%HAART after OI report
\documentclass[11pt]{article}
\usepackage[margin=1.0in]{geometry}
\usepackage[pdftex]{lscape}   % allows tables to be landscape when
\usepackage{threeparttable}
\title{Time to HAART initiation after OI report}
\author{Yanink Caro \& Bryan Shepherd}
%\date{}
%\SweaveOpts{prefix.string=graphics/plot} % Created a "graphics" subdirectory to save graph files in
\begin{document}
\SweaveOpts{concordance=TRUE}
\maketitle

% Hidden R code chunk --- reading in the data
<<echo = false, results = hide>>=
rm(list=ls())
setwd("~/CCASAnet/Brenda_ CCASAnet/OI HAART/R files")
source("table_functions_ycv.R")
load("basic8CD4crypto.rda")
library(quantreg)
library("rms")
@



<<echo = false, results = hide>>=
getmedian <- function(var,digits=1){
  m1 <- round(median(var,na.rm=TRUE),digits)
    paste0(m1)
}
getquantiles <- function(var,digits=1){
  q1 <- round(quantile(var,na.rm=TRUE,prob = 0.25),digits)
  q3 <- round(quantile(var,na.rm=TRUE,prob = 0.75),digits)
  paste0("(",q1,"--",q3,")")
}
cub.cd4<-(basic8CD4crypto$cd4Enrol)^(1/3)
cd4enrol.imp<-lm(cub.cd4~site+age+male+year+route,data=basic8CD4crypto)
summary(cd4enrol.imp)
aux<-predict(cd4enrol.imp, basic8CD4crypto[is.na(basic8CD4crypto$cd4Enrol),c('site','age','male','year','route')])

basic8CD4crypto$CD4EnrolIMP<-with(basic8CD4crypto, ifelse(!is.na(cd4Enrol),cd4Enrol,aux^3))

basic8CD4crypto$included<-basic8CD4crypto$drop_y<-basic8CD4crypto$EXCL<-basic8CD4crypto$include_ce<-basic8CD4crypto$exclude_b<-NULL
@



% R code chunk that generates LaTeX code to create table
<<echo = false, results = hide>>=
library(xtable)
getmedianIQR <- function(var,digits=1){
  m1 <- round(median(var,na.rm=TRUE),digits)
  q1 <- round(quantile(var,na.rm=TRUE,prob = 0.25),digits)
  q3 <- round(quantile(var,na.rm=TRUE,prob = 0.75),digits)
  paste0(m1," (",q1,"--",q3,")")
}
getmedianIQR(basic8CD4crypto$age)
tapply(basic8CD4crypto$age,basic8CD4crypto$site,getmedianIQR)
line1 <- getmedtex(var=basic8CD4crypto$age,by=as.character(basic8CD4crypto$site),label="Patient age (years)",digits=0,inc.pval=FALSE)
line2 <- getnp1line(var=ifelse(basic8CD4crypto$male==1,1,NA),by=as.character(basic8CD4crypto$site),rowlabel="Male",inc.pval=FALSE,indent=FALSE)
getmedianIQR(basic8CD4crypto$cd4Enrol)
tapply(basic8CD4crypto$cd4Enrol,basic8CD4crypto$site,getmedianIQR)
line3 <- getmedtex(var=basic8CD4crypto$cd4Enrol,by=as.character(basic8CD4crypto$site),label="CD4 at enrol",digits=0,inc.pval=FALSE, lower.label=FALSE)
line4 <- getnp1line(var=ifelse(basic8CD4crypto$TB==1,1,NA),by=as.character(basic8CD4crypto$site),rowlabel="TB",inc.pval=FALSE,indent=FALSE)
line5 <- getnp1line(var=ifelse(basic8CD4crypto$Crypto==1,1,NA),by=as.character(basic8CD4crypto$site),rowlabel="Cryptococcocis",inc.pval=FALSE,indent=FALSE)
line6 <- getnptex(var=basic8CD4crypto$route,by=as.character(basic8CD4crypto$site),label="Probable Infection Route",inc.pval=FALSE)
line7 <- getnptex(var=basic8CD4crypto$regimen_class_new,by=as.character(basic8CD4crypto$site),label="HAART regimen",inc.pval=FALSE)
tapply(basic8CD4crypto$timeOI,basic8CD4crypto$site,getmedianIQR)
line8 <- getmedtex(var=basic8CD4crypto$timeOI/7,by=as.character(basic8CD4crypto$site),label="time since OI to HAART (weeks)",digits=1,inc.pval=FALSE,lower.label=FALSE)
line9<-getnp1line(var=ifelse(basic8CD4crypto$before4==1,1,NA),by=as.character(basic8CD4crypto$site),rowlabel="Patients in the Early group",inc.pval=FALSE,indent=FALSE)
crosstab2 <- table(as.character(basic8CD4crypto$site))
names(crosstab2) <- c("Argentina","Brazil","Chile","Honduras","Mexico")
site.n2 <- printheader(crosstab2)
table1  <- paste(line1,line2,line3$line.incmiss,line4,line5,line6,line7,line8,line9, sep=" \\\\\\\\ ")
@


