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Recent observations, especially in cancer immunotherapy clinical trials with time‐to‐event outcomes, show that the commonly used proportional hazard assumption is often not justifiable, hampering an appropriate analysis of the data by hazard ratios. An attractive alternative advocated is given by the restricted mean survival time (RMST), which does not rely on any model assumption and can always be interpreted intuitively. Since methods for the RMST based on asymptotic theory suffer from inflated type‐I error under small sample sizes, a permutation test was proposed recently leading to more convincing results in simulations. However, classical permutation strategies require an exchangeable data setup between comparison groups which may be limiting in practice. Besides, it is not possible to invert related testing procedures to obtain valid confidence intervals, which can provide more in‐depth information. In this paper, we address these limitations by proposing a studentized permutation test as well as respective permutation‐based confidence intervals. In an extensive simulation study, we demonstrate the advantage of our new method, especially in situations with relatively small sample sizes and unbalanced groups. Finally, we illustrate the application of the proposed method by re‐analyzing data from a recent lung cancer clinical trial. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) and food allergy (FA) share similar type 2 inflammation and commonly co‐occur, but the precise proportion of AD patients with FA and vice versa, as well as the effect of AD disease severity on the strength of this association remains uncertain. The aim of this comprehensive systematic review and meta‐analysis was to determine the prevalence and bidirectional associations of AD with food sensitivity (FS), FA and challenge‐proven food allergy (CPFA). We searched PubMed and EMBASE and three independent reviewers performed title/abstract and full‐text review and data extraction. Overall, 557 articles (n = 225,568 individuals with AD, n = 1,128,322 reference individuals; n = 1,357,793 individuals with FS, FA or CPFA, n = 1,244,596 reference individuals) were included in quantitative analyses. The overall pooled prevalence of FS, FA and CPFA in individuals with AD were 48.4% (95% confidence interval: 43.7–53.2), 32.7% (28.8–36.6) and 40.7% (34.1–47.5) respectively. AD prevalence among individuals with FS, FA and CPFA were 51.2% (46.3–56.2), 45.3% (41.4–49.3) and 54.9% (47.0–62.8) respectively. Children with AD had higher pooled FS (49.8% (44.4–55.1)) and FA (31.4% (26.9–36.1)) prevalences than adults with AD (28.6% (13.4–46.8) and 24.1% (12.1–38.7) respectively). Prevalences of FS and FA numerically increased with AD severity. FS, FA and CPFA are common comorbidities of AD and are closely related. Physicians should be attentive to this relationship to optimize management and treatment strategies in patients. [ABSTRACT FROM AUTHOR]

Background: Patients presenting to the emergency department (ED) with acute vertigo or dizziness represent a diagnostic challenge. Neuroimaging has variable indications and yield. We aimed to conduct a systematic review and meta‐analysis of the diagnostic test accuracy of neuroimaging for patients presenting with acute vertigo or dizziness. Methods: An electronic search was designed following patient–intervention–control–outcome (PICO) question—(P) adult patients with acute vertigo or dizziness presenting to the ED; (I) neuroimaging including computed tomography (CT), CT angiography (CTA), magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), and ultrasound (US); (C) MRI/clinical criterion standard; and (O) central causes (stroke, hemorrhage, tumor, others) versus peripheral causes of symptoms. Articles were assessed in duplicate. The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines were followed. Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) was used to assess certainty of evidence in pooled estimates. Results: We included studies that reported diagnostic test accuracy. From 6309 titles, 460 articles were retrieved, and 12 were included: noncontrast CT scan—six studies, 771 patients, pooled sensitivity 28.5% (95% confidence interval [CI] 14.4%–48.5%, moderate certainty) and specificity 98.9% (95% CI 93.4%–99.8%, moderate certainty); MRI—five studies, 943 patients, sensitivity 79.8% (95% CI 71.4%–86.2%, high certainty) and specificity 98.8% (95% CI 96.2%–100%, high certainty); CTA—one study, 153 patients, sensitivity 14.3% (95% CI 1.8%–42.8%) and specificity 97.7% (95% CI 93.8%–99.6%), CT had higher sensitivity than CTA (21.4% and 14.3%) for central etiology; MRA—one study, 24 patients, sensitivity 60.0% (95% CI 26.2%–87.8%) and specificity 92.9% (95% CI 66.1%–99.8%); US—three studies, 258 patients, sensitivity ranged from 30% to 53.6%, specificity from 94.9% to 100%. Conclusions: Noncontrast CT has very low sensitivity and MRI will miss approximately one in five patients with stroke if imaging is obtained early after symptom onset. The evidence does not support neuroimaging as the only tool for ruling out stroke and other central causes in patients with acute dizziness or vertigo presenting to the ED. [ABSTRACT FROM AUTHOR]

Commonly used prediction models have been primarily constructed without taking physical activity into account. Using the Kailuan physical activity cohorts from Asymptomatic Polyvascular Abnormalities in Community (APAC) study, we developed a 9‐year cardiovascular or cerebrovascular disease (CVD) risk prediction equation. Participants in this study were included from APAC cohort, which included 5440 participants from the Kailuan cohort in China. Cox proportional hazard regression model was applied to construct sex‐specific risk prediction equations for the physical activity cohort (PA equation). Proposed equations were compared with the 10‐year risk prediction model, which is developed for atherosclerotic cardiovascular disease risk in Chinese cohorts (China‐PAR equation). C statistics of PA equations were 0.755 (95% confidence interval, 0.750–0.758) for men and 0.801 (95% confidence interval, 0.790–0.813) for women. The estimated area under the receiver operating characteristic curves in the validation set shows that the PA equations perform as good as the China‐PAR. From calibration among four categories of predicted risks, the predicted risk rates by PA equations were almost identical to the Kaplan–Meier observed rates. Therefore, our developed sex‐specific PA equations have effective performance for predicting CVD for physically active cohorts in the physical activity cohort in Kailuan. [ABSTRACT FROM AUTHOR]

