Myocardial relaxation is impaired in almost all cases with left ventricular diastolic dysfunction (LVDD) and is a strong predictor of cardiovascular and all-cause mortality.
This study investigated ...the feasibility of signal-processed surface electrocardiography (spECG) as a diagnostic tool for predicting the presence of abnormal cardiac muscle relaxation.
A total of 188 outpatients referred for coronary computed tomography (CT) angiography underwent an echocardiogram for assessment of LVDD. The use of 12-lead spECG for predicting myocardial relaxation abnormalities as identified using tissue Doppler echocardiography was validated with machine-learning approaches.
A total of 188 subjects underwent diagnostic testing, with 133 (70%) showing abnormal myocardial relaxation on tissue Doppler imaging. A 12-lead spECG showed an area under the curve of 91% (95% confidence interval: 86% to 95%) for prediction of abnormal myocardial mechanical relaxation with a sensitivity and specificity of 80% and 84%, respectively. The spECG demonstrated more accurate diagnostic performance in individuals age ≥60 years as well as those with obesity or hypertension, compared with their respective counterparts. Prediction of low early diastolic relaxation velocity (e′) also correctly identified concomitant significant underlying coronary artery disease in 23 of 28 cases (82%). Furthermore, a superior integrated discrimination and net reclassification improvement was observed for spECG over clinical features and traditional ECG.
The spECG provides a robust prediction of abnormal myocardial relaxation. These data suggest a potential role for spECG as a novel screening strategy for identifying patients at risk for LVDD who would benefit undergoing echocardiographic evaluations.
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Respiratory syncytial virus (RSV) is a highly contagious pathogen with a huge global health impact. It is a major cause of hospital-acquired infection; a large number of those exposed develop ...infection. Those infected in hospital are at increased risk of a severe clinical course. Prevention of nosocomial spread currently focuses on spread by hand and large droplets. There is little research evidence to determine if aerosol spread of infectious RSV is possible.
To determine if the air surrounding infants with RSV-positive bronchiolitis contains RSV in aerosolized particles that remain capable of causing infection.
The amount of RSV contained in aerosolized particles produced by infants with bronchiolitis due to RSV was measured using viable impactor sampling. The ability of RSV contained in these particles to infect healthy and chronic obstructive pulmonary disease (COPD) human ciliated respiratory epithelium was determined.
We showed for the first time that infants with RSV-positive bronchiolitis nursed in a ward setting or ventilated in intensive care produced large numbers of aerosol particles containing RSV that remained infectious and were capable of infecting healthy and COPD human ciliated epithelium. A significant amount of RSV was found in particles with aerodynamic diameters less than 5 μm.
Many of the aerosolized particles that contained RSV in the air surrounding infants with bronchiolitis were sufficiently small to remain airborne for a significant length of time and small enough to be inhaled and deposited throughout the respiratory tract. It is likely that this leads to spread of infection to others, with dissemination of infection throughout the respiratory tract.
The classical transmission disequilibrium test (TDT) based on a trio design uses information only on the allele transmitted by a heterozygous parent at a marker locus as homozygous parents are ...non-informative about linkage. However, the phenotype of an offspring depends on the alleles transmitted by both parents, irrespective of whether the parents are homozygous or heterozygous, and hence carry useful information on association. In this article, we propose modifications to the TDT procedures by incorporating transmission data on both parents in an informative trio to explore possible gain in power in detecting association. For a binary trait, we use a goodness-of-fit χ
test, whereas for a quantitative trait, we devise two tests: one based on a bivariate response logistic model and the other using a quasi-likelihood approach. We evaluate the type 1 errors and the powers of the proposed tests with those of the classical TDT procedures for both binary and quantitative traits based on extensive simulations. We find that the inclusion of transmission data on non-informative parents yields marginally higher power in the logistic regression approach but results in substantial gain in power in the quasi-likelihood approach. We apply our proposed methods to analyze a count phenotype related to alcoholism.
Although DNA methylation is now recognized as an important mediator of complex diseases, the extent to which the genetic basis of such diseases is accounted for by DNA methylation is unknown. In the ...setting of large, extended families representing a minority, high-risk population of the USA, we aimed to characterize the role of epigenome-wide DNA methylation in type 2 diabetes (T2D). Using Illumina HumanMethylation450 BeadChip arrays, we tested for association of DNA methylation at 446 356 sites with age, sex and phenotypic traits related to T2D in 850 pedigreed Mexican-American individuals. Robust statistical analyses showed that (i) 15% of the methylome is significantly heritable, with a median heritability of 0.14; (ii) DNA methylation at 14% of CpG sites is associated with nearby sequence variants; (iii) 22% and 3% of the autosomal CpG sites are associated with age and sex, respectively; (iv) 53 CpG sites were significantly associated with liability to T2D, fasting blood glucose and insulin resistance; (v) DNA methylation levels at five CpG sites, mapping to three well-characterized genes (TXNIP, ABCG1 and SAMD12) independently explained 7.8% of the heritability of T2D (vi) methylation at these five sites was unlikely to be influenced by neighboring DNA sequence variation. Our study has identified novel epigenetic indicators of T2D risk in Mexican Americans who have increased risk for this disease. These results provide new insights into potential treatment targets of T2D.
