No effect of acidification or freezing on urinary metanephrine levels.

BACKGROUND: Urinary metanephrine is a reliable method to estimate catecholamine secretion. Traditionally, urinary metanephrines are collected into chilled containers containing hydrochloric acid (HCl) and most laboratories freeze urinary samples before analysis. It is uncertain if these pre-analytic procedures alter metanephrine values. AIM: To evaluate if acidifying and freezing urine samples affect the accuracy of urinary metanephrine measurements. METHODS: Random urine samples from healthy individuals were collected. Urine samples were distributed into two containers: with HCl 50% homogenized with urine to obtain pH < 2, and without HCl. Each container was divided again into aliquots for immediate measurement or freezing. One aliquot with acid (group 1) and another without acid (group 2) were sent immediately to the laboratory for testing (HPLC), while the other two aliquots, one with acid (group 3) and another without it (group 4) were frozen for 3 months at - 20 °C. Bland-Altman's test was used to analyze inter-assay agreement between measurements. RESULTS: A total of 15 individuals were included (mean age 27.5 ± 5.9 years, 8 male and 14 white). No difference was observed on mean urinary metanephrine/creatinine ratio between groups: group 1: 0.23 ± 0.11, group 2: 0.22 ± 0.07, group 3: 0.25 ± 0.13, group 4: 0.25 ± 0.15 mg/g creatinine; P > 0.05 for all the comparisons). Bland-Altman's analysis showed agreement between the standard method (group 1) and the experimental method (group 4). CONCLUSION: Measurement of urinary metanephrines by HPLC method is not influenced by sample acidification nor freezing at - 20 °C for 3 months.

The prognostic value of tumour-stroma ratio in primary breast cancer with special attention to triple-negative tumours: a review.

PURPOSE: There is a strong need to improve the prognostication of breast cancer patients in order to prevent over- and undertreatment, especially when considering adjuvant chemotherapy. Tumour stroma characteristics might be valuable in predicting disease progression. METHODS: Studies regarding the prognostic value of tumour-stroma ratio (TSR) in breast cancer are evaluated. RESULTS: A high stromal content is related to a relatively poor prognosis. The most pronounced prognostic effect of this parameter seems to be observed in the triple-negative breast cancer (TNBC) subtype. CONCLUSIONS: TSR assessment might represent a simple, fast and reproducible prognostic factor at no extra costs, and could possibly be incorporated into routine pathological diagnostics. Despite these advantages, a robust clinical validation of this parameter has yet to be established in prospective studies.

Attitudes toward HIV testing, awareness of HIV campaigns, and using social networking sites to deliver HIV testing messages in the age of social media: a qualitative study of young black men.

This study assessed attitudes toward HIV and awareness of previous HIV prevention campaigns among young black men in the United States of America (USA). The study also ascertained the appropriateness of HIV testing messages for young black men and explored the use of social networking sites to deliver HIV testing messages for social media marketing campaigns. Nineteen (n = 19) black male college students attending a public university in Atlanta, GA, USA from September 2016 to October 2016 participated in three focus groups. The focus groups consisted of a group interview querying experiences with HIV and STI testing, awareness of HIV campaigns, solicited feedback on campaign messages and the use of social networking sites to deliver messages. Data analysis involved the grounded theory approach to identify emergent themes. Fear, stigma and low risk perception were discussed as barriers to HIV testing. HIV prevention, social support and new sexual partners were discussed as reasons for testing. There was a general lack of awareness of existing HIV testing campaigns. Messaging with a universal appeal and disseminated through Twitter, Instagram and Snapchat may counter narratives of fear, stigma and low risk perception to increase HIV testing among young black men.

Guidelines for training in cardiovascular magnetic resonance (CMR).

These "Guidelines for training in Cardiovascular Magnetic Resonance" were developed by the Certification Committee of the Society for Cardiovascular Magnetic Resonance (SCMR) and approved by the SCMR Board of Trustees.

Comparison of the Nephrotoxicity of Vancomycin in Combination With Cefepime, Meropenem, or Piperacillin/Tazobactam: A Prospective, Multicenter Study.