Summary: Background: Neighbourhood socio‐economic environment (SEE) is associated with obesity in older children and adults, but little is known about this relationship in younger children. Breastfeeding is an important preventative of adiposity in childhood, but its relationship with neighbourhood SEE is unknown. Aims: We assessed differences in adiposity and obesity in children before age two by neighbourhood SEE, controlling for family socio‐demographics and breastfeeding duration. Materials and Methods: Family socio‐demographics, child body mass index z scores (BMIz), and breastfeeding duration were collected at periodic study visits from participants in PREVAIL (n = 245), a birth cohort in Cincinnati, OH. Addresses were assigned a Deprivation Index score, a validated measure of SEE, and dichotomized into highest SEE (least deprived quartile of scores) and not highest SEE (remaining quartiles). Longitudinal and Poisson models assessed differences in BMIz by SEE over the second year of life and obesity risk at age two, respectively (highest SEE, reference), while attenuation of obesity risk by breastfeeding duration was tested in mediation models. Results: Residing outside of the highest SEE neighbourhoods was associated with an increased BMIz of 0.04 (95%CI 0.02, 0.06) per month of life and increased obesity risk at age two (aRR: 3.7, 95%CI 1.2, 16.2), controlling for family socio‐demographics. Breastfeeding duration attenuated >9% of the obesity risk attributable to SEE (mediated RR: 3.4, 95%CI 1.1, 14.8). Discussion: In the PREVAIL Cohort, residing outside of the highest SEE neighbourhoods predicted a significant increase in BMIz and obesity risk in children before age two, a relationship that was partially mediated by breastfeeding duration. Conclusion: Breastfeeding support may play an important role in reducing obesity rates in children in lower SEE neighbourhoods. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to assess the impact of hepatitis B virus (HBV) infection on non‐liver malignancies in people living with HIV (PLWH). Methods: All persons aged ≥ 18 years with known hepatitis B virus (HBV) surface antigen (HBsAg) status after the latest of 1 January 2001 and enrolment in the EuroSIDA cohort (baseline) were included in the study; persons were categorized as HBV positive or negative using the latest HBsAg test and followed to their first diagnosis of nonliver malignancy or their last visit. Results: Of 17 485 PLWH included in the study, 1269 (7.2%) were HBV positive at baseline. During 151 766 person‐years of follow‐up (PYFU), there were 1298 nonliver malignancies, 1199 in those currently HBV negative [incidence rate (IR) 8.42/1000 PYFU; 95% confidence interval (CI) 7.94–8.90/1000 PYFU] and 99 in those HBV positive (IR 10.54/1000 PYFU; 95% CI 8.47–12.62/1000 PYFU). After adjustment for baseline confounders, there was a significantly increased incidence of nonliver malignancies in HBV‐positive versus HBV‐negative individuals [adjusted incidence rate ratio (aIRR) 1.23; 95% CI 1.00–1.51]. Compared to HBV‐negative individuals, HBsAg‐positive/HBV‐DNA‐positive individuals had significantly increased incidences of nonliver malignancies (aIRR 1.37; 95% CI 1.00–1.89) and NHL (aIRR 2.57; 95% CI 1.16–5.68). There was no significant association between HBV and lung or anal cancer. Conclusions: We found increased rates of nonliver malignancies in HBsAg‐positive participants, the increases being most pronounced in those who were HBV DNA positive and for NHL. If confirmed, these results may have implications for increased cancer screening in HIV‐positive subjects with chronic HBV infection. [ABSTRACT FROM AUTHOR]

Previous articles in Statistics in Medicine describe how to calculate the sample size required for external validation of prediction models with continuous and binary outcomes. The minimum sample size criteria aim to ensure precise estimation of key measures of a model's predictive performance, including measures of calibration, discrimination, and net benefit. Here, we extend the sample size guidance to prediction models with a time‐to‐event (survival) outcome, to cover external validation in datasets containing censoring. A simulation‐based framework is proposed, which calculates the sample size required to target a particular confidence interval width for the calibration slope measuring the agreement between predicted risks (from the model) and observed risks (derived using pseudo‐observations to account for censoring) on the log cumulative hazard scale. Precise estimation of calibration curves, discrimination, and net‐benefit can also be checked in this framework. The process requires assumptions about the validation population in terms of the (i) distribution of the model's linear predictor and (ii) event and censoring distributions. Existing information can inform this; in particular, the linear predictor distribution can be approximated using the C‐index or Royston's D statistic from the model development article, together with the overall event risk. We demonstrate how the approach can be used to calculate the sample size required to validate a prediction model for recurrent venous thromboembolism. Ideally the sample size should ensure precise calibration across the entire range of predicted risks, but must at least ensure adequate precision in regions important for clinical decision‐making. Stata and R code are provided. [ABSTRACT FROM AUTHOR]

Restricted mean survival time (RMST) is one measure now used to summarize time‐to‐event type data, but it has been pointed out that the distribution of differences in RMST deviates markedly from a normal distribution for controlled clinical trials with small sample sizes. Therefore, we conducted a numerical simulation of the RMST in which the one‐sample survival time follows a Weibull distribution, comparing eight different confidence intervals combining two types of variance with four types of variable transformations, including no transformation. The evaluation items were the coverage probability and the above and below error probabilities for the true value. The variance types were based on Greenwood's formula and its Kaplan–Meier correction. The arcsine square root transformation, logit transformation, and complementary log–log transformation were used as the variable transformations. When the sample size was small and the event rate was low, the confidence interval of the untransformed RMST tended to have a small coverage probability and to be overestimated. Variance by Kaplan–Meier correction improved the coverage. The problems of coverage and overestimation were also improved by variable transformations, and in particular, applying the logit transformation and the complementary log–log transformation both resulted in substantial improvements. Our study suggested that it is preferable to construct the confidence intervals of RMST using the logit transformation for variances based on Greenwood's formula in small sample size trials. The SAS code to replicate the analyses is available at https://github.com/HiroyaHashimoto/SAS-Programs. [ABSTRACT FROM AUTHOR]

Aim: To investigate the association between the left atrial volume index (LAVI) and the incidence of cardiovascular events in patients with acute coronary syndrome (ACS) who did not have atrial fibrillation (AF). Methods: In this sub‐analysis of the HIJ‐PROPER study, 226 ACS patients who did not have a history of AF were enrolled. Participants were divided into two groups according to the LAVI cut‐off level calculated by receiver operating characteristic (ROC) curve analysis to predict the primary endpoint, and cardiovascular events were compared between groups. The primary endpoint was the first occurrence of all‐cause death, non‐fatal myocardial infarction, non‐fatal stroke, and hospitalization for heart failure. Results: ROC curve analysis for the occurrence of composite of cardiovascular events indicated a LAVI cut‐off point of 34 mL/m2. Based on this, 131 patients (58.0%) were in the LAVI < 34 mL/m2 group and 95 (42.0%) were in the LAVI ≥ 34 mL/m2 group. Over a median follow‐up period of 4.0 years [interquartile range: 3.2, 5.1], cardiovascular events were noted in 7 and 15 patients in the LAVI < 34 mL/m2 and LAVI ≥ 34 mL/m2 groups, corresponding to an incidence rate of 5.3% and 15.8%, respectively. Patients with a LAVI value ≥ 34 mL/m2 had a significantly higher risk of cardiovascular events than those with a LAVI value < 34 mL/m2 (hazard ratio: 2.93; 95% confidence interval: 1.19–7.22; P =.014). The tendency was similar after adjusting for several confounders (P =.025). Conclusion: In ACS patients without AF, elevated LAVI was associated with increased cardiovascular events. Clinical trial registration: International standard randomized controlled trial (URL: https://www.umin.ac.jp; UMIN000002742). [ABSTRACT FROM AUTHOR]

