Optimization of Alcohol Dehydrogenase for Industrial Scale Oxidation of Lactols.

Alcohol dehydrogenases (ADH) are widely used to enantioselectively reduce ketones to chiral alcohols, but their application in industrial scale oxidations is rare. Reasons are the need for an NAD(P) cofactor regeneration system, often low performance in oxidative reactions and the limited substrate scope of ADHs. ADHA from Candida magnoliae DSMZ 70638 is identified to efficiently catalyze the regio-selective hydroxy-lactone oxidations to hydroxy-lactones.

Risk of acute myocardial infarction during use of individual NSAIDs: A nested case-control study from the SOS project.

Background: Use of selective COX-2 non-steroidal anti-inflammatory drugs (NSAIDs) (coxibs) has been associated with an increased risk of acute myocardial infarction (AMI). However, the risk of AMI has only been studied for very few NSAIDs that are frequently used.

Objectives: To estimate the risk of AMI for individual NSAIDs.

Risk of ischemic stroke and the use of individual non-steroidal anti-inflammatory drugs: A multi-country European database study within the SOS Project.

Background And Purpose: A multi-country European study using data from six healthcare databases from four countries was performed to evaluate in a large study population (>32 million) the risk of ischemic stroke (IS) associated with individual NSAIDs and to assess the impact of risk factors of IS and co-medication.

Methods: Case-control study nested in a cohort of new NSAID users. For each case, up to 100 sex- and age-matched controls were selected and confounder-adjusted odds ratios for current use of individual NSAIDs compared to past use calculated.

Relation Between Different Measures of Glycemic Exposure and Microvascular and Macrovascular Complications in Patients with Type 2 Diabetes Mellitus: An Observational Cohort Study.

Introduction: This retrospective cohort study investigated the relation between different measures of glycemic exposure and micro- and macrovascular complications among patients with type 2 diabetes.

Methods: The analysis included patients receiving oral antihyperglycemic agents between 1 January 2006 and 31 December 2014 from the General Practitioner Database from the PHARMO Database Network. All recorded HbA1c levels during follow-up were used to express glycemic exposure in four ways: index HbA1c, time-dependent HbA1c, exponential moving average (EMA) and glycemic burden.

Non-steroidal anti-inflammatory drugs and risk of heart failure in four European countries: nested case-control study.

Objectives: To investigate the cardiovascular safety of non-steroidal anti-inflammatory drugs (NSAIDs) and estimate the risk of hospital admission for heart failure with use of individual NSAIDs.

Design: Nested case-control study.

Setting: Five population based healthcare databases from four European countries (the Netherlands, Italy, Germany, and the United Kingdom).

Defining small-for-gestational-age: prescriptive versus descriptive birthweight standards.

Unlabelled: Descriptive population-based birthweight standards possess low sensitivity in detecting infants with growth impairment. A prescriptive birthweight standard based on a 'healthy' subpopulation without risk factors for intrauterine growth restriction might be superior. We created two birthweight standards based on live born, singleton infants with gestational age 24-42 weeks and born in The Netherlands between 2000 and 2007.

Population-based analysis of non-steroidal anti-inflammatory drug use among children in four European countries in the SOS project: what size of data platforms and which study designs do we need to assess safety issues?

Background: Data on utilization patterns and safety of non-steroidal anti-inflammatory drugs (NSAIDs) in children are scarce. The purpose of this study was to investigate the utilization of NSAIDs among children in four European countries as part of the Safety Of non-Steroidal anti-inflammatory drugs (SOS) project.

Methods: We used longitudinal patient data from seven databases (GePaRD, IPCI, OSSIFF, Pedianet, PHARMO, SISR, and THIN) to calculate prevalence rates of NSAID use among children (0-18 years of age) from Germany, Italy, Netherlands, and United Kingdom.

Replication of the OMOP experiment in Europe: evaluating methods for risk identification in electronic health record databases.

Background: The Observational Medical Outcomes Partnership (OMOP) has just completed a large scale empirical evaluation of statistical methods and analysis choices for risks identification in longitudinal observational healthcare data. This experiment drew data from four large US health insurance claims databases and one US electronic health record (EHR) database, but it is unclear to what extend the findings of this study apply to other data sources.

Objective: To replicate the OMOP experiment in six European EHR databases.

Using electronic health care records for drug safety signal detection: a comparative evaluation of statistical methods.

Background: Drug safety monitoring relies primarily on spontaneous reporting, but electronic health care record databases offer a possible alternative for the detection of adverse drug reactions (ADRs).

Objectives: To evaluate the relative performance of different statistical methods for detecting drug-adverse event associations in electronic health care record data representing potential ADRs.