\begin{landscape}
%%%%%%%%%%%%%%%%%%%%
  %     TABLE 1      %
  %%%%%%%%%%%%%%%%%%%%
  \begin{center}
\setlength{\tabcolsep}{4pt}
\begin{threeparttable}
\footnotesize
\centering{
  \caption{Summary of Patient Demographics by Site}
  \label{tab:base}
  \begin{tabular}{lllllll}
  \hline
  \Sexpr{site.n2}\\ 
  \hline \\
  \Sexpr{table1}\\ \tabularnewline  \hline
  \end{tabular}
}
\begin{tablenotes}
\item[a] Continuous variables are reported as medians (interquartile range).
\item[b] Other regimen of HAART include regimens with Maraviroc or with 3 nucleotides. 
\end{tablenotes}
\end{threeparttable}
\end{center}
\bigskip
\bigskip


\end{landscape}


\begin{landscape}

%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
  %% Figure 1        %%%%%%%%%%
  %%%%%%%%%%%%%%%%%%%%%%%%%%%%%

\begin{figure}
\caption{Probability of Starting ART during the first year in OI non TB or cryptococcocis, only TB, and only cryptococcocis}
\begin{center}
<<echo=FALSE, fig=TRUE>>=
par(mfrow = c(2, 2), mai=c(1.2,1.2,0.3,0.3))  # 2 rows and 2 columns
with(basic8CD4crypto, plot(survfit(Surv(timeOI,auxart)~pre2009),mark.time=FALSE,
                                           fun="event", xlim=c(0,365) , xlab="Months from all OI",
                                           ylab="Probability of Starting ART",axes=FALSE, col=c(1,2)))
axis(2,cex.axis=0.9)
axis(1, at=365*c(0,1/4,2/4,3/4,1), labels=c(0,3,6,9,12),cex.axis=0.9)
legend("bottomright",legend=c("2009 and after","before 2009"),col=c(1,2),lty=c(1,1),inset=0.05,cex=0.8)
legend("center",legend="p<0.01", bty = "n",inset=0.05)



with(basic8CD4crypto[basic8CD4crypto$TB==0 & basic8CD4crypto$Crypto==0,], plot(survfit(Surv(timeOI,auxart)~pre2009),mark.time=FALSE,
                                           fun="event", xlim=c(0,365) , xlab="Months from OI (non TB or CM) ",
                                           ylab="Probability of Starting ART",axes=FALSE, col=c(1,2)))
axis(2,cex.axis=0.9)
axis(1, at=365*c(0,1/4,2/4,3/4,1), labels=c(0,3,6,9,12),cex.axis=0.9)
legend("bottomright",legend=c("2009 and after","before 2009"),col=c(1,2),lty=c(1,1),inset=0.05,cex=0.8)
legend("center",legend="p<0.01", bty = "n",inset=0.05)


with(basic8CD4crypto[basic8CD4crypto$TB==1 & basic8CD4crypto$Crypto==0,], plot(survfit(Surv(timeOI,auxart)~pre2009),mark.time=FALSE,
                                           fun="event", xlim=c(0,365), xlab="Months from TB",
                                           ylab="Probability of Starting ART",axes=FALSE, col=c(1,2)))
axis(2,cex.axis=0.9)
axis(1, at=365*c(0,1/4,2/4,3/4,1), labels=c(0,3,6,9,12),cex.axis=0.9)
legend("bottomright",legend=c("2009 and after","before 2009"),col=c(1,2),lty=c(1,1),inset=0.05,cex=0.8)
legend("center",legend="p<0.01",bty = "n", inset=0.05)

with(basic8CD4crypto[basic8CD4crypto$Crypto==1 & basic8CD4crypto$TB==0,], plot(survfit(Surv(timeOI,auxart)~pre2009),mark.time=FALSE,
                                           fun="event", xlim=c(0,365), xlab="Months from CM",
                                           ylab="Probability of Starting ART",axes=FALSE, col=c(1,2)))
axis(2,cex.axis=0.9)
axis(1, at=365*c(0,1/4,2/4,3/4,1), labels=c(0,3,6,9,12),cex.axis=0.9)
legend("bottomright",legend=c("2009 and after","before 2009"),col=c(1,2),lty=c(1,1),inset=0.05,cex=0.8)
legend("center",legend="p=0.96",bty = "n", inset=0.05)

