An electronic SAPS 3-based risk adjustment score for critical illness in an

integrated healthcare system

Vincent Liu, Benjamin J Turk, Arona I Ragins, Patricia Kipnis, Gabriel J Escobar Supplemental Digital Content

TABLE OF CONTENTS. Section 1. Supplemental Figures and Tables Figure S1 Cohort flow diagram.

Figure S2 Duration of ICU data collection. Figure S3 Schematic representation of data extraction. Figure S4 Vital sign cleaning algorithm. Figure S5 Sample heart rate cleaning algorithm. Figure S6 Hosmer-Lemeshow goodness-of-fit plots in the sample (global). Figure S7 Hosmer-Lemeshow goodness-of-fit plots (North American). Figure S8 Hosmer-Lemeshow goodness-of-fit plots from 2009-2011 cohorts. Table S1 Comparison between eSAPS3 and audited SAPS 3 values. Table S2 Derivation and validation cohort characteristics. Table S3 eSAPS3 model performance by hospital. Section 2. Electronic methods for capturing SAPS 3 variables Table S4 Overview of electronic methods by variable. Table S5 Comorbidity adaptation. Table S6 Reason for ICU admission adaptation. Table S7 Hierarchy for ICU admission diagnosis timing. Table S8 Ventilatory support and oxygenation adaptation. Section 3. eSAPS3 detail tables Table S9 Antimicrobial listing. Table S10 Surgery table. Table S11 Chemotherapy and immunosuppressive medication listing.

Section 1. Supplemental Figures and Tables Figure S1.Cohort flow diagram.Intensive care unit (ICU); Kaiser Permanente Northern California (KPNC); KPHC (KP HealthConnect)

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Figure S5. Sample Heart rate cleaning algorithm.

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Table S1.Comparison of values between the eSAPS3 and manually audited SAPS 3 results.

Disagreement between eSAPS3 and audit

SAPS 3 Variable % Kappa

Overall 7.9

Box 1 (pre-ICU) Age 0 1.0 Co-morbidities 3.3 0.48 – 1.0 Pre-ICU location 15.5 0.70 Pre-ICU Length of stay 2.1 0.33 Pre-ICU major therapeutics 6.2 0.33

Box 2 (at ICU) Reason for ICU admission 37.8 0.32 Planned/unplanned admission 2.1 0.64 Infection at ICU admission 7.0 Surgical status 14.5 0.64 Site of surgery (if applicable) 5.7 0.71

Box 3 (physiology) Glasgow Coma Scale 14.0 0.83 Total bilirubin* 3.6 0.79 Body temperature 7.8 1.0 Creatinine* 3.1 0.92 Heart rate 3.1 0.69 Leukocytes* 4.2 0.87 pH* 12.4 0.47 Platelets* 2.3 0.93 Systolic blood pressure 8.8 0.72 Ventilation + oxygenation* 5.2 0.61

Table S2. Cohort characteristics of the derivation and validation samplesfor first-level customization of the eSAPS3 score.P-value based on Students’ t-test or chi-square test. Cohort

Variable Derivation Validation p-value

Number 27,155 (40.0) 40,734 (60.0)

Hospital tertile 0.95 Large 15,982 (58.9) 23,929 (58.7) Medium 6,308 (23.2) 9,503 (23.3) Small 4,865 (17.9) 7,302 (17.9)

Mean age 65 ± 17 65 ± 17 0.78 Mean eSAPS3 score 46.8 ± 12.6 46.8 ± 12.5 0.60

Hospital mortality, no (%) 3,046 (11.2) 4,561 (11.2) 0.94

Table S3.eSAPS3 model performance at each hospital in the validation dataset, measured by Hosmer-Lemeshow goodness-of-fitχ2 and area under the receiver operating characteristic curve (AUC) values. Hosmer-Lemeshow

Hospital No. of patients AUC χ2

1 4881 0.81 11.6 * 2 3807 0.83 40.8 3 3497 0.84 12.2 * 4 4030 0.81 10.5 * 5 3079 0.79 20.9 6 2648 0.80 43.6 7 2365 0.77 21.4 8 1987 0.84 18.0 9 1712 0.82 14.5 *

10 1761 0.82 11.9 * 11 1438 0.81 8.0 * 12 1400 0.83 7.3 * 13 1335 0.83 5.9 * 14 1379 0.84 19.7 15 1137 0.78 13.0 * 16 1171 0.81 15.5 * 17 716 0.85 14.4 * 18 739 0.79 11.8 * 19 673 0.82 12.3 * 20 557 0.79 5.7 * 21 422 0.83 12.7 *

* Hosmer-Lemeshow goodness-of-fit chi-square p-value >0.05.

Section 2. Electronic methods for capturing SAPS 3 variables The table below provides an overview of mapping availability for data elements within the KP HealthConnect (KPHC) paradigm. For each variable that is ‘adapted’, we provide a summary description of the electronic methods to approximate the original SAPS 3 criteria (Table E4). Detailed descriptions of these methods and strategies are then outlined in the following pages. Table S4. Overview of variable mapping availability within KP HealthConnect (KPHC) Mapping availability in KP HealthConnect

SAPS 3 Variable Direct Adapted

Box 1 (pre-ICU) Age X Co-morbidities ICD-9-CM diagnosis coding and medication records Pre-ICU location X Pre-ICU Length of stay X Pre-ICU major therapeutics Medication administration records

Box 2 (at ICU) Reason for ICU admission Timing and priority designation of treating physician-derived

diagnosis coding (ICD-9-CM) Planned/unplanned admission Pre-ICU hospital location and surgery Infection at ICU admission Antibiotic utilization and timing throughout hospitalization Surgical status X Site of surgery (if applicable) Operating room procedural coding

Box 3 (physiology) Glasgow Coma Scale X Total bilirubin* X Body temperature X Creatinine* X Heart rate X Leukocytes* X pH* X Platelets* X Systolic blood pressure X Ventilation + oxygenation* Linked records of ventilator support, arterial blood gases, and

fractional inspired oxygen values

ICU: intensive care unit; ICD-9-CM: International Classification of Diseases, version 9, Clinical Modification *Laboratory values extracted from the Kaiser Permanente Laboratory Utilization Reporting System (LURS).

