Chronic Disease Research Research Articles

Meta-Analysis and Multivariate GWAS Analyses in 80,950 Individuals of African Ancestry Identify Novel Variants Associated with Blood Pressure Traits.

High blood pressure (HBP) has been implicated as a major risk factor for cardiovascular diseases in several populations, including individuals of African ancestry. Despite the elevated burden of HBP-induced cardiovascular diseases in Africa and other populations of African descent, limited genetic studies have been carried out to explore the genetic mechanism driving this phenomenon. We performed genome-wide association univariate and multivariate analyses of both systolic (SBP) and diastolic blood pressure (DBP) traits in 80,950 individuals of African ancestry. We used summary statistics data from six independent cohorts, including the African Partnership for Chronic Disease Research (APCDR), the UK Biobank, and the Million Veteran Program (MVP). FUMA was used to annotate, prioritize, visualize, and interpret our findings to gain a better understanding of the molecular mechanism(s) underlying the genetics of BP traits. Finally, we undertook a Bayesian fine-mapping analysis to identify potential causal variants. Our meta-analysis identified 10 independent variants associated with SBP and 9 with DBP traits. Whilst our multivariate GWAS method identified 21 independent signals, 18 of these SNPs have been previously identified. SBP was linked to gene sets involved in biological processes such as synapse assembly and cell-cell adhesion via plasma membrane adhesion. Of the 19 independent SNPs identified in the BP meta-analysis, only 11 variants had posterior probability (PP) of > 50%, including one novel variant: rs562545 (MOBP, PP = 77%). To facilitate further research and fine-mapping of high-risk loci/variants in highly susceptible groups for cardiovascular disease and other related traits, large-scale genomic datasets are needed. Our findings highlight the importance of including ancestrally diverse populations in large GWASs and the need for diversity in genetic research.

Long COVID and mental health correlates: a new chronic condition fits existing patterns

ABSTRACT Background Emerging Long COVID research indicates the condition has major population health consequence. Other chronic conditions have previously been associated with functional and mental health challenges – including depression, anxiety, post-traumatic stress disorder (PTSD), suicide ideation, substance use and lower life satisfaction. Methods This study explores correlations between self-reported Long COVID, functional and mental health challenges among a random community-based sample of people (n = 655) aged 20–50 years who contracted COVID-19 prior to vaccination in a Texas county. A random sample of eligible participants was mailed a link to participate in a semi-structured questionnaire. Participant responses, including open-ended responses regarding their experience following COVID-19, were paired with health system data. Results Long COVID was associated with increased presence of depression (13% increase), anxiety (28% increase), suicide ideation (10% increase), PTSD (20% increase), and decreased life satisfaction and daily functioning. Structural equation modeling, controlling for sociodemographic variables and imposing a theoretical framework from existing chronic disease research, demonstrated correlations between Long COVID and higher PTSD, suicide ideation and lower life satisfaction were mediated by higher daily functional challenges and common mental disorders. Conclusions Basic and applied, interdisciplinary research is urgently needed to characterize the population-based response to the new challenge of Long COVID.

Reserve and resilience in CKD: concept introduction and baseline results from the Physical REsilience Prediction in Advanced REnal Disease (PREPARED) study

BackgroundThe purpose of this manuscript is to introduce reserve and resilience as novel concepts in chronic kidney disease (CKD) research and present baseline data from a unique prospective cohort study designed to characterize recovery from functional decline after a health event.MethodsThe Physical REsilience Prediction in Advanced REnal Disease (PREPARED) study recruited a national, prospective cohort of Veterans ≥70 years old with an estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73 m2, prior nephrology care, and at high risk for hospitalization. Electronic health record data were paired with telephone surveys. Self-reported measures of reserve included physical, psychological, and cognitive capacity and environmental resources. We calculated counts (frequencies) and medians (25th, 75th percentiles) for baseline measures of reserve. The study’s longitudinal follow-up of physical function every 8 weeks or following an acute care encounter, which will be used to define resilience, is ongoing.ResultsParticipants had a median (25th, 75th percentile) age of 76.3 (72.8, 81.4) years and eGFR of 23.4 (18.2, 28.8) ml/min/1.73 m2; 23.3% were Black, and 97.4% were male, 91.6% had hypertension, 67.4% had diabetes mellitus, 46.0% had coronary heart disease, and 39.8% had heart failure. Baseline measures of physical, psychological, and cognitive domains showed low reserve on average, but with wide ranges.ConclusionsDespite similar levels of kidney function, older adults participating in PREPARED had a wide range of measures of reserve in other health domains. Non-renal measures of reserve may be important indicators of capacity of CKD patients to recover after acute care encounters.