Research Design: Data from 7 databases across 3 countries in Europe comprising over 20 million subjects were used to compute the relative risk estimates for drug-event pairs using 10 different methods, including those developed for spontaneous reporting systems, cohort methods such as the longitudinal gamma poisson shrinker, and case-based methods such as case-control.

Platelet aggregation inhibitors, vitamin K antagonists and risk of subarachnoid hemorrhage.

Background: Use of platelet aggregation inhibitors and vitamin K antagonists has been associated with an increased risk of intracranial hemorrhage (ICH). Whether the use of these antithrombotic drugs is associated with an increased risk of subarachnoid hemorrhage (SAH) remains unclear, especially as confounding by indication might play a role.

Objective: The aim of the present study was to investigate whether use of platelet aggregation inhibitors or vitamin K antagonists increase the risk of SAH.

In primary breast cancer the mitotic activity yields similar prognostic information as the histological grade: a study with long-term follow-up.

We evaluated with long-term follow-up, the prognostic value of the mitotic activity index (MAI) and the volume corrected mitotic index (M/V-index) compared with that of the histological grade in breast cancer patients not treated with adjuvant systemic therapy. Of 739 consecutive patients living in the city of Nijmegen, the Netherlands, 477 patients with primary unilateral breast cancer were not treated with adjuvant systemic therapy and eligible for the study. In multivariate survival analyses the MAI and M/V-index showed similar hazard ratios (HRs) compared to HRs of histological grade for overall survival (OS) (HR: 1.

Withdrawal of statins and risk of subarachnoid hemorrhage.

Background And Purpose: Vascular endothelium, which can be affected by statins, is believed to play a substantial role in subarachnoid hemorrhage (SAH). Our objective was to estimate the association between use and withdrawal of statins and the risk of SAH.

Methods: We conducted a population-based case-control study within the PHARMO database.

Intravascular volume administration: a contributing risk factor for intracranial hemorrhage during extracorporeal membrane oxygenation?

Objective: The objective of this study was to determine the relationship between the frequency and total volume of intravascular volume administration and the development of intracranial hemorrhage during venoarterial extracorporeal membrane oxygenation.

Methods: In a retrospective, matched, case-control study, 24 newborns who developed an intracranial hemorrhage during venoarterial extracorporeal membrane oxygenation treatment were compared with 40 control subjects. Both groups were analyzed for gestational age, gender, race, Apgar scores at 1 and 5 minutes, birth weight, cardiopulmonary resuscitation before venoarterial extracorporeal membrane oxygenation, age at the start of treatment, duration of treatment, worst arterial blood gas sample preceding treatment, activated clotting time values, need for platelet transfusions, mean blood pressure, and the use of inotropics and steroids before the treatment.

Panel perception of change in facial aesthetics following orthodontic treatment in adolescents.

The aim of the study was to evaluate the influence of the characteristics of panel members, the effects of gender and Angle Class of adolescent patients on their change in facial aesthetics following orthodontic treatment, and to assess the optimal panel size for epidemiological studies on changes in facial aesthetics after orthodontic treatment. A panel of 74 adult laymen (35 males and 39 females) and a panel of 87 orthodontists (37 males and 50 females) evaluated sets of three post-treatment standardized photographs (one frontal, one three-quarter smiling, and one lateral) of 64 adolescent orthodontic patients in relation to the pre-treatment sets of the same patient on a five-point scale. The main effects of professional background, age, gender, and geographic region of the panel members on the aesthetic scores, as well as their first order interactions were evaluated by multilevel models.

Facial esthetics in adolescents and its relationship to "ideal" ratios and angles.

Introduction: Many guidelines, norms, and ideal ratios and angles for attractive faces have been proposed in the literature. The aim of this study was to test the hypothesis that facial attractiveness in adolescents is related to ideal angles and ratios, as indicated in the literature.

Methods: Seventy-six laypeople viewed sets of photographs of 64 adolescents and rated them on a visual analog scale (VAS) from 0 to 100.

The relation between postural stability and weight distribution in healthy subjects.

Knowledge of the effects of leg-loading asymmetry on postural control and control asymmetry during quiet upright standing in healthy young and middle-aged subjects is necessary before these relationships in patients with lateralized disorders can be assessed and understood. A posturographic procedure was developed, using a dual-plate force platform, during which 10 younger and 10 middle-aged healthy individuals were required to adopt various degrees of (a) symmetrical weight distributions (0, 5, 10, 20 and 30% of extra body weight loaded onto either leg). Postural control and control asymmetry were quantified by centre of pressure (CP) fluctuations in the lateral (LAT) and anterior-posterior (AP) directions under both feet together and individually.

Influence of panel composition on aesthetic evaluation of adolescent faces.

The objective of this study was to evaluate the influence of professional background, age, gender, and geographical region of panel members on their evaluation of the facial aesthetics of adolescents, and to assess the optimal panel size for epidemiological studies on facial aesthetics. A panel of 76 adult laymen from two different regions (Belgium and The Netherlands) and a panel of 89 orthodontists from the same two regions, evaluated photographic sets (one frontal, one three-quarter smiling, and one lateral view) of 64 adolescents (32 boys, 32 girls) on a visual analogue scale (VAS) in relation to a reference set of photographs. The effects of the characteristics of the panel members on the VAS scores for boys and girls separately, as well as their interactions, were evaluated by multilevel models.

A randomized clinical trial of clomiphene citrate versus low dose recombinant FSH for ovarian hyperstimulation in intrauterine insemination cycles for unexplained and male subfertility.

Background: Controlled ovarian hyperstimulation with intrauterine insemination (IUI) is a widely accepted treatment for unexplained and male subfertility. No consensus exists about the drug of first choice to be used as hyperstimulation. This randomized multicentre trial using a parallel design compares the efficacy of clomiphene citrate (CC) with that of recombinant FSH (rFSH).

Gene expression analysis for the prediction of recurrence in patients with primary Ta urothelial cell carcinoma.

Objectives: The individual recurrence-free period after primary surgery of patients with Ta urothelial cell carcinoma (UCC) cannot be predicted accurately. This study aims at discriminating between patients with primary Ta UCC and long or short recurrence-free periods.

Methods: We investigated mRNA expression of 23 genes in 44 primary Ta tumours (23 and 21 tumours were from patients with long [>or=4 yr] or short [ View Article and Find Full Text PDF

Prediction of recurrence in Ta urothelial cell carcinoma by real-time quantitative PCR analysis: a microarray validation study.

Accurate prediction of tumor recurrence in patients with superficial urothelial cell carcinoma (UCC) might result in a significant reduction of invasive follow-up cystoscopies. A recent study identified a panel of 26 genes from a large cDNA microarray analysis of bladder tumors that discriminated between early- and late-recurring patients with superficial Ta tumors (Dyrskjøt et al., Nat Genet 2003;33:90-6).

Accurate prediction of need for invasive treatment in alpha1-blocker treated patients with benign prostatic hyperplasia not possible: bootstrap validation analysis.

Objectives: Frequently, statistically significant prognostic factors are reported in published studies with suggestions that disease management should be modified. However, the clinical relevance of such factors is rarely quantified. We evaluated the accuracy of predicting the need for invasive treatment among patients with benign prostatic hyperplasia treated conservatively with alpha1-blockers.

Identification of novel genomic markers related to progression to glioblastoma through genomic profiling of 25 primary glioma cell lines.

Identification of genetic copy number changes in glial tumors is of importance in the context of improved/refined diagnostic, prognostic procedures and therapeutic decision-making. In order to detect recurrent genomic copy number changes that might play a role in glioma pathogenesis and/or progression, we characterized 25 primary glioma cell lines including 15 non glioblastoma (non GBM) (I-III WHO grade) and 10 GBM (IV WHO grade), by array comparative genomic hybridization, using a DNA microarray comprising approx. 3500 BACs covering the entire genome with a 1 Mb resolution and additional 800 BACs covering chromosome 19 at tiling path resolution.

Immune status and eustachian tube function in recurrence of otitis media with effusion.

Objective: To study the combined role of immune status and eustachian tube function in the development of recurrent bilateral otitis media with effusion (OME).

Design: Prospective cohort study.

Setting: Three academic and general hospitals.

Identification of androgen-responsive genes that are alternatively regulated in androgen-dependent and androgen-independent rat prostate tumors.

The vast majority of androgen-dependent prostate tumors progress toward incurable, androgen-independent tumors. The identification of androgen-responsive genes, which are still actively transcribed in the tumors of patients who have undergone androgen ablation, may shed light on the molecular mechanisms underlying this phenomenon. To address this question, we chose the Dunning R3327 rat model system, in which the progression from androgen-dependent to -independent tumors is represented by several transplantable prostate-derived tumors.

Bayes' theorem: a negative example of a RCT on grommets in children with glue ear.

Bayesian inference presupposes that practitioners' belief in the effectiveness of medical intervention is the product of prior belief and recent evidence from studies. Although increasingly used, up to now the posterior belief calculated according to the theorem has not been compared with an empirically measured posterior belief. We conducted a RCT, which was preceded by elicitation of prior beliefs among ENT-surgeons, and which was followed by elicitation of posterior beliefs among ENT-surgeons, 1 year after completion of the trial.