Electronic adaptation of SAPS 3 variables, detailed. Box 1. Age. Age at the time of ICU admission; directly extracted from KP-HC. Co-morbidities.

SAPS 3: Several co-morbid conditions that contribute points to the SAPS3 model are identified; they include the presence of cancer (disease and treatment), other immunosuppression (primarily medication-related), heart failure (New York Heart Association class IV), cirrhosis, and acquired immunodeficiency disease syndrome (AIDS) with specifications outlined in the table below. eSAPS3: Adaptation based on ICD-9-CM diagnosis coding, history of medication use, Current Procedural Terminology (CPT) coding for procedures below (Table 2.2).

Table S5. Comorbidity adaptation Variable Criteria

AIDS SAPS3 Patients meeting the CDC/WHO definition of AIDS eSAPS3 adaptation Patients maintained in the KP Northern California regional registry for AIDS or ICD-9-CM

based diagnosis code of 042

Steroid treatment SAPS3 ≥0.3 mg/kg prednisolone or equivalent corticosteroid, daily, in 6 months before ICU admit eSAPS3 adaptation ≥0.3 mg/kg prednisone or equivalent, based on outpatient medication prescriptions

covering 70% of a 6 month period (i.e. 135 of 180 days). Excludes topical or inhaled forms.

Radiotherapy SAPS3 Within 6 months prior to admission excluding non-invasive skin tumors, enteral/parenteral

radioisotope therapy, radioactive implants, radiotherapy for prevention of heterotopic bone formation

eSAPS3 adaptation Radiation within 6 months prior to ICU admission based on KP regional registry of radiotherapy (based on CPT coding)

Chemotherapy SAPS3 Within 6 months prior to admission, including immunosuppression resulting from the

treatment of malignancy, vasculitis, or rheumatoid arthritis eSAPS3 adaptation Based on medication records including the usage of any of the medications listed in

eSAPS3 Data Table 3 (Chemotherapy and Immunosuppression) below within 6 months.

Metastatic cancer SAPS3 Cancer with proven distant metastasis (not regional lymph nodes) by surgery, radiology, or

other method eSAPS3 adaptation Outpatient ICD-9-CM based diagnosis coding for primary malignancy (first 3 digits: 140-

195 and 199) as well as metastasis (196-198)

Hematologic cancer SAPS3 Lymphoma, acute leukemia, or multiple myeloma eSAPS3 adaptation Outpatient ICD-9-CM based diagnosis coding (first 3 digits: 200-208)

Congestive heart failure SAPS3 New York Heart Association class IV criteria eSAPS3 adaptation Inpatient hospital admission within the past year in which the principal ICD-9-CM diagnosis

code (i.e., reason for hospitalization) includes: all 428, 402.01, 402.11, 402.91, 785.51

Cirrhosis SAPS3 Documented by biopsy prior to admission or clinical symptoms of portal hypertension,

including: variceal disease, retrograde splenic-venous flow by ultrasound, or prior episodes of hepatic failure/encephalopathy/coma.

eSAPS3 adaptation Outpatient ICD-9-CM based diagnosis coding, including: 571.2, 571.5, 571.6, 571.9

Hospital length of stay prior to ICU. Directly extracted based on bed history tracking.

Hospital location prior to ICU.

SAPS 3: Values for this variable include: ward, emergency room, other ICU, intermediate care unit, operative room, recovery room, and other. Differing point values were assigned only to: (1) emergency room; (2) other ICU; and (3) any other location. eSAPS3: Assignments to each value were based on bed tracking history and SAPS 3 criteria. Patients in the ‘other’ category included only those transferred from the wards or other location (not including the operating room, recovery area, and transitional/intermediate care units), based on SAPS 3 instructions. Since KP Northern California is primarily a community-hospital system, nearly all facilities have only a single ICU; thus, ‘other ICU’ was not applicable. Additionally, our study inclusion criteria excluded patients whose hospitalization did not begin within the KPNC system.

Use of major therapeutic options before ICU admission.

SAPS 3: This variable denotes major (or emergency) therapeutic procedures administered to the patient prior to ICU admission. They include: cardiopulmonary resuscitation, vasoactive drugs, and mechanical ventilation. In the final model only the use of vasoactive drugs contributed to SAPS 3 points—these were defined as dopamine ≥5 microgram/kg/minute or any dose of dobutamine, epinephrine, or norepinephrine administered intravenously continuously for more than 1 hour prior to ICU admission. eSAPS3: We used medication administration records in the one hour prior to ICU admission to identify patients who were receiving dopamine (of any weight-based dose), dobutamine, epinephrine, or norepinephrine via continuous or intravenous infusion during the 1 hour preceding ICU admission.

Box 2. Reason for ICU admission.

SAPS 3: Determined based on a ‘concrete’ reason for ICU admission. Numerous values could be assigned based on organ systems and reasons. For example, the neurological category included: (1) coma, stupor, obtunded patient, vigilance disturbances, confusion, agitation, delirium; (2) seizures; (3) focal neurological deficit (hemiplegia, paraplegia, tetraplegia); (4) intracranial mass effect; and (5) other. Cases in which there was no clearly defined reason for ICU admission could be categorized as ‘basic and observational intensive care’. In the final model, only 9 reasons for admission were assigned point values (outlined in the table below). eSAPS3: Because no single field that outlined the ‘concrete’ reason for ICU admission could be identified, we utilized diagnosis coding by physicians in the KPHC ‘Problem List’ category. The ‘Problem List’ diagnoses are derived from ICD-9-CM diagnosis codes and are added and removed from KPHC at physician

discretion in both inpatient and outpatient settings. When a patient is admitted to the hospital, outpatient diagnoses can be migrated into the inpatient problem list and labeled with a ‘hospital problem’ flag. New diagnoses can also be added to the problem list. Priority flags, such as ‘Principal’, ‘Highest’, ‘High’, or ‘Medium’, can be assigned to prioritize hospital problems. The ‘Problem List’ differs from diagnostic coding traditionally available in administrative data because it is: (1) inputted directly by treating physicians, (2) not altered by non-clinical manual coders, (3) is not retrospectively assigned, and (4) is available to clinicians at the bedside.ICD-9-CM diagnosis codes were cross-matched against SAPS 3-based categories for point assignment (Table E6).

