Dispositional mindfulness and psychological health : a systematic review

Interest in the influence of dispositional mindfulness (DM) on psychological health has been gathering pace over recent years. Despite this, a systematic review of this topic has not been conducted. A systematic review can benefit the field by identifying the terminology and measures used by researchers and by highlighting methodological weaknesses and empirical gaps. We systematically reviewed non-interventional, quantitative papers on DM and psychological health in non-clinical samples published in English up to June 2016, following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A literature search was conducted using PsycINFO, PubMED, Medline and Embase, and 93 papers met the inclusion criteria. Within these, three main themes emerged, depicting the relationship between DM and psychological health: (1) DM appears to be inversely related to psychopathological symptoms such as depressive symptoms, (2) DM is positively linked to adaptive cognitive processes such as less rumination and pain catastrophizing and (3) DM appears to be associated with better emotional processing and regulation. These themes informed the creation of a taxonomy. We conclude that research has consistently shown a positive relationship between DM and psychological health. Suggestions for future research and conceptual and methodological limitations within the field are discussed

Epithelial Ovarian Cancer

Epithelial ovarian cancer generally presents at an advanced stage and is the most common cause of gynaecological cancer death. Treatment requires expert multidisciplinary care. Population-based screening has been ineffective, but new approaches for early diagnosis and prevention that leverage molecular genomics are in development. Initial therapy includes surgery and adjuvant therapy. Epithelial ovarian cancer is composed of distinct histological subtypes with unique genomic characteristics, which are improving the precision and effectiveness of therapy, allowing discovery of predictors of response such as mutations in breast cancer susceptibility genes BRCA1 and BRCA2, and homologous recombination deficiency for DNA damage response pathway inhibitors or resistance (cyclin E1). Rapidly evolving techniques to measure genomic changes in tumour and blood allow for assessment of sensitivity and emergence of resistance to therapy, and might be accurate indicators of residual disease. Recurrence is usually incurable, and patient symptom control and quality of life are key considerations at this stage. Treatments for recurrence have to be designed from a patient's perspective and incorporate meaningful measures of benefit. Urgent progress is needed to develop evidence and consensus-based treatment guidelines for each subgroup, and requires close international cooperation in conducting clinical trials through academic research groups such as the Gynecologic Cancer Intergroup.status: publishe

Dose-Finding Studies Among Orphan Drugs Approved in the EU : A Retrospective Analysis

In the development process for new drugs, dose-finding studies are of major importance. Absence of these studies may lead to failed phase 3 trials and delayed marketing authorization. In our study we investigated to what extent dose-finding studies are performed in the case of orphan drugs for metabolic and oncologic indications. We identified all orphan drugs that were authorized until August 1, 2017. European Public Assessment Reports were used to extract the final dose used in the summary of product characteristics, involvement of healthy volunteers, study type, end points used, number of patients, number of doses, studies in special populations, and dose used for phase 3 studies. Each drug was checked for major objections and dose changes postmarketing. We included 49 orphan drugs, of which 28 were indicated for metabolic disorders and 21 for oncologic indications. Dose-finding studies were performed in 32 orphan drugs, and studies in healthy volunteers in 26. The absence of dose-finding studies was mostly due to the rarity of the disease. In this case the dose was determined based on factors such as animal studies or clinical experience. Dose-related major objections were raised for 9 orphan drugs. Postmarketing dose-finding studies were conducted in 18 orphan drugs, but dose changes were applied in only 2 drugs. In conclusion, dose-finding studies in the case of metabolic and oncologic orphan drugs were conducted in the development programs of two thirds of orphan drugs. Dose-finding studies performed postmarketing suggest that registered doses are not always optimal. It is thus important to perform more robust dose-finding studies both pre- and postmarketing

Phase 2 study evaluating intermittent and continuous linsitinib and weekly paclitaxel in patients with recurrent platinum resistant ovarian epithelial cancer

Background. Linsitinib, an oral, dual inhibitor of insulin-like growth factor-1 receptor and insulin receptor, in combination with weekly paclitaxel, may improve clinical outcomes compared with paclitaxel alone in patients with refractory or platinum-resistant ovarian cancer. Patients and methods. This open-label phase 1/2 clinical trial (NCT00889382) randomized patients with refractory or platinum-resistant ovarian cancer (1:1:1) to receive either oral intermittent linsitinib (600 mg once daily on Days 1-3 per week) combined with paclitaxel (80 mg/m(2) on Days 1, 8, and 15; Arm A) or continuous linsitinib (150 mg twice daily) in combination with paclitaxel (Arm B), or paclitaxel alone (Arm C). Primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), overall response rate (ORR), disease control rate (DCR), and safety/tolerability. Results. A total of 152 women were randomized to treatment (n = 51 Arm A; n = 51 Arm B, n = 50 Arm C). In combination with paclitaxel, neither intermittent linsitinib (median PFS 2.8 months; 95% confidence interval [CI]:2.5-4.4) nor continuous linsitinib (median PFS 4.2 months; 95% CI:2.8-5.1) improved PFS over weekly paclitaxel alone (median PFS 5.6 months; 95% CI:3.2-6.9). No improvement in ORR, DCR, or OS in either linsitinib dosing schedule was observed compared with paclitaxel alone. Adverse event (AE) rates, including all-grade and grade 3/4 treatment-related AEs, and treatment-related AEs leading to discontinuation, were higher among patients receiving intermittent linsitinib compared with the other treatment arms. Conclusion. Addition of intermittent or continuous linsitinib with paclitaxel did not improve outcomes in patients with platinum-resistant/refractory ovarian cancer compared with paclitaxel alone. (C) 2018 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)