Shared Risk Research Articles

Comorbidity between major depressive disorder and physical diseases: a comprehensive review of epidemiology, mechanisms and management.

Populations with common physical diseases - such as cardiovascular diseases, cancer and neurodegenerative disorders - experience substantially higher rates of major depressive disorder (MDD) than the general population. On the other hand, people living with MDD have a greater risk for many physical diseases. This high level of comorbidity is associated with worse outcomes, reduced adherence to treatment, increased mortality, and greater health care utilization and costs. Comorbidity can also result in a range of clinical challenges, such as a more complicated therapeutic alliance, issues pertaining to adaptive health behaviors, drug-drug interactions and adverse events induced by medications used for physical and mental disorders. Potential explanations for the high prevalence of the above comorbidity involve shared genetic and biological pathways. These latter include inflammation, the gut microbiome, mitochondrial function and energy metabolism, hypothalamic-pituitary-adrenal axis dysregulation, and brain structure and function. Furthermore, MDD and physical diseases have in common several antecedents related to social factors (e.g., socioeconomic status), lifestyle variables (e.g., physical activity, diet, sleep), and stressful live events (e.g., childhood trauma). Pharmacotherapies and psychotherapies are effective treatments for comorbid MDD, and the introduction of lifestyle interventions as well as collaborative care models and digital technologies provide promising strategies for improving management. This paper aims to provide a detailed overview of the epidemiology of the comorbidity of MDD and specific physical diseases, including prevalence and bidirectional risk; of shared biological pathways potentially implicated in the pathogenesis of MDD and common physical diseases; of socio-environmental factors that serve as both shared risk and protective factors; and of management of MDD and physical diseases, including prevention and treatment. We conclude with future directions and emerging research related to optimal care of people with comorbid MDD and physical diseases.

Polygenic risk of major depressive disorder as a risk factor for venous thromboembolism.

Major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ) are associated with an increased risk of cardiovascular diseases, including venous thromboembolism (VTE). The reasons for this are complex and include obesity, smoking, and use of hormones and psychotropic medications. Genetic studies have increasingly provided evidence of the shared genetic risk of psychiatric and cardiometabolic illnesses. This study aimed to determine whether a genetic predisposition to MDD, BD, or SCZ is associated with an increased risk of VTE. Genetic correlations using the largest genome-wide genetic meta-analyses summary statistics for MDD, BD, and SCZ (Psychiatric Genetics Consortium) and a recent genome-wide genetic meta-analysis of VTE (INVENT Consortium) demonstrated a positive association between VTE and MDD but not BD or SCZ. The same summary statistics were used to construct polygenic risk scores for MDD, BD, and SCZ in UK Biobank participants of self-reported White British ancestry. These were assessed for impact on self-reported VTE risk (10 786 cases, 285 124 controls), using logistic regression, in sex-specific and sex-combined analyses. We identified significant positive associations between polygenic risk for MDD and the risk of VTE in men, women, and sex-combined analyses, independent of the known risk factors. Secondary analyses demonstrated that this association was not driven by those with lifetime experience of mental illness. Meta-analyses of individual data from 6 additional independent cohorts replicated the sex-combined association. This report provides evidence for shared biological mechanisms leading to MDD and VTE and suggests that, in the absence of genetic data, a family history of MDD might be considered when assessing the risk of VTE.

Assessment of common risk factors of diabetes and chronic kidney disease: a Mendelian randomization study.

The increasing prevalence of diabetes and its significant impact on mortality and morbidity rates worldwide has led to a growing interest in understanding its common risk factors, particularly in relation to chronic kidney disease (CKD). This research article aims to investigate the shared risk factors between type 1 diabetes (T1D), type 2 diabetes (T2D), and CKD using a Mendelian randomization (MR) design. The study utilized genome-wide association study (GWAS) datasets for T1D, T2D, and CKD from the FinnGen research project. GWAS summary statistics datasets for 118 exposure traits were obtained from the IEU OpenGWAS database. MR analyses were conducted to examine the causal relationships between exposure traits and each of the three outcomes. Multiple methods, including inverse-variance weighted, weighted median, and MR-Egger, were employed for the MR studies. Phenome-wide MR analyses revealed that eosinophil percentage exhibited a significant and suggestive causal association with T1D and CKD, respectively, suggesting its potential as a shared risk factor for T1D and CKD. For T2D, 34 traits demonstrated significant associations. Among these 34 traits, 14 were also significantly associated with CKD, indicating the presence of common risk factors between T2D and CKD, primarily related to obesity, height, blood lipids and sex hormone binding globulin, blood pressure, and walking pace. This research has uncovered the eosinophil percentage as a potential common risk factor for both T1D and CKD, while also identifying several traits, such as obesity and blood lipids, as shared risk factors for T2D and CKD. This study contributes to the understanding of the common risk factors between diabetes and CKD, emphasizing the need for targeted interventions to reduce the risk of these diseases.