Table S6. Reason for ICU admission diagnosis ICD-9-CM mapping strategy ICD-9-CM Diagnosis SAPS 3 Category Point Codes Categories

Cardiovascular Rhythm disturbances -5 427 Cardiac dysrhythmia 426 Conduction disorders 785.0, 785.1 Tachycardia, palpitations Hypovolemic shock 3 578 Gastrointestinal hemorrhage 666 Postpartum hemorrhage Other shock 3 458 Hypotension 785.5 Shock 995.0 Anaphylactic shock 995.4 Shock due to anesthesia 995.6 Shock due to food reaction 995.91 to 995.94 Sepsis

Hepatic Liver failure 6 570 to 573 Disorders of the liver

Digestive Severe pancreatitis 9 577 Diseases of the pancreas Acute abdomen 3 530 to 538 Diseases of the esophagus, stomach, duodenum 540 to 543 Appendicitis 550 to 553 Hernia of abdominal cavity 555 to 558 Enteritis and colitis 574 to 576 Disorders of the biliary tract 560 to 562 Intestinal obstruction and diverticula 567 to 569 Peritonitis 590 Kidney infections 614 to 615 Inflammatory disease of female organs 619 Fistula involving the female tract 789.0 Abdominal pain 789.4 Abdominal rigidity 789.6 Abdominal tenderness

Neurologic Intracranial mass effect 10 324.0 Intracranial abcess 348.4 Compression of brain Focal neurological sign 7 342 Hemiplegia and hemiparesis 344 Other paralytic syndromes 438.2 to 438.5 Hemiplegia and hemiparesis 781.4 Transient paralysis of limbs Seizures -4 345 Epilepsy and recurrent seizures 780.3 Convulsions Coma, stupor, etc. 4 290 to 298 Psychoses 303.0, 303.9 Alcohol intoxication 348.1 Anoxic brain damage 348.3 Encephalopathy 349.82 Toxic encephalopathy 437.2 Hypertensive encephalopathy 780.0 to 780.2 Alteration of consciousness 780.97 Altered mental status

In order to assign the most pertinent and timely reason for ICU admission, we generated a diagnosis hierarchy based on diagnosis code timing, content, and assigned flags for hospital diagnoses. For example, the highest diagnosis position was given to any diagnosis code that was entered on the same day as ICU admission and flagged as ‘Principal’. Next highest positioning was given to the diagnoses given the day after ICU admission with the ‘Principal’ flag. This was followed by diagnoses given the ‘Primary’ flag on either the day of admission or the day after. The subsequent process followed the algorithm displayed below (Table E7). A total of three top diagnoses were allowed; only the highest point-scoring diagnosis (if applicable) was then added to the eSAPS3 score.

Table S7.Hierarchy of diagnosis for ‘Reason for ICU admission’.

Hierarchy Diagnosis flag Timing, relative to ICU admission day

1 Principal Same day 2 Principal Day after 3 Principal Day before 4 Highest Same day 5 Highest Day after 6 Highest Day before 7 High Same day 8 High Day after 9 High Day before 10 Principal Two days after 11 Principal Two days before 12 Highest Two days after 13 Highest Two days before 14 High Two days after 15 High Two days before 16 Principal Any other ICU day 17 Highest Any other ICU day 18 High Any other ICU day

Planned or unplanned ICU admission.

SAPS 3: ICU admissions are divided into those that were planned at least 12 hours in advance and those that were not. eSAPS3: No clear source for the determination of whether an ICU admission was planned or unplanned could be identified within structured data fields of KPHC. We adapted the SAPS3 criteria to include two groups as ‘planned’ ICU admissions: (1) those in the ED for more than 12 hours who were directly admitted to the ICU; and (2) patients who went from the OR directly to the ICU without stopping at other hospital locations. All other ICU admissions were labeled as ‘unplanned’.

Acute infection at ICU admission (acquisition and site).

SAPS 3: Types and sites of infections are expanded and defined (e.g., lower respiratory tract or meningitis) as well as the community- and hospital-acquired distinction (if an infection is present). In the final model, two values were used: nosocomial (4 points) and respiratory (5 points).

eSAPS3: Adaptations for the SAPS 3 variable were drawn from indirect information based on clinician usage of antibiotics. Thus, the distinction between community- or hospital-acquired infection was based on the initiation timing for any antibiotic. Antibiotic administration was based on a review of medication usage timing, route, and type records (see Antibiotics table; Table E9). For example, if a patient had been on antimicrobial agents continuously from the time of hospital admission til ICU admission we considered any infection to be ‘community-acquired’. In the case that patients were not initiated on antibiotics until after 48 hours of hospital admission, and were on antibiotics in the peri-ICU period, we considered an infection to be ‘hospital-acquired’. Lower respiratory tract infections were based on ICD-9-CM coding for either primary hospital diagnosis or reason for ICU admission within the following categories: 480-488, 507, 510, and 513.

Surgical status at ICU admission.

SAPS 3: Categories included: (1) patients not submitted to surgery; (2) scheduled surgery (planned more than 24 hours in advance); and (3) emergency surgery (planned less than 24 hours in advance). eSAPS3: The urgency of surgical procedures was classified based on operating room-inputted data denoting the urgency of surgery. Values included: (a) cancer; (b) elective; (c) within 2 weeks; (d) within 48 hour; and (e) within 24 hours. Surgical procedures entered as required ‘within 24 hours’ were considered emergency surgery.

Anatomical site of surgery.

SAPS 3: Multiple sites of surgery were defined in the model; examples include thoracic surgery (eg, pneumonectomy, lobectomy, etc) or upper gastrointestinal surgery (defined as surgery up to and including the jejunum). In the final model, however, only 4 types of surgery contributed points towards the SAPS 3 score. These included: transplantation surgery; trauma surgery; cardiac surgery (CABG without valvular repair); and neurosurgery (cerebrovascular surgery). All other surgeries did not contribute to the final SAPS 3 score. eSAPS3: We adapted the SAPS 3 score using operating room (OR) procedural tables that provided structured coding for surgery types. The relevant surgical definitions are listed below (see Surgery Type table; Table S10). Procedural codes for the Neurosurgery (cerebrovascular surgery) category were derived empirically based on a sample of patients hospitalized for cerebrovascular accident who then underwent a neurosurgical procedure. Procedural codes for Trauma (simple and multiple) surgical codes were also based on empirical analysis of surgeries among patients admitted with Trauma diagnoses. In the eSAPS3 score, only trauma surgical codes among patients with trauma diagnosis coding were counted.

