SToRytelling to Improve Disease outcomes in Gout (STRIDE-GO): A multicenter, randomized controlled trial in African American veterans with gout

BACKGROUND: Urate-lowering therapy (ULT) adherence is low in gout, and few, if any, effective, low-cost, interventions are available. Our objective was to assess if a culturally appropriate gout-storytelling intervention is superior to an attention control for improving gout outcomes in African-Americans (AAs). METHODS: In a 1-year, multicenter, randomized controlled trial, AA veterans with gout were randomized to gout-storytelling intervention vs. a stress reduction video (attention control group; 1:1 ratio). The primary outcome was ULT adherence measured with MEMSCap™, an electronic monitoring system that objectively measured ULT medication adherence. RESULTS: The 306 male AA veterans with gout who met the eligibility criteria were randomized to the gout-storytelling intervention (n = 152) or stress reduction video (n = 154); 261/306 (85%) completed the 1-year study. The mean age was 64 years, body mass index was 33 kg/m CONCLUSIONS: A culturally appropriate gout-storytelling intervention was not superior to attention control for improving gout outcomes in AAs with gout. TRIAL REGISTRATION: Registered at ClinicalTrials.gov NCT02741700

Mediation of smoking-associated postoperative mortality by perioperative complications in veterans undergoing elective surgery: data from Veterans Affairs Surgical Quality Improvement Program (VASQIP)--a cohort study

OBJECTIVE: To assess the mediation of smoking-associated postoperative mortality by postoperative complications. DESIGN: Observational cohort study. SETTING: Using data from the Veterans Affairs (VA) Surgical Quality Improvement Programme, a quality assurance programme for major surgical procedures in the VA healthcare system, we assessed the association of current smoking at the time of the surgery with 6-month and 1-year mortality. PRIMARY AND SECONDARY OUTCOME MEASURES: Using mediation analyses, we calculated the relative contribution of each smoking-associated complication to smoking-associated postoperative mortality, both unadjusted and adjusted for age, race/ethnicity, work relative value unit of the operation, surgeon specialty, American Society of Anesthesiologists class and year of surgery. Smoking-associated complications included surgical site infection (SSI), cardiovascular complications (myocardial infarction, cardiac arrest and/or stroke) and pulmonary complications (pneumonia, failure to wean and/or reintubation). RESULTS: There were 186 632 never smokers and 135 741 current smokers. The association of smoking and mortality was mediated by smoking-related complications with varying effects. In unadjusted analyses, the proportions of mediation of smoking to 6-month mortality explained by the complications were as follows: SSIs 22%, cardiovascular complications 12% and pulmonary complications 89%. In adjusted analyses, the per cents mediated by each complication were as follows: SSIs 2%, cardiovascular complications 4% and pulmonary complications 22%. In adjusted analyses for 1-year mortality, respective per cents mediated were 2%, 3% and 16%. CONCLUSIONS: Pulmonary complications, followed by cardiovascular complications and SSIs were mediators of smoking-associated 6-month and 1-year mortality. Interventions targeting smoking cessation and prevention and early treatment of pulmonary complications has the likelihood of reducing postoperative mortality after elective surgery

Life in Hampton Roads Report: The 11th Annual Life in Hampton Roads Survey

[From the Executive Summary] The Social Science Research Center (SSRC) at Old Dominion University is pleased to present the results from the 11th annual Life in Hampton Roads (LIHR) survey. The purpose of the survey was to gain insight into residents’ perceptions of the quality of life in Hampton Roads. It is important to note that the methodology for this year’s survey differs from previous Life in Hampton Roads surveys. The first ten years of the survey were conducted using a random sample of Hampton Roads residents via telephone. However, this year state and university COVID-19 restrictions did not allow for staffing of the SSRC call center during the survey period. Therefore, on-line survey panels were used to solicit respondents to complete a web-based survey. Given the pandemic conditions in Hampton Roads and the rest of the world, many of this year’s questions focused on residents’ experiences with and responses to COVID-19 conditions

