Converging or Crossing Curves: Untie the Gordian Knot or Cut it? Appropriate Statistics for Non-Proportional Hazards in Decitabine DACO-016 Study (AML)

Introduction: Among patients with acute myeloid leukemia (AML), the DACO-016 randomized study showed reduction in mortality for decitabine [Dacogen® (DAC), Eisai Inc., Woodcliff Lake, NJ, USA] compared with treatment choice (TC): at primary analysis the hazard ratio (HR) was 0.85 (95% confidence interval 0.69-1.04; stratified log-rank P=0.108). With two interim analyses, two-sided alpha was adjusted to 0.0462. With 1-year additional follow-up the HR reached 0.82 (nominal P=0.0373). These data resulted in approval of DAC in the European Union, though not in the United States. Though pre-specified, the log-rank test could be considered not optimal to assess the observed survival difference because of the non-proportional hazard nature of the survival curves. Methods: We applied the Wilcoxon test as a sensitivity analysis. Patients were randomized to DAC (N=242) or TC (N=243). One-hundred and eight (44.4%) patients in the TC arm and 91 (37.6%) patients in the DAC arm selectively crossed over to subsequent disease modifying therapies at progression, which might impact the survival beyond the median with resultant converging curves (and disproportional hazards). Results: The stratified Wilcoxon test showed a significant improvement in median (CI 95%) overall survival with DAC [7.7 (6.2; 9.2) months] versus TC [5.0 (4.3; 6.3) months; P=0.0458]. Conclusion: Wilcoxon test indicated significant increase in survival for DAC versus TC compared to log-rank test. Funding: Janssen-Cilag GmbH

Adjusted Comparison of Outcomes between Patients from CARTITUDE-1 versus Multiple Myeloma Patients with Prior Exposure to PI, Imid and Anti-CD-38 from a German Registry

Ciltacabtagene autoleucel (cilta-cel) is a Chimeric antigen receptor T-cell therapy with the potential for long-term disease control in heavily pre-treated patients with relapsed/refractory multiple myeloma (RRMM). As cilta-cel was assessed in the single-arm CARTITUDE-1 clinical trial, we used an external cohort of patients from the Therapie Monitor registry fulfilling the CARTITUDE-1 inclusion criteria to evaluate the effectiveness of cilta-cel for overall survival (OS) and time to next treatment (TTNT) vs. real-world clinical practice. Individual patient data allowed us to adjust the comparisons between both cohorts, using the inverse probability of treatment weighting (IPW; average treatment effect in the treated population (ATT) and overlap population (ATO) weights) and multivariable Cox proportional hazards regression. Outcomes were compared in intention-to-treat (HR, IPW-ATT: TTNT: 0.13 (95% CI: 0.07, 0.24); OS: 0.14 (95% CI: 0.07, 0.25); IPW-ATO: TTNT: 0.24 (95% CI: 0.12, 0.49); OS: 0.26 (95% CI: 0.13, 0.54)) and modified intention-to-treat (HR, IPW-ATT: TTNT: 0.24 (95% CI: 0.09, 0.67); OS: 0.26 (95% CI: 0.08, 0.84); IPW-ATO: TTNT: 0.26 (95% CI: 0.11, 0.59); OS: 0.31 (95% CI: 0.12, 0.79)) populations. All the comparisons were statistically significant in favor of cilta-cel. These results highlight cilta-cel’s potential as a novel, effective treatment to address unmet needs in patients with RRMM

Comparative effectiveness of depot and oral second generation antipsychotic drugs in schizophrenia: A nationwide study in Hungary.

We conducted a nationwide, full-population based investigation to evaluate the comparative effectiveness of all marketed second generation antipsychotic drugs (SGA) prescribed for outpatients with the diagnosis of schizophrenia in Hungary. Using the national central register, our observational follow-up study included all patients with schizophrenia or related disorder between 01/01/2006 and 30/06/2008. The study cohort comprised 9567 patients who started new SGA during the inclusion period (01/07/2007-30/06/2008). All-cause medication discontinuation of 8 SGAs (1 depot and 7 oral formulations) marketed during the inclusion period, and the time to all-cause discontinuation were the main outcomes. Statistical models included the Kaplan-Meier and the Cox proportional hazards models with propensity score adjustment. Patients treated with a depot formulation risperidone had the longest time to discontinuation with a median of 215 days (95%CI:181-242 days), which was statistically significantly different compared to patients treated with the rest of the medications: olanzapine (136 days, 95%CI:121-153 days), aripiprazole (102 days, 95%CI:81-126 days), ziprasidone (93 days, 95%CI:82-119 days), quetiapine (89 days, 95%CI:81-100 days), clozapine (76 days, 95%CI:54-92 days), amisulpride (73 days, 95%CI:62-85 days), and risperidone (55 days, 95%CI: 41-63 days). Our results in Hungary are partly similar to those of a recent register-based study in Finland with patients who were discharged from their first hospitalization for schizophrenia (Tiihonen et al., 2006, 2011); namely the median times to all-cause medication discontinuation were <120 days for the majority of the oral SGA. In terms of medication differences, our data support the superior effectiveness of the depot formulation regarding all-cause discontinuation, followed by olanzapine at the efficacy rank order