@
\end{center}
\end{figure}

\end{landscape}


<<echo = false, results = hide>>=
dd<-datadist(basic8CD4crypto)
options(datadist="dd")
ourknots.year <- quantile(basic8CD4crypto$year, probs=c(0.25,0.5,0.75),na.rm=TRUE) 
Modelbefore<-lrm(before4 ~ male + I(age/10) + cd4Enrol+  TB + as.factor(route) + rcs(year,ourknots.year) + as.factor(site)+ Crypto, data=basic8CD4crypto,  x=TRUE, y=TRUE)

MB<-summary(Modelbefore,  age=c(20,30),cd4Enrol=c(25,50),year=c(2002,2004), site="brazil",route="Heterosexual")
MB1<-summary(Modelbefore,  age=c(20,40))
MB2<-summary(Modelbefore,  age=c(20,50))
MB3<-summary(Modelbefore,  cd4Enrol=c(25,100))
MB4<-summary(Modelbefore,  cd4Enrol=c(25,150))
MB5<-summary(Modelbefore,  cd4Enrol=c(25,200))
MB6<-summary(Modelbefore,  year=c(2002,2006))
MB7<-summary(Modelbefore,  year=c(2002,2008))
MB8<-summary(Modelbefore,  year=c(2002,2010))
MB9<-summary(Modelbefore,  year=c(2002,2012))

av<-anova(Modelbefore)

all.OR<-round(c(MB[2,4],MB[4,4],MB1[4,4],MB2[4,4],MB[6,4],MB3[6,4],MB4[6,4],MB5[6,4],MB[8,4],MB[12,4],MB[14,4],MB[16,4],
                MB[18,4],MB[10,4],MB6[10,4],MB7[10,4],MB8[10,4],MB9[10,4],MB[20,4],MB[22,4],MB[24,4],MB[26,4] ),2)

all.low<-round(c(MB[2,6],MB[4,6],MB1[4,6],MB2[4,6],MB[6,6],MB3[6,6],MB4[6,6],MB5[6,6],MB[8,6],MB[12,6],MB[14,6],MB[16,6]  ,MB[18,6],MB[10,6],MB6[10,6],MB7[10,6],
          MB8[10,6],MB9[10,6],MB[20,6],MB[22,6],MB[24,6],MB[26,6] ),2)

all.up<-round(c(MB[2,7],MB[4,7],MB1[4,7],MB2[4,7],MB[6,7],MB3[6,7],MB4[6,7],MB5[6,7],MB[8,7],MB[12,7],MB[14,7],MB[16,7],
                MB[18,7],MB[10,7],MB6[10,7],MB7[10,7],
          MB8[10,7],MB9[10,7],MB[20,7],MB[22,7],MB[24,7],MB[26,7] ),2)

p.values<-round(c(av[1,3],av[2,3],av[3,3],av[4,3],av[9,3],av[5,3],av[6,3],av[8,3]),3)
 
@


%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
  %% Figure 2        %%%%%%%%%%
  %%%%%%%%%%%%%%%%%%%%%%%%%%%%%


<<echo=FALSE, fig=FALSE>>=
jpeg("prob-early-haart.jpg",width=1200, height=1500, res=150)
fitted<-Predict(Modelbefore, year, fun=function(x) {exp(x)/(1+exp(x))})
with(fitted, plot(year,yhat,type="l", xlab="Year of opportunistic infection", ylim=c(0,1),xlim=c(2002,2012),ylab="Estimated Probability of starting HAART within 4 weeks of OI",cex.lab=1.3,axes=F,xaxs="i", yaxs="i",xaxs="i", yaxs="i"))
axis(2, cex.axis=1.5)
axis(1, cex.axis=1.5)
with(fitted,polygon(c(year,rev(year)),c(lower,rev(upper)),
col = "grey", border = FALSE))
with(fitted,lines(year,yhat,type="s",lty=1,col="blue"))
box()
@





\begin{figure}
\begin{center}
\caption{Probability of Early HAART initiation}
\includegraphics[width=5 in, height=4 in, angle=0]{prob-early-haart.jpg}
\end{center}
\end{figure}