Еволюція ролі державних банків у економіці

The aggravation of global challenges of economic instability, climate change and local physical destruction of infrastructure as a result of war and man-made disasters leads to a review of assessments regarding the expediency of the existence of banks with state participation. The successful experience of using them to solve large socio-economic projects in a number of countries encourages this. Based on a theoretical generalization of the methodological recommendations of scientists and specialists of international institutions and a comparative analysis of current foreign experience, the article presents a scientific rationale for the feasibility of preserving the state share in the capital of leading banking institutions in Ukraine to ensure the stability of the economy during the war and post-war recovery. It was determined that the key directions of solving these tasks with the participation of state banks should be the preservation of the financial market stability, the support of solvent demand and the solvency of small enterprises, and the implementation of large infrastructure projects. At the same time, it was noted that a significant risk of an excessive share of the state in the banking market is the restriction of competition and the deterioration of the quality of services. Due to existing preferences, state banks are prone to violating the laws of market competition. At the same time, acting not according to the laws of the market, but in line with the government’s socially oriented policy, state banks limit the self-regulatory function of the market, which determines their transitional status. The general conclusion states that at certain stages of economic cycles, banks with state participation are a necessary tool that ensures the achievement of macroeconomic goals, infrastructure reconstruction, financing of priority sectors of the economy and, thereby, increasing the country’s competitiveness on the international market. In the presence of such tasks, banks with state participation take on the role of temporarily leading institutions of the development of the transitional stage.

Adiposity is not associated with caries among youth in the United States

BackgroundBody mass index has been traditionally used to determine the nutritional status of children in studies on obesity and caries. Imaging methods provide a superior assessment of body fat. This study investigated the relationship between measures of adiposity and caries in permanent teeth in children and adolescents. MethodsThe analysis included 5,694 participants in the National Health and Nutrition Examination Survey from 2011 through 2018, aged 8 through 19 years. The body fat percentage (BF%) and fat mass index (FMI) were determined from whole-body dual-energy x-ray absorptiometry scans. Excess adiposity was defined as a sex- and age-specific value at or above the 75th percentile according to the US reference standards for BF% or FMI. Caries was measured with the decayed teeth and decayed, missing, and filled teeth indexes; prevalence of untreated dentin caries; and lifetime caries prevalence. The associations between adiposity and caries were tested in confounding variables–adjusted regression models. ResultsThe FMI score was associated with the decayed, missing, and filled teeth score (rate ratio, 1.03; 95% CI, 1.01 to 1.05) and lifetime caries prevalence (odds ratio, 1.06; 95% CI, 1.03 to 1.08), but the associations attenuated after adjustment for confounding variables. Neither the BF% score nor the presence of excess adiposity, defined according to the BF% or FMI reference standards, were associated with caries. ConclusionThe authors found no association between measures of adiposity and caries among US children and adolescents. Practical ImplicationsCaries is a multifactorial disease, and any observed association between obesity and caries is most likely due to the shared determinants and risk factors of both conditions.

Genome-wide association study of esophageal squamous cell cancer identifies shared and distinct risk variants in African and Chinese populations

