Contested effects and chaotic policies: the 2020 story of (hydroxy) chloroquine for treating COVID‐19

During the past 12 months chloroquine and hydroxychloroquine have been touted as miracle cures for COVID‐19 and introduced into COVID‐19 treatment protocols in Asia, Africa, and North and South America (see Figure 1). This has led to massive increases in demand such that patients with rheumatoid arthritis and lupus have been deprived of effective treatments. A Cochrane Review by Bhagteshwar Singh and colleagues definitively concludes that hydroxychloroquine has no clinical benefit in treating COVID‐19 in hospitalized patients.[1] The dissemination of information on these drugs in the scientific press and other media has been rapid and tumultuous with strong and polarized opinions among scientists, politicians, and the general public, building a climate of mistrust. Potential resulting harms included wasted resources (including research capacity) and drug shortages for evidence‐based indications. The false hope instilled may have also led to unsupervised use of potentially harmful medications. While most national and health system‐level guidance is evidence based, how did we get into such a chaotic and confusing situation with the assessment of chloroquine and hydroxychloroquine efficacy

Feature coding dataset for trained and untrained working memory tasks in randomized controlled trials of working memory training.

The data presented in this article are produced as part of the original research article entitled "Working memory training involves learning new skills" (Gathercole, Dunning, Holmes & Norris, in press). This article presents a dataset of coded features for pairs of trained and untrained working memory (WM) tasks from randomized controlled trials of WM training with active control groups. Feature coding is provided for 113 untrained WM tasks each paired with the most similar task in the training program, taken from 23 training studies. A spreadsheet provides summary information for each task pair, its transfer effect size, and coding of the following features for each task: stimulus category, stimulus domain, stimulus modality, response modality, and recall paradigm

Biotic controls on solute distribution and transport in headwater catchments

Solute concentrations in stream water vary with discharge in patterns that record complex feedbacks between hydrologic and biogeochemical processes. In a comparison of headwater catchments underlain by shale in Pennsylvania, USA (Shale Hills) 5 and Wales, UK (Plynlimon), dissimilar concentration-discharge behaviors are best explained by contrasting landscape distributions of soil solution chemistry – especially dissolved organic carbon (DOC) – that have been established by patterns of vegetation. Specifically, elements that are concentrated in organic-rich soils due to biotic cycling (Mn, Ca, K) or that form strong complexes with DOC (Fe, Al) are spatially heteroge- 10 neous in pore waters because organic matter is heterogeneously distributed across the catchments. These solutes exhibit non-chemostatic “bioactive” behavior in the streams, and solute concentrations either decrease (Shale Hills) or increase (Plynlimon) with increasing discharge. In contrast, solutes that are concentrated in soil minerals and form only weak complexes with DOC (Na, Mg, Si) are spatially homogeneous in pore waters 15 across each catchment. These solutes are chemostatic in that their stream concentrations vary little with stream discharge, likely because these solutes are released quickly from exchange sites in the soils during rainfall events. Differences in the hydrologic connectivity of organic-rich soils to the stream drive differences in concentration behavior between catchments. As such, in catchments where soil organic matter (SOM) is dom- 20 inantly in lowlands (e.g., Shale Hills), bioactive elements are released to the stream early during rainfall events, whereas in catchments where SOM is dominantly in uplands (e.g., Plynlimon), bioactive elements are released later during rainfall events. The distribution of vegetation and SOM across the landscape is thus a key component for predictive models of solute transport in headwater catchments

Conflict of Interest Policies for Organizations Producing a Large Number of Clinical Practice Guidelines

Conflict of interest (COI) of clinical practice guideline (CPG) sponsors and authors is an important potential source of bias in CPG development. The objectives of this study were to describe the COI policies for organizations currently producing a significant number of CPGs, and to determine if these policies meet 2011 Institute of Medicine (IOM) standards.We identified organizations with five or more guidelines listed in the National Guideline Clearinghouse between January 1, 2009 and November 5, 2010. We obtained the COI policy for each organization from publicly accessible sources, most often the organization's website, and compared those polices to IOM standards related to COI. 37 organizations fulfilled our inclusion criteria, of which 17 (46%) had a COI policy directly related to CPGs. These COI policies varied widely with respect to types of COI addressed, from whom disclosures were collected, monetary thresholds for disclosure, approaches to management, and updating requirements. Not one organization's policy adhered to all seven of the IOM standards that were examined, and nine organizations did not meet a single one of the standards.COI policies among organizations producing a large number of CPGs currently do not measure up to IOM standards related to COI disclosure and management. CPG developers need to make significant improvements in these policies and their implementation in order to optimize the quality and credibility of their guidelines

NFATc2 Modulates Microglial Activation in the AβPP/PS1 Mouse Model of Alzheimer\u27s Disease

