Case sampling for psychotherapy practice,theory, and policy guidance: Qualities and quantities

Random sampling of cases is usually infeasible for psychotherapy research, so opportunistic and purposive sampling must be used instead. Such sampling does not justify generalizations from sample to population-distribution statistics, but does justify reporting what independent-variable value configurations are associated with what dependent-variable value configurations. This allows only the generalization that these associations occur at least that frequently in the population sampled from, which is enough for suggesting and testing some psychotherapy theories and informing some psychotherapy practice. Although psychotherapy practice is a longitudinal process, formal psychotherapy outcome research is so far most feasible and most widely done in the form of two-phase cross-sectional input-outcome studies. Thus, the analysis of sampling for psychotherapy research here will be in terms of the independent- and dependent-variable value configurations produced in such two-phase studies.     

Glioblastoma multiforme: emerging treatments and stratification markers beyond new drugs

Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults. The standard therapy for GBM is maximal surgical resection followed by radiotherapy with concurrent and adjuvant temozolomide (TMZ). In spite of the extensive treatment, the disease is associated with poor clinical outcome. Further intensification of the standard treatment is limited by the infiltrating growth of the GBM in normal brain areas, the expected neurological toxicities with radiation doses >60 Gy and the dose-limiting toxicities induced by systemic therapy. To improve the outcome of patients with GBM, alternative treatment modalities which add low or no additional toxicities to the standard treatment are needed. Many Phase II trials on new chemotherapeutics or targeted drugs have indicated potential efficacy but failed to improve the overall or progression-free survival in Phase III clinical trials. In this review, we will discuss contemporary issues related to recent technical developments and new metabolic strategies for patients with GBM including MR (spectroscopy) imaging, (amino acid) positron emission tomography (PET), amino acid PET, surgery, radiogenomics, particle therapy, radioimmunotherapy and diets.     

Laser in der Endodontie

Der Freie Zahnarzt -     

Population pharmacokinetics and pharmacodynamics of ponesimod,a selective S1P1 receptor modulator

Ponesimod (ACT-128800), a reversible, orally active, selective S1P₁ receptor modulator, prevents the egress of lymphocytes from the lymph node into the systemic circulation. It is currently in clinical development for the treatment of relapsing multiple sclerosis. Modulation of circulating lymphocytes serves as biomarker of efficacy and safety, such that the quantitative characterization of the pharmacokinetic/pharmacodynamic (PK/PD) relationship guides the clinical development of the compound. The availability of a variety of doses, dosing regimens, and treatment durations permitted estimation of the pharmacokinetics characterized by an absorption lag time followed by a sequential zero/first-order absorption and two compartments with first-order elimination. The PD are modeled as an indirect-effect model with rates of appearance and disappearance of lymphocytes in blood with a circadian rhythm and a drug effect on the rate of appearance. The model suggests a circadian variation of 9 % and a maximum inhibition of 86 % of total lymphocyte count with high doses at steady state. It was instrumental for the selection of doses for subsequent studies that confirmed the effect plateau in total lymphocyte count at approximately 0.5 × 10⁹ counts/L.