\begin{landscape}
%%%%%%%%%%%%%%%%%%%%
  %     TABLE 2      %
  %%%%%%%%%%%%%%%%%%%%
  \begin{center}
\setlength{\tabcolsep}{15pt}
\begin{threeparttable}
\footnotesize
\centering{
  \caption{Factors associated with early HAART initiation after an OI}
  \begin{tabular}{lcccc}
  \hline
  & OR & 95 \% confidence & interval & p-value\\ 
  \hline
  Male & \Sexpr{all.OR[1]} & \Sexpr{all.low[1]} & \Sexpr{all.up[1]} & \Sexpr{p.values[1]}\\
  \\
  Age (years) &  &  &  & \Sexpr{p.values[2]}\\
  20 & 1&  &  & \\
  30 & \Sexpr{all.OR[2]} & \Sexpr{all.low[2]} & \Sexpr{all.up[2]} & \\
  40 & \Sexpr{all.OR[3]} & \Sexpr{all.low[3]} & \Sexpr{all.up[3]} & \\
  50 & \Sexpr{all.OR[4]} & \Sexpr{all.low[4]} & \Sexpr{all.up[4]} & \\
  \\
  CD4 at Enrol   & &  &  & \Sexpr{p.values[3]}\\
  25 & 1 &  &  & \\
  50 & \Sexpr{all.OR[5]} & \Sexpr{all.low[5]} & \Sexpr{all.up[5]} &  \\
  100 & \Sexpr{all.OR[6]} & \Sexpr{all.low[6]} & \Sexpr{all.up[6]} &  \\
  150 & \Sexpr{all.OR[7]} & \Sexpr{all.low[7]} & \Sexpr{all.up[7]} &  \\
  200 & \Sexpr{all.OR[8]} & \Sexpr{all.low[8]} & \Sexpr{all.up[8]} &  \\
  \\
  TB  & \Sexpr{all.OR[9]} & \Sexpr{all.low[9]} & \Sexpr{all.up[9]} & \Sexpr{p.values[4]}\\
  \\
  Crypto  & \Sexpr{all.OR[10]} & \Sexpr{all.low[10]} & \Sexpr{all.up[10]} & \Sexpr{p.values[5]}\\
 \\
  Route of transmission & & & &\Sexpr{p.values[6]} \\
  Heterosexual & 1 & & & \\
  MSM & \Sexpr{all.OR[11]} & \Sexpr{all.low[11]} & \Sexpr{all.up[11]} & \\
  Other &\Sexpr{all.OR[12]} & \Sexpr{all.low[12]} & \Sexpr{all.up[12]} &  \\
  Unknown &  \Sexpr{all.OR[13]} & \Sexpr{all.low[13]} & \Sexpr{all.up[13]} &\\
  \\
  Year of OI & & & & \Sexpr{p.values[7]}\\
  2002 & 1 & & & \\
  2004 & \Sexpr{all.OR[14]} &\Sexpr{all.low[14]} & \Sexpr{all.up[14]}& \\
  2006 & \Sexpr{all.OR[15]} & \Sexpr{all.low[15]} & \Sexpr{all.up[15]}& \\
  2008 & \Sexpr{all.OR[16]} & \Sexpr{all.low[16]} & \Sexpr{all.up[16]}& \\
  2010 & \Sexpr{all.OR[17]} & \Sexpr{all.low[17]} & \Sexpr{all.up[17]}& \\
  2012 & \Sexpr{all.OR[18]} & \Sexpr{all.low[18]} & \Sexpr{all.up[18]} &\\
  \\
 Site & & & & \Sexpr{p.values[8]}\\
 Brazil & 1 & & & \\
 Argentina & \Sexpr{all.OR[19]} & \Sexpr{all.low[19]} & \Sexpr{all.up[19]} &\\ 
 Chile &   \Sexpr{all.OR[20]} & \Sexpr{all.low[20]} & \Sexpr{all.up[20]} &\\
 Honduras & \Sexpr{all.OR[21]} & \Sexpr{all.low[21]} & \Sexpr{all.up[21]} &\\
 Mexico &  \Sexpr{all.OR[22]} & \Sexpr{all.low[22]} & \Sexpr{all.up[22]} &\\

  \tabularnewline
   \hline
    \end{tabular}
}
\end{threeparttable}
\end{center}
\bigskip
\bigskip

\end{landscape}



%%%Imputation of CD4 at enrol
<<echo = false, results = hide>>=
dd<-datadist(basic8CD4crypto)
options(datadist="dd")
ourknots.year <- quantile(basic8CD4crypto$year, probs=c(0.25,0.5,0.75),na.rm=TRUE) 
ModelbeforeIMP<-lrm(before4 ~ male + I(age/10) + CD4EnrolIMP+  TB + as.factor(route) + rcs(year,ourknots.year) + as.factor(site)+ Crypto, data=basic8CD4crypto,  x=TRUE, y=TRUE)