N-Terminal Pro-B-Type Natriuretic Peptide and Microsize Myocardial Infarction Risk in the Reasons for Geographic and Racial Differences in Stroke Study

Background: N-terminal pro B-type peptide (NT-proBNP) has been associated with risk of myocardial infarction (MI), but less is known about the relationship between NT-proBNP and very small non ST-elevation MI, also known as microsize MI. These events are now routinely detectable with modern troponin assays and are emerging as a large proportion of all MI. Here, we sought to compare the association of NT-proBNP with risk of incident typical MI and microsize MI in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study. Methods: The REGARDS Study is a national cohort of 30,239 US community-dwelling black and white adults aged ≥ 45 years recruited from 2003 to 2007. Expert-adjudicated outcomes included incident typical MI (definite/probable MI with peak troponin ≥ 0.5 μg/L), incident microsize MI (definite/probable MI with peak troponin \u3c 0.5 μg/L), and incident fatal CHD. Using a case-cohort design, we estimated the hazard ratio of the outcomes as a function of baseline NT-proBNP. Competing risk analyses tested whether the associations of NT-proBNP differed between the risk of incident microsize MI and incident typical MI as well as if the association of NT-proBNP differed between incident non-fatal microsize MI and incident non-fatal typical MI, while accounting for incident fatal coronary heart disease (CHD) as well as heart failure (HF). Results: Over a median of 5 years of follow-up, there were 315 typical MI, 139 microsize MI, and 195 incident fatal CHD. NT-proBNP was independently and strongly associated with all CHD endpoints, with significantly greater risk observed for incident microsize MI, even after removing individuals with suspected HF prior to or coincident with their incident CHD event. Conclusion: NT-proBNP is associated with all MIs, but is a more powerful risk factor for microsize than typical MI

Implementation of a provider-focused intervention for maximizing human papillomavirus (HPV) vaccine uptake in young cancer survivors receiving follow-up care in pediatric oncology practices: Protocol for a cluster-randomized trial of the HPV PROTECT intervention

BACKGROUND: Childhood cancer survivors are at high risk for developing new cancers (such as cervical and anal cancer) caused by persistent infection with the human papillomavirus (HPV). HPV vaccination is effective in preventing the infections that lead to these cancers, but HPV vaccine uptake is low among young cancer survivors. Lack of a healthcare provider recommendation is the most common reason that cancer survivors fail to initiate the HPV vaccine. Strategies that are most successful in increasing HPV vaccine uptake in the general population focus on enhancing healthcare provider skills to effectively recommend the vaccine, and reducing barriers faced by the young people and their parents in receiving the vaccine. This study will evaluate the effectiveness and implementation of an evidence-based healthcare provider-focused intervention (HPV PROTECT) adapted for use in pediatric oncology clinics, to increase HPV vaccine uptake among cancer survivors 9 to 17 years of age. METHODS: This study uses a hybrid type 1 effectiveness-implementation approach. We will test the effectiveness of the HPV PROTECT intervention using a stepped-wedge cluster-randomized trial across a multi-state sample of pediatric oncology clinics. We will evaluate implementation (provider perspectives regarding intervention feasibility, acceptability and appropriateness in the pediatric oncology setting, provider fidelity to intervention components and change in provider HPV vaccine-related knowledge and practices [e.g., providing vaccine recommendations, identifying and reducing barriers to vaccination]) using a mixed methods approach. DISCUSSION: This multisite trial will address important gaps in knowledge relevant to the prevention of HPV-related malignancies in young cancer survivors by testing the effectiveness of an evidence-based provider-directed intervention, adapted for the pediatric oncology setting, to increase HPV vaccine initiation in young cancer survivors receiving care in pediatric oncology clinics, and by procuring information regarding intervention delivery to inform future implementation efforts. If proven effective, HPV PROTECT will be readily disseminable for testing in the larger pediatric oncology community to increase HPV vaccine uptake in cancer survivors, facilitating protection against HPV-related morbidities for this vulnerable population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04469569, prospectively registered on July 14, 2020