Box 3. Body temperature (highest).Highest temperature (farenheit) at ICU admission; extracted and cleaned from KPHC vital sign flow sheets. Creatinine (highest).Highest creatinine (mg/dL) at ICU admission; directly extracted from Laboratory Utilization Reporting System (LURS). Estimated Glasgow Coma Scale (lowest). Glasgow Coma scale components (eye, motor, and verbal responses); extracted from KPHC flow sheets based on bedside nurse coding and previous work. Heart rate (highest).Highest heart rate (bpm) at ICU admission (KPHC flow sheets). Leukocytes (highest).Highest leukocytes (cells x 103/mm3; LURS). pH (hydrogen ion concentration; lowest). Lowest pH at ICU admission (LURS). Platelets (lowest).Lowest platelets (cells x 103/mm3; LURS). Systolic blood pressure (lowest).Lowest systolic blood pressure (mm Hg; KPHC) Total bilirubin (highest).Highest bilirubin (mg/dL; LURS). Ventilatory support and oxygenation.

SAPS 3:Ventilatory support was defined as methods of non-invasive positive pressure ventilation (CPAP, BiPAP, PSV) or invasive ventilation (CPAP, PSV, SIMV, SIMV+PSV, PCV, CMV, A/CMV). Values varied based on the presence of ventilation, the partial pressure of arterial oxygen (PaO2), and the fractional inspired concentration of oxygen (FiO2). Categories included:

(1) PaO2/FiO2< 100 + ventilation (2) PaO2/FiO2≥ 100 + ventilation (3) PaO2< 60 and no ventilation (4) PaO2≥ 60 and no ventilation

eSAPS3: We identified patients who received ventilator support (both non-invasive and invasive) based on structured data available within KP-HC data fields that were updated by bedside nurses and respiratory therapists. We extracted corresponding data values for FiO2 and LURS values for PaO2 (where available). The above categories were then approximated (Table E8).

Table S8. Ventilation/oxygenation mapping strategy

eSAPS3 ventilation/oxygenation data fields and profile Adapted SAPS3 category

Ventilation FiO2 PaO2 O2 saturation P/F ratio Group Points

Yes Yes Yes -- <100 (1) P/F<100+vent 11 Yes Yes Yes -- ≥100 (2) P/F≥100+vent 7 Yes Yes No Yes -- (2) P/F≥100+vent 7 No -- Yes, <60 -- -- (3) PaO2<60 5 No -- No Yes, <88% -- (3) PaO2<60 5 No -- Yes, ≥60 -- (4) PaO2≥60 0 No -- No Yes, ≥88% -- (4) PaO2≥60 0

Table S9.eSAPS3 alphabetic list of Antimicrobials.Routes of administration included oral, feeding tubes, intravenous, intradialysis, and intramuscular.

ACYCLOVIR CEFTRIAXONE HALOFANTRINE PRIMAQUINE ALATROFLOXACIN CEFUROXIME HYDROXYCHLOROQUINE PYRANTEL

ALBENDAZOLE CEPHALEXIN IMIPENEM PYRAZINAMIDE AMIKACIN CEPHALOTHIN ISONIAZID PYRIMETHAMINE

AMINOSALICYLIC CEPHAPIRIN ITRACONAZOLE QUININE AMOX CEPHRADINE IVERMECTIN QUINUPRISTIN

AMOXICILLIN CHLORAMPHENICOL KANAMYCIN RIBAVIRIN AMPHOTERICIN CHLOROQUINE KETOCONAZOLE RIFABUTIN

AMPICILLIN CIDOFOVIR LEVOFLOXACIN RIFAMPIN ANIDULAFUNGIN CIPROFLOXACIN LINCOMYCIN RIFAPENTINE

ARTEMETHER CLARITHROMYCIN LINEZOLID RIMANTADINE ATOVAQUONE CLINDAMYCIN LOMEFLOXACIN SPARFLOXACIN

AZITHROMYCIN CLOXACILLIN LORACARBEF STREPTOMYCIN AZTREONAM COLISTIMETHATE MEBENDAZOLE SULFADIAZINE

BACAMPICILLIN CYCLOSERINE MEFLOQUINE SULFAMETHOXAZOLE CAPREOMYCIN DALFOPRISTIN MEROPENEM SULFISOXAZOLECARBENICILLIN DAPSONE METRONIDAZOLE TELAVANCIN CASPOFUNGIN DAPTOMYCIN MICAFUNGIN TELITHROMYCIN

CEFACLOR DICLOXACILLIN MINOCYCLINE TETRACYCLINE CEFADROXIL DIRITHROMYCIN MOXIFLOXACIN THIABENDAZOLE

CEFAMANDOLE DORIPENEM NAFCILLIN TICARCILLIN CEFAZOLIN DOXYCYCLINE NETILMICIN TICARCILLINCEFDINIR ENOXACIN NICLOSAMIDE TOBRAMYCIN

CEFDITOREN ERTAPENEM NITROFURANTOIN TRIMETHOPRIMCEFEPIME ERYTHROMYCIN NORFLOXACIN TROVAFLOXACIN CEFIXIME ETHAMBUTOL OFLOXACIN VALACYCLOVIR

CEFONICID ETHIONAMIDE OSELTAMIVIR VALGANCICLOVIR CEFOPERAZONE FAMCICLOVIR OXACILLIN VANCOMYCIN

CEFOTAXIME FLUCONAZOLE OXYTETRACYCLINE VORICONAZOLE CEFOTETAN FOSCARNET PALIVIZUMAB ZANAMIVIRCEFOXITIN FURAZOLIDONE PENICILLIN