Objectives: Typically, prognostic capability of gene expression profiling (GEP) is studied in the context of clinical trials, for which 50%‐80% of patients are not eligible, possibly limiting the generalizability of findings to routine practice. Here, we evaluate GEP analysis outside clinical trials, aiming to improve clinical risk assessment of multiple myeloma (MM) patients. Methods: A total of 155 bone marrow samples from MM patients were collected from which RNA was analyzed by microarray. Sixteen previously developed GEP‐based markers were evaluated, combined with survival data, and studied using Cox proportional hazard regression. Results: Gene expression profiling‐based markers SKY92 and the PR‐cluster were shown to be independent prognostic factors for survival, with hazard ratios and 95% confidence interval of 3.6 [2.0‐6.8] (P <.001) and 5.8 [2.7‐12.7] (P <.01) for overall survival (OS). A multivariate model proved only SKY92 and the PR‐cluster to be independent prognostic factors compared to cytogenetic high‐risk patients, the International Staging System (ISS), and revised ISS. A substantial number of high‐risk individuals could be further identified when SKY92 was added to the cytogenetic, ISS, or R‐ISS. In the cytogenetic standard‐risk group, ISS I/II, and R‐ISS I/II, 13%, 23%, and 23% of patients with adverse survivals were identified. Conclusions: For the first time, this study confirmed the prognostic value of GEP markers outside clinical trials. Conventional prognostic models to define high‐risk MM are improved by the incorporation of GEP markers. [ABSTRACT FROM AUTHOR]

Objectives: Only 5% to 10% of patients who visit the emergency department (ED) with isolated dizziness without neurologic abnormalities may have central lesions; however, it is important to distinguish central lesions through brain imaging. This study was conducted to create a nomogram to provide an objective medical basis for selectively performing magnetic resonance imaging (MRI) among patients with isolated dizziness. Methods: This retrospective observational study enrolled patients who visited the ED of a tertiary hospital with isolated dizziness and underwent diffusion‐weighted MRI and subsequently consulted with the departments of neurology, neurosurgery, or otorhinolaryngology. Multivariable logistic regression analysis was performed to identify risk factors in patients diagnosed with central lesions to create a nomogram with the significant variables. Results: Of the 1,078 patients who were screened, 119 were diagnosed with central lesions. Significant variables in the multivariable logistic regression analysis were albumin levels (odds ratio [OR] = 0.339, 95% confidence interval [CI] = 0.188 to 0.610, p = 0.0003), inorganic phosphate levels (OR = 0.891, 95% CI = 0.832 to 0.954, p = 0.0010), history of ischemic stroke (OR = 3.170, 95% CI = 1.807 to 5.560, p < 0.0001), presyncope (OR = 3.152, 95% CI = 1.184 to 8.389, p = 0.0216), and nystagmus (OR = 0.365, 95% CI = 0.237 to 0.561, p < 0.0001). The area under the receiver operating characteristic curve of the nomogram created with these variables was 0.7315 (95% CI = 0.6842 to 0.7788, p < 0.0001). Conclusions: Albumin, inorganic phosphate, previous stroke, presyncope, and nystagmus were associated with the predictive diagnosis of central lesions among patients admitted to the ED with isolated dizziness. The novel nomogram created using these variables can help in objectively determining the need for MRI in patients presenting with isolated dizziness to the ED. [ABSTRACT FROM AUTHOR]

Objective: In aortic stenosis (AS), chronic pressure overload on left ventricle (LV) leads to LV hypertrophy, impaired relaxation, increased chamber stiffness, fibrosis and left atrial (LA) dilatation. An enlarged LA may be a marker of longstanding diastolic dysfunction (DD) and more advanced disease in AS. We aimed to assess the impact of LA volume index (LAVI) on events in patients with moderate or severe AS. Methods: A total of 324 patients (mean age 69 ± 13 years, 61% men) were included. LA volume was measured by biplane Simpson's method using apical four‐ and two‐chamber views and indexed to body surface area. An increased LAVI was defined as > 34 ml/m2. Results: The mean EF was 64 ± 8%, LAVI 35 ± 14 ml/m2 and flow rate 244 ± 70 ml/s. The number of total events was 275 (85%): 243 (75%) aortic valve replacement and 32 (10%) deaths. Mean follow‐up 23.7 ± 23.8 months (median 15.2 months). An increased LAVI (45% [n = 145]) was associated with adverse events (HR 1.86; 95% CI 1.24–2.82, p = 0.003) independent of age, smoking, diabetes, atrial fibrillation, LV ejection fraction, LV mass, aortic valve area, and low flow rate (<200 ml/s). In the same multivariate model, when increased LAVI was replaced by E/e′ ratio ≥14 cm, no association was found between E/e' ratio ≥14 cm and adverse events (HR 1.18; 95% CI.78–1.78, p = 0.430). Conclusion: LAVI was an independent predictor of adverse events in patients with moderate or severe AS and preserved ejection fraction. Including LAVI in the risk assessment of AS patients may further improve risk stratification. [ABSTRACT FROM AUTHOR]

The restricted mean survival time (RMST) has been popularly used to assess the treatment effect in survival trials. Greenwood's formula is often used to estimate the variance of RMST, and the resulting Wald confidence interval (CI) tends to be liberal in small and moderate samples. We propose the empirical likelihood ratio, score‐type, and loglog transformed CIs for RMST in a single sample. The method of variance estimates recovery technique is used to derive the CIs for the difference and ratio parameters in the two sample inference. A variance estimate, which assumes equal survival curves, but possibly different censoring rates in the two groups, is proposed for comparing two groups. The new variance estimate shows excellent performance in testing for superiority, and also works well for a noninferiority test with a small margin, and for the interval estimation when the two survival curves are close. We use similar techniques to construct CIs for comparing two milestone survival probabilities. Numerical examples are used to assess these interval estimation methods. [ABSTRACT FROM AUTHOR]

