Directed functional connectivity using dynamic graphical models.

There are a growing number of neuroimaging methods that model spatio-temporal patterns of brain activity to allow more meaningful characterizations of brain networks. This paper proposes dynamic graphical models (DGMs) for dynamic, directed functional connectivity. DGMs are a multivariate graphical model with time-varying coefficients that describe instantaneous directed relationships between nodes.

Application of a novel tool for diagnosing bile acid diarrhoea.

Bile acid diarrhoea (BAD) is a common disease that requires expensive imaging to diagnose. We have tested the efficacy of a new method to identify BAD, based on the detection of differences in volatile organic compounds (VOC) in urine headspace of BAD vs. ulcerative colitis and healthy controls.

Severity of bias of a simple estimator of the causal odds ratio in Mendelian randomization studies.

Mendelian randomization studies estimate causal effects using genetic variants as instruments. Instrumental variable methods are straightforward for linear models, but epidemiologists often use odds ratios to quantify effects. Also, odds ratios are often the quantities reported in meta-analyses.

Is MRI better than CT for detecting a vascular component to dementia? A systematic review and meta-analysis.

Background: Identification of causes of dementia soon after symptom onset is important, because appropriate treatment of some causes of dementia can slow or halt its progression or enable symptomatic treatment where appropriate. The accuracy of MRI and CT, and whether MRI is superior to CT, in detecting a vascular component to dementia in autopsy confirmed and clinical cohorts of patients with VaD, combined AD and VaD ("mixed dementia"), and AD remain unclear. We conducted a systematic review and meta-analysis to investigate this question.

Instrumental variable estimation of causal risk ratios and causal odds ratios in Mendelian randomization analyses.

In this paper, the authors describe different instrumental variable (IV) estimators of causal risk ratios and odds ratios with particular attention to methods that can handle continuously measured exposures. The authors present this discussion in the context of a Mendelian randomization analysis of the effect of body mass index (BMI; weight (kg)/height (m)(2)) on the risk of asthma at age 7 years (Avon Longitudinal Study of Parents and Children, 1991-1992). The authors show that the multiplicative structural mean model (MSMM) and the multiplicative generalized method of moments (MGMM) estimator produce identical estimates of the causal risk ratio.

Mendelian randomization studies do not support a role for raised circulating triglyceride levels influencing type 2 diabetes, glucose levels, or insulin resistance.

Objective: The causal nature of associations between circulating triglycerides, insulin resistance, and type 2 diabetes is unclear. We aimed to use Mendelian randomization to test the hypothesis that raised circulating triglyceride levels causally influence the risk of type 2 diabetes and raise normal fasting glucose levels and hepatic insulin resistance.

Research Design And Methods: We tested 10 common genetic variants robustly associated with circulating triglyceride levels against the type 2 diabetes status in 5,637 case and 6,860 control subjects and four continuous outcomes (reflecting glycemia and hepatic insulin resistance) in 8,271 nondiabetic individuals from four studies.

Using multiple genetic variants as instrumental variables for modifiable risk factors.

Mendelian randomisation analyses use genetic variants as instrumental variables (IVs) to estimate causal effects of modifiable risk factors on disease outcomes. Genetic variants typically explain a small proportion of the variability in risk factors; hence Mendelian randomisation analyses can require large sample sizes. However, an increasing number of genetic variants have been found to be robustly associated with disease-related outcomes in genome-wide association studies.

Using genetic loci to understand the relationship between adiposity and psychological distress: a Mendelian Randomization study in the Copenhagen General Population Study of 53,221 adults.

Objective: We used genetic variants that are robustly associated with adiposity to examine the causal association of adiposity with psychological distress.

Methods: We examined the association of adiposity with psychological distress in a large (N = 53,221) general population cohort of 20- to 99-year-old adults from Copenhagen, Denmark. Psychological distress was assessed using four questions that asked about: feeling stressed; not accomplishing very much; wanting to give up; and regular use of antidepressants/sedatives.

C-reactive protein levels and body mass index: elucidating direction of causation through reciprocal Mendelian randomization.

Context: The assignment of direction and causality within networks of observational associations is problematic outside randomized control trials, and the presence of a causal relationship between body mass index (BMI) and C-reactive protein (CRP) is disputed.

Objective: Using reciprocal Mendelian randomization, we aim to assess the direction of causality in relationships between BMI and CRP and to demonstrate this as a promising analytical technique.

Participants And Methods: The study was based on a large, cross-sectional European study from Copenhagen, Denmark.