Esophageal squamous cell carcinoma (ESCC) has a high disease burden in sub-Saharan Africa and has a very poor prognosis. Genome-wide association studies (GWASs) of ESCC in predominantly East Asian populations indicate a substantial genetic contribution to its etiology, but no genome-wide studies have been done in populations of African ancestry. Here, we report a GWAS in 1,686 African individualswith ESCC and 3,217 population-matched control individuals to investigate its genetic etiology. We identified a genome-wide-significant risk locus on chromosome 9 upstream of FAM120A (rs12379660, p= 4.58×10-8, odds ratio= 1.28, 95% confidence interval= 1.22-1.34), as well as a potential African-specific risk locus on chromosome 2 (rs142741123, p= 5.49×10-8) within MYO1B. FAM120A is a component of oxidative stress-induced survival signals, and the associated variants at the FAM120A locus co-localized withhighly significant cis-eQTLs in FAM120AOS in both esophageal mucosa and esophageal muscularis tissue. A trans-ethnic meta-analysis was then performed with the African ESCC study and a Chinese ESCC study in a combined total of 3,699 ESCC-affected individuals and 5,918 control individuals, which identified three genome-wide-significant loci on chromosome 9 at FAM120A (rs12379660, pmeta= 9.36×10-10), chromosome 10 at PLCE1 (rs7099485, pmeta= 1.48×10-8), and chromosome 22 at CHEK2 (rs1033667, pmeta= 1.47×10-9). This indicates the existence of both shared and distinct genetic risk loci for ESCC in African and Asian populations. Our GWAS of ESCC conducted in a population of African ancestry indicates a substantial genetic contribution to ESCC risk in Africa.

Response to anti-IL17 therapy in inflammatory disease is not strongly impacted by genetic background

Response to the anti-IL17 monoclonal antibody secukinumab is heterogeneous, and not all participants respond to treatment. Understanding whether this heterogeneity is driven by genetic variation is a key aim of pharmacogenetics and could influence precision medicine approaches in inflammatory diseases. Using changes in disease activity scores across 5,218 genotyped individuals from 19 clinical trials across four indications (psoriatic arthritis, psoriasis, ankylosing spondylitis, and rheumatoid arthritis), we tested whether genetics predicted response to secukinumab. We did not find any evidence of association between treatment response and common variants, imputed HLA alleles, polygenic risk scores of disease susceptibility, or cross-disease components of shared genetic risk. This suggests that anti-IL17 therapy is equally effective regardless of an individual's genetic background, a finding that has important implications for future genetic studies of biological therapy response in inflammatory diseases.

OP19_3. The role of shared risk factors for COVID-19 and preeclampsia: an observational study

OP19_3. The role of shared risk factors for COVID-19 and preeclampsia: an observational study

Familial coaggregation of MASLD with hepatocellular carcinoma and adverse liver outcomes: Nationwide multigenerational cohort study

Metabolic dysfunction-associated steatotic liver disease (MASLD; formerly NAFLD) is the fastest growing cause of hepatocellular carcinoma (HCC) worldwide. However, whether family members of individuals with MASLD also share an increased risk of developing HCC is unknown. This nationwide multigenerational cohort study involved family members of all Swedish adults diagnosed with biopsy-proven MASLD (1969-2017), and matched general population comparators. Using the Swedish Multi-generation Register, we identified 38,018 first-degree relatives (FDRs: parents, siblings, offspring) and 9,381 spouses of patients with MASLD, as well as 197,303 comparator FDRs and 47,572 comparator spouses. We used Cox proportional hazards models to calculate adjusted hazard ratios (aHRs) for HCC, major adverse liver outcomes (cirrhosis, decompensated liver disease or liver transplantation), liver-related mortality, extrahepatic cancer, and non-liver-related mortality. Over a median of 17.6 years, the rate of the primary outcome HCC was higher in MASLD FDRs vs. comparator FDRs (13 vs. 8/100,000 person-years [PY]; aHR 1.80, 95% CI 1.36-2.37). The HCC risk was further increased in FDRs of individuals with liver fibrosis/cirrhosis (aHR 2.14, 95% CI 1.07-4.27; PHeterogeneity= 0.03). MASLD FDRs also had higher rates of major adverse liver outcomes (73 vs. 51/100,000 PY; aHR 1.52, 95% CI 1.36-1.69) and liver-related mortality (20 vs. 11/100,000 PY; aHR 2.14, 95% CI 1.67-2.74). MASLD FDRs with any concomitant chronic liver condition experienced accelerated progression of liver disease (aHR 1.47, 95% CI 1.29-1.67). MASLD spouses were at higher risks of major adverse liver outcomes (86 vs. 74/100,000 PY; aHR 1.23, 95% CI 1.01-1.51) and liver-related mortality (25 vs. 19/100,000 PY; aHR 1.93, 95% CI 1.15-3.23), but not of HCC (aHR 1.43, 95% CI 0.87-2.35). There is distinct familial clustering of adverse liver-related outcomes in families of individuals with biopsy-proven MASLD, with higher relative risks of HCC, progressive liver disease, and liver-related mortality, but absolute risks are low. Metabolic dysfunction-associated steatotic liver disease (MASLD; formerly termed NAFLD) clusters in families with high genetic susceptibility and shared environmental risk factors, but the risks of developing hepatocellular carcinoma and other major liver-related outcomes in family members of individuals with MASLD are largely unknown. This large nationwide multigenerational cohort study involving family members (first-degree relatives and spouses) of individuals with biopsy-proven MASLD and of matched general population comparators found slightly increased risks of hepatocellular carcinoma in first-degree relatives, and of developing cirrhosis and liver-related mortality in all family members of individuals with biopsy-proven MASLD. The findings of this study provide large-scale evidence to inform clinical practice guidelines for recommendations on the early identification of individuals at higher risk of liver-related morbidity and mortality.

