Effectivity of play-based interventions in children with autism spectrum disorder and their parents: a systematic review

Education and Child Studie

Irinotecan-Induced Toxicity:A Pharmacogenetic Study Beyond UGT1A1

Background and objective: Side effects of irinotecan treatment can be dose limiting and may impair quality of life. In this study, we investigated the correlation between single nucleotide polymorphisms (SNPs) in genes encoding enzymes involved in the irinotecan metabolism and transport, outside UGT1A1, and irinotecan-related toxicity. We focused on carboxylesterases, which are involved in formation of the active metabolite SN-38 and on drug transporters. Methods: Patients who provided written informed consent at the Erasmus Medical Center Cancer Institute to the Code Geno study (local protocol: MEC02-1002) or the IRI28-study (NTR-6612) were enrolled in the study and were genotyped for 15 SNPs in the genes CES1, CES2, SLCO1B1, ABCB1, ABCC2, and ABCG2. Results: From 299 evaluable patients, 86 patients (28.8%) developed severe irinotecan-related toxicity. A significantly higher risk of toxicity was seen in ABCG2 c.421C&gt;A variant allele carriers (P = 0.030, OR 1.88, 95% CI 1.06–3.34). Higher age was associated with all grade diarrhea (P = 0.041, OR 1.03, 95% CI 1.00–1.06). In addition, CES1 c.1165-41C&gt;T and CES1 n.95346T&gt;C variant allele carriers had a lower risk of all-grade thrombocytopenia (P = 0.024, OR 0.42, 95% CI 0.20–0.90 and P = 0.018, OR 0.23, 95% CI 0.08–0.79, respectively). Conclusion: Our study indicates that ABCG2 and CES1 SNPs might be used as predictive markers for irinotecan-induced toxicity.</p

Generalized AA-amyloidosis in Siamese and Oriental cats

During a 7 year period (1987-1994), 194 Siamese cats including a colour variant designated Oriental cat, were presented for post-mortem examination. Twelve of these animals (6.2%) were diagnosed with amyloidosis. Major gross pathological findings included enlarged pale livers with haemorrhages, pale and swollen spleens, and dilated intestines. Deposits of amyloid were found in these tissues. The amyloid was found to cross-react with anti dog AA- antiserum when examined with peroxidase antiperoxidase (PAP) staining (four cases). Amyloid fibrils were purified by the water extraction method and its major constituting protein (AA) was isolated by gel filtration. Amino acid sequence analysis of this protein from a Siamese cat and an Abyssinian cat revealed a significant difference between these breeds. In the Siamese protein AA two amino acid substitutions (46 R for Q and 52 V for A) were encountered. This finding indicates the existence of a new feline amyloid A protein occurring in the Siamese breed which differs from presently known (apoS)AA-proteins. Additionally, the pedigree analysis of affected cats suggests a familial trait

Generalized AA-amyloidosis in Siamese and Oriental cats

During a 7 year period (1987-1994), 194 Siamese cats including a colour variant designated Oriental cat, were presented for post-mortem examination. Twelve of these animals (6.2%) were diagnosed with amyloidosis. Major gross pathological findings included enlarged pale livers with haemorrhages, pale and swollen spleens, and dilated intestines. Deposits of amyloid were found in these tissues. The amyloid was found to cross-react with anti dog AA- antiserum when examined with peroxidase antiperoxidase (PAP) staining (four cases). Amyloid fibrils were purified by the water extraction method and its major constituting protein (AA) was isolated by gel filtration. Amino acid sequence analysis of this protein from a Siamese cat and an Abyssinian cat revealed a significant difference between these breeds. In the Siamese protein AA two amino acid substitutions (46 R for Q and 52 V for A) were encountered. This finding indicates the existence of a new feline amyloid A protein occurring in the Siamese breed which differs from presently known (apoS)AA-proteins. Additionally, the pedigree analysis of affected cats suggests a familial trait

Biological Consequences of Psychological Distress in Caregivers of Children with Autism Spectrum Disorder and its Potential Relevance to Other Chronic Diseases Including Cancer

