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Analyzing Health Data in R
for SAS Users
Analyzing Health Data in R
for SAS Users
Monika Wahi
Peter Seebach
CRC Press
Taylor & Francis Group
6000 Broken Sound Parkway NW, Suite 300
Boca Raton, FL 33487-2742
© 2018 by Taylor & Francis Group, LLC

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Library of Congress Cataloging‑in‑Publication Data
Names: Wahi, Monika, author. | Seebach, Peter, author

Title: Analyzing health data in R for SAS users / Monika Wahi and Peter
Seebach
Description: Boca Raton : CRC Press, 2017. | Includes bibliographical
References, Identifiers: LCCN 2017021131 | ISBN 9781498795883 Subjects: LCSH:
Bioinformatics. | Medical informatics. | R (Computer program language) | SAS
(Computer file) Classification: LCC QH324.2 .W34 2017 | DDC 610.285--dc23
LC record available at https://lccn.loc.gov/2017021131
Visit the Taylor & Francis Web site at

http://www.taylorandfrancis.com
and the CRC Press Web site at

http://www.crcpress.com
Contents
Preface ......................................................................................................................ix
Acknowledgments .................................................................................................xi
Authors ................................................................................................................. xiii
1. Differences between SAS and R .................................................................1

Structure of Program.......................................................................................1
Installation of PC Version: SAS versus R .................................................2
Licensing Differences: SAS versus R ........................................................ 3
SAS Components versus R Packages .......................................................3
What is RStudio? .........................................................................................4
Maintaining Current Versions in SAS versus R .....................................4
SAS versus R User Communities .............................................................. 6
SAS versus R User Interfaces ..................................................................... 7
Code Documentation and Metadata: SAS versus R ............................... 9
Handling of Data ........................................................................................... 12
A Focus on SAS Data Handling .............................................................. 12
Comparison to R Data Handling ............................................................ 13
Basic Differences in Code Syntax: R versus SAS .................................. 15
SAS Formats and Labels versus R Approaches .................................... 17
SAS versus R—What to Choose? .................................................................22
Why R Can Be a Difficult Choice for Public Health Efforts................22
Considerations When Choosing R versus SAS ..................................... 24
Optional Exercises ......................................................................................... 25
All Sections ................................................................................................ 25
Questions ............................................................................................... 25
Answers ................................................................................................. 25
2. Preparing Data for Analysis....................................................................... 27

Reading Data into R....................................................................................... 27
Importing Data .......................................................................................... 27
Checking the Dataset after Reading It in .............................................. 28
Checking Data in R........................................................................................ 33
Statistics on Continuous Data in R ......................................................... 33
Visualizing Continuous Data in R.......................................................... 37
Statistics on Categorical Data in R: One Variable ................................. 40
Statistics on Categorical Data in R: Crosstabs.......................................44
Editing Data in R............................................................................................ 48
Trimming off Unneeded Variables ......................................................... 48
Applying Qualification Criteria through Subsetting Datasets .......... 50
Creating Grouping Variables................................................................... 53
v
vi Contents
Creating Indicator Variables for Two-Level Categories....................... 61

Creating Indicator Variables for Three-Level Categories .................... 62
Creating Indicator Variables for Multilevel Ordinal Categories ........ 63
Creating Indicator Variables for Multilevel Nominal Categories ...... 65
Creating Missing Flags............................................................................. 67
Preparing Binary Outcome Variable ...................................................... 68
Planning a Survival Analysis Dataset with Time-to-Event
Variables ..................................................................................................... 68
Developing the Survival Dataset ............................................................ 70
Dealing with Dates ................................................................................... 82
Recoding and Classifying Continuous Variables................................. 88
Recoding a Continuous Outcome Variable ........................................... 89
Data Validation in R ...................................................................................... 92
Bivariate Relationships between Continuous Variables...................... 93
Bivariate Relationships between Categorical and
Continuous Variables ............................................................................... 99
Bivariate Relationships between Categorical Variables .................... 106
Power Calculations ................................................................................. 108
Write Out Analytic File .......................................................................... 115
Optional Exercises ....................................................................................... 116
Section “Reading Data into R” .............................................................. 116
Questions ............................................................................................. 116
Answers ............................................................................................... 116
Section “Checking Data in R” ............................................................... 117
Questions ............................................................................................. 117
Answers ............................................................................................... 118
Section “Editing Data in R” ................................................................... 122
Questions ............................................................................................. 122
Answers ............................................................................................... 124
Section “Data Validation in R” .............................................................. 127
Questions ............................................................................................. 127
Answers ............................................................................................... 128
3. Basic Descriptive Analysis ....................................................................... 133