Two-year follow-up of post-traumatic stress disorder symptoms in healthcare workers after the COVID-19 pandemic in China.

This study aimed to conduct a 2-year follow-up of mental disorders in healthcare workers (HCWs) in a region of China outside the epidemic's core zone who happened to be directly or possibly exposed to persons with COVID-19. A cognitive analysis scale was utilized in the evaluation the mental or emotional state of HCWs at Xuzhou Medical University's affiliated hospital in the city of Xuzhou, China (a non-core epidemic area) 2 years after the first assessment during the COVID-19 pandemic. A total of 165 HCWs were selected as the study subjects. In accordance to the exposure risk of COVID-19 patients, the subjects were separated into 2 categories: a group with a high risk HCW (HHCW) (HCWs working in COVID-19-positive wards; N = 91) and a group with a minimal risk HCW (LHCW) (HCWs who worked in wards without COVID-19 patients at the same hospital; N = 75). The clinical as well as demographic information of every HCWs were collected. The demographic data revealed significant differences in terms of occupation, remuneration, and selfless concerns amidst both categories (p < 0.05). There lacked a statistically notable difference in the occurrence of PTSD between the 2 groups. Data was analyzed for factors associated with PTSD, and the results showed that psychological resilience, job risk, and stress in the workplace were risk factors for PTSD. Additionally, the results of the logistic regression analysis showed that psychological resilience was a significant shared risk factor for PTSD in HCWs after the COVID-19 pandemic. The 2-year follow-up showed no statistical difference in the incidence of PTSD between the HHCW group and the LHCW group. Workplace stress, occupational hazards, and psychological resilience were the major contributing risk factors for PTSD in HCWs. Int J Occup Med Environ Health. 2023;36(3):324-32.

Preterm birth and the risk of multimorbidity in adolescence: a multiregister-based cohort study

Multimorbidity affects people of all ages, but the risk factors of multimorbidity in adolescence are unclear. The aim of this study was to examine preterm birth (<37 weeks) as a shared risk factor for multiple health outcomes and the role of gestational age (degree of prematurity) in the development of increasingly complex multimorbidity (two, three, or four health outcomes) in adolescence (age 10-18 years). We used population-wide data from Finland (1 187 610 adolescents born 1987-2006) and Norway (555 431 adolescents born 1998-2007). Gestational age at birth was ascertained from medical birth registers and categorised as 23-27 weeks (extremely preterm), 28-31 weeks (very preterm), 32-33 weeks (moderately preterm), 34-36 weeks (late preterm), 37-38 weeks (early term), 39-41 weeks (term, reference category) and 42-44 weeks (post-term). Children who died or emigrated before their 10th birthday, and those with missing or implausible data on gestational age, birthweight, or covariates, were excluded. Health outcomes at age 10-18 years were ascertained from specialised health care and mortality registers. We calculated hazard ratios (HRs) and population attributable fractions (PAFs) with 95% CIs for multiple health outcomes during adolescence. Individuals were followed up from age 10 to 18 years (mean follow-up: 6 years, SD: 3 years). Preterm birth was associated with increased risks of 20 hospital-treated malignant, cardiovascular, endocrinological, neuropsychiatric, respiratory, genitourinary, and congenital health outcomes, after correcting for multiple testing and ignoring small effects (HR <1·2). Confounder-adjusted HRs comparing preterm with term-born adolescents were 2·29 (95% CI 2·19-2·39) for two health outcomes (PAF 9·0%; 8·3-9·6), and 4·22 (3·66-4·87) for four health outcomes (PAF 22·7%; 19·4-25·8) in the Finnish data. Results in the Norwegian data showed a similar pattern. We observed a consistent dose-response relationship between an earlier gestational age and elevated risks of increasingly complex multimorbidity in both datasets. Preterm birth is associated with increased risks of diverse multimorbidity patterns at age 10-18 years. Adolescents with a preterm-born background could benefit from diagnostic vigilance directed at multimorbidity and a multidisciplinary approach to health care. European Union Horizon 2020, Academy of Finland, Foundation for Pediatric Research, Sigrid Jusélius Foundation, Signe and Ane Gyllenberg Foundation.

