The code in this script imports libraries, initializes constants, and performs other such preparatory work for the main analysis.
The full R script is available at:
The analysis relies on a set of open-source R packages for data management, cohort construction, visualization, and statistical modeling. These libraries were selected based on their stability, community support, and suitability for large-scale longitudinal health data.
# Libraries necessary for the analysis
#Data management libraries
library(tidyverse)
library(lubridate)
#Core library for the USRDS
library(usRds)
#Flowchart libraries
library(strobe)
library(flowchart)
#Table libraries
library(gt)
library(gtsummary)
#Plotting libraries
library(ggplot2)
library(ggbeeswarm)
library(patchwork)
#Statistical modeling libraries
library(glmmTMB)
library(emmeans)
library(geepack)
library(broom)
library(broom.mixed)
library(multcomp)The table below lists the required packages along with links to their primary documentation.
| Required R Packages | ||
|---|---|---|
| Libraries used for data processing, visualization, and statistical modeling | ||
| Category | R package | Documentation |
| Data management | tidyverse | tidyverse.org |
| Data management | lubridate | lubridate.tidyverse.org |
| USRDS-specific | usRds | GitHub – usRds |
| Flowcharting | strobe | GitHub – strobe |
| Flowcharting | flowchart | CRAN – flowchart |
| Tables | gt | gt documentation |
| Tables | gtsummary | gtsummary documentation |
| Plotting | ggplot2 | ggplot2.tidyverse.org |
| Plotting | ggbeeswarm | CRAN – ggbeeswarm |
| Plotting | patchwork | patchwork documentation |
| Statistical modeling | glmmTMB | CRAN – glmmTMB |
| Statistical modeling | emmeans | CRAN – emmeans |
| Statistical modeling | geepack | CRAN – geepack |
| Statistical modeling | broom | broom documentation |
| Statistical modeling | broom.mixed | broom.mixed documentation |
| Statistical modeling | multcomp | CRAN – multcomp |
A number of analysis parameters are reused across cohort construction, matching, and cost modeling steps.
These constants are defined in the R/setup.R file.
#Constants
censor_date<-as.Date("2022-01-01")
minimum_followup<-1 #Minimum followup in days
maximum_followup<-365 #Maximum followup in days
number_controls_per_case<-2 #Number of controls per case
inflation_month<-"January"
inflation_year<-2021
baseline_months_cost<-3 #N
full_months <- -baseline_months_cost:11 #Range of months for longitudinal analysisFor clarity, these constants are summarized below along with brief explanations of their role in the analysis.
| Analysis Constants | ||
|---|---|---|
| Matching, follow-up, and cost-model parameters | ||
| Constant | Value | Explanation |
| censor_date | 2022-01-01 | Administrative censoring date for follow-up |
| minimum_followup | 1 | Minimum required follow-up time (days) |
| maximum_followup | 365 | Maximum allowed follow-up time (days) |
| number_controls_per_case | 2 | Number of matched controls per case |
| inflation_month | January | Reference month for cost inflation adjustment |
| inflation_year | 2021 | Reference year for cost inflation adjustment |
| baseline_months_cost | 3 | Number of months included in baseline cost window prior to index date |
| full_months | -3, -2, -1, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 | Month indices used for longitudinal cost analysis |
Lists of ICD-9-CM and ICD-10-CM diagnosis codes were used to define cryptococcosis and relevant comorbid conditions. These code sets were curated prior to analysis and include both legacy ICD-9 codes and corresponding ICD-10 codes to allow consistent identification of conditions across the study period.