BACKGROUND: Patients often receive broad-spectrum antibiotics for nosocomial infections commonly with activity against Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus. Previous retrospective and/or single-center studies have suggested that the combination of vancomycin and piperacillin/tazobactam might be associated with an increased risk of acute kidney injury. OBJECTIVES: To compare the incidence of nephrotoxicity in patients receiving intravenous vancomycin in combination with cefepime, meropenem, or piperacillin/tazobactam. METHODS: This was a prospective, multicenter observational study of patients receiving vancomycin in combination with piperacillin/tazobactam versus cefepime or meropenem. Adult patients 18 years of age or older who were hospitalized and received 72 or more hours of intravenous vancomycin and 72 hours or more of cefepime, meropenem, or piperacillin/tazobactam were eligible. Patient and medication characteristics were examined for the 242 patients included. RESULTS: The incidence of acute kidney injury for patients treated with vancomycin and piperacillin/tazobactam was significantly higher than for those treated with vancomycin and cefepime or meropenem, 29.8% versus 8.8%, respectively, P < 0.001. Binary logistic regression demonstrated that patients receiving vancomycin and piperacillin/tazobactam were 6.7 times more likely to develop acute kidney injury compared with the other cohort. CONCLUSIONS: The combination of vancomycin with piperacillin/tazobactam significantly increases the risk of acute kidney injury compared with other broad-spectrum antibiotic combinations. Clinicians should be vigilant when employing this regimen.

Fetal sex and maternal risk of pre-eclampsia/eclampsia: a systematic review and meta-analysis.

BACKGROUND: A preponderance of male fetuses in pregnancies complicated by pre-eclampsia was described over 40 years ago. Since then, however, there has been conflicting evidence in the literature, with some studies supporting a male preponderance, some demonstrating no relationship with fetal sex, and others reporting increased risk in pregnancies bearing females. OBJECTIVES: In this context, we sought to conduct a systematic review and meta-analysis to objectively evaluate the relationship between fetal sex and maternal risk of pre-eclampsia/eclampsia. SEARCH STRATEGY: Studies from January 1950 to April 2015 were identified from PUBMED and EMBASE. SELECTION CRITERIA: This systematic review and meta-analysis evaluated 22 articles reporting data on fetal sex and prevalence of pre-eclampsia/eclampsia. DATA COLLECTION AND ANALYSIS: Data were extracted by two independent reviewers. Pooled estimates of the relative risk (RR) were calculated by random-effects model. MAIN RESULTS: Male fetus was considered the exposure and prevalence of maternal pre-eclampsia/eclampsia was the outcome of interest. We identified 534 studies through electronic searches and three studies through manual searches. Twenty-two studies fulfilled the inclusion criteria, yielding data on 3 163 735 women. Pooled analyses of these studies showed no association between male fetal sex and maternal risk of pre-eclampsia/eclampsia (RR 1.01; 95% confidence interval, 95% CI 0.97-1.05); however, a subgroup analysis including only studies that evaluated the non-Asian population (n = 2 931 771 women) demonstrated that male fetal sex was associated with increased maternal risk of pre-eclampsia/eclampsia (RR 1.05; 95% CI 1.03-1.06; I2 = 10%; P = 0.33). CONCLUSION: Male fetal sex is associated with maternal risk of pre-eclampsia/eclampsia in the non-Asian population. TWEETABLE ABSTRACT: Fetal sex is associated with maternal risk of pre-eclampsia/eclampsia in the non-Asian population.

Enrolling African-American and Latino patients with asthma in comparative effectiveness research: Lessons learned from 8 patient-centered studies.

BACKGROUND: African-American and Latino patients are often difficult to recruit for asthma studies. This challenge is a barrier to improving asthma care and outcomes for these populations. OBJECTIVES: We sought to examine the recruitment experiences of 8 asthma comparative effectiveness studies that specifically targeted African-American and Latino patients, and identify the solutions they developed to improve recruitment. METHODS: Case report methodology was used to gather and evaluate information on study design, recruitment procedures and outcomes from study protocols and annual reports, and in-depth interviews with each research team. Data were analyzed for themes, commonalities, and differences. RESULTS: There were 4 domains of recruitment challenges: individual participant, institutional, research team, and study intervention. Participants had competing demands for time and some did not believe they had asthma. Institutional challenges included organizational policies governing monetary incentives and staff hiring. Research team challenges included ongoing training needs of recruitment staff, and intervention designs often were unappealing to participants because of inconveniences. Teams identified a host of strategies to address these challenges, most importantly engagement of patients and other stakeholders in study design and troubleshooting, and flexibility in data collection and intervention application to meet the varied needs of patients. CONCLUSIONS: Asthma researchers may have greater success with recruitment by addressing uncertainty among patients about asthma diagnosis, engaging stakeholders in all aspects of study design and implementation, and maximizing flexibility of study and intervention protocols. However, even with such efforts, engagement of African-American and Latino patients in asthma research may remain low. Greater investment in research on engaging these populations in asthma research may ultimately be needed to improve their asthma care and outcomes.

