Reliability analysis of a newly developed questionnaire for quality control of follow-up visits in polyiran study

Background: The PolyIran study is a large-scale pragmatic cluster randomized controlled trial of fixed-dose combination therapy (Polypill) for prevention of cardiovascular diseases (CVD) in Iran. The PolyIran Quality Control Program (PIQCP) including a new questionnaire was developed to assess the quality of data collection during follow-up visits. The aim of this study was to assess the inter-rater reliability of PIQCP questionnaire. Methods: The study was conducted in 26 (11%) randomly selected clusters (from a total of 236 PolyIran clusters). All participants within these 26 clusters were enrolled. The quality scores were measured according to the PIQCP guidelines by two independent raters. The intraclass correlation coefficients (ICC) were measured. In addition, the quality scores were categorized into good (370%) and poor (<70%). The kappa coefficient was used to assess inter-rater agreement for this categorical quality scores. Results: A total number of 945 PolyIran participants were enrolled of which, 501 (53%) were from intervention arm. In 934 participants (98.8%), the quality score could be successfully identified by both raters. The ICC (95%CI) ofthe overall quality scores was 0.985 (0.983-0.987). It was 0.976 (0.972-0.980) and 0.988 (0.986-0.990) in intervention and control arms, respectively. We found excellent agreement between the two raters in identifying participants with good and poor quality scores (kappa = 0.988, P < 0.001). The kappa values were 0.972 (P < 0.001) and 1.000 (P < 0.001) in intervention and control arms, respectively. Discussion: Our results suggested that the PIQCP questionnaire is a reliable tool for assessing quality of data collection in PolyIran follow-up visits. Using this measure will help us in efficient monitoring of the PolyIran follow-ups and may ensure high quality data. © 2016, Academy of Medical Sciences of I.R. Iran. All rights reserved

Extracellular volume-guided late gadolinium enhancement analysis for non-ischemic cardiomyopathy: The Women's Interagency HIV Study

Background Quantification of non-ischemic myocardial scar remains a challenge due to the patchy diffuse nature of fibrosis. Extracellular volume (ECV) to guide late gadolinium enhancement (LGE) analysis may achieve a robust scar assessment. Methods Three cohorts of 80 non-ischemic-training, 20 non-ischemic-validation, and 10 ischemic-validation were prospectively enrolled and underwent 3.0 Tesla cardiac MRI. An ECV cutoff to differentiate LGE scar from non-scar was identified in the training cohort from the receiver-operating characteristic curve analysis, by comparing the ECV value against the visually-determined presence/absence of the LGE scar at the highest signal intensity (SI) area of the mid-left ventricle (LV) LGE. Based on the ECV cutoff, an LGE semi-automatic threshold of n-times of standard-deviation (n-SD) above the remote-myocardium SI was optimized in the individual cases ensuring correspondence between LGE and ECV images. The inter-method agreement of scar amount in comparison with manual (for non-ischemic) or full-width half-maximum (FWHM, for ischemic) was assessed. Intra- and inter-observer reproducibility were investigated in a randomly chosen subset of 40 non-ischemic and 10 ischemic cases. Results The non-ischemic groups were all female with the HIV positive rate of 73.8% (training) and 80% (validation). The ischemic group was all male with reduced LV function. An ECV cutoff of 31.5% achieved optimum performance (sensitivity: 90%, specificity: 86.7% in training; sensitivity: 100%, specificity: 81.8% in validation dataset). The identified n-SD threshold varied widely (range 3 SD-18 SD), and was independent of scar amount (beta = -0.01, p = 0.92). In the non-ischemic cohorts, results suggested that the manual LGE assessment overestimated scar (%) in comparison to ECV-guided analysis [training: 4.5 (3.2-6.4) vs. 0.92 (0.1-2.1); validation: 2.5 (1.2-3.7) vs. 0.2 (0-1.6); P < 0.01 for both]. Intra- and inter-observer analyses of global scar (%) showed higher reproducibility in ECV-guided than manual analysis with CCC = 0.94 and 0.78 versus CCC = 0.86 and 0.73, respectively (P < 0.01 for all). In ischemic validation, the ECV-guided LGE analysis showed a comparable scar amount and reproducibility with the FWHM. Conclusions ECV-guided LGE analysis is a robust scar quantification method for a non-ischemic cohort. Trial registration ClinicalTrials.gov; NCT00000797, retrospectively-registered 2 November 1999; NCT02501811, registered 15 July 2015.Cardiovascular Aspects of Radiolog

