Background
Physical activity is increasingly recognized as an important modifiable factor for depression. However, the extent to which individuals with stable risk factors for depression, such as ...high genetic vulnerability, can benefit from the protective effects of physical activity, remains unknown. Using a longitudinal biobank cohort integrating genomic data from 7,968 individuals of European ancestry with high‐dimensional electronic health records and lifestyle survey responses, we examined whether physical activity was prospectively associated with reduced risk for incident depression in the context of genetic vulnerability.
Methods
We identified individuals with incident episodes of depression, based on two or more diagnostic billing codes for a depressive disorder within 2 years following their lifestyle survey, and no such codes in the year prior. Polygenic risk scores were derived based on large‐scale genome‐wide association results for major depression. We tested main effects of physical activity and polygenic risk scores on incident depression, and effects of physical activity within stratified groups of polygenic risk.
Results
Polygenic risk was associated with increased odds of incident depression, and physical activity showed a protective effect of similar but opposite magnitude, even after adjusting for BMI, employment status, educational attainment, and prior depression. Higher levels of physical activity were associated with reduced odds of incident depression across all levels of genetic vulnerability, even among individuals at highest polygenic risk.
Conclusions
Real‐world data from a large healthcare system suggest that individuals with high genetic vulnerability are more likely to avoid incident episodes of depression if they are physically active.
GLP-1R (glucagon-like peptide-1 receptor) agonists are approved to treat type 2 diabetes mellitus and obesity. GLP-1R agonists reduce airway inflammation and hyperresponsiveness in preclinical ...models.
To compare rates of asthma exacerbations and symptoms between adults with type 2 diabetes and asthma prescribed GLP-1R agonists and those prescribed SGLT-2 (sodium-glucose cotransporter-2) inhibitors, DPP-4 (dipeptidyl peptidase-4) inhibitors, sulfonylureas, or basal insulin for diabetes treatment intensification.
This study was an electronic health records-based new-user, active-comparator, retrospective cohort study of patients with type 2 diabetes and asthma newly prescribed GLP-1R agonists or comparator drugs at an academic healthcare system from January 2000 to March 2018. The primary outcome was asthma exacerbations; the secondary outcome was encounters for asthma symptoms. Propensity scores were calculated for GLP-1R agonist and non-GLP-1R agonist use. Zero-inflated Poisson regression models included adjustment for multiple covariates.
Patients initiating GLP-1R agonists (
= 448), SGLT-2 inhibitors (
= 112), DPP-4 inhibitors (
= 435), sulfonylureas (
= 2,253), or basal insulin (
= 2,692) were identified. At 6 months, asthma exacerbation counts were lower in persons initiating GLP-1R agonists (reference) compared with SGLT-2 inhibitors (incidence rate ratio IRR, 2.98; 95% confidence interval CI, 1.30-6.80), DPP-4 inhibitors (IRR, 2.45; 95% CI, 1.54-3.89), sulfonylureas (IRR, 1.83; 95% CI, 1.20-2.77), and basal insulin (IRR, 2.58; 95% CI, 1.72-3.88). Healthcare encounters for asthma symptoms were also lower among GLP-1R agonist users.
Adult patients with asthma prescribed GLP-1R agonists for type 2 diabetes had lower counts of asthma exacerbations compared with other drugs initiated for treatment intensification. GLP-1R agonists may represent a novel treatment for asthma associated with metabolic dysfunction.
Sleep Apnea and COVID-19 Mortality and Hospitalization Cade, Brian E; Dashti, Hassan S; Hassan, Syed M ...
American journal of respiratory and critical care medicine,
11/2020, Letnik:
202, Številka:
10
Journal Article
Typically, algorithms to classify phenotypes using electronic medical record (EMR) data were developed to perform well in a specific patient population. There is increasing interest in analyses which ...can allow study of a specific outcome across different diseases. Such a study in the EMR would require an algorithm that can be applied across different patient populations. Our objectives were: (1) to develop an algorithm that would enable the study of coronary artery disease (CAD) across diverse patient populations; (2) to study the impact of adding narrative data extracted using natural language processing (NLP) in the algorithm. Additionally, we demonstrate how to implement CAD algorithm to compare risk across 3 chronic diseases in a preliminary study.