Making “Table 1”—Categorical Outcome ................................................ 133
Structure of Categorical Table 1 ............................................................ 133
SAS Approaches to Categorical Table 1 Structure.............................. 136
SAS Approaches to Table Presentation Using Excel .......................... 141
SAS Bivariate Categorical Tests ............................................................. 142
The Table Command in R ...................................................................... 143
R Approaches to Categorical Table 1 .................................................... 145
Approaches to Automating Table Generation in R ............................ 153
R Bivariate Statistical Tests .................................................................... 155
Contents vii
Making “Table 1”—Continuous Outcome ............................................... 156

Structure of Continuous Table 1 ........................................................... 156
SAS Approaches to Continuous Table 1 .............................................. 156
Continuous Bivariate Statistical Tests in SAS ..................................... 163
R Approaches to Continuous Table 1 ................................................... 165
Continuous Bivariate Statistical Tests in R .......................................... 171
Descriptive Analysis of Survival Data...................................................... 176
Summary Statistics and Plots on Time Variable................................. 176
Generating and Plotting Survival Curves ........................................... 177
Bivariate Tests of Survival Curves ........................................................ 185
Section “Making ‘Table 1’—Categorical Outcome” ........................... 189
Questions ............................................................................................. 189
Answers ............................................................................................... 189
Section “Making ‘Table 1’—Continuous Outcome”........................... 190
Questions ............................................................................................. 190
Answers ............................................................................................... 190
Section “Descriptive Analysis of Survival Data” ............................... 193
Questions ............................................................................................. 193
Answers ............................................................................................... 194
4. Basic Regression Analysis ........................................................................ 197

This Book’s Approach ................................................................................. 197
Selection of Modeling Approach .......................................................... 197
Selection of Manual Approach .............................................................. 199
Operationalizing the Stepwise Selection Process .............................. 200
Prespecifying Hypotheses and Avoiding Fishing ............................. 201
Linear Regression and ANOVA ................................................................. 203
Preparing to Run Linear Regression .................................................... 203
Linear Regression Modeling and Model Fit Statistics ....................... 205
Selecting the Final Linear Regression Model ..................................... 211
Considerations in Improving the Final Model ................................... 214
Considering Collinearity ....................................................................... 214
Adding Interactions ................................................................................ 215
Goodness-of-Fit Statistics....................................................................... 217
Linear Regression Model Presentation ................................................ 218
Plot to Assist Interpretation ...................................................................225
Logistic Regression ...................................................................................... 228
Estimates Produced by Logistic Regression ....................................... 229
Logistic Regression Considerations ..................................................... 229
Introduction to Logistic Regression Modeling ................................... 231
Logistic Regression Modeling and Model Fitting .............................. 232
Selecting the Final Logistic Regression Model ................................... 239
viii Contents
Logistic Regression Model Presentation ............................................. 249

Plot to Assist Interpretation ................................................................... 255
Survival Analysis Regression .................................................................... 256
Selecting a Parametric Distribution in Survival Analysis ................ 257
Selecting a Semiparametric Distribution for Survival Analysis ...... 262
Introduction to Survival Analysis Regression Modeling ................. 264
Survival Analysis Regression Modeling and Model Fitting ............ 265
Parametric Survival Analysis................................................................ 265
Semiparametric Survival Analysis ....................................................... 270
Issues to Consider in Survival Analysis .............................................. 274
Selecting the Final Survival Analysis Model ...................................... 275
Survival Analysis Model Presentation ................................................ 275
A Note about Macros................................................................................... 276
Section “This Book’s Approach” ........................................................... 278
Questions ............................................................................................. 278
Answers ............................................................................................... 278
Section “Linear Regression and ANOVA” .......................................... 278
Questions ............................................................................................. 278
Answers ............................................................................................... 279
Section “Logistic Regression” ............................................................... 280
Questions ............................................................................................. 280
Answers ............................................................................................... 280
Section “Survival Analysis Regression” .............................................. 281
Questions ............................................................................................. 281
Answers ............................................................................................... 282
Section “A Note about Macros” ............................................................ 285
Questions ............................................................................................. 285
Answers ............................................................................................... 285
References ........................................................................................................... 287

Index ..................................................................................................................... 297
Preface
When I, Monika Wahi, gave a presentation at the Effective Applications of the

