Objectives This study sought to determine the accuracy of 3-dimensional, quantitative measurements of coronary plaque by computed tomography angiography (CTA) against intravascular ultrasound with ...radiofrequency backscatter analysis (IVUS/VH). Background Quantitative, 3-dimensional coronary CTA plaque measurements have not been validated against IVUS/VH. Methods Sixty patients in a prospective study underwent coronary X-ray angiography, IVUS/VH, and coronary CTA. Plaque geometry and composition was quantified after spatial coregistration on segmental and slice-by-slice bases. Correlation, mean difference, and limits of agreement were determined. Results There was significant correlation for all pre-specified parameters by segmental and slice-by-slice analyses (r = 0.41 to 0.84; all p < 0.001). On a segmental basis, CTA underestimated minimal lumen diameter by 21% and overestimated diameter stenosis by 39%. Minimal lumen area was overestimated on CTA by 27% but area stenosis was only underestimated by 5%. Mean difference in noncalcified plaque volume and percent and calcified plaque volume and percent were 38%, −22%, 104%, and 64%. On a slice-by-slice basis, lumen, vessel, noncalcified-, and calcified-plaque areas were overestimated on CTA by 22%, 19%, 44%, and 88%. There was significant correlation for percentage of atheroma volume (0.52 vs. 0.54; r = 0.51; p < 0.001). Compositional analysis suggested that high-density noncalcified plaque on CTA best correlated with fibrous tissue and low-density noncalcified plaque correlated with necrotic core plus fibrofatty tissue by IVUS/VH. Conclusions This is the first validation that standardized, 3-dimensional, quantitative measurements of coronary plaque correlate with IVUS/VH. Mean differences are small, whereas limits of agreement are wide. Low-density noncalcified plaque correlates with necrotic core plus fibrofatty tissue on IVUS/VH.
The objective of this study was to compare the diagnostic accuracy of quantitative coronary angiography (QCA), coronary computed tomography angiography (CTA), and intravascular ultrasound (IVUS) with ...fractional flow reserve (FFR) measurements. Eighty-five lesions (40% to 99% diameter stenosis) in 85 patients were prospectively interrogated by QCA, CTA, IVUS, and FFR. Minimal lumen diameter (MLD), percent diameter stenosis (%DS), minimal lumen area (MLA), and percent area stenosis (%AS) were measured. Correlation, receiver operating characteristic analysis, kappa statistics, and multivariable logistic regression was used to assess relation between anatomic measurements and FFR. Average age was 61.3 ± 7.8; 62% were men. QCA-derived mean %DS was 55.3% ± 19.5%; mean FFR 0.81 ± 0.17; 27% had FFR ≤0.75. QCA had the strongest correlation, followed by CTA and then IVUS for MLD (r = 0.67, 0.47, and 0.29, respectively) and for %DS (r = −0.63, −0.52, and −0.22, respectively); QCA-derived MLD had area under the curve of 0.96, with 95% sensitivity and 82% specificity. Cut-point, area under the curve, sensitivity, and specificity for CTA-MLA and IVUS-MLA were 3.11 mm2 , 0.86, 81%, and 81% and 2.68 mm2 , 0.75, 70%, and 80%. In multivariable analysis for each modality, MLD on QCA (odds ratio OR: 0.002), %AS on CTA (OR: 1.09) and MLA on IVUS (OR: 0.28) remained independent predictors. In conclusion, in intermediate-to-severe lesions, QCA-, CTA-, and IVUS-derived quantitative anatomic measurements correlated with FFR. CTA-derived cut-points were similar to respective measurements on QCA and IVUS and had similar or better diagnostic performance compared with IVUS.
