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# ==================================================================== #
# TITLE #
# Antimicrobial Resistance (AMR) Analysis #
# #
# AUTHORS #
# Berends MS (m.s.berends@umcg.nl), Luz CF (c.f.luz@umcg.nl) #
# #
# LICENCE #
# This program is free software; you can redistribute it and/or modify #
# it under the terms of the GNU General Public License version 2.0, #
# as published by the Free Software Foundation. #
# #
# This program is distributed in the hope that it will be useful, #
# but WITHOUT ANY WARRANTY; without even the implied warranty of #
# MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the #
# GNU General Public License for more details. #
# ==================================================================== #
#' Determine first (weighted) isolates
#'
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#' Determine first (weighted) isolates of all microorganisms of every patient per episode and (if needed) per specimen type.
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#' @param tbl a \code{data.frame} containing isolates.
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#' @param col_date column name of the result date (or date that is was received on the lab)
#' @param col_patient_id column name of the unique IDs of the patients
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#' @param col_mo column name of the unique IDs of the microorganisms, see \code{\link{mo}}. If this column has another class than \code{"mo"}, values will be coerced using \code{\link{as.mo}}.
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#' @param col_testcode column name of the test codes. Use \code{col_testcode = NA} to \strong{not} exclude certain test codes (like test codes for screening). In that case \code{testcodes_exclude} will be ignored. Supports tidyverse-like quotation.
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#' @param col_specimen column name of the specimen type or group
#' @param col_icu column name of the logicals (\code{TRUE}/\code{FALSE}) whether a ward or department is an Intensive Care Unit (ICU)
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#' @param col_keyantibiotics column name of the key antibiotics to determine first \emph{weighted} isolates, see \code{\link{key_antibiotics}}. Supports tidyverse-like quotation.
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#' @param episode_days episode in days after which a genus/species combination will be determined as 'first isolate' again
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#' @param testcodes_exclude character vector with test codes that should be excluded (case-insensitive)
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#' @param icu_exclude logical whether ICU isolates should be excluded
#' @param filter_specimen specimen group or type that should be excluded
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#' @param output_logical return output as \code{logical} (will else be the values \code{0} or \code{1})
#' @param type type to determine weighed isolates; can be \code{"keyantibiotics"} or \code{"points"}, see Details
#' @param ignore_I logical to determine whether antibiotic interpretations with \code{"I"} will be ignored when \code{type = "keyantibiotics"}, see Details
#' @param points_threshold points until the comparison of key antibiotics will lead to inclusion of an isolate when \code{type = "points"}, see Details
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#' @param info print progress
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#' @param col_bactid (deprecated, use \code{col_mo} instead)
#' @param col_genus (deprecated, use \code{col_mo} instead) column name of the genus of the microorganisms
#' @param col_species (deprecated, use \code{col_mo} instead) column name of the species of the microorganisms
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#' @details \strong{WHY THIS IS SO IMPORTANT} \cr
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#' To conduct an analysis of antimicrobial resistance, you should only include the first isolate of every patient per episode \href{https://www.ncbi.nlm.nih.gov/pubmed/17304462}{[1]}. If you would not do this, you could easily get an overestimate or underestimate of the resistance of an antibiotic. Imagine that a patient was admitted with an MRSA and that it was found in 5 different blood cultures the following week. The resistance percentage of oxacillin of all \emph{S. aureus} isolates would be overestimated, because you included this MRSA more than once. It would be \href{https://en.wikipedia.org/wiki/Selection_bias}{selection bias}.
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#' @section Key antibiotics:
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#' There are two ways to determine whether isolates can be included as first \emph{weighted} isolates which will give generally the same results: \cr
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#'
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#' \strong{1. Using} \code{type = "keyantibiotics"} \strong{and parameter} \code{ignore_I} \cr
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#' Any difference from S to R (or vice versa) will (re)select an isolate as a first weighted isolate. With \code{ignore_I = FALSE}, also differences from I to S|R (or vice versa) will lead to this. This is a reliable method and 30-35 times faster than method 2. \cr
#'
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#' \strong{2. Using} \code{type = "points"} \strong{and parameter} \code{points_threshold} \cr
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#' A difference from I to S|R (or vice versa) means 0.5 points, a difference from S to R (or vice versa) means 1 point. When the sum of points exceeds \code{points_threshold}, an isolate will be (re)selected as a first weighted isolate.
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#' @keywords isolate isolates first
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#' @seealso \code{\link{key_antibiotics}}
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#' @export
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#' @importFrom dplyr arrange_at lag between row_number filter mutate arrange
#' @return A vector to add to table, see Examples.
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#' @source Methodology of this function is based on: \strong{M39 Analysis and Presentation of Cumulative Antimicrobial Susceptibility Test Data, 4th Edition}, 2014, \emph{Clinical and Laboratory Standards Institute (CLSI)}. \url{https://clsi.org/standards/products/microbiology/documents/m39/}.
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#' @examples
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#' # septic_patients is a dataset available in the AMR package. It is true, genuine data.
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#' ?septic_patients
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#'
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#' library(dplyr)
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#' my_patients <- septic_patients %>%
#' mutate(first_isolate = first_isolate(.,
#' col_date = "date",
#' col_patient_id = "patient_id",
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#' col_mo = "mo"))
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#'
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#' # Now let's see if first isolates matter:
#' A <- my_patients %>%
#' group_by(hospital_id) %>%
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#' summarise(count = n_rsi(gent), # gentamicin availability
#' resistance = portion_IR(gent)) # gentamicin resistance
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#'
#' B <- my_patients %>%
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#' filter(first_isolate == TRUE) %>% # the 1st isolate filter
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#' group_by(hospital_id) %>%
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#' summarise(count = n_rsi(gent), # gentamicin availability
#' resistance = portion_IR(gent)) # gentamicin resistance
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#'
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#' # Have a look at A and B.
#' # B is more reliable because every isolate is only counted once.
#' # Gentamicin resitance in hospital D appears to be 5.4% higher than
#' # when you (erroneously) would have used all isolates!
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#'
#' ## OTHER EXAMPLES:
#'
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#' \dontrun{
#'
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#' # set key antibiotics to a new variable
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#' tbl$keyab <- key_antibiotics(tbl)
#'
#' tbl$first_isolate <-
#' first_isolate(tbl)
#'
#' tbl$first_isolate_weighed <-
#' first_isolate(tbl,
#' col_keyantibiotics = 'keyab')
#'
#' tbl$first_blood_isolate <-
#' first_isolate(tbl,
#' filter_specimen = 'Blood')
#'
#' tbl$first_blood_isolate_weighed <-
#' first_isolate(tbl,
#' filter_specimen = 'Blood',
#' col_keyantibiotics = 'keyab')
#'
#' tbl$first_urine_isolate <-
#' first_isolate(tbl,
#' filter_specimen = 'Urine')
#'
#' tbl$first_urine_isolate_weighed <-
#' first_isolate(tbl,
#' filter_specimen = 'Urine',
#' col_keyantibiotics = 'keyab')
#'
#' tbl$first_resp_isolate <-
#' first_isolate(tbl,
#' filter_specimen = 'Respiratory')
#'
#' tbl$first_resp_isolate_weighed <-
#' first_isolate(tbl,
#' filter_specimen = 'Respiratory',
#' col_keyantibiotics = 'keyab')
#' }
first_isolate <- function ( tbl ,
col_date ,
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col_patient_id ,
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col_mo = NA ,
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col_testcode = NA ,
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col_specimen = NA ,
col_icu = NA ,
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col_keyantibiotics = NA ,
episode_days = 365 ,
testcodes_exclude = ' ' ,
icu_exclude = FALSE ,
filter_specimen = NA ,
output_logical = TRUE ,
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type = " keyantibiotics" ,
ignore_I = TRUE ,
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points_threshold = 2 ,
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info = TRUE ,
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col_bactid = NA ,
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col_genus = NA ,
col_species = NA ) {
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if ( ! is.na ( col_bactid ) ) {
col_mo <- col_bactid
warning ( " Use of `col_bactid` is deprecated. Use `col_mo` instead." )
}
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# bactid OR genus+species must be available
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if ( is.na ( col_mo ) & ( is.na ( col_genus ) | is.na ( col_species ) ) ) {
stop ( ' `col_mo` or both `col_genus` and `col_species` must be available.' )
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}
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# check if columns exist
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check_columns_existance <- function ( column , tblname = tbl ) {
if ( NROW ( tblname ) <= 1 | NCOL ( tblname ) <= 1 ) {
stop ( ' Please check tbl for existance.' )
}
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if ( ! is.na ( column ) ) {
if ( ! ( column %in% colnames ( tblname ) ) ) {
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stop ( ' Column `' , column , ' ` not found.' )
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}
}
}
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check_columns_existance ( col_date )
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check_columns_existance ( col_patient_id )
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check_columns_existance ( col_mo )
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check_columns_existance ( col_genus )
check_columns_existance ( col_species )
check_columns_existance ( col_testcode )
check_columns_existance ( col_icu )
check_columns_existance ( col_keyantibiotics )
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if ( ! is.na ( col_mo ) ) {
if ( ! tbl %>% pull ( col_mo ) %>% is.mo ( ) ) {
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tbl [ , col_mo ] <- as.mo ( tbl [ , col_mo ] )
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}
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# join to microorganisms data set
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tbl <- tbl %>% left_join_microorganisms ( by = col_mo )
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col_genus <- " genus"
col_species <- " species"
}
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if ( is.na ( col_testcode ) ) {
testcodes_exclude <- NA
}
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# remove testcodes
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if ( ! is.na ( testcodes_exclude [1 ] ) & testcodes_exclude [1 ] != ' ' & info == TRUE ) {
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cat ( ' [Criteria] Excluded test codes:\n' , toString ( testcodes_exclude ) , ' \n' )
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}
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if ( is.na ( col_icu ) ) {
icu_exclude <- FALSE
} else {
tbl <- tbl %>%
mutate ( col_icu = tbl %>% pull ( col_icu ) %>% as.logical ( ) )
}
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if ( is.na ( col_specimen ) ) {
filter_specimen <- ' '
}
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# filter on specimen group and keyantibiotics when they are filled in
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if ( ! is.na ( filter_specimen ) & filter_specimen != ' ' ) {
check_columns_existance ( col_specimen , tbl )
if ( info == TRUE ) {
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cat ( ' [Criteria] Excluded other than specimen group \'' , filter_specimen , ' \'\n' , sep = ' ' )
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}
} else {
filter_specimen <- ' '
}
if ( col_keyantibiotics %in% c ( NA , ' ' ) ) {
col_keyantibiotics <- ' '
} else {
tbl <- tbl %>% mutate ( key_ab = tbl %>% pull ( col_keyantibiotics ) )
}
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if ( is.na ( testcodes_exclude [1 ] ) ) {
testcodes_exclude <- ' '
}
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# create new dataframe with original row index and right sorting
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tbl <- tbl %>%
mutate ( first_isolate_row_index = 1 : nrow ( tbl ) ,
date_lab = tbl %>% pull ( col_date ) ,
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patient_id = tbl %>% pull ( col_patient_id ) ,
species = tbl %>% pull ( col_species ) ,
genus = tbl %>% pull ( col_genus ) ) %>%
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mutate ( species = if_else ( is.na ( species ) | species == " (no MO)" , " " , species ) ,
genus = if_else ( is.na ( genus ) | genus == " (no MO)" , " " , genus ) )
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if ( filter_specimen == ' ' ) {
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if ( icu_exclude == FALSE ) {
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if ( info == TRUE & ! is.na ( col_icu ) ) {
cat ( ' [Criteria] Included isolates from ICU.\n' )
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}
tbl <- tbl %>%
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arrange_at ( c ( col_patient_id ,
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col_genus ,
col_species ,
col_date ) )
row.start <- 1
row.end <- nrow ( tbl )
} else {
if ( info == TRUE ) {
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cat ( ' [Criteria] Excluded isolates from ICU.\n' )
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}
tbl <- tbl %>%
arrange_at ( c ( col_icu ,
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col_patient_id ,
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col_genus ,
col_species ,
col_date ) )
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suppressWarnings (
row.start <- which ( tbl %>% pull ( col_icu ) == FALSE ) %>% min ( na.rm = TRUE )
)
suppressWarnings (
row.end <- which ( tbl %>% pull ( col_icu ) == FALSE ) %>% max ( na.rm = TRUE )
)
}
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} else {
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# sort on specimen and only analyse these row to save time
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if ( icu_exclude == FALSE ) {
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if ( info == TRUE & ! is.na ( col_icu ) ) {
cat ( ' [Criteria] Included isolates from ICU.\n' )
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}
tbl <- tbl %>%
arrange_at ( c ( col_specimen ,
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col_patient_id ,
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col_genus ,
col_species ,
col_date ) )
suppressWarnings (
row.start <- which ( tbl %>% pull ( col_specimen ) == filter_specimen ) %>% min ( na.rm = TRUE )
)
suppressWarnings (
row.end <- which ( tbl %>% pull ( col_specimen ) == filter_specimen ) %>% max ( na.rm = TRUE )
)
} else {
if ( info == TRUE ) {
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cat ( ' [Criteria] Excluded isolates from ICU.\n' )
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}
tbl <- tbl %>%
arrange_at ( c ( col_icu ,
col_specimen ,
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col_patient_id ,
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col_genus ,
col_species ,
col_date ) )
suppressWarnings (
row.start <- which ( tbl %>% pull ( col_specimen ) == filter_specimen
& tbl %>% pull ( col_icu ) == FALSE ) %>% min ( na.rm = TRUE )
)
suppressWarnings (
row.end <- which ( tbl %>% pull ( col_specimen ) == filter_specimen
& tbl %>% pull ( col_icu ) == FALSE ) %>% max ( na.rm = TRUE )
)
}
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}
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if ( abs ( row.start ) == Inf | abs ( row.end ) == Inf ) {
if ( info == TRUE ) {
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message ( ' No isolates found.' )