CEFPODOXIME GANCICLOVIR PERAMIVIR CEFPROZIL GATIFLOXACIN PIPERACILLIN

CEFTAZIDIME GEMIFLOXACIN POLYMYXINCEFTIBUTEN GENTAMICIN POSACONAZOLE CEFTIZOXIME GREPAFLOXACIN PRAZIQUANTEL

Table S10.eSAPS3 alphabetical list of eligible surgical procedures from KPHC operating room schedule tables. Category Operating Room Procedure Name

CABG AORTOCORONARY BYPASS OF 1 CORONARY ARTERY W ARM VEIN GRAFT AORTOCORONARY BYPASS OF 1 CORONARY ARTERY W FEMOROPOPLITEAL VEIN HARVEST AORTOCORONARY BYPASS OF 2 CORONARY ARTERIES W ARM VEIN HARVEST AORTOCORONARY BYPASS OF 2 CORONARY ARTERIES W FEMOROPOPLITEAL VEIN HARVEST AORTOCORONARY BYPASS OF 3 CORONARY ARTERIA GRAFT W ARM VEIN AORTOCORONARY BYPASS OF 3 CORONARY ARTERIES W FEMOROPOPLITEAL VEIN HARVEST AORTOCORONARY BYPASS OF 4 OR MORE CORONARY ARTERIES W ARM VEIN GRAFT AORTOCORONARY BYPASS OF 4 OR MORE CORONARY ARTERIES W FEMOROPOPLITEAL VEIN HARVEST AORTOCORONARY BYPASS OF FOUR OR MORE CORONARY ARTERIES AORTOCORONARY BYPASS OF ONE CORONARY ARTERY AORTOCORONARY BYPASS OF THREE CORONARY ARTERIES AORTOCORONARY BYPASS OF TWO CORONARY ARTERIES AORTOCORONARY BYPASS REVISION, 1 GRAFT AORTOCORONARY BYPASS REVISION, 1 GRAFT W ARM VEIN AORTOCORONARY BYPASS REVISION, 2 GRAFTS AORTOCORONARY BYPASS REVISION, 2 GRAFTS W ARM VEIN AORTOCORONARY BYPASS REVISION, 2 GRAFTS W FEMOROPOPLITEAL VEIN HARVEST AORTOCORONARY BYPASS REVISION, 3 GRAFTS AORTOCORONARY BYPASS REVISION, 3 GRAFTS W ARM VEIN AORTOCORONARY BYPASS REVISION, 3 GRAFTS W FEMOROPOPLITEAL VEIN HARVEST AORTOCORONARY BYPASS REVISION, 4 GRAFTS OR MORE AORTOCORONARY BYPASS REVISION, 4 GRAFTS OR MORE W ARM VEIN AORTOCORONARY BYPASS REVISION, 4 OR MORE GRAFTS W FEMOROPOPLITEAL VEIN HARVEST AORTOCORONARY BYPASS REVISION,1 GRAFT W FEMOROPOPLITEAL VEIN HARVEST CABG REVISION W ENDOSCOPIC VEIN HARVEST, 3 OR MORE VEIN, OFF PUMP CABG REVISION W ENDOSCOPIC VEIN HARVEST, 3 OR MORE VEIN, ON PUMP CABG REVISION W ENDOSCOPIC VEIN HARVEST, SINGLE OR DOUBLE VEIN, OFF PUMP CABG REVISION W ENDOSCOPIC VEIN HARVEST, SINGLE OR DOUBLE VEIN, ON PUMP CABG REVISION W RADIAL ARTERY, SINGLE OR DOUBLE, OFF PUMP CABG REVISION, 3 OR MORE RADIAL ARTERY, OFF PUMP CABG REVISION, 3 OR MORE RADIAL ARTERY, ON PUMP CABG REVISION, SINGLE OR DOUBLE RADIAL ARTERY, ON PUMP CABG W ENDOSCOPIC VEIN HARVEST, 3 OR MORE VEIN, OFF PUMP CABG W ENDOSCOPIC VEIN HARVEST, 3 OR MORE VEIN, ON PUMP CABG W ENDOSCOPIC VEIN HARVEST, SINGLE OR DOUBLE VEIN, OFF PUMP CABG W ENDOSCOPIC VEIN HARVEST, SINGLE OR DOUBLE VEIN, ON PUMP CABG W INTERNAL MAMMARY ARTERY

CABG W SAPHENOUS ARTERY VEIN GRAFT, OFF PUMP CABG W SAPHENOUS ARTERY VEIN GRAFT, ON PUMP CABG W SAPHENOUS VEIN GRAFT OFF PUMP CABG W SAPHENOUS VEIN GRAFT ON PUMP CABG, 3 OR MORE RADIAL ARTERY, OFF PUMP CABG, 3 OR MORE RADIAL ARTERY, ON PUMP CABG, SINGLE OR DOUBLE RADIAL ARTERY, OFF PUMP CABG, SINGLE OR DOUBLE RADIAL ARTERY, ON PUMP CORONARY ARTERY BYPASS GRAFT REVISION THROUGH LEFT THORACOTOMY CORONARY ARTERY BYPASS GRAFT REVISION W ENDOSCOPIC VEIN HARVEST, PORT ACCESS CORONARY ARTERY BYPASS GRAFT W ENDOSCOPIC VEIN HARVEST, PORT ACCESS CORONARY ARTERY BYPASS GRAFTING, OFF PUMP CORONARY ARTERY RIGHT, REPAIR ANOMALOUS CORONARY VENOUS GRAFT DOUBLE, CABG CORONARY VENOUS GRAFT FIVE, CABG CORONARY VENOUS GRAFT FOUR, CABG CORONARY VENOUS GRAFT SINGLE, CABG CORONARY VENOUS GRAFT SIX OR MORE, CABG CORONARY VENOUS GRAFT THREE, CABG INTERNAL MAMMARY CORONARY ARTERY BYPASS GRAFT THORACOSCOPIC CABG THROUGH LEFT THORACOTOMY