R Language (EARL) Conference in Boston in November 2015, there I attended
a panel discussion of the event leaders, although it was a very open dis-
cussion, with the audience enthusiastically participating. The goals of the
R Consortium were delineated, which led to the consideration of how to
promote the increased usage of the R language by statisticians. After all,
R is open source software, so it does not have a marketing department per se.
Someone in the audience brought up with the specific topic of healthcare
analytics, asking the attendees why R is not used more often in healthcare.
After a pause, someone pointed out the domination of SAS in the indus-
try, which crowds out R. But then, another person speculated that the Food
and Drug Administration (FDA) would only accept analysis in SAS (a myth
which we debunked in Chapter 1). It became clear that there seemed to be
many barriers to promoting R among healthcare analysts.
After further consideration, this was ironic, because both R and SAS are
very extensive languages, but what we do in healthcare analytics on a day-to-
day basis is relatively straightforward. We are not modeling any spaceship
trajectories, or building complex economic models, or predicting weather or
the outcome of sports games. It occurred to me that as we generally do the
same things over and over again in healthcare analytics, and because most
people in healthcare analytics do these things in SAS, a book that focuses
only on explaining how to do what we normally do in SAS in R would help
healthcare analysts who may want to use R also.
Therefore, this book is aimed at the healthcare analyst who is a SAS user
looking to learn R. Chapter 1: “Differences between SAS and R” is written
mainly for those who are interested in the backstory of how SAS and R are
run differently. Readers who want to get immediately to coding should
skip to Chapter 2: “Preparing Data for Analysis”, which describes editing
and validating an analytic dataset in R rather than using SAS data steps.
Chapter 3: “Basic Descriptive Analysis” will explain how to use the analytic
dataset developed to produce a basic descriptive analysis (often presented
as Table 1 in manuscripts). Finally, Chapter 4: “Basic Regression Analysis”
covers linear and logistic regression and basic survival analysis. As R pro-
duces such lovely plots, an insert with 16 color plots is included in the center
of this book.
We hope this book encourages you to try R for some healthcare analysis
tasks.
Monika Wahi and Peter Seebach
ix
Acknowledgments
The number of people who have helped us with this book is large, and we
are eternally grateful. But after controlling for age, relevant skills, and educa-
tion, it turns out that specifically no one individual contributed significantly
more to help us with this book than another. Our conclusion is that you are
all amazing, and we thank you very much for your support!
xi
Authors
Monika Wahi, MPH, CPH obtained a bachelor of science in costume design

and textiles and clothing (with a concentration in Journalism) from the College
of Human Ecology, University of Minnesota, St. Paul, Minnesota, and, then
went on to complete her masters in public health from the University of
Minnesota School of Public Health, Minneapolis, Minnesota. After serving
in several different scientific and administrative roles at Hennepin County
in Minnesota, a nonprofit Alzheimer’s research institute in Florida, and at
the U.S. Army at a site in the Greater Boston area, she struck out on her own
to build her consulting business, DethWench Professional Services (DPS).
Since 2012, she has been serving as a lecturer at the Labouré College, Milton,
Massachusetts, teaching classes in the U.S. healthcare system and statistics.
Monika has also led to the expansion of DPS to serving an international
clientele through providing online educational material and services as well
as public health research consulting.
Peter Seebach was raised by mathematicians, and never fully recovered.

He earned his bachelor’s degree in psychology from St. Olaf College,
Northfield, Minnesota, and then went on to apply it to a career as a software
developer and writer. He enjoys computers, writing, and writing about com-
puters. He is an outlier, and therefore tends to throw off the average.
xiii
1
Differences between SAS and R
This chapter is meant to help the SAS user conceptualize the important dif-
ferences between R and SAS that will affect the work of the healthcare ana-
lyst who knows SAS but is looking to learn how to use R. The first section
describes important differences in the structures of the SAS and R programs.
This leads to the discussion in the second section, which focuses on how
these differences in structure affect the differences in data handling between
the two programs. The third section of this chapter contextualizes the choice
between using R versus SAS for a healthcare analytics project and provides
a guide for selecting which software to use. Optional practice exercises are
included in the fourth section.
Structure of Program
Perhaps the most important difference between SAS and R is the structure
of how the program is built and maintained. To begin to explain this differ-
ence, we will start with considering how different the download and install
process is between PC SAS and R. Next, we will cover how these differences
are also reflected in the differences in the way licensing is maintained in the
two programs. Third, the differences between SAS components and their
parallel in R, called R packages, will be discussed, and after that, differences
between SAS and R in approach to maintaining the most current version in
a production environment will be explained. The differences between the
activities of SAS and R user communities will be described, followed by the
differences between the SAS and R user interfaces. Finally, some thoughts on
the principles of organizing code, metadata, and documentation in SAS and
R are presented.
1
2 Analyzing Health Data in R for SAS Users
Installation of PC Version: SAS versus R

