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The ongoing COVID-19 pandemic is causing significant morbidity and mortality across the US. In this ecological study, we identified county-level variables associated with the COVID-19 case-fatality rate (CFR) using publicly available datasets and a negative binomial generalized linear model. Variables associated with decreased CFR included a greater number of hospitals per 10,000 people, banning religious gatherings, a higher percentage of people living in mobile homes, and a higher percentage of uninsured people. Variables associated with increased CFR included a higher percentage of the population over age 65, a higher percentage of Black or African Americans, a higher asthma prevalence, and a greater number of hospitals in a county. By identifying factors that are associated with COVID-19 CFR in US counties, we hope to help officials target public health interventions and healthcare resources to locations that are at increased risk of COVID-19 fatalities.

Increasingly, public health research standards call for engaging communities who live with health issues under investigation to help ensure that results translate into effective public health measures. Here, we share guiding principles for community-driven epidemiologic research developed over a decade conducting research sought and controlled by participating communities. These principles provide a roadmap for epidemiologic research that effectively addresses community priorities while meeting academic standards: research questions are developed collaboratively in community-university partnerships; knowledge takes shape from information donated by participants through methods that turn information into scientifically useful data and analysis that reveals data patterns that address research questions; thus, knowledge is generated collaboratively by academic researchers and community partners; academic researchers are bound by ethical, professional, scientific, contractual, and other legal standards to be responsible stewards of information donated by participants; community review protocols ensure that interpretation and presentation of research results reflect the voices of all partners; meaningful community review creates the trust needed for open access to research results as required of academic researchers; all partners share credit for achievements. Lacking models for operationalizing these principles, we developed specific guidelines for research project initiation, data use, authorship, acknowledgment, and data dissemination. Conventions in academia present formidable challenges to effective community engagement and are often at odds with calls from community organizations and funding agencies to conduct research driven by community priorities and values. We hope others can benefit from time and effort we have spent crafting solutions that bridge this divide.

BACKGROUND: Helicobacter pylori (Hp) infection is a health concern in Arctic Canada, where prevalence of Hp and gastric cancer rates are high. The Canadian North Helicobacter pylori (CANHelp) Working Group conducts community projects to address public concerns, describe the disease burden, and inform regional health policy. Projects were launched projects during 2007–2017 in Aklavik, Tuktoyaktuk, Fort McPherson, and Inuvik in the Northwest Territories and Old Crow, Teslin, Ross River, Carmacks, and Pelly Crossing in Yukon. AIMS: To provide summary data on success of anti-Hp therapies in the NWT and Yukon METHODS: In each community, a planning committee guided the research design and conduct. Projects included UBT screening, upper GI endoscopy, treatment, and knowledge exchange. All Hp-positive participants ≥15 years old could enroll in a series of randomized treatment trials to one of the following anti-Hp therapies: - CA: 10-day combination of proton pump inhibitor (PPI), clarithromycin and amoxicillin - Sequential therapy (ST) 10 day: PPI and amoxicillin for days 1–5, followed by PPI, clarithromycin and metronidazole for days 6–10 - BMT quadruple (BMT): 10–14 day bismuth quadruple therapy with PPI, bismuth, metronidazole, and tetracycline - CAM 14 day quadruple therapy with PPI, clarithromycin, amoxicillin, and metronidazole - AL: 14 day PPI, amoxicillin and levofloxacin Treatment adjustments: CA therapy was discontinued in 2008 after initial results showed poor effectiveness. Based on ST results and new Canadian guidelines ST was replaced by CAM in 2015 and treatment duration became 14 days. Treatment success is defined as a negative UBT at >=10 weeks post treatment. RESULTS: To date, of 1421 community Hp project participants, 1305 were tested for Hp by UBT (positivity=52%), 398 had endoscopy with gastric biopsy, 268 enrolled in the treatment trial, and 225 had a post-treatment UBT. In 5 patients the UBT was equivocal and these were excluded. TREATMENT TRIAL RESULTS: Of trial participants with a follow-up UBT, the proportion with treatment success was: PPI-CA 62% (29/47; 95%CI 46–75%); ST 72% (70/97; 95%CI 62–81%); BMT 92% (56/61; 95%CI 82–97%) and 100% (15/15; 95%CI 82–100%) of those randomized to CAM. Of 68 participants treated outside the clinical trial with a follow-up UBT, the proportion with treatment success was: PPI-CA 41% (7/17; 95%CI 18–67%); ST 47% (8/17; 95%CI 23–72%); BMT 92% (15/18; 95%CI 59–96%), CAM 67% (2/3; 95%CI 9–99%)and AL 3/3(100%, 95%CI 37–100%), In 10 patients the treatment was unknown. CONCLUSIONS: While treatment success estimates from this treatment trial in Canadian Arctic communities are somewhat imprecise, results demonstrate superiority of bismuth based quadruple and non-bismuth quadruple (CAM) therapies to sequential or triple therapy. Compliance with follow up UBT testing is suboptimal. FUNDING AGENCIES: CIHRInuvialuit Regional Corporation, Alberta Innovates Health Solutions, ArcticNet