Age acquired skewed X chromosome inactivation is associated with adverse health outcomes in humans.

Ageing is a heterogenous process characterised by cellular and molecular hallmarks, including changes to haematopoietic stem cells and is a primary risk factor for chronic diseases. X chromosome inactivation (XCI) randomly transcriptionally silences either the maternal or paternal X in each cell of 46, XX females to balance the gene expression with 46, XY males. Age acquired XCI-skew describes the preferential selection of cells across a tissue resulting in an imbalance of XCI, which is particularly prevalent in blood tissues of ageing females, and yet its clinical consequences are unknown. We assayed XCI in 1575 females from the TwinsUK population cohort using DNA extracted from whole blood. We employed prospective, cross-sectional, and intra-twin study designs to characterise the relationship of XCI-skew with molecular and cellular measures of ageing, cardiovascular disease risk, and cancer diagnosis. We demonstrate that XCI-skew is independent of traditional markers of biological ageing and is associated with a haematopoietic bias towards the myeloid lineage. Using an atherosclerotic cardiovascular disease risk score, which captures traditional risk factors, XCI-skew is associated with an increased cardiovascular disease risk both cross-sectionally and within XCI-skew discordant twin pairs. In a prospective 10 year follow-up study, XCI-skew is predictive of future cancer incidence. Our study demonstrates that age acquired XCI-skew captures changes to the haematopoietic stem cell population and has clinical potential as a unique biomarker of chronic disease risk. KSS acknowledges funding from the Medical Research Council [MR/M004422/1 and MR/R023131/1]. JTB acknowledges funding from the ESRC [ES/N000404/1]. MM acknowledges funding from the National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London. TwinsUK is funded by the Wellcome Trust, Medical Research Council, European Union, Chronic Disease Research Foundation (CDRF), Zoe Global Ltd and the National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London.

Selected Bibliography of Recent Research in Chronic Obstructive Pulmonary Disease.

Selected Bibliography of Recent Research in Chronic Obstructive Pulmonary Disease.

Interstitial fibrosis and tubular atrophy measurement via hierarchical extractions of kidney and atrophy regions with deep learning method

Background and objective:Interstitial fibrosis and tubular atrophy (IFTA) are the most critical characteristics of chronic kidney disease, and it is superior to glomerular pathology in predicting the decrease of glomerular filtration rate (eGFR) for chronic kidney disease (CKD). However, measurement of IFTA usually depends on manual operation, which is laborious and may lead to significant differences among pathologists. Therefore, the long-term focus of chronic kidney disease research has been on the glomerulus with relatively prominent morphological characteristics. There are few types of research on IFTA. Methods:We proposed an IFTA measurement method based on hierarchically extracting renal tissue, interstitial fibrosis and tubular atrophy regions. Our proposed method first extracts the whole renal tissue region (cortex and medulla) on WSIs by employing the Kidney Tissue Module and then recognizes the interstitial fibrosis and tubular atrophy regions via Interstitial fibrosis and Tubular atrophy Module. Finally, the proportion of the IFTA area to the entire renal tissue area is calculated to obtain the end-to-end output IFTA ratio. Results:Experimental results confirmed that the proposed method outperforms recently proposed approaches by comparing accuracy in segmenting IFTA area and thus achieved state-of-the-art performance. ITNet also achieved a faster-processing speed in calculating the proportion of IFTA than pathologists. Furthermore, the results showed that our proposed hierarchical extraction method could make full use of feature information, effectively combine the advantages of different scales, and segment IFTA with high accuracy and reasonable acceptability. Conclusion:Quantitative analysis of IFTA by the proposed method can reduce pathologists’ measurement time to diagnose and decrease the assessment difference between different pathologists. Therefore, the proposed method can assist pathologists in improving the efficiency of diagnosis and supplying consistent measurement accuracy.

