Classification and occurrence of clinically significant drug interactions with irinotecan and oxaliplatin in patients with metastatic colorectal cancer

Background: Pharmacokinetic and pharmacodynamic drug interactions with cytotoxic drugs may significantly influence the efficacy and toxicity of chemotherapy. Objective: The purpose of this study was to identify drug interactions with irinotecan and oxaliplatin reported in the literature, to assess their clinical significance, and to examine the occurrence of these interactions in patients with metastatic colorectal cancer treated with either irinotecan or oxaliplatin or both. Methods: To obtain data on drug-drug interactions with irinotecan and oxaliplatin, a literature search of PubMed and EMBASE was conducted using the search terms irinotecan, oxaliplatin, and interactions (English-language studies only published between 1980 and August 2004). The interactions found were subsequently classified for documentation evidence and severity of clinical effect, according to a 5-level classification system of a standard reference text, by a study panel of medical oncologists and clinical pharmacists. Comedication of patients who were treated with irinotecan or oxaliplatin, or both, was then examined to determine the occurrence of clinically significant interactions. Results: Ninety-eight patients (50 women, 48 men; mean age, 60 years) were included in the study. Seventeen interactions with irinotecan were found in the literature, and 11 were classified as clinically significant. Only 1 nonspecific, clinically significant interaction was identified for oxaliplatin. Irinotecan-treated patients received a mean of 8 different comedications and oxaliplatin-treated patients received a mean of 6. Apart from antiemetic and antidiarrheal drugs that were prescribed for treatment-related toxicities, only 1 patient appeared to be exposed to a possible clinically significant interaction (between irinotecan and phenytoin). Conclusions: Eleven of the 17 interactions with irinotecan that were found in the literature were classified as clinically significant versus 1 clinically significant interaction with oxaliplatin. The occurrence of these interactions in the study patients with metastatic colorectal cancer was low. For medication surveillance purposes, however, the significant interactions should be considered in clinical practice. Copyright (c) 2005 Excerpta Medica, Inc

Genetic contribution to the P3 in young and middle-aged adults.

Previous studies in young and adolescent twins suggested substantial genetic contributions to the amplitude and latency of the P3 evoked by targets in an oddball paradigm. Here we examined whether these findings can be generalized to adult samples. A total of 651 twins and siblings from 292 families participated in a visual oddball task. In half of the subjects the age centered around 26 (young adult cohort), in the other half the age centered around 49 (middle-aged adult cohort). P3 peak amplitude and latency were scored for 3 midline leads Pz, Cz, and Fz. No cohort differences in heritability were found. P3 amplitude (∼50%) and latency (∼45%) were moderately heritable for the 3 leads. A single genetic factor influenced latency at all electrodes, suggesting a single P3 timing mechanism. Specific genetic factors influenced amplitude at each lead, suggesting local modulation of the P3 once triggered. Genetic analysis of the full event-related potential waveform showed that P3 heritability barely changes from about 100 ms before to 100 ms after the peak. Age differences are restricted to differences in means and variances, but the proportion of genetic variance as part of the total variance of midline P3 amplitude and latency does not change from young to middle-aged adulthood

Phylogeny and Taxonomy of the Round-Eared Sengis or Elephant-Shrews, Genus Macroscelides (Mammalia, Afrotheria, Macroscelidea)

The round-eared sengis or elephant-shrews (genus Macroscelides) exhibit striking pelage variation throughout their ranges. Over ten taxonomic names have been proposed to describe this variation, but currently only two taxa are recognized (M. proboscideus proboscideus and M. p. flavicaudatus). Here, we review the taxonomic history of Macroscelides, and we use data on the geographic distribution, morphology, and mitochondrial DNA sequence to evaluate the current taxonomy. Our data support only two taxa that correspond to the currently recognized subspecies M. p. proboscideus and M. p. flavicaudatus. Mitochondrial haplotypes of these two taxa are reciprocally monophyletic with over 13% uncorrected sequence divergence between them. PCA analysis of 14 morphological characters (mostly cranial) grouped the two taxa into non-overlapping clusters, and body mass alone is a relatively reliable distinguishing character throughout much of Macroscelides range. Although fieldworkers were unable to find sympatric populations, the two taxa were found within 50 km of each other, and genetic analysis showed no evidence of gene flow. Based upon corroborating genetic data, morphological data, near sympatry with no evidence of gene flow, and differences in habitat use, we elevate these two forms to full species

The feasibility of using Apple's ResearchKit for recruitment and data collection: Considerations for mental health research