Objective Under Food and Drug Administration investigational device exemption, the Prospective Randomized On-X Anticoagulation Clinical Trial (PROACT) has been testing the safety of less aggressive ...anticoagulation than recommended by the American College of Cardiology/American Heart Association guidelines after implantation of an approved bileaflet mechanical valve. Methods In this first limb of the PROACT, patients with elevated risk factors for thromboembolism were randomized at 33 US centers to receive lower dose warfarin (test international normalized ratio INR, 1.5-2.0) or continue standard warfarin (control INR, 2.0-3.0), 3 months after mechanical aortic valve replacement. The INR was adjusted by home monitoring; all patients received 81 mg aspirin daily. Adverse events were independently adjudicated. Results A total of 375 aortic valve replacement patients were randomized into control (n = 190) and test (n = 185) groups from September 2006 to December 2009. The mean age ± standard deviation was 55.2 ± 12.5 years; 79% were men; and 93% were in sinus rhythm preoperatively. Calcific degeneration was present in 67%; active endocarditis was excluded. Concomitant procedures included coronary artery bypass grafting (27%), aortic aneurysm repair (14%), and other (25%). The follow-up duration averaged 3.82 years (755.7 patient-years pt-yrs for control; 675.2 pt-yrs for test). The mean INR was 2.50 ± 0.63 for the control and 1.89 ± 0.49 for the test groups ( P < .0001). The test group experienced significantly lower major (1.48% vs 3.26%/pt-yr; P = .047) and minor (1.32% vs 3.41%/pt-yr; P = .021) bleeding rates. The incidence of stroke, transient ischemic attack, total neurologic events, and all-cause mortality were similar between the 2 groups. Conclusions INR can be safely maintained between 1.5 and 2.0 after aortic valve replacement with this approved bileaflet mechanical prosthesis. With low-dose aspirin, this resulted in a significantly lower risk of bleeding, without a significant increase in thromboembolism.
Summary Background Whether the addition of radiation therapy (RT) improves overall survival in men with locally advanced prostate cancer managed with androgen deprivation therapy (ADT) is unclear. ...Our aim was to compare outcomes in such patients with locally advanced prostate cancer. Methods Patients with: locally advanced (T3 or T4) prostate cancer (n=1057); or organ-confined disease (T2) with either a prostate-specific antigen (PSA) concentration more than 40 ng/mL (n=119) or PSA concentration more than 20 ng/mL and a Gleason score of 8 or higher (n=25), were randomly assigned (done centrally with stratification and dynamic minimisation, not masked) to receive lifelong ADT and RT (65–69 Gy to the prostate and seminal vesicles, 45 Gy to the pelvic nodes). The primary endpoint was overall survival. The results presented here are of an interim analysis planned for when two-thirds of the events for the final analysis were recorded. All efficacy analyses were done by intention to treat and were based on data from all patients. This trial is registered at controlledtrials.com as ISRCTN24991896 and Clinicaltrials.gov as NCT00002633. Results Between 1995 and 2005, 1205 patients were randomly assigned (602 in the ADT only group and 603 in the ADT and RT group); median follow-up was 6·0 years (IQR 4·4–8·0). At the time of analysis, a total of 320 patients had died, 175 in the ADT only group and 145 in the ADT and RT group. The addition of RT to ADT improved overall survival at 7 years (74%, 95% CI 70–78 vs 66%, 60–70; hazard ratio HR 0·77, 95% CI 0·61–0·98, p=0·033). Both toxicity and health-related quality-of-life results showed a small effect of RT on late gastrointestinal toxicity (rectal bleeding grade >3, three patients (0·5%) in the ADT only group, two (0·3%) in the ADT and RT group; diarrhoea grade >3, four patients (0·7%) vs eight (1·3%); urinary toxicity grade >3, 14 patients (2·3%) in both groups). Interpretation The benefits of combined modality treatment—ADT and RT—should be discussed with all patients with locally advanced prostate cancer. Funding Canadian Cancer Society Research Institute, US National Cancer Institute, and UK Medical Research Council.
Substantial changes are needed to achieve a more targeted and strategic approach to investment in the response to the HIV/AIDS epidemic that will yield long-term dividends. Until now, advocacy for ...resources has been done on the basis of a commodity approach that encouraged scaling up of numerous strategies in parallel, irrespective of their relative effects. We propose a strategic investment framework that is intended to support better management of national and international HIV/AIDS responses than exists with the present system. Our framework incorporates major efficiency gains through community mobilisation, synergies between programme elements, and benefits of the extension of antiretroviral therapy for prevention of HIV transmission. It proposes three categories of investment, consisting of six basic programmatic activities, interventions that create an enabling environment to achieve maximum effectiveness, and programmatic efforts in other health and development sectors related to HIV/AIDS. The yearly cost of achievement of universal access to HIV prevention, treatment, care, and support by 2015 is estimated at no less than US$22 billion. Implementation of the new investment framework would avert 12·2 million new HIV infections and 7·4 million deaths from AIDS between 2011 and 2020 compared with continuation of present approaches, and result in 29·4 million life-years gained. The framework is cost effective at $1060 per life-year gained, and the additional investment proposed would be largely offset from savings in treatment costs alone.