Transplant KIDNEY TRANSPLANT

Neurosurgery BURR HOLE HEMATOMA EVACUATION BURR HOLE PLACEMENT BURR HOLE W INSERTION INTER CRANIAL PRESSURE MONITOR CEREBRAL VENTRICLE SHUNT TO EXTRACRANIAL SITE CRANIECTOMY CRANIECTOMY SAGITTAL STRIP CRANIECTOMY SUBOCCIPITAL CRANIOPLASTY CRANIOTOMY ANEURYSM CRANIOTOMY ANEURYSM. CRANIOTOMY BI FRONTAL CRANIOTOMY CRANIAL NERVE EXPLORATION CRANIOTOMY DEBRIDEMENT CRANIOTOMY ELEVATE SKULL FRACTURE CRANIOTOMY ENDOSCOPIC CRANIOTOMY HEMATOMA EVACUATION CRANIOTOMY MIDDLE FOSSA CRANIOTOMY POSTERIOR FOSSA

CRANIOTOMY POSTERIOR FOSSA FOR CYST CRANIOTOMY SUBOCCIPITAL CRANIOTOMY TRANSCORTICAL CRANIOTOMY TUMOR EXCISION CRANIOTOMY W DRAINAGE OF CYST CRANIOTOMY, POSTERIOR FOSSA WITH NAVIGATION ENDARTERECTOMY OF INTRACRANIAL ARTERY INTRACRANIAL VESSEL EXCISION OF LESION INTRACRANIAL VESSEL RESECTION AND ANASTOMOSIS OPERATION ON SKULL, BRAIN, AND CEREBRAL MENINGES PERCUTANEOUS TRANSLUMINAL CORONARY ANGIOPLASTY SKULL BONE FLAP REMOVAL VENTRICULAR DRAIN INSERTION VENTRICULAR SHUNT IRRIGATION VENTRICULAR SHUNT IRRIGATION AND EXPLORATION VENTRICULAR SHUNT REMOVAL VENTRICULAR SHUNT REPLACEMENT VENTRICULAR SHUNT TO HEAD OR NECK STRUCTURE VENTRICULO ATRIAL SHUNT INSERTION VENTRICULO ATRIAL SHUNT REVISION VENTRICULO PERITONEAL SHUNT EXTERNALIZATION OF PERITONEAL END VENTRICULO PERITONEAL SHUNT INSERTION VENTRICULO PERITONEAL SHUNT INSERTION ENDOSCOPIC VENTRICULO PERITONEAL SHUNT REVISION, LAPAROSCOPIC VENTRICULO PERITONEAL SHUNT REVISION, OPEN VENTRICULO PLEURAL SHUNT INSERTION VENTRICULOSCOPY BRAIN VENTRICULOSTOMY BRAIN VENTRICULOSTOMY BURR HOLE VENTRICULOSTOMY ENDOSCOPIC

Trauma ABDOMEN CLOSURE OF WOUND ABDOMEN DEBRIDEMENT OF WOUND OR LACERATION ABDOMEN REMOVAL OF FOREIGN BODY ABDOMEN REPAIR OF WOUND OR LACERATION ABDOMEN WOUND INCISION AND DRAINAGE ABDOMINAL EVACUATION OF CLOT ABDOMINAL WALL EXPLORATION ACHILLES TENDON LENGTHENING, OPEN ACHILLES TENDON REPAIR AMPUTATION STUMP REVISION ANEURYSM REPAIR PSEUDOANEURYSM PERIPHERAL

ANGIOGRAM ANGIOPLASTY OF ARTERY ANKLE DEBRIDEMENT ANKLE INCISION AND DRAINAGE ANKLE ORIF FRACTURE ANTERIOR CRUCIATE LIGAMENT ARTHROSCOPICALLY AIDED RECONSTRUCTION APPENDECTOMY INCIDENTAL APPENDECTOMY OPEN APPLICATION OF EXTERNAL FIXATOR SYSTEM ARM BICEPS, TENDON REPAIR ARM EXCISION SOFT TISSUE MASS, SUBCUTANEOUS ARM FALSE ANEURYSM REPAIR ARM INCISION AND DRAINAGE ARM NERVE REPAIR ARM NERVE REPAIR BY GRAFT ARM TRICEPS, TENDON REPAIR ARTHROTOMY ATTACHMENT OF PEDICLE FLAP GRAFT AXILLO-AXILLARY BYPASS BACK INCISION AND DRAINAGE BACK WOUND INCISION AND DRAINAGE BLOOD VESSEL REPAIR W PATCH GRAFT BONE GRAFT BRACHIAL ARTERY EVACUATION OF CLOT BRONCHOSCOPY RIGID DIAGNOSTIC BURR HOLE HEMATOMA EVACUATION BURR HOLE W INSERTION INTER CRANIAL PRESSURE MONITOR BUTTOCKS DEBRIDEMENT OF WOUND CALCANEUS ORIF FRACTURE CARDIAC PACEMAKER INSERTION PERMANENT INTRAVENOUS CATARACT SURGERY W IOL-PHACO CECECTOMY CESAREAN SECTION CHEST WALL EXPLORATION CHEST WOUND INCISION AND DRAINAGE CHOLECYSTECTOMY CHOLECYSTECTOMY LAPAROSCOPIC CLAVICLE ORIF FRACTURE CLAVICLE RESECTION DISTAL ARTHROSCOPIC COLECTOMY PARTIAL OPEN COLLATERAL LIGAMENTS REPAIR