Machine learning integration of multimodal data identifies key features of blood pressure regulation.

SummaryBackgroundAssociation studies have identified several biomarkers for blood pressure and hypertension, but a thorough understanding of their mutual dependencies is lacking. By integrating two different high-throughput datasets, biochemical and dietary data, we aim to understand the multifactorial contributors of blood pressure (BP).MethodsWe included 4,863 participants from TwinsUK with concurrent BP, metabolomics, genomics, biochemical measures, and dietary data. We used 5-fold cross-validation with the machine learning XGBoost algorithm to identify features of importance in context of one another in TwinsUK (80% training, 20% test). The features tested in TwinsUK were then probed using the same algorithm in an independent dataset of 2,807 individuals from the Qatari Biobank (QBB).FindingsOur model explained 39·2% [4·5%, MAE:11·32 mmHg (95%CI, +/- 0·65)] of the variance in systolic BP (SBP) in TwinsUK. Of the top 50 features, the most influential non-demographic variables were dihomo-linolenate, cis-4-decenoyl carnitine, lactate, chloride, urate, and creatinine along with dietary intakes of total, trans and saturated fat. We also highlight the incremental value of each included dimension. Furthermore, we replicated our model in the QBB [SBP variance explained = 45·2% (13·39%)] cohort and 30 of the top 50 features overlapped between cohorts.InterpretationWe show that an integrated analysis of omics, biochemical and dietary data improves our understanding of their in-between relationships and expands the range of potential biomarkers for blood pressure. Our results point to potentially key biological pathways to be prioritised for mechanistic studies.FundingChronic Disease Research Foundation, Medical Research Council, Wellcome Trust, Qatar Foundation.

Long COVID: which symptoms can be attributed to SARS-CoV-2 infection?

Long COVID: which symptoms can be attributed to SARS-CoV-2 infection?

Policy by Pilot? Learning From Demonstration Projects for Integrated Care Comment on "Integration or Fragmentation of Health Care? Examining Policies and Politics in a Belgian Case Study".

Analysis of policy implementation for chronic disease in Belgium highlights the difficulties of launching experiments for integrated care in a health system with fragmented governance. It also entreats us to consider the inherent challenges of piloting integrated care for chronic disease. Sociomedical characteristics of chronic disease -political, social, and economic aspects of improving outcomes - pose distinct problems for pilot projects, particularly because addressing health inequity requires collaboration across health and social sectors and a long-term, life-course perspective on health. Drawing on recent US experience with demonstration projects for health service delivery reform and on chronic disease research, I discuss constraints of and lessons from pilot projects. The policy learning from pilots lies beyond their technical evaluative yield. Pilot projects can evince political and social challenges to achieving integrated chronic disease care, and can illuminate overlooked perspectives, such as those of community-based organizations (CBOs), thereby potentially extending the terms of policy debate.

Multimorbidity and depression among older adults in India: Mediating role of functional and behavioural health.