When using a typical PC SAS license from a university, the data analyst
has to download and install the program on his or her Windows personal
computer (PC), as the current operating system (OS) for Macintosh is not
supported.* To do this, the analyst is provided access to either many CDs
that her computer will tell you to put in or take out of her CD/DVD drive
during the installation process, or alternatively, an extremely large setup
file that takes a very long time to download (plan for hours, not minutes).
The analyst is also provided a small text file with unique license information
for her institution’s license.
Once the analyst has access to these setup files, a setup file is run on the
analyst’s PC, and this setup file takes a while to extract. The installation
must be monitored because the user has to click through many menus. This
is because these SAS institutional licenses are very extensive and include
many add-ons and components. This heavy-handed installation process is
designed to make sure the analyst has access to all the components to which
she is entitled under the license (which, at a university, tends to be a large
volume).
However, when working in SAS, the analyst may encounter the rare case
in which she is using an analytic function that is not included in the SAS
license components, and this throws up an error message. This is a confus-
ing situation because the error message does not usually point to a miss-
ing component; it simply rejects the code as being incorrect in some way, so
troubleshooting can be challenging.
Because R is open source, meaning that R developers are volunteers and
make the code and documentation for how R runs readily available on the
Internet, there is no need for the advanced functions to control licensing
that SAS employs. This makes the way R is distributed different from
SAS. Anyone can go to the public website called “The Comprehensive
R Archive Network” (CRAN) (https://cran.r-project.org) [1] and down-
load the latest version of R for Mac or Windows and install the core
program. The user interface (UI) looks slightly different on Mac versus
Windows, but the differences are minor.† The R installation file is small
relative to the SAS installation file, and once the user downloads this file
and runs it, the setup wizard is clear and easy, making for a quick instal-
lation process.
* Per SAS, SAS versions developed since Macintosh OS X came out are not supported on OS
X. A modification of SAS called JMP (pronounced “jump”) has been developed for Mac and
Windows users alike, although it has greatly reduced functionality. SAS also has a web-based
version that can run in Mac and Windows browsers which is mainly used in teaching rather
than production environments.
† The examples given in this book refer to the Windows version of R.
Differences between SAS and R 3
Licensing Differences: SAS versus R

The exact components of the SAS institutional license make are communi-
cated to SAS during the installation process at the step where the user is
asked by the setup wizard to reference the small text file provided with the
setup files. As stated earlier, the list of components included in a SAS insti-
tutional license are usually large. When SAS negotiates enterprise licenses
with universities, they are set up such that a large volume of components is
included, and the student or faculty pays only a negligible fee or nothing to
obtain this licensed version, provided they can prove their status with the
university. This is because SAS wants to promote use and learning of all its
components at universities.
Importantly, SAS prices their licenses for non-university businesses dif-
ferently. As an example, an independent nonprofit research institute on
the campus of a state university in Florida contacted SAS and asked if the
research institute could use the university license. SAS did not agree, and
instead, prepared a license for PC SAS strictly for the research institute. This
license only had one seat, and only had the base component of SAS (“base
SAS”) and the basic engine that runs regression functions (“SAS STAT”). This
one-seat license cost the nonprofit approximately $10,000 per year in 2007, so
the nonprofit could not add extra seats. Hence, researchers who learned SAS
at the university and then went on to be hired as scientists at the nonprofit
research institute were not able to use their extensive knowledge of all the
components of SAS due to the prohibitively expensive licensing approach.
Because R is open source, there is no licensing fee, so R is perfectly suited
for public health work in low- to middle-income (LME) countries, nonprof-
its, and businesses with a low profit margin. This book can hopefully help
bridge the gap between SAS and R for SAS-experienced healthcare analysts
who are priced out of the market by this situation.
SAS Components versus R Packages

