Toeval en vertekening

Oratie uitgesproken door Prof.dr. S. le Cessie bij de aanvaarding van het ambt van hoogleraar in de Statistische Methoden in Observationeel (klinisch) Epidemiologisch Onderzoek aan de Universiteit Leiden op vrijdag 22 september 2017LUMC / Geneeskund

Low birth weight and fetal anaemia as risk factors for infant morbidity in rural Malawi

Low birth weight (LBW) and fetal anaemia (FA) are common in malaria endemic areas. To investigate the incidence of infectious morbidity in infants in rural Malawi in relation to birth weight and fetal anaemia, a cohort of babies was followed for a year on the basis of LBW

T wave alternans in idiopathic long QT syndrome

AbstractObjectives. The study evaluates the association between T wave alternans and the risk of cardiac events (syncope, aborted cardiac arrest or cardiac death) in a large population of patients with idiopathic long QT syndrome.Background. T wave alternans is an infrequently recorded electrocardiographic (ECG) finding in patients with delayed repolarization, and its clinical significance is not clear.Methods. A total of 4,656 ECG recordings in 2,442 patients enrolled in the International Long QT Syndrome Registry were reviewed for episodes of T wave alternans. To determine the risk associated with T wave alternans, independent of corrected QT interval (QTc) duration, patients with T wave alternans were matched for QTc value (every 0.025 s1/2) to patients with long QT syndrome without T wave alternans.Results. T wave alternans was identified in 39 patients (25 of whom had a QTc interval >0.50 s1/2). A strong association between QTc prolongation and T wave alternans was observed (odds ratio 1.23 per 0.01-s1/2unit increase in QTc, p < 0.0001). Conditional logistic regression analyses with adjustment for age, gender, status and QTc value revealed that T wave alternans did not make a significant independent contribution to the risk of cardiac events. The risk of experiencing a major cardiac event was primarily related to length of QTc.Conclusions. T wave alternans, a marker of electrical instability and regional heterogeneity of repolarization, identifies a high risk subset of patients with prolonged repolarization. Patients with T wave alternans have an increased risk of cardiac events, but this risk is primarily related to the magnitude of repolarization delay (QTc prolongation). T wave alternans does not make an independent contribution to the risk of cardiac events after adjustment for QTc length

Using unstructured profile information for gender classification of Portuguese and English

This paper reports experiments on automatically detecting the gender of Twitter users, based on unstructured information found on their Twitter profile. A set of features previously proposed is evaluated on two datasets of English and Portuguese users, and their performance is assessed using several supervised and unsupervised approaches, including Naive Bayes variants, Logistic Regression, Support Vector Machines, Fuzzy c-Means clustering, and k-means. Results show that features perform well in both languages separately, but even best results were achieved when combining both languages. Supervised approaches reached 97.9 % accuracy, but Fuzzy c-Means also proved suitable for this task achieving 96.4 % accuracy.info:eu-repo/semantics/acceptedVersio

How measurements affected by medication use are reported and handled in observational research: a literature review

Purpose In epidemiological research, measurements affected by medication, for example, blood pressure lowered by antihypertensives, are common. Different ways of handling medication are required depending on the research questions and whether the affected measurement is the exposure, the outcome, or a confounder. This study aimed to review handling of medication use in observational research. Methods PubMed was searched for etiological studies published between 2015 and 2019 in 15 high-ranked journals from cardiology, diabetes, and epidemiology. We selected studies that analyzed blood pressure, glucose, or lipid measurements (whether exposure, outcome or confounder) by linear or logistic regression. Two reviewers independently recorded how medication use was handled and assessed whether the methods used were in accordance with the research aim. We reported the methods used per variable category (exposure, outcome, confounder). Results A total of 127 articles were included. Most studies did not perform any method to account for medication use (exposure 58%, outcome 53%, and confounder 45%). Restriction (exposure 22%, outcome 23%, and confounders 10%), or adjusting for medication use using a binary indicator were also used frequently (exposure: 18%, outcome: 19%, confounder: 45%). No advanced methods were applied. In 60% of studies, the methods' validity could not be judged due to ambiguous reporting of the research aim. Invalid approaches were used in 28% of the studies, mostly when the affected variable was the outcome (36%). Conclusion Many studies ambiguously stated the research aim and used invalid methods to handle medication use. Researchers should consider a valid methodological approach based on their research question.Clinical epidemiolog

The analysis of longitudinal quality of life measures with informative drop-out: a pattern mixture approach