Researchers have long been concerned about the association between depression and the prevalence of multiple chronic diseases or multimorbidity in older persons. However, the underlying pathway or mechanism in the multimorbidity-depression relationship is still unknown. Data were extracted from a baseline survey of the Longitudinal Ageing Survey of India (LASI) conducted during 2017-18 (N = 31,464; aged ≥ 60 years). Depression was assessed using the 10-item Centre for Epidemiological Studies Depression Scale (CES-D-10). Multivariable logistic regression was used to examine the association. The Karlson-Holm-Breen (KHB) method was adopted for mediation analysis. The prevalence of depression among older adults was nearly 29% (men: 26% and women 31%). Unadjusted and adjusted estimates in binary logistic regression models suggested an association between multimorbidity and depression (UOR = 1.28; 95% CIs 1.27-1.44 and AOR = 1.12; 95% CIs 1.12-1.45). The association was particularly slightly strong in the older men. In addition, the association was mediated by functional health such as Self Rated Health (SRH) (proportion mediated: 40%), poor sleep (35.15%), IADL disability (22.65%), ADL disability (21.49%), pain (7.92%) and by behavioral health such as physical inactivity (2.28%). However, the mediating proportion was higher among older women as compared to older men. Physical inactivity was not found to be significant mediator for older women. The findings of this population-based study revealed that older people with multimorbidity are more likely to suffer depressive symptoms in older ages, suggesting the need for more chronic disease management and research. Multimorbidity and depression may be mediated by certain functional health factors, especially in older women. Further longitudinal research is needed to better understand the underlying mechanisms of this association so that future preventive initiatives may be properly guided.

Spatial lifecourse epidemiology in chronic non-communicable disease research

In recent years, the research focus on determinants of chronic non-communicable diseases has shifted from non-spatial factors (e.g., lifestyle behaviors) to spatial factors (e.g., natural and built environments). As the intersection of lifecourse epidemiology and spatial epidemiology, spatial lifecourse epidemiology is a research area in the field of health geography. It combines advanced spatial technologies, including geographic information systems, surveying, remote sensing, location-based services and artificial intelligence, to accurately retrace, measure, and simulate individuals' exposures across the life course (i.e., exposome); and adopts lifecourse models, including the accumulation of risk model and critical/sensitive period models, to investigate the impact of individuals' exposures in the past on their health status at different stages of life. This paper introduces the theories, main analysis approaches and focus of spatial lifecourse epidemiology in the research of chronic non-communicable diseases for the purpose of better understanding and applications of spatial lifecourse epidemiology in the research of determinants of chronic non-communicable diseases, providing important reference for future research, facilitating the development of health geography to eventually achieve precise health management over the lifecourse.

COVID-19 vaccine waning and effectiveness and side-effects of boosters: a prospective community study from the ZOE COVID Study

BackgroundWith the surge of new SARS-CoV-2 variants, countries have begun offering COVID-19 vaccine booster doses to high-risk groups and, more recently, to the adult population in general. However, uncertainty remains over how long primary vaccination series remain effective, the ideal timing for booster doses, and the safety of heterologous booster regimens. We aimed to investigate COVID-19 primary vaccine series effectiveness and its waning, and the safety and effectiveness of booster doses, in a UK community setting.MethodsWe used SARS-CoV-2 positivity rates in individuals from a longitudinal, prospective, community-based study (ZOE COVID Study), in which data were self-reported through an app, to assess the effectiveness of three COVID-19 vaccines (ChAdOx1 nCov19 [Oxford-AstraZeneca], BNT162b2 [Pfizer-BioNtech], and mRNA1273 [Moderna]) against infection in the 8 months after completion of primary vaccination series. In individuals receiving boosters, we investigated vaccine effectiveness and reactogenicity, by assessing 16 self-reported systemic and localised side-effects. We used multivariate Poisson regression models adjusting for confounders to estimate vaccine effectiveness.FindingsWe included 620 793 participants who received two vaccine doses (204 731 [33·0%] received BNT162b2, 405 239 [65·3%] received ChAdOx1 nCoV-19, and 10 823 [1·7%] received mRNA-1273) and subsequently had a SARS-CoV-2 test result between May 23 (chosen to exclude the period of alpha [B.1.1.7] variant dominance) and Nov 23, 2021. 62 172 (10·0%) vaccinated individuals tested positive for SARS-CoV-2 and were compared with 40 345 unvaccinated controls (6726 [16·7%] of whom tested positive). Vaccine effectiveness waned after the second dose: at 5 months, BNT162b2 effectiveness was 82·1% (95% CI 81·3–82·9), ChAdOx1 nCoV-19 effectiveness was 75·7% (74·9–76·4), and mRNA-1273 effectiveness was 84·3% (81·2–86·9). Vaccine effectiveness decreased more among individuals aged 55 years or older and among those with comorbidities. 135 932 individuals aged 55 years or older received a booster (2123 [1·6%] of whom tested positive). Vaccine effectiveness for booster doses in 0–3 months after BNT162b2 primary vaccination was higher than 92·5%, and effectiveness for heterologous boosters after ChAdOx1 nCoV-19 was at least 88·8%. For the booster reactogenicity analysis, in 317 011 participants, the most common systemic symptom was fatigue (in 31 881 [10·1%] participants) and the most common local symptom was tenderness (in 187 767 [59·2%]). Systemic side-effects were more common for heterologous schedules (32 632 [17·9%] of 182 374) than for homologous schedules (17 707 [13·2%] of 134 637; odds ratio 1·5, 95% CI 1·5–1·6, p<0·0001).InterpretationAfter 5 months, vaccine effectiveness remained high among individuals younger than 55 years. Booster doses restore vaccine effectiveness. Adverse reactions after booster doses were similar to those after the second dose. Homologous booster schedules had fewer reported systemic side-effects than heterologous boosters.FundingWellcome Trust, ZOE, National Institute for Health Research, Chronic Disease Research Foundation, National Institutes of Health, Medical Research Council