Base SAS, the core of SAS, is a rather large program. As mentioned before, the
main R program that is downloaded from CRAN is much smaller than the SAS
setup program, and therefore, downloading it is fast and installing it is very easy.
The drawback is that just about anything the user tries to do once installing R will
require an outside component not in the base program, called an R “package.”
Because R is not licensed for purchase, it is much more efficient for each
user to simply build their version of R by installing the packages needed.
Admittedly, this can be a daunting task, as some packages are based on other
packages, so these all need to be installed. For example, to make a Kaplan–
Meier plot in R, the user must install the “survival” package, as well as the
“KMSurv” package [2]. More recently, packages are designed to automati-
cally install packages on which they are dependent, so this problem does not
occur as frequently anymore.
Luckily, as with the base R program, all the packages are free and are easy
to install from within the program. In the native R UI, there is a menu with
only seven selections, and “packages” is one of them. If the user chooses the
“packages” menu and selects “load package,” the UI presents a list of pack-
ages that can be installed, and the user just needs to select the correct ones
and install them. Packages can also be installed using commands, but the
load package menu makes the process extremely easy.
What is RStudio?
This book gives guidance on using the PC version of R in Windows as it
appears with its native UI. R’s native UI is typically sufficient to be used by
healthcare analysts to develop statistical models. However, there is also an
integrated development environment (IDE) that can be used called RStudio.
This is supported by the R Consortium, which is a collaboration between the
R Foundation (which maintains CRAN), RStudio (a collection of R develop-
ers working on the IDE), and other big tech companies such as Microsoft and
Google [3]. Like R, RStudio is also open source and free to individual users.
RStudio is different than R in that it is an IDE and includes a source code
editor, build automation tools, and a debugger. RStudio can be run as a desk-
top or server version, so it is used at universities in programs that teach pro-
gramming in IDEs [4]. It is an excellent tool for deploying Shiny, which is
an R package that interfaces R with the web and turns R analyses into web
applications [5].
Generally, the capabilities afforded by RStudio are required for deploying
web applications, but for hypothesis-driven healthcare analytics, RStudio
can be overkill. For example, RStudio has several windows that are associ-
ated specifically with the IDE, and would not appear in R. Therefore, unless
the analyst needs an IDE, using R rather than RStudio is preferred.
Maintaining Current Versions in SAS versus R

When using a university SAS license, there is a month in the year that the
license expires because these are set up as yearly licenses. When the license
expires, the user can still open the SAS program, but it throws up an error
message indicating the user will need an updated text file with a new license,
and does not let the user unlock the program until this is loaded. At this
point, the user must obtain the new text file from the university, and from
within SAS, load this license, thus unlocking the program. Although SAS
does update its base program with new version from time to time, it does not
do it often, so renewing the license is much more common than installing a
new version of SAS.
Part of the reason SAS does not update its base program often has to do
with how it determines what to put in updates. Independent SAS program-
mers typically develop macros (canned code procedures) in SAS macro
language and make these available on the Internet. These are not held in a
central repository but posted all over the Internet, and are also highlighted
in SAS white papers presented for regional as well as national and interna-
tional user groups [6–8], which are also not available in a central indexed
repository (although they are posted on SAS-sponsored websites and are
easy to find through a search on the web).
If a particular macro becomes popular with SAS users, some may choose
to write a peer-reviewed article about it [9], fostering discussion of the macro
in the SAS community. If SAS receives enough requests to include the macro
as a main function in SAS, and can verify the functioning of the macro, SAS
may choose to include it in its next build. This is a decision made by SAS
on a business level, not by the SAS user community, so opinions may differ
between the user community and the business as to what macros should be
included as procedures, or “PROCs,” in new versions of SAS.
R does not have the constraints SAS has with respect to innovation and
change management. First, its base program is very lean, which means it
is not difficult to update and disseminate. For this reason, new versions of
R can be released quite often (at least once per year). The penalty for the
R user is that if she wants to update her core version of R, she will have to
reload all the R packages she has been using to carry on with her analy-
sis. An advantage is that the newest version is always available on the
CRAN site for free, as are the packages, and this means that the only loss
in efficiency is through time required to update the R core program and
reload the packages. Also, R developers have created packages available
on CRAN that can be loaded and configured to run automated functions
to help R shops keep their base R and all its packages updated on a regular
basis.
SAS macros that are not available within the program are documented all
over the Internet by individual programmers, just like R packages that are
not official or are under development. However, macros built into SAS as
commands or “PROCs” are well-documented in SAS’s online and paper help
files. Similarly, R’s published packages are well-documented on the CRAN
website [10], as standardized comprehensive documentation is required to
be approved to have a package published to CRAN.
When SAS updates its program, it includes updates to its core, new mac-
ros built in as PROCs, and updates to old PROCs and functions as well. This
means that production operations dependent on SAS can effectively plan
for change management. Conversely, because R updates its core regularly,
and the authors of their packages also update their packages idiosyncrati-
cally, maintaining the most up-to-date version of R is actually rather chal-
lenging in a production environment. Independent tools, functions, and
routines have been developed to assist with this task [11], but it is impor-
tant to emphasize that those running R in production must be proactive in
maintaining the most up-to-date versions of R and packages being used in
production.
It must be noted that R has a different method than SAS in deciding what
packages to include on CRAN. Like with SAS, R users can prepare and pub-
lish unverified packages for R online [12,13], and adventurous R users can
test them. If the package is deemed worthy by many, the author may apply
to have the package included on the CRAN site (and thus have it show up
in the “load package” menu). But depending upon the package, installing
a new package may effectively require devoting 15 min or more to loading
different packages on which a new package might be based, and testing the
results to make sure the new package can actually run. When this happens,
the R user may nostalgically muse about how easy it is to run macros and
PROCs in SAS by comparison, but once the packages are sufficiently loaded
in R and running well, this nostalgia generally passes.
SAS versus R User Communities