Aim: This scoping review aims to identify and map the extent of published literature on Hepatitis B vaccination in stage 4/5 chronic kidney disease (CKD) and dialysis patients, the availability of ...standardised practice guidelines, the optimal CKD stage to commence the vaccination for efficient response, and seroconversion rate.
Background: Hepatitis B vaccination remains 'standard-of-care' in the haemodialysis (HD) population despite immunological challenges. CKD patients have decreasing immunity as the disease progresses, prompting further research to investigate the response of Hepatitis B vaccination in earlier stages of CKD for better response rate prior to requiring dialysis.
Method: This scoping review was conducted using the Arksey and O’Malley (2005) five-stage approach: 1) identifying the research question; 2) identifying the relevant studies; 3) selecting the studies; 4) data charting; and 5) collating, summarising and reporting the results. Medline, PubMed, PubMed Central (PMC) and Cochrane databases were used to access research literature published between 2012-2022.
Results: Of the 602 eligible articles, 183 full text papers were identified. There were 41 studies retained for this review which were sorted out into domains relating to the vaccine immunogenicity, vaccine response and clinical practice guidelines. Although there were studies suggesting immunosuppression in declining renal function leads to low vaccine response, most of the studies were focused on HD patients. There have been no large, randomised control trials on optimal vaccination policy in CKD patients. This scoping review provided important knowledge for future studies to explore the efficiency of commencing vaccination at an earlier stage of CKD before reaching dialysis.
The clinical benefits of using "biocompatible" neutral pH solutions containing low levels of glucose degradation products for peritoneal dialysis compared with standard solutions are uncertain. In ...this multicenter, open-label, parallel-group, randomized controlled trial, we randomly assigned 185 incident adult peritoneal dialysis patients with residual renal function to use either biocompatible or conventional solution for 2 years. The primary outcome measure was slope of renal function decline. Secondary outcome measures comprised time to anuria, fluid volume status, peritonitis-free survival, technique survival, patient survival, and adverse events. We did not detect a statistically significant difference in the rate of decline of renal function between the two groups as measured by the slopes of GFR: -0.22 and -0.28 ml/min per 1.73 m(2) per month (P=0.17) in the first year in the biocompatible and conventional groups, respectively, and, -0.09 and -0.10 ml/min per 1.73 m(2) per month (P=0.9) in the second year. The biocompatible group exhibited significantly longer times to anuria (P=0.009) and to the first peritonitis episode (P=0.01). This group also had fewer patients develop peritonitis (30% versus 49%) and had lower rates of peritonitis (0.30 versus 0.49 episodes per year, P=0.01). In conclusion, this trial does not support a role for biocompatible fluid in slowing the rate of GFR decline, but it does suggest that biocompatible fluid may delay the onset of anuria and reduce the incidence of peritonitis compared with conventional fluid in peritoneal dialysis.
The authors explored the development and validation of machine-learning models for augmenting the echocardiographic grading of aortic stenosis (AS) severity.
In AS, symptoms and adverse events ...develop secondarily to valvular obstruction and left ventricular decompensation. The current echocardiographic grading of AS severity focuses on the valve and is limited by diagnostic uncertainty.
Using echocardiography (ECHO) measurements (ECHO cohort, n = 1,052), we performed patient similarity analysis to derive high-severity and low-severity phenogroups of AS. We subsequently developed a supervised machine-learning classifier and validated its performance with independent markers of disease severity obtained using computed tomography (CT) (CT cohort, n = 752) and cardiovascular magnetic resonance (CMR) imaging (CMR cohort, n = 160). The classifier’s prognostic value was further validated using clinical outcomes (aortic valve replacement AVR and death) observed in the ECHO and CMR cohorts.
In 1,964 patients from the 3 multi-institutional cohorts, 1,346 (68%) subjects had either nonsevere or discordant AS severity. Machine learning identified 1,117 (57%) patients as having high-severity and 847 (43%) as having low-severity AS. High-severity patients in CT and CMR cohorts had higher valve calcium scores and left ventricular mass and fibrosis, respectively than the low-severity group. In the ECHO cohort, progression to AVR and progression to death in patients who did not receive AVR was faster in the high-severity group. Compared with the conventional classification of disease severity, machine-learning–based severity classification improved discrimination (integrated discrimination improvement: 0.07; 95% confidence interval: 0.02 to 0.12) and reclassification (net reclassification improvement: 0.17; 95% confidence interval: 0.11 to 0.23) for the outcome of AVR at 5 years. For both ECHO and CMR cohorts, we observed prognostic value of the machine-learning classifications for subgroups with asymptomatic, nonsevere or discordant AS.