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}
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# NAs where genus is unavailable
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tbl <- tbl %>%
mutate ( real_first_isolate = if_else ( genus == ' ' , NA , FALSE ) )
if ( output_logical == FALSE ) {
tbl $ real_first_isolate <- tbl %>% pull ( real_first_isolate ) %>% as.integer ( )
}
return ( tbl %>% pull ( real_first_isolate ) )
}
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# suppress warnings because dplyr want us to use library(dplyr) when using filter(row_number())
suppressWarnings (
scope.size <- tbl %>%
filter (
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row_number ( ) %>% between ( row.start ,
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row.end ) ,
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genus != " " ,
species != " " ) %>%
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nrow ( )
)
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# Analysis of first isolate ----
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all_first <- tbl %>%
mutate ( other_pat_or_mo = if_else ( patient_id == lag ( patient_id )
& genus == lag ( genus )
& species == lag ( species ) ,
FALSE ,
TRUE ) ,
days_diff = 0 ) %>%
mutate ( days_diff = if_else ( other_pat_or_mo == FALSE ,
( date_lab - lag ( date_lab ) ) + lag ( days_diff ) ,
0 ) )
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weighted.notice <- ' '
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if ( col_keyantibiotics != ' ' ) {
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weighted.notice <- ' weighted '
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if ( info == TRUE ) {
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if ( type == ' keyantibiotics' ) {
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cat ( ' [Criteria] Inclusion based on key antibiotics, ' )
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if ( ignore_I == FALSE ) {
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cat ( ' not ' )
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}
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cat ( ' ignoring I.\n' )
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}
if ( type == ' points' ) {
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cat ( paste0 ( ' [Criteria] Inclusion based on key antibiotics, using points threshold of '
, points_threshold , ' .\n' ) )
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}
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}
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type_param <- type
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# suppress warnings because dplyr want us to use library(dplyr) when using filter(row_number())
suppressWarnings (
all_first <- all_first %>%
mutate ( key_ab_lag = lag ( key_ab ) ) %>%
mutate ( key_ab_other = ! key_antibiotics_equal ( x = key_ab ,
y = key_ab_lag ,
type = type_param ,
ignore_I = ignore_I ,
points_threshold = points_threshold ,
info = info ) ) %>%
mutate (
real_first_isolate =
if_else (
between ( row_number ( ) , row.start , row.end )
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& genus != " "
& species != " "
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& ( other_pat_or_mo
| days_diff >= episode_days
| key_ab_other ) ,
TRUE ,
FALSE ) )
)
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} else {
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# suppress warnings because dplyr want us to use library(dplyr) when using filter(row_number())
suppressWarnings (
all_first <- all_first %>%
mutate (
real_first_isolate =
if_else (
between ( row_number ( ) , row.start , row.end )
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& genus != " "
& species != " "
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& ( other_pat_or_mo
| days_diff >= episode_days ) ,
TRUE ,
FALSE ) )
)
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}
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# first one as TRUE
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all_first [row.start , ' real_first_isolate' ] <- TRUE
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# no tests that should be included, or ICU
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if ( ! is.na ( col_testcode ) ) {
all_first [which ( all_first [ , col_testcode ] %in% tolower ( testcodes_exclude ) ) , ' real_first_isolate' ] <- FALSE
}
if ( icu_exclude == TRUE ) {
all_first [which ( all_first [ , col_icu ] == TRUE ) , ' real_first_isolate' ] <- FALSE
}
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# NAs where genus is unavailable
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all_first <- all_first %>%
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mutate ( real_first_isolate = if_else ( genus %in% c ( ' ' , ' (no MO)' , NA ) , NA , real_first_isolate ) )
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all_first <- all_first %>%
arrange ( first_isolate_row_index ) %>%
pull ( real_first_isolate )
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if ( info == TRUE ) {
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message ( paste0 ( ' Found ' ,
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all_first %>% sum ( na.rm = TRUE ) ,
' first ' , weighted.notice , ' isolates (' ,
( all_first %>% sum ( na.rm = TRUE ) / scope.size ) %>% percent ( ) ,
' of isolates in scope [where genus was not empty] and ' ,
( all_first %>% sum ( na.rm = TRUE ) / tbl %>% nrow ( ) ) %>% percent ( ) ,
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' of total)' ) )
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}
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if ( output_logical == FALSE ) {
all_first <- all_first %>% as.integer ( )
}
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all_first
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}