A randomized trial on chlorhexidine dressings for the prevention of catheter-related bloodstream infections in neutropenic patients.

BACKGROUND: Central venous catheter (CVC)-related bloodstream infections (CRBSI) are a frequent cause of morbidity and mortality in patients with chemotherapy-induced neutropenia. Chlorhexidine containing catheter securement dressings may prevent CRBSI. PATIENTS AND METHODS: A multicenter randomized, controlled trial was conducted at 10 German hematology departments. We compared chlorhexidine-containing dressings with non-chlorhexidine control dressings in neutropenic patients. The primary end point was the incidence of definite CRBSI within the first 14 days (dCRBSI14) of CVC placement. Secondary end points included combined incidence of definite or probable CRBSI within 14 days (dpCRBSI14), overall (dpCRBSI), incidence of unscheduled dressing changes and adverse events. RESULTS: From February 2012 to September 2014, 613 assessable patients were included in the study. The incidence of dCRBSI14 was 2.6% (8/307) in the chlorhexidine and 3.9% (12/306) in the control group (P = 0.375). Both dpCRBSI14 and dpCRBSI were significantly less frequent in the study group with dpCRBSI14 in 6.5% (20/307) of the chlorhexidine group when compared with 11% (34/306) in the control group (P = 0.047), and dpCRBSI in 10.4% (32/307) versus 17% (52/306), respectively (P = 0.019). The frequency of dressing intolerance with cutaneous and soft tissue abnormalities at the contact area was similar in both groups (12.4% and 11.8%; P = 0.901). CONCLUSIONS: Although the trial failed its primary end point, the application of chlorhexidine containing catheter securement dressings reduces the incidence of definite or probable CRBSI in neutropenic patients. CLINICAL TRIALS NUMBER: NCT01544686 (Clinicaltrials.gov).

Immune dysregulation mediated by the oral microbiome: potential link to chronic inflammation and atherosclerosis.

Cardiovascular disease is an inflammatory disorder characterized by the progressive formation of plaque in coronary arteries, termed atherosclerosis. It is a multifactorial disease that is one of the leading causes of death worldwide. Although a number of risk factors have been associated with disease progression, the underlying inflammatory mechanisms contributing to atherosclerosis remain to be fully delineated. Within the last decade, the potential role for infection in inflammatory plaque progression has received considerable interest. Microbial pathogens associated with periodontal disease have been of particular interest due to the high levels of bacteremia that are observed after routine dental procedures and every day oral activities, such as tooth brushing. Here, we explore the potential mechanisms that may explain how periodontal pathogens either directly or indirectly elicit immune dysregulation and consequently progressive inflammation manifested as atherosclerosis. Periodontal pathogens have been shown to contribute directly to atherosclerosis by disrupting endothelial cell function, one of the earliest indicators of cardiovascular disease. Oral infection is thought to indirectly induce elevated production of inflammatory mediators in the systemic circulation. Recently, a number of studies have been conducted focusing on how disruption of the gut microbiome influences the systemic production of proinflammatory cytokines and consequently exacerbation of inflammatory diseases such as atherosclerosis. It is clear that the immune mechanisms leading to atherosclerotic plaque progression, by oral infection, are complex. Understanding the immune pathways leading to disease progression is essential for the future development of anti-inflammatory therapies for this chronic disease.

Devastating Delayed Leukoencephalopathy Associated with Bath Salt Inhalation.

BACKGROUND: "Bath salts" or synthetic cathinone toxicity remains a potentially deadly clinical condition. We report a delayed leukoencephalopathy with persistent minimally conscious state. METHODS: Case report. RESULTS: A 36-year-old man presents with delayed encephalopathy, dysautonomia, fulminant hepatic failure, and renal failure from severe rhabdomyolysis after consuming bath salts. MRI showed diffusion restriction in the splenium of the corpus callosum and subcortical white matter. CONCLUSIONS: The combination of acute leukoencephalopathy, rhabdomyolysis and fulminant hepatic failure may point to bath salt inhalation and should be known to neurointensivists.

