Patterns of Complex Comorbidity in Older Patients with Heart Failure

Background Heart failure (HF) carries a high burden of comorbidity with approximately one half of patients with HF having at least one additional comorbid condition present. Rates of comorbidity in patients with HF have steadily increased over the past 2 decades. Objective To examine patterns of comorbidity among older patients with HF in the Cardiovascular Research Network PRESERVE cohort. Methods PRESERVE Cohort Data are from the CVRN PRESERVE cohort which is a multicenter cohort of 37,054 patients [mean age = 74 years (SD = 12.4 yrs); 46% female] with HF diagnosed between 2005 and 2008 currently being conducted at 4 CVRN sites: KPNC, KPCO, KPNW, and FCHP. The primary data source for the PRESERVE cohort was the HMO Research Network Virtual Data Warehouse. Identification of Coexisting Diseases Coexisiting illnesses at the time of HF diagnosis were based on diagnoses and procedures mapped to relevant International Classification of Diseases, Ninth Edition (ICD-9) codes. For the purposes of characterizing clusters of comorbidities, we focused on coexisting conditions with a prevalence rate of ≥3%. Statistical Analysis We used the Agglomerative Clustering technique to characterize patterns of comorbidity. Over multiple iterations, each condition is clustered with the condition with which it has the highest squared correlation. This process is repeated to determine whether assigning a condition to a different cluster increases the amount of explained variance [ranging from 1.0 (all variance explained) to 0.0 (no variance explained)]. The conditions in each cluster are as correlated as possible among themselves and as uncorrelated as possible with conditions in other clusters. Results Burden of Comorbidity There was a high degree of comorbidity and multi-morbidity among patients with HF. (Table 1) Hypertension and arrhythmias were the comorbidities of HF that occurred most often in the absence of other chronic conditions (4.8% and 4.7%, respectively). The average number of comorbid conditions varied from 3.5 to 5.2. Patients with HF and unstable angina or other thromboembolic disorders had the highest multi-morbidity (mean = 5.2 conditions), whereas those with HF and hypertension had the lowest (mean = 3.5). Clustering of Comorbiditites A five-cluster structure was derived. Cluster 1: Dyslipidemia, Hypertension, Diabetes Mellitus, Visual Impairment Cluster 2: Acute Myocardial Infarction, Unstable Angina, Thromboembolic Disorder, Dementia Cluster 3: Aortic Valvular Disease, Cancer, Hearing Impairment, Arrthythmia Cluster 4: Peripheral Arterial Disease, Stroke Cluster 5: Lung Disease, Liver Disease, Depression Discussion and Conclusions Cluster analysis is an innovative approach to examining the co-occurrence of diseases and allows for identification of broad patterns of multi-morbidity beyond the pairings of diseases or disease counts. Patients with HF have a high rate of multi-morbidity, with an average of 4 co-occurring conditions. Intuitive and unintuitive patterns of clustering were identified. Randomized clinical trials in HF will need to include more diverse patient populations in order to adapt to the increasingly complex patient population. A cluster analysis approach to characterizing patterns of comorbidity may help indentify important patient subgroups

Atrial fibrillation and outcomes in heart failure with preserved versus reduced left ventricular ejection fraction

BACKGROUND: Atrial fibrillation (AF) and heart failure (HF) are 2 of the most common cardiovascular conditions nationally and AF frequently complicates HF. We examined how AF has impacts on adverse outcomes in HF-PEF versus HF-REF within a large, contemporary cohort. METHODS AND RESULTS: We identified all adults diagnosed with HF-PEF or HF-REF based on hospital discharge and ambulatory visit diagnoses and relevant imaging results for 2005-2008 from 4 health plans in the Cardiovascular Research Network. Data on demographic features, diagnoses, procedures, outpatient pharmacy use, and laboratory results were ascertained from health plan databases. Hospitalizations for HF, stroke, and any reason were identified from hospital discharge and billing claims databases. Deaths were ascertained from health plan and state death files. Among 23 644 patients with HF, 11 429 (48.3%) had documented AF (9081 preexisting, 2348 incident). Compared with patients who did not have AF, patients with AF had higher adjusted rates of ischemic stroke (hazard ratio [HR] 2.47 for incident AF; HR 1.57 for preexisting AF), hospitalization for HF (HR 2.00 for incident AF; HR 1.22 for preexisting AF), all-cause hospitalization (HR 1.45 for incident AF; HR 1.15 for preexisting AF), and death (incident AF HR 1.67; preexisting AF HR 1.13). The associations of AF with these outcomes were similar for HF-PEF and HF-REF, with the exception of ischemic stroke. CONCLUSIONS: AF is a potent risk factor for adverse outcomes in patients with HF-PEF or HF-REF. Effective interventions are needed to improve the prognosis of these high-risk patients

