Is dose modification or discontinuation of nilotinib necessary in nilotinib-induced hyperbilirubinemia?

Nilotinib is a specific breakpoint cluster region-Abelson leukemia virus-tyrosine kinase inhibitor that is used as an effective first- or second-line treatment in imatinib-resistant chronic myelogenous leukemia (CML) patients. Hepatotoxicity due to nilotinib is a commonly reported side effect; however, abnormal liver function test (LFT) results have been reported in asymptomatic cases. When alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels are more than five-fold the upper limit of the normal (ULN) or when the serum total bilirubin level is more than three-fold the ULN, dose modification or discontinuation of nilotinib is recommended, resulting in decreased levels of hematological indicators in certain patients with CML. Nilotinib-induced hyperbilirubinemia typically manifests as indirect bilirubinemia without elevated ALT or AST levels. Such abnormal liver functioning is thus not attributed to the presence of a true histologic lesion of the liver. The underlying mechanism may be related to the inhibition of uridine diphosphate glucuronosyltransferase activity. Therefore, nilotinib dose adjustment is not recommended for this type of hyperbilirubinemia, and in the absence of elevated liver enzyme levels or presence of abnormal LFT findings, physicians should consider maintaining nilotinib dose intensity without modifications.     

Role of theories in school-based diabetes care interventions: A critical review

BACKGROUNDDiabetes is one of the most common chronic diseases of childhood. School plays an essential role in the management of student diabetes, which reduces the risk of short- and long-term diabetes complications and ensures that students are well-positioned for optimal academic performance and growth.AIMThe aim of this review was to systematically identify and synthesize the literature concerning theory-based diabetes care interventions in K-12 schools in the United States. It critically assessed the specific role of theories and associated essential constructs in intervention design, implementation, outcome measurement, and evaluation.METHODSRelevant literature was identified by keyword searches of the Cochrane Library, PubMed, and Web of Science.RESULTSFour interventions met the eligibility criteria and were included in the review. Of those, two evaluated online diabetes education programs for school personnel and the other two assessed in-person interventions. Three studies adopted a one-group pre-post study design, and the remaining one adopted a one-shot case-study design. Three of the interventions adopted social cognitive theory, and the remaining one was guided by the diffusion of innovations theory. Three studies identified core constructs of a theory as predictors of behavioral change. Two used theory to select or develop intervention techniques. Two studies used theory to customize participant intervention techniques. Two studies discussed their findings in the context of theory. No study used theory to select potential intervention participants.CONCLUSIONIn conclusion, despite the value of theory in intervention design and evaluation, theory-based diabetes interventions at school remain scarce. Future research may seek ways to better integrate theory and empirical research.     

Mutaciones y variaciones estructurales en el gen catecol-O-metiltransferasa de los pacientes que exhiben dolor quirúrgico persistente crónico

ObjectivesMutations in the exon 4 of the COMT gene are associated with chronic persistent surgical pain (CPSP). Especially COMT mutated allele G472A (Val158Met) associated with CPSP patients is reported in different ethnic population. The purpose of this study is to evaluate the prevalence of genetic mutations and structural variations in exon 4 of COMT that can be related to the appearance of CPSP in patients under sternotomy.Materials and methodsOne hundred patients with American Society of Anesthesiologists (ASA) physical status grades i, ii and iii, who underwent sternotomy procedures, were selected to assess the development and magnitude of the CPSP evaluated with pain questionaries’ at the end of three months after surgery. This was correlated with COMT allele presence. The exon 4 of COMT gene (that contains the G472A allele) was studied. The polymerase chain reaction (PCR) products were sequenced and mutated sequences were deposited in GenBank®. The structural analysis of COMT was performed using ProCheck® and distortions of three-dimensional tertiary structural orientation was evaluated with root-mean-square deviation (RMSD) score.ResultsGenetic analysis carried out through PCR showed 220 bp amplicons. The 25% of patients with CPSP showed a Numeric Rating Scale (NRS) > 4 pain score. The 20% of these patients have known Val158Met mutation, 5% of patients showed novel mutations c.382C>G, c.383G>C, p.(Arg128Ala). The mutations in COMT gene contributed major structural variations in COMT leading to the formation of inactive COMT that correlates with CPSP.ConclusionThe results of the present study showed that both novel and previously reported mutations in COMT gene has strong association with CPSP.