Antipneumococcal activity of neuraminidase inhibiting artocarpin.

Streptococcus (S.) pneumoniae is a major cause of secondary bacterial pneumonia during influenza epidemics. Neuraminidase (NA) is a virulence factor of both pneumococci and influenza viruses. Bacterial neuraminidases (NAs) are structurally related to viral NA and susceptible to oseltamivir, an inhibitor designed to target viral NA. This prompted us to evaluate the antipneumococcal potential of two NA inhibiting natural compounds, the diarylheptanoid katsumadain A and the isoprenylated flavone artocarpin. Chemiluminescence, fluorescence-, and hemagglutination-based enzyme assays were applied to determine the inhibitory efficiency (IC(50) value) of the tested compounds towards pneumococcal NAs. The mechanism of inhibition was studied via enzyme kinetics with recombinant NanA NA. Unlike oseltamivir, which competes with the natural substrate of NA, artocarpin exhibits a mixed-type inhibition with a Ki value of 9.70 µM. Remarkably, artocarpin was the only NA inhibitor (NAI) for which an inhibitory effect on pneumococcal growth (MIC: 0.99-5.75 µM) and biofilm formation (MBIC: 1.15-2.97 µM) was observable. In addition, we discovered that the bactericidal effect of artocarpin can reduce the viability of pneumococci by a factor of >1000, without obvious harm to lung epithelial cells. This renders artocarpin a promising natural product for further investigations.

Clinical predictors and time course of the improvement in ß-cell function with short-term intensive insulin therapy in patients with Type 2 diabetes.

AIMS: In patients with Type 2 diabetes, a short course of intensive insulin therapy can improve ß-cell function and even induce transient remission of diabetes. However, not all patients respond to this therapy. Although the achievement of fasting glucose  < 7.0 mmol/l one day after stopping intensive insulin therapy can identify patients in whom ß-cell function has improved, we sought to determine clinical predictors for the early identification of such responders and the time course of response. METHODS: We pooled data from two studies in which 97 patients with Type 2 diabetes mellitus (median 3 years duration) and HbA1c 51 ± 8.7 mmol/mol (6.8 ± 0.8%) underwent 4-8 weeks of intensive insulin therapy, consisting of basal detemir and pre-meal insulin aspart. They were classified as responders (n = 74) or non-responders (n = 23), defined by the achievement of fasting glucose  < 7.0 mmol/l after stopping intensive insulin therapy. RESULTS: On logistic regression analyses, duration of diabetes (odds ratio [OR] = 0.72, 95% confidence interval [CI] 0.56-0.92, P = 0.009) and baseline fasting glucose (OR = 0.40, 95% CI 0.24-0.68, P = 0.001) emerged as predictors of the likelihood of responding. Ninety per cent of patients with duration ≤ 4 years and fasting glucose ≤ 8.0 mmol/l responded to intensive insulin therapy. Despite having lower glucose levels during intensive insulin therapy, responders had less hypoglycaemia than non-responders (median 0.3 vs. 1.6 episodes/week, P < 0.0001), with rates of hypoglycaemia diverging sharply from the third week onwards. CONCLUSION: At baseline, shorter duration of diabetes and lower fasting glucose can identify patients most likely to benefit from short-term intensive insulin therapy. Most importantly, during therapy, responders had less hypoglycaemia from the third week onwards, despite lower glycaemia, suggesting that 2 weeks of intensive insulin therapy may be needed to improve endogenous islet function.

Hemorrhage or Ischemia? The Importance of 'Spotting' it Right.

BACKGROUND: A 78-year-old woman was transferred directly to an ICU because of intracerebral hemorrhage. However, on careful review of the initial imaging, the likely diagnosis was ischemic stroke and reperfusion hemorrhage. METHODS: Case report was explained. RESULTS: The patient suffered significant reperfusion hemorrhage. A CT angiogram revealed contrast extravasation "spot sign" in the bed of the expanding hemorrhage and an occlusive thromboembolism distal to the initial ischemic insult. CONCLUSION: In this case of embolic ischemic stroke with reperfusion hemorrhage, contrast extravasation "spot sign" was associated with hematoma expansion.

c-myc in whitefish (Coregonus lavaretus): structure, expression, and insights into possible posttranscriptional regulatory mechanism.

