Predictive Factors for Efficacy and Safety of Prophylactic Theophylline for Extubation in Infants with Apnea of Prematurity.

This study aimed to evaluate predictive factors involved in efficacy and safety in Japanese infants who received theophylline therapy to prevent apnea of prematurity (AOP) after weaning from mechanical ventilation.We retrospectively reviewed the medical records of infants who were administered intravenous aminophylline (theophylline ethylenediamine) for AOP at the neonatal intensive care unit, Kagoshima University Hospital, Japan, between January 2009 and June 2013.A total of 100 infants were evaluated as two separate groups in terms of efficacy and safety of theophylline. Sixty-seven (67.0%) infants had effective theophylline therapy. Multivariate logistic regression analysis showed that gestational age at birth was significant, with an odds ratio of 0.59 (p < 0.001). Receiver operating characteristic analysis showed that the cut-off value was 31.1 weeks old for predicting the efficacy of theophylline (specificity, 66.7%; sensitivity, 86.6%; p < 0.001; area under the curve, 0.750; 95% confidence interval, 0.45-0.74). Adverse reactions were identified in 21 (21.0%) infants. Multivariate logistic regression analysis showed that the number of days of theophylline administration from birth was associated with an increased risk of adverse reactions after theophylline administration (p = 0.01).Physicians need to be aware of the possibility that theophylline fails to produce therapeutic effects for extubation in infants aged less than 31.1 weeks old, and adverse reactions can easily develop when theophylline is administered soon after birth

Characteristics of infants who were classified by the appearance of adverse reactions.

<p>Characteristics of infants who were classified by the appearance of adverse reactions.</p

Multivariate logistic regression analysis of factors associated with an increased risk of adverse reactions.

<p>Multivariate logistic regression analysis of factors associated with an increased risk of adverse reactions.</p

Basic protocol of theophylline administration when weaning from mechanical ventilation.

<p>Basic protocol of theophylline administration when weaning from mechanical ventilation.</p

A Prospective Stratified Case-Cohort Study on Statins and Multiple Adverse Events in Japan

<div><p>Purpose</p><p>To assess the association between statins and diverse adverse events in Japanese population.</p><p>Methods</p><p>New users of statin who started statin after 6-month period of non-use were identified in 68 hospitals between January 2008 and July 2010. In addition to the random sample subcohort, we selected additional subcohort members to make the stratified sample subcohort have at least one patient in all subgroups stratified by each combination of statin and hospital. By abstraction from medical records, detailed information was obtained for all potential cases and pre-selected subcohort members. The event review committee consisting of 3 specialists judged whether possible cases met the definition of one of the adverse events of interest, and for adjudicated cases the committee further judged whether statin was a certain, probable or possible cause of the occurrence of the event. Adjusted for covariates including age, gender, status of “switcher”, use of high daily dose and comorbidities at baseline, hazard ratio (HR) was estimated by the Cox proportional hazards model with Barlow’s weighting method. Data were also analyzed by the method proposed by Breslow in 2009.</p><p>Results</p><p>A total of 6,877 new users of a statin were identified (median age: 66 years; males: 52%). The hazard ratios of increase in serum creatinine for atorvastatin and fluvastatin have wide confidence intervals, but both of the point estimates were around 2.5. Estimates of hazard ratios by the method of Barlow (1999) were similar to those by the method of Breslow (2009).</p><p>Conclusions</p><p>Use of statin was not associated with a significant increased risk for renal, liver and muscle events. However, the hazard ratio of increase in serum creatinine tended to be high with atorvastatin and fluvastatin to require further studies.</p></div

Characteristics of study population.

<p>Abbreviations: AST, aspartate aminotransferase; ALT, alanine aminotransferase; CK, creatinine kinase.</p><p>*Absolute value of standardised difference >0.1.</p>†<p>High daily dose (higher than the “usual” daily dose recommended in the package insert).</p

Association between statin and events estimated by the case-cohort analysis using the stratified sample subcohort.

<p>Abbreviations: HR, hazard ratio; CI, confidence interval; AST, aspartate aminotransferase; ALT, alanine aminotransferase.</p><p>*Definition of event is given in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096919#pone-0096919-t001" target="_blank">Table 1</a>.</p>†<p>Adjusted for age, male, switcher from other lipid-lowering drug, use of high daily dose, hypertension, diabetes, heart disease, liver disease and renal disease.</p>‡<p>Estimates using “standard weights” in ref 20 are shown.</p

Definition of adverse events.

<p>Abbreviations: ULN, upper limit of normal; AST, aspartate aminotransferase; ALT, alanine aminotransferase; CK, creatinine phosphokinase.</p><p>*Modified from Bellomo et al. 2004 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096919#pone.0096919-Bellomo1" target="_blank">[30]</a>.</p>†<p>Criteria used in Klepper MJ and Covert B. 2010 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096919#pone.0096919-Klepper1" target="_blank">[31]</a>.</p>‡<p>Criteria used in Guidance of FDA. 2009 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096919#pone.0096919-FDA2" target="_blank">[32]</a>. Increase of one or both of AST and ALT was counted as one event.</p>§<p>Criteria used in Pasternak RC et al. 2002 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096919#pone.0096919-Pasternak1" target="_blank">[33]</a>.</p