No abstract

In ages >45 years, the prevalence of COPD according to the BTS guidelines was 8%, and it was 14% according to the GOLD criteria. Fifty percent of elderly smokers had developed COPD. The large majority of subjects having COPD were symptomatic, while the proportion of those diagnosed as having COPD or similar diagnoses was small.

Different risk-factor patterns were found for asthma and type-1 allergy. In addition, the risk factors for atopic or allergic asthma diverged from those for nonatopic asthma.

We propose a model that characterizes and links the complexity and diversity of clinically observed hepatitis C viral kinetics to sustained virologic response (SVR)—the primary clinical end point of hepatitis C treatment, defined as an undetectable viral load at 24 weeks after completion of treatment)—in patients with chronic hepatitis C (CHC) who have received treatment with peginterferon α‐2a ± ribavirin. The new attributes of our hepatitis C viral kinetic model are (i) the implementation of a cure/viral eradication boundary, (ii) employment of all hepatitis C virus (HCV) RNA measurements, including those below the lower limit of quantification (LLOQ), and (iii) implementation of a population modeling approach. The model demonstrated excellent positive (99.3%) and negative (97.1%) predictive values for SVR as well as high sensitivity (96.6%) and specificity (99.4%). The proposed viral kinetic model provides a framework for mechanistic exploration of treatment outcome and permits evaluation of alternative CHC treatment options with the ultimate aim of developing and testing hypotheses for personalizing treatments in this disease. Clinical Pharmacology & Therapeutics (2010) 87 6, 706–713. doi:

As a first step in an intervention study of asthma and allergic diseases among school children, a cross-sectional study was performed during Winter 1996 in three towns (Kiruna, Luleå and Piteå) in the northernmost province of Sweden, Norrbotten. The cross-sectional study aimed to measure the prevalence of asthma, type-1 allergy and allergic diseases in order to make it possible to measure the incidence of the diseases, conditions and symptoms related to the diseases. Another aim was to perform a screening for possible risk factors. All children enrolled in the first and second classes at school, 7 and 8 years old, were invited to take part in this study. The ISAAC questionnaire with added questions about symptoms, morbidity, heredity and environment was distributed by the schools to the parents. The response rate was 97%, and 3431 completed questionnaires were returned. The children in two of the municipalities were also invited to skin test, and 2149 (88%) were tested with 10 common airborne allergens. The results showed that 7% of the children were currently using or had used asthma medicines during the last 12 months. Six percent had asthma diagnosed by a physician, and 4% were using inhaled corticosteroids. The prevalence of wheezing during the last 12 months was 12%, rhinitis without colds 14%, and eczema 27%, while 21% had a positive skin test. The respiratory symptoms and conditions were significantly greater in boys and, further, they were most prevalent in Kiruna in the very north, though not significantly. Type-1 allergy and asthma had different risk factor patterns. The main risk factors for asthma were a family history of asthma (OR = 3.2) followed by past or present house dampness (OR = 1.9), male sex (OR = 1.7) and a smoking mother (OR = 1.6). In Kiruna, when none of these three risk factors were present, none of the children had asthma, but when all three were present, 38% of these children were using asthma medicines.

No abstract

The aim of this study was to compare 2 stepwise covariate model-building strategies, frequently used in the analysis of pharmacokineticpharmacodynamic (PK-PD) data using nonlinear mixedeffects models, with respect to included covariates and predictive performance. In addition, the effects of stepwise regression on the estimated covariate coefficients were assessed. Using simulated and real PK data, covariate models were built applying (1) stepwise generalized additive models (GAM) for identifying potential covariates, followed by backward elimination in the computer program NONMEM, and (2) stepwise forward inclusion and backward elimination in NONMEM. Different versions of these procedures were tried (eg, treating different study occasions as separate individuals in the GAM, or fixing a part of the parameters when the NONMEM procedure was used). The final covariate models were compared, including their ability to predict a separate data set or their performance in crossvalidation. The bias in the estimated coefficients (selection bias) was assessed. The model-building procedures performed similarly in the data sets explored. No major differences in the resulting covariate models were seen, and the predictive performances overlapped. Therefore, the choice of model-building procedure in these examples could be based on other aspects such as analystand computer-time efficiency. There was a tendency to selection bias in the estimates, although this was small relative to the overall variability in the estimates. The predictive performances of the stepwise models were also reasonably good. Thus, selection bias seems to be a minor problem in this typical PK covariate analysis.ously estimated by the use of nonlinear mixed-effects models. One of the important aims in population PK-PD modeling is the establishment of relationships between parameters and covariates (ie, patient specific variables) to explain parameter variability and facilitate dose adjustment decisions.Stepwise model building is frequently employed in population PK(-PD) covariate model building with NONMEM (the most widely used program for population PK(-PD) modeling).1 For example, 58 of 60 papers (1999-2001) related to covariate model building in NONMEM included stepwise procedures (the reference list is available from the authors). No previous comparison between covariate model building procedures has been reported in the literature. In this article we assess the performances of 2 (objective) model-building strategies that make use of stepwise procedures. In addition, we explore how the results of a (typical) covariate analysis can be affected by selection bias, a general problem in stepwise regression. The search for important covariates is not always straightforward, especially if there are large numbers of covariate-parameter relations to consider. In addition to finding the "right" (ie, true or predictive) covariate, the right functional form of the relation must be identified. This may require considerable analyst-and/or computer run-time...

Only limited data are available about the incidence of asthma based on longitudinal prospective studies. Further, the results from different studies on incidence vary considerably depending on the age composition of the cohorts under study, the used methods and the criteria for disease. Also among adults high incidence rates have been reported during recent years. The aim of this study was to examine to what extent the incidence of physician-diagnosed asthma could be explained by a real incidence of the disease, and to what extend by an increased diagnostic activity or altered diagnostic praxis. Another aim was to study risk factors for asthma based on incident cases. Three cross-sectional surveys have been performed in the same population sample living in the northern-most province of Sweden, Norrbotten. The first survey was performed in 1986, and 5698 subjects, 86% of those invited, responded to a postal questionnaire. Of these, 4754 subjects (83%) participated at the third survey in 1996. After exclusion of all subjects who had reported that they had asthma in 1986, or had been classified as having asthma in 1986, 68 men and 98 women (P=0.02) reported in 1996 that they had been diagnosed as having asthma by a physician. Thus, the cumulative incidence for the 10-year period was 3.2% among men and 4.5% among women. After correction for subjects who already in 1986 had reported symptoms common in asthma, or had been classified as having chronic bronchitis, 97 subjects with incident asthma remained, which corresponded to an annual incidence rate among men of 1.7 and among women of 2.9/1000 persons year(-1) (P=0.1). Clinical examinations confirmed asthma in a large majority of these 97 subjects. Significant risk factors were family history of asthma, both ex- and current smoking, and female sex. The socio-economic groups manual workers and assistant non-manual employees were associated with incident asthma, although not significantly. The increasing prevalence of asthma among adults during recent 10-20 years may to a considerable extent be explained by an increased diagnostic activity or altered diagnostic praxis. Use of different methods when measuring incidence may in part explain the extremely diverging incidence rates of asthma found in different studies.