Does delayed measurement affect patient reports of provider performance? Implications for performance measurement of medical assistance with tobacco cessation: A Dental PBRN study

<p>Abstract</p> <p>Background:</p> <p>We compared two methods of measuring provider performance of tobacco control activities: immediate "exit cards" versus delayed telephone follow-up surveys. Current standards, e.g. HEDIS, use delayed patient measures that may over or under-estimate overall performance.</p> <p>Methods:</p> <p>Patients completed exit cards in 60 dental practices immediately after a visit to measure whether the provider "asked" about tobacco use, and "advised" the patient to quit. One to six months later patients were asked the same questions by telephone survey. Using the exit cards as the standard, we quantified performance and calculated sensitivity (agreement of those responding yes on telephone surveys compared with exit cards) and specificity (agreement of those responding no) of the delayed measurement.</p> <p>Results:</p> <p>Among 150 patients, 21% reporting being asked about tobacco use on the exit cards and 30% reporting being asked in the delayed surveys. The sensitivity and specificity were 50% and 75%, respectively. Similarly, among 182 tobacco users, 38% reported being advised to quit on the exit cards and this increased to 51% on the delayed surveys. The sensitivity and specificity were 75% and 64%, respectively. Increasing the delay from the visit to the telephone survey resulted in increasing disagreement.</p> <p>Conclusion:</p> <p>Patient reports differed considerably in immediate versus delayed measures. These results have important implications because they suggest that our delayed measures may over-estimate performance. The immediate exit cards should be included in the armamentarium of tools for measuring providers' performance of tobacco control, and perhaps other service delivery.</p

Practices participating in a dental PBRN have substantial and advantageous diversity even though as a group they have much in common with dentists at large

<p>Abstract</p> <p>Background</p> <p>Practice-based research networks offer important opportunities to move recent advances into routine clinical practice. If their findings are not only generalizable to dental practices at large, but can also elucidate how practice characteristics are related to treatment outcome, their importance is even further elevated. Our objective was to determine whether we met a key objective for The Dental Practice-Based Research Network (DPBRN): to recruit a diverse range of practitioner-investigators interested in doing DPBRN studies.</p> <p>Methods</p> <p>DPBRN participants completed an enrollment questionnaire about their practices and themselves. To date, more than 1100 practitioners from the five participating regions have completed the questionnaire. The regions consist of: Alabama/Mississippi, Florida/Georgia, Minnesota, Permanente Dental Associates, and Scandinavia (Denmark, Norway, and Sweden). We tested the hypothesis that there are statistically significant differences in key characteristics among DPBRN practices, based on responses from dentists who participated in DPBRN's first network-wide study (n = 546).</p> <p>Results</p> <p>There were statistically significant, substantive regional differences among DPBRN-participating dentists, their practices, and their patient populations.</p> <p>Conclusion</p> <p>Although as a group, participants have much in common with practices at large; their substantial diversity offers important advantages, such as being able to evaluate how practice differences may affect treatment outcomes, while simultaneously offering generalizability to dentists at large. This should help foster knowledge transfer in both the research-to-practice and practice-to-research directions.</p

Evolutionary Genetics of an S-Like Polymorphism in Papaveraceae with Putative Function in Self-Incompatibility

