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The Unknown Health Burden of Herpes Zoster Hospitalizations: the Effect on Chronic Disease Course in Adult Patients ≥50 Years

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The Unknown Health Burden of Herpes Zoster Hospitalizations: the Effect on Chronic Disease Course in Adult Patients ≥50 Years Article The Unknown Health Burden of Herpes Zoster Hospitalizations: The Effect on Chronic Disease Course in Adult Patients ≥50 Years Maria Francesca Piazza 1,2, Chiara Paganino 2,*, Daniela Amicizia 1,2, Cecilia Trucchi 2, Andrea Orsi 1,3 , Matteo Astengo 1, Paolo Romairone 4, Simona Simonetti 4, Giancarlo Icardi 1,3 and Filippo Ansaldi 1,2 1 Department of Health Sciences, University of Genoa, Via Antonio Pastore 1, 16132 Genoa, Italy; [email protected] (M.F.P.); [email protected] (D.A.); [email protected] (A.O.); [email protected] (M.A.); [email protected] (G.I.); fi[email protected] (F.A.) 2 A.Li.Sa., Liguria Health Authority, Piazza della Vittoria 15, 16121 Genoa, Italy; [email protected] 3 Hygiene Unit, San Martino Polyclinic Hospital, Largo Rosanna Benzi 10, 16132 Genoa, Italy 4 Liguria Digitale S.p.A., Via Enrico Melen 77, 16152 Genoa, Italy; [email protected] (P.R.); [email protected] (S.S.) * Correspondence: [email protected]; Tel.: +39-010-5484826 Received: 27 December 2019; Accepted: 8 January 2020; Published: 10 January 2020 Abstract: The effect of severe Herpes Zoster (HZ) on chronic diseases is a component of the real burden of this vaccine-preventable disease that is not commonly considered. A retrospective cohort study was conducted to assess the health burden of severe HZ in adults 50 years residing in Liguria ≥ Region from 2015 to 2017. Subjects hospitalized with and without HZ were matched (1:6 ratio). 437 subjects in the HZ cohort and 2622 subjects in the non-HZ cohort were enrolled. Previous immunodeficiency, autoimmune, and rare diseases are identified as main chronic conditions related to HZ hospitalization. Higher incidences of autoimmune (1.4% vs. 0.22%, p = 0.002) and gastrointestinal (7.04% vs. 3.62%, p = 0.015) diseases after hospitalization were observed in the HZ cohort compared to the non-HZ cohort. Significantly higher incidences were found after hospitalization versus the previous period for cardiovascular diseases (11.17% vs. 2.09%, p < 0.001), cerebral vasculopathy (6.13% vs. 0.60%, p < 0.001), non-arrhythmic myocardiopathy (4.31% vs. 0.59%, p = 0.002), and neuropathy (2.62% vs. 0.56%, p = 0.033). The HZ cohort showed a relative risk 10-fold higher for cerebral vasculopathy, 5-fold higher for cardiovascular diseases, and 7-fold higher for non-arrhythmic myocardiopathy. HZ causes a substantial impact on the chronic conditions. These data could suggest an implementation of HZ vaccination programs in the elderly and in high-risk groups. Keywords: Herpes Zoster; hospitalizations; chronic diseases; risk factors; high-risk groups; elderly; cerebral vasculopathy; readmissions and drug therapy 1. Introduction Herpes Zoster (HZ) is the clinical manifestation of reactivation of varicella-zoster virus remained latent in dorsal root or cranial nerve sensory ganglia after primary infection. It is a considerable cause of morbidity, especially in elderly, immunosuppressed, or critically ill patients [1]. In Europe, approximately 1.7 million new cases of HZ are expected each year with an incidence rate in adults aged 50 years and older, between 6 and 8 cases per 1000 person-years [2–5]. Vaccines 2020, 8, 20; doi:10.3390/vaccines8010020 www.mdpi.com/journal/vaccines Vaccines 2020, 8, 20 2 of 11 The incidence shows a growing trend with increasing age until reaching over 10 cases per 1000 person-years after 80 years old [3,5,6]. The most common complications related to HZ are post-herpetic neuralgia (PHN), a long-lasting pain that does not end with the disappearance of the rash, but persists for some weeks, and even months or years; ocular lesions involving the ophthalmic division of the trigeminal nerve; neurological sequelae; and visceral inflammation [5,7–9]. Severe cases with these complications often require hospitalization [6,10,11]. The health and economic burden of HZ in terms of incidence and neurological complications— PHN, ocular HZ, etc.