127 Reciprocal Innovation Workshops: Identify Shared Health Challenges for Mutual Benefit in Global Health

OBJECTIVES/GOALS: Our concept of reciprocal innovation (RI) supports global health (GH) research partnerships that address shared health challenges for mutual benefit in both high and low- and middle-income (LMIC) settings. To advance this GH approach, the Indiana CTSI launched a RI program building on longstanding global health partnerships in East Africa METHODS/STUDY POPULATION: A core component of the program is annual RI workshops to promote reciprocal approaches in GH, identify priority areas for reciprocal research, and link investigators and stakeholders across settings. The first meeting in 2019 was in-person and focused on identifying health priority areas from the perspective of Indiana stakeholders. The second meeting was held virtually and focused on priority areas in East Africa. The third meeting focused on shared priority areas and discussing potential RI research projects. Agenda sessions include (1) presenting successful examples of funded RI projects; (2) breakout groups to share proposal ideas in preparation for the RI grants program; (3) building partnerships with colleagues in similar fields RESULTS/ANTICIPATED RESULTS: As of 2021, three RI workshops have been held with an average of 60 attendees at each workshop. Participants identified several overlapping priority areas for research and RI in Indiana and East Africa, including research in chronic disease, substance abuse, infant and maternal health, and access to healthcare. A Global Health Innovation Exchange of RI projects was created to support connections between locally- and globally-focused investigators. The repository is used to share updates on project progress, outcomes, and published materials. Workshops have also been used to explore a reciprocal innovation virtual platform to facilitate and foster more regular collaborations between globally and locally-focused investigators and pursue research projects on shared health challenges for mutual benefit DISCUSSION/SIGNIFICANCE: The collaboration at the stakeholder meetings set the foundation for continued partnership building, strong proposals for RI grants, and dissemination and translation of successful RI projects. To leverage momentum from the meetings, we are building a virtual RI platform to connect PIs across multiple CTSAs and increase the footprint of RI efforts

Symptom prevalence, duration, and risk of hospital admission in individuals infected with SARS-CoV-2 during periods of omicron and delta variant dominance: a prospective observational study from the ZOE COVID Study