c-myc has a crucial function in growth control, differentiation, and apoptosis of vertebrate cells. Despite the important role of c-myc in mediating the biological effects, studies of c-myc gene expression and factors that control it in organisms other than mammals, such as fish, have been rare. In the current study, we asked whether c-myc mRNA of whitefish, a feasible organism for pollution monitoring in aquatic systems and a model in toxicological research, contains activity sites for regulatory motifs in its 5'- and 3'-UTRs, similar to those found in mammals. We were particularly interested in whether miRNA-34, a known negative regulator of c-myc's in mammals, is able to regulate c-myc in fish. To answer these questions, we determined the mRNA sequence of whitefish c-myc and inferred the structure of the protein that it codes for. We found that the active sites of mRNA and structures of the inferred c-myc protein are similar to those found in mammals and other fish. Remarkably, levels of c-myc mRNA expression were very high in ovaries compared to other tissues of whitefish, thus corroborating previous data in fish. Using bioinformatic searches on c-myc 3'-UTR, we confirmed the presence of two miRNA-34a (miR-34a) response elements. Luciferase reporter assay showed that activity of reporters containing either the miR response elements or entire c-myc 3'-UTR was significantly reduced (p < 0.001) by ectopic expression of miR-34a. Therefore, we further investigated possible involvement of miR-34a in c-myc gene silencing by profiling the expression of both genes in livers of whitefish treated for 8, 24, 48 h with MC-LR, a potent c-myc inducer in mammals. Although the difference was only significant at p = 0.08, the expression of c-myc mRNA in challenged whitefish after 24 h of the treatment was notably higher than that in livers of control fish. Concurrently, we noticed slight but significant up-regulation of miR-34a after 24 and 48 h of the challenge (p < 0.05); however, we found no significant correlation of the c-myc mRNA levels and miR-34a expression. Together, these results suggest that miR-34a might regulate c-myc gene expression in whitefish liver; however, their involvement in MC-LR hepatotoxicity should be clarified in future studies.

Improving docking results via reranking of ensembles of ligand poses in multiple X-ray protein conformations with MM-GBSA.

There is a tendency in the literature to be critical of scoring functions when docking programs perform poorly. The assumption is that existing scoring functions need to be enhanced or new ones developed in order to improve the performance of docking programs for tasks such as pose prediction and virtual screening. However, failures can result from either sampling or scoring (or a combination of the two), although less emphasis tends to be given to the former. In this work, we use the programs GOLD and Glide on a high-quality data set to explore whether failures in pose prediction and binding affinity estimation can be attributable more to sampling or scoring. We show that identification of the correct pose (docking power) can be improved by incorporating ligand strain into the scoring function or rescoring an ensemble of diverse docking poses with MM-GBSA in a postprocessing step. We explore the use of nondefault docking settings and find that enhancing ligand sampling also improves docking power, again suggesting that sampling is more limiting than scoring for the docking programs investigated in this work. In cross-docking calculations (docking a ligand to a noncognate receptor structure) we observe a significant reduction in the accuracy of pose ranking, as expected and has been reported by others; however, we demonstrate that these alternate poses may in fact be more complementary between the ligand and the rigid receptor conformation, emphasizing that treating the receptor rigidly is an artificial constraint on the docking problem. We simulate protein flexibility by the use of multiple crystallographic conformations of a protein and demonstrate that docking results can be improved with this level of protein sampling. This work indicates the need for better sampling in docking programs, especially for the receptor. This study also highlights the variable descriptive value of RMSD as the sole arbiter of pose replication quality. It is shown that ligand poses within 2 Å of the crystallographic one can show dramatic differences in calculated relative protein-ligand energies. MM-GBSA rescoring of distinct poses overcomes some of the sensitivities of pose ranking experienced by the docking scoring functions due to protein preparation and binding site definition.

Evaluating an equity-focused approach to assess climate resilience and disaster priorities through a community survey.

