Hazard ratio for death in new user of anticancer drugs or antidepressants drugs.

<p>Abbreviation: SSRI, selective serotonin reuptake inhibitor; 95% CI, 95% confidence interval.</p>*<p>Definition 3.3 in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0066116#pone-0066116-t001" target="_blank">Table 1</a> is used.</p>†<p>Information of death in the insurer’s enrollment data is used.</p>‡<p>Adjusted for age and sex by Cox regression model.</p

Sensitivity, specificity and PPVs of claims-based definition of death.

<p>Abbreviation: PPV, positive predictive value; 95% CI, 95% confidence interval.</p>*<p>Definitions are given in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0066116#pone-0066116-t001" target="_blank">Table 1</a>.</p

Characteristics of beneficiaries in three health insurance unions.

<p>Characteristics of beneficiaries in three health insurance unions.</p

Claims-based definitions of death.

<p>Abbreviation: CCI, charlson comorbidity index.</p

Sensitivity, specificity and PPVs for claims-based Definition 3.3^*.

<p>Abbreviation: PPV, positive predictive value; 95%CI, 95% confidence interval; SSRI, selective serotonin reuptake inhibitor; NSAID, non-steroidal anti-inflammatory drug.</p>*<p>Definition 3.3 in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0066116#pone-0066116-t001" target="_blank">Table 1</a>.</p>†<p>The gold standard information.</p>‡<p>Definition yielded no false positive cases.</p>¶<p>SSRIs with or without other oral antidepressants.</p>§<p>Oral antidepressants except for SSRIs.</p

Deaths identified by the gold standard definition and Definition 1.1^*.

*<p>Definitions 1.1 given in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0066116#pone-0066116-t001" target="_blank">Table 1</a>.</p>†<p>‘Zombie’ claims are the claims without ‘death’ issued after the index claim with ‘death’ given as the discharge/disease status.</p>‡<p>Information on death in enrollment file provided by insurers was considered to be the gold standard information.</p>¶<p>‘Zombie’ claims issued up to 1 or 2 months after the index claim.</p>§<p>‘Zombie’ claims issued up to 3 or more months after the index claim.</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

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

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