SummaryBackgroundThe SARS-CoV-2 variant of concern, omicron, appears to be less severe than delta. We aim to quantify the differences in symptom prevalence, risk of hospital admission, and symptom duration among the vaccinated population.MethodsIn this prospective longitudinal observational study, we collected data from participants who were self-reporting test results and symptoms in the ZOE COVID app (previously known as the COVID Symptoms Study App). Eligible participants were aged 16–99 years, based in the UK, with a body-mass index between 15 and 55 kg/m2, had received at least two doses of any SARS-CoV-2 vaccine, were symptomatic, and logged a positive symptomatic PCR or lateral flow result for SARS-CoV-2 during the study period. The primary outcome was the likelihood of developing a given symptom (of the 32 monitored in the app) or hospital admission within 7 days before or after the positive test in participants infected during omicron prevalence compared with those infected during delta prevalence.FindingsBetween June 1, 2021, and Jan 17, 2022, we identified 63 002 participants who tested positive for SARS-CoV-2 and reported symptoms in the ZOE app. These patients were matched 1:1 for age, sex, and vaccination dose, across two periods (June 1 to Nov 27, 2021, delta prevalent at >70%; n=4990, and Dec 20, 2021, to Jan 17, 2022, omicron prevalent at >70%; n=4990). Loss of smell was less common in participants infected during omicron prevalence than during delta prevalence (16·7% vs 52·7%, odds ratio [OR] 0·17; 95% CI 0·16–0·19, p<0·001). Sore throat was more common during omicron prevalence than during delta prevalence (70·5% vs 60·8%, 1·55; 1·43–1·69, p<0·001). There was a lower rate of hospital admission during omicron prevalence than during delta prevalence (1·9% vs 2·6%, OR 0·75; 95% CI 0·57–0·98, p=0·03).InterpretationThe prevalence of symptoms that characterise an omicron infection differs from those of the delta SARS-CoV-2 variant, apparently with less involvement of the lower respiratory tract and reduced probability of hospital admission. Our data indicate a shorter period of illness and potentially of infectiousness which should impact work–health policies and public health advice.FundingWellcome Trust, ZOE, National Institute for Health Research, Chronic Disease Research Foundation, National Institutes of Health, and Medical Research Council

IDF21-0422 Two Anniversaries, Two Pandemics, Two Histories

Background: As we remember the therapeutic development of insulin one hundred years ago, in Tulsa, Oklahoma we remember a race massacre in the same year. Are these connected? How? Elbert Huang, University of Chicago’s Center for Chronic Disease Research and Policy, writes that diabetes has been called a “slow moving pandemic.” As U.S. outbreaks surge, a study finds 40% of people who have died with COVID-19 had diabetes (Terhune et al, 7/24/2020 Reuters). The Center for Disease Control (2020) shows the prevalence of diabetes is highest among American Indians/Alaska Natives (14.7%) Hispanics (12.5%), non-Hispanic Blacks (11.7%), and non-Hispanic whites (7.5%). American Indians, Latinos and Blacks are suffering from COVID-19 in the same disproportionate numbers. COVID-19 can grow vigorously in a high blood sugar environment and may cause new cases of diabetes. A woman with diabetes loses a longtime relationship when her friend refuses to wear a mask around her. There are complex interactions between previously adaptive survival mechanisms, pre-Columbian culture and diet. Conquest by Europeans resulted in genocide, great poverty and oppression of indigenous peoples across the Americas. It brought slavery to the Americas when large numbers were needed to grow tobacco and sugar cane from new demands. During high or chronic levels of stress, the adaptive mechanism known as fight or flight allows people to protect themselves in emergency conditions, becomes destructive when people are not allowed to fight or flee. Cortisol, produced during these times, becomes toxic to the body and the brain, impairs immune systems, increases heart and vascular diseases, and lowers resistance to diabetes. In the extreme situation of genocide and slavery, stress becomes chronic and the levels of cortisol remain elevated. In times of famine, the ability of the individual to “store” fat in the abdomen was critical. In times of feast, the survival mechanism is no longer adaptive and can result in obesity, diabetics and death. What then are the factors that make these populations vulnerable to obesity, diabetes and Covid? Violence, poverty and racism remain for peoples whose once adaptive survival responses now contribute to disease and death. Many in the Hispanic community have the same story of conquest. The majority are poor. To the extent that they are considered to be “undocumented aliens,” their lives are precarious. “Black Lives Matter” is the response not only to poverty and racism but violence, especially the killing of innocent blacks by law enforcement. The legitimate fear of driving while black and brown is part of daily life. Native Americans have the highest numbers of violence of any group. It is statistically Caucasian male against Native male and female. Present examples are the large numbers of trafficking and murder of Native American women. These concerns are important to understand in our Native American organization with minority clients. Their concerns are about obesity, genetics, intergenerational/ongoing trauma, medication side effects, racism, community mistrust, lack of education, blame, confusion about diets, surgical intervention, family/friend support, and possibility of remission.

