Background
Methods
Data sources and search strategy
Inclusion and exclusion criteria
Data extraction study verification and quality assessment
Statistical analysis
Results
Search results and study characteristics
Breuer | Kang | Kwon | Langan | Lin | Minassian | Sreenivasan | Sundström | Yawn | |
---|---|---|---|---|---|---|---|---|---|
Year | 2014 | 2009 | 2016 | 2014 | 2010 | 2015 | 2013 | 2015 | 2016 |
Design | Retrospective Matched Cohort | Retrospective Matched Cohort | Retrospective Matched Cohort | Self-Controlled Case Series | Retrospective Matched Cohort | Self-Controlled Case Series | Retrospective Cohort | Retrospective Cohort | Retrospective Matched Cohort |
Data Source, Country | The Health Improvement Network (THIN) general practice database, United Kingdom | Taiwan National Health Insurance Research Database (NHIRD), Taiwan | Korea Health Insurance Database, Korea | UK Clinical Practice Research Datalink (CPRD) general practice database, United Kingdom | Taiwan National Health Insurance Research Database (NHIRD), Taiwan | Medicare administrative data claims, USA | Danish Civil Registration System (CRS), Denmark | Västra Götaland County Primary Health Care Register and the Swedish Patient Register, Sweden | Rochester Epidemiology Project, USA |
HZ diagnosis period | 2002–2010 | 1997–2001 | 2003–2013 | 1987–2012 | 2003–2004 | 2006–2011 | 1995–2008 | 2008–2010 | 1986–2011 |
Number of Cases (HZ and HZO) | 106,601 | 7,760 | 70,424 | 6,584 | 658 | 42,954 | 117,926 | 13,296 | 4,478 |
Number of Controls | 213,202 | 23,280 | 695,755 | 0 | 1,974 | 0 | 4,503,054 | ~1,500,000 | 16,800 |
Follow-Up Period | 24 years | 1 year | 11 years | 1 year | 1 year | 1 year | 14 years | 1 year | 3 years |
Gender, % female | 59 | 52 | 49 | 57 | 51 | 71 | 51 | 60 | 62 |
Mean age at zoster diagnosis, years | 59 | 47 | 41 | Median age at stroke onset 77 years | 57 | 80 | Not reported | 59 | 68 |
% Receiving AV Therapy | Not reported | Not reported | Not reported | 55% | 24% of cases | 100% | 50% | Not reported | Not reported |
Case Inclusion Criteria | Adults 18 years of age or older diagnosed with incident HZ or HZO (index date as recorded in database) | Adults 18 years of age or older presenting to ambulatory clinic with incident HZ or HZO (index date as recorded in database) | Adults 18 years of age or older with incident HZ | Adults 18 years of age or older with incident HZ or HZO and incident stroke | Adults 18 years of age or older presenting to ambulatory clinic with incident HZO (index date as recorded in database) | Adults 65 years of age or older with evidence of incident HZ or HZO and an incident ischemic/nonspecific stroke | Adults 18 years of age or older who received acyclovir 800 mg in packs of 35 | All individuals recorded in either of the two databases with incident HZ | Adults 50 years and older with incident HZ |
Case Exclusion Criteria | Patients who experienced cardiovascular/stroke event (MI, TIA, stroke) before index date and those with recurrent HZ | Patients who had been diagnosed with stroke before the index date | Patients who had been diagnosed with stroke before HZ | Patients with evidence of HZ, postherpetic neuralgia, or stroke before the study period. Patients with incident episodes of TIA and subarachnoid hemorrhage or risk factors for subarachnoid hemorrhage. Patients with encephalitis 12 months after stroke. Patients with nonspecific cerebral aneurysms. | Patients diagnosed with HZO during the previous 1-year period. Patients diagnosed with any type of stroke prior to index ambulatory care visit. Patients with systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, HIV, malignancy, and use of steroids or immunosuppressants for more than 1 month within 1 year prior to index date. | Individuals with evidence of vascular events or HZ before observation period. Secondary inpatient diagnosis of zoster or cardiovascular events. Individuals with subarachnoid hemorrhage (or established risk factors of) or encephalitis diagnosed up to 12 months after stroke | Patients who received a second acyclovir prescription of same strength and pack size. Patients with a stroke or TIA diagnoses before the start of the follow up period as per the ICD10 codes below as well as ICD8 codes 430-438 | Patients diagnosed with HZ during the previous 1-year | Recurrent herpes simplex infection, history of stroke great than 1 month before index date, MI before index date |
