A Phase Ib/II,open-label,multicenter study of INC280 (capmatinib) alone and in combination with buparlisib (BKM120) in adult patients with recurrent glioblastoma

Journal of Neuro-Oncology - To estimate the maximum tolerated dose (MTD) and/or identify the recommended Phase II dose (RP2D) for combined INC280 and buparlisib in patients with recurrent...     

Ocular Redness Measured with the Keratograph 5M in Patients Using Anti-Glaucoma Eye Drops

Purpose: To examine correlations between ocular redness measured with the new topographer Keratograph 5M and the use of topical anti-glaucoma medication. Methods: A total of 211 eyes of 211 patients with open-angle glaucoma or ocular hypertension on topical medication and 51 eyes of 51 healthy volunteers were recruited over 10 months. Outcome variables were keratograph redness scores (RS): overall, bulbar temporal (BT), bulbar nasal (BN), limbar temporal (LT), and limbar nasal (LN). In each subject, we also recorded the intraocular pressure-lowering eye drops used, daily doses and daily and cumulative preservative concentrations, fluorescein corneal staining score (OXFORD), lower tear meniscus height (Fourier-domain OCT), non-invasive tear film breakup time (Keratograph 5M), and ocular surface disease questionnaire index (OSDI). Results: Higher RS were recorded in the medication than control group (P < 0.01 all scores). Within the medication group, older patients returned greater RS (P < 0.05 all scores). Prostaglandin was a strong predictor of higher scores, except LN RS. A higher OSDI was associated with a higher LN RS (β = 0.007; P < 0.05), while the use of β-blockers was linked to a lower LN RS (β = ?0.225; P < 0.05). The use of ≥3 daily eye drops with preservative gave rise to a higher BN RS and ≥3 daily eye drops to a higher LN RS (β = 0.366, P < 0.01; β = 0.296, P < 0.05, respectively). Conclusion: Keratograph 5M can objectively detect the hyperaemia induced by glaucoma medication. The factors contributing to ocular redness were advanced age, more daily eye drops (nasal sectors), a higher OSDI, and prostaglandin as the medication used.     

Deficits of entropy modulation of the EEG: A biomarker for altered function in schizophrenia and bipolar disorder?

BackgroundThe synchronized activity of distributed neural assemblies — reflected in the electroencephalogram (EEG) — underpins mental function. In schizophrenia, modulation deficits of EEG spectral content during a P300 task have been replicated. The effects of treatment, chronicity and specificity in these deficits and their possible relationship with anatomic connectivity remain to be explored.MethodsWe assessed spectral entropy modulation of the EEG during a P300 task in 79 patients with schizophrenia (of those, 31 were in their first episode), 29 patients with bipolar disorder and 48 healthy controls. Spectral entropy values summarize EEG characteristics by quantifying the irregularity of spectral content. In a subsample, we calculated the network architecture of structural connectivity using diffusion tensor imaging and graph-theory parameters.ResultsWe found significant spectral entropy modulation deficits with task performance in patients with chronic or first-episode schizophrenia and in patients with bipolar disorder, without significant pre-stimulus spectral entropy differences. The deficits were unrelated to treatment doses, and spectral entropy modulation did not differ between patients taking or not taking antipsychotics, lithium, benzodiazepines or antidepressants. Structural connectivity values were unrelated to spectral entropy modulation. In patients with schizophrenia, spectral entropy modulation was inversely related to negative symptoms and directly related to verbal memory.LimitationsAll patients were taking medication. Patients with bipolar disorder were euthymic and chronic. The cross-sectional nature of this study prevented a more thorough analysis of state versus trait criteria for spectral entropy changes.ConclusionSpectral entropy modulation with task performance is decreased in patients with schizophrenia and bipolar disorder. This deficit was not an effect of psychopharmacological treatment or structural connectivity and might reflect a deficit in the synchronization of the neural assemblies that underlie cognitive activity.     

Quantification of hormonal changes by effects of hippotherapy in the autistic population

Zootherapy, more specifically in its equine form, has proliferated recently as a therapeutic activity and is one of the most common applications in the stimulation of autistic individuals. At the same time, the influence of certain hormones was recently revealed in the behavior of autistic spectrum disorders. We propose to objectify the influence of analyzing equestrian therapies through laboratory methods and non-invasive techniques (salivary samples), in the hormone levels of cortisol and progesterone, thus indirectly those of oxytocin, before and after hippotherapy sessions for people with Autism Spectrum Disorder (ASD). The main results indicated that equine therapy decreased (p ?? 0.05) the levels of salivary Cortisol in the rest of the sessions (before Hippotherapy 33.11 ± 0.96 ng/mL vs. after Hippotherapy 2.23 ± 0.75 ng/mL). And also the levels of salivary progesterone in the first session (before Hippotherapy 28.63 ± 12.81 ng/mL vs. after Hippotherapy 51.59 ± 33.11 ng/mL) and in the rest of the sessions (before hippotherapy 21.58 ± 12 pg/mL vs. after Hippotherapy 26.03 ± 11.98 pg/mL) which was always on the rise. These effective results were corroborated with the Cortisol/Progesterone Balance which reduced after equine therapy in the first session (before Hippotherapy 99.87 vs. after Hippotherapy 76.24) and the other sessions (before Hippotherapy 181.31 vs. after Hippotherapy 110.48). In conclusion, the Hippotherapy sessions for the population with ASD generated leads to an improvement in social attitudes, and it is confirmed with the effective modulation of the implicating hormones.     

Inter-cycle and inter-observer variability of the antral follicle count in routine clinical practice

Antral follicle count (AFC) is a reliable predictor of ovarian response to stimulation and its inter-cycle and inter-observer variability has been extensively studied on in vitro fertilization (IVF), mostly in highly selected populations within studies not originally designed for this purpose. In this retrospective cohort study, we assess the inter-cycle variation of AFC in a setting similar to that of the daily practice. We included only patients undergoing mild stimulation for intrauterine insemination (IUI). One hundred and forty-eight patients had two (62 patients, group A), three (49 patients, group B) or four (37 patients, group C) IUI cycles and AFC was measured on early follicular phase of each cycle by one of the members of the medical team within daily practice. Intra-class correlation coefficients were used to estimate variability. Inter-cycle variability rendered ICCs above 0.70 in all groups improving along with the number of cycles [Group A ICC 0.78 (95%CI 0.66–0.86), Group B ICC 0.87 (95%CI 0.80–0.92) and Group C ICC 0.91 (95%CI 0.85–0.95)]. Inter-observer variability showed a high degree of concordance with ICCs above 0.95. We provide the closest approximation to real inter-cycle and inter-observer AFC variability expected in routine clinical practice.