Biomedical subjects

Edwin P Martens

Publications and source records attributed to Edwin P Martens.

4 recordsLinked to original sources

PubMed2006

Instrumental variables: application and limitations.

To correct for confounding, the method of instrumental variables (IV) has been proposed. Its use in medical literature is still rather limited because of unfamiliarity or inapplicability. By introducing the method in a nontechnical way, we show that IV in a linear model is quite easy to understand and easy to apply once an appropriate instrumental variable has been identified. We also point out some limitations of the IV estimator when the instrumental variable is only weakly correlated with the exposure. The IV estimator will be imprecise (large standard error), biased when sample size is small, and biased in large samples when one of the assumptions is only slightly violated. For these reasons, it is advised to use an IV that is strongly correlated with exposure. However, we further show that under the assumptions required for the validity of the method, this correlation between IV and exposure is limited. Its maximum is low when confounding is strong, such as in case of confounding by indication. Finally, we show that in a study in which strong confounding is to be expected and an IV has been used that is moderately or strongly related to exposure, it is likely that the assumptions of IV are violated, resulting in a biased effect estimate. We conclude that instrumental variables can be useful in case of moderate confounding but are less useful when strong confounding exists, because strong instruments cannot be found and assumptions will be easily violated.

Bias↗

PubMed2005

Hyphal differentiation in the exploring mycelium of Aspergillus niger.

Mycelial fungi play a central role in element cycling in nature by degrading dead organic material such as wood. Fungal colonization of a substrate starts with the invasion of exploring hyphae. These hyphae secrete enzymes that convert the organic material into small molecules that can be taken up by the fungus to serve as nutrients. Using green fluorescent protein (GFP) as a reporter, we show for the first time that exploring hyphae of Aspergillus niger differentiate with respect to enzyme secretion; some strongly express the glucoamylase gene glaA, while others hardly express it at all. When a cytoplasmic GFP was used, 27% of the exploring hyphae of a 5-day-old colony belonged to the low expressing hyphae. By fusing GFP to glucoamylase and by introducing an ER retention signal, this number increased to 50%. This difference is due to cytoplasmic streaming of the reporter in the former case, as was shown by using a photo-activatable GFP. Our findings indicate that a fungal mycelium is highly differentiated, especially when taking into account that hyphae in the exploration zone were exposed to the same nutritional conditions.

Aspergillus niger↗

PubMed2004

Methods to assess intended effects of drug treatment in observational studies are reviewed.

BACKGROUND AND OBJECTIVE: To review methods that seek to adjust for confounding in observational studies when assessing intended drug effects. METHODS: We reviewed the statistical, economical and medical literature on the development, comparison and use of methods adjusting for confounding. RESULTS: In addition to standard statistical techniques of (logistic) regression and Cox proportional hazards regression, alternative methods have been proposed to adjust for confounding in observational studies. A first group of methods focus on the main problem of nonrandomization by balancing treatment groups on observed covariates: selection, matching, stratification, multivariate confounder score, and propensity score methods, of which the latter can be combined with stratification or various matching methods. Another group of methods look for variables to be used like randomization in order to adjust also for unobserved covariates: instrumental variable methods, two-stage least squares, and grouped-treatment approach. Identifying these variables is difficult, however, and assumptions are strong. Sensitivity analyses are useful tools in assessing the robustness and plausibility of the estimated treatment effects to variations in assumptions about unmeasured confounders. CONCLUSION: In most studies regression-like techniques are routinely used for adjustment for confounding, although alternative methods are available. More complete empirical evaluations comparing these methods in different situations are needed.

Confounding Factors, Epidemiologic↗

PubMed2003

Thiazolidinediones and blood lipids in type 2 diabetes.

We evaluated study population characteristics and treatment effects on blood lipids between studies in which either rosiglitazone (RSG) or pioglitazone (PIO) was investigated in patients with type 2 diabetes. We performed a summary analysis of all published double-blind, placebo-controlled studies with RSG (4 and 8 mg/d) and PIO (15, 30, and 45 mg/d). Data were analyzed by the random-effects model. Nineteen trials met our inclusion criteria, yielding 5304 patients, 3236 in studies with RSG and 2068 in studies with PIO. Subjects treated with PIO were more obese and showed more pronounced hyperglycemia and dyslipidemia (increased triglycerides and decreased HDL cholesterol) at baseline than did subjects treated with RSG. By weighted linear-regression analysis, studies with PIO showed greater beneficial effects on triglycerides, total cholesterol, and LDL cholesterol, after adjustment for the respective lipid levels at baseline. RSG 8 mg/d showed greater increases in total cholesterol and LDL cholesterol than did RSG 4 mg/d. PIO 30 mg/d showed greater reductions in triglycerides than did PIO 15 mg/d. Studies conducted with PIO showed more beneficial effects on blood lipids, but also different study population characteristics in comparison with studies conducted with RSG. Differences in both pharmacologic properties between agents and study population characteristics are likely to have influenced the results.

Cholesterol↗