Objectives Helicobacter pylori infection, linked to gastric cancer, is responsible for a large worldwide disease burden. H pylori prevalence and gastric cancer rates are elevated among indigenous Arctic communities, but implementation of prevention strategies is hampered by insufficient information. Some communities in northern Canada have advocated for H pylori prevention research. As a first step, community-driven research was undertaken to describe the H pylori- associated disease burden in concerned communities. Design Participants in this cross-sectional study completed a clinical interview and gastroscopy with gastric biopsies taken for histopathological examination in February 2008. Setting Study procedures were carried out at the health centre in Aklavik, Northwest Territories, Canada (population ∼600). Participants All residents of Aklavik were invited to complete a clinical interview and gastroscopy; 194 (58% female participants; 91% Aboriginal; age range 10–80 years) completed gastroscopy and had gastric biopsies taken. Primary and secondary outcome measures This analysis estimates the prevalence of gastric abnormalities detected by endoscopy and histopathology, and associations of demographic and clinical variables with H pylori prevalence. Results Among 194 participants with evaluable gastric biopsies, 66% were H pylori- positive on histology. Among H pylori -positive participants, prevalence was 94% for acute gastritis, 100% for chronic gastritis, 21% for gastric atrophy and 11% for intestinal metaplasia of the gastric mucosa, while chronic inflammation severity was mild in 9%, moderate in 47% and severe in 43%. In a multivariable model, H pylori prevalence was inversely associated with previous gastroscopy, previous H pylori therapy and aspirin use, and was positively associated with alcohol consumption. Conclusions In this population, H pylori -associated gastric histopathology shows a pattern compatible with elevated risk of gastric cancer. These findings demonstrate that local concern about health risks from H pylori is warranted and provide an example of how epidemiological research can address health priorities identified by communities.

The classical nuclear factor kappa B (NF-κB) signaling pathway is an important regulator of inflammation and innate immunity that is activated by a wide variety of stimuli, including virus infection, tumor necrosis factor alpha (TNF-α), and interleukin 1β (IL-1β). Poxviruses, including vaccinia virus (VV) and ectromelia virus, encode multiple proteins that function in immune evasion. Recently, a growing number of genes encoded by poxviruses have been shown to target and disrupt the NF-κB signaling pathway. To determine if additional gene products that interfere with NF-κB signaling existed, we used a vaccinia virus deletion mutant, VV811, which is missing 55 open reading frames lacking all known inhibitors of TNF-α-induced NF-κB activation. Immunofluorescence analysis of HeLa cells treated with TNF-α and IL-1β revealed that NF-κB translocation to the nucleus was inhibited in VV811-infected cells. This was further confirmed through Western blotting of cytoplasmic and nuclear extracts for NF-κB. Additionally, VV811 infection inhibited TNF-α-induced IκBα degradation. In contrast to vaccinia virus strain Copenhagen (VVCop)-infected cells, VV811 infection resulted in the dramatic accumulation of phosphorylated IκBα. Correspondingly, coimmunoprecipitation assays demonstrated that the NF-κB-inhibitory IκBα-p65-p50 complex was intact in VV811-infected cells. Significantly, cells treated with 1-β- d -arabinofuranosylcytosine, an inhibitor of poxvirus late gene expression, demonstrated that an additional vaccinia virus late gene was involved in the stabilization of IκBα. Overall, this work indicates that unidentified inhibitors of NF-κB exist in vaccinia virus. The complex inhibition of NF-κB by vaccinia virus illustrates the importance of NF-κB activation in the antiviral response.