High-dose chemotherapy:studies on supportive care, quality of life and late effects of treatment

Drug resistance is a major problem in the treatment of malignancies. Based on steep dose-response relationship for certain chemotherapeutic drugs in vitro on tumor cell survival, high-dose chemotherapy was considered of interest for the treatment of malignancies. Introduction of autologous bone-marrow toxic chemotherapy while thereafter the bone-marrow was rescued. Initially there were high expectations for the application in solid tumors. Nowadays, following numerous phase 2 and a number of phase 3 studies its precise role in solid tumors is unknown. Therefore, the meta-analysis of especially high-dose chemotherapy in the adjuvant breast cancer setting is eagerly awaited. High-dose chemotherapy induces considerable morbidity. The balance between side effects and survival benefit will finally determine the indication(s) for this treatment modality in solid tumors. This thesis aims to give in depth insight in a number of short-term and long-term side effects that are consequences of high-dose chemotherapy

Cost-effectiveness of a pressure ulcer quality collaborative

ABSTRACT. BACKGROUND: A quality improvement collaborative (QIC) in the Dutch long-term care sector (nursing homes, assisted living facilities, home care) used evidence-based prevention methods to reduce the incidence and prevalence of pressure ulcers (PUs). The collaborative consisted of a core team of experts and 25 organizational project teams. Our aim was to determine its cost-effectiveness from a healthcare perspective. METHODS: We used a non-controlled pre-post design to establish the change in incidence and prevalence of PUs in 88 patients over the course of a year. Staff indexed data and prevention methods (activities, materials). Quality of life (Qol) weights were assigned to the PU states. We assessed the costs of activities and materials in the project. A Markov model was built based on effectiveness and cost data, complemented with a probabilistic sensitivity analysis. To illustrate the results of longer term, three scenarios were created in which change in incidence and prevalence measures were (1) not sust

Geographic and temporal validity of prediction models: different approaches were useful to examine model performance

AbstractObjectiveValidation of clinical prediction models traditionally refers to the assessment of model performance in new patients. We studied different approaches to geographic and temporal validation in the setting of multicenter data from two time periods.Study Design and SettingWe illustrated different analytic methods for validation using a sample of 14,857 patients hospitalized with heart failure at 90 hospitals in two distinct time periods. Bootstrap resampling was used to assess internal validity. Meta-analytic methods were used to assess geographic transportability. Each hospital was used once as a validation sample, with the remaining hospitals used for model derivation. Hospital-specific estimates of discrimination (c-statistic) and calibration (calibration intercepts and slopes) were pooled using random-effects meta-analysis methods. I2 statistics and prediction interval width quantified geographic transportability. Temporal transportability was assessed using patients from the earlier period for model derivation and patients from the later period for model validation.ResultsEstimates of reproducibility, pooled hospital-specific performance, and temporal transportability were on average very similar, with c-statistics of 0.75. Between-hospital variation was moderate according to I2 statistics and prediction intervals for c-statistics.ConclusionThis study illustrates how performance of prediction models can be assessed in settings with multicenter data at different time periods

Elucidation of the Structure of Solanoeclepin A, a Natural Hatching Factor of Potato and Tomato Cyst Nematodes, by Single-crystal X-ray Diffraction

Potato crops can be severely damaged by potato cyst nematodes Globodera rostochiensis and Globodera pallida, nematodes highly specific to potatoes and some other Solanaceae. Hatching of juveniles is controlled by agents excreted by the roots of some Solanaceae species. Over seventy years much effort has been expended by many groups to isolate these agents and to determine their structures. However, all attempts have failed. We report here the structure determination of a hatching factor excreted from potato and tomato roots. The hatching factor bears some resemblance to Glycinoeclepins as found by Masamune et al.2-5 and is hence designated as Solanoeclepin A.1 C27H30O9.3H2O, Mr = 498.5, monoclinic, P21, a = 11.289(2), b = 20.644(4), c = 11.632(12) Å, β = 90.81(4), V = 2711(3) Å3, Z = 4, Dx = 1.35 g cm–3, λ(Cu-K&alpha ) = 1.5418 Å, μ(Cu-Kα ) = 9.0 cm–1, F(000) = 1176, –60 °C. Final R = 0.117 for 3721 observed reflections