Atrial fibrillation (AF) is a leading cause of total and fatal ischemic stroke. Stroke risk after AF ablation appears to be favorably affected; however, it is largely unknown whether the benefit ...extends to all stroke CHADS2 risk profiles of AF patients.
To determine if ablation of atrial fibrillation reduces stroke rates in all risk groups.
A total of 4212 consecutive patients who underwent AF ablation were compared (1:4) with 16,848 age-/sex-matched controls with AF (no ablation) and to 16,848 age-/sex-matched controls without AF. Patients were enrolled from the large ongoing prospective Intermountain Atrial Fibrillation Study and were followed for at least 3 years.
Of the 37,908 patients, the mean age was 65.0 ± 13 years and 4.4% (no AF), 6.3% (AF, no ablation), and 4.5% (AF ablation) patients had a prior stroke (P < .0001). The profile of CHADS2 scores between comparative groups was similar: 0-1 (69.3%, no AF; 62.3%, AF, no ablation; 63.6%, AF ablation), 2-3 (26.5%, no AF; 29.7%, AF, no ablation; 28.7%, AF ablation), and ≥4 (4.3%, no AF; 8.0%, AF, no ablation; 7.7%, AF ablation). A total of 1296 (3.4%) patients had a stroke over the follow-up period. Across all CHADS2 profiles and ages, AF patients with ablation had a lower long-term risk of stroke compared to patients without ablation. Furthermore, AF ablation patients had similar long-term risks of stroke across all CHADS2 profiles and ages compared to patients with no history of AF.
In our study populations, AF ablation patients have a significantly lower risk of stroke compared to AF patients who do not undergo ablation independent of baseline stroke risk score.
The mechanisms behind the association of atrial fibrillation (AF) and dementia are unknown. One possibility is that exposure to chronic microembolism or microbleeds results in repetitive cerebral ...injury that is manifest by cognitive decline.
The purpose of this study was to test the hypothesis that AF patients with a low percentage of time in the therapeutic range (TTR) are at higher risk for dementia due to under- or overanticoagulation.
Patients anticoagulated with warfarin (target international normalized ratio INR 2-3), managed by the Intermountain Healthcare Clinical Pharmacist Anticoagulation Service with no history of dementia or stroke/transient ischemic attack, were included in the study. The primary outcome was dementia incidence defined by ICD-9 codes. Percent time in TTR was calculated using the method of linear interpolation and stratified as >75%, 51%-75%, 26%-50%, and ≤25%. Multivariable Cox hazard regression was used to determine dementia incidence by percentage categories of TTR.
A total of 2605 patients (age 73.7 ± 10.8 years, 1408 54.0% male) were studied. The CHADS2 score distribution was 0: 216 (8.3%); 1: 579 (22.2%); 2: 859(33.0%); 3: 708 (27.2%); and ≥4: 243 (9.3%). The percent TTR averaged 63.1 ± 21.3, with percent INR <2.0: 25.6% ± 17.9% and percent INR >3.0: 16.2% ± 13.6%. Dementia was diagnosed in 109 patients (4.2%) (senile: 37 1.4%; vascular: 8 0.3%; Alzheimer: 64 (2.5%). After adjustment, decreasing categories of percent TTR were associated with increased dementia risk (vs >75%): <25%: hazard ratio (HR) 5.34, P < .0001; 26%-50%: HR 4.10, P < .0001; and 51%-75%: HR = 2.57, P = .001.
Quality of anticoagulation management represented as percent TTR among AF patients without dementia was associated with dementia incidence. These data support the possibility of chronic cerebral injury as a mechanism that underlies the association of AF and dementia.
Colorectal Cancer Screening provides a complete overview of colorectal cancer screening, from epidemiology and molecular abnormalities, to the latest screening techniques such as stool DNA and FIT, ...Computerized Tomography (CT) Colonography, High Definition Colonoscopes and Narrow Band Imaging. As the text is devoted entirely to CRC screening, it features many facts, principles, guidelines and figures related to screening in an easy access format. This volume provides a complete guide to colorectal cancer screening which will be informative to the subspecialist as well as the primary care practitioner. It represents the only text that provides this up to date information about a subject that is continually changing. For the primary practitioner, information on the guidelines for screening as well as increasing patient participation is presentedd. For the subspecialist, information regarding the latest imaging techniques as well as flat adenomas and chromoendoscopy are covered. The section on the molecular changes in CRC will appeal to both groups. The text includes up to date information about colorectal screening that encompasses the entire spectrum of the topic and features photographs of polyps as well as diagrams of the morphology of polyps as well as photographs of CT colonography images. Algorithms are presented for all the suggested guidelines. Chapters are devoted to patient participation in screening and risk factors as well as new imaging technology. This useful volume explains the rationale behind screening for CRC. In addition, it covers the different screening options as well as the performance characteristics, when available in the literature, for each test. This volume will be used by the sub specialists who perform screening tests as well as primary care practitioners who refer patients to be screened for colorectal cancer.