Machine learning can integrate ECHO measurements to augment the classification of disease severity in most patients with AS, with major potential to optimize the timing of AVR.
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Ethnically endogamous populations can shed light on the genetics of type 2 diabetes. Such studies are lacking in India. We conducted this study to determine the genetic and environmental ...contributions of anthropometric traits to type 2 diabetes risk in the Sindhi families in central India.
We conducted a family study in Indian Sindhi families with at least one case of type 2 diabetes. Variance components methods were used to quantify the genetic association of 18 anthropometric traits with eight type 2 diabetes related traits. Univariate and bivariate polygenic models were used to determine the heritability, genetic and environmental correlation of anthropometric traits with type 2 diabetes related traits.
We included 1,152 individuals from 112 phenotyped families. The ascertainment-bias corrected prevalence of type 2 diabetes was 35%. Waist circumference, hip circumference and the biceps, triceps, subscapular and medial calf skinfold thicknesses were polygenically and significantly associated with type 2 diabetes. The range of heritability of the anthropometric traits and type 2 diabetes related traits was 0.27-0.73 and 0.00-0.39, respectively. Heritability of type 2 diabetes as a discrete trait was 0.35. Heritability curves demonstrated a substantial local influence of type 2 diabetes related traits. Bivariate trait analyses showed that biceps and abdominal skinfold thickness and all waist-containing indexes were strongly genetically correlated with type 2 diabetes.
In this first study of Sindhi families, we found evidence for genetic and environmental concordance of anthropometric traits with type 2 diabetes. Future studies need to probe into the genetics of type 2 diabetes in this population.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Contrast-induced acute kidney injury (AKI) is a common and severe complication of percutaneous coronary intervention (PCI). Despite its substantial burden, contemporary data on the incremental costs ...of AKI are lacking. We designed this large, nationally representative study to examine: (1) the independent, incremental costs associated with AKI after PCI and (2) to identify the departmental components of cost contributing to the incremental costs associated with AKI. In this observational cross-sectional study from the Premier database, we analyzed 1,443,297 PCI patients at 518 US hospitals from 1/2006 to 12/2015. Incremental cost of AKI from a hospital perspective obtained by a microcosting approach, was estimated using mixed-effects, multivariable linear regression with hospitals as random effects. Costs were inflation-corrected to 2016 US$. AKI occurred in 82,683 (5.73%) of the PCI patients. Those with AKI had higher hospitalization cost than those without ($38,869, SD 42,583 vs $17,167 SD 13,994, p <0.001). After adjustment, the incremental cost associated with an AKI was $9,448 (95% confidence interval $9,338 to $9,558, p <0.001). AKI was also independently associated with an incremental length of stay of 3.6 days (p <0.001). Room and board costs were the largest driver of AKI costs ($4,841). Extrapolated to the United States, our findings imply an annual AKI cost burden of 411.3 million US$. In conclusion, in this national study of PCI patients, AKI was common and independently associated with ∼$10,000 incremental costs, implying a substantial burden of AKI costs in US hospitals. Successful efforts to prevent AKI in patients who underwent PCI could result in meaningful cost savings.
Anemia is highly prevalent in low- and middle-income countries, where prevalence of acute coronary syndrome (ACS) is also rising. Evidence indicates that baseline anemia status can prognosticate ACS. ...However, the Global Registry of Acute Coronary Events (GRACE) score that is popularly used all over the world does not include information on anemia.
Our objective was to investigate if anemia at admission, along with the GRACE score, improves the prediction of adverse outcomes within 6 months in rural Indian patients of ACS.
We enrolled 200 ACS patients at the Acharya Vinoba Bhave Rural Hospital-a rural, tertiary care hospital in central India. Patients were followed for 6 months for death and major adverse cardiac event (MACE). Improvement in the prediction of adverse events by including anemia in addition to the GRACE score was quantified using area under the receiver operating characteristic curve (AUC), integrated discrimination improvement (IDI) and the net reclassification index (NRI).
There were 31 deaths due to MACE and an additional 28 non-fatal MACE events during follow-up. Baseline hemoglobin was strongly and independently associated with both outcomes even after adjusting for a multivariable propensity score. For the outcome of death and death/MACE there was a moderate improvement in the AUC of 1% and 6%, respectively. However, for these outcomes the IDI for baseline hemoglobin was 6% (p = 0.03) and 12% (p << 0.0001), respectively, while the NRI was 0.50 (p = 0.01) and 0.78 (p << 0.0001), respectively.
Inclusion of baseline anemia in addition to the GRACE score improves prognostication of ACS patients.
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