In 2015, Apple launched an open-source software framework called ResearchKit. ResearchKit provides an infrastructure for conducting remote, smartphone-based research trials through the means of Apple's App Store. Such trials may have several advantages over conventional trial methods including the removal of geographic barriers, frequent assessments of participants in real-life settings, and increased inclusion of seldom-heard communities. The aim of the current study was to explore the feasibility of participant recruitment and the potential for data collection in the non-clinical population in a smartphone-based trial using ResearchKit. As a case example, an app called eMovit, a behavioural activation (BA) app with the aim of helping users to build healthy habits was used. The study was conducted over a 9-month period. Any iPhone user with access to the App Stores of The Netherlands, Belgium, and Germany could download the app and participate in the study. During the study period, the eMovit app was disseminated amongst potential users via social media posts (Twitter, Facebook, LinkedIn), paid social media advertisements (Facebook), digital newsletters and newspaper articles, blogposts and other websites. In total, 1,788 individuals visited the eMovit landing page. A total of 144 visitors subsequently entered Apple's App Store through that landing page. The eMovit product page was viewed 10,327 times on the App Store. With 79 installs, eMovit showed a conversion rate of 0.76% from product view to install of the app. Of those 79 installs, 53 users indicated that they were interested to participate in the research study and 36 subsequently consented and completed the demographics and the participants quiz. Fifteen participants completed the first PHQ-8 assessment and one participant completed the second PHQ-8 assessment. We conclude that from a technological point of view, the means provided by ResearchKit are well suited to be integrated into the app process and thus facilitate conducting smartphone-based studies. However, this study shows that although participant recruitment is technically straightforward, only low recruitment rates were achieved with the dissemination strategies applied. We argue that smartphone-based trials (using ResearchKit) require a well-designed app dissemination process to attain a sufficient sample size. Guidelines for smartphone-based trial designs and recommendations on how to work with challenges of mHealth research will ensure the quality of these trials, facilitate researchers to do more testing of mental health apps and with that enlarge the evidence-base for mHealth

Differential effects of Atomoxetine on executive functioning and lexical decision in Attention-Deficit/Hyperactivity Disorder and Reading Disorder

Objective: The effects of a promising pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD), atomoxetine, were studied on executive functions in both ADHD and reading disorder (RD) because earlier research demonstrated an overlap in executive functioning deficits in both disorders. In addition, the effects of atomoxetine were explored on lexical decision. Methods: Sixteen children with ADHD, 20 children with ADHD + RD, 21 children with RD, and 26 normal controls were enrolled in a randomized placebo-controlled crossover study. Children were measured on visuospatial working memory, inhibition, and lexical decision on the day of randomization and following two 28-day medication periods. Results: Children with ADHD + RD showed improved visuospatial working memory performance and, to a lesser extent, improved inhibition following atomoxetine treatment compared to placebo. No differential effects of atomoxetine were found for lexical decision in comparison to placebo. In addition, no effects of atomoxetine were demonstrated in the ADHD and RD groups. Conclusion: Atomoxetine improved visuospatial working memory and to a lesser degree inhibition in children with ADHD + RD, which suggests differential developmental pathways for co-morbid ADHD + RD as compared to ADHD and RD alone

Renal dysfunction is associated with shorter telomere length in heart failure

Renal dysfunction is a frequent comorbidity associated with high mortality in patients with chronic heart failure (CHF). The intrinsic biological age might affect the ability of the kidney to cope with the challenging environment caused by CHF. We explored the association between leukocyte telomere length, a marker for biological age, and renal function in patients with CHF. Telomere length was determined by a real-time quantitative polymerase chain reaction in 866 CHF patients. Renal function was estimated with the simplified Modification of Diet in Renal Disease equation. The median age was 74 (interquartile range 64-79) years, 61% male, left ventricular ejection fraction of 30 (23-44)%, and the estimated glomerular filtration rate was 53 (40-68) ml/min/1.73 m(2). Telomere length was associated with renal function (correlation coefficient 0.123, P <0.001). This relationship remained significant after adjustment for age, gender, age of CHF onset (standardized-beta 0.091, P = 0.007). Also additionally adjusting for the severity of CHF and baseline differences did not change our findings. The association between shorter leukocyte telomere length and reduced renal function in heart failure suggests that intrinsic biological aging affects the ability of the kidney to cope with the systemic changes evoked by heart failure

Neuropsychological intervention in kindergarten children with subtyped risks of reading retardation

Kindergarten children at risk of developing language problems were administered the Florida Kindergarten Screening Battery. A principal components analysis revealed a verbal and a visual-spatial component and subsequent discriminant function analyses a high verbal/low visual-spatial group (LAL: Latent L) and a high visual-spatial/low verbal group (LAP: Latent P). LAL- and LAP-children were considered at risk for developing an L- or P-type of dyslexia, respectively. As is common practice with children suffering from manifest L- or Pdyslexia, the LAL- and LAP-kindergartners received right and left hemisphere stimulation, respectively. The outcomes were compared with those of bilateral hemispheric stimulation and no intervention. Reading tests were administered in primary school Grades 1 and 5/6; teachers' evaluation of reading took place in Grade 5/6. Overall, the LAL- and LAP- groups showed significant backwardness in word and text reading, both at early and late primary school. Types of intervention made a difference though: not significantly backward in early word, late word, and late text reading were the LAL-children who had received right hemisphere stimulation. Nonintervened LAP-children did not show significant backwardness in early word reading and late text reading, nor did LAP-children who had received left hemisphere or bilateral stimulation. Early text reading was not affected by any treatment. Teacher's evaluations were in support of these findings. Copyright © 2005 by The International Dyslexia Association®