The analysis of longitudinal health-related quality of life measures (HRQOL) can be seriously hampered due to informative drop-out. Random effects models assume Missing At Random and do not take into account informative drop-out. We therefore aim to correct the bias due to informative drop-out. Analyses of data from a trial comparing standard-dose and high-dose chemotherapy for patients with breast cancer with respect to long-term impact on HRQOL will serve as illustration. The subscale Physical Function (PF) of the SF36 will be used. A pattern mixture approach is proposed to account for informative drop-out. Patterns are defined based on events related to HRQOL, such as death and relapse. The results of this pattern mixture approach are compared to the results of the commonly used random effects model. The findings of the pattern mixture approach are well interpretable, and different courses over time in different patterns are distinguished. In terms of estimated differences between standard dose and high dose, the results of both approaches are slightly different, but have no consequences for the clinical evaluation of both doses. Under the assumption that drop-out is at random within the patterns, the pattern mixture approach adjusts the estimates to a certain degree. This approach accounts in a relatively simple way for informative drop-out

Diet-derived circulating antioxidants and risk of coronary heart disease a Mendelian randomization study

BACKGROUND Previously, observational studies have identified associations between higher levels of dietary-derived antioxidants and lower risk of coronary heart disease (CHD), whereas randomized clinical trials showed no reduction in CHD risk following antioxidant supplementation.OBJECTIVES The purpose of this study was to investigate possible causal associations between dietary-derived circulating antioxidants and primary CHD risk using 2-sample Mendelian randomization (MR).METHODS Single-nucleotide polymorphisms for circulating antioxidants (vitamins E and C, retinol, 13-carotene, and lycopene), assessed as absolute levels and metabolites, were retrieved from the published data and were used as genetic instrumental variables. Summary statistics for gene-CHD associations were obtained from 3 databases: the CARDIoGRAMplusC4D consortium (60,801 cases; 123,504 control subjects), UK Biobank (25,306 cases; 462,011 control subjects), and FinnGen study (7,123 cases; 89,376 control subjects). For each exposure, MR analyses were performed per outcome database and were subsequently meta-analyzed.RESULTS Among an analytic sample of 768,121 individuals (93,230 cases), genetically predicted circulating antioxidants were not causally associated with CHD risk. For absolute antioxidants, the odds ratio for CHD ranged between 0.94 (95% confidence interval [CI]: 0.63 to 1.41) for retinol and 1.03 (95% CI: 0.97 to 1.10) for 13-carotene per unit increase in ln-transformed antioxidant values. For metabolites, the odds ratio ranged between 0.93 (95% CI: 0.82 to 1.06) for g-tocopherol and 1.01 (95% CI: 0.95 to 1.08) for ascorbate per 10-fold increase in metabolite levels.CONCLUSIONS Evidence from our study did not support a protective effect of genetic predisposition to high dietaryderived antioxidant levels on CHD risk. Therefore, it is unlikely that taking antioxidants to increase blood antioxidants levels will have a clinical benefit for the prevention of primary CHD. (C) 2021 by the American College of Cardiology Foundation.Clinical epidemiolog

Multiple testing: when 's many too much?

In almost all medical research, more than a single hypothesis is being tested or more than a single relation is being estimated. Testing multiple hypotheses increases the risk of drawing a false-positive conclusion. We briefly discuss this phenomenon, which is often called multiple testing. Also, methods to mitigate the risk of false-positive conclusions are discussed.Clinical epidemiolog

Diarrhoea in general practice: when should a Clostridium difficile infection be considered? Results of a nested case-control study

AbstractClostridium difficile infections (CDIs) are frequent in hospitals, but also seem to increase in the community. Here, we aim to determine the incidence of CDI in general practice and to evaluate current testing algorithms for CDI. Three Dutch laboratories tested all unformed faeces (12 714) for C. difficile when diagnostic testing (for any enteric pathogen) was requested by a general practitioner (GP). Additionally, a nested case-control study was initiated, including 152 CDI patients and 304 age and sex-matched controls. Patients were compared using weighted multivariable logistic regression. One hundred and ninety-four samples (1.5%) were positive for C. difficile (incidence 0.67/10 000 patient years). This incidence was comparable to that of Salmonella spp. Compared with diarrhoeal controls, CDI was associated with more severe complaints, underlying diseases, antibiotic use and prior hospitalization. In our study, GPs requested a test for C. difficile in 7% of the stool samples, thereby detecting 40% of all CDIs. Dutch national recommendations advise testing for C. difficile when prior antibiotic use or hospitalization is present (18% of samples). If these recommendations were followed, 61% of all CDIs would have been detected. In conclusion, C. difficile is relatively frequent in general practice. Currently, testing for C. difficile is rare and only 40% of CDI in general practice is detected. Following recommendations that are based on traditional risk factors for CDI, would improve detection of CDI