Trust In US Federal, State, And Local Public Health Agencies During COVID-19: Responses And Policy Implications.

Public health agencies' ability to protect health in the wake of COVID-19 largely depends on public trust. In February 2022 we conducted a first-of-its-kind nationally representative survey of 4,208 US adults to learn the public's reported reasons for trust in federal, state, and local public health agencies. Among respondents who expressed a "great deal" of trust, that trust was not related primarily to agencies' ability to control the spread of COVID-19 but, rather, to beliefs that those agencies made clear, science-based recommendations and provided protective resources. Scientific expertise was a more commonly reported reason for "a great deal" of trust at the federal level, whereas perceptions of hard work, compassionate policy, and direct services were emphasized more at the state and local levels. Although trust in public health agencies was not especially high, few respondents indicated that they had no trust. Lower trust was related primarily to respondents' beliefs that health recommendations were politically influenced and inconsistent. The least trusting respondents also endorsed concerns about private-sector influence and excessive restrictions and had low trust in government overall. Our findings suggest the need to support a robust federal, state, and local public health communications infrastructure; ensure agencies' authority to make science-based recommendations; and develop strategies for engaging different segments of the public.

A systematic evaluation of the safety and toxicity of fingolimod for its potential use in the treatment of acute myeloid leukaemia.

Treatment of acute myeloid leukaemia (AML) is challenging and emerging treatment options include protein phosphatase 2A (PP2A) activators. Fingolimod is a known PP2A activator that inhibits multiple signalling pathways and has been used extensively in patients with multiple sclerosis and other indications. The initial positive results of PP2A activators in vitro and mouse models of AML are promising; however, its safety for use in AML has not been assessed. From human studies of fingolimod in other indications, it is possible to evaluate whether the safety and toxicity profile of the PP2A activators will allow their use in treating AML. A literature review was carried out to assess safety before the commencement of Phase I trials of the PP2A activator Fingolimod in AML. From human studies of fingolimod in other indications, it is possible to evaluate whether the safety and toxicity profile of the PP2A activators will allow their use in treating AML. A systematic review of published literature in Medline, EMBASE and the Cochrane Library of critical reviews was carried out. International standards for the design and reporting of search strategies were followed. Search terms and medical subject headings used in trials involving PP2A activators as well as a specific search were performed for 'adverse events', 'serious adverse events', 'delays in treatment', ' side effects' and 'toxicity' for primary objectives. Database searches were limited to papers published in the last 12 years and available in English. The search yielded 677 articles. A total of 69 journal articles were identified as relevant and included 30 clinical trials, 24 review articles and 15 case reports. The most frequently reported adverse events were nausea, diarrhoea, fatigue, back pain, influenza viral infections, nasopharyngitis and bronchitis. Specific safety concerns include monitoring of the heart rate and conduction at commencement of treatment as cardiotoxicity has been reported. There is little evidence to suggest specific bone marrow toxicity. Lymophopenia is a desired effect in the management of multiple sclerosis, but may have implications in patients with acute leukaemia as it may potentially increase susceptibility to viral infections such as influenza. Fingolimod is a potential treatment option for AML with an acceptable risk to benefit ratio, given its lack of bone marrow toxicity and the relatively low rate of serious side effects. As most patients with AML are elderly, specific monitoring for cardiac toxicity as well as infection would be required.