COLOSTOMY CRANIECTOMY CRANIOTOMY BI FRONTAL CRANIOTOMY HEMATOMA EVACUATION CRANIOTOMY TRANSSPHENOIDAL TUMOR EXCISION CRANIOTOMY W DRAINAGE OF CYST CYSTOSCOPY CYSTOSTOMY, SUPRAPUBIC ELBOW HARDWARE REMOVAL ELBOW NERVE REPAIR ESOPHAGOSCOPY RIGID DIAGNOSTIC ESOPHAGUS DILATION EXCISION OF LESION OF SOFT TISSUE EXOSTOSIS REMOVAL EXTREMITIES LAYER CLOSURE OF WOUNDS FASCIOTOMY FASCIOTOMY CALF FEMORAL ARTERY EVACUATION OF CLOT FEMORAL FEMORAL VASCULAR BYPASS FEMOROPERONEAL VASCULAR BYPASS FEMOROTIBIAL VASCULAR BYPASS, ANTERIOR OR POSTERIOR FEMUR SUPRACONDYLAR FRACTURE, ORIF FINGER AMPUTATION FLAP GRAFT OPERATION FOOT AMPUTATION FOOT AMPUTATION SYMES TYPE FOOT AMPUTATION TRANSMETATARSAL FOOT CLOSURE OF WOUND FOOT DEBRIDEMENT OF WOUND FOOT DEBRIDEMENT OF WOUND OR LACERATION FOOT EXCISION OF SESAMOID BONE FOOT EXCISION SOFT TISSUE FOOT HARDWARE REMOVAL FOOT INCISION AND DRAINAGE OF SKIN AND SUBCUTANEOUS TISSUE FOOT ORIF FRACTURE FOOT RECONSTRUCTION OF SKIN DEFECT W FASCIAL FLAP FOOT REMOVAL OF FOREIGN BODY FOOT SKIN PLASTY FOOT TENDON MUSCLE OR FASCIA GRAFT FOOT TENDON REPAIR FOOT WOUND INCISION AND DRAINAGE

FOREARM DEBRIDEMENT OF WOUND FOREARM DEBRIDEMENT OF WOUND OR LACERATION FOREARM FREE FLAP FOREARM FULL THICKNESS SKIN GRAFT FOREARM INCISION AND DRAINAGE OF SKIN AND SUBCUTANEOUS TISSUE FOREARM ORIF FOREARM REPAIR OF TENDON FOREIGN BODY REMOVAL FRONTAL SINUS OBLITERATION FULL THICKNESS SKIN GRAFT FUSION OF SUBTALAR JOINT FUSION TARSOMETATARSAL GASTROSTOMY TUBE PLACEMENT GASTROTOMY GROIN EXPLORATION HAND ARTHRODESIS HAND DEBRIDEMENT OF WOUND OR LACERATION HAND INCISION AND DRAINAGE HAND ORIF FRACTURE HAND REPAIR NERVE HAND REPAIR OF TENDON HAND TENDON ADVANCEMENT HAND TENDON GRAFT HAND WOUND INCISION AND DRAINAGE HEAD REPAIR OF WOUND OR LACERATION HEMICOLECTOMY RIGHT HIP ARTHROSCOPY HIP HEMIARTHROPLASTY HIP INCISION AND DRAINAGE HIP REPLACEMENT REVISION ACETABULAR LINER AND FEMORAL HEAD HIP RESURFACING TOTAL, ACETABULUM AND FEMORAL HEAD HUMERUS ORIF FRACTURE INCISION AND DRAINAGE INTESTINE ANASTOMOSIS INTESTINE LYSIS OF ADHESIONS INTRA ABDOMINAL LYSIS OF ADHESIONS KNEE ACL RECONSTRUCTION KNEE ACL RECONSTRUCTION W ALLOGRAFT KNEE ACL RECONSTRUCTION W AUTOGRAFT KNEE ARTHROPLASTY, REVISION KNEE ARTHROSCOPY

KNEE ARTHROSCOPY W DEBRIDEMENT KNEE ARTHROSCOPY W MENISCAL REPAIR KNEE ARTHROSCOPY W MENISECTOMY KNEE ARTHROTOMY KNEE ARTHROTOMY REMOVAL OF PROSTHESIS KNEE DEBRIDEMENT OF WOUND KNEE INCISION AND DRAINAGE OF SKIN AND SUBCUTANEOUS TISSUE KNEE JOINT MANIPULATION KNEE MICROFRACTURE CHONDROPLASTY KNEE OR LOWER LEG HARDWARE REMOVAL KNEE ORIF FRACTURE KNEE POSTERIOR CRUCIATE LIGAMENT RECONSTRUCTION KNEE REPAIR COLLATERAL LIGAMENT, OPEN KNEE REPAIR TENDON, OPEN LAPAROSCOPY EXPLORATORY LAPAROSCOPY DIAGNOSTIC LAPAROTOMY LAPAROTOMY EXPLORATORY LARYNGOSCOPY DIRECT LARYNGOSCOPY W REMOVAL OF FOREIGN BODY LEG AMPUTATION ABOVE KNEE LEG AMPUTATION BELOW KNEE LEG CLOSURE OF WOUND LEG DEBRIDEMENT OF WOUND LEG EXCISION OF LESION SOFT TISSUE LEG EXTERNAL FIXATION DEVICE REMOVAL LEG FASCIOCUTANEOUS FLAP GRAFT LEG INCISION AND DRAINAGE OF SKIN AND SUBCUTANEOUS TISSUE LEG NERVE REPAIR W NERVE GRAFT LEG TENDON RELEASE LEG VASCULAR REPAIR LIGAMENT REPAIR LOWER EXTREMITY HARDWARE REMOVAL LOWER EXTREMITY INCISION AND DRAINAGE LOWER LEG CLOSURE OF WOUND LOWER LEG FASCIOTOMY LOWER LEG SPLIT THICKNESS SKIN GRAFT MEDIASTINAL EXPLORATION MENISCUS REPAIR MIDFOOT AMPUTATION MIDFOOT ARTHRODESIS