Building an island of state capacity: How the UK state implemented the Thames Tideway Tunnel with market-based finance

This article contributes to the literature on state capacity in financialized political economies by studying the market-based investment setting for the Thames Tideway Tunnel, a £4.2 billion sewer, built underneath central London to prevent raw sewage from spilling into the River Thames. Most analyses conclude that financial statecraft undermines state capacities, as it empowers finance and exposes states to uncontrollable risks. This article moves beyond these accounts by arguing that public policy officials engage with finance instrumentally, taking on risks to solve the governing challenges they face. It demonstrates that state action can build islands of state capacity with financial statecraft in fragmented policy environments. Based on expert interviews and documentary analysis, the article traces how the UK’s Ministry of the Environment experimented with a policy instrument and used investment capacities from different levels of government, to implement the Thames Tideway Tunnel through institutional equity investment and share risks in the privatized and financialized environmental sector. The paper concludes that under the current conjuncture, financial statecraft will play an important role in addressing the climate crisis. Therefore, further comparative research is required to explore its normative paradox.

Genetic Evidence Strongly Supports Managing Weight and Blood Pressure in Addition to Glycemic Control in Preventing Vascular Complications in People With Type 2 Diabetes.

To investigate the causal association of type 2 diabetes and its components with risk of vascular complications independent of shared risk factors obesity and hypertension and to identify the main driver of this risk. We conducted Mendelian randomization (MR) using independent genetic variants previously associated with type 2 diabetes, fasting glucose, HbA1c, fasting insulin, BMI, and systolic blood pressure as instrumental variables. We obtained summary-level data for 18 vascular diseases (15 for type 2 diabetes) from FinnGen and publicly available genome-wide association studies as our outcomes. We conducted univariable and multivariable MR, in addition to sensitivity tests to detect and minimize pleiotropic effects. Univariable MR analysis showed that type 2 diabetes was associated with 9 of 15 outcomes; BMI and systolic blood pressure were associated with 13 and 15 of 18 vascular outcomes, respectively; and fasting insulin was associated with 4 and fasting glucose with 2. No robust association was found for HbA1c instruments. With adjustment for correlated traits in the multivariable test, BMI and systolic blood pressure, consistent causal effects were maintained, while five associations with type 2 diabetes (chronic kidney disease, ischemic heart disease, heart failure, subarachnoid hemorrhage, and intracerebral hemorrhage) were attenuated to null. Our findings add strong evidence to support the importance of BMI and systolic blood pressure in the development of vascular complications in people with type 2 diabetes. Such findings strongly support the need for better weight and blood pressure management in type 2 diabetes, independent of glucose lowering, to limit important complications.

Genetic Evidence for Causal Association Between Atrial Fibrillation and Dementia: AMendelian Randomization Study.

Background The knowledge gap regarding whether the correlation between atrial fibrillation (AF) and dementia in observational studies is causation or driven by other shared risk factors remains substantially unfilled. Methods and Results We performed a comprehensive 2-sample Mendelian randomization study to evaluate the causal effect of AF on overall dementia and its subtypes, including vascular dementia, Alzheimer dementia, Lewy body dementia, and frontotemporal dementia. The primary results in inverse variance-weighted analyses were further validated by various Mendelian randomization sensitivity analyses. Additionally, we conducted multivariable Mendelian randomization to examine 10 candidate mediators of the causal association of AF and dementia. Genetic predisposition to AF was modestly associated with an increased risk of overall dementia (odds ratio, 1.140 [95% CI, 1.023-1.271]; P=0.018) and strongly associated with vascular dementia (odds ratio, 1.350 [95% CI, 1.076-1.695]; P=0.010). Genetically predicted AF indicated neutral effects on Alzheimer dementia, Lewy body dementia, and frontotemporal dementia. In multivariable Mendelian randomization analysis, the total effect of AF on overall dementia was remarkably attenuated by adjusting for genetic effect for ischemic stroke (odds ratio, 1.068 [95% CI, 0.953-1.197]; P=0.259) and low cardiac output (odds ratio, 1.046 [95% CI, 0.926-1.181]; P=0.475), indicating that the causal association of genetically predicted AF with dementia was potentially mediated by ischemic stroke and low cardiac output. The causal effect of genetically predicted AF on dementia was independent of cerebral small-vessel disease and brain volume phenotypes. Conclusions Our findings provided novel evidence supporting the causal effect of genetically predicted AF on dementia mediated by ischemic stroke and low cardiac output. Future clinical trials are warranted to evaluate the potential role of appropriate AF management in dementia prevention.