As the Duwamish Valley community in Seattle, Washington, U.S.A. and other environmental justice communities nationally contend with growing risks from climate change, there have been calls for a more community-centered approach to understanding impacts and priorities to inform resilience planning. To engage community members and identify climate justice and resilience priorities, a partnership of community leaders, government-based practitioners, and academics co-produced a survey instrument and collected data from the community using the Seattle Assessment for Public Health Emergency Response (SASPER), an approach adapted from the Centers for Disease Control and Prevention's Community Assessment for Public Health Emergency Response (CASPER). In addition, we conducted a process and outcome project evaluation using quantitative survey data collected from volunteers and qualitative semi-structured interviews with project team members. In October and November 2022, teams of volunteers from partner organizations collected 162 surveys from households in the Duwamish Valley. Poor air quality, extreme heat, and wildfires were among the highest reported hazards of concern. Most Duwamish Valley households agreed or strongly agreed that their neighborhood has a strong sense of community (64%) and that they have people nearby to call when they need help (69%). Forty-seven percent of households indicated willingness to get involved with resilience planning, and 62% of households said that they would use a Resilience Hub during an emergency. Survey volunteers evaluated their participation positively, with over 85% agreeing or strongly agreeing that they learned new skills, were prepared for the survey, and would participate in future assessments. The evaluation interviews underscored that while the SASPER may have demonstrated feasibility in a pre-disaster phase, CASPER may not meet all community/partner needs in the immediate disaster response phase because of its lack of focus on equity and logistical requirements. Future research should focus on identifying less resource intensive data collection approaches that maintain the rigor and reputation of CASPER while enabling a focus on equity.

Concordance of retinopathy and nephropathy over time in Type 1 diabetes: an analysis of data from the Diabetes Control and Complications Trial.

AIMS: Little is known about the dynamic relationship over time between diabetic retinopathy and nephropathy. Thus, we sought to evaluate the concordance over time of retinopathy and nephropathy in patients with Type 1 diabetes during the Diabetes Control and Complications Trial. METHODS: This analysis was conducted in patients with Type 1 diabetes participating in the Diabetes Control and Complications Trial. Only participants with urinary albumin excretion rate < 40 mg/24 h were included in the analysis (n = 1365). We evaluated the relationship between the progression of retinopathy and the development of nephropathy over a mean 6.5 years of follow-up. Progression of retinopathy was defined by 3-step change in Early Treatment Diabetic Retinopathy Study score on consecutive annual evaluations. Development of nephropathy was defined as incidence of urinary albumin excretion rate ≥ 40 mg/24 h on annual evaluation. RESULTS: Over a mean 6.5 years of follow-up, the incidence of progression of retinopathy was higher in those who developed nephropathy than in those who did not (36.2 vs. 13.4%; P < 0.001). The development of nephropathy independently increased the risk for progression of retinopathy (hazard ratio 1.62, 95% CI 1.23-2.13, P = 0.001), after adjustment for age, gender, diabetes duration, treatment, HbA1c , BMI, HDL cholesterol and blood pressure. Similarly, the incidence of nephropathy was higher in participants who had progression of retinopathy than in those who did not (40.7 vs. 15.7%; P < 0.001). Furthermore, progression of retinopathy independently increased the risk for development of nephropathy (hazard ratio 1.72, 95% CI 1.30-2.27, P < 0.001). CONCLUSIONS: Progression of retinopathy and development of nephropathy each increase the risk for incidence of the other, independent of established risk factors for microvascular complications, supporting the notion of a shared aetiologic basis.

Why do men have worse COVID-19-related outcomes? A systematic review and meta-analysis with sex adjusted for age.

We aimed to study the mechanism behind worse coronavirus disease-19 (COVID-19) outcomes in men and whether the differences between sexes regarding mortality as well as disease severity are influenced by sex hormones. To do so, we used age as a covariate in the meta-regression and subgroup analyses. This was a systematic search and meta-analysis of observational cohorts reporting COVID-19 outcomes. The PubMed (Medline) and Cochrane Library databases were searched. The primary outcome was COVID-19-associated mortality and the secondary outcome was COVID-19 severity. The study was registered at PROSPERO: 42020182924. For mortality, men had a relative risk of 1.36 (95%CI: 1.17 to 1.59; I2 63%, P for heterogeneity <0.01) compared to women. Age was not a significant covariate in meta-analysis heterogeneity (P=0.393) or subgroup analysis. For disease severity, being male was associated with a relative risk of 1.29 (95%CI: 1.19 to 1.40; I2 48%, P for heterogeneity <0.01) compared to the relative risk of women. Again, age did not influence the outcomes of the meta-regression (P=0.914) or subgroup analysis. Men had a higher risk of COVID-19 mortality and severity regardless of age, decreasing the odds of hormonal influences in the described outcomes.

Stakeholder engagement in eight comparative effectiveness trials in African Americans and Latinos with asthma.