NECK INCISION AND EXPLORATION NECK REMOVAL OF FOREIGN BODY NECK REPAIR OF WOUND OR LACERATION NEPHRECTOMY TOTAL OPEN REDUCTION OF FRACTURE W INTERNAL FIXATION ORCHIECTOMY OSTEOTOMY OF CALCANEUS PATELLA ORIF FRACTURE PATELLA REPAIR RECURRENT DISLOCATION PATELLA TENDON TRANSFER PECTORALIS MAJOR MYOCUTANEOUS FLAP PECTORALIS TENDON REPAIR PELVIS EXCISION SOFT TISSUE MASS, DEEP PELVIS ORIF FRACTURE PERICARDIAL WINDOW PERIPHERAL NERVE INCISIONAL BIOPSY PERIPHERAL NERVE, BRACHIAL PLEXUS EXPLORATION PERONEAL TENDON REPAIR PHALANGES OF HAND ORIF FRACTURE POPLITEAL ARTERY PATCH REPAIR POPLITEAL PERONEAL BYPASS POSTERIOR CRUCIATE LIGAMENT ARTHROSCOPICALLY AIDED RECONSTRUCTION PROCTOSIGMOIDOSCOPY RIGID QUADRICEPS REPAIR RADIAL ARTERY EXPLORATION RADIAL NERVE REPAIR RADIUS AND ULNA ORIF FRACTURE RECTAL EXAM UNDER ANESTHESIA RECTAL EXCISION OF LESION TRANSANAL RECTUM AND ANUS REMOVAL INTRALUMINAL FB WO INCISION RESPIRATORY TRACT INTUBATION RETROGRADE CHOLANGIOPANCREATOGRAPHY ENDOSCOPIC RETROGRADE PYELOGRAM SCROTUM INCISION AND DRAINAGE W EXCISION OF LESION SCROTUM INCISION AND EXPLORATION SHOULDER ARTHROPLASTY TOTAL SHOULDER ARTHROSCOPY SHOULDER ARTHROSCOPY W DECOMPRESSION SHOULDER ARTHROSCOPY W MUMFORD SHOULDER ARTHROSCOPY W OPEN REPAIR ROTATOR CUFF SHOULDER ARTHROSCOPY W REPAIR ROTATOR CUFF

SHOULDER JOINT ANTERIOR DECOMPRESSION SHOULDER JOINT MANIPULATION SHOULDER REPAIR ARTHROSCOPIC, SUBACROMIAL DECOMPRESSION SHOULDER REPAIR ROTATOR CUFF OPEN SHOULDER REPAIR, ARTHROSCOPIC BANKART SHOULDER REPAIR, ARTHROSCOPIC SLAP SHOULDER REPLACEMENT TOTAL SHOULDER ROTATOR CUFF REPAIR ACROMIO OR DECOMPRESSION SHOULDER STABILIZATION OPEN SHOULDER WEAVER DUNN PROCEDURE SIGMOIDOSCOPY RIGID SKIN DEBRIDEMENT OF WOUND SKIN GRAFT OPERATION SMALL INTESTINE SEGMENTAL RESECTION SPLENECTOMY SPLIT THICKNESS SKIN GRAFT TENDON GASTROCNEMIUS RECESSION TENDON TRANSFER THIGH SKIN GRAFT THORACOSCOPY TRANSPLEURAL THORACOSCOPY W PLEURODESIS THORACOTOMY EXPLORATORY THORAX INCISION AND DRAINAGE THROMBOEMBOLECTOMY TIBIA AND FIBULA DEBRIDEMENT OF OPEN FRACTURE TIBIA EXTERNAL FIXATION FRACTURE TIBIA INTRAMEDULLARY RODDING TIBIA ORIF FRACTURE TIBIA OSTEOTOMY TIBIA PLATEAU FRACTURE ORIF TRACHEOSTOMY TEMPORARY UPPER ARM CLOSURE OF WOUND UPPER ARM WOUND INCISION AND DRAINAGE UPPER LEG WOUND INCISION AND DRAINAGE URETER REIMPLANTATION URETERAL STENT PLACEMENT URETEROSCOPY URETHRAL DILATION VAGINAL REPAIR VEIN SEGMENTAL EXCISION OF LEG VENTRAL HERNIA REPAIR, OPEN

VENTRICULAR DRAIN INSERTION WOUND HEMATOMA EVACUATION WRIST ARTHROSCOPY WRIST EXTERNAL FIXATION WRIST HARDWARE REMOVAL WRIST RECONSTRUCTION LIGAMENT WRIST REPAIR NERVE

Table S11.eSAPS3 eligible medications for categorizing chemotherapy and immunosuppression. ABATACEPT ETANERCEPT PACLITAXEL ADALIMUMAB ETOPOSIDE PANITUMUMAB ALDESLEUKIN EVEROLIMUS PAZOPANIB ALEMTUZUMAB EXEMESTANE PEGASPARGASE ALTRETAMINE FLOXURIDINE PEMETREXED AMINOGLUTETHIMIDE FLUDARABINE PENICILLAMINE ANAKINRA FLUOROURACIL PENTOSTATIN ANASTROZOLE FLUTAMIDE PIMECROLIMUS ARSENIC FULVESTRANT PLICAMYCIN ASPARAGINASE GEFITINIB PRALATREXATE AZACITIDINE GEMCITABINE PROBENECID AZATHIOPRINE GEMTUZUMAB PROCARBAZINE BASILIXIMAB GOLIMUMAB RITUXIMAB BENDAMUSTINE HYDROXYUREA ROMIDEPSIN BEVACIZUMAB IBRITUMOMAB SIPULEUCEL-T BEXAROTENE IDARUBICIN SIROLIMUS BLEOMYCIN IFOSFAMIDE SORAFENIB BORTEZOMIB IMATINIB STREPTOZOCIN BUSULFAN INTERFERON SULFINPYRAZONE CABAZITAXEL IRINOTECAN SUNITINIB CAPECITABINE IXABEPILONE TACROLIMUS CARBOPLATIN LAPATINIB TAMOXIFEN CARMUSTINE LEFLUNOMIDE TEMOZOLOMIDE CETUXIMAB LENALIDOMIDE TEMSIROLIMUS CHLORAMBUCIL LETROZOLE TENIPOSIDE CISPLATIN LEUPROLIDE THIOGUANINE CLADRIBINE LEVAMISOLE THIOTEPA CLOFARABINE LOMUSTINE TOCILIZUMAB CYCLOPHOSPHAMIDE MECHLORETHAMINE TOPOTECAN CYCLOSPORINE MELPHALAN TOREMIFENE CYTARABINE MERCAPTOPURINE TOSITUMOMAB DACARBAZINE MESNA TRASTUZUMAB DACLIZUMAB METHOTREXATE TRETINOIN DACTINOMYCIN METHOXSALEN URACIL DASATINIB MITOMYCIN USTEKINUMAB DAUNORUBICIN MITOTANE VALRUBICIN DECITABINE MITOXANTRONE VINBLASTINE DENILEUKIN MUROMONAB-CD3 VINCRISTINE DOCETAXEL MYCOPHENOLATE VINORELBINE DOXORUBICIN NELARABINE VORINOSTAT EPIRUBICIN NILOTINIB ERLOTINIB OFATUMUMAB