Search

BACKGROUND Functional variants of inosine triphosphatase (ITPA) were recently found to protect against ribavirin (RBV)-induced hemolytic anemia. However, no definitive data are yet available on the role of plasma RBV concentrations on hemoglobin (Hb) decrement. Moreover, no data have been published on the possible interplay between these 2 factors. METHODS A retrospective analysis included 167 patients. The ITPA variants rs7270101 and rs1127354 were genotyped and tested using the χ test for association with Hb reduction at week 4. We also investigated, using multivariate logistic regression, the impact of RBV plasma exposure on Hb concentrations. RESULTS Both single nucleotide polymorphisms were associated with Hb decrease. The carrier of at least 1 variant allele in the functional ITPA single nucleotide polymorphisms was associated with a lower decrement of Hb (-1.1 g/dL), as compared with patients without a variant allele (-2.75 g/dL; P = 4.09 × 10). RBV concentrations were not influenced by ITPA genotypes. A cut-off of 2.3 μg/mL of RBV was found to be associated with anemia (area-under-receiver operating characteristic = 0.630, sensitivity = 50.0%, and specificity = 69.5%, P = 0.008). In multivariate logistic regression analyses, the carrier of a variant allele (P = 0.005) and plasma RBV concentrations

BACKGROUND Imatinib (Gleevec, STI-571), a 2-phenylaminopyrimidine-type competitive inhibitor of Bcr-Abl kinase, is the current frontline therapy for patients with chronic myeloid leukemia, and it induces durable responses and prolonging event-free and progression-free survival. Monitoring imatinib trough plasma concentration is a simple and rapid way to determine if the drug exposure exceeds the clinical efficacy threshold (1 mcg/mL). Because the target enzyme is located within cells, adequate drug intracellular concentrations are needed to inhibit its function. METHODS Chromatographic methods were used to quantify imatinib concentrations in both plasma and peripheral blood mononuclear cells collected from adult patients with chronic myeloid leukemia at the Department of Hematology. Samples were collected at steady state, and trough concentrations (24 ± 2 hours after last drug intake) were evaluated. Associations between variables were tested using the Pearson test; results are presented as mean (±SD). RESULTS Thirty-five samples from 24 patients were collected; patients were mainly men (16, 66.7%), aged 60 years old (±13.1) and with a body mass index of 24.8 (±4.4). A positive and significant correlation (r = 0.203; P = 0.027) was found between imatinib plasma and intracellular concentrations. CONCLUSIONS The observed correlation between plasma and intracellular imatinib concentrations suggests that they may be used to monitor drug exposure and treatment efficacy.

Information retrieval algorithms based on natural language processing (NLP) of the free text of medical records have been used to find documents of interest from databases. Homelessness is a high priority non-medical diagnosis that is noted in electronic medical records of Veterans in Veterans Affairs (VA) facilities. Using a human-reviewed reference standard corpus of clinical documents of Veterans with evidence of homelessness and those without, an open-source NLP tool (Automated Retrieval Console v2.0, ARC) was trained to classify documents. The best performing model based on document level work-flow performed well on a test set (Precision 94%, Recall 97%, F-Measure 96). Processing of a naïve set of 10,000 randomly selected documents from the VA using this best performing model yielded 463 documents flagged as positive, indicating a 4.7% prevalence of homelessness. Human review noted a precision of 70% for these flags resulting in an adjusted prevalence of homelessness of 3.3% which matches current VA estimates. Further refinements are underway to improve the performance. We demonstrate an effective and rapid lifecycle of using an off-the-shelf NLP tool for screening targets of interest from medical records.

Intraductal papillary mucinous neoplasms (IPMNs) are rare pancreatic tumors, accounting for less than 1-2% of all neoplasms of the pancreas. The main characteristic of IPMNs is their favorable prognosis, as these pre-malignant or malignant lesions are usually slow-growing tumors and radical surgery is frequently possible. According to the localization of the lesions, three different tumor types have been identified: the main-duct IPMN, the branch-duct IPMN and the mixed-type IPMN (involving both the main pancreatic duct and the side branches). IMPNs do not present pathognomonic signs or symptoms. The obstruction of the main pancreatic duct system may cause abdominal pain and acute pancreatitis (single or recurrent episodes). The tumor may be incidentally discovered in asymptomatic patients, particularly in those with branch-duct IPMNs. In clinical practice, any non-inflammatory cystic lesion of the pancreas should be considered as possible IPMN. Computed tomography, magnetic resonance imaging with cholangiopancreatography and endoscopic ultrasonography can localize an IPMN and assess its morphology and size. The choice between non-operative and surgical management depends on the risk of malignancy and on the definitive distinction between benign and malignant IPMNs. Main-duct IPMNs have a high risk of malignant degeneration, especially in older patients. The clinical and radiological features, as well as treatment and outcome, of eight patients with IPMN (five with main-duct, two with branch-duct and one with mixed-type) observed by the authors over the last ten years are presented.

Introduction Raltegravir (RAL) is the first in class integrase inhibitor and is licensed for administration at 400 mg twice daily. RAL pharmacokinetics are characterized by high interpatient variability and recently RAL plasma exposure has been correlated with efficacy. RAL is primarily metabolized by glucuronidation via uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) and UGT1A1*28 considered to be the main genetic variant associated with decreased UGT1A1 expression. This study investigated variability in RAL trough plasma concentrations (Ctrough) in the clinical setting, the effect of UGT1A1*28 and concomitant antiretrovirals. Methods A total of 86 patients, from Turin, Italy, and Madrid, Spain, were included in the analysis. Blood samples were obtained 10-14 hours postdose. Genotyping for UGT1A1*28 was conducted by sequencing. Results High interpatient and intrapatient variabilities were observed; 13 patients had ≥3 samples available, and the median coefficient of variation was 128 (64-265). Coadministration of RAL with atazanavir (ATV, n = 9) resulted in higher raltegravir Ctrough, 517 (307-2706) ng/mL when compared with patients not receiving ATV (n = 77) 223 (95-552; P = 0.02). UGT1A1*28 did not influence RAL plasma exposure. Discussion We have documented large intersubject and intrasubject variabilities in RAL plasma concentrations and confirmed the interaction with ATV. Further studies are required to better understand the mechanisms that influence the pharmacokinetics of RAL.

La Emergencia del Saber desde el abordaje cualitativo, del grupo de investigadores del Centro de investigaciones Educacionales Paradigma (CIEP), es una obra de obligada referencia para docentes e investigadores que se aproximen a la investigación cualitativa desde la reflexión de la práctica pedagógica. Uno de los aspectos más importantes de este libro es que cada una de las investigaciones que lo componen es producto de una indagación con enfoque cualitativo, pero hecha en nuestros propios contextos, construyendo no sólo saberes académicos emergentes sino, también, develando nuestras propias creencias ante la práctica pedagógica y hacia el mismo acto de investigar, propiciando de esta forma, procesos reflexivos que permiten observarnos desde nuestro quehacer para poder entender la acción del otro. Los artículos presentes en esta obra muestran un cambio en el enfoque del objeto de estudio ya que revelan que la investigación, en el campo educacional, sólo es posible en la interacción entre el investigador y el investigado dentro de la dinámica social. The Emergence of Knowledge from the qualitative approach, is a book write by researchers of the Centre for Educational Research Paradigm (CIEP), and is a required reference work for teachers and researchers that approach to qualitative research from the reflection of pedagogical practice. One of the most important aspects of this book is that each of its component research results from this qualitative inquiry, but made in our own contexts, building not only emerging academic knowledge but also revealing our own beliefs to pedagogical practice and to the same act of research, thus promoting, reflective processes that enable Watching from our work to understand the other's action. The articles present in this work show a shift in focus from the object of study and research showing that, in the educational field is only possible in the interaction between the researcher and the researched within social dynamics.

ObjectivesSymptomatic remission is increasingly perceived as a realistic objective of pharmacological treatment in patients with schizophrenia (2). However the relationships between symptomatic remission, as defined by standardized criteria, and functional outcome remain controversial. In the present study, we designed a one-year follow-up of clinically stable patients with schizophrenia and examined the relationships of clinical remission with several indices of psychosocial functioning.MethodsThirty-six patients with schizophrenia were included. All the evaluations were carried out both at baseline (T0) and after a one-year follow-up (T12). The categorization in psychosocial remission/non-remission was done by means of the Psychosocial Remission in Schizophrenia (PSRS) scale.ResultsBoth at T0 and at T12, R showed, with respect to NR, a better social functioning and a better quality of life. Correlation analysis revealed that the better the psychosocial functioning, the lower the scores on all psychopathological dimensions, except “anxiety/depression” and “hostility” at T0 as well as “anxiety/depression” at T12. At T0, 65% of R resulted also in psychosocial remission; at T12, this percentage reached 90%.ConclusionsOur findings suggest that symptomatic remission in schizophrenia is associated to functional outcome in the majority of cases, especially when both symptomatic and chronological criteria are met.

We assessed the activity and toxicity of the XELBEVOCT regimen in patients with metastatic well-to-moderately differentiated neuroendocrine neoplasms (WMD-NEN). Ancillary studies evaluated hypertension, proteinuria, and vascular endothelial growth factor (VEGF) polymorphisms in predicting progression-free survival (PFS) and the predictive role of serum vitamin D in progression-free survival and proteinuria onset. This prospective phase 2 study included 45 patients with WMD-NEN arising from various primary sites. The treatment regimen was octreotide long-acting release (LAR), 20 mg monthly, metronomic capecitabine, 2000 mg/daily, and intravenous bevacizumab, 5 mg/kg every 2 weeks, without interruption for 9 months. Bevacizumab was continued until disease progression. Partial response was obtained in 8 patients (17.8%, 95% confidence interval [CI], 6.4%-28.2%); tumor response was more frequent in pancreatic than in non-pancreatic malignancies. The median PFS was 14.9 months; median overall survival was not attained. Biochemical and symptomatic responses were observed in 52.9% and 82.3% of cases, respectively. The treatment was well tolerated. Grade 3 toxicities included hand and foot syndrome (11.1%), proteinuria (4.4%), and renal toxicity (2.2%). Proteinuria (all grades) was correlated with longer PFS (p = 0.017). There was an inverse relationship between proteinuria and vitamin D levels. VEGF polymorphisms were not associated with patient outcome. The XELBEVOCT regimen is active and well tolerated in patients with metastatic WMD-NEN. Proteinuria correlated with hypovitaminosis D status and was the best predictive factor of treatment efficacy. Trial registration number NCT01203306 .