Opium use, cigarette smoking, and alcohol consumption in relation to pancreatic cancer

Background and Aims: Although several studies have suggested opium as a risk factor for cancers of the esophagus, stomach, larynx, lung, and bladder, no previous study has examined the association of opium with pancreatic cancer. We aimed to study the association between opium use and risk of pancreatic cancer in Iran, using a case-control design. We also studied the association of cigarette smoking and alcohol consumption with pancreatic cancer, for which little information was available from this population. Methods: Cases and controls were selected from patients who were referred to 4 endoscopic ultrasound centers in Tehran, Iran. We recruited 316 histopathologically (all adenocarcinoma) and 41 clinically diagnosed incident cases of pancreatic cancer, as well as 328 controls from those with a normal pancreas in enodosonography from January 2011 to January 2015. We used logistic regression models to calculate odds ratios (ORs) and 95 confidence intervals (CIs). Results: After adjustment for potential confounders, opium use (OR 1.91; 95 CI 1.06-3.43) and alcohol consumption (OR 4.16; 95 CI 1.86-9.31) were significantly associated with an increased risk of pancreatic cancer. We did not find an association between ever tobacco smoking and pancreatic cancer risk (OR 0.93; 95 CI 0.62-1.39). Conclusion: In our study, opium use and alcohol consumption were associated with an increased risk of pancreatic cancer, whereas cigarette smoking was not. Copyright © 2016 the Author(s). Published by Wolters Kluwer Health, Inc. All rights reserved

Nonalcoholic fatty liver: The association with metabolic abnormalities, body mass index and central obesity - A population-based study

Background: To assess the prevalence of nonalcoholic fatty liver (NAFL) in Iran and to evaluate correlates of NAFL in categories of body mass index (BMI). Methods: Using a cluster random sampling approach, 7723 subjects over 18 years of age underwent abdominal ultrasonography, laboratory evaluations, blood pressure, and anthropometric measurements and were interviewed to obtain baseline characteristics. Prevalence of NAFL according to BMI and waist to hip ratio and its association with metabolic abnormalities in categories of BMI were assessed in multivariate analysis. Results: The overall prevalence of NAFL was 35.2 95% confidence interval (CI) 34.1-36.3. A significant number of subjects with BMI <30 had NAFL 22.1% (CI 21.0-23.2). Waist to hip ratio for 38.2% (CI 35.6-40.8) of the subjects with NAFL, and BMI <30 was higher than normal values. The odds ratio for association of NAFL and dyslipidemias were higher in subjects with BMI <30 versus those with BMI �30: (1) hypertriglyceridemia: 2.21 vs. 1.57, P=0.006; (2) lower high-density lipoprotein: 1.29 versus 0.98, P=0.046. Higher low-density lipoprotein also revealed greater association with NAFL in subjects with BMI <25 than those with BMI �25 (odds ratio 1.84 vs. 1.1, P=0.015). Conclusions: NAFL shows stronger association with central obesity compared to high BMI. NAFL has stronger association with dyslipidemias in subjects with low compared with high BMI. © Mary Ann Liebert, Inc. 2015

Immune responses to hepatitis B immunization 10–18 years after primary vaccination: a population-based cohort study

