Background
Results from observational studies may be inconsistent because of variations in methodological and clinical factors that may be intrinsically related to the database (DB) where the study ...is performed.
Objectives
The objectives of this paper were to evaluate the impact of applying a common study protocol to study benzodiazepines (BZDs) (anxiolytics, hypnotics, and related drugs) and the risk of hip/femur fracture (HFF) across three European primary care DBs and to investigate any resulting discrepancies.
Methods
To measure the risk of HFF among adult users of BZDs during 2001–2009, three cohort and nested case control (NCC) studies were performed in Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP) (Spain), Clinical Practice Research Datalink (CPRD) (UK), and Mondriaan (The Netherlands). Four different models (A–D) with increasing levels of adjustment were analyzed. The risk according to duration and type of BZD was also explored. Adjusted hazard ratios (cohort), odds ratios (NCC), and their 95% confidence intervals were estimated.
Results
Adjusted hazard ratios (Model C) were 1.34 (1.23–1.47) in BIFAP, 1.66 (1.54–1.78) in CPRD, and 2.22 (1.55–3.29) in Mondriaan in cohort studies. Adjusted odds ratios (Model C) were 1.28 (1.16–1.42) in BIFAP, 1.60 (1.49–1.72) in CPRD, and 1.48 (0.89–2.48) in Mondriaan in NCC studies. A short‐term effect was suggested in Mondriaan, but not in CPRD or BIFAP. All DBs showed an increased risk with the concomitant use of anxiolytic and hypnotic drugs.
Conclusions
Applying similar study methods to different populations and DBs showed an increased risk of HFF in BZDs users but differed in the magnitude of the risk, which may be because of inherent differences between DBs.
We aimed to improve the understanding of potential associations between commonly available hematological biomarkers and the coronary artery calcification (CAC) score, which may help unravel the ...pathophysiology of coronary calcifications and subclinical coronary artery disease.
A cross-sectional study was performed within the Utrecht Patient Oriented Database (UPOD). Patients with suspected or known coronary artery disease who underwent CT CAC scoring as well as standard hematology analysis that was part of routine clinical care (within 3 months of CT acquisition) were included. Complete hematology datasets were extracted from hematology analyzers. Linear regression adjusted for potential confounders was used to assess if hematological biomarkers were related to the CAC score.
In total, 1504 patients were included, of whom 43% (n = 647) had a CAC score of 0. Mean age (±SD) was 53 ± 13 years, and 34% of patients were women. Red blood cell distribution width (RDW, β = 0.20 0.05–0.36, p=0.007), the fraction of immature reticulocytes (β = 0.97 0.10–6.43, p=0.004), coefficient of variation of neutrophil lobularity (β = 0.13 0.01–0.25, p=0.040) and mean lymphocyte cell size (β = 0.21 0.08–0.34, p=0.001) were positively associated with the CAC score after adjustment for age, sex, body mass index (BMI), diabetes, glomerular filtration rate (GFR) and high-density lipoprotein (HDL).
This study confirms the known association of RDW with the CAC score, and presents the fraction of immature reticulocytes, coefficient of variation of neutrophil lobularity, and mean lymphocyte cell size as new markers associated with a higher CAC score.
•The association between hematologic biomarkers and the CAC score was studied.•Four biomarkers, including the RDW, were associated with the CAC score.•These biomarkers implicate that acute inflammation is a cause or consequence of CAC.
Vitamin D plays a role in host defence against infection. Vitamin D deficiency has been associated with an increased risk of respiratory tract infections in children and adults. This study aimed to ...examine whether vitamin D supplementation is associated with a lower pneumonia risk in adults.
Three independent case-control studies were performed including a total of 33 726 cases with pneumonia in different settings with respect to hospitalisation status and a total of 105 243 controls. Cases and controls were matched by year of birth, gender and index date. The major outcome measure was exposure to vitamin D supplementation at the time of pneumonia diagnosis. Conditional logistic regression was used to compute ORs for the association between vitamin D supplementation and occurrence of pneumonia.
Vitamin D supplementation was not associated with a lower risk of pneumonia. In studies 1 and 2, adjustment for confounding resulted in non-significant ORs of 1.814 (95% CI 0.865 to 3.803) and 1.007 (95% CI 0.888 to 1.142), respectively. In study 3, after adjustment for confounding, the risk of pneumonia remained significantly higher among vitamin D users (OR 1.496, 95% CI 1.208 to 1.853). Additional analyses showed significant modification of the association through co-use of corticosteroids and drugs that affect bone mineralisation. For patients using these drugs, ORs below one were found combined with higher ORs for patients not using these drugs.
This study showed no preventive association between vitamin D supplementation and the risk of pneumonia in adults.
With the ageing European population, the incidence of coronary artery disease (CAD) is expected to rise. This will likely result in an increased imaging use. Symptom recognition can be complicated, ...as symptoms caused by CAD can be atypical, particularly in women. Early CAD exclusion may help to optimize use of diagnostic resources and thus improve the sustainability of the healthcare system. To develop sex-stratified algorithms, trained on routinely available electronic health records (EHRs), raw electrocardiograms, and haematology data to exclude CAD in patients upfront.
