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b/Covid19EstimationHydroxychloroquine/data/preference_score_dist_t2_c28_VA.rds differ diff --git a/Covid19EstimationHydroxychloroquine/data/preference_score_dist_tNA_cNA_Optum.rds b/Covid19EstimationHydroxychloroquine/data/preference_score_dist_tNA_cNA_Clinformatics.rds similarity index 100% rename from Covid19EstimationHydroxychloroquine/data/preference_score_dist_tNA_cNA_Optum.rds rename to Covid19EstimationHydroxychloroquine/data/preference_score_dist_tNA_cNA_Clinformatics.rds diff --git a/Covid19EstimationHydroxychloroquine/data/preference_score_dist_tNA_cNA_PanTher.rds b/Covid19EstimationHydroxychloroquine/data/preference_score_dist_tNA_cNA_OptumEHR.rds similarity index 100% rename from Covid19EstimationHydroxychloroquine/data/preference_score_dist_tNA_cNA_PanTher.rds rename to Covid19EstimationHydroxychloroquine/data/preference_score_dist_tNA_cNA_OptumEHR.rds diff --git a/Covid19EstimationHydroxychloroquine/data/propensity_model_All.rds b/Covid19EstimationHydroxychloroquine/data/propensity_model_All.rds index 228ef9f7..ee044fe9 100644 Binary files a/Covid19EstimationHydroxychloroquine/data/propensity_model_All.rds and b/Covid19EstimationHydroxychloroquine/data/propensity_model_All.rds differ diff --git a/Covid19EstimationHydroxychloroquine/dataClean.R b/Covid19EstimationHydroxychloroquine/dataClean.R deleted file mode 100644 index a0e993a7..00000000 --- a/Covid19EstimationHydroxychloroquine/dataClean.R +++ /dev/null @@ -1,86 +0,0 @@ -outcomeOfInterest$definition <- NULL -outcomeOfInterest <- outcomeOfInterest[!duplicated(outcomeOfInterest), ] - -exposureOfInterest$definition <- NULL -exposureOfInterest <- exposureOfInterest[!duplicated(exposureOfInterest), ] - -cohortMethodAnalysis$definition <- NULL -cohortMethodAnalysis <- cohortMethodAnalysis[!duplicated(cohortMethodAnalysis), ] - -cohortMethodResult$i2 <- round(cohortMethodResult$i2, 2) - -drops <- - (cohortMethodResult$databaseId == "PanTher" & cohortMethodResult$analysisId == 1) | # panther on-treatment - (cohortMethodResult$databaseId %in% c("CCAE", "DAGermany", "JMDC", "MDCD", "MDCR", "PanTher", "OpenClaims", "AmbEMR") & cohortMethodResult$outcomeId %in% c(18, 19)) | # death - (cohortMethodResult$databaseId %in% c("AmbEMR", "CPRD", "DAGermany", "IMRD", "SIDIAP") & cohortMethodResult$outcomeId %in% c(22, 13, 20, 21, 17, 8, 11)) # databases with no IP -cohortMethodResult <- cohortMethodResult[!drops, ] - -database$order <- match(database$databaseId, c(database$databaseId[database$databaseId != "Meta-analysis"], "Meta-analysis")) -database <- database[order(database$order), ] -database$order <- NULL - -blinds <- - (cohortMethodResult$databaseId == "CPRD" & cohortMethodResult$targetId == 137) | - (cohortMethodResult$databaseId == "JMDC" & cohortMethodResult$targetId == 2) | - (cohortMethodResult$databaseId == "DAGermany" & cohortMethodResult$targetId == 137) | - (cohortMethodResult$databaseId == "IMRD" & cohortMethodResult$targetId == 137) | - (cohortMethodResult$databaseId == "SIDIAP" & cohortMethodResult$targetId %in% c(137, 2)) - (cohortMethodResult$databaseId == "ICPI" & cohortMethodResult$targetId %in% c(137, 2)) - -cohortMethodResult$rr[blinds] <- NA -cohortMethodResult$ci95Ub[blinds] <- NA -cohortMethodResult$ci95Lb[blinds] <- NA -cohortMethodResult$logRr[blinds] <- NA -cohortMethodResult$seLogRr[blinds] <- NA -cohortMethodResult$p[blinds] <- NA -cohortMethodResult$calibratedRr[blinds] <- NA -cohortMethodResult$calibratedCi95Ub[blinds] <- NA -cohortMethodResult$calibratedCi95Lb[blinds] <- NA -cohortMethodResult$calibratedLogRr[blinds] <- NA -cohortMethodResult$calibratedSeLogRr[blinds] <- NA -cohortMethodResult$calibratedP[blinds] <- NA - -outcomeOfInterest$outcomeName[outcomeOfInterest$outcomeName == "[LEGEND HTN] Persons with chest pain or angina"] <- "Chest pain or angina" -outcomeOfInterest$outcomeName[outcomeOfInterest$outcomeName == "[LEGEND HTN] Venous thromboembolic (pulmonary embolism and deep vein thrombosis) events"] <- "Venous thromboembolism" -outcomeOfInterest$outcomeName[outcomeOfInterest$outcomeName == "[LEGEND HTN] Acute renal failure events"] <- "Acute renal failure" -outcomeOfInterest$outcomeName[outcomeOfInterest$outcomeName == "[LEGEND HTN] Persons with end stage renal disease"] <- "End stage renal disease" -outcomeOfInterest$outcomeName[outcomeOfInterest$outcomeName == "[LEGEND HTN] Persons with hepatic failure"] <- "Hepatic failure" -outcomeOfInterest$outcomeName[outcomeOfInterest$outcomeName == "[LEGEND HTN] Acute pancreatitis events"] <- "Acute pancreatitis" -outcomeOfInterest$outcomeName[outcomeOfInterest$outcomeName == "[LEGEND HTN] Persons with heart failure"] <- "Heart failure" -outcomeOfInterest$outcomeName[outcomeOfInterest$outcomeName == "[LEGEND HTN] Total cardiovascular disease events"] <- "Cardiovascular events" -outcomeOfInterest$outcomeName[outcomeOfInterest$outcomeName == "[LEGEND HTN] Person with cardiac arrhythmia"] <- "Cardiac arrhythmia" -outcomeOfInterest$outcomeName[outcomeOfInterest$outcomeName == "[LEGEND HTN] Persons with bradycardia"] <- "Bradycardia" -outcomeOfInterest$outcomeName[outcomeOfInterest$outcomeName == "[LEGEND HTN] Gastrointestinal bleeding events"] <- "Gastrointestinal bleeding" -outcomeOfInterest$outcomeName[outcomeOfInterest$outcomeName == "[LEGEND HTN] All-cause mortality"] <- "All-cause mortality" -outcomeOfInterest$outcomeName[outcomeOfInterest$outcomeName == "[LEGEND HTN] Cardiovascular-related mortality"] <- "Cardiovascular-related mortality" -outcomeOfInterest$outcomeName[outcomeOfInterest$outcomeName == "[LEGEND HTN] Transient ischemic attack events"] <- "Transient ischemic attack" -outcomeOfInterest$outcomeName[outcomeOfInterest$outcomeName == "[LEGEND HTN] Stroke (ischemic or hemorrhagic) events"] <- "Stroke" -outcomeOfInterest$outcomeName[outcomeOfInterest$outcomeName == "[LEGEND HTN] Acute myocardial infarction events"] <- "Myocardial infarction" -outcomeOfInterest$order <- match(outcomeOfInterest$outcomeName, c("All-cause mortality", - "Cardiovascular-related mortality", - "Myocardial infarction", - "Chest pain or angina", - "Heart failure", - "Cardiovascular events", - "Cardiac arrhythmia", - "Bradycardia", - "Transient ischemic attack", - "Stroke", - "Venous thromboembolism", - "Gastrointestinal bleeding", - "Acute renal failure", - "End stage renal disease", - "Hepatic failure", - "Acute pancreatitis")) -outcomeOfInterest <- outcomeOfInterest[order(outcomeOfInterest$order), ] -outcomeOfInterest$order <- NULL - -exposureOfInterest$exposureName[exposureOfInterest$exposureName == "[OHDSI-Covid19] Hydroxychloroquine + Azithromycin"] <- "Hydroxychloroquine + Azithromycin with prior RA" -exposureOfInterest$exposureName[exposureOfInterest$exposureName == "[OHDSI Cov19] New users of Hydroxychloroquine with prior rheumatoid arthritis"] <- "Hydroxychloroquine with prior RA" -exposureOfInterest$exposureName[exposureOfInterest$exposureName == "[OHDSI-Covid19] Hydroxychloroquine + Amoxicillin"] <- "Hydroxychloroquine + Amoxicillin with prior RA" -exposureOfInterest$exposureName[exposureOfInterest$exposureName == "[OHDSI Cov19] New users of sulfasazine with prior rheumatoid arthritis"] <- "Sulfasalazine with prior RA" -exposureOfInterest <- exposureOfInterest[order(exposureOfInterest$exposureId), ] - -cohortMethodAnalysis$description[cohortMethodAnalysis$description == "No prior outcome in last 30d, 5 PS strata, TAR on-treatment+14d"] <- "5 PS strata, on-treatment + 14 days follow-up" -cohortMethodAnalysis$description[cohortMethodAnalysis$description == "No prior outcome in last 30d, 5 PS strata, TAR 30d fixed"] <- "5 PS strata, 30 days follow-up" -cohortMethodAnalysis <- cohortMethodAnalysis[order(cohortMethodAnalysis$analysisId, decreasing = TRUE), ] diff --git a/Covid19EstimationHydroxychloroquine/global.R b/Covid19EstimationHydroxychloroquine/global.R index c06df553..4c5bea75 100644 --- a/Covid19EstimationHydroxychloroquine/global.R +++ b/Covid19EstimationHydroxychloroquine/global.R @@ -33,9 +33,7 @@ loadFile <- function(file, removePart) { camelCaseName <- SqlRender::snakeCaseToCamelCase(tableName) if (!(tableName %in% splittableTables)) { newData <- readRDS(file.path(dataFolder, file)) - colnames(newData) <- SqlRender::snakeCaseToCamelCase(colnames(newData)) - if (exists(camelCaseName, envir = .GlobalEnv)) { existingData <- get(camelCaseName, envir = .GlobalEnv) newData <- rbind(existingData, newData) diff --git a/Covid19EstimationHydroxychloroquine/ui.R b/Covid19EstimationHydroxychloroquine/ui.R index 84521eef..a0cac6d8 100644 --- a/Covid19EstimationHydroxychloroquine/ui.R +++ b/Covid19EstimationHydroxychloroquine/ui.R @@ -3,7 +3,7 @@ library(DT) shinyUI( fluidPage(style = "width:1500px;", - titlePanel(paste("Safety of hydroxychloroquine with azythromycin: a multi-national study", if(blind) "***Blinded***" else "")), + titlePanel(paste("Safety of hydroxychloroquine alone and in combination with azithromycin: a multi-national study", if(blind) "***Blinded***" else "")), tags$head(tags$style(type = "text/css", " #loadmessage { position: fixed; @@ -29,9 +29,9 @@ shinyUI( HTML("
"), HTML("