We evaluated the immune response to neonatal HBV immunization in children of infected parents 10–18 years after primary vaccination. Healthy individuals immunized with an infantile course of three doses of HBV vaccine were tested for persistence of anti-HB surface antibody (HBsAb). Those with an HBsAb level of <10 IU/mL received a booster dose of the vaccine with subsequent doses to those without protective titres. HBsAb concentrations were determined 4 weeks after each dose of the booster vaccine. The data were analysed separately for three age groups: 10–11, 12–14 and 15–18 years old. A total of 541 healthy individuals were studied. The highest seroprotection rate of 48% was observed in the youngest vaccinees (10–11 years old). This declined to 26.5% in the oldest (15–18 years old) group (P = 0.008). The youngest vaccinees showed the highest rate of anamnestic immune responses (96%). However, 25% of oldest individuals failed to mount an anamnestic immune response in challenge with a booster dose of the vaccine (P = 0.005), suggesting waning immunity with increasing age. Age (OR: 0.80; P = 0.01) and prebooster HBsAb levels (OR: 0.37; P = 0.01) identified responders to first booster doses of the vaccine by logistic regression analysis. The majority of high-risk vaccinees showed anamnestic immune response 10–11 years after primary immunization. However, we found a significant proportion (25%) of older individuals with no anamnetic response, which suggests a waning of immune memory. Detailed long-term follow-up studies are necessary to determine the risk of natural infection among these individuals before a booster schedule can be recommended. © 2016 John Wiley & Sons Lt

Ischemia and No Obstructive Stenosis (INOCA) at CT Angiography, CT Myocardial Perfusion, Invasive Coronary Angiography, and SPECT: The CORE320 Study

Background: CT allows evaluation of atherosclerosis, coronary stenosis, and myocardial ischemia. Data on the characterization of ischemia and no obstructive stenosis (INOCA) at CT remain limited.Purpose: This was an observational study to describe the prevalence of INOCA defined at coronary CT angiography with CT perfusion imaging and associated clinical and atherosclerotic characteristics. The analysis was also performed for the combination of invasive coronary angiography (ICA) and SPECT as a secondary aim.Materials and Methods: The prospective CORE320 study (ClinicalTrials.gov: NCT00934037) enrolled participants between November 2009 and July 2011 who were symptomatic and referred for clinically indicated ICA. Participants underwent CT angiography, rest-adenosinestress CT perfusion, and rest-stress SPECT prior to ICA. For this ancillary study, the following three phenotypes were considered, using either CT angiography/CT perfusion or ICA/SPECT data: (a) participants with obstructive (>= 50%) stenosis, (b) participants with no obstructive stenosis but ischemia (ie, INOCA) on the basis of abnormal perfusion imaging results, and (c) participants with no obstructive stenosis and normal perfusion imaging results. Clinical characteristics and CT angiography athero-scleroticplaque measures were compared by using the Pearson chi(2) or Wilcoxon rank-sum test.Results: A total of 381 participants (mean age, 62 years [interquartile range, 56-68 years]; 129 [34%] women) were evaluated. A total of 31 (27%) of 115 participants without obstructive (>= 50%) stenosis at CT angiography had abnormal CT perfusion findings. The corresponding value for ICA/SPECT was 45 (30%) of 151. The prevalence of INOCA was 31 (8%) of 381 (95% confidence interval [CI]: 5%, 11%) with CT angiography/CT perfusion and 45 (12%) of 381 (95% CI: 9%, 15%) with ICA/SPECT. Participants with CT-defined INOCA had greater total atheroma volume (118 vs 60 mm(3), P =.008), more positive remodeling (13% vs 1%, P =.006), and greater low-attenuation atheroma volume (20 vs 10 mm(3), P =.007) than participants with no obstructive stenosis and no ischemia. Comparisons for ICA/SPECT showed similar trends.Conclusion: In CORE320, ischemia and no obstructivestenosis (INOCA) prevalence was 8% and 12% at CT angiography/CT perfusion and invasive coronary angiography/SPECT, respectively. Participants with INOCA had greater atherosclerotic burden and more adverse plaque features at CT compared with those with no obstructive stenosis and no ischemia. (C) RSNA, 2019Cardiolog

Diagnostic accuracy of semi-automatic quantitative metrics as an alternative to expert reading of CT myocardial perfusion in the CORE320 study

Cardiolog

Intracoronary ALLogeneic heart STem cells to Achieve myocardial Regeneration (ALLSTAR): A randomized, placebo-controlled, double-blinded trial