Abstract P3155: Cardiac Extracellular Vesicles Mediate The Neoplastic Properties Of Heart Failure

Background: Heart failure (HF) is associated with an increased incidence of cancer independently of shared risk factors. The mechanism behind this link is complex and not entirely clear. We aimed to test the hypothesis that cardiac extracellular vesicles (cEVs) contribute to the link between HF and cancer. Methods &amp; Results: We used a mouse model of heterotopic lung cancer and post-myocardial infarction (MI) HF. To determine the role of cEVs in tumor growth, we focused on cardiac mesenchymal stromal cells (cMSCs) derived EVs, isolated by size exclusion chromatography. cMSCs after MI secreted twice more EVs, characterized with unique proteome, compared to cMSCs from sham-MI ( Fig A, B ). cMSC-EVs from HF harbored more tumor trophic cytokines and microRNA (miR), such as Periostin, Osteopontin, IL-6, TNFα, miR 221, and miR 21. Next, lung cancer cells were inoculated into mice. While HF accelerated tumor growth, EV depletion by GW4869 attenuated this effect. We found that labeled cMSC-EVs targeted lung cancer tumors, and adoptive transfer of cMSC-EVs from failing hearts accelerated tumor growth with and without systemic EV depletion ( Fig C, D ). Finally, we found that spironolactone, a renin-angiotensin-aldosterone inhibitor, mitigated the neoplastic effects of HF, attenuated tumor growth ( Fig E ), and reduced the secretion of cMSC-EVs by 26%. Conclusions: Our results provide new insight into the link between heart failure and cancer. We show, for the first time, that cardiac extracellular vesicles promote tumor growth independently of other secreted factors. Moreover, spironolactone reduces the number of cardiac extracellular vesicles and the neoplastic effects of heart failure.

Prevalence and shared risk factors of HIV in three key populations in Vietnam: A systematic review and meta-analysis.

This study aims to estimate the prevalence of HIV among each of the three key populations in Vietnam: people who inject drugs (PWID), female sex workers (FSW), and men who have sex with men (MSM) and quantify their shared risk factors for HIV infection through a systematic review and meta-analysis of recent literature (published in 2001-2017) in the relevant topics. A total of 17 studies consisting of 16,304 participants were selected in this review. The meta-analysis results revealed that the pooled prevalence estimates with 95% confidence intervals (CIs) among PWID, FSW, and MSM were: 0.293 (0.164, 0.421), 0.075 (0.060, 0.089), and 0.085 (0.044, 0.126), respectively. The findings also indicated that injecting drug use (OR: 9.88, 95%CI: 4.47-15.28), multiperson use of injecting equipment (OR: 2.91, 95%CI: 1.69, 4.17), and inconsistent condom use (OR: 2.11, 95%CI: 1.33, 2.90) were the shared risk factors for HIV infection among these population groups. The findings highlighted the importance of HIV prevention approaches to addressing the shared sexual and drug-related practices among the key populations in consideration of their overlapping social networks.

Identifying shared transcriptional risk patterns between atherosclerosis and cancer

Cancer and cardiovascular disease (CVD) are the leading causes of death worldwide. Numerous overlapping pathophysiologic mechanisms have been hypothesized to drive the development of both diseases. Further investigation of these common pathways could allow for the identification of mutually detrimental processes and therapeutic targeting to derive mutual benefit. In this study, we intersect transcriptomic datasets correlated with disease severity or patient outcomes for both cancer and atherosclerotic CVD. These analyses confirmed numerous pathways known to underlie both diseases, such as inflammation and hypoxia, but also identified several novel shared pathways. We used these to explore common translational targets by applying the drug prediction software, OCTAD, to identify compounds that simultaneously reverse the gene expression signature for both diseases. These analyses suggest that certain tumor-specific therapeutic approaches may be implemented so that they avoid cardiovascular consequences, and in some cases may even be used to simultaneously target co-prevalent cancer and atherosclerosis.