The baby‐friendly hospital initiative (BFHI) promotes exclusive breastfeeding (EBF) in hospitals, but this is not accessible in rural settings where mothers give birth at home, hence the need for a community intervention. We tested the effectiveness of the baby‐friendly community initiative (BFCI) on EBF in rural Kenya. This cluster randomized study was conducted in 13 community units in Koibatek sub‐county. Pregnant women aged 15–49 years were recruited and followed up until their children were 6 months old. Mothers in the intervention group received standard maternal, infant and young child nutrition counselling, support from trained community health volunteers, health professionals and community and mother support groups, whereas those in the control group received standard counselling only. Data on breastfeeding practices were collected longitudinally. The probability of EBF up to 6 months of age and the restricted mean survival time difference were estimated. A total of 823 (intervention group n = 351) pregnant women were recruited. Compared with children in the control group, children in the intervention group were more likely to exclusively breastfeed for 6 months (79.2% vs. 54.5%; P <.05). Children in the intervention group were also exclusively breastfed for a longer time, mean difference (95% confidence interval [CI]) 0.62 months (0.38, 0.85; P <.001). The BFCI implemented within the existing health system and including community and mother support groups led to a significant increase in EBF in a rural Kenyan setting. This intervention has the potential to improve EBF rates in similar settings. [ABSTRACT FROM AUTHOR]

In single‐arm clinical trials with survival outcomes, the Kaplan–Meier estimator and its confidence interval are widely used to assess survival probability and median survival time. Since the asymptotic normality of the Kaplan–Meier estimator is a common result, the sample size calculation methods have not been studied in depth. An existing sample size calculation method is founded on the asymptotic normality of the Kaplan–Meier estimator using the log transformation. However, the small sample properties of the log transformed estimator are quite poor in small sample sizes (which are typical situations in single‐arm trials), and the existing method uses an inappropriate standard normal approximation to calculate sample sizes. These issues can seriously influence the accuracy of results. In this paper, we propose alternative methods to determine sample sizes based on a valid standard normal approximation with several transformations that may give an accurate normal approximation even with small sample sizes. In numerical evaluations via simulations, some of the proposed methods provided more accurate results, and the empirical power of the proposed method with the arcsine square‐root transformation tended to be closer to a prescribed power than the other transformations. These results were supported when methods were applied to data from three clinical trials. [ABSTRACT FROM AUTHOR]

Objectives: The relationship between marijuana use and markers of chronic lung disease in people living with HIV (PLWH) is poorly understood. Methods: We performed a cross‐sectional analysis of the Examinations of HIV‐Associated Lung Emphysema (EXHALE) study, including 162 HIV‐positive patients and 138 participants without HIV. We modelled marijuana exposure as: (i) current daily or weekly marijuana smoking vs. monthly or less often; or (ii) cumulative marijuana smoking (joint‐years). Linear and logistic regression estimated associations between marijuana exposure and markers of lung disease, adjusted for tobacco smoking and other factors. Results: In PLWH, current daily or weekly marijuana use was associated with a larger forced vital capacity (FVC), larger total lung capacity and increased odds of radiographic emphysema compared with marijuana non‐smokers in adjusted models; these associations were not statistically significant in participants without HIV. Marijuana joint‐years were associated with higher forced expiratory volume in 1 s and FVC in PLWH but not with emphysema. Conclusions: In PLWH, marijuana smoking was associated with higher lung volumes and potentially with radiographic emphysema. No consistently negative associations were observed between marijuana and measures of chronic lung health. [ABSTRACT FROM AUTHOR]

Assessing and comparing the performance of correlated predictive scores are of current interest in precision medicine. Given the limitations of available theoretical approaches for assessing and comparing the predictive accuracy, numerical methods are highly desired which, however, have not been systematically developed due to technical challenges. The main challenges include the lack of a general strategy on effectively simulating many kinds of correlated predictive scores each with some given level of predictive accuracy in either concordance index or the area under a receiver operating characteristic curve area under the curves (AUC). To fill in this important knowledge gap, this paper is to provide a general copula-based numeric framework for assessing and comparing predictive performance of correlated predictive or risk scores. The new algorithms are designed to effectively simulate correlated predictive scores with given levels of predictive accuracy as measured in terms of concordance indices or time-dependent AUC for predicting survival outcomes. The copula-based numerical strategy is convenient for numerically evaluating and comparing multiple measures of predictive accuracy of correlated risk scores and for investigating finite-sample properties of test statistics and confidence intervals as well as assessing for optimism of given performance measures using cross-validation or bootstrap. [ABSTRACT FROM AUTHOR]

Background: There are two main choices of administration route of recombinant human endostatin (Endostar) available and the treatment options of concurrent chemoradiotherapy (CCRT) have changed over time. The aim of this study was to observe the long‐term efficacy and safety of different administration routes of Endostar combined with CCRT. Methods: Patients with unresectable stage III non‐small cell lung cancer (NSCLC) from two phase II trials were included as two cohorts. Both were treated with Endostar combined with CCRT. Endostar was administrated by intravenous injection (7.5 mg/m2/day, seven days) in the IV arm and by continuous intravenous pumping (7.5 mg/m2/24 hours, 120 hours) in the CIV arm. Results: A total of 48 patients were included in the IV arm and 67 patients in the CIV arm. The median progression‐free survival (PFS), overall survival (OS), local recurrence‐free survival (LRFS) and distant metastasis‐free survival (DMFS) in the IV arm and CIV arm were 9.9 months versus 15.4 months (HR = 0.751, 95% CI 0.487–1.160, P = 0.200), 24.0 months versus 38.5 months (HR = 0.746, 95% CI 0.473–1.178, P = 0.209), 32.3 months versus 27.1 months (HR = 1.193, 95% CI 0.673–2.115, P = 0.546), 20.1 months versus 49.7 months (HR = 0.603, 95% CI 0.351–1.036, P = 0.067). The one, three, five‐year PFS in the IV arm and CIV arm was 45.8% versus 52.9%, 18.3% versus 31.4%, and 18.3% versus 27.7% and the one, three, five‐year OS was 81.2% versus 82.1%, 31.1% versus 50.3%, and 31.1% versus 41%, respectively. Incidence of hematological adverse reactions were numerically lower in the CIV arm than the IV arm. Conclusions: Endostar delivered by CIV with CCRT may be a better option than IV in terms of potential survival and safety for unresectable stage III NSCLC. Key points: Significant findings of the study Endostar delivered by continuous intravenous pumping might achieve more favorable survival over intravenous injection and reduce adverse hematological reactions in patients with unresectable stage III NSCLC treated with Endostar combined with CCRT.What this study adds The administration route of recombinant human endostatin is also one key factor for survival and safety to consider when treating patients with unresectable stage III NSCLC. [ABSTRACT FROM AUTHOR]

