A hospital-based retrospective cohort study was conducted based on the database of the Tazuke Kofukai Medical Research Institute, Kitano Hospital.
Data were collected from adult patients with histories of 1 of 17 specific underlying diseases, who had visited the emergency departments, outpatient clinics, and inpatient departments. This hospital, located in the center of the Kita ward in Osaka, plays a central role in community health care. In the Japanese system, patients are free to consult any provider—primary care or specialist—at any time . The patients usually visit the same hospital even when they present only mild clinical symptoms and signs. The study period was September 1, 2001 to December 31, 2007.
Inpatient and outpatient records were reviewed. They included data of patient age, sex, and underlying comorbidity, date of the first outpatient visit, admission and discharge, vital status at discharge, and outpatient and inpatient diagnoses (ICD-10-CM codes). Medical records of all patients were also reviewed for patient data and clinical characteristics from the day of diagnosis of the selected diseases to the day of occurrence of HZ, the last day of follow-up, death, or end of data abstraction (December 31, 2007). The institutional ethics committee provided approval for the retrospective review of the patient data.
The cohort included patients who had ICD-10-CM code diagnoses of the underlying diseases of interest. To assist in estimating associations between the underlying diseases and HZ, we selected diseases that had been reported previously to be related with HZ (i.e., eight malignant diseases of brain tumor, lung cancer, breast cancer, esophageal cancer, gastric cancer, colorectal cancer, gynecologic cancer, and malignant lymphoma; three autoimmune diseases of SLE, RA, Sjögren’s syndrome; and one psychiatric disease of depression) or might plausibly be associated with VZV infection or with impaired immunological responses to VZV (one metabolic disease of DM, one cardiovascular disease of hypertension, and one renal disorder of renal failure). Patients with diseases that had no plausible association with HZ (e.g., one osteoskeletal disease; disk hernia, one ocular disease; cataract) were selected as controls.
This study evaluated 17 diseases. Patients with one of those 17 diseases were enrolled at the first diagnosis recorded in the patient file. Diseases of enrolled patients were as follows (ICD-10-CM codes): cancer—brain tumor (C719, D320, 330–332, 420, 430–432), lung cancer (C330, 340–343, 348–349), breast cancer (C501–505, 509, 792, 795), esophageal cancer (C150–155, 159), gastric cancer (C161–164, 169), colorectal cancer (C180–190, 200), gynecologic cancer (C538–539, 541, 542, 549, 550, 560), and malignant lymphoma (C810–813, 819–822, 829–844, 851, 857, 859); autoimmune diseases—SLE (M320–321, 329), RA (M0530, 0590, 0600, 0690–0697), and Sjögren’s syndrome (M350); metabolic disease—DM (E100–107, 109–117, 119, 120, 130–137, 139–146, 149); cardiovascular disease—hypertension (I100, 110, 119,120, 129, 39, 141, 150-152, 159); renal disorder—renal failure (N179, 180, 189,190, 990); osteoskeletal disease—disk hernia (M502, 512); ocular disease—cataract (H250–252, 258–264, 268–269); and mood disorder—depression (F030, 063, 107, 191, 197, 204, 251, 313–315, 318–323, 328–334, 339, 341, 348, 349, 381, 412, 432, 530, 920).
The study endpoint was the first occurrence of HZ. Incident cases were defined as the first incidence of HZ based on the record of a doctor’s diagnosis and identified from inpatient and outpatient encounters that included ICD-10-CM code B020–023, 027–029 (HZ). For all analyses, incident cases of HZ occurring after the patient’s cohort entry date were ascertained using the first HZ diagnosis recorded in the patient file in the Kitano Hospital database. Patients who had HZ at any time prior to the diagnosis of the 17 underlying diseases and those with recurrent HZ were excluded. The incidence of HZ was calculated as the number of events per 1,000 patient-years.
The Kaplan–Meier estimation, defined as the base hazard function for the acquisition of HZ along with age, was used to determine the cumulative HZ-free survival rate incidence during the first 6 years of underlying disease. The Cox proportional hazards models were used to compare the rates of HZ among patients with each of the 17 diseases and to determine the risks of developing HZ. The hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated after adjustment for age and other comorbidities. Statistical significance was inferred for p value <0.05. All statistical tests were two-sided and were performed using a statistical software package (Stata ver. 10 for Windows; StataCorp LP, College Station, TX).