Lipid traits and type 2 diabetes risk in African ancestry individuals: A Mendelian Randomization study.

SummaryBackgroundDyslipidaemia is highly prevalent in individuals with type 2 diabetes mellitus (T2DM). Numerous studies have sought to disentangle the causal relationship between dyslipidaemia and T2DM liability. However, conventional observational studies are vulnerable to confounding. Mendelian Randomization (MR) studies (which address this bias) on lipids and T2DM liability have focused on European ancestry individuals, with none to date having been performed in individuals of African ancestry. We therefore sought to use MR to investigate the causal effect of various lipid traits on T2DM liability in African ancestry individuals.MethodsUsing univariable and multivariable two-sample MR, we leveraged summary-level data for lipid traits and T2DM liability from the African Partnership for Chronic Disease Research (APCDR) (N = 13,612, 36.9% men) and from African ancestry individuals in the Million Veteran Program (Ncases = 23,305 and Ncontrols = 30,140, 87.2% men), respectively. Genetic instruments were thus selected from the APCDR after which they were clumped to obtain independent instruments. We used a random-effects inverse variance weighted method in our primary analysis, complementing this with additional sensitivity analyses robust to the presence of pleiotropy.FindingsIncreased genetically proxied low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels were associated with increased T2DM liability in African ancestry individuals (odds ratio (OR) [95% confidence interval, P-value] per standard deviation (SD) increase in LDL-C = 1.052 [1.000 to 1.106, P = 0.046] and per SD increase in TC = 1.089 [1.014 to 1.170, P = 0.019]). Conversely, increased genetically proxied high-density lipoprotein cholesterol (HDL-C) was associated with reduced T2DM liability (OR per SD increase in HDL-C = 0.915 [0.843 to 0.993, P = 0.033]). The OR on T2DM per SD increase in genetically proxied triglyceride (TG) levels was 0.884 [0.773 to 1.011, P = 0.072] . With respect to lipid-lowering drug targets, we found that genetically proxied 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) inhibition was associated with increased T2DM liability (OR per SD decrease in genetically proxied LDL-C = 1.68 [1.03-2.72, P = 0.04]) but we did not find evidence of a relationship between genetically proxied proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition and T2DM liability.InterpretationConsistent with MR findings in Europeans, HDL-C exerts a protective effect on T2DM liability and HMGCR inhibition increases T2DM liability in African ancestry individuals. However, in contrast to European ancestry individuals, LDL-C may increase T2DM liability in African ancestry individuals. This raises the possibility of ethnic differences in the metabolic effects of dyslipidaemia in T2DM.FundingSee the Acknowledgements section for more information.

Prevalence and Risk Factors of COPD in Nepal: A Systematic Review and Meta-Analysis.

Chronic Obstructive Pulmonary Disease is a common, preventable, and treatable disease. Here, we conducted a systematic review of Chronic Obstructive Pulmonary Disease and its risk factors in Nepal for the last two decades. We systematically searched databases to find all relevant Chronic Obstructive Pulmonary Disease research papers from 2000 to 2020. Two reviewers screened the literature using Covidence based on the study protocol. Data extraction was done using Microsoft Excel from selected studies. Final data analysis was done using CMA v.3. Our review protocol is available in PROSPERO (CRD42020215486) on 20 November 2020. The database search revealed 1416 studies of which 13 were included in quantitative analysis. The prevalence of Chronic Obstructive Pulmonary Disease in the adult population was 22·7% (CI, 12·5-37·7) of whom 54·9% were female (CI, 51·9-57·9). Nearly three-fourth of the participants (73·1%) of Chronic Obstructive Pulmonary Disease patients had informal education (CI, 58·6-84·0). The commonest primary occupation was agriculture and farming in 39·4% (CI, 31·3-48·2), followed by homemaker (36·8%). It was observed that 28·5% of the Chronic Obstructive Pulmonary Disease patients were former smokers, 25·8% non-smokers, and 59·4% were current smokers. More than two-third (76·2%) of Chronic Obstructive Pulmonary Disease patients relied upon traditional firewood cooking, whereas only 14.6% was adopted fireless cooking. The pooled prevalence of Chronic Obstructive Pulmonary Disease in Nepal was significantly high with more cases in females compared to males. Smoking and traditional firewood cooking were major risk factors among Chronic Obstructive Pulmonary Disease cases in Nepal.