Genetic variation at the SLC23A1 locus is associated with circulating concentrations of L-ascorbic acid (vitamin C): evidence from 5 independent studies with >15,000 participants.

Background: L-ascorbic acid is an essential part of the human diet and has been associated with a wide range of chronic complex diseases, including cardiovascular outcomes. To date, there are no confirmed genetic correlates of circulating concentrations of L-ascorbic acid.

Objective: We aimed to confirm the existence of an association between common variation at the SLC23A1 gene locus and circulating concentrations of L-ascorbic acid.

Can lactase persistence genotype be used to reassess the relationship between renal cell carcinoma and milk drinking? Potentials and problems in the application of Mendelian randomization.

Background: Increased risk of renal cell carcinoma (RCC) with milk consumption has been reported from observational studies. Whether this represents a causal association or is a result of confounding or bias is unclear. We assessed the potential for using genetic variation in lactase persistence as a tool for the study of this relationship.

Meta-analysis of low molecular weight heparin versus placebo in patients undergoing total hip replacement and post-operative morbidity and mortality since their introduction.

Objectives: 1) To establish the clinical validity for in-patient low molecular weight heparin (LMWH) following total hip replacement (THR) through a meta-analysis of peer reviewed and published randomised placebo controlled trials (RCTs). 2) To establish whether modern peri-operative practices were associated with changes in rates of clinical venous thromboembolic (VTE) and all-cause mortality after THR by review of series of patients receiving in-patient LMWH published between 1985 and 2000. DATASOURCES: Medline and Embase (from 1980 to 2005), Datastar and Proquest databases were searched and references from bibliographies traced.

Systematic review: accuracy of anti-citrullinated Peptide antibodies for diagnosing rheumatoid arthritis.

Background: Early recognition and treatment of rheumatoid arthritis is important to prevent irreversible joint damage. Anti-citrullinated peptide antibodies (ACPA) have been suggested for early diagnosis.

Purpose: To compare the accuracy of ACPA and rheumatoid factor in diagnosing rheumatoid arthritis in patients with early symptoms of the disease.

Colour vision testing for diabetic retinopathy: a systematic review of diagnostic accuracy and economic evaluation.

Objective: To determine the diagnostic performance and cost-effectiveness of colour vision testing (CVT) to identify and monitor the progression of diabetic retinopathy (DR).

Data Sources: Major electronic databases including MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Database of Systematic Reviews were searched from inception to September 2008.

Review Methods: A systematic review of the evidence was carried out according to standard methods.

Does greater adiposity increase blood pressure and hypertension risk?: Mendelian randomization using the FTO/MC4R genotype.

Elevated blood pressure increases the risk of experiencing cardiovascular events like myocardial infarction and stroke. Current observational data suggest that body mass index may have a causal role in the etiology of hypertension, but this may be influenced by confounding and reverse causation. Through the use of instrumental variable methods, we aim to estimate the strength of the unconfounded and unbiased association between body mass index/adiposity and blood pressure.

An empirical comparison of methods for meta-analysis of diagnostic accuracy showed hierarchical models are necessary.

Objective: Meta-analysis of studies of the accuracy of diagnostic tests currently uses a variety of methods. Statistically rigorous hierarchical models require expertise and sophisticated software. We assessed whether any of the simpler methods can in practice give adequately accurate and reliable results.

Evidence-based diagnosis.

Making an accurate diagnosis is essential to ensure that a patient receives appropriate treatment and correct information regarding their prognosis. Characteristics of diagnostic tests are quantified in test accuracy studies, but many such studies have methodological flaws. The HSRC evidence-based diagnosis programme has focused on methods for systematic reviews of test accuracy studies, and the wider context in which tests are ordered and interpreted.

The association of C-reactive protein and CRP genotype with coronary heart disease: findings from five studies with 4,610 cases amongst 18,637 participants.

Background: It is unclear whether C-reactive protein (CRP) is causally related to coronary heart disease (CHD). Genetic variants that are known to be associated with CRP levels can be used to provide causal inference of the effect of CRP on CHD. Our objective was to examine the association between CRP genetic variant +1444C>T (rs1130864) and CHD risk in the largest study to date of this association.

Graphical presentation of diagnostic information.

Background: Graphical displays of results allow researchers to summarise and communicate the key findings of their study. Diagnostic information should be presented in an easily interpretable way, which conveys both test characteristics (diagnostic accuracy) and the potential for use in clinical practice (predictive value).

Methods: We discuss the types of graphical display commonly encountered in primary diagnostic accuracy studies and systematic reviews of such studies, and systematically review the use of graphical displays in recent diagnostic primary studies and systematic reviews.