Dissecting direct and indirect genetic effects on chronic obstructive pulmonary disease (COPD) susceptibility

Cigarette smoking is the major environmental risk factor for chronic obstructive pulmonary disease (COPD). Genome-wide association studies have provided compelling associations for three loci with COPD. In this study, we aimed to estimate direct, i.e., independent from smoking, and indirect effects of those loci on COPD development using mediation analysis. We included a total of 3,424 COPD cases and 1,872 unaffected controls with data on two smoking-related phenotypes: lifetime average smoking intensity and cumulative exposure to tobacco smoke (pack years). Our analysis revealed that effects of two linked variants (rs1051730 and rs8034191) in the AGPHD1/CHRNA3 cluster on COPD development are significantly, yet not entirely, mediated by the smoking-related phenotypes. Approximately 30 % of the total effect of variants in the AGPHD1/CHRNA3 cluster on COPD development was mediated by pack years. Simultaneous analysis of modestly (r(2) = 0.21) linked markers in CHRNA3 and IREB2 revealed that an even larger (~42 %) proportion of the total effect of the CHRNA3 locus on COPD was mediated by pack years after adjustment for an IREB2 single nucleotide polymorphism. This study confirms the existence of direct effects of the AGPHD1/CHRNA3, IREB2, FAM13A and HHIP loci on COPD development. While the association of the AGPHD1/CHRNA3 locus with COPD is significantly mediated by smoking-related phenotypes, IREB2 appears to affect COPD independently of smoking

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

The epidemiology of type I diabetes in children 0-14 years of age in Philadelphia

The goal of diabetes prevention has fostered many studies to identify the risk factors of Insulin Dependent Diabetes Mellitus (IDDM) throughout the world. Because of the paucity of diabetes registries, the risk of developing IDDM is unknown in more than 94% of the world\u27s population. There were no data on the incidence of diabetes in Philadelphia. The purpose of this study was to determine the epidemiology of IDDM in children in Philadelphia via a retrospective population-based registry. All hospitals in Philadelphia that admit children were identified and permission to review records was obtained. All charts meeting the following criteria were reviewed: (1) newly diagnosed IDDM, (2) ages 0-14 yrs., (3) residing in Philadelphia at the time of diagnosis, and (4) diagnosed from 1/1/85 to 12/31/89. Standard IDDM registry data were abstracted from the charts: name, address, birthdate, sex, race, date when insulin treatment started. Ascertainment of the completeness of the hospital registry was validated by a secondary source, review of diabetes camp records from 1985-1990. The relationship between variables was analyzed using the chi square statistic. Differences in incidence levels were determined to be significant if the 95% confidence intervals of the rates did not overlap. A total of 210 cases were identified and the combined hospital/camp registry was determined to be 92% complete. The overall age adjusted incidence rate in Philadelphia was 13/100,000 per year. The incidence in 1986 was significantly less than the average for the other four years. The highest incidence was in females, Hispanics and children 10-14 years old. The risk of developing IDDM in children younger than age 5 was 2.6 times greater in Whites than Blacks. Neither socioeconomic status nor seasonality was found to be significantly related to IDDM in Philadelphia. The determination of the distribution of IDDM allows for interpopulation comparisons which facilitate the identification of risk factors. The ultimate goal of this type of research is to identify and define the environmental determinants of IDDM. Identifying and altering diabetogenic environmental factors may be effective in reducing the incidence, or even preventing, this serious disease which afflicts 12,000 children per year

The epidemiology of type I diabetes in children 0-14 years of age in Philadelphia

The goal of diabetes prevention has fostered many studies to identify the risk factors of Insulin Dependent Diabetes Mellitus (IDDM) throughout the world. Because of the paucity of diabetes registries, the risk of developing IDDM is unknown in more than 94% of the world\u27s population. There were no data on the incidence of diabetes in Philadelphia. The purpose of this study was to determine the epidemiology of IDDM in children in Philadelphia via a retrospective population-based registry. All hospitals in Philadelphia that admit children were identified and permission to review records was obtained. All charts meeting the following criteria were reviewed: (1) newly diagnosed IDDM, (2) ages 0-14 yrs., (3) residing in Philadelphia at the time of diagnosis, and (4) diagnosed from 1/1/85 to 12/31/89. Standard IDDM registry data were abstracted from the charts: name, address, birthdate, sex, race, date when insulin treatment started. Ascertainment of the completeness of the hospital registry was validated by a secondary source, review of diabetes camp records from 1985-1990. The relationship between variables was analyzed using the chi square statistic. Differences in incidence levels were determined to be significant if the 95% confidence intervals of the rates did not overlap. A total of 210 cases were identified and the combined hospital/camp registry was determined to be 92% complete. The overall age adjusted incidence rate in Philadelphia was 13/100,000 per year. The incidence in 1986 was significantly less than the average for the other four years. The highest incidence was in females, Hispanics and children 10-14 years old. The risk of developing IDDM in children younger than age 5 was 2.6 times greater in Whites than Blacks. Neither socioeconomic status nor seasonality was found to be significantly related to IDDM in Philadelphia. The determination of the distribution of IDDM allows for interpopulation comparisons which facilitate the identification of risk factors. The ultimate goal of this type of research is to identify and define the environmental determinants of IDDM. Identifying and altering diabetogenic environmental factors may be effective in reducing the incidence, or even preventing, this serious disease which afflicts 12,000 children per year

University–Community Partnerships Using a Participatory Action Research Model to Evaluate the Impact of Dance for Health

Little is known about fostering sustainable, collaborative community-academic partnerships that effectively improve physical activity and health in residents of under resourced communities using Participatory Action Research (PAR) driven models. The purpose of this PAR study was to evaluate the impact of an urban, intergenerational, and physical activity dance program by identifying community preferred measurable outcomes that promote program participation and sustainability. A descriptive, qualitative design was employed using semi-structured interview guides to facilitate discussions for two adult focus groups and one youth focus group. Exactly 19 community-residing adults and six youth who lived in urban neighborhoods in West Philadelphia participated in the discussions. The audiotapes were transcribed and analyzed using directed content analysis. Five outcome themes emerged and included: (1). Enhancing the psychological and emotional well-being of the individual, (2). Enhancement of social well-being and management of interpersonal relationships and responsibilities (3). Enhancing and promoting physiologic well-being (4). Changes in health promoting behaviors and skill acquisition, and (5). Concerns about accessibility of dance for health and other physical activity programs in the community. Focused attention to measuring community preferred outcomes can promote sustainability of Dance for Health and possibly other urban-based physical activity dance programs

ZnT8 autoantibody prevalence is low in youth with type 2 diabetes and associated with higher insulin sensitivity, lower insulin secretion, and lower disposition index

Aim: ZnT8 autoantibody positivity (ZnT8+) is associated with risk for type 1 diabetes and with metabolic complications in adults. Our aim was to assess prevalence of ZnT8 + in the Treatment of T2D in Adolescents and Youth (TODAY) cohort and describe associated phenotypic outcomes. Methods: TODAY participants were 13.98 ± 2.03 years with a confirmed diagnosis of T2D, BMI percentile of 97.69 ± 3.32 (64% female), and GAD- and IA2- at baseline. ZnT8 autoantibodies were measured at baseline and end of study. Results: 3 of 687 participants (0.29%) were ZnT8 + and there was one conversion (0.15%) from ZnT8- to ZnT8 + during the study. ZnT8A + individuals had higher HbA1c, HDL and LDL cholesterol, and IL-1β concentrations, and lower BMI, IL-6, and triglyceride concentrations compared to the TODAY cohort and ZnT8A- individuals. They also had higher insulin sensitivity with lower insulin secretion and disposition index, metabolically resembling T1D. All ZnT8 + participants experienced loss of glycemic control on randomized treatment, but exhibited lower rates of diabetic complications than other groups. Conclusion: Given the low rate of complications in ZnT8 + individuals, ZnT8 likely does not impact the clinical course of the disease in this population

Fostering Health Equity: Clinical and Research Training Strategies from Nursing Education

Racism, ethnocentrism, segregation, stereotyping, and classism are tightly linked to health equity and social determinants of health. They lead to lack of power, money, resources, and education which may result in poor health care access and outcomes. Health profession faculties must address the complex relationships that exist between individual, interpersonal, institutional, social and political factors that influence health outcomes in both clinical and research training. Thus, the purposes of this paper are to provide examples of training strategies from nursing education that foster cultural sensitivity. First, assumptions about health equity, culture, ethnicity and race are explored. Second, clinical training within an undergraduate and graduate context are explored, including an undergraduate cancer case study and in a graduate pediatric nursing program are described to demonstrate how cultural models can be used to integrate the biomedical and psychosocial content in a course. Third, research training for summer scholars and doctoral and post doctoral fellows (short and long term) is described to demonstrate how to increase the number and quality of scholars prepared to conduct research with vulnerable populations. Research training strategies include a summer research institute, policy fellowship, and a scholars “pipeline” program. A unique perspective is presented through collaboration between a nursing school and a center for health disparities research

A community-engaged approach to the design of a population-based prospective cohort study to promote bladder health.

INTRODUCTION: Community engagement is increasingly recognized as a critical component of research, but few studies provide details on how to successfully incorporate community perspectives in urological research. This manuscript describes the community engagement strategy used by the Prevention of Lower Urinary Tract Symptoms Research Consortium (PLUS) to design RISE FOR HEALTH (RISE), a multicenter, population-based, prospective cohort study to promote bladder health. METHODS AND RESULTS: The PLUS Community Engagement Subcommittee, guided by a set of antiracist community engagement principles and practices, organized, implemented, and communicated findings for all RISE community engagement activities. Community engagement was conducted through a diverse network of community partners at PLUS clinical research centers called Rapid Assessment Partners (RAPs). Via online surveys (4), virtual discussion groups (14), and one-on-one interviews (12), RAPs provided input on RISE processes and materials, including in-person visit procedures, specimen collection instructions, survey data collection instruments, recruitment materials, the study website, and the study name. This process resulted in significant changes to these aspects of the study design with reciprocal benefits for the community partners. DISCUSSION: Meaningful community engagement improved the design and implementation of RISE. PLUS will continue to engage community partners to interpret the RISE study results, disseminate RISE findings, and inform other PLUS studies toward the development of interventions to promote bladder health. Future urological studies would also benefit from community participation in determining priority research questions to address