Abstract: The difference between the pth quantiles of 2 survival functions can be used to compare patients' survival between 2 therapies. Setting p = 0.5 yields the median survival time difference. Varying p between 0 and 1 defines the quantile survival time difference curve which can be straightforwardly estimated by the horizontal differences between 2 Kaplan‐Meier curves. The estimate's variability can be visualized by adding either a bundle of resampled bootstrap step functions or, alternatively, approximate bootstrap confidence bands. The user‐friendly SAS software macro %kmdiff enables the straightforward application of this exploratory graphical approach. The macro is described, and its application is exemplified with breast cancer data. The advantages and limitations of the approach are discussed. [ABSTRACT FROM AUTHOR]

Background: Prior studies have shown that both heart failure (HF) and atrial fibrillation (AF) are factors that impact left atrial function and structure. However, right atrial (RA) function measured as RA emptying fraction (RAEF) on echocardiography has not been analyzed systematically in a chronic HF population. The aim of this study was to assess RA volume index (RAVI) and RAEF in patients with chronic HF and patients with hypertension (HTN) and to relate these findings to other cardiopulmonary ultrasound parameters and 12‐month outcomes. Methods and Results: In this prospective observational study, we identified 119 patients with chronic HF (64 patients without a history of AF [HF without AF], 55 with AF [HF with AF]), and 127 patients with HTN but without important cardiac disease who underwent routine outpatient transthoracic echocardiography. We found that RAEF was impaired in patients with HF without AF compared to patients with HTN (35% ±2 vs 50% ±1, P < .001), whereas RAVI did not differ between these two groups. Lower RAEF was associated with larger RAVI and higher estimated RA pressures but not with a higher degree of pulmonary congestion by lung ultrasound. Both lower RAEF and higher RAVI were associated with an increased risk of 12‐month HF hospitalizations or all‐cause death (age, sex, and AF adjusted HR: 4.07, 95% CI: 1.69–9.79; P = .002, vs 2.74, 95% CI: 1.15–6.54, P = .023). Conclusions: In an outpatient HF cohort, both lower RAEF and increased RAVI were associated with other markers of impaired cardiac function and 12‐month adverse events. [ABSTRACT FROM AUTHOR]

Background: Left ventricular ejection fraction (LVEF) is fundamental for risk stratification after ST‐segment elevation myocardial infarction (STEMI). However, it lacks discrimination power within normal range. Novel echocardiographic deformation parameters may be of benefit for those with post‐MI preserved LVEF. Objectives: We hypothesized that semiautomated calculation of baseline global longitudinal strain (GLS) can identify high‐risk group among patients with LVEF ≥ 50% following STEMI. Methods: During the period from January to July 2017, 110 patients with successful reperfusion of STEMI and LVEF ≥ 50% were prospectively included. Within 48 hours, patients underwent a baseline GLS study with follow‐up study at 30 days. The endpoint was a composite of cardiovascular mortality, rehospitalization for heart failure, and urgent revascularization. Results: Mean GLS value changed from −16 ± 4% at baseline to −12 ± 4% at 30‐day follow‐up (P < .001). At 30 days, cardiovascular mortality was reported in 4.5%, 11.8% were rehospitalized due to heart failure, and 5.4% underwent urgent revascularization. ROC curve analysis showed that a cutoff baseline GLS value >−12.65% predicted 30‐day MACEs with a sensitivity and specificity of 77.8% and 83.7%, respectively (AUC 0.784, 95% CI 0.646–0.921, P < .001). An adjusted multivariate logistic regression analysis revealed that baseline GLS value >−12.65% to be the only significant independent predictor for occurrence of MACEs (OR 19.54, 95% CI 6.3–61.1, P < .001). Conclusion: Early GLS calculation predicts 30‐day outcome in patients with preserved LVEF following reperfusion of STEMI. [ABSTRACT FROM AUTHOR]

Aims: Left ventricular mechanical dyssynchrony has been described in heart failure with preserved ejection fraction (HFpEF), but its prognostic significance is not known.Methods and Results: Of 3445 patients with HFpEF enrolled in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, dyssynchrony analysis was performed on 424 patients (12%) by multiple speckle tracking echocardiography strain-based criteria. The primary dyssynchrony analysis was the standard deviation of the time to peak longitudinal strain (SD T2P LS). Cox proportional hazards models assessed the association of dyssynchrony with the composite outcome of cardiovascular death or heart failure hospitalization. Mean age was 70 ± 10 years, LVEF was 60 ± 8%, and QRS duration was 101 ± 27 ms. Worse dyssynchrony, reflected in SD T2P LS, was associated with wider QRS, prior myocardial infarction, larger LV volume and mass, and worse systolic (lower LVEF and global longitudinal strain) and diastolic (lower e' and higher E/e') function. During a median follow-up of 2.6 (interquartile range 1.5-3.8) years, 107 patients experienced the composite outcome. Worse dyssynchrony was associated with the composite outcome in unadjusted analysis [hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.01-1.07; P = 0.021, per 10 ms increase], but not after adjusting for clinical characteristics, or after further adjustment for LVEF, AF, NYHA class, stroke, heart rate, creatinine, haematocrit, and QRS duration (HR 1.03, 95% CI 0.99-1.06; P = 0.16, per 10 ms increase).Conclusion: Worse LV mechanical dyssynchrony, assessed by speckle tracking echocardiography, is not an independent predictor of adverse outcomes in HFpEF, suggesting that mechanical dyssynchrony is unlikely to be an important mechanism underlying this syndrome. These findings warrant validation in an independent study specifically designed to assess the prognostic utility of mechanical dyssynchrony in HFpEF.Trial Registration: NCT00094302. [ABSTRACT FROM AUTHOR]

Rationale, aims and objectives Variation in the workup of rectal bleeding may result in guideline-discordant care and delayed diagnosis of colorectal cancer. Accordingly, we undertook this study to characterize primary care clinicians' initial rectal bleeding evaluation. Methods We studied 438 patients at 10 adult primary care practices affiliated with three Boston, Massachusetts, academic medical centres and a multispecialty group practice, performing medical record reviews of subjects with visit codes for rectal bleeding, haemorrhoids or bloody stool. Nurse reviewers abstracted patients' sociodemographic characteristics, rectal bleeding-related symptoms and components of the rectal bleeding workup. Bivariate and multivariable logistic regression models examined factors associated with guideline-discordant workups. Results Clinicians documented a family history of colorectal cancer or polyps at the index visit in 27% of cases and failed to document an abdominal or rectal examination in 21% and 29%. Failure to order imaging or a diagnostic procedure occurred in 32% of cases and was the only component of the workup associated with guideline-discordant care, which occurred in 27% of cases. Compared with patients at hospital-based teaching sites, patients at urban clinics or community health centres had 2.9 (95% confidence interval 1.3-6.3) times the odds of having had an incomplete workup. Network affiliation was also associated with guideline concordance. Conclusion Workup of rectal bleeding was inconsistent, incomplete and discordant with guidelines in one-quarter of cases. Research and improvements strategies are needed to understand and manage practice and provider variation. [ABSTRACT FROM AUTHOR]