Aims Cardiosphere-derived cells (CDCs) are cardiac progenitor cells that exhibit disease-modifying bioactivity in various models of cardiomyopathy and in previous clinical studies of acute myocardial infarction (MI), dilated cardiomyopathy, and Duchenne muscular dystrophy. The aim of the study was to assess the safety and efficacy of intracoronary administration of allogeneic CDCs in the multicentre, randomized, double-blinded, placebo-controlled, intracoronary ALLogeneic heart STem cells to Achieve myocardial Regeneration (ALLSTAR) trial. Methods and We enrolled patients 4 weeks to 12 months after MI, with left ventricular ejection fraction (LVEF) &lt;_45% and LV results scar size &gt;_15% of LV mass by magnetic resonance imaging (MRI). A pre-specified interim analysis was performed when 6-month MRI data were available. The trial was subsequently stopped due to the low probability of detecting a significant treatment effect of CDCs based on the primary endpoint. Patients were randomly allocated in a 2:1 ratio to receive CDCs or placebo in the infarct-related artery by stop-flow technique. The primary safety endpoint was the occurrence, during 1-month post-intracoronary infusion, of acute myocarditis attributable to allogeneic CDCs, ventricular tachycardia- or ventricular fibrillation-related death, sudden unexpected death, or a major adverse cardiac event (death or hospitalization for heart failure or non-fatal MI or need for left ventricular assist device or heart transplant). The primary efficacy endpoint was the relative percentage change in infarct size at 12 months post-infusion as assessed by contrast-enhanced cardiac MRI. We randomly allocated 142 eligible patients of whom 134 were treated (90 to the CDC group and 44 to the placebo group). The mean baseline LVEF was 40% and the mean scar size was 22% of LV mass. No primary safety endpoint events occurred. There was no difference in the percentage change from baseline in scar size (P = 0.51) between CDCs and placebo groups at 6 months. Compared with placebo, there were significant reductions in LV end-diastolic volume (P = 0.02), LV end-systolic volume (P = 0.02), and N-terminal pro b-type natriuretic peptide (NT-proBNP) (P = 0.02) at 6 months in CDC-treated patients. Conclusion Intracoronary infusion of allogeneic CDCs in patients with post-MI LV dysfunction was safe but did not reduce scar size relative to placebo at 6 months. Nevertheless, the reductions in LV volumes and NT-proBNP reveal disease-modifying bioactivity of CDCs. © 2020 Oxford University Press. All rights reserved

Polypill for the prevention of cardiovascular disease (PolyIran): Study design and rationale for a pragmatic cluster randomized controlled trial

Background The complexity of treatment regimens, costs and pill burden decrease the medication adherence and contribute to shortfall in cardiovascular preventive drug coverage. The polypill, a fixed dose combination pill of established drugs, is expected to increase adherence and reduce the costs whilst preventing major cardiovascular events (MCVE). Design and methods The PolyIran trial is a pragmatic cluster randomized trial nested within the Golestan Cohort Study (GCS). Subjects were randomized to either non-pharmacological preventive interventions alone (minimal care arm) or together with a polypill (polypill arm) comprising hydrochlorothiazide, aspirin, atorvastatin and either enalapril or valsartan. This study benefits from the infrastructure of the primary health care system in Iran and the interventions are delivered by the local auxiliary health workers (Behvarz) to the participants. The primary outcome of the study is the occurrence of first MCVE within five years defined as non-fatal and fatal myocardial infarction, unstable angina, sudden death, heart failure, coronary artery revascularization procedures, and non-fatal and fatal stroke. Trial status From February 2011 to April 2013, 8410 individuals (236 clusters) attended the eligibility assessment. Of those, 3421 in the polypill arm and 3417 in the minimal care arm were eligible. The study is ongoing. Conclusion The infrastructure of GCS and the primary health care system in Iran enabled the conduct of this pragmatic large-scale trial. If the polypill strategy proves effective, it may be implemented to prevent cardiovascular disease in developing countries. © European Society of Cardiology 2014

Patient Preferences for Coronary CT Angiography with Stress Perfusion, SPECT, or Invasive Coronary Angiography

Cardiovascular Aspects of Radiolog