Validiteit van IZIKA/IZIIK instrument voor doelgroep kinderen en jongeren met een handicap

Voorliggend rapport sluit aan bij breder onderzoek rond de implementatie van het IZIKA en IZIIK-instrument in het kader van de Intersectorale Toegangspoort voor Jeugdhulp. Het focust meerbepaald op de inschatting van zorgintensiteit voor kinderen en jongeren met een verstandelijke, motorische, zintuiglijke en/of meervoudige handicap. Het project zal de invulling en determinerende elementen van het begrip zorgintensiteit uit literatuur te vergelijken met de invulling van zorgniveaus/-items in IZIKA/IZIIK en voor elk van de geformuleerde subdoelgroepen te deze vergelijking te toetsen aan de mening van praktijkdeskundigen (professionele deskundigen m.b.t. de respectievelijke subdoelgroepen ). Verder tracht het onderzoek bij bestaande geanonimiseerde dossiers het geïndiceerde IZIKA/IZIIK – zorgniveau te correleren met een gemiddeld klinisch ordinaal oordeel. Het project geeft aanbevelingen bij gebruik van het instrument, en aan hulpverleners/verwijzers de aansluiting met andere mogelijke zorgzwaarte-instrumenten te duiden.status: publishe

De Oer-Faust : Overdruk van het afschrift van Fräulein von Göchhausen / Goethe. Met een vertaling door Joris Diels en een inleiding en een voordracht van Carl Niessen

DE OER-FAUST : OVERDRUK VAN HET AFSCHRIFT VAN FRÄULEIN VON GÖCHHAUSEN / GOETHE. MET EEN VERTALING DOOR JORIS DIELS EN EEN INLEIDING EN EEN VOORDRACHT VAN CARL NIESSEN De Oer-Faust : Overdruk van het afschrift van Fräulein von Göchhausen / Goethe. Met een vertaling door Joris Diels en een inleiding en een voordracht van Carl Niessen (1) Einband (1) Kapitel (10) Titelblatt (12) Kapitel (14) Bildtafel: Faust en Greetje / Greetje (15) Voorwoord van den uitgever (16) Bildtafel: Faust en Wagner (18) Bildtafel: Tooverteekens ... (19) Bildtafel: Faust en Wagner (doppelt) (20) Bildtafel: Tooverteekens ... (doppelt) (21) Verantwoording van den vertaler (22) Bezetting (23) Inkleeding en Tooneel voor de Vlaamsche opvoering van Goethe's Oer-Faust (Carl Niessen) (24) Bildtafel: Figurinen Siebel en Frosch (26) Bildtafel: Martha's kamer (27) Bildtafel: Figurinen Siebel en Frosch (doppelt) (28) Bildtafel: Martha's kamer (doppelt) (29) Inkleeding en Tooneel voor de Vlaamsche opvoering van Goethe's Oer-Faust (Carl Niessen) (30) Bildtafel: Mephisto en de Student / Mephisto en Martha (36) Inkleeding en Tooneel voor de Vlaamsche opvoering van Goethe's Oer-Faust (Carl Niessen) (37) Der Urfaust / De Oer-Faust (41) Goethe's Oer-Faust (Carl Niessen) (178) Bildtafel: In Auerbach's kelder (200) Goethe's Oer-Faust (Carl Niessen) (201) Bildtafel: Figurinen Faust en Greetje (206) Bildtafel: Decorontwerpen voor Tuin- en Spinnewielmonologen (207) Goethe's Oer-Faust (Carl Niessen) (208) Bildtafel: Greetje's gebed (212) Bildtafel: Figurinen Valentijn en Liesje (213) Goethe's Oer-Faust (Carl Niessen) (214) Bildtafel: Kerker (216) Goethe's Oer-Faust (Carl Niessen) (217) Literatuur (220) Inhoudsopgave, Drukfouten (222