For appropriate references, see:
#Create list of ICD9 and ICD10 codes for cryptococcus
cryptococcus_ICD_list<-c("1175", "3210", "B450", "B451", "B452", "B453", "B457", "B458", "B459", "B45")
comorbidity_ICD_list<-list()
comorbidity_ICD_list[["cryptococcus"]]<-c("1175", "3210", "B450", "B451", "B452", "B453", "B457", "B458", "B459", "B45")
comorbidity_ICD_list[["HIV"]]<-c("042",
"07953",
"V08",
"79571",
"B20",
"Z21"
)
comorbidity_ICD_list[["Heart transplant"]]<- c("V421", # ICD-9-CM: Heart transplant status
"Z941") # ICD-10-CM: Heart transplant status
comorbidity_ICD_list[["Heart-lung transplant"]]<-c("Z943") # ICD-10-CM: Heart and lungs transplant status
comorbidity_ICD_list[["Lung transplant"]]<- c("V426", # ICD-9-CM: Lung transplant status
"Z942") # ICD-10-CM: Lung transplant status
comorbidity_ICD_list[["Pancreas transplant"]]<- c("V4283", # ICD-9-CM: Pancreas transplant status
"Z9483") # ICD-10-CM: Pancreas transplant status
comorbidity_ICD_list[["Liver transplant"]]<- c("V427", # ICD-9-CM: Liver transplant status
"Z944") # ICD-10-CM: Liver transplant status
comorbidity_ICD_list[["Intestinal transplant"]]<- c("V4284", # ICD-9-CM: Intestinal transplant status
"Z9482") # ICD-10-CM: Intestinal transplant status
comorbidity_ICD_list[["cirrhosis"]]<-c("5712", # Alcoholic cirrhosis of liver
"5715", # Cirrhosis of liver without mention of alcohol
"5716", # Biliary cirrhosis
"5722", # Hepatic encephalopathy
"5723", # Portal hypertension
"5724", # Hepatorenal syndrome
"5728", #Other sequelae of chronic liver disease#
"K7030", # Alcoholic cirrhosis of liver with ascites
"K7031", # Alcoholic cirrhosis of liver without ascites
"K7460", # Unspecified cirrhosis of liver
"K7469", # Other cirrhosis of liver
"K743", # Primary biliary cirrhosis
"K744", # Secondary biliary cirrhosis
"K745", # Biliary cirrhosis, unspecified
"K7290", # Hepatic failure, unspecified
"K7291", # Acute and subacute hepatic failure with coma
"K766", # Portal hypertension
"K767") # Hepatorenal syndrome
comorbidity_ICD_list[["CMV"]] <- c(
"0785", # Cytomegaloviral disease (ICD-9)
"B250", # CMV pneumonitis
"B251", # CMV hepatitis
"B252", # CMV pancreatitis
"B258", # Other CMV diseases
"B259", # CMV disease, unspecified
"B2710", # Cytomegaloviral mononucleosis without complication
"B2711" # Cytomegaloviral mononucleosis with complication
)
comorbidity_ICD_list[["Diabetes"]]<-c("25000",
"E0800",
"E0900",
"E1000",
"E1100",
"E1300",
"25001",
"E0801",
"E0901",
"E1001",
"E1101",
"E1301",
"25002",
"E0802",
"E0902",
"E1002",
"E1102",
"E1302",
"25003",
"E0803",
"E0903",
"E1003",
"E1103",
"E1303",
"25004",
"E0804",
"E0904",
"E1004",
"E1104",
"E1304",
"25005",
"E0805",
"E0905",
"E1005",
"E1105",
"E1305",
"25006",
"E0806",
"E0906",
"E1006",
"E1106",
"E1306",
"25007",
"E0807",
"E0907",
"E1007",
"E1107",
"E1307",
"25008",
"E0808",
"E0908",
"E1008",
"E1108",
"E1308",
"25009",
"E0809",
"E0909",
"E1009",
"E1109",
"E1309",
"25010",
"E0810",
"E0910",
"E1010",
"E1110",
"E1310",
"25011",
"E0811",
"E0911",
"E1011",
"E1111",
"E1311",
"25012",
"E0812",
"E0912",
"E1012",
"E1112",
"E1312",
"25013",
"E0813",
"E0913",
"E1013",
"E1113",
"E1313",
"25014",
"E0814",
"E0914",
"E1014",
"E1114",
"E1314",
"25015",
"E0815",
"E0915",
"E1015",
"E1115",
"E1315",
"25016",
"E0816",
"E0916",
"E1016",
"E1116",
"E1316",
"25017",
"E0817",
"E0917",
"E1017",
"E1117",
"E1317",
"25018",
"E0818",
"E0918",
"E1018",
"E1118",
"E1318",
"25019",
"E0819",
"E0919",
"E1019",
"E1119",
"E1319",
"25020",
"E0820",
"E0920",
"E1020",
"E1120",
"E1320",
"25021",
"E0821",
"E0921",
"E1021",
"E1121",
"E1321",
"25022",
"E0822",
"E0922",
"E1022",
"E1122",
"E1322",
"25023",
"E0823",
"E0923",
"E1023",
"E1123",
"E1323",
"25024",
"E0824",
"E0924",
"E1024",
"E1124",
"E1324",
"25025",
"E0825",
"E0925",
"E1025",
"E1125",
"E1325",
"25026",
"E0826",
"E0926",
"E1026",
"E1126",
"E1326",
"25027",
"E0827",
"E0927",
"E1027",
"E1127",
"E1327",
"25028",
"E0828",
"E0928",
"E1028",
"E1128",
"E1328",
"25029",
"E0829",
"E0929",
"E1029",
"E1129",
"E1329",
"25030",
"E0830",
"E0930",
"E1030",
"E1130",
"E1330",
"25031",
"E0831",
"E0931",
"E1031",
"E1131",
"E1331",
"25032",
"E0832",
"E0932",
"E1032",
"E1132",
"E1332",
"25033",
"E0833",
"E0933",
"E1033",
"E1133",
"E1333",
"25034",
"E0834",
"E0934",
"E1034",
"E1134",
"E1334",
"25035",
"E0835",
"E0935",
"E1035",
"E1135",
"E1335",
"25036",
"E0836",
"E0936",
"E1036",
"E1136",
"E1336",
"25037",
"E0837",
"E0937",
"E1037",
"E1137",
"E1337",
"25038",
"E0838",
"E0938",
"E1038",
"E1138",
"E1338",
"25039",
"E0839",
"E0939",
"E1039",
"E1139",
"E1339",
"25040",
"E0840",
"E0940",
"E1040",
"E1140",
"E1340",
"25041",
"E0841",
"E0941",
"E1041",
"E1141",
"E1341",
"25042",
"E0842",
"E0942",
"E1042",
"E1142",
"E1342",
"25043",
"E0843",
"E0943",
"E1043",
"E1143",
"E1343",
"25044",
"E0844",
"E0944",
"E1044",
"E1144",
"E1344",
"25045",
"E0845",
"E0945",
"E1045",
"E1145",
"E1345",
"25046",
"E0846",
"E0946",
"E1046",
"E1146",
"E1346",
"25047",
"E0847",
"E0947",
"E1047",
"E1147",
"E1347",
"25048",
"E0848",
"E0948",
"E1048",
"E1148",
"E1348",
"25049",
"E0849",
"E0949",
"E1049",
"E1149",
"E1349",
"25050",
"E0850",
"E0950",
"E1050",
"E1150",
"E1350",
"25051",
"E0851",
"E0951",
"E1051",
"E1151",
"E1351",
"25052",
"E0852",
"E0952",
"E1052",
"E1152",
"E1352",
"25053",
"E0853",
"E0953",
"E1053",
"E1153",
"E1353",
"25054",
"E0854",
"E0954",
"E1054",
"E1154",
"E1354",
"25055",
"E0855",
"E0955",
"E1055",
"E1155",
"E1355",
"25056",
"E0856",
"E0956",
"E1056",
"E1156",
"E1356",
"25057",
"E0857",