Exploring genetic risk for catatonia in a genome wide association study and polygenic risk score analysis

BackgroundCatatonia is an under-recognized disorder characterized by psychomotor (increased, decreased, or abnormal) changes, affective symptoms, and disturbance of volition, which may arise in the setting of decompensated psychiatric or non-psychiatric medical disorders. Genetic studies of catatonia are limited, and to the best of our knowledge no prior genome wide association studies of catatonia have been performed to date. MethodsFirst we performed a genome wide association study of catatonia regardless of etiology (psychiatric or non-psychiatric). Secondarily we evaluated whether there was an elevated genetic risk profile for predisposing psychiatric disorders (schizophrenia spectrum disorder, bipolar affective disorder, etc.) in patients with catatonia. We used a matched case control design and applied polygenic risk scores to evaluate for a shared polygenetic contribution to catatonia from common psychiatric phenotypes that show a high prevalence of catatonia in their decompensated states. ResultsAnxiety, bipolar affective disorder, schizophrenia spectrum disorder and cross disorder polygenic risk scores were significantly associated with catatonia case status in both unadjusted and adjusted logistic regression models for the European Ancestry set even after correcting for multiple comparisons. Depression, Alzheimer's, Autism Spectrum Disorder and Obsessive Disorder polygenic risk scores were not significantly associated with catatonia status in participants of European Ancestry. In the African Ancestry set, no psychiatric polygenic risk scores were significantly associated with catatonia status in either the unadjusted or adjusted regression models. ConclusionsEven after controlling for relevant covariates, anxiety, bipolar affective disorder, schizophrenia spectrum disorder and cross disorders were significantly associated with catatonia status suggesting that there might be a shared genetic risk for those disorders amongst patients with catatonia.

Shared Lifestyle-Related Risk Factors of Cardiovascular Disease and Cancer: Evidence for Joint Prevention.

Cardiovascular disease (CVD) and cancer are leading causes of mortality and morbidity worldwide and are the major focus of the World Health Organization's joint prevention programs. While, diverse diseases, CVD and cancer, have many similarities. These include common lifestyle-related risk factors and shared environmental, metabolic, cellular, inflammatory, and genetic pathways. In this review, we will discuss the shared lifestyle-related and environmental risk factors central to both diseases and how the strategies commonly used to prevent atherosclerotic vascular disease can be applied to cancer prevention.

Association Between Race/Ethnicity and 90-Day Emergency Department Visits in Patients Undergoing Elective Total Knee Arthroplasty or Total Hip Arthroplasty in a Universally Insured Population

BackgroundResearch has identified disparities in returns to care by race/ethnicity following primary total joint arthroplasty. We sought to identify risk factors for 90-day emergency department (ED) returns following primary total knee arthroplasty (TKA) or total hip arthroplasty (THA) for these populations. MethodsBlack, Hispanic, and non-Hispanic White patients who underwent elective primary unilateral TKA and THA in an integrated US healthcare system were identified. Risk factors for 90-day postoperative ED visits including patient demographics, household income and education, comorbidities, preoperative healthcare utilization, and copay data were identified with multivariable logistic regression. ResultsPostoperative 90-day ED visits occurred in 13.3% of 79,565 TKA patients (17.2% Black; 14.9% Hispanic; 12.5% White) and 11.0% of THA patients (13.4% Black; 12.1% Hispanic; 10.7% White). Across racial/ethnic categories, patients who had an ED visit within 1 year of their TKA or THA date were more likely to have a 90-day ED return. Shared risk factors for TKA patients were chronic lung disease and outpatient utilization (25th and 75th percentile), while peripheral vascular disease was a shared risk factor for THA patients. Risk factors for multiple races of TKA and THA patients included depression, drug abuse, and psychosis. Prior copay for White (TKA) and Hispanic (TKA and THA) patients was protective, while preoperative primary care was protective for Black THA patients. ConclusionFuture strategies to reduce postoperative ED returns should include directed patient outreach for patients who had ED visits and mental health in the year prior to TKA and THA. Level of EvidenceIII.