Exposure–Response Analysis of Osimertinib in EGFR Mutation Positive Non-Small Cell Lung Cancer Patients in a Real-Life Setting

Pharmaceutical Research - Osimertinib, an irreversible inhibitor of the epidermal growth factor receptor (EGFR) is an important drug in the treatment of EGFR-mutation positive non-small cell lung...     

Predictors of health-related quality of life and participation after brain injury rehabilitation: The role of neuropsychological factors

The aims of this longitudinal study were: (1) to assess associations between neuropsychological factors and health-related quality of life (HRQoL) and participation three months after discharge from inpatient acquired brain injury (ABI) rehabilitation; and (2) to determine the best neuropsychological predictor of HRQoL and participation after controlling for demographic and injury-related factors. Patients with ABI (n?=?100) were assessed within approximately two weeks of enrolment in inpatient rehabilitation. Predictor variables included demographic and injury-related characteristics and the following neuropsychological factors: active and passive coping, attention, executive functioning, verbal memory, learning potential, depressive symptoms, motivation, extraversion, neuroticism and self-awareness. Bivariate analyses revealed that passive coping, executive functioning, depressive symptoms, extraversion, and neuroticism were significantly associated with HRQoL and/or participation. Neuropsychological factors significantly explained additional variance in HRQoL (18.1–21.6%) and participation (6.9–20.3%) after controlling for demographic and injury-related factors. However, a higher tendency towards passive coping was the only significant neuropsychological predictor (β?=??0.305 to ?0.464) of lower HRQoL and participation. This study shows that neuropsychological functioning, and in particular passive coping, plays a role in predicting HRQoL and participation after inpatient ABI rehabilitation and emphasises the importance of addressing patients’ coping styles in an early phase of ABI rehabilitation.     

Biological properties and molecular biology of the human macrophage growth factor, CSF-1

CSF-1 is a growth and differentiation factor for the production of mononuclear phagocytes from undifferentiated bone marrow progenitors. In addition to previously described effects on mature cells, we show here that CSF-1 stimulates the production by monocytes of interferon, tumor necrosis factor, and myeloid CSF that produces mainly mixed neutrophil-macrophage colonies in bone marrow culture. Pretreatment with CSF-1 also promotes resistance to viral infection and tumor cytotoxicity in murine peritoneal macrophages. Based on amino acid sequence data of purified human urinary and murine L cell CSF-1, we have cloned the complementary DNA (cDNA) from messenger RNA (mRNA) of the human CSF-1 producing MIA PaCa cell line. The cDNA specifies a 32 amino acid signal peptide followed by a protein of 224 amino acids. Several facts suggest, however, that one-third of the molecule at the C-terminal end is processed off intracellularly to derive the secreted growth factor. The gene is about 18 kilobases (kb) in length and contains 9 exons. Although there appears to be a single copy gene for CSF-1, cells expressing the factor contain several mRNA species, suggesting that the gene may have several functions or levels of regulation. High level expression of the recombinant protein will allow preclinical testing in several disease models for therapeutic efficacy that has been suggested from in vitro and in vivo biological properties of CSF-1.     

Exploring the relation between learning style and cognitive impairment in patients with acquired brain injury

The way a patient prefers to approach or choose a learning situation represents the patient's learning style. The objective of this chart review study was to explore the relation between learning style and cognitive impairment in patients with acquired brain injury (ABI). We used data from files of 92 adult patients with ABI referred to inpatient rehabilitation, who completed the Adapted Learning Style Inventory (A-LSI) and at least one of the following neuropsychological tests: Trail Making Test, Rey Auditory Verbal Learning Test, WAIS-III Digit Span, Rey-Osterrieth Complex Figure Test-Copy, Stroop Color-Word Test, or the Brixton Spatial Anticipation Test. The A-LSI yielded the following distribution of learning styles: 4 doers, 48 observers, 2 deciders and 38 thinkers. No significant correlation coefficients were found between the neuropsychological tests and the A-LSI. Furthermore, Chi-square tests revealed no significant associations between learning style (observer, thinker) and cognitive impairment. The results of this exploratory study suggest that learning style and cognitive impairment are independent in patients with ABI.     

Ritonavir-Boosted Exposure of Kinase Inhibitors: an Open Label,Cross-over Pharmacokinetic Proof-of-Concept Trial with Erlotinib

Pharmaceutical Research - Although kinase inhibitors (KIs) are generally effective, their use has a large impact on the current health care budget. Dosing strategies to reduce treatment costs are...     

Validity of the Barrow Neurological Institute (BNI) Screen for Higher Cerebral Functions in Stroke Patients with Good Functional Outcome

Cognitive impairments are often under diagnosed in stroke patients with good functional outcome. There is a need for a cognitive screening instrument that is sufficiently sensitive to cognitive impairments in these stroke patients. For this goal, we tested the feasibility and validity of the Barrow Neurological Institute Screen for Higher Cerebral Functions (BNIS). Stroke patients with good functional outcome (Barthel Index 19/20) within 1 year poststroke were administered the BNIS and a brief neuropsychological assessment (NPA) including tests for perception, language, memory, attention, reasoning, and executive functioning. We compared the BNIS with the NPA to investigate its feasibility, internal consistency, floor and ceiling effects, concurrent validity, sensitivity and specificity. Fifty-four stroke patients were included. It took significantly less time to administer the BNIS (median = 16 minutes) than the NPA (median = 32.7 minutes). The BNIS showed good internal consistency (alpha = .82) and no floor or ceiling effects. The recommended cutoff values yielded good sensitivity and low to good specificity, depending on age. Except for perception (Spearman correlation .33), BNIS domain scores were significantly (0.44–0.55) associated with matching neuropsychological tests. This study provides promising results for the BNIS as a measure to detect cognitive impairments in stroke patients with good functional outcome.     

Further validation of the Motivation for Traumatic Brain Injury Rehabilitation Questionnaire (MOT-Q) in patients with acquired brain injury

The Motivation for Traumatic Brain Injury Rehabilitation Questionnaire (MOT-Q) evaluates motivation for rehabilitation in four subscales: Interest in rehabilitation, Lack of anger, Lack of denial, and Reliance on professional help. The objective of this study was to further validate the MOT-Q in 122 inpatients and 92 outpatients with acquired brain injury (ABI). The main measures were motivation for rehabilitation (MOT-Q), self-awareness (Patient Competency Rating Scale), and treatment motivation (Visual Analogue Scale). The MOT-Q showed adequate feasibility in terms of few items with missing responses and few undecided responses. We found no floor or ceiling effects, and significant item-total MOT-Q correlations for 29 of 31 items. Internal consistency was good for the MOT-Q total and acceptable to good for the subscales. The MOT-Q scores were significantly intercorrelated except for the subscales Lack of denial and Reliance on professional help in the inpatient group. The MOT-Q total and subscales were significantly associated with treatment motivation. The Lack of denial subscale showed no significant association with treatment motivation and no to moderate significant associations with self-awareness. In conclusion, the overall MOT-Q is a valid instrument to assess motivation for rehabilitation in patients with ABI. Further research is needed to examine the validity of the subscales.