The importance of critically short telomere in myelodysplastic syndrome

A few critically short telomeres trigger genomic instability regardless of average telomere length (TL). Recently, the telomere shortest length assay (TeSLA) was developed to detect critically short telomeres and measure absolute telomeres. Using TeSLA with the internally labeled biotin probe, we measured the TL of bone marrow (BM) aspirates from 52 patients with myelodysplastic syndrome (MDS). A percentage of shortest telomeres (< 1.0 kb (ShTL1.0)) were calculated. ShTL1.0 was correlated to IPSS-R risk (spearman’s rho = 0.35 and p = 0.0196), and ShTL1.0 and BM blast (2.61% in < 5% blast, 4.15% in 5–10% blast, and 6.80% in 10–20% blast, respectively, p = 0.0332). Interestingly, MDS patients with a shortest TL ≥ 0.787 kb at the time of diagnosis showed better overall survival (OS) and progression-free survival (PFS) than patients with a shortest TL < 0.787 kb in the multivariate analyses (HR = 0.13 and 0.30, p = 0.011 and 0.048 for OS and PFS, respectively). Our results clearly show the presence and abundance of critically short telomeres in MDS patients. These pathologic telomeres are associated with IPSS-R which is a validated prognostic scoring system in MDS. Furthermore, they are independent prognostic factors for OS in MDS patients. Future prospective studies are needed to validate our results.Highlights Telomere length (TL) has been reported to be important in myelodysplastic syndrome (MDS).A novel TeSLA method demonstrated the presence and abundance of extremely short telomeres (<1.0kb) in MDS.Critically short TL rather than an average TL is associated with the IPSS-R and BM blast in MDS.The shortest TL is an independent prognostic factor for PFS and OS.Short TL should be incorporated into the risk scoring system in MDS in the future.This work was supported by the Ministry of Science and ICT(MSIT) of the Republic of Korea and the National Research Foundation of Korea (NRF-2020R1A3B3079653)

Attributable fraction of alcohol consumption on cancer using population-based nationwide cancer incidence and mortality data in the Republic of Korea

BACKGROUND: In the Republic of Korea, cancer is the most common cause of death, and cancer incidence and mortality rates are the highest in East Asia. As alcoholic beverages are carcinogenic to humans, we estimated the burden of cancer related to alcohol consumption in the Korean population. METHODS: The cancer sites studied were those for which there is convincing evidence of a positive association with alcohol consumption: oral cavity, pharynx, esophagus, colon, rectum, liver, larynx and female breast. Sex- and cancer-specific population attributable fractions (PAF) were calculated based on: 1) the prevalence of alcohol drinkers among adults ≥ 20 years of age in 1989; 2) the average daily alcohol consumption (g/day) among drinkers in 1998; 3) relative risk (RR) estimates for the association between alcohol consumption and site-specific cancer incidence obtained either from a large Korean cohort study or, when more than one Korean study was available for a specific cancer site, meta-analyses were performed and the resulting meta-RRs were used; 4) national cancer incidence and mortality data from 2009. RESULTS: Among men, 3% (2,866 cases) of incident cancer cases and 2.8% (1,234 deaths) of cancer deaths were attributable to alcohol consumption. Among women, 0.5% (464 cancer cases) of incident cancers and 0.1% (32 deaths) of cancer deaths were attributable to alcohol consumption. In particular, the PAF for alcohol consumption in relation to oral cavity cancer incidence among Korean men was 29.3%, and the PAFs for pharyngeal and laryngeal cancer incidence were 43.3% and 25.8%, respectively. Among Korean women, the PAF for colorectal cancer incidence was the highest (4.2%) and that for breast cancer incidence was only 0.2%. Avoiding alcohol consumption, or reducing it from the median of the highest 4th quartile of consumption (56.0 g/day for men, 28.0 g/day for women) to the median of the lowest quartile (2.80 g/day for men, 0.80 g/day for women), would reduce the burden of alcohol-related cancers in Korea. CONCLUSIONS: A reduction in alcohol consumption would decrease the cancer burden and a significant impact is anticipated specifically for the cancers oral cavity, pharynx, and larynx among men in the Republic of Korea

Device Therapies Among Patients Receiving Primary Prevention Implantable Cardioverterâ Defibrillators in the Cardiovascular Research Network

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143721/1/jah33061_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143721/2/jah33061.pd

Genome-Wide Association Study in East Asians Identifies Novel Susceptibility Loci for Breast Cancer

Genetic factors play an important role in the etiology of both sporadic and familial breast cancer. We aimed to discover novel genetic susceptibility loci for breast cancer. We conducted a four-stage genome-wide association study (GWAS) in 19,091 cases and 20,606 controls of East-Asian descent including Chinese, Korean, and Japanese women. After analyzing 690,947 SNPs in 2,918 cases and 2,324 controls, we evaluated 5,365 SNPs for replication in 3,972 cases and 3,852 controls. Ninety-four SNPs were further evaluated in 5,203 cases and 5,138 controls, and finally the top 22 SNPs were investigated in up to 17,423 additional subjects (7,489 cases and 9,934 controls). SNP rs9485372, near the TGF-β activated kinase (TAB2) gene in chromosome 6q25.1, showed a consistent association with breast cancer risk across all four stages, with a P-value of 3.8×10−12 in the combined analysis of all samples. Adjusted odds ratios (95% confidence intervals) were 0.89 (0.85–0.94) and 0.80 (0.75–0.86) for the A/G and A/A genotypes, respectively, compared with the genotype G/G. SNP rs9383951 (P = 1.9×10−6 from the combined analysis of all samples), located in intron 5 of the ESR1 gene, and SNP rs7107217 (P = 4.6×10−7), located at 11q24.3, also showed a consistent association in each of the four stages. This study provides strong evidence for a novel breast cancer susceptibility locus represented by rs9485372, near the TAB2 gene (6q25.1), and identifies two possible susceptibility loci located in the ESR1 gene and 11q24.3, respectively

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI