Factors Affecting Blood Pressure Variability: Lessons Learned from Two Systematic Reviews of Randomized Controlled Trials

Systematic reviews can often reveal much more than the original objective of the work. The objectives of this retrospective analysis were to answer three basic questions about blood pressure variability: 1) Does blood pressure entry criterion have an effect on baseline blood pressure variability? 2) Do thiazide diuretics have a significant effect on blood pressure variability? and 3) Does systolic blood pressure vary to the same degree as diastolic blood pressure? This analysis of blood pressure variability is based on resting standardized research setting BP readings from two systematic reviews evaluating blood pressure lowering efficacy of thiazide diuretics from double blind randomized controlled trials in 33,611 patients with primary hypertension. The standard deviation reported in trials was the focus of the research and the unit of analysis. When a threshold systolic or diastolic blood pressure value is used to determine entry into a trial, baseline variability is significantly decreased, systolic from 14.0 to 9.3 mmHg and diastolic from 8.4 to 5.3 mmHg. Thiazides do not change BP variability as the standard deviation and coefficient of variation of systolic blood pressure and diastolic blood pressure did not differ between thiazide and placebo groups at end of treatment. The coefficient of variation of systolic blood pressure was significantly greater than the coefficient of variation of diastolic blood pressure. Entry criterion decreases the baseline blood pressure variability. Treatment with a thiazide diuretic does not affect blood pressure variability. Systolic blood pressure varies to a greater degree than diastolic blood pressure

Acute myocardial infarction incidence and hospital mortality: routinely collected national data versus linkage of national registers

Background and Objective To compare levels of and trends in incidence and hospital mortality of first acute myocardial infarction (AMI) based on routinely collected hospital morbidity data and on linked registers. Cases taken from routine hospital data are a mix of patients with recurrent and first events, and double counting occurs when cases are admitted for an event several times during 1 year. By linkage of registers, recurrent events and double counts can be excluded. Study Design and Setting In 1995 and 2000, 28,733 and 25,864 admissions for AMI were registered in the Dutch national hospital discharge register. Linkage with the population register yielded 21,565 patients with a first AMI in 1995 and 20,414 in 2000. Results In 1995 and 2000, the incidence based on the hospital register was higher than based on the linked registers in men (22% and 23% higher) and women (18% and 20% higher). In both years, hospital mortality based on the hospital register and on linked registers was similar. The decline in incidence between 1995 and 2000 was comparable whether based on standard hospital register data or linked data (18% and 20% in men, 15% and 17% in women). Similarly, the decline in hospital mortality was comparable using either approach (11% and 9% in both men and women). Conclusion Although the incidence based on routine hospital data overestimates the actual incidence of first AMI based on linked registers, hospital mortality and trends in incidence and hospital mortality are not changed by excluding recurrent events and double counts. Since trends in incidence and hospital mortality of AMI are often based on national routinely collected data, it is reassuring that our results indicate that findings from such studies are indeed valid and not biased because of recurrent events and double counts

Microparticles from patients with metabolic syndrome induce vascular hypo-reactivity via Fas/Fas-ligand pathway in mice

Peer reviewedPublisher PD

Mortality in Dutch hospitals: Trends in time, place and cause of death after admission for myocardial infarction and stroke. An observational study

<p>Abstract</p> <p>Background</p> <p>Patterns in time, place and cause of death can have an important impact on calculated hospital mortality rates. Objective is to quantify these patterns following myocardial infarction and stroke admissions in Dutch hospitals during the period 1996–2003, and to compare trends in the commonly used 30-day in-hospital mortality rates with other types of mortality rates which use more extensive follow-up in time and place of death.</p> <p>Methods</p> <p>Discharge data for all Dutch admissions for index conditions (1996–2003) were linked to the death certification registry. Then, mortality rates within the first 30, 90 and 365 days following admissions were analyzed for deaths occurring within and outside hospitals.</p> <p>Results</p> <p>Most deaths within a year after admission occurred within 30 days (60–70%). No significant trends in this distribution of deaths over time were observed. Significant trends in the distribution over place of death were observed for both conditions. For myocardial infarction, the proportion of deaths after transfer to another hospital has doubled from 1996–2003. For stroke a significant rise of the proportion of deaths outside hospital was found. For MI the proportion of deaths attributed to a circulatory disease has significantly fallen ovtime. Seven types of hospital mortality indicators, different in scope and observation period, all show a drop of hospital mortality for both MI and stroke over the period 1996–2003. For stroke the observed absolute reduction in death rate increases for the first year after admission, for MI the observed drop in 365-day overall mortality almost equals the observed drop in 30-day in hospital mortality over 1996–2003.</p> <p>Conclusion</p> <p>Changes in the timing, place and causes of death following admissions for myocardial infarction and stroke have important implications for the definitions of in-hospital and post-admission mortality rates as measures of hospital performance. Although necessary for understanding mortality patterns over time, including within mortality rates deaths which occur outside hospitals and after longer periods following index admissions remain debatable and may not reflect actual hospital performance but probably mirrors transfer, efficiency, and other health care policies.</p

Diagnostic accuracy of contrast-enhanced MR angiography in severe carotid stenosis: meta-analysis with metaregression of different techniques

Contrast-enhanced magnetic resonance angiography (CE-MRA) has become a well-established noninvasive imaging method for the assessment of severe carotid stenosis (70–99% by NASCET criteria). However, CE-MRA is not a standardised technique, but encompasses different concurrent techniques. This review analyses possible differences. A bivariate random effects meta-analysis of 17 primary diagnostic accuracy studies confirmed a high pooled sensitivity of 94.3% and specificity of 93.0% for carotid CE-MRA in severe carotid stenosis. Sensitivity was fairly uniform among the studies, while specificity showed significant variation (I2 = 73%). Metaregressions found significant differences for specificity with two covariates: specificity was higher when using not only maximum intensity projection (MIP) images, but also three-dimensional (3D) images (P = 0.01). Specificity was also higher with electronic images than with hardcopies (P = 0.02). The timing technique (bolus-timed, fluoroscopically triggered or time-resolved) did not result in any significant differences in diagnostic accuracy. Some nonsignificant trends were found for the percentages of severe carotid disease, acquisition time and voxel size. In conclusion, in CE-MRA of severe carotid stenosis the three major timing techniques yield comparably high diagnostic accuracy, electronic images are more specific than hardcopies, and 3D images should be used in addition to MIP images to increase the specificity

Rapid Analysis of Vessel Elements (RAVE): A Tool for Studying Physiologic, Pathologic and Tumor Angiogenesis

Quantification of microvascular network structure is important in a myriad of emerging research fields including microvessel remodeling in response to ischemia and drug therapy, tumor angiogenesis, and retinopathy. To mitigate analyst-specific variation in measurements and to ensure that measurements represent actual changes in vessel network structure and morphology, a reliable and automatic tool for quantifying microvascular network architecture is needed. Moreover, an analysis tool capable of acquiring and processing large data sets will facilitate advanced computational analysis and simulation of microvascular growth and remodeling processes and enable more high throughput discovery. To this end, we have produced an automatic and rapid vessel detection and quantification system using a MATLAB graphical user interface (GUI) that vastly reduces time spent on analysis and greatly increases repeatability. Analysis yields numerical measures of vessel volume fraction, vessel length density, fractal dimension (a measure of tortuosity), and radii of murine vascular networks. Because our GUI is open sourced to all, it can be easily modified to measure parameters such as percent coverage of non-endothelial cells, number of loops in a vascular bed, amount of perfusion and two-dimensional branch angle. Importantly, the GUI is compatible with standard fluorescent staining and imaging protocols, but also has utility analyzing brightfield vascular images, obtained, for example, in dorsal skinfold chambers. A manually measured image can be typically completed in 20 minutes to 1 hour. In stark comparison, using our GUI, image analysis time is reduced to around 1 minute. This drastic reduction in analysis time coupled with increased repeatability makes this tool valuable for all vessel research especially those requiring rapid and reproducible results, such as anti-angiogenic drug screening

Meta-DiSc: a software for meta-analysis of test accuracy data

BACKGROUND: Systematic reviews and meta-analyses of test accuracy studies are increasingly being recognised as central in guiding clinical practice. However, there is currently no dedicated and comprehensive software for meta-analysis of diagnostic data. In this article, we present Meta-DiSc, a Windows-based, user-friendly, freely available (for academic use) software that we have developed, piloted, and validated to perform diagnostic meta-analysis. RESULTS: Meta-DiSc a) allows exploration of heterogeneity, with a variety of statistics including chi-square, I-squared and Spearman correlation tests, b) implements meta-regression techniques to explore the relationships between study characteristics and accuracy estimates, c) performs statistical pooling of sensitivities, specificities, likelihood ratios and diagnostic odds ratios using fixed and random effects models, both overall and in subgroups and d) produces high quality figures, including forest plots and summary receiver operating characteristic curves that can be exported for use in manuscripts for publication. All computational algorithms have been validated through comparison with different statistical tools and published meta-analyses. Meta-DiSc has a Graphical User Interface with roll-down menus, dialog boxes, and online help facilities. CONCLUSION: Meta-DiSc is a comprehensive and dedicated test accuracy meta-analysis software. It has already been used and cited in several meta-analyses published in high-ranking journals. The software is publicly available at

Estimating the Accuracy of Anal Cytology in the Presence of an Imperfect Reference Standard

Background: The study aim is to estimate sensitivity and specificity of anal cytology for histologic HSIL in analyses adjusted for the imperfect biopsy reference standard. Methods and Principal Findings: Retrospective cohort study of an anal dysplasia screening program for HIV infected adults. We estimated the prevalence of histologic HSIL by concurrent cytology category and the associated cytology ROC area. Cytology operating characteristics for HSIL were estimated and adjusted for the imperfect reference standard by 3 methodologies. The study cohort included 261 patients with 3 available measures: (1) referral cytology; (2) HRA cytology; and (3) HRA directed biopsy. The prevalence of biopsy HSIL varied according to the concurrent HRA cytology result: 64.5

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation