Thyroid dysfunctions induced by tyrosine kinase inhibitors

INTRODUCTION: Recently, tyrosine kinase inhibitors (TKIs) have emerged as a new class of anticancer therapy. Although generally considered less toxic than cytotoxic chemotherapy, TKIs do cause significant side effects including fatigue and hypertension. In addition, thyroid dysfunction is a well-known adverse effect of TKI. AREAS COVERED: This review provides a comprehensive assessment of TKI-induced thyroid dysfunctions by sunitinib, sorafenib, pazopanib, imatinib, dasatinib, nilotinib, vandetanib, axitinib, motesanib and tivozanib. Furthermore, the potential mechanisms that result in this toxicity, the clinical impact of thyroid dysfunction in these patients and the controversies regarding treatment with thyroid hormone (TH) therapy are evaluated. EXPERT OPINION: Detection of TKI-induced thyroid dysfunction requires routine monitoring of thyroid function and may necessitate treatment. Potential benefits in developing thyroid dysfunction and potential harm in treating it necessitate controlled studies. Finally, if treatment is pursued, appropriate dosing and timing of TH replacement will require prospective clinical evaluation

Can environment or allergy explain international variation in prevalence of wheeze in childhood?

Asthma prevalence in children varies substantially around the world, but the contribution of known risk factors to this international variation is uncertain. The International Study of Asthma and Allergies in Childhood (ISAAC) Phase Two studied 8–12 year old children in 30 centres worldwide with parent-completed symptom and risk factor questionnaires and aeroallergen skin prick testing. We used multilevel logistic regression modelling to investigate the effect of adjustment for individual and ecological risk factors on the between-centre variation in prevalence of recent wheeze. Adjustment for single individual-level risk factors changed the centre-level variation from a reduction of up to 8.4% (and 8.5% for atopy) to an increase of up to 6.8%. Modelling the 11 most influential environmental factors among all children simultaneously, the centre-level variation changed little overall (2.4% increase). Modelling only factors that decreased the variance, the 6 most influential factors (synthetic and feather quilt, mother’s smoking, heating stoves, dampness and foam pillows) in combination resulted in a 21% reduction in variance. Ecological (centre-level) risk factors generally explained higher proportions of the variation than did individual risk factors. Single environmental factors and aeroallergen sensitisation measured at the individual (child) level did not explain much of the between-centre variation in wheeze prevalence

A Systematic Review of Case-Identification Algorithms Based on Italian Healthcare Administrative Databases for Two Relevant Diseases of the Respiratory System: Asthma and Chronic Obstructive Pulmonary Disease

to identify and describe all asthma and Chronic Obstructive Pulmonary Disease (COPD) case-identification algorithms by means of Italian Healthcare Administrative Databases (HADs), through the review of papers published in the past 10 years

Analisi dell'appropriatezza organizzativa dei ricoveri ospedalieri mediante PRUO in un ospedale del Molise

It has been carried out a survey to evaluate the appropriateness of hospital stay in a university hospital. The aims of the study were: to determine the amount of inappropriate hospital admissions and inappropriate days of stay in relation to either wards and characteristics of admission; to analyse the reasons for inappropriate patient stay. A randomised sample stratified by ward of discharge of 224 medical records were analysed using the Italian version of the Appropriateness Evaluation Protocol. 37.9% of the hospital admissions and 18.9% of hospitalisation days were judged to be inappropriate. The main reasons for categorising an admission or a day of stay as inappropriate were a) delay in performing elective surgery procedures; b) that the patient's problem could be treated on an outpatient basis; c) delay in performing diagnostic examinations. The univariate statistical analysis showed an association between appropriateness of hospital stay and gender age, ward of discharge, length of hospital stay and DRG type (medical/surgical). The study highlights a lower level of inappropriateness compared to the results of other investigations. Hints were also identified for achieving an improved efficiency at hospital leve

Perinatal and antibiotic exposures and the risk of developing childhood-onset inflammatory bowel disease: A nested case-control study based on a population-based birth cohort

The role of early-life environmental exposures on Inflammatory Bowel Disease (IBD) onset remains unclear. We aimed to quantify the impact of perinatal conditions and antibiotic use in the first 6 and 12 months of life, on the risk of childhood-onset IBD, in a birth cohort of the region Friuli-Venezia Giulia (Italy). A nested case-control design on a longitudinal cohort of 213,515 newborns was adopted. Conditional binomial regression models were used to estimate Odds Ratios (OR) with 95% confidence intervals (CI) for all analyzed risk factors. We identified 164 individuals with IBD onset before the age of 18 years and 1640 controls. None of the considered perinatal conditions were associated with IBD. Analyses on antibiotic exposure were based on 70 cases and 700 controls. Risks were significantly higher for children with 654 antibiotic prescriptions in the first 6 and 12 months of life (OR = 6.34; 95%CI 1.68\u201324.02 and OR = 2.91; 95%CI 1.31\u20136.45, respectively). This association was present only among patients with Crohn\u2019s disease and those with earlier IBD onset. We found that perinatal characteristics were not associated to IBD, while the frequent use of antibiotics during the first year of life was associated to an increased risk of developing subsequent childhood-onset IBD

A Systematic Review of Case-Identification Algorithms Based on Italian Healthcare Administrative Databases for Three Relevant Diseases of the Digestive and Genitourinary System: Inflammatory Bowel Diseases, Celiac Disease, and Chronic Kidney Disease

to identify and describe all Inflammatory Bowel Disease (IBD), Celiac Disease (CD), and Chronic Kidney Disease (CKD) case-identification algorithms by means of Italian Healthcare Administrative Databases (HADs), through a review of papers published in the past 10 years

Nuclear metabolic changes induced by tumor necrosis factor in Daudi lymphoma cells; a multiparametric analysis.

The effects of r-TNF alpha on cell cycle progression and DNA polymerase activity in Daudi lymphoma cells have been analyzed. Cytofluorimetric analysis of the cell cycle after 6 to 24 hr of treatment revealed both a decrease of BrdU incorporation per cell and a light inhibition of S phase as assessed by the analysis of the percentual distribution of cell cycle compartments. The reduction of BrdU incorporation can be related to the early decrease in the rate of DNA synthesis that follows r-TNF alpha treatment. These results suggest that one of the early events induced by r-TNF alpha at nuclear level is the slowering of DNA synthesis leading to a reduced cell cycle progression