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1 Supplementary Online Content Lee C-C, Lee M-tG, Chen Y-S. Risk of aortic dissection and aortic aneurysm in patients taking oral fluoroquinolone. JAMA Internal Medicine. Published online October 5, doi: /jamainternmed efigure. Graphical timeline of the study design etable 1. ICD-9-CM Codes for infectious disease etable 2. Propensity score model for use of fluoroquinolones etable 3. Annual population prevalence of fluoroquinolone use in Taiwan eequations. Population Attributable Risk (PAR) This supplementary material has been provided by the authors to give readers additional information about their work.
2 efigure. Graphical timeline of the study design
3 etable 1. ICD-9-CM Codes for infectious disease Disease ICD-9-CM Codes Infectious colitis, enteritis, and gastroenteritis Infectious diarrhea Tuberculosis of meninges and central nervous system 013 Tuberculosis peritonitis 014 Tuberculosis of bones and joints 015 Tuberculosis of genitourinary system 016 Tuberculosis of other organs 017 Miliary tuberculosis 018 Bacterial meningitis 320 Acute and subacute bacterial endocarditis Acute and subacute infective endocarditis in diseases classified elsewhere Acute sinusitis 461 Acute bronchitis and bronchiolitis 466 Pneumococcal pneumonia 481 Other bacterial pneumonia 482 Pneumonia due to other specified organism 483 Pneumonia in infectious diseases classified elsewhere 484 Bronchopneumonia, organism unspecified 485 Pneumonia, organism unspecified 486 Bronchitis, not specified as acute or chronic 490 Chronic bronchitis 491 Bronchiectasis 494 Peritonitis and retroperitoneal infections 567 Acute cholecystitis Other cholecystitis Cholangitis Infections of kidney 590 Urinary tract infection, site not specified Carbuncle and furuncle 680 Cellulitis and abscess of finger and toe 681 Other cellulitis and abscess 682 Acute lymphadenitis 683 Impetigo 684
4 Pilonidal cyst 685 Other local infections of skin and subcutaneous tissue 686 Osteomyelitis periostitis and other infections involving bone 730 Fever and other physiologic disturbances of temperature regulation 780.6
5 etable 2. Propensity score model for use of fluoroquinolones Characteristics IRR (95%CI) for use of Fluoroquinolone AUC 0.78 Demographics Age 1.01 ( ) Age square 1.00 ( ) Gender : male (female as reference) 0.93 ( ) Area : mid-size central city (large central city 1.03 ( ) as reference) Area : suburban area (large central city as 1.09 ( ) reference) Area : countryside area (large central city as 1.10 ( ) reference) Premium rate : 1 19,999 New Taiwan 1.00 ( ) Dollars (dependent as reference) Premium rate : 20,000 39,999 New Taiwan 0.89 ( ) Dollars (dependent as reference) Premium rate : >40,000 New Taiwan Dollars 0.83 ( ) (dependent as reference) Calendar year 2001 (year 2000 as reference) 0.79 ( ) Calendar year 2002 (year 2000 as reference) 0.88 ( ) Calendar year 2003 (year 2000 as reference) 1.03 ( ) Calendar year 2004 (year 2000 as reference) 1.11 ( ) Calendar year 2005 (year 2000 as reference) 0.83 ( ) Calendar year 2006 (year 2000 as reference) 0.84 ( ) Calendar year 2007 (year 2000 as reference) 0.94 ( ) Calendar year 2008 (year 2000 as