BACKGROUND: The effects of stakeholder engagement, particularly in comparative effectiveness trials, have not been widely reported. In 2014, eight comparative effectiveness studies targeting African Americans and Hispanics/Latinos with uncontrolled asthma were funded by the Patient-Centered Outcomes Research Institute (PCORI) as part of its Addressing Disparities Program. Awardees were required to meaningfully involve patients and other stakeholders. Using specific examples, we describe how these stakeholders substantially changed the research protocols and in other ways participated meaningfully as full partners in the development and conduct of the eight studies. METHODS: Using the method content analysis of cases, we identified themes regarding the types of stakeholders, methods of engagement, input from the stakeholders, changes made to the research protocols and processes, and perceived benefits and challenges of the engagement process. We used summaries from meetings of the eight teams, results from an engagement survey, and the final research reports as our data source to obtain detailed information. The descriptive data were assessed by multiple reviewers using inductive and deductive qualitative methods and discussed in the context of engagement literature. RESULTS: Stakeholders participated in the planning, conduct, and dissemination phases of all eight asthma studies. All the studies included clinicians and community representatives as stakeholders. Other stakeholders included patients with asthma, their caregivers, advocacy organizations, and health-system representatives. Engagement was primarily by participation in advisory boards, although six of the eight studies (75%) also utilized focus groups and one-on-one interviews. Difficulty finding a time and location to meet was the most reported challenge to engagement, noted by four of the eight teams (50%). Other reported challenges and barriers to engagement included recruitment of stakeholders, varying levels of enthusiasm among stakeholders, controlling power dynamics, and ensuring that stakeholder involvement was reflected and had true influence on the project. CONCLUSION: Engagement-driven modifications led to specific changes in study design and conduct that were felt to have increased enrollment and the general level of trust and support of the targeted communities. The level of interaction described, between investigators and stakeholders in each study and between investigator-stakeholder groups, is-we believe-unprecedented and may provide useful guidance for other studies seeking to improve the effectiveness of community-driven research.

The goal of comparative clinical effectiveness research is to compare healthcare options and learn which work best for patients depending on their preferences and circumstances. Research efforts can be more effective when researchers engage stakeholders, such as patients, healthcare providers, and other members of the community­especially those communities or groups targeted by the planned research. Stakeholders can give their input throughout the research process to make sure the study will address questions and concerns that are most important and useful for participants. In 2014, the PCORI funded eight research studies that evaluated various ways to help African Americans and Hispanics/Latinos with poorly controlled asthma. These groups are underrepresented in asthma research but have higher rates of and more severe asthma for reasons that are poorly understood. The goal of this report is to show how stakeholders­including patients with asthma from these underrepresented groups, healthcare providers who care for patients with asthma, key representatives from the communities and others­participated as full partners in the eight studies and helped to improve the overall quality of the research and the relationship between the researchers and the community.

Development of an Asthma Home-Visit Training Program for Community Health Workers and Their Supervisors in Washington State.

The community health worker (CHW) asthma home-visiting model developed by Public Health-Seattle & King County (PHSKC) is an evidence-based approach proven to improve health outcomes and quality of life. In addition, it has been shown to be an effective and culturally appropriate approach to helping people with asthma understand the environmental and behavioral causes of uncontrolled asthma, while acquiring the skills they need to control their asthma. This paper describes the development and implementation of training curricula for CHWs and supervisors in the asthma home visiting program. To facilitate dissemination, this program took advantage of the current healthcare landscape in Washington State resulting from Centers for Medicare & Medicaid Services (CMS) approval of the 1115 Medicaid Waiver project. Key aspects of the training program development included: (1) Engagement: forming a Community Advisory Board with multiple stakeholders to help prioritize training content; (2) Curriculum Development: building the training on evidence-based home-visit protocols previously developed at PHSKC; (3) Implementation of the training program; (4) Evaluation of the training; and (5) Adaptation of the training based on lessons learned. We describe key factors in the training program's improvement including the use of a community-based participatory approach to engage stakeholders at multiple phases of the project and ensure regional adaption; combining in-person and online modules for delivery; and holding learning collaboratives for post-training and technical support. We also outline our training program evaluation plan and the planned evaluation of the home visit program which the trainees will deliver, both of which follow the RE-AIM framework. However, because the COVID-19 pandemic has curtailed training activities and prohibited the trainees from implementation of these CHW home visit practices, our evaluation is currently incomplete. Therefore, this case study provides insight into the adaptation of the training program, but not the delivery of the home visit program, the outcomes of which remain to be seen.