Omgevings– en procesanalyse van gastopvang voor ouderen als startende inclusieve woonzorgvorm

status: publishe

L.ink: Actief netwerkgericht werken voor mensen met een beperkingen meten van sociaal kapitaal via inclusieweb

Dit project vertrekt vanuit de beleidsnota â Perspectief 2020â . Het ondersteuningsaanbod voor mensen met een beperking zal daardoor meer vraaggestuurd en flexibel worden, in de hoop ook meer inclusief te werken. Begeleiders zullen hun competenties als netwerkers moeten ontwikkelen of versterken. Op het niveau van de cliënt moet een actieve ondersteuning te gebeuren om de persoon met een beperking te â linkenâ in een breder ondersteunend formeel of informeel netwerk. Ondersteuning (vanuit een netwerk) is van enorm belang voor de kwaliteit van bestaan voor mensen met een beperking. 'Active support', ondersteuning waarin onder andere veel nieuwe initiatieven worden genomen, is de meest bepalende factor voor die kwaliteit van bestaan. Dit onderzoeksproject gaat op zoek naar methoden om organisaties en personen te helpen groeien naar meer en beter netwerken in functie van inclusie. Het gehanteerde meetinstrument is een zelf ontwikkelde online versie van het â Inclusion webâ (Bates, 2008;2010). De eerste resultaten van de baseline worden voorgesteld. Respondenten (n=73) hebben gemiddeld 13,2 contacten. Tevredenheid met het netwerk, frequentie van contacten, gegeven en ontvangen steun en emotionele afstand komen ook aan bod als afhankelijke variabelen voor verdere metingen.status: publishe

Comparative Efficacy of Ibrutinib Versus Obinutuzumab + Chlorambucil in First-Line Treatment of Chronic Lymphocytic Leukemia: A Matching-Adjusted Indirect Comparison

<p><strong>Article full text</strong></p> <p><br> The full text of this article can be found <a href="https://link.springer.com/article/10.1007/s12325-017-0564-1"><b>here</b>.</a><br> <br> <strong>Provide enhanced digital features for this article</strong><br> If you are an author of this publication and would like to provide additional enhanced digital features for your article then please contact <u>[email protected]</u>.<br> <br> The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.<br> <br> Other enhanced features include, but are not limited to:<br> • Slide decks<br> • Videos and animations<br> • Audio abstracts<br> • Audio slides<u></u></p

Yield response of Cauliflower to different 'just-in-time' fertilization treatments in an online-monitored approach

Today more than ever, increased crop production depends on judicious use of resources. In addition, issues such as climate change, climatic variability and environmental sequestration have become important issues. The objective of this study is to provide user-friendly ways for farmers to control the amount of nitrogen fertilizer in a very precise matter, in order to avoid overuse of fertilizer, which is not only harmful to the environment, but also a mayor production cost factor. This however should be realized without suffering from production or quality losses. An experimental site was set up, allowing real time follow-up of all fertilization and irrigation inputs and outputs. Drainage water per plot is being retained (impenetrable foil at depth of 90 cm) so that the volume can measured and sampled regularly for nitrogen content, as are the soil and the plants. Four different nitrogen application rates and 4 different treatments of fertilization resulted in a 4 by 4 completely randomized factorial design, replicated in two blocks. A broadcasting of calcium ammonium nitrate (CAN), a band fertilization with ammonium sulphate nitrate, a band fertilization of ammonium sulphate nitrate with a nitrification inhibitor and 2-weekly fertigation with CAN were the different administered fertilization schemes. Nitrogen target values were set at 50,100,150,200 kg N/ha at planting and 100,150,200,250 kg N/ha 5 weeks after planting. The corrective nitrogen application was done by subtracting the measured mineral nitrogen still present in the root zone from these target values). The values were chosen as such that the third highest dose coincides with the recommended value of the KNSsystem (Kulturbegleitenden Nmin Sollwerte), a generally accepted reference. In this way luxury nitrogen availability as well as restricted availability was present in the experiment. Destructive growth analysis of plant biomass, both leaves and curd, was carried out on fortnight basis. At harvest time, about 83 days after planting, plants were sampled, commercially (i.e. with leaf crown) and non-commercially (i.e. the whole plant). Both the curd and leaves were analyzed for fresh weight, dry weight and nitrogen content. No significant differences, in commercial quality of cauliflower, were found when the different fertilization methods were compared. However, a significant difference was found between the nitrogen-doses applied. The third and fourth dose had a significant higher output in fresh weight, dry weight and quality. Growth curves for the different treatments were calculated and analyzed.Poster Presentationstatus: publishe