MB<-summary(ModelbeforeIMP,  age=c(20,30),CD4EnrolIMP=c(25,50),year=c(2002,2004), site="brazil",route="Heterosexual")
MB1<-summary(ModelbeforeIMP,  age=c(20,40))
MB2<-summary(ModelbeforeIMP,  age=c(20,50))
MB3<-summary(ModelbeforeIMP,  CD4EnrolIMP=c(25,100))
MB4<-summary(ModelbeforeIMP,  CD4EnrolIMP=c(25,150))
MB5<-summary(ModelbeforeIMP,  CD4EnrolIMP=c(25,200))
MB6<-summary(ModelbeforeIMP,  year=c(2002,2006))
MB7<-summary(ModelbeforeIMP,  year=c(2002,2008))
MB8<-summary(ModelbeforeIMP,  year=c(2002,2010))
MB9<-summary(ModelbeforeIMP,  year=c(2002,2012))

avIMP<-anova(ModelbeforeIMP)

allIMP.OR<-round(c(MB[2,4],MB[4,4],MB1[4,4],MB2[4,4],MB[6,4],MB3[6,4],MB4[6,4],MB5[6,4],MB[8,4],MB[12,4],MB[14,4],MB[16,4],
                MB[18,4],MB[10,4],MB6[10,4],MB7[10,4],MB8[10,4],MB9[10,4],MB[20,4],MB[22,4],MB[24,4],MB[26,4] ),2)

allIMP.low<-round(c(MB[2,6],MB[4,6],MB1[4,6],MB2[4,6],MB[6,6],MB3[6,6],MB4[6,6],MB5[6,6],MB[8,6],MB[12,6],MB[14,6],MB[16,6]  ,MB[18,6],MB[10,6],MB6[10,6],MB7[10,6],
          MB8[10,6],MB9[10,6],MB[20,6],MB[22,6],MB[24,6],MB[26,6] ),2)

allIMP.up<-round(c(MB[2,7],MB[4,7],MB1[4,7],MB2[4,7],MB[6,7],MB3[6,7],MB4[6,7],MB5[6,7],MB[8,7],MB[12,7],MB[14,7],MB[16,7],
                MB[18,7],MB[10,7],MB6[10,7],MB7[10,7],
          MB8[10,7],MB9[10,7],MB[20,7],MB[22,7],MB[24,7],MB[26,7] ),2)

p.values<-round(c(avIMP[1,3],avIMP[2,3],avIMP[3,3],avIMP[4,3],avIMP[9,3],avIMP[5,3],avIMP[6,3],avIMP[8,3]),3)

@


%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
  %% Figure 2   CD4 at Enrol IMP     %%%%%%%%%%
  %%%%%%%%%%%%%%%%%%%%%%%%%%%%%

<<echo=FALSE, fig=FALSE>>=
jpeg("prob-early-haart-imp.jpg",width=1200, height=1500, res=150)
fitted<-Predict(ModelbeforeIMP, year, fun=function(x) {exp(x)/(1+exp(x))})
with(fitted, plot(year,yhat,type="l", xlab="Year of opportunistic infection", ylim=c(0,1),xlim=c(2002,2012),ylab="Estimated Probability of starting HAART within 4 weeks of OI (CD4 IMP)",cex.lab=1.3,axes=F,xaxs="i", yaxs="i",xaxs="i", yaxs="i"))
axis(2, cex.axis=1.5)
axis(1, cex.axis=1.5)
with(fitted,polygon(c(year,rev(year)),c(lower,rev(upper)),
col = "grey", border = FALSE))
with(fitted,lines(year,yhat,type="s",lty=1,col="blue"))
box()
@





\begin{figure}
\begin{center}
\caption{Adjusted Probability of Early HAART initiation}
\includegraphics[width=5 in, height=4 in, angle=0]{prob-early-haart-imp.jpg}
\end{center}
\end{figure}



\begin{landscape}
%%%%%%%%%%%%%%%%%%%%
  %     TABLE 2      %
  %%%%%%%%%%%%%%%%%%%%
  \begin{center}
\setlength{\tabcolsep}{15pt}
\begin{threeparttable}
\footnotesize
\centering{
  \caption{Factors associated with early HAART initiation after an OI (CD4 at Enrol imp)}
  \begin{tabular}{lcccc}
  \hline
  & OR & 95 \% confidence & interval & p-value\\ 
  \hline
  Male & \Sexpr{allIMP.OR[1]} & \Sexpr{allIMP.low[1]} & \Sexpr{allIMP.up[1]} & \Sexpr{p.values[1]}\\
  \\
  Age (years) &  &  &  & \Sexpr{p.values[2]}\\
  20 & 1&  &  & \\
  30 & \Sexpr{allIMP.OR[2]} & \Sexpr{allIMP.low[2]} & \Sexpr{allIMP.up[2]} & \\
  40 & \Sexpr{allIMP.OR[3]} & \Sexpr{allIMP.low[3]} & \Sexpr{allIMP.up[3]} & \\
  50 & \Sexpr{allIMP.OR[4]} & \Sexpr{allIMP.low[4]} & \Sexpr{allIMP.up[4]} & \\
  \\
  CD4 at Enrol  & &  &  & \Sexpr{p.values[3]}\\
  25 & 1 &  &  & \\
  50 & \Sexpr{allIMP.OR[5]} & \Sexpr{allIMP.low[5]} & \Sexpr{allIMP.up[5]} &  \\
  100 & \Sexpr{allIMP.OR[6]} & \Sexpr{allIMP.low[6]} & \Sexpr{allIMP.up[6]} &  \\
  150 & \Sexpr{allIMP.OR[7]} & \Sexpr{allIMP.low[7]} & \Sexpr{allIMP.up[7]} &  \\
  200 & \Sexpr{allIMP.OR[8]} & \Sexpr{allIMP.low[8]} & \Sexpr{allIMP.up[8]} &  \\
  \\
  TB  & \Sexpr{allIMP.OR[9]} & \Sexpr{allIMP.low[9]} & \Sexpr{allIMP.up[9]} & \Sexpr{p.values[4]}\\
  \\
  Crypto  & \Sexpr{allIMP.OR[10]} & \Sexpr{allIMP.low[10]} & \Sexpr{allIMP.up[10]} & \Sexpr{p.values[5]}\\
 \\
  Route of transmission & & & &\Sexpr{p.values[6]} \\
  Heterosexual & 1 & & & \\
  MSM & \Sexpr{allIMP.OR[11]} & \Sexpr{allIMP.low[11]} & \Sexpr{allIMP.up[11]} & \\
  Other &\Sexpr{allIMP.OR[12]} & \Sexpr{allIMP.low[12]} & \Sexpr{allIMP.up[12]} &  \\
  Unknown &  \Sexpr{allIMP.OR[13]} & \Sexpr{allIMP.low[13]} & \Sexpr{allIMP.up[13]} &\\
  \\
  Year of OI & & & & \Sexpr{p.values[7]}\\
  2002 & 1 & & & \\
  2004 & \Sexpr{allIMP.OR[14]} &\Sexpr{allIMP.low[14]} & \Sexpr{allIMP.up[14]}& \\
  2006 & \Sexpr{allIMP.OR[15]} & \Sexpr{allIMP.low[15]} & \Sexpr{allIMP.up[15]}& \\
  2008 & \Sexpr{allIMP.OR[16]} & \Sexpr{allIMP.low[16]} & \Sexpr{allIMP.up[16]}& \\
  2010 & \Sexpr{allIMP.OR[17]} & \Sexpr{allIMP.low[17]} & \Sexpr{allIMP.up[17]}& \\
  2012 & \Sexpr{allIMP.OR[18]} & \Sexpr{allIMP.low[18]} & \Sexpr{allIMP.up[18]} &\\
  \\
 Site & & & & \Sexpr{p.values[8]}\\
 Brazil & 1 & & & \\
 Argentina & \Sexpr{allIMP.OR[19]} & \Sexpr{allIMP.low[19]} & \Sexpr{allIMP.up[19]} &\\ 
 Chile &   \Sexpr{allIMP.OR[20]} & \Sexpr{allIMP.low[20]} & \Sexpr{allIMP.up[20]} &\\
 Honduras & \Sexpr{allIMP.OR[21]} & \Sexpr{allIMP.low[21]} & \Sexpr{allIMP.up[21]} &\\
 Mexico &  \Sexpr{allIMP.OR[22]} & \Sexpr{allIMP.low[22]} & \Sexpr{allIMP.up[22]} &\\

  \tabularnewline
   \hline
    \end{tabular}
}
\end{threeparttable}
\end{center}
\bigskip
\bigskip