—and its costs were deeply investigated, as well as risk factors and chronic diseases (i.e., chronic renal failure, chronic obstructive pulmonary disease (COPD), diabetes, asthma, and depression) associated with HZ onset [12–15]. The effect of severe HZ on the clinical course of chronic diseases was poorly explored in terms of new cases due to clinical onset of latent disease, worsening of course, hospitalizations, and increase of medication use. A retrospective cohort study was carried out to assess the health effects of severe HZ requiring hospitalization on clinical progression of chronic diseases in Ligurian residents aged 50 years or older. Prevalence of chronic diseases at 6 months before hospitalization and incidence observed during the 6 months after hospitalization were compared in patients hospitalized for HZ and in an age- and gender-matched non-HZ cohort. Furthermore, incidence rates in the 6 month periods before and after hospitalization were compared in patients who accessed the hospital for HZ. 2. Materials and Methods 2.1. Study Design and Patients Selection Criteria This retrospective cohort study was conducted to assess the epidemiological health burden of severe HZ in adults 50 years residing in the Liguria Region from January 2015 to December 2017. ≥ Subjects were included in the HZ cohort on the basis of International Classification of Diseases 9th Revision, Clinical Modification (ICD-9-CM) diagnosis and procedure codes selecting patients who were hospitalized with a primary or secondary diagnosis of HZ (ICD-9-CM codes 053.xx) [16,17]. The HZ cohort subjects were matched to hospitalized patients without a diagnosis of HZ infection (non-HZ cohort) according to age, gender, and admission date in a 1:6 ratio. The subjects in the non-HZ cohort were enrolled at the same time as each matched HZ patient ( 15 days) by random selection. The ± subjects of the HZ cohort and non-HZ cohort were randomly selected among all hospitalized patients resident in Liguria who had access to a hospital of the National Health Service. In Italy, hospital access is free of charge. All patients were monitored in the 6 months preceding hospital admission (pre-H) and following the discharge (post-H) in order to estimate the prevalence and incidence of chronic diseases. Chronic disease cases captured during hospitalization were excluded from the analysis. Days of drug therapy and further hospitalizations were also compared during pre-H and post-H periods. Drugs were classified using the Anatomical Therapeutic Chemical (ATC) international classification system. 2.2. Data Sources and Information Flows Administrative healthcare data (AHD), or data warehouse, is a regional service that collects Hospital Discharge Records (HDRs), the flow of outpatient visits, and pharmaceutical and was used as a data source. The HDRs include patient demographic data, admission and discharge dates, discharge status, main and secondary discharge diagnoses, and diagnostic/therapeutic procedures. HDR data are recorded with the consent of the patient and can be used for scientific studies in the form of aggregated and de-identified data. Data about the chronic diseases were obtained through the Liguria Chronic Condition Data Warehouse (CCDWH) platform, recorded in the Liguria region since 2010 [18]. 2.3. Data Analysis Data were analyzed by JMP version 13.0.0 software (SAS Institute, Cary, NC, USA). Continuous variables were summarized as medians and interquartile range, and categorical variables as frequency Vaccines 2020, 8, x FOR PEER REVIEW 3 of 11 2.3. Data Analysis VaccinesData2020, were8, 20 analyzed by JMP version 13.0.0 software (SAS Institute, Cary, NC, USA). Continuous3 of 11 variables were summarized as medians and interquartile range, and categorical variables as frequency distributions and 95% confidence intervals. Prevalence, incidence, and risk measures, i.e., distributions and 95% confidence intervals. Prevalence, incidence, and risk measures, i.e., odds ratio odds ratio and relative risk, were reported with a 95% confidence interval. and relativeThe chi risk,-square were test reported (Pearson with Test) a 95%and confidenceMann–Whitney interval. U test were used to compare the general features,The chi-square comorbidities, test (Pearsonreadmissions Test), andand Mann–Whitneydays of drug therap U testy in were HZ usedcohort to compareand non-HZ the generalcohort features,groups. Comparison comorbidities, of readmissions,variables at the and 6 months days of before drug and therapy after inhospitalization HZ cohort and in non-HZthe HZ cohort cohort groups.and non Comparison-HZ cohort of groups variables was at thecarried 6 months out using before the and Mann after hospitalization–Whitney test inwhen the HZappropriate. cohort and non-HZStatistical cohort significance groups was was defined carried a outs p- usingvalue < the 0.05. Mann–Whitney test when appropriate. Statistical significance was defined as p-value < 0.05. 2.4. Ethical Statement 2.4. Ethical Statement Data collected in the AHD regional service are transmitted by the Ligurian Local Health Units (LHUs)Data and collected hospitals in the to AHDthe regional regional health service authority are transmitted “Azienda by Ligure the Ligurian Sanitaria Local” (A.Li.Sa.). Health UnitsThe (LHUs)institutional and hospitalsactivities toof the A.Li.Sa. regional include health handling authority regional “Azienda healthcare Ligure Sanitaria”administrative (A.Li.Sa.). data and The institutionalconduct epidemiological activities of A.Li.Sa. studies,
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