Review of epidemiologic data on the debate over smokeless tobacco's role in harm reduction

Some tobacco researchers have argued that the European Union should remove its ban on a form of low-nitrosamine smokeless tobacco referred to as Swedish 'snus'. This argument has developed in to an international debate over the use of smokeless tobacco as a measure of harm reduction for smokers. Leading authorities in the USA have firmly stated that there is no safe tobacco - a message which does not allow for any discussion of comparative tobacco risks. This commentary is intended to review the origin of the controversy over Swedish 'snus', to examine briefly the meta-analysis on cancer risks by Peter Lee and Jan Hamling (published in July in BMC Medicine) and to discuss the anticipated direction of the debate on tobacco-harm reduction in the USA. We anticipate that much of the debate will shift from the discussion of epidemiologic data to the discussion of the marketing, health communication and economics of smokeless tobacco. While the Food and Drug Administration's newly approved authority over tobacco will undoubtedly affect the smokeless products, it may not be the sole determinant of harm reduction's fate in the USA

The Endoplasmic Reticulum Stress Response in Neuroprogressive Diseases: Emerging Pathophysiological Role and Translational Implications

The endoplasmic reticulum (ER) is the main cellular organelle involved in protein synthesis, assembly and secretion. Accumulating evidence shows that across several neurodegenerative and neuroprogressive diseases, ER stress ensues, which is accompanied by over-activation of the unfolded protein response (UPR). Although the UPR could initially serve adaptive purposes in conditions associated with higher cellular demands and after exposure to a range of pathophysiological insults, over time the UPR may become detrimental, thus contributing to neuroprogression. Herein, we propose that immune-inflammatory, neuro-oxidative, neuro-nitrosative, as well as mitochondrial pathways may reciprocally interact with aberrations in UPR pathways. Furthermore, ER stress may contribute to a deregulation in calcium homoeostasis. The common denominator of these pathways is a decrease in neuronal resilience, synaptic dysfunction and even cell death. This review also discusses how mechanisms related to ER stress could be explored as a source for novel therapeutic targets for neurodegenerative and neuroprogressive diseases. The design of randomised controlled trials testing compounds that target aberrant UPR-related pathways within the emerging framework of precision psychiatry is warranted

Community-based HCV screening: knowledge and attitudes in a high risk urban population.

BACKGROUND: In an attempt to curtail the rising morbidity and mortality from undiagnosed HCV (hepatitis C virus) in the United States, screening guidelines have been expanded to high-risk individuals and persons born 1945-1965. Community-based screening may be one strategy in which to reach such persons; however, the acceptance of HCV testing, when many high-risk individuals may not have access to HCV specific medications, remains unknown. METHODS: We set out to assess attitudes about HCV screening and knowledge about HCV disease at several community-based testing sites that serve high-risk populations. This assessment was paired with a brief HCV educational intervention, followed by post-education evaluation. RESULTS: Participants (n = 140) were surveyed at five sites; two homeless shelters, two drug rehabilitation centers, and a women's "drop-in" center. Personal acceptance of HCV testing was almost unanimous, and 90% of participants reported that they would still want to be tested even if they were unable to receive HCV treatment. Baseline hepatitis C knowledge was poor; however, the brief educational intervention significantly improved knowledge and increased acceptability of testing when medical access issues were explicitly stated. CONCLUSIONS: Despite inconsistencies in access to care and treatment, high-risk communities want to know their HCV status. Though baseline HCV knowledge was poor in this population, a brief on-site educational intervention improved both knowledge and acceptability of HCV testing and care. These data support the establishment of programs that utilize community-based screening, and also provide initial evidence for acceptance of the implementation of the recently expanded screening guidelines among marginalized communities

Multicenter Initial Guidance on Use of Antivirals for Children With Coronavirus Disease 2019/Severe Acute Respiratory Syndrome Coronavirus 2

BACKGROUND: Although coronavirus disease 2019 (COVID-19) is mild in nearly all children, a small proportion of pediatric patients develop severe or critical illness. Guidance is therefore needed regarding use of agents with potential activity against severe acute respiratory syndrome coronavirus 2 in pediatrics. METHODS: A panel of pediatric infectious diseases physicians and pharmacists from 18 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a set of guidance statements was developed and refined based on review of best available evidence and expert opinion. RESULTS: Given the typically mild course of pediatric COVID-19, supportive care alone is suggested for the overwhelming majority of cases. The panel suggests a decision-making framework for antiviral therapy that weighs risks and benefits based on disease severity as indicated by respiratory support needs, with consideration on a case-by-case basis of potential pediatric risk factors for disease progression. If an antiviral is used, the panel suggests remdesivir as the preferred agent. Hydroxychloroquine could be considered for patients who are not candidates for remdesivir or when remdesivir is not available. Antivirals should preferably be used as part of a clinical trial if available. CONCLUSIONS: Antiviral therapy for COVID-19 is not necessary for the great majority of pediatric patients. For those rare cases of severe or critical disease, this guidance offers an approach for decision-making regarding antivirals, informed by available data. As evidence continues to evolve rapidly, the need for updates to the guidance is anticipated