SAS is known for its expansive support for its user community. SAS orga-
nizes “SUGs,” or SAS User Groups, and provides logistic and financial
support for conferences requested by user groups [6–8,14,15]. These confer-
ences produce an extensive set of non-peer-reviewed white papers that pro-
mote the use of all of SAS’s various components by helping the user deal
with the unnecessary complexity of SAS. These white papers are unfor-
tunately of varying quality; some are well-written and helpful, whereas
others are poorly written and confusing, and there seems to be little in the
way of consistent standards as to what is accepted as a SAS white paper.
Nevertheless, SAS users are provided a fertile opportunity to thrive aca-
demically with SAS given the many opportunities offered to publish white
papers and present them at meetings of SUGs, as well as the vast amount
of documentation available online that results from the publication of these
white papers, which effectively facilitates the adoption of SAS’s more com-
plex functions.
On the other hand, R, which is an open-source software and therefore
does not have a conference or marketing department, has a different land-
scape when it comes to user groups and community gatherings. Meetup.
com, an online platform designed with tools meant to be used to build com-
munities through the scheduling of informal meetings or “Meetups,” has
been used extensively by the R community to gather old hands as well as
early adopters together informally for mutual presentations [16]. Unlike
with SUGs, these Meetups are community-initiated and supported, so they
are held in cheaply available spaces, and often garner little or no industry
financial support.
Happily, this trend is changing, as R is piquing interest with big play-
ers, most notably Microsoft, which purchased Revolution Analytics in 2015.
Revolution Analytics was an R shop that specialized in improving data han-
dling in R so as to enable it to process larger datasets [17]. In addition, larger
scale gatherings, such as the Effective Applications of the R Language (EARL)
conference, which is now held twice per year on two different continents, is
sponsored by various members of industry, including Mango Solutions, a
long-time big-ticket R analytics consulting group founded in 2002, as well as
Microsoft itself [18].
SAS versus R User Interfaces

