RESUMO
Objective:The objectives were to assess regional differences in the safety outcomes of telaprevir-based triple therapy(T/PR) in Japan and evaluate a suitable generalized linear mixed model for estimating regional differences.Design and Methods:This study targeted individuals infected with genotype 1 chronic hepatitis C virus registered in a nationwide Japanese interferon database from December 2009 to August 2015. The rate of dropout from treatmentattributable to adverse events was calculated in every prefecture where ≥ 20 cases were reported. We constructed the following four models and evaluated the best-fit model based on Akaike information criterion (AIC) and Bayesian information criterion (BIC):1)prefecture as a fixed-effect,2)prefecture and identified confounding factors as fixed-effects,3)prefecture as a random-effect,and 4)prefecture as a random-effect and identified confounding factors as fixed-effects.Results:A total of 25,989 individuals from 38 prefectures were registered during the study period;among them,1,591 from18 prefectures were included as the study population. The dropout rate ranged from 7.0 to 23.1%among 17 prefectures.The model considering prefecture as a random-effect and confounding factors as fixed-effects showed the best-fit for the databased on both the AIC (1,108.06)and BIC (1,113.41).Conclusion:It is difficult to determine if regional differences exist in the safety outcomes of T/PR in Japan because of the limited number of cases. However, the model using prefecture as a random-effect and other confounding factors as fixed-effects would be suitable for estimating parameters that reflect the influence of the prefecture. Further studies using the model would help inform chronic hepatitis C treatment.
RESUMO
<b>Objective: </b>This study aimed to confirm whether the methods for assessing the reported causal relationship between dietary supplement intake and adverse events are reliable in the clinical setting.<br><b>Design: </b>The relationships between supplement intake and adverse events were assessed using two algorithms proposed in our previous report, and causal relationships were evaluated.<br><b>Methods: </b>Twelve raters with a high probability of handling adverse event information examined 200 records of dialogues with supplement users. Each rater independently assessed the causal relationship using the two algorithms. The relationships between supplement intake and adverse events were assessed for all 200 cases. Variability in the evaluation among raters was analyzed for each occupation and the whole group of raters. The distributions of evaluation were analyzed, and inter-rater reliability was evaluated using the intraclass correlation coefficient (ICC) and Fleiss’ kappa coefficient.<br><b>Results: </b>All events of 200 cases seemed to be slight and within the range of variation in daily life. Almost all cases were classified into two categories as “Possible” and “Lack of Information” by each rater. The ICC values for all raters, pharmacists, dieticians, and health care workers were 0.644, 0.573, 0.678, and 0.694, respectively, and the kappa coefficients using the two algorithms were 0.466, 0.426, 0.468, and 0.519 and 0.481, 0.478, 0.465, and 0.517, respectively. There were moderate levels of agreement based on the kappa coefficients and ICC values.<br><b>Conclusion: </b>The two algorithms proposed in our previous report may be reliable in the clinical setting. Their reliability could be enhanced by establishing a unified method of accumulation and recording adverse events for supplement intake, which should be evaluated by more raters using more cases of adverse events.
