture assessment by dual-energy X-ray absorptiometry is a low cost, low radiation, convenient, and reliable method to identify VFs. The finding of a previously unrecognized VF may change the assessment of fracture risk, diagnostic classification, and treatment strategies. Vertebral fracture assessment or radiographic lateral spine imaging should be repeated in patients with continued high risk for fracture (e.g., historical height loss >4 cm [>1.5 inches], self-reported but undocumented vertebral fracture, or glucocorticoid therapy equivalent to ≥5 mg of prednisone or equivalent per day for greater than or equal to 3 months).