Background Three-dimensional (3D) speckle tracking echocardiography ( STE) has been developed to overcome the limitations of two-dimensional (2D) STE and has been applied in the several clinical settings. However, no data exist about the prognostic value of 3D STE-based strain on clinical outcome after myocardial infarction ( MI). This study was designed to investigate the prognostic value of area strain ( AS) by 3D speckle tracking in predicting clinical outcome after acute MI. Methods We assessed 96 patients (62±14 years, 72% male) with acute MI and who had undergone a coronary angiography. Clinical parameters and conventional echocardiographic measurements including the left atrial ( LA) size and tissue Doppler measurements were evaluated. The global left ventricular ( LV) AS was measured using 3D speckle tracking software. The relationship between the AS and clinical outcome of death or hospitalization for heart failure ( HF) was assessed. Results During a median follow-up of 33±10 months, primary endpoint of death or HF occurred in 12 patients (12.5%). AS was predictive of death or HF after adjustment for age, gender, peak CK- MB, LA volume, LV end-systolic volume, LV mass, the ratio of early mitral inflow velocity to early mitral annular velocity, and LV ejection fraction in a multivariate Cox model ( HR 1.23, 95% CI 1.02-1.47, P=.03). In addition, AS added incremental value in predicting death or heart failure on a model based on clinical and standard echocardiographic measures ( P=.008). Conclusion AS is independently associated with increased risk of death or HF after acute MI, suggesting that it can be a useful prognostic parameter in the patients following MI. [ABSTRACT FROM AUTHOR]

Aims To investigate the risk prediction and the risk stratification performances of the Chronic Kidney Disease Epidemiology Collaboration ( CKD- EPI) equation and the Modification of Diet in Renal Disease ( MDRD) equation for estimated glomerular filtration rate ( eGFRCKD- EPI vs. eGFRMDRD) on heart failure in patients with Type 2 diabetes. Methods The study cohort included 12 258 White and 16 886 African American low-income patients with Type 2 diabetes who were 30-90 years old at baseline. Heart failure risk according to different eGFRCKD- EPI and eGFRMDRD categories was prospectively assessed. Results During a mean follow-up of 6.5 years, 5043 incident heart failure cases were identified. Multivariable-adjusted hazard ratios ( HRs) of heart failure associated with the eGFRCKD- EPI categories [≥ 90 (reference group), 75-89, 60-74, 30-59 and < 30 ml/min/1.73 m2] were 1.00, 1.11, 1.31, 1.75 and 2.93 ( Ptrend < 0.001) for African American patients, and 1.00, 1.11, 1.08, 1.59 and 2.92 ( Ptrend < 0.001) for White patients, respectively. The model with eGFRCKD- EPI and the other risk factors had significantly higher Harrell's C than the model with eGFRMDRD and other risk factors. Patients reclassified downward from eGFRMDRD 60-74 to eGFRCKD- EPI 30-59 and from eGFRMDRD 30-59 to eGFRCKD- EPI < 30 ml/min/1.73 m2 showed higher heart failure risk than those who were not reclassified. Conclusions Impaired kidney function (i.e. GFR < 60 ml/min/1.73 m2), and even mildly decreased GFR (60-74 ml/min/1.73 m2) estimated by both equations is associated with an increased risk of heart failure. Compared with GFR estimated using the MDRD equation, GFR estimated using the CKD- EPI equation added more predictive power to the model with the other risk factors. Also, eGFRCKD- EPI provided more accurate heart failure risk stratification than eGFRMDRD . [ABSTRACT FROM AUTHOR]

Aim To investigate glucose and insulin metabolism in participants with ataxia telangiectasia in the absence of a diagnosis of diabetes. Methods A standard oral glucose tolerance test was performed in participants with ataxia telangiectasia ( n = 10) and in a control cohort ( n = 10). Serial glucose and insulin measurements were taken to permit cohort comparisons of glucose-insulin homeostasis and indices of insulin secretion and sensitivity. Results During the oral glucose tolerance test, the 2-h glucose (6.75 vs 4.93 mmol/l; P = 0.029), insulin concentrations (285.6 vs 148.5 pmol/l; P = 0.043), incremental area under the curve for glucose (314 vs 161 mmol/l/min; P = 0.036) and incremental area under the curve for insulin (37,720 vs 18,080 pmol/l/min; P = 0.03) were higher in participants with ataxia telangiectasia than in the controls. There were no significant differences between groups in fasting glucose, insulin concentrations or insulinogenic index measurement (0.94 vs 0.95; P = 0.95). The Matsuda index, reflecting whole-body insulin sensitivity, was lower in participants with ataxia telangiectasia (5.96 vs 11.03; P = 0.019) than in control subjects. Conclusions Mutations in Ataxia Telangiectasia Mutated ( ATM) that cause ataxia telangiectasia are associated with elevated glycaemia and low insulin sensitivity in participants without diabetes. This indicates a role of ATM in glucose and insulin metabolic pathways. [ABSTRACT FROM AUTHOR]

Pediatric Resynchronization Patients Introduction Cardiac resynchronization therapy indications and management are well described in adults. Echocardiography (ECHO) has been used to optimize mechanical synchrony in these patients; however, there are issues with reproducibility and time intensity. Pediatric patients add challenges, with diverse substrates and limited capacity for cooperation. Electrocardiographic (ECG) methods to assess electrical synchrony are expeditious but have not been extensively studied in children. We sought to compare ECHO and ECG CRT optimization in children. Methods Prospective, pediatric, single-center cross-over trial comparing ECHO and ECG optimization with CRT. Patients were assigned to undergo either ECHO or ECG optimization, followed for 6 months, and crossed-over to the other assignment for another 6 months. ECHO pulsed-wave tissue Doppler and 12-lead ECG were obtained for 5 VV delays. ECG optimization was defined as the shortest QRSD and ECHO optimization as the lowest dyssynchrony index. ECHOs/ECGs were interpreted by readers blinded to optimization technique. After each 6 month period, these data were collected: ejection fraction, velocimetry-derived cardiac index, quality of life, ECHO-derived stroke distance, M-mode dyssynchrony, study cost, and time. Outcomes for each optimization method were compared. Results From June 2012 to December 2013, 19 patients enrolled. Mean age was 9.1 ± 4.3 years; 14 (74%) had structural heart disease. The mean time for optimization was shorter using ECG than ECHO (9 ± 1 min vs. 68 ± 13 min, P < 0.01). Mean cost for charges was $4,400 ± 700 less for ECG. No other outcome differed between groups. Conclusion ECHO optimization of synchrony was not superior to ECG optimization in this pilot study. ECG optimization required less time and cost than ECHO optimization. [ABSTRACT FROM AUTHOR]