"E0957",
"E1057",
"E1157",
"E1357",
"25058",
"E0858",
"E0958",
"E1058",
"E1158",
"E1358",
"25059",
"E0859",
"E0959",
"E1059",
"E1159",
"E1359",
"25060",
"E0860",
"E0960",
"E1060",
"E1160",
"E1360",
"25061",
"E0861",
"E0961",
"E1061",
"E1161",
"E1361",
"25062",
"E0862",
"E0962",
"E1062",
"E1162",
"E1362",
"25063",
"E0863",
"E0963",
"E1063",
"E1163",
"E1363",
"25064",
"E0864",
"E0964",
"E1064",
"E1164",
"E1364",
"25065",
"E0865",
"E0965",
"E1065",
"E1165",
"E1365",
"25066",
"E0866",
"E0966",
"E1066",
"E1166",
"E1366",
"25067",
"E0867",
"E0967",
"E1067",
"E1167",
"E1367",
"25068",
"E0868",
"E0968",
"E1068",
"E1168",
"E1368",
"25069",
"E0869",
"E0969",
"E1069",
"E1169",
"E1369",
"25070",
"E0870",
"E0970",
"E1070",
"E1170",
"E1370",
"25071",
"E0871",
"E0971",
"E1071",
"E1171",
"E1371",
"25072",
"E0872",
"E0972",
"E1072",
"E1172",
"E1372",
"25073",
"E0873",
"E0973",
"E1073",
"E1173",
"E1373",
"25074",
"E0874",
"E0974",
"E1074",
"E1174",
"E1374",
"25075",
"E0875",
"E0975",
"E1075",
"E1175",
"E1375",
"25076",
"E0876",
"E0976",
"E1076",
"E1176",
"E1376",
"25077",
"E0877",
"E0977",
"E1077",
"E1177",
"E1377",
"25078",
"E0878",
"E0978",
"E1078",
"E1178",
"E1378",
"25079",
"E0879",
"E0979",
"E1079",
"E1179",
"E1379",
"25080",
"E0880",
"E0980",
"E1080",
"E1180",
"E1380",
"25081",
"E0881",
"E0981",
"E1081",
"E1181",
"E1381",
"25082",
"E0882",
"E0982",
"E1082",
"E1182",
"E1382",
"25083",
"E0883",
"E0983",
"E1083",
"E1183",
"E1383",
"25084",
"E0884",
"E0984",
"E1084",
"E1184",
"E1384",
"25085",
"E0885",
"E0985",
"E1085",
"E1185",
"E1385",
"25086",
"E0886",
"E0986",
"E1086",
"E1186",
"E1386",
"25087",
"E0887",
"E0987",
"E1087",
"E1187",
"E1387",
"25088",
"E0888",
"E0988",
"E1088",
"E1188",
"E1388",
"25089",
"E0889",
"E0989",
"E1089",
"E1189",
"E1389",
"25090",
"E0890",
"E0990",
"E1090",
"E1190",
"E1390",
"25091",
"E0891",
"E0991",
"E1091",
"E1191",
"E1391",
"25092",
"E0892",
"E0992",
"E1092",
"E1192",
"E1392",
"25093",
"E0893",
"E0993",
"E1093",
"E1193",
"E1393",
"25094",
"E0894",
"E0994",
"E1094",
"E1194",
"E1394",
"25095",
"E0895",
"E0995",
"E1095",
"E1195",
"E1395",
"25096",
"E0896",
"E0996",
"E1096",
"E1196",
"E1396",
"25097",
"E0897",
"E0997",
"E1097",
"E1197",
"E1397",
"25098",
"E0898",
"E0998",
"E1098",
"E1198",
"E1398",
"25099",
"E0899",
"E0999",
"E1099",
"E1199",
"E1399",
"250",
"E08",
"E09",
"E10",
"E11",
"E13",
"3572",
"36202",
"3620",
"36641",
"E08",
"E09",
"E10",
"E11",
"E13",
"2500",
"2501",
"2502",
"2503",
"2504",
"2505",
"2506",
"2507",
"2508",
"2509",
"E080",
"E081",
"E082",
"E083",
"E084",
"E085",
"E086",
"E087",
"E088",
"E089",
"E090",
"E091",
"E092",
"E093",
"E094",
"E095",
"E096",
"E097",
"E098",
"E099",
"E100",
"E101",
"E102",
"E103",
"E104",
"E105",
"E106",
"E107",
"E108",
"E109",