reference) 0.96 ( ) Calendar year 2009 (year 2000 as reference) 1.02 ( ) Calendar year 2010 (year 2000 as reference) 1.22 ( ) Calendar year 2011 (year 2000 as reference) 1.16 ( ) Charlson index score Charlson comorbidity index 1.08 ( ) Charlson comorbidity index : quadratic 0.99 ( ) Cardiovascular disease related Congestive heart failure 0.98 ( ) Cerebrovascular disease 1.06 ( ) Myocardial infarction/acute coronary 1.04 ( ) syndromes Stroke or transient ischemic attack 1.25 ( ) Peripheral arterial disease 0.94 ( ) Angina 0.96 ( ) Other ischemic heart disease 0.98 ( ) Cerebral atherosclerosis 0.96 ( )
6 Percutaneous coronary/coronary artery bypass 1.08 ( ) graft intervention bed-ridden status 1.09 ( ) Risk factors Diabetes 1.01 ( ) Amphetamines abuse 0.59 ( ) Tobacco 1.09 ( ) Hypertension 1.05 ( ) Lipid disorder 0.92 ( ) Marfan syndrome 12.2 ( ) Bicuspid aortic value <.0001 Coarctation of the aortic <.0001 Giant cell arteritis 1.58 ( ) Takayasu disease <.0001 Cardio vascular syphilis 1.92 ( ) Turner syndrome <.0001 Trauma(motor vehicle traffic accident) 0.90 ( ) Aortic valve disorders 1.13 ( ) Obstructive sleep apnea 1.00 ( ) Chronic obstructive pulmonary disease 1.02 ( ) Ischemic heart disease 0.88 ( ) Chronic kidney disease 1.18 ( ) Asthma 0.94 ( ) Cardiac valve disease 0.95 ( ) Conduction disorder 1.09 ( ) Atrial fibrillation 1.20 ( ) Obesity 0.93 ( ) Malignant hypertension 0.92 ( ) Schizophrenia 0.69 ( ) Opioid poisoning 2.87 ( ) Psychotropic poisoning 0.90 ( ) Seizure disorder(epilepsy) 1.04 ( ) Decubitus ulcer 1.68 ( ) Amputation 0.81 ( ) Any infection disease past 365 days 2.08 ( ) Outpatient visits 1.04 ( ) Outpatient visits : quadratic 1.00 ( ) Emergency department visits 1.07 ( ) Emergency department visits : quadratic 1.00 ( ) The number of hospitalization 1.58 ( ) The number of hospitalization : quadratic 0.97 ( ) Drugs use NSAIDs 1.14 ( ) Aspirin 1.01 ( )
7 Systemic immunosuppressive agents and 1.05 ( ) biologics Systemic corticosteroids 1.19 ( ) DMARDs 1.25 ( ) Statin 0.93 ( ) ACE inhibitors 0.91 ( ) Beta agonist 1.22 ( ) Angiotensin receptor blocker 0.87 ( ) Anticoagulant(antithrombotic agents) 1.04 ( ) Antiarrhythmic 1.11 ( ) Beta blocker(selective + non-selective) 0.93 ( ) Calcium channel blockers 1.00 ( ) Digoxin 0.99 ( ) Loop diuretics 1.24 ( ) Insulin 1.24 ( ) Oral hypoglycemic 1.12 ( ) Fibrate lipid-lowering agent 0.98 ( ) Nitrate anti-anginal 1.00 ( ) Peripheral vasodilators 0.85 ( ) Antidepressants 0.96 ( ) Benzodiazepine 0.96 ( ) Parkinson s medication 1.01 ( ) Antipsychotics 1.04 ( ) Lithium 1.33 ( ) Hydroxyzine 1.09 ( ) Anticonvulsants 0.80 ( )
8 etable 3. Annual population prevalence of fluoroquinolone use in Taiwan Year Percentage Note: Fluoroquinolone user is defined as having a 3 days prescription of fluoroquinolone, and within 30 days of the index episode of infection. Values are obtained from the NHIRD database. eequations. Population Attributable Risk (PAR) PAR = P e (RR e -1) / [1 + P e (RR e -1)] In 2011, P e = PS adjusted RR = 2.43 PS matched RR= 1.75 PAR (using PS adjusted RR) = 0.038(2.43-1)/[ (2.43-1)] = PAR (using PS matched RR) = 0.038(1.75-1)/[ (1.75-1)] = 0.028
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