Purpose of Review Caregivers of children with a chronic illness are a neglected group in medical research and patient care, and are frequently confronted with chronic psychological distress. The biological consequences of this chronic distress are unclear but highly relevant, as these caregivers have a lifelong task in caring for their child. In this review, the authors specifically describe caregiver distress related to autism spectrum disorder (ASD), but the review may be relevant to other chronic diseases, including cancer. Recent Findings Epidemiological evidence illustrates the increased mortality risk in caregivers of children with ASD although some individual factors appear to diminish these risks. Biological studies demonstrate that caregiver distress can lead to dysregulation of the hypothalamic-pituitary-adrenal-axis, a pro-inflammatory state of the immune and central nervous system, and gut microbiome imbalance. Caregivers of children with a chronic illness like ASD deserve more health-related attention with respect to their psychological and physical well-being. Such attention would benefit individual caregivers, as well as their children, as both are highly interconnected. Structural psychological and physical screening of caregivers can be considered.New methods for child psychiatric diagnosis and treatment outcome evaluatio

Early Identification of Patients at Risk of Cabazitaxel-induced Severe Neutropenia

BACKGROUND: Cabazitaxel frequently causes severe neutropenia. A higher cabazitaxel systemic exposure is related to a lower nadir absolute neutrophil count (ANC).OBJECTIVE: To describe the effect of cabazitaxel systemic exposure on ANC by a population pharmacokinetic/pharmacodynamic (POP-PK/PD) model, and to identify patients at risk of severe neutropenia early in their treatment course using a PK threshold.DESIGN, SETTING, AND PARTICIPANTS: Data from five clinical studies were pooled to develop a POP-PK/PD model using NONMEM, linking both patient characteristics and cabazitaxel systemic exposure directly to ANC.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A PK threshold, predictive of severe neutropenia (grade ≥3), was determined using a receiver operating characteristic curve.RESULTS AND LIMITATIONS: Ninety-six patients were included with a total of 1726 PK samples and 1081 ANCs. The POP-PK/PD model described both cabazitaxel PK and ANC accurately. A cabazitaxel plasma concentration of &gt;4.96 ng/ml at 6 h after the start of infusion was found to be predictive of severe neutropenia, with a sensitivity of 76% and a specificity of 65%.CONCLUSIONS: Early cabazitaxel plasma levels are predictive of severe neutropenia. Implementation of the proposed PK threshold results in early identification of almost 76% of all severe neutropenias. If prospectively validated, patients at risk could benefit from prophylactic administration of granulocyte colony stimulating factors, preventing severe neutropenia in an early phase of treatment. Implementation of this threshold permits a less restricted use of the 25 mg/m2 dose, potentially increasing the therapeutic benefit.PATIENT SUMMARY: Treatment with cabazitaxel chemotherapy often causes neutropenia, leading to susceptibility to infections, which might be life threatening. We found that a systemic cabazitaxel concentration above 4.96 ng/ml 6 h after the start of infusion is predictive of the occurrence of severe neutropenia. Measurement of systemic cabazitaxel levels provides clinicians with the opportunity to prophylactically stimulate neutrophil growth.</p

γ-Ray spectroscopy using a binned likelihood approach

The measurement of a reaction cross section from a pulse height spectrum is a ubiquitous problem in experimental nuclear physics. In γ-ray spectroscopy, this is accomplished frequently by measuring the intensity of full-energy primary transition peaks and correcting the intensities for experimental artifacts, such as detection efficiencies and angular correlations. Implicit in this procedure is the assumption that full-energy peaks do not overlap with any secondary peaks, escape peaks, or environmental backgrounds. However, for complex γ-ray cascades, this is often not the case. Furthermore, this technique is difficult to adapt for coincidence spectroscopy, where intensities depend not only on the detection efficiency, but also the detailed decay scheme. We present a method that incorporates the intensities of the entire spectrum (e.g., primary and secondary transition peaks, escape peaks, Compton continua, etc.) into a statistical model, where the transition intensities and branching ratios can be determined using Bayesian statistical inference. This new method provides an elegant solution to the difficulties associated with analyzing coincidence spectra. We describe it in detail and examine its efficacy in the analysis of 18O(p,γ)19F and 25Mg(p,γ)26Al resonance data. For the 18O(p,γ)19F reaction, the measured branching ratios improve upon the literature values, with a factor of 3 reduction in the uncertainties