Arnošt Komárek

Infliximab trough levels may predict sustained response to infliximab in patients with Crohn's disease

BACKGROUND AND AIMS Over 10% of Crohns disease (CD) patients annually lose response to infliximab. Infliximab trough levels (TL), concomitant immunosuppressants and endoscopic healing were proposed as predictors of favourable infliximab outcome. We assessed infliximab TL measured after induction therapy as predictors of sustained clinical response. Furthermore, we tried to identify other predictors of long-term benefit of infliximab therapy. METHODS We included CD patients treated with infliximab between October 2007 and March 2010 who responded to 3-dose induction followed by maintenance therapy and in whom blood samples taken at treatment week 14 or 22 were available in blood bank. Sustained response to infliximab was defined as absence of treatment failure due to loss of response or drug intolerance. RESULTS Eighty four patients were included. Sustained response to infliximab was observed in 47 (56%) patients during a median follow-up of 25 months (14-37). Infliximab TL>3μg/ml were associated with a decreased risk of treatment failure (HR 0.34; 95% CI: 0.16-0.75), whereas the presence of antibodies against infliximab and need for corticosteroids increased this risk (HR 4.34; 95% CI: 1.51-12.5 and HR 2.49, 95% CI: 1.08-5.73, respectively). No impact of concomitant thiopurines was observed, although patients receiving thiopurines had higher infliximab TL than those without immunomodulators (5.51 vs. 0.71μg/ml; p=0.01). CONCLUSION During a median follow up of 2 years sustained response to infliximab was observed in slightly more than half of CD patients. Infliximab TL>3μg/ml at the start of maintenance regime were predicative of sustained response to infliximab.

Impact of local and systemic factors on the incidence of late oral implant loss

BACKGROUND This retrospective study was set to assess the influence of systemic and local bone and intra-oral factors on the occurrence of implant loss from abutment connection up to 2 years. MATERIALS AND METHODS The files of 700 patients, have been collected randomly from the total patient group treated by means of endosseous Brånemark system implants (Nobel Biocare, Gothenburg, Sweden) at the Department of Periodontology of the University Hospital of the Catholic University of Leuven. The end point observation was evaluating the loss of the implants 2 years after abutment installation. The study involved all implants that did not encounter early loss and implants for which it was possible to evaluate its status 2 years after abutment surgery. Thus, data of 412 patients (240 females) provided with 1514 implants were analyzed. For each patient, the medical history was carefully checked. Data collection and analysis were mainly focused on endogenous factors such as hypertension, coagulation problems, osteoporosis, hypo- hyperthyroidism, chemotherapy, diabetes type I or II, Crohns disease, some local factors [e.g. bone quality and quantity, implant (length, diameter, location), type of edentulism, PTV, radiotherapy], smoking habits, and breach of sterility during surgery. RESULTS Radiotherapy, implant (diameter and location), and higher PTV at implant insertion and abutment connection, all affected significantly the implant loss. CONCLUSION Implant location in the oral cavity and radiotherapy seem predominant to explain the occurrence of implant loss. On the other hand, smoking and systemic health factors do not seem to be prominent players in the etiology of late implant loss.

Motor and Functional Recovery After Stroke A Comparison of 4 European Rehabilitation Centers

Background and Purpose— Outcome after first stroke varies significantly across Europe. This study was designed to compare motor and functional recovery after stroke between four European rehabilitation centers. Methods— Consecutive stroke patients (532 patients) were recruited. They were assessed on admission and at 2, 4, and 6 months after stroke with the Barthel Index, Rivermead Motor Assessment of Gross Function, Rivermead Motor Assessment of Leg/Trunk, Rivermead Motor Assessment of Arm, and Nottingham Extended Activities of Daily Living (except on admission). Data were analyzed using random effects ordinal logistic models adjusting for case-mix and multiple testing. Results— Patients in the UK center were more likely to stay in lower Rivermead Motor Assessment of Gross Function classes compared with patients in the German center (&Dgr;OR, 2.4; 95% CI, 1.3 to 4.3). In the Swiss center, patients were less likely to stay in lower Nottingham Extended Activities of Daily Living classes compared with patients in the UK center (&Dgr;OR, 0.7; 95% CI, 0.5 to 0.9). The latter were less likely to stay in lower Barthel Index classes compared with the patients in the German center (&Dgr;OR, 0.6; 95%CI, 0.4 to 0.8). Recovery patterns of Rivermead Motor Assessment of Leg/Trunk and Rivermead Motor Assessment of Arm were not significantly different between centers. Conclusions— Gross motor and functional recovery were better in the German and Swiss centers compared with the UK center, respectively. Personal self-care recovery was better in the UK compared with the German center. Previous studies in the same centers indicated that German and Swiss patients received more therapy per day. This was not the result of more staff but of a more efficient use of human resources. This study indicates potential for improving rehabilitation outcomes in the UK and Belgian centers.