We trained XGBoost algorithms on data from patients from the Utrecht Patient-Oriented Database, who underwent coronary computed tomography angiography (CCTA), and/or stress cardiac magnetic resonance (CMR) imaging, or stress single-photon emission computerized tomography (SPECT) in the UMC Utrecht. Outcomes were extracted from radiology reports. We aimed to maximize negative predictive value (NPV) to minimize the false negative risk with acceptable specificity. Of 6808 CCTA patients (31% female), 1029 females (48%) and 1908 males (45%) had no diagnosis of CAD. Of 3053 CMR/SPECT patients (45% female), 650 females (47%) and 881 males (48%) had no diagnosis of CAD. On the train and test set, the CCTA models achieved NPVs and specificities of 0.95 and 0.19 (females) and 0.96 and 0.09 (males). The CMR/SPECT models achieved NPVs and specificities of 0.75 and 0.041 (females) and 0.92 and 0.026 (males).
Coronary artery disease can be excluded from EHRs with high NPV. Our study demonstrates new possibilities to reduce unnecessary imaging in women and men suspected of CAD.
Optimize and assess the performance of an existing data mining algorithm for smoking status from hospital electronic health records (EHRs) in general practice EHRs.
We optimized an existing algorithm ...in a training set containing all clinical notes from 498 individuals (75 712 contact moments) from the Julius General Practitioners' Network (JGPN). Each moment was classified as either 'current smoker', 'former smoker', 'never smoker', or 'no information'. As a reference, we manually reviewed EHRs. Algorithm performance was assessed in an independent test set (
= 494, 78 129 moments) using precision, recall, and F1-score. Test set algorithm performance for 'current smoker' was precision 79.7%, recall 78.3%, and F1-score 0.79. For former smoker, it was precision 73.8%, recall 64.0%, and F1-score 0.69. For never smoker, it was precision 92.0%, recall 74.9%, and F1-score 0.83. On a patient level, performance for ever smoker (current and former smoker combined) was precision 87.9%, recall 94.7%, and F1-score 0.91. For never smoker, it was 98.0, 82.0, and 0.89%, respectively. We found a more narrative writing style in general practice than in hospital EHRs.
Data mining can successfully retrieve smoking status information from general practice clinical notes with a good performance for classifying ever and never smokers. Differences between general practice and hospital EHRs call for optimization of data mining algorithms when applied beyond a primary development setting.
Highlights • About 6% of the UK female population is a diagnosed type 2-diabetes patient. • Of those women with diabetes, 2880 are diagnosed with breast cancer each year. • Incidence of breast cancer ...among women with diabetes remained stable over 2000–2012. • Age-standardized breast cancer incidence was similar in women with and without diabetes.
Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding ...variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
Modern omics research involves the application of high-throughput technologies that generate vast volumes of data. These data need to be pre-processed, analyzed and integrated with existing knowledge ...through the use of diverse sets of software tools, models and databases. The analyses are often interdependent and chained together to form complex workflows or pipelines. Given the volume of the data used and the multitude of computational resources available, specialized pipeline software is required to make high-throughput analysis of large-scale omics datasets feasible.
We have developed a generic pipeline system called Cyrille2. The system is modular in design and consists of three functionally distinct parts: 1) a web based, graphical user interface (GUI) that enables a pipeline operator to manage the system; 2) the Scheduler, which forms the functional core of the system and which tracks what data enters the system and determines what jobs must be scheduled for execution, and; 3) the Executor, which searches for scheduled jobs and executes these on a compute cluster.
The Cyrille2 system is an extensible, modular system, implementing the stated requirements. Cyrille2 enables easy creation and execution of high throughput, flexible bioinformatics pipelines.
Clindamycin and taste disorders De Groot, Mark C. H.; Van Puijenbroek, Eugène P.
British journal of clinical pharmacology,
October 2007, Letnik:
64, Številka:
4
Journal Article
Recenzirano
Odprti dostop
What is already known about this subject.
• The antibiotic clindamycin has a bitter taste when it is used orally.
What this study adds
• A case series on oral as well as i.v. use of clindamycin ...associated with taste disorders is presented.
• After corrections in a case‐by‐case analysis for several possible confounders such as indication, clindamycin is disproportionally associated with taste disorders.
• Serum and hence saliva and sputum clindamycin levels seem to be responsible for this reversible adverse drug reaction.
Aims
Topical use of clindamycin has been associated with taste disorders in the literature, but little is known about the nature of this adverse drug reaction. The aim of this article was to describe reports of clindamycin‐induced taste disorders and to analyse the factors involved.
Methods
The adverse drug reaction database of the Netherlands Pharmacovigilance Centre was searched for reports concerning taste disorders with antibiotics. Clinical review of the cases and statistical analysis with logistic regression were performed. Characteristics of patients who reported taste disorders were compared for age, gender and formulation in clindamycin vs. other antibiotic users.
Results
Taste disorders were reported in seven (18%) of the clindamycin cases. In five reports an oral formulation was involved, in one report intravenous (i.v.) administration and in one report both formulations were used. Latency was <1 day after start and in one case taste disorders were present repeatedly at 10 min after every i.v. application. The adjusted reporting odds ratio was 7.0 (95% confidence interval 2.8, 17.3) and supports a possible causal relationship.
Conclusions
The association of clindamycin and taste disorders is supported by disproportionality analysis and seems to be independent of possible confounders such as age, gender and infections. The case reports suggest a role for clindamycin concentrations excreted in body fluids like saliva.
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