Alzheimer’s disease (AD) brains are characterized by fibrillar amyloid-β (Aβ) peptide containing plaques and associated reactive microglia. The proinflammatory phenotype of the microglia suggests that they may negatively affect disease course and contribute to behavioral decline. This hypothesis predicts that attenuating microglial activation may provide benefit against disease. Prior work from our laboratory and others has characterized a role for the transcription factor, nuclear factor of activated T cells (NFAT), in regulating microglial phenotype in response to different stimuli, including Aβ peptide. We observed that the NFATc2 isoform was the most highly expressed in murine microglia cultures, and inhibition or deletion of NFATc2 was sufficient to attenuate the ability of the microglia to secrete cytokines. In order to determine whether the NFATc2 isoform, in particular, was a valid immunomodulatory target in vivo, we crossed an NFATc2–/– line to a well-known AD mouse model, an AβPP/PS1 mouse line. As expected, the AβPP/PS1 x NFATc2–/– mice had attenuated cytokine levels compared to AβPP/PS1 mice as well as reduced microgliosis and astrogliosis with no effect on plaque load. Although some species differences in relative isoform expression may exist between murine and human microglia, it appears that microglial NFAT activity is a viable target for modulating the proinflammatory changes that occur during AD

WHO guidance for refugees in camps: systematic review

Objectives The circumstances of people living in refugee camps means that they have distinct medical care requirements. Our objective is to describe clinical guidance in published WHO guidelines that refer to people living in refugee camps; and how evidence and context are used and reported in making recommendations. Design Systematic review and analysis of WHO guidelines approved by the organisation’s quality oversight body and published between 2007 and 2018. We sought for key terms related to camps and humanitarian settings, and identified text that included guidance. We compared this to Mèdecins Sans Frontièrs (MSF) guidelines. Results No WHO guideline published in the last 10 years focused exclusively on clinical guidance for healthcare in camp settings. Seven guidelines contained guidance about camps; three made recommendations for camps—but only two used formal evidence summaries. We did not find any structured consideration of the situation in camps used in the decision-making process. We examined seven WHO guidelines and six chapters within guidelines that concerned humanitarian settings: none of these documents contained recommendations based on formal evidence summaries for camp settings. One of the eight MSF guidelines was devoted to clinical care in refugees and the authors had clearly linked the health problems and recommendations to the setting, but this guideline is now >20 years old. Conclusions There is an absence of up-to-date, evidence-based medical treatment guidelines from WHO and MSF that comprehensively address the clinical needs for people living in camps; and there is no common framework to help guideline groups formulate recommendations in these settings. WHO may wish to consider context of special populations more formally in the evidence to decision-making approach for clinical guidelines relevant to primary care

Human Monocyte Chemotaxis: A Quantitative in Vivo Technique

This report describes a new quantitative technique for evaluating monocyte chemotaxis to a site of superficial epidermal abrasion. Micro-acrylic chambers containing 50% Zymosan activated autologous serum were separated from a 5-mm diameter epidermal abrasion by 2 Nucleopore filters which entrapped migrating monocytes but allowed free neutrophil migration. Monocytes were specifically identified by alpha napthyl acetate esterase activity. Monocytes accumulated within the filters by 4 hr and maximized at 16 and 20 hr.This technique is superior to previous skin chamber techniques in the high yield of monocytes and in specific histochemical identification of monocytes. In contrast to the Rebuck window, it does not generate attractants and has greater reproducibility.This technique will be useful in the study of diseases characterized by monocytic infiltrates, in contrasting the function of peripheral blood monocytes to those available in the skin, and in testing the effects of drugs, immunodeficiency and infection on monocyte function in vivo

Types of Prayer and Depressive Symptoms among Cancer Patients: The Mediating Role of Rumination and Social Support

We examined the association between different types of prayer and depressive symptoms—with rumination and social support as potential mediators—in a sample of predominantly White, Christian, and female ambulatory cancer patients. In a cross-sectional design, 179 adult cancer outpatients completed measures of prayer, rumination, social support, depressive symptoms, and demographic variables. Type and stage of cancer were collected from electronic medical charts. Depressive symptoms were negatively correlated with adoration prayer (r = −.15), reception prayer (r = −.17), thanksgiving prayer (r = −.29), and prayer for the well-being of others (r = −.26). In the path analysis, rumination fully mediated the link between thanksgiving prayer and depressive symptoms (β for indirect effect = −.05), whereas social support partially mediated the link between prayer for others and depressive symptoms (β for indirect effect = −.05). These findings suggest that unique mechanisms may link different prayer types to lower depressive symptoms among cancer patients

Effectiveness of Personal Protective Equipment for Healthcare Workers Caring for Patients with Filovirus Disease: A Rapid Review

BACKGROUND: A rapid review, guided by a protocol, was conducted to inform development of the World Health Organization’s guideline on personal protective equipment in the context of the ongoing (2013-present) Western African filovirus disease outbreak, with a focus on health care workers directly caring for patients with Ebola or Marburg virus diseases. METHODS: Electronic databases and grey literature sources were searched. Eligibility criteria initially included comparative studies on Ebola and Marburg virus diseases reported in English or French, but criteria were expanded to studies on other viral hemorrhagic fevers and non-comparative designs due to the paucity of studies. After title and abstract screening (two people to exclude), full-text reports of potentially relevant articles were assessed in duplicate. Fifty-seven percent of extraction information was verified. The Grading of Recommendations Assessment, Development and Evaluation framework was used to inform the quality of evidence assessments. RESULTS: Thirty non-comparative studies (8 related to Ebola virus disease) were located, and 27 provided data on viral transmission. Reporting of personal protective equipment components and infection prevention and control protocols was generally poor. CONCLUSIONS: Insufficient evidence exists to draw conclusions regarding the comparative effectiveness of various types of personal protective equipment. Additional research is urgently needed to determine optimal PPE for health care workers caring for patients with filovirus