Below is the abstract of the manuscript that summarizes the findings:

"), HTML("

Background: Hydroxychloroquine has recently received Emergency Use Authorization by the FDA and is currently prescribed in combination with azithromycin for COVID-19 pneumonia. We studied the safety of hydroxychloroquine, alone and in combination with azithromycin.

"), - HTML("

Methods: New user cohort studies were conducted including 16 severe adverse events (SAEs). Rheumatoid arthritis patients aged 18+ and initiating hydroxychloroquine were compared to those initiating sulfasalazine and followed up over 30 days. Self-controlled case series (SCCS) were conducted to further establish safety in wider populations. Separately, SAEs associated with hydroxychloroquine-azithromycin (compared to hydroxychloroquine-amoxicillin) were studied. Data comprised 14 sources of claims data or electronic medical records from Germany, Japan, Netherlands, Spain, UK, and USA. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate calibrated hazard ratios (CalHRs) according to drug use. Estimates were pooled where I2<40%.

"), - HTML("

Results: Overall, 956,374 and 310,350 users of hydroxychloroquine and sulfasalazine, and 323,122 and 351,956 users of hydroxychloroquine-azithromycin and hydroxychloroquine-amoxicillin were included. No excess risk of SAEs was identified when 30-day hydroxychloroquine and sulfasalazine use were compared. SCCS confirmed these findings. However, when azithromycin was added to hydroxychloroquine, we observed an increased risk of 30-day cardiovascular mortality (CalHR 2.19 [95% CI 1.22-3.94]), chest pain/angina (CalHR 1.15 [95% CI 1.05-1.26]), and heart failure (CalHR 1.22 [95% CI 1.02-1.45]).

"), - HTML("

Conclusions: Short-term hydroxychloroquine treatment is safe, but addition of azithromycin may induce heart failure and cardiovascular mortality, potentially due to synergistic effects on QT length. We call for caution if such combination is to be used in the management of Covid-19.

"), + HTML("

Methods: New user cohort studies were conducted including 16 severe adverse events (SAEs). Rheumatoid arthritis patients aged 18+ and initiating hydroxychloroquine were compared to those initiating sulfasalazine and followed up over 30 days. Self-controlled case series (SCCS) were conducted to further establish safety in wider populations. Separately, SAEs associated with hydroxychloroquine-azithromycin (compared to hydroxychloroquine-amoxicillin) were studied. Data comprised 14 sources of claims data or electronic medical records from Germany, Japan, Netherlands, Spain, UK, and USA. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate calibrated hazard ratios (CalHRs) according to drug use. Estimates were pooled where I2<40%.

"), + HTML("

Findings: Overall, 956,374 and 310,350 users of hydroxychloroquine and sulfasalazine, and 323,122 and 351,956 users of hydroxychloroquine-azithromycin and hydroxychloroquine-amoxicillin were included. No excess risk of SAEs was identified when 30-day hydroxychloroquine and sulfasalazine use were compared. SCCS confirmed these findings. However, when azithromycin was added to hydroxychloroquine, we observed an increased risk of 30-day cardiovascular mortality (CalHR 2.19 [95% CI 1.22-3.94]), chest pain/angina (CalHR 1.15 [1.05-1.26]), and heart failure (CalHR 1.22 [1.02-1.45]). Cardiovascular mortality was also increased in long term on-treatment analysis of hydroxychloroquine versus sulfasalazine (CalHR 1.65 [1.12-2.44]).

"), + HTML("

Interpretation: Hydroxychloroquine treatment appears safe during the 30 days post-initiation in rheumatoid arthritis, but combination use of hydroxychloroquine and azithromycin may induce heart failure and cardiovascular mortality. Extended use of hydroxychloroquine may increase mortality risk in RA. Given that hydroxychloroquine, alone and in combination with azithromycin, is being actively considered for treatment in COVID-19, we call for caution and careful consideration about the benefit-risk trade-off of the uncertain efficacy and this identified risk when managing patients with COVID-19.

"), HTML("
"), HTML("

Below are links for study-related artifacts that have been made available as part of this study:

"), HTML("