"E110",
"E111",
"E112",
"E113",
"E114",
"E115",
"E116",
"E117",
"E118",
"E119",
"E130",
"E131",
"E132",
"E133",
"E134",
"E135",
"E136",
"E137",
"E138",
"E139")| ICD-9 and ICD-10 Codes Used to Define Comorbidities | |
|---|---|
| Codes grouped by clinical condition | |
| Comorbidity | ICD Codes |
| cryptococcus | 1175, 3210, B450, B451, B452, B453, B457, B458, B459, B45 |
| HIV | 042, 07953, V08, 79571, B20, Z21 |
| Heart transplant | V421, Z941 |
| Heart-lung transplant | Z943 |
| Lung transplant | V426, Z942 |
| Pancreas transplant | V4283, Z9483 |
| Liver transplant | V427, Z944 |
| Intestinal transplant | V4284, Z9482 |
| cirrhosis | 5712, 5715, 5716, 5722, 5723, 5724, 5728, K7030, K7031, K7460, K7469, K743, K744, K745, K7290, K7291, K766, K767 |
| CMV | 0785, B250, B251, B252, B258, B259, B2710, B2711 |
| Diabetes | 25000, E0800, E0900, E1000, E1100, E1300, 25001, E0801, E0901, E1001, E1101, E1301, 25002, E0802, E0902, E1002, E1102, E1302, 25003, E0803, E0903, E1003, E1103, E1303, 25004, E0804, E0904, E1004, E1104, E1304, 25005, E0805, E0905, E1005, E1105, E1305, 25006, E0806, E0906, E1006, E1106, E1306, 25007, E0807, E0907, E1007, E1107, E1307, 25008, E0808, E0908, E1008, E1108, E1308, 25009, E0809, E0909, E1009, E1109, E1309, 25010, E0810, E0910, E1010, E1110, E1310, 25011, E0811, E0911, E1011, E1111, E1311, 25012, E0812, E0912, E1012, E1112, E1312, 25013, E0813, E0913, E1013, E1113, E1313, 25014, E0814, E0914, E1014, E1114, E1314, 25015, E0815, E0915, E1015, E1115, E1315, 25016, E0816, E0916, E1016, E1116, E1316, 25017, E0817, E0917, E1017, E1117, E1317, 25018, E0818, E0918, E1018, E1118, E1318, 25019, E0819, E0919, E1019, E1119, E1319, 25020, E0820, E0920, E1020, E1120, E1320, 25021, E0821, E0921, E1021, E1121, E1321, 25022, E0822, E0922, E1022, E1122, E1322, 25023, E0823, E0923, E1023, E1123, E1323, 25024, E0824, E0924, E1024, E1124, E1324, 25025, E0825, E0925, E1025, E1125, E1325, 25026, E0826, E0926, E1026, E1126, E1326, 25027, E0827, E0927, E1027, E1127, E1327, 25028, E0828, E0928, E1028, E1128, E1328, 25029, E0829, E0929, E1029, E1129, E1329, 25030, E0830, E0930, E1030, E1130, E1330, 25031, E0831, E0931, E1031, E1131, E1331, 25032, E0832, E0932, E1032, E1132, E1332, 25033, E0833, E0933, E1033, E1133, E1333, 25034, E0834, E0934, E1034, E1134, E1334, 25035, E0835, E0935, E1035, E1135, E1335, 25036, E0836, E0936, E1036, E1136, E1336, 25037, E0837, E0937, E1037, E1137, E1337, 25038, E0838, E0938, E1038, E1138, E1338, 25039, E0839, E0939, E1039, E1139, E1339, 25040, E0840, E0940, E1040, E1140, E1340, 25041, E0841, E0941, E1041, E1141, E1341, 25042, E0842, E0942, E1042, E1142, E1342, 25043, E0843, E0943, E1043, E1143, E1343, 25044, E0844, E0944, E1044, E1144, E1344, 