Aim The aim of the study was to evaluate the left ventricle ( LV) function with speckle tracking echocardiography ( STE) and to assess its relation to prognosis in patients after acute myocardial infarction ( AMI). Methods Sixty-three patients (F/M = 16/47 pts; 62.33 ± 11.85 years old) with AMI ( NSTEMI/ STEMI 24/39 pts) and successful percutaneous coronary intervention ( PCI) with stent implantation (thrombolysis in myocardial infarction; TIMI 3 flow) were enrolled in this study. All patients underwent baseline two-dimensional conventional echocardiography and STE 3 days (baseline) and 30 days after PCI. All patients were followed up for cardiovascular clinical endpoints, major adverse cardiovascular endpoint ( MACE), and functional status (Canadian Cardiovascular Society and New York Heart Association). Results During the follow-up (31.9 ± 5.1 months), there were 3 cardiovascular deaths, 15 patients had AMI, 2 patients had cerebral infarction, 24 patients reached the MACE. Baseline LV torsion (P = 0.035), but none of the other strain parameters were associated with the time to first unplanned cardiovascular hospitalization. Univariate analysis showed that baseline longitudinal two-chamber and four-chamber strain ( sLa2 0 and sLa4 0) and the same parameters obtained 30 days after the AMI together with transverse four-chamber strain ( sLa2 30, sLa4 30, and sTa4 30) were significantly associated with combined endpoint (MACE). The strongest association in the univariate analysis was found for the baseline sLa2. However, in multivariable analysis only a left ventricular remodeling (LVR - 27% pts) was significantly associated with MACE and strain parameters were not associated with the combined endpoint. Conclusion The assessment of LV function with STE may improve cardiovascular risk prediction in postmyocardial infarction patients. [ABSTRACT FROM AUTHOR]

Introduction Myocardial iron overload leading to congestive heart failure (HF) or arrhythmias is a recognized complication in thalassemia patients undergoing chronic blood transfusion. The relationship between myocardial iron load, subclinical systolic dysfunction, and clinical events remains less well known. Materials and Methods We studied a total of 77 subjects, comprising 37 thalassemia patients (mean age: 24.2 ± 5.5 years) with a history of repeated blood transfusions, in addition to 40 age- and gender-matched controls (mean age: 24 ± 4.5 years). Serum ferritin levels were checked in all subjects, as well as semiautomated quantification of left ventricular ( LV) longitudinal, circumferential, and radial deformations assessed by two-dimensional (2D) speckle tracking analysis. Results Compared with the control group, thalassemia patients showed significantly larger LV mass index and lower myocardial deformations (P < 0.05), but left ventricular ejection fraction ( LVEF) did not differ significantly (P = 0.233). There was a significant linear correlation between serum ferritin level and longitudinal (r = 0.44, P = 0.0078) and radial strain (r = −0.46, P = 0.0051), with optimal cutoff provided to be −15.48%, −21.31%, and 26.67% for longitudinal, circumferential, and radial strain in predicting clinical events, respectively. During a median of 802.5 days follow-up, 11 clinical composites (HF incidence, ventricular tachyarrhythmia, and death) occurred (N = 9 subjects); subjects with composites had significantly reduced longitudinal and radial strain compared to those without (both P < 0.05). After adjusting for age, sex, serum ferritin level, and LV mass index, a worsening of longitudinal strain remained as an independent predictor of clinical events and death ( HR: 6.05, P = 0.033). Conclusion Subclinical systolic dysfunction appears more likely in thalassemia subjects with a history of repeated blood transfusions, which further correlated with serum ferritin levels. In addition, worsening LV myocardial deformation parameters may play an independent role in predicting clinical outcomes beyond traditional measures in this population. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to determine whether the Chronic Kidney Disease Epidemiology Collaboration ( CKD-EPI)- or Cockcroft− Gault ( CG)-based estimated glomerular filtration rates ( eGFRs) performs better in the cohort setting for predicting moderate/advanced chronic kidney disease ( CKD) or end-stage renal disease ( ESRD). Methods A total of 9521 persons in the EuroSIDA study contributed 133 873 eGFRs. Poisson regression was used to model the incidence of moderate and advanced CKD (confirmed eGFR < 60 and < 30 mL/min/1.73 m2, respectively) or ESRD (fatal/nonfatal) using CG and CKD-EPI eGFRs. Results Of 133 873 eGFR values, the ratio of CG to CKD-EPI was ≥ 1.1 in 22 092 (16.5%) and the difference between them ( CG minus CKD-EPI) was ≥ 10 mL/min/1.73 m2 in 20 867 (15.6%). Differences between CKD-EPI and CG were much greater when CG was not standardized for body surface area ( BSA). A total of 403 persons developed moderate CKD using CG [incidence 8.9/1000 person-years of follow-up ( PYFU); 95% confidence interval ( CI) 8.0-9.8] and 364 using CKD-EPI (incidence 7.3/1000 PYFU; 95% CI 6.5-8.0). CG-derived eGFRs were equal to CKD-EPI-derived eGFRs at predicting ESRD ( n = 36) and death ( n = 565), as measured by the Akaike information criterion. CG-based moderate and advanced CKDs were associated with ESRD [adjusted incidence rate ratio ( aIRR) 7.17; 95% CI 2.65-19.36 and aIRR 23.46; 95% CI 8.54-64.48, respectively], as were CKD-EPI-based moderate and advanced CKDs ( aIRR 12.41; 95% CI 4.74-32.51 and aIRR 12.44; 95% CI 4.83-32.03, respectively). Conclusions Differences between e GFRs using CG adjusted for BSA or CKD-EPI were modest. In the absence of a gold standard, the two formulae predicted clinical outcomes with equal precision and can be used to estimate GFR in HIV-positive persons. [ABSTRACT FROM AUTHOR]