\end{landscape}



<<echo = false, results = hide>>=
medians<-c(
median(basic8CD4crypto$timeOI[basic8CD4crypto$year==2000]),
median(basic8CD4crypto$timeOI[basic8CD4crypto$year==2001]),
median(basic8CD4crypto$timeOI[basic8CD4crypto$year==2002]),
median(basic8CD4crypto$timeOI[basic8CD4crypto$year==2003]),
median(basic8CD4crypto$timeOI[basic8CD4crypto$year==2004]),
median(basic8CD4crypto$timeOI[basic8CD4crypto$year==2005]),
median(basic8CD4crypto$timeOI[basic8CD4crypto$year==2006]),
median(basic8CD4crypto$timeOI[basic8CD4crypto$year==2007]),
median(basic8CD4crypto$timeOI[basic8CD4crypto$year==2008]),
median(basic8CD4crypto$timeOI[basic8CD4crypto$year==2009]),
median(basic8CD4crypto$timeOI[basic8CD4crypto$year==2010]),
median(basic8CD4crypto$timeOI[basic8CD4crypto$year==2011]),
median(basic8CD4crypto$timeOI[basic8CD4crypto$year==2012]),
median(basic8CD4crypto$timeOI[basic8CD4crypto$year==2013]),
median(basic8CD4crypto$timeOI[basic8CD4crypto$year==2014]))

                     
regyear<-with(basic8CD4crypto, rq(timeOI/7~rcs(year,ourknots.year), tau=.5))

basic8CD4crypto$mediantime<-with(basic8CD4crypto, ifelse(year==2000,medians[1], ifelse(year==2001, medians[2], ifelse(year==2002, medians[3], ifelse(year==2003,medians[4], ifelse(year==2004, medians[5], ifelse(year==2005, medians[6], 
              ifelse(year==2006,medians[7], ifelse(year==2007, medians[8], ifelse(year==2008, medians[9],                                                                                                                                                                                         
                 ifelse(year==2009,medians[10], ifelse(year==2010, medians[11], ifelse(year==2011, medians[12],                                                                 
                        ifelse(year==2012, medians[13], ifelse(year==2013, medians[14], medians[15])))))))))) ) ) )) )
@


<<echo=FALSE, fig=FALSE>>=
jpeg("median-time-by-year.jpg",width=1200, height=1500, res=150)
plot(basic8CD4crypto$year,basic8CD4crypto$mediantime/7, pch=19,xlab="Year of opportunistic infection", ylab="Median time to HAART (weeks)",ylim=c(1,10),
     xlim=c(2002,2012),
     cex.lab=1.3,axes=F,xaxs="i",yaxs="i")
axis(2, cex.axis=1.5)
axis(1, cex.axis=1.5)
lines(spline(basic8CD4crypto$year,(predict(regyear))), lwd=3, col=2)
@



\begin{figure}
\begin{center}
\caption{Median regression for time since OI by year of OI}
\includegraphics[width=5 in, height=4 in, angle=0]{median-time-by-year.jpg}
\end{center}
\end{figure}


<<echo = false, results = hide>>=
options(datadist="dd")
ourknots.year <- quantile(basic8CD4crypto$year, probs=c(0.25,0.5,0.75),na.rm=TRUE) 
regmedtimeOIR<-with(basic8CD4crypto, Rq(timeOI/7 ~ as.factor(route) + male + rcs(year,ourknots.year) + TB + I(age/10) + cd4Enrol + site +Crypto ,tau=0.5), se="boot" ,model=TRUE)    

summary(regmedtimeOIR,  year=c(2004,2007))
summary(regmedtimeOIR,  year=c(2004,2009))
summary(regmedtimeOIR,  year=c(2004,2010))
anova(regmedtimeOIR)

@

<<echo=FALSE, fig=FALSE>>=
jpeg("adjusted-median-time-by-year.jpg",width=1200, height=1500, res=150)
fitted<-Predict(regmedtimeOIR, year)
with(fitted, plot(year,yhat,type="l", xlab="Year of opportunistic infection", ylim=c(1,7),xlim=c(2002,2012),ylab="Adjusted Median time to HAART (weeks)",cex.lab=1.3,axes=F,xaxs="i", yaxs="i",xaxs="i", yaxs="i"))
axis(2, cex.axis=1.5)
axis(1, cex.axis=1.5)
with(fitted,polygon(c(year,rev(year)),c(lower,rev(upper)),
col = "grey", border = FALSE))
with(fitted,lines(year,yhat,type="s",lty=1,col="blue"))
box()
@

\begin{figure}
\begin{center}
\caption{Adjusted Median Regression for time since OI by year of OI}
\includegraphics[width=5 in, height=4 in, angle=0]{adjusted-median-time-by-year.jpg}
\end{center}
\end{figure}

%%%%%%%%%%%%%CD4 at enrol imputated
<<echo = false, results = hide>>=
basic8CD4crypto$Site<-factor(basic8CD4crypto$site, levels=c('argentina','brazil','chile','honduras','mexico'))
basic8CD4crypto$site<-NULL
options(datadist="dd")
ourknots.year <- quantile(basic8CD4crypto$year, probs=c(0.25,0.5,0.75),na.rm=TRUE) 
regmedtimeOIRimp<-with(basic8CD4crypto, Rq(timeOI/7 ~ as.factor(route) + male + rcs(year,ourknots.year) + TB + I(age/10) + CD4EnrolIMP + Site +Crypto ,tau=0.5), se="boot" ,model=TRUE)    

summary(regmedtimeOIRimp,  year=c(2004,2007), Site="brazil")
summary(regmedtimeOIRimp,  year=c(2004,2009), Site="brazil")
summary(regmedtimeOIRimp,  year=c(2004,2010), Site="brazil")
anova(regmedtimeOIRimp)

@

<<echo=FALSE, fig=FALSE>>=
jpeg("adjusted-median-time-by-year-imp.jpg",width=1200, height=1500, res=150)
fitted<-Predict(regmedtimeOIRimp, year,Site="brazil")
with(fitted, plot(year,yhat,type="l", xlab="Year of opportunistic infection", ylim=c(1,7),xlim=c(2002,2012),ylab="Adjusted Median time to HAART (weeks).",cex.lab=1.3,axes=F,xaxs="i", yaxs="i",xaxs="i", yaxs="i"))
axis(2, cex.axis=1.5)
axis(1, cex.axis=1.5)
with(fitted,polygon(c(year,rev(year)),c(lower,rev(upper)),
col = "grey", border = FALSE))
with(fitted,lines(year,yhat,type="s",lty=1,col="blue"))
box()
@

\begin{figure}
\begin{center}
\caption{Adjusted Median Regression for time since OI by year of OI (IMP)}
\includegraphics[width=5 in, height=4 in, angle=0]{adjusted-median-time-by-year-imp.jpg}
\end{center}
\end{figure}

\end{document}

\begin{figure}
\caption{}
\begin{center}
<<echo=FALSE, fig=TRUE>>=
jpeg("all_graphs-imp.jpg",width=1500, height=1200, res=150)
par(mfrow = c(1, 3), mai=c(0.7,0.8,0.3,0.4)) 
plot(basic8CD4crypto$year,basic8CD4crypto$mediantime/7, pch=19,xlab="Year of opportunistic infection", ylab="Median time to HAART (weeks)",ylim=c(1,10),
     xlim=c(2002,2012),
     cex.lab=1.3,axes=F,xaxs="i",yaxs="i")
axis(2, cex.axis=1.5)
axis(1, cex.axis=1.5)
lines(spline(basic8CD4crypto$year,(predict(regyear))), lwd=3, col=2)
box()

fitted<-Predict(regmedtimeOIRimp, year, Site="brazil")
with(fitted, plot(year,yhat,type="l", xlab="Year of opportunistic infection", ylim=c(1,7),xlim=c(2002,2012),ylab="Adjusted Median time to HAART (weeks)",cex.lab=1.3,axes=F,xaxs="i", yaxs="i",xaxs="i", yaxs="i"))
axis(2, cex.axis=1.5)
axis(1, cex.axis=1.5)
with(fitted,polygon(c(year,rev(year)),c(lower,rev(upper)),
col = "grey", border = FALSE))
with(fitted,lines(year,yhat,type="s",lty=1,col="blue"))
box()

fitted<-Predict(ModelbeforeIMP, year, fun=function(x) {exp(x)/(1+exp(x))})
with(fitted, plot(year,yhat,type="l", xlab="Year of opportunistic infection", ylim=c(0,1),xlim=c(2002,2012),ylab="Estimated Probability of starting HAART within 4 weeks of OI",cex.lab=1.3,axes=F,xaxs="i", yaxs="i",xaxs="i", yaxs="i"))
axis(2, cex.axis=1.5)
axis(1, cex.axis=1.5)
with(fitted,polygon(c(year,rev(year)),c(lower,rev(upper)),
col = "grey", border = FALSE))
with(fitted,lines(year,yhat,type="s",lty=1,col="blue"))
box()
@
\end{center}
\end{figure}

\begin{figure}
\begin{center}
\caption{Adjusted models for time since OI by year of OI}
\includegraphics[width=5 in, height=4 in, angle=0]{all_graphs-imp.jpg}
\end{center}
\end{figure}


\end{document}