Summary Background Emergence of artemisinin resistance in southeast Asia poses a serious threat to the global control of Plasmodium falciparum malaria. Discovery of the K13 marker has transformed ...approaches to the monitoring of artemisinin resistance, allowing introduction of molecular surveillance in remote areas through analysis of DNA. We aimed to assess the spread of artemisinin-resistant P falciparum in Myanmar by determining the relative prevalence of P falciparum parasites carrying K13-propeller mutations. Methods We did this cross-sectional survey at malaria treatment centres at 55 sites in ten administrative regions in Myanmar, and in relevant border regions in Thailand and Bangladesh, between January, 2013, and September, 2014. K13 sequences from P falciparum infections were obtained mainly by passive case detection. We entered data into two geostatistical models to produce predictive maps of the estimated prevalence of mutations of the K13 propeller region across Myanmar. Findings Overall, 371 (39%) of 940 samples carried a K13-propeller mutation. We recorded 26 different mutations, including nine mutations not described previously in southeast Asia. In seven (70%) of the ten administrative regions of Myanmar, the combined K13-mutation prevalence was more than 20%. Geospatial mapping showed that the overall prevalence of K13 mutations exceeded 10% in much of the east and north of the country. In Homalin, Sagaing Region, 25 km from the Indian border, 21 (47%) of 45 parasite samples carried K13-propeller mutations. Interpretation Artemisinin resistance extends across much of Myanmar. We recorded P falciparum parasites carrying K13-propeller mutations at high prevalence next to the northwestern border with India. Appropriate therapeutic regimens should be tested urgently and implemented comprehensively if spread of artemisinin resistance to other regions is to be avoided. Funding Wellcome Trust–Mahidol University–Oxford Tropical Medicine Research Programme and the Bill & Melinda Gates Foundation.
Objective
Observational studies point to an inverse correlation between low‐density lipoprotein (LDL) cholesterol levels and risk of intracerebral hemorrhage (ICH), but it remains unclear whether ...this association is causal. We tested the hypothesis that genetically elevated LDL is associated with reduced risk of ICH.
Methods
We constructed one polygenic risk score (PRS) per lipid trait (total cholesterol, LDL, high‐density lipoprotein HDL, and triglycerides) using independent genomewide significant single nucleotide polymorphisms (SNPs) for each trait. We used data from 316,428 individuals enrolled in the UK Biobank to estimate the effect of each PRS on its corresponding trait, and data from 1,286 ICH cases and 1,261 matched controls to estimate the effect of each PRS on ICH risk. We used these estimates to conduct Mendelian Randomization (MR) analyses.
Results
We identified 410, 339, 393, and 317 lipid‐related SNPs for total cholesterol, LDL, HDL, and triglycerides, respectively. All four PRSs were strongly associated with their corresponding trait (all p < 1.00 × 10‐100). While one SD increase in the PRSs for total cholesterol (odds ratio OR = 0.92; 95% confidence interval CI = 0.85–0.99; p = 0.03) and LDL cholesterol (OR = 0.88; 95% CI = 0.81–0.95; p = 0.002) were inversely associated with ICH risk, no significant associations were found for HDL and triglycerides (both p > 0.05). MR analyses indicated that 1mmol/L (38.67mg/dL) increase of genetically instrumented total and LDL cholesterol were associated with 23% (OR = 0.77; 95% CI = 0.65–0.98; p = 0.03) and 41% lower risks of ICH (OR = 0.59; 95% CI = 0.42–0.82; p = 0.002), respectively.
Interpretation
Genetically elevated LDL levels were associated with lower risk of ICH, providing support for a potential causal role of LDL cholesterol in ICH. ANN NEUROL 2020 ANN NEUROL 2020;88:56–66
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