Papaver rhoeas possesses a gametophytic self-incompatibility (SI) system not homologous to any other SI mechanism characterized at the molecular level. Four previously published full length stigmatic S-alleles from the genus Papaver exhibited remarkable sequence divergence, but these studies failed to amplify additional S-alleles despite crossing evidence for more than 60 S-alleles in Papaver rhoeas alone.Using RT-PCR we identified 87 unique putative stigmatic S-allele sequences from the Papaveraceae Argemone munita, Papaver mcconnellii, P. nudicuale, Platystemon californicus and Romneya coulteri. Hand pollinations among two full-sib families of both A. munita and P. californicus indicate a strong correlation between the putative S-genotype and observed incompatibility phenotype. However, we also found more than two S-like sequences in some individuals of A. munita and P. californicus, with two products co-segregating in both full-sib families of P. californicus. Pairwise sequence divergence estimates within and among taxa show Papaver stigmatic S-alleles to be the most variable with lower divergence among putative S-alleles from other Papaveraceae. Genealogical analysis indicates little shared ancestral polymorphism among S-like sequences from different genera. Lack of shared ancestral polymorphism could be due to long divergence times among genera studied, reduced levels of balancing selection if some or all S-like sequences do not function in incompatibility, population bottlenecks, or different levels of recombination among taxa. Preliminary estimates of positive selection find many sites under selective constraint with a few undergoing positive selection, suggesting that self-recognition may depend on amino acid substitutions at only a few sites.Because of the strong correlation between genotype and SI phenotype, sequences reported here represent either functional stylar S-alleles, tightly linked paralogs of the S-locus or a combination of both. The considerable complexity revealed in this study shows we have much to learn about the evolutionary dynamics of self-incompatibility systems

Genome-Wide Association Study Identifies Single Nucleotide Polymorphism in DYRK1A Associated with Replication of HIV-1 in Monocyte-Derived Macrophages

Background: HIV-1 infected macrophages play an important role in rendering resting T cells permissive for infection, in spreading HIV-1 to T cells, and in the pathogenesis of AIDS dementia. During highly active anti-retroviral treatment (HAART), macrophages keep producing virus because tissue penetration of antiretrovirals is suboptimal and the efficacy of some is reduced. Thus, to cure HIV-1 infection with antiretrovirals we will also need to efficiently inhibit viral replication in macrophages. The majority of the current drugs block the action of viral enzymes, whereas there is an abundance of yet unidentified host factors that could be targeted. We here present results from a genome-wide association study identifying novel genetic polymorphisms that affect in vitro HIV-1 replication in macrophages. Methodology/Principal Findings: Monocyte-derived macrophages from 393 blood donors were infected with HIV-1 and viral replication was determined using Gag p24 antigen levels. Genomic DNA from individuals with macrophages that had relatively low (n = 96) or high (n = 96) p24 production was used for SNP genotyping with the Illumina 610 Quad beadchip. A total of 494,656 SNPs that passed quality control were tested for association with HIV-1 replication in macrophages, using linear regression. We found a strong association between in vitro HIV-1 replication in monocyte-derived macrophages and SNP rs12483205 in DYRK1A (p = 2.16×10-5). While the association was not genome-wide significant (p<1×10-7), we could replicate this association using monocyte-derived macrophages from an independent group of 31 individuals (p = 0.0034). Combined analysis of the initial and replication cohort increased the strength of the association (p = 4.84×10-6). In addition, we found this SNP to be associated with HIV-1 disease progression in vivo in two independent cohort studies (p = 0.035 and p = 0.0048). Conclusions/Significance: These findings suggest that the kinase DYRK1A is involved in the replication of HIV-1, in vitro in macrophages as well as in vivo. © 2011 Bol et al

Searches for Neutrinos from Gamma-Ray Bursts Using the IceCube Neutrino Observatory

Gamma-ray bursts (GRBs) are considered as promising sources of ultra-high-energy cosmic rays (UHECRs) due to their large power output. Observing a neutrino flux from GRBs would offer evidence that GRBs are hadronic accelerators of UHECRs. Previous IceCube analyses, which primarily focused on neutrinos arriving in temporal coincidence with the prompt gamma-rays, found no significant neutrino excess. The four analyses presented in this paper extend the region of interest to 14 days before and after the prompt phase, including generic extended time windows and targeted precursor searches. GRBs were selected between 2011 May and 2018 October to align with the data set of candidate muon-neutrino events observed by IceCube. No evidence of correlation between neutrino events and GRBs was found in these analyses. Limits are set to constrain the contribution of the cosmic GRB population to the diffuse astrophysical neutrino flux observed by IceCube. Prompt neutrino emission from GRBs is limited to ≲1% of the observed diffuse neutrino flux, and emission on timescales up to 10$^{4}$ s is constrained to 24% of the total diffuse flux