HZ Definition | Read codes corresponding to diagnoses of incident HZ (index date as recorded in database) | Incident HZ diagnosis using ICD9 codes 053x (index date as recorded in database) | ICD10 codes corresponding to diagnoses of incident HZ (index date as recorded in database) | Read or ICD10 codes corresponding to diagnoses of incident HZ | N/A | HZ diagnosis using ICD-9 codes 053x AND antiviral therapy 7 days before or after diagnosis | Patients who filled a single prescription of acyclovir 800 mg for 35 tablets | Incident HZ diagnosis using ICD-10 code B02.X | Incident HZ diagnosis using ICD-9 codes, and confirmed by medical record review |
HZO Definition | Read codes corresponding to diagnoses of incident HZO | Incident HZO diagnosis using ICD9 code 053 | N/A | Read codes corresponding to diagnoses of incident HZO | Incident HZO diagnosis based on the ICD9 code 053.2 | HZO diagnosis using ICD-9 codes AND antiviral therapy 7 days before or after diagnosis | N/A | N/A | N/A |
Stroke Definition | Read codes corresponding to stroke, diagnosis | Stroke/TIA diagnosis as per ICD9 codes 430-438 | Stroke/TIA diagnosis as per ICD10 codes | Read or ICD10 codes corresponding to stroke diagnosis | Stroke/TIA diagnosis as per ICD9 codes 430-438 | Ischemic/nonspecific stroke diagnosis as per ICD9 codes 436, 433x1, or 434x1 | Diagnosis in hospital of stroke/TIA as per ICD10 I60-64 and G45 | Stroke diagnosis as per ICD-10 codes I61-I64 (excluding I62) | Stroke diagnosis using ICD-9 codes |
Control selection | Patients who had no record of HZ, matched (2:1) by age (+/−2 years), sex, and general practice | Patients with no HZ or stroke before 2001, matched (3:1) on age and sex, and defined their index date as their first ambulatory care visit in 2001 | Patients without HZ, matched on age group | Self controlled | Selected from remaining patients, matched (3:1) on age group and gender, and defined their index date as their first ambulatory care visit in 2004 | Self controlled | Patients who had no prior history of acyclovir, valacyclovir, or famciclovir use (as a proxy for unexposed) | Total remaining population without HZ | Matching each patient with HZ with up to 4 patients whose birthday was +/− 1 year, who were the same sex, and no HZ in the past 5 years |
Confounders (Adjusted for) | Age, sex, obesity, smoking, high cholesterol recording, hypertension, diabetes, ischemic heart disease, atrial fibrillation, intermittent arterial claudication, carotid stenosis, and valvular heart disease | Age, sex, hypertension, diabetes, coronary heart disease, hyperlipidemia, renal disease, atrial fibrillation, heart failure, heart valve/myocardium disease, carotid/peripheral vascular disease, monthly income, urbanization level, and geographical region | Age, male gender, hypertension, hyperlipidaemia, ischaemic heart disease, diabetes, heart failure, peripheral vascular disease, arterial fibrillation or atrial flutter, renal disease and valvular heart disease | Confounders are implicitly controlled for due to study design | Age, sex, hypertension, diabetes, hyperlipidemia, coronary heart disease, chronic rheumatic heart disease, other forms of heart disease, and medication habits | Confounders are implicitly controlled for due to study design | Age, sex, calendar period, acute MI, atrial fibrillation, education, cancer, medications (antihypertensives, drugs used to treat dyslipidemia and atrial fibrillation, immunosuppressive drugs) | Age and sex | Age, sex, hypertension, dyslipidemia, coronary artery disease (including MI), arrhythmias, congestive heart failure, diabetes, depression, chronic obstructive pulmonary disorder, vasculopathies, stroke, and anxiety |
Relevant study outcomes | Stroke HR after >1 year follow up, with analyses stratified by age <40 and ≥40 years, and by HZO. | Stroke HR after 1 year follow up since HZ, with analyses stratified by age (<45 and ≥ 45 years), gender and by HZO | Stroke HR after 11 years of follow up, stratified by age 18–30, 30–40, 40–50, 50–60, 60–70, and >70 years | Stroke IR 1–4, 5–12, 13–26, and 27–52 weeks after HZ or HZO +/−head and neck involvement, with analyses stratified by those who received antiviral therapy and by HZO | Stroke HR after 1 year follow up since HZO, with analyses stratified by those who received antiviral therapy | Stroke IR at 1, 2–4, 5–12, 13–26, and 27–52 weeks since HZ diagnosis, with analyses stratified by gender, HZO | Stroke IRR after <2 weeks, 2–52 weeks, and >1 year follow up since HZ, with analyses stratified by age <40, 40–59, and ≥60 years and by gender | Stroke IRR after 1 year follow up, with analyses stratified by age <40, 40–49, 50–59, 60–69, 70–79, and ≥80 years and gender | Stroke OR 3 and 6 months and 1 and 3 years after zoster. |