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  • National Health Insurance (NHI) is a mandatory health insurance program in Taiwan that provided comprehensive coverage for medical for care up to 99% of the population in 2009. Because NHI is a single-payer compulsory program that covers all forms of health care for residents in Taiwan, the NHIRD comprehensively includes claim data on both outpatient and inpatient services for nearly the entire 23.7 million population of this country. All claims data are collected in the NHI Research Database (NHIRD) and are managed by the Taiwan National Health Research Institutes (NHRI). Data files in the NHIRD include all ambulatory claims, inpatient claims, details of ambulatory care and inpatient orders, and prescriptions dispensed at contracted pharmacies. Data used to perform the analyses conducted in this study were retrieved from the LHID 2005 (LHID2005), a subset of the NHIRD. The LHID2005 consists of all the original medical claims for 1,000,000 enrollees' historical ambulatory data and inpatient care data under the Taiwan NHI program from 1997 to 2010, and the database was created and is publicly released to researchers. The NHRI reported that there were no statistically significant differences in age or gender between the randomly sampled group and all beneficiaries of the NHI program. To maintain claims data accuracy, the NHI’s routine practice of performing cross-checks and validations of medical claims ensures the accuracy of the NHIRD diagnostic coding. Because we used de-identified secondary data released to the public for research purposes, our study was exempt from full review by the Institutional Review Board after consultation with the Director of the Kaohsiung Medical University Institutional Review Board. We used a study cohort and a comparison cohort to examine the relationship between LC and herpes zoster. We identified 4667 first-time hospitalizations with a discharge diagnosis of LC or patients who had at least have two ambulatory care visits for LC (International Classification of Disease, 9th Revision, Clinical Modification (ICD-9-CM) codes 571.2, 571.5, 571.6) between January 1998 and December 2005. The date of the initial diagnosis of LC was assigned as the index date for each LC patient. To the improve data accuracy, the LC selection criteria required that all cases with the ICD-9 code be assigned by an internist. We also established selection criteria for herpes zoster patient. We only included herpes zoster cases in this study if they received ≥2 herpes zoster diagnoses for ambulatory care visit or ≥1 diagnose for inpatient care, and the ICD-9 code was assigned by a dermatologist. Our study used a study cohort and comparison cohort to examine the relationship between LC and herpes zoster. Each LC cohort patient was matched based on age, gender, and index year to five randomly identified beneficiaries without LC to build the comparison cohort. Patients diagnosed with herpes zoster (ICD-9-CM codes 053–053.9) before index date were excluded from both cohorts. We also identified relevant comorbidities, including hypertension (ICD-9-CM codes 401–405), DM (ICD-9-CM codes 250), hyperlipidemia (ICD-9-CM codes 272), HIV (ICD-9-CM codes 042), hepatitis B (ICD-9-CM codes 070.2,070.3, V02.61), hepatitis C (ICD-9-CM codes 070.41, 070.44, 070.51, 070.54, V02.62), organ transplantation (ICD-9-CM codes 996, V042), chronic renal failure (ICD-9-CM codes 585), SLE (ICD-9-CM codes 710), RA (ICD-9-CM 714), COPD (ICD-9-CM 491, 492, 496), cancer (ICD-9-CM codes 140–208), and alcoholism-associated disorders (ICD-9-CM codes 291, 303, 305.0, 357.5, 425.5, 571.0, 571.1, 571.2, 571.3, 980.0, V11.3). For the urbanization level in our study, all 365 townships in Taiwan were stratified into 4 levels according to standards established by the Taiwanese NHRI based on a cluster analysis of the 2000 Taiwan census data, with 1 referring to the most urbanized area and 4 referring to the least urbanized. The criteria on which these strata were determined included the population density (persons/km2), the number of physicians per 100,000 people, the percentage of people with a college education, the percentage of people over 65 years of age, and the percentage of agricultural workers. All data processing and statistical analyses were performed with the Statistical Package for Social Science (SPSS) software, vers. 18.0 (SPSS, Chicago, IL, USA) and SAS vers. 8.2 (SAS System for Windows, SAS Institute, Cary, NC, USA). Pearson X 2 tests were used to compare differences in geographic location, monthly income, and urbanization level of patients’ residences between the study and comparison groups. We also performed a survival analysis using the Kaplan-Meier method, and used the log-rank test to compare survival distributions between cohorts. The survival period was calculated for patients who suffered from LC until an occurrence of hospitalization, an ambulatory visit for herpes zoster, or the end of the study period (December 31, 2010), whichever came first. After adjusting for urbanization level, monthly income, region, and comorbidities as potential confounders, we performed a Cox proportional-hazards analysis stratified by gender, age group, and index year to examine the risk of herpes zoster during the 5-year follow-up in both cohorts. We further classified the duration of follow up period in both groups. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to quantify the risk of herpes zoster. The results of comparisons with a two-sided p value of <0.05 were considered to represent statistically significant differences. Insurance reimbursement claims data used in this study were from Taiwan’s NHIRD, which is available for research purposes. This study was conducted in accordance with the Helsinki Declaration. This study was also evaluated and approved by the Kaohsiung Medical University’s Institutional Review Board (KMUH-IRB-EXEMPT-20130059).
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