The PC SAS interface provides a birds-eye-view of many of SAS’s functions
all at once. On the left panel, the user can toggle between a list of results
(output) and an explorer window that will show the contents of “work” (the
temporary directory where SAS puts datasets while it is running) as well as
other libraries mapped with the LIBNAME statement. Through this panel,
the user can easily open and view the datasets (in *.sas7bdat format) in the
mapped libraries.
In the main panel, users can display multiple windows at once. The user
can open multiple code windows (which can be saved as *.sas files), display
the log window (which shows the log of executed statements as well as error
messages, and can be saved as a *.log file), as well as view an output file
that can be displayed in hypertext markup language (HTML) and saved
separately.
R’s interface runs differently. Like SAS, the R PC interface allows for multi-
ple windows to be opened at once, but the function of the windows is differ-
ent. When R is launched, only one window is opened automatically, and this
is called the R console. This window is where statements will be executed,
log statements will be recorded, and tabular and numeric output will appear.
Next, the user can open one or more code editing windows. R has a menu
with only five choices: File, Edit, Packages (described earlier), Windows, and
Help. Choosing File—New Script from the menu will open a new code edit-
ing window. If the users saves a file from this window (Choose File—Save
As when the code window is selected), it will be saved as an *.R file.* Please
note that it is easy to open *.R files in Notepad or another word processing
program without needing to load R.
Once the user has a code window open, she can prepare code and run it
in the console by either copy/pasting it from the code editing window into
the console and pressing “enter,” or by highlighting the code in the code
window, right-clicking and choosing “Run line or selection” (also Control-R),
and this will transfer the code to the console and run it. Or, she can simply
type code directly into the console and hit “enter,” and the code will run.
An important point to be made here is that although R has an extensive
array of statements that could be used to do the equivalent of mapping a
LIBNAME in SAS, probably the easiest way to set a singular default directory
* Our experience is that occasionally, the *.log extension used in SAS is already designated to
default to another application in Windows (thus prompting a dialogue box during installa-
tion). So far, we have not encountered extension conflicts in R.
is to run the R program, select the console, then using the menu, choose
File—Change Dir. This will allow the user to navigate to the directory on her
PC or server where most of her R project is stored, and this will make loading
code from that directory much simpler throughout the session. Please note
that this designation will end at the end of the R session. Also, please take
notice of the fact that if the code window is selected and the user chooses
File—Open Script, the browser will default to the last code directory used,
but if the console is selected, the same operation will bring the user to the
directory designated during the File—Change Dir function.
The console is the place where the following appear: log messages, error
messages, and non-graphical output. For example, if the user requests a fre-
quency table, or conducts a calculation, or asks for the number of observa-
tions in a dataset, after the line of code is run in the console (displayed in red
text), this information will be reported subsequent to the code (displayed in
blue text). The console will continue to fill up with a history unless the user
chooses Edit—Clear Console. Clearing the console from time to time may be
helpful for the user involved in a large project, and might be seen as equiva-
lent to clearing the log file in SAS.
Because so many different types of messages appear in the console when
R code is run, saving “log files” is not as straightforward in R as it is in SAS.
(Please notice that the menus change depending upon whether the console
or the code window is highlighted.) Other options exist in the console’s set
of menus, but it may serve the user best if the user wants to save elements of
the session (such as error messages for later troubleshooting, spontaneously
formed code in the console, or log messages) to select the console window
and choose Edit—Select All, and then choose Edit—Copy.* Next, the user
can switch to a word processing environment (such as Notepad or Microsoft
Word) and choose Paste or Control−V.
At this point, it is important for the user to edit the pasted text to remove
the elements of the output not wanted to be saved in the manually edited
“log file.”† Because the R log files require some hand-editing, there are both
pros and cons. An advantage in R, unlike in SAS, is that the user can easily
remove parts of the text that are unimportant to her (such as confirmation
of reading in a data file, or reports of successful execution of simple com-
mands). It is also easy to annotate these parts to provide insight into the doc-
umentation being kept. The disadvantage is that this effort constitutes work
that is generally not done when SAS log files are saved. In reality, however,
anyone who has dug through SAS log files to troubleshoot the execution of
a large batch of code might not consider this feature of R a disadvantage!
* Please note that the menu must be used to execute the Select All command, but after that,
Control-C can be used in lieu of Edit – Copy command.
† Users familiar with SPSS will consider this reminiscent of the output window in SPSS, which
is easy to save in an SPSS analysis, but hard to understand after the fact if the file is not some-
how reduced, rearranged, or annotated.
This is because actually organizing a log file into what is important and
annotating it builds in efficiency later when troubleshooting may be neces-
sary, especially when a programming team is involved. Otherwise, it may
not be helpful to save the log file in the first place.
Finally, R handles graphical output files somewhat similarly to PC SAS in that
it opens and displays graphics in a separate window. The window automatically
opens when graphics requests are run in the console, and the window is titled
R Graphics. Once this window is open, the user can select it (which changes the
menu options) and choose Save As, where the user is presented a list of formats
to choose from, including the popular *.pdf, *.png, and *.jpg. If *.jpg is chosen, the
user is offered the selection between 50%, 75%, and 100% quality.
R’s handling of graphics represents a strong advantage over SAS, because in
SAS, the output function for graphics always involves the rigid and complex
“output delivery system,” or ODS, which produces files that generally need
to be post-processed in another program to be made even minimally pre-
sentable for journal publication or even presentation in an informal meeting.
In SAS, the alternative to this requires advanced expertise on the part of the
programmer to set options in SAS to modify the output as SAS commands
are executed so the resulting graph does not need extensive post-processing.
With R, this entire complexity is avoided, and even a basic graphics editor
such as Paint can be used to manually add detail to *.png and *.jpg graph-
ics files saved from R in this way. Further, as will be demonstrated later in
this book, but most specifically in Chapter 2, little expertise is required to
add elements through programming code to graphical output in R, such as
adding labels to x and y-axes, whereas these functions require much more
programming ability when done in SAS.
Code Documentation and Metadata: SAS versus R

A classic common challenge in any statistical program when working with large
datasets to complete a complex, long-term health data analytics project involv-
ing an interdisciplinary team, a lot of data, a lot of code, and a lot of time, is
entropy.* A part of this entropy that can drive the programmer to distraction is
having trouble keeping track of the meaning, content, and method of generation
of both the native variables (the variables present in the original data file used in
the analysis) and the new variables the programmer creates through code that
edits data. For this reason, in both SAS and R as well as any other statistical program,
the following modern process for maintaining code files is recommended:
1. Code files should be relatively short and focused on only one func-
tion (e.g., reading in a dataset, running histograms, running fre-
quencies, running regressions).
* A close colleague has referred to this phenomenon as “biostatistics paper hell.”