We studied 3 established EMR based patient cohorts: diabetes mellitus (DM, n = 65,099), inflammatory bowel disease (IBD, n = 10,974), and rheumatoid arthritis (RA, n = 4,453) from two large academic centers. We developed a CAD algorithm using NLP in addition to structured data (e.g. ICD9 codes) in the RA cohort and validated it in the DM and IBD cohorts. The CAD algorithm using NLP in addition to structured data achieved specificity >95% with a positive predictive value (PPV) 90% in the training (RA) and validation sets (IBD and DM). The addition of NLP data improved the sensitivity for all cohorts, classifying an additional 17% of CAD subjects in IBD and 10% in DM while maintaining PPV of 90%. The algorithm classified 16,488 DM (26.1%), 457 IBD (4.2%), and 245 RA (5.0%) with CAD. In a cross-sectional analysis, CAD risk was 63% lower in RA and 68% lower in IBD compared to DM (p<0.0001) after adjusting for traditional cardiovascular risk factors.
We developed and validated a CAD algorithm that performed well across diverse patient populations. The addition of NLP into the CAD algorithm improved the sensitivity of the algorithm, particularly in cohorts where the prevalence of CAD was low. Preliminary data suggest that CAD risk was significantly lower in RA and IBD compared to DM.
Objective
To evaluate rheumatoid arthritis (RA) disease activity and risk of RA‐associated interstitial lung disease (RA‐ILD).
Methods
We investigated disease activity and risk of RA‐ILD using the ...Brigham RA Sequential Study (BRASS, 2003–2016). All patients were diagnosed as having RA according to accepted criteria. Disease Activity Scores in 28 joints (DAS28) and covariate data were measured prospectively at annual study visits. Diagnosis of RA‐ILD was determined by review of images from clinically indicated chest computed tomography scans. We analyzed patients without RA‐ILD at baseline. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for RA‐ILD, using annually updated DAS28 data, with adjustment for known RA‐ILD risk factors (age, sex, smoking status, RA duration, and serologic status). We performed alternative analyses that did not censor at the time of missing DAS28 data and included adjustment for use of methotrexate, use of glucocorticoids, presence of bone erosions, and presence of rheumatoid nodules.
Results
Among 1,419 participants, the mean ± SD age was 55.8 ± 14.2 years, and 68.6% were seropositive for either cyclic citrullinated peptide or rheumatoid factor. We identified 85 incident cases of RA‐ILD during a mean ± SD follow‐up duration of 8.9 ± 4.2 years per patient. The moderate/high disease activity group had a multivariable HR of 2.22 (95% CI 1.28–3.82) for RA‐ILD compared to the remission/low disease activity group. Risk of RA‐ILD increased across disease activity categories: multivariable HR 1.00 (reference) for remission, 1.41 (95% CI 0.61–3.28) for low disease activity, 2.08 (95% CI 1.06–4.05) for moderate disease activity, and 3.48 (95% CI 1.64–7.38) for high disease activity (P for trend = 0.001). For each unit increase in the DAS28, the risk of RA‐ILD increased by 35% (95% CI 14–60%). Results were similar in analyses that included follow‐up for missing DAS28 data and with adjustment for use of methotrexate, use of glucocorticoids, presence of bone erosions, or presence of rheumatoid nodules.
Conclusion
Active articular RA was associated with an increased risk of developing RA‐ILD. These results suggest that decreasing systemic inflammation may alter the natural history of RA‐ILD development.
Multiple environmental factors including hormones, dietary factors, infections, and exposure to tobacco smoke, as well as gene-environment interactions, have been associated with increased risk for ...rheumatoid arthritis (RA). The growing understanding of the prolonged period before the first onset of symptoms of RA suggests that these environmental and genetic factors are likely acting to drive the development of RA-related autoimmunity long before the appearance of the first joint symptoms and clinical findings that are characteristic of RA. This article reviews these factors and interactions, especially those that have been investigated in a prospective fashion before the symptomatic onset of RA.
Electronic medical records are emerging as a major source of data for clinical and translational research studies, although phenotypes of interest need to be accurately defined first. This article ...provides an overview of how to develop a phenotype algorithm from electronic medical records, incorporating modern informatics and biostatistics methods.
Objective
To investigate elevation of anti–citrullinated protein antibodies (ACPAs) before diagnosis of rheumatoid arthritis (RA) and risks for chronic obstructive pulmonary disease (COPD) or asthma.