25045, E0845, E0945, E1045, E1145, E1345, 25046, E0846, E0946, E1046, E1146, E1346, 25047, E0847, E0947, E1047, E1147, E1347, 25048, E0848, E0948, E1048, E1148, E1348, 25049, E0849, E0949, E1049, E1149, E1349, 25050, E0850, E0950, E1050, E1150, E1350, 25051, E0851, E0951, E1051, E1151, E1351, 25052, E0852, E0952, E1052, E1152, E1352, 25053, E0853, E0953, E1053, E1153, E1353, 25054, E0854, E0954, E1054, E1154, E1354, 25055, E0855, E0955, E1055, E1155, E1355, 25056, E0856, E0956, E1056, E1156, E1356, 25057, E0857, E0957, E1057, E1157, E1357, 25058, E0858, E0958, E1058, E1158, E1358, 25059, E0859, E0959, E1059, E1159, E1359, 25060, E0860, E0960, E1060, E1160, E1360, 25061, E0861, E0961, E1061, E1161, E1361, 25062, E0862, E0962, E1062, E1162, E1362, 25063, E0863, E0963, E1063, E1163, E1363, 25064, E0864, E0964, E1064, E1164, E1364, 25065, E0865, E0965, E1065, E1165, E1365, 25066, E0866, E0966, E1066, E1166, E1366, 25067, E0867, E0967, E1067, E1167, E1367, 25068, E0868, E0968, E1068, E1168, E1368, 25069, E0869, E0969, E1069, E1169, E1369, 25070, E0870, E0970, E1070, E1170, E1370, 25071, E0871, E0971, E1071, E1171, E1371, 25072, E0872, E0972, E1072, E1172, E1372, 25073, E0873, E0973, E1073, E1173, E1373, 25074, E0874, E0974, E1074, E1174, E1374, 25075, E0875, E0975, E1075, E1175, E1375, 25076, E0876, E0976, E1076, E1176, E1376, 25077, E0877, E0977, E1077, E1177, E1377, 25078, E0878, E0978, E1078, E1178, E1378, 25079, E0879, E0979, E1079, E1179, E1379, 25080, E0880, E0980, E1080, E1180, E1380, 25081, E0881, E0981, E1081, E1181, E1381, 25082, E0882, E0982, E1082, E1182, E1382, 25083, E0883, E0983, E1083, E1183, E1383, 25084, E0884, E0984, E1084, E1184, E1384, 25085, E0885, E0985, E1085, E1185, E1385, 25086, E0886, E0986, E1086, E1186, E1386, 25087, E0887, E0987, E1087, E1187, E1387, 25088, E0888, E0988, E1088, E1188, E1388, 25089, E0889, E0989, E1089, E1189, E1389, 25090, E0890, E0990, E1090, E1190, E1390, 25091, E0891, E0991, E1091, E1191, E1391, 25092, E0892, E0992, E1092, E1192, E1392, 25093, E0893, E0993, E1093, E1193, E1393, 25094, E0894, E0994, E1094, E1194, E1394, 25095, E0895, E0995, E1095, E1195, E1395, 25096, E0896, E0996, E1096, E1196, E1396, 25097, E0897, E0997, E1097, E1197, E1397, 25098, E0898, E0998, E1098, E1198, E1398, 25099, E0899, E0999, E1099, E1199, E1399, 250, E08, E09, E10, E11, E13, 3572, 36202, 3620, 36641, E08, E09, E10, E11, E13, 2500, 2501, 2502, 2503, 2504, 2505, 2506, 2507, 2508, 2509, E080, E081, E082, E083, E084, E085, E086, E087, E088, E089, E090, E091, E092, E093, E094, E095, E096, E097, E098, E099, E100, E101, E102, E103, E104, E105, E106, E107, E108, E109, E110, E111, E112, E113, E114, E115, E116, E117, E118, E119, E130, E131, E132, E133, E134, E135, E136, E137, E138, E139 |