Association of the serum albumin level with prognosis in chronic kidney disease patients.

Chronic kidney disease (CKD) is an important contributor to the overall morbidity and mortality due to noncommunicable diseases. We investigated the relationship between serum albumin and the clinical prognosis in patients with stage G2-G5 CKD who were not undergoing dialysis. This was a post hoc analysis of 1138 patients enrolled from 2010 to 2011 in the Chronic Kidney Disease Research of Outcomes in Treatment and Epidemiology (CKD-ROUTE) study. The primary endpoints were CKD progression, cardiovascular disease (CVD) development, and all-cause mortality. Cox proportional hazards models were used. During a median follow-up time of 35months, the number of patients who experienced CKD progression, CVD development, and all-cause mortality was 278 (24.7%), 116 (10.3%), and 78 (6.9%), respectively. In multivariable-adjusted Cox proportional hazards models, the adjusted hazard ratios (HRs) for CKD progression, CVD development, and all-cause mortality in patients with the highest quartile of serum albumin concentrations compared to those with the lowest quartile of serum albumin concentrations were 0.13 (P < 0.0001), 0.29 (P = 0.0002), and 0.27 (P = 0.0009), respectively, in the model adjusted for demographic factors, hypertension, diabetes, and a history of CVD. After further adjustment for the estimated glomerular filtration rate (eGFR), urinary protein/creatinine ratio (UPCR), and systolic blood pressure (SBP), the results remained significant (HR for CKD progression 0.37, P < 0.0001; HR for CVD development 0.41, P = 0.0120; HR for all-cause mortality 0.37, P = 0.0158). Serum albumin levels were inversely associated with the risks of CKD progression, CVD development, and all-cause mortality among patients with stage G2-G5 CKD who were not undergoing dialysis.

Advancing Patient-Centered Research: Enabling the Patient Voice to Be Heard.

The authors of “ Patient and Caregiver Experiences and Attitudes about Their Involvement in Research in Chronic Kidney Disease, ” published in this issue of CJASN , address an important research gap in which scant evidence exists ([1][1]). Moreover, the research topic is very relevant to me on

Patient and Caregiver Experiences and Attitudes about Their Involvement in Research in Chronic Kidney Disease.

Although patient and caregiver involvement in research is widely advocated to improve the relevance and uptake of study findings, barriers and uncertainties in achieving this goal remain. This study aimed to describe patient and caregiver experiences and perspectives of their previous involvement in research, to inform strategies to strengthen patient involvement in research. Semistructured interviews were conducted with 23 adult patients with CKD and caregivers who had previously been involved in research, from Australia, the United States, the United Kingdom, and Denmark. Transcripts were analyzed thematically. We identified six themes: grappling with CKD diagnosis (overwhelmed by the burden of illness, silenced by stigma and shame, absence of advocacy, and awareness), bearing the responsibility for involvement (autonomy in their own care, forced to be proactive to access opportunities, infrastructural support to connect researchers and patients), battling big agendas (struggling in a system of disincentive, changing research culture, becoming equals), seeing the person behind the patient (harnessing broader knowledge, expertise, skills and interests, understanding patient needs, motivations for involvement), sensitivity to complexities of payment (accounting for individual circumstances, denoting value, enabling diverse involvement), and championing the patient voice (links to important stakeholders, drivers of innovation, responsibility to end users). The burden of CKD, limited opportunities, and power asymmetry between patients/caregivers and researchers were challenges to meaningful involvement in research. Building trust, awareness of opportunities, and recognizing the broad expertise and value of patients/caregivers, including and beyond their illness experience, may better support patient and caregiver involvement in research in CKD.