...Methods
We performed a matched cohort study nested within the Nurses’ Health Studies among women who donated blood. Women with incident RA after blood draw (self‐reported, then confirmed by medical records) were each matched to 3 controls by age, cohort, year, and menopausal factors. Pre‐RA ACPA positivity was defined as >99th percentile of control distribution by a research assay or by cyclic citrullinated peptide in a subset. Incident COPD and asthma after index date (date of blood draw) were identified by questionnaires. Cox regression estimated hazard ratios (HRs) for incident COPD or asthma (in separate analyses) associated with pre‐RA, pre‐RA ACPA+, or pre‐RA ACPA– phenotypes each compared to their matched non‐RA controls.
Results
We analyzed 283 women who were pre‐RA and 842 controls; blood was donated a mean ± SD of 9.7 ± 5.8 years before RA diagnosis. Fifty‐nine women (20.8%) were pre‐RA ACPA+. There were 107 cases of incident COPD and 105 incident asthma cases during 21,489 person‐years of follow‐up. Pre‐RA ACPA+ was associated with increased COPD risk (HR 3.04 95% confidence interval (95% CI) 1.33–7.00) after adjusting for covariates including smoking pack‐years. Pre‐RA ACPA+ had an HR for asthma of 1.74 (multivariable 95% CI 0.72–4.24), similar to the risk of asthma for pre‐RA ACPA– (HR 1.65 95% CI 1.11–2.46).
Conclusion
Women with elevated ACPA before RA diagnosis had increased risk for developing COPD compared to controls. Women who later developed RA were more likely to develop asthma than controls, regardless of pre‐RA ACPA status.
CD4
T cells are central mediators of autoimmune pathology; however, defining their key effector functions in specific autoimmune diseases remains challenging. Pathogenic CD4
T cells within affected ...tissues may be identified by expression of markers of recent activation. Here we use mass cytometry to analyse activated T cells in joint tissue from patients with rheumatoid arthritis, a chronic immune-mediated arthritis that affects up to 1% of the population. This approach revealed a markedly expanded population of PD-1
CXCR5
CD4
T cells in synovium of patients with rheumatoid arthritis. However, these cells are not exhausted, despite high PD-1 expression. Rather, using multidimensional cytometry, transcriptomics, and functional assays, we define a population of PD-1
CXCR5
'peripheral helper' T (T
) cells that express factors enabling B-cell help, including IL-21, CXCL13, ICOS, and MAF. Like PD-1
CXCR5
T follicular helper cells, T
cells induce plasma cell differentiation in vitro through IL-21 secretion and SLAMF5 interaction (refs 3, 4). However, global transcriptomics highlight differences between T
cells and T follicular helper cells, including altered expression of BCL6 and BLIMP1 and unique expression of chemokine receptors that direct migration to inflamed sites, such as CCR2, CX3CR1, and CCR5, in T
cells. T
cells appear to be uniquely poised to promote B-cell responses and antibody production within pathologically inflamed non-lymphoid tissues.
The association between alcohol consumption and risk of gout has been suspected since ancient times, but has not been prospectively confirmed. Additionally, potential differences in risk of gout ...posed by different alcoholic beverages have not been assessed.
Over 12 years (1986–98) we used biennial questionnaires to investigate the relation between alcohol consumption and risk of incident gout in 47 150 male participants with no history of gout at baseline. We used a supplementary questionnaire to ascertain whether reported cases of gout met the American College of Rheumatology survey gout criteria.
We documented 730 confirmed incident cases of gout. Compared with men who did not drink alcohol, the multivariate relative risk (RR) of gout was 1·32 (95% CI 0·99–1·75) for alcohol consumption 10·0–14·9 g/day, 1·49 (1·14–1·94) for 15·0–29·9 g/day, 1·96 (1·48–2·60) for 30·0–49·9 g/day, and 2·53 (1·73–3·70) for ≥50 g/day (p for trend <0·0001). Beer consumption showed the strongest independent association with the risk of gout (multivariate RR per 12-oz serving per day 1·49; 95% CI 1·32–1·70). Consumption of spirits was also significantly associated with gout (multivariate RR per drink or shot per day 1·15; 95% CI 1·04–1·28); however, wine consumption was not (multivariate RR per 4-oz serving per day 1·04; 95% CI 0·88–1·22).
Alcohol intake is strongly associated with an increased risk of gout. This risk varies substantially according to type of alcoholic beverage: beer confers a larger risk than spirits, whereas moderate wine drinking does not increase the risk.
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