2. Code files should have a numerical prefix that causes the code files
to line up in the order in which they should be run, followed by a
shorthand label indicating the function of that code (e.g., 100_Read
in data, 105_Run summary statistics, 110_Create age group variable).
3. Advanced users can designate logic and naming conventions with
respect to these prefixes (code starting with 00n indicates pre-
processing, code starting with 10n indicates code that edits data,
code starting with 20n indicates analytic code that does not edit
data, code starting with 70n indicates exploratory code).
4. Prefixes should not be named in increments of 1 to allow for insertion
of code in between code files at a later date (e.g., naming code “100_
read in data,” with the next code being named “105_create age group
variable” will allow for the possibility of insertion of code “103_*”
after the fact, in case minor post-processing is found to be required
after reading the data in).
An analogy can be made to making a movie. Although viewers perceive the

movie as happening in chronological order, the director and actors are aware
that the scenes are actually not shot in chronological order. As a data “director,”
the programmer may develop “scenes” (programming commands) for later
in the “movie” (such as regression code), only to find that to make the story
straight and clear, she has to redo scenes from earlier in the movie (such as
generating a new variable in the analytic dataset). This way, if the age group
variable she created has an error or needs to be changed, she can go back to
the code earlier in the “movie,” edit this code properly, then start from the
beginning and run the whole “movie” of code from the beginning to the pres-
ent state to make sure the story hangs together after the edit.
Along with this principle, the importance of prolific and well-organized
comments in code, in both SAS and R as well as any other statistical program,
cannot be overstated. In SAS, commenting is done in between bookends of
/* and */ (e.g., /*This is a comment*/) or by simply using * at the beginning
of the line (e.g., *This is a comment). R uses the second approach to com-
menting (e.g., #This is a comment), but not the first. Therefore, although old
hands at SAS might be familiar with SAS banners that precede the code in
code files, these are not used in R.
This discarding of banners before code actually represents an innovation;
modernly, SAS banners (as well as banners in other statistical code) are to
be strongly discouraged in health data analysis. Instead, the information that
would have belonged in the SAS banners of the 1980s and 1990s programming
styles should now be placed instead in an outside program that is more accessi-
ble (such as Microsoft Word or Excel) and follow an organized standard. Banners
contain information that is human-generated, such as notes on interpretation of
variables or variances from standards in programming, not information that can
be automatically generated, such as a list of field names and attributes.
Many long-term SAS programmers have not learned this new principle,
and this inhibits clear communication and discussion about the nature of
the data, code, and analysis, as non-programmer managers and subject mat-
ter experts in other fields in healthcare and science cannot easily view this
metadata reported in the SAS banners. Hence, today, SAS banners should
be avoided in code, and R code should also not include banners, and should
only include prolific, carefully-worded and carefully-placed comments.
While some programmers shun excessive commenting, given the modular
approach recommended to developing code files, many code files are short,
so the comments do not complicate comprehension of the code.
Additionally, datasets themselves should not be documented in actual
code anymore, and all dataset metadata should be developed and made
available in easily accessible word processing and spreadsheet applications
(such as Microsoft Word and Excel) or else in the less-recommended PDF
format.* This means that SAS “labels” and “formats” should no longer be
used, and instead, this information should appear in a data dictionary docu-
ment, preferably in a spreadsheet format. An excellent example of publicly
available metadata that is presented in optimal format is the set of metadata
developed for the US Military Health System Data Repository, the MDR [19].†
The MDR’s use of this approach to metadata ensures that those receiving
MDR data files can study them adequately before attempting to read them
into any statistical software. This excellent set of metadata also provides
researchers from all fields necessary documentation to aid them in develop-
ing intelligent and informed data requests prior to receiving the data.
SAS programmers have historically embedded the metadata of variable
meanings, meanings of various categories in categorical variables, or infor-
mation about complex code functions that require explanation in their actual
SAS files, not in external metadata. This means that the actual file of SAS
code that assigns labels to variables in a dataset, and SAS FORMAT code
that labels the meanings of various levels of a categorical variable, would
sometimes be the only documentation of what these variables mean. This
effectively limits the ability of an interdisciplinary team to use the metadata
and complicates the interdisciplinary communication required to complete a
health analytics project successfully. It also essentially quashes the prospect
of group troubleshooting if multiple programmers are using different types
of statistical software.
On the other hand, using the methods described here of code organiza-
tion, naming conventions, and metadata maintained external to the statisti-
cal program, the programmer can not only reduce the time and complexity
associated with troubleshooting but also make sure that such a “movie” can
* PDF format is harder to navigate, copy, and paste, compared to Microsoft Word and Excel.
† For an excellent example, the reader is encouraged to download the M2 data dictionary from
the MDR web site, which is formatted in Microsoft Excel, and browse the different tabs to
better understand the optimal format of metadata described in this section.
be watched and understood by an outside programmer. This is especially

important for scientific writers who may be lucky enough to have their work
accepted in a top-tiered journal, such as the