Novel treatments for multiple myeloma ( MM) have shown promising results in clinical trials, but the advantage in unselected patients is still unclear. In order to evaluate whether novel therapies impact survival of MM patients, we performed a population-based analysis on data collected by the Modena Cancer Registry from 1989 to 2009. The analysis evaluated 1206 newly diagnosed MM patients collected in the years 1988-96 (conventional therapy), 1997-05 (high dose melphalan and autologous transplant), and 2006-09 (novel agents era). Both relative survival ( RS) and overall survival ( OS) improved over the years, but not equally in the three groups. For patients aged <65 years, RS improved in 1997-05 and 2006-09 compared with previous years and a trend to improvement was observed from 1997-05 to 2006-09. For patients aged 65-74 years, RS improved significantly in 2006-09 compared with 1988-96 and 1997-05. No amelioration was observed for patients 75+ years old. OS confirmed RS. In conclusion, the survival of MM patients aged <65 and, in particular, 65-74 years, has improved over time, especially after 2006. This observation provides circumstantial evidence that novel therapies might impact patient survival. Despite the limits of this study, these data refer to an unselected population, giving a picture of every day clinical practice. [ABSTRACT FROM AUTHOR]

Background Several meta-analyses of the implantable cardioverter-defibrillator (ICD) clinical trials have demonstrated that while men derived a mortality reduction with prophylactic ICD implantation, women did not. These trials also observed that women receive less appropriate ICD shock therapy compared to men. We aimed to investigate this 'gender-paradox' among a heterogeneous community cohort of patients receiving ICDs. Methods We identified 1,445 consecutive patients undergoing ICD implantation from 1997 to 2007. The study population consisted of 582 patients, of whom 291 were women who could be propensity matched to 291 men, based on age, ejection fraction, implantation indication (primary or secondary), etiology of cardiomyopathy (ischemic or nonischemic), and the presence of a cardiac resynchronization therapy-defibrillator (CRT-D) device. The impact of gender difference on the probability of death and appropriate ICD shocks for ventricular arrhythmias was calculated using multivariable Cox proportional hazards analyses. Results During a mean follow-up of 909 ± 901 days, compared to men, women demonstrated a similar risk of death (25% vs 25%, adjusted hazard ratio [AHR] 1.05 [95% confidence interval (CI) 0.81-1.35], P = 0.74). In contrast, women demonstrated a decreased probability of appropriate ICD-shock therapy (14% vs 19%, AHR 0.80 [95% CI 0.59-0.88], P = 0.03) compared to men, and among cohorts with a nonischemic cardiomyopathy (10% vs 20%, P < 0.001) and CRT-D devices (7% vs 19%, P = 0.01). Conclusion Among a community cohort with ICDs, women have a similar mortality compared to men while experiencing less appropriate ICD therapy. These results support the findings of a lower arrhythmic mortality among women. [ABSTRACT FROM AUTHOR]

Objectives Antiretroviral ( ARV) therapy has prolonged the life expectancy of HIV-infected persons, increasing their risk of age-associated diseases, including atherosclerosis ( AS). Decreased risk of AS has been associated with the prevention and control of hypertension ( HTN). We conducted a cohort study of perimenopausal women and older men with or at risk of HIV infection to identify risk factors for incident HTN. Methods Standardized interviews, physical examinations, and laboratory examinations were scheduled at 6-month intervals. Interview data included demographics, medical, family, sexual behaviour and drug use histories, and physical activity. Results There were 330 women and 329 men eligible for inclusion in the study; 27% and 35% of participants developed HTN during a median follow-up period of 1080 and 1071 days, respectively. In gender-stratified analysis, adjusting for traditional HTN risk factors (age, race, body mass index, smoking, diabetes, family history of HTN, alcohol dependence, physical activity and high cholesterol), HIV infection was not associated with incident HTN in women [hazard ratio ( HR) 1.31; 95% confidence interval ( CI) 0.56, 3.06] or men ( HR 1.67; 95% CI 0.75, 3.74). Among HIV-infected women, although exposure to ARVs was not significantly associated with incident HTN ( HR 0.72; 95% CI 0.26, 1.99), CD4 T-cell count was positively associated with incident HTN ( HR 1.15 per 100 cells/μ L; 95% CI 1.03, 1.28). Among physically active HIV-infected men, exposure to ARVs was negatively associated with incident HTN ( HR 0.15; 95% CI 0.03, 0.78). Conclusions HIV infection was not associated with incident HTN in older men or women. This study provides additional evidence supporting a causal relationship between immune function and incident HTN, which warrants further study. [ABSTRACT FROM AUTHOR]

Cardiac Resynchronization Therapy and QRS Axis. Background: Mildly symptomatic heart failure (HF) patients derive substantial clinical benefit from cardiac resynchronization therapy with defibrillator (CRT-D) as shown in MADIT-CRT. The presence of QRS axis deviation may influence response to CRT-D. The objective of this study was to determine whether QRS axis deviation will be associated with differential benefit from CRT-D. Methods : Baseline electrocardiograms of 1,820 patients from MADIT-CRT were evaluated for left axis deviation (LAD: quantitative QRS axis -30 to -90) or right axis deviation (RAD: QRS axis 90-180) in left bundle branch block (LBBB), right bundle branch block (RBBB), and nonspecific interventricular conduction delay QRS morphologies. The primary endpoints were the first occurrence of a HF event or death and the separate occurrence of all-cause mortality as in MADIT-CRT. Results: Among LBBB patients, those with LAD had a higher risk of primary events at 2 years than non-LAD patients (20% vs 16%; P = 0.024). The same was observed among RBBB patients (20% vs 10%; P = 0.05) but not in IVCD patients (22% vs 23%; P = NS). RAD did not convey any increased risk of the primary combined endpoint in any QRS morphology subgroup. When analyzing the benefit of CRT-D in the non-LBBB subgroups, there was no significant difference in hazard ratios for CRT-D versus ICD for either LAD or RAD. However, LBBB patients without LAD showed a trend toward greater benefit from CRT therapy than LBBB patients with LAD (HR for no LAD: 0.37, 95% CI: 0.26-0.53 and with LAD: 0.54, 95% CI: 0.36-0.79; P value for interaction = 0.18). Conclusions: LAD in non-LBBB patients (RBBB or IVCD) is not associated with an increased benefit from CRT. In LBBB patients, those without LAD seem to benefit more from CRT-D than those with LAD. (J Cardiovasc Electrophysiol, Vol. 24, pp. 442-448, April 2013) [ABSTRACT FROM AUTHOR]