Anxiety and depression in the first six months after stroke. A longitudinal multicentre study

Purpose. To document the prevalence, severity and time course of anxiety and depression in stroke rehabilitation patients in four European countries. Method. At two, four and six months post-stroke, the prevalence and severity of anxiety and depression were determined in 532 consecutively recruited patients, using the Hospital Anxiety and Depression Scale. Time course of prevalence and severity was examined, using Cochran-Q and Friedman-tests, respectively. We identified whether the numbers of anxious/depressed patients at each time point comprised the same individuals. Results. Prevalence of anxiety ranged between 22% and 25%; depression between 24% and 30%. Median severity ranged between 4 and 5. No significant differences between centres occurred (p > 0.05). Prevalence of both disorders was not significantly different over time. Severity of anxiety decreased between four and six months; severity of depression remained stable. About 40% of the patients with initial anxiety remained anxious at six months. Some 11% and 7% of those initially not anxious became anxious at four or six months after stroke, respectively. Depression showed a similar pattern. Conclusions. Despite differences in patient profiles and intensity of rehabilitation, no significant differences occurred between centres in prevalence and severity of both disorders. Anxiety was almost as common as depression and additional patients became anxious/depressed at each time point.

Generalized linear mixed model with a penalized Gaussian mixture as a random effects distribution

Generalized linear mixed models are popular for regressing a discrete response when there is clustering, e.g. in longitudinal studies or in hierarchical data structures. It is standard to assume that the random effects have a normal distribution. Recently, it has been examined whether wrongly assuming a normal distribution for the random effects is important for the estimation of the fixed effects parameters. While it has been shown that misspecifying the distribution of the random effects has a minor effect in the context of linear mixed models, the conclusion for generalized mixed models is less clear. Some studies report a minor impact, while others report that the assumption of normality really matters especially when the variance of the random effect is relatively high. Since it is unclear whether the normality assumption is truly satisfied in practice, it is important that generalized mixed models are available which relax the normality assumption. A replacement of the normal distribution with a mixture of Gaussian distributions specified on a grid whereby only the weights of the mixture components are estimated using a penalized approach ensuring a smooth distribution for the random effects is proposed. The parameters of the model are estimated in a Bayesian context using MCMC techniques. The usefulness of the approach is illustrated on two longitudinal studies using R-functions.

Accelerated Failure Time Model for Arbitrarily Censored Data With Smoothed Error Distribution

This article develops a semiparametric procedure to estimate parameters of an accelerated failure time model. To express the density of the error distribution, we use the P-spline (B-splines with penalties) smoothing technique. To accommodate error densities with infinite support (and for other reasons) we replace the B-splines with their limits as the degree of the B-spline goes to infinity; namely, with normal densities. The spline coefficients as well as any number of regression parameters are quickly and accurately estimated via penalized maximum likelihood. The method directly provides predictive survival distributions for fixed values of covariates while allowing for left-, right-, and interval-censored data. The approach has been implemented as an R package and is applied here to the problem of predicting AIDS-free survival in the presence of interval censoring.

Bayesian Accelerated Failure Time Model With Multivariate Doubly Interval-Censored Data and Flexible Distributional Assumptions

In this article we consider the relationship of covariates to the time to caries of permanent first molars. This involves an analysis of multivariate doubly interval-censored data. To describe this relationship, we suggest an accelerated failure time model with random effects, taking into account that the observations are clustered. Indeed, up to four permanent molars per child enter into the analysis, implying up to four caries times for each child. Each distributional part of the model is specified in a flexible way as a penalized Gaussian mixture with an overspecified number of mixture components. A Bayesian approach with the Markov chain Monte Carlo methodology is used to estimate the model parameters, and a software package in the R language has been written that implements it.

Fast measurements of parameters of the Solar Wind using the BMSW instrument

Design of the plasma spectrometer BMSW (Fast Monitor of the Solar Wind, possessing high temporal resolution) is described in the paper, as well as its characteristics and modes of operation. Some examples of measurements of various properties of the solar wind, made with this instrument installed onboard the high-apogee satellite Spektr-R, are presented.

Experimental evidence for mobility/immobility of metals in peat.

The biogeochemical cycles of most toxic metals have been significantly altered by anthropogenic activities. Anaerobic, rain-fed organic soils are believed to record historical changes in atmospheric pollution. Suspected postdepositional mobility of trace elements, however, hinders the usefulness of peat bogs as pollution archives. To lower this uncertainty, we quantified the mobility of six trace metals in peat during an 18-month field manipulation. A replicated, reciprocal peat transplant experiment was conducted between a heavily polluted and a relatively unpolluted peatland, located 200 km apart in the Czech Republic (Central Europe). Both peatlands were Sphagnum-derived, lawn-dominated, and had water table close to the surface. A strikingly different behavior was observed for two groups of elements. Elements of group I, Fe and Mn, adjusted their abundances and vertical patterns to the host site, showing an extremely high degree of mobility. In contrast, elements of group II, Pb, Cu, Zn, and Ti, preserved their original vertical patterns at the host site, showing a high degree of immobility. Our experimental results suggest that not just lead, but also copper and zinc concentration profiles in peat are a reliable archive of temporal pollution changes within a wide pH range (2.5-5.8).

An overview of methods for interval-censored data with an emphasis on applications in dentistry.

Interval-censored time-to-event data occur in many medical areas, with dentistry or AIDS research being typical representatives. This article reviews methods for the analysis of such data, with an emphasis on the use of the accelerated failure time (AFT) model. A flexible AFT model (avoiding parametric assumptions on the distribution of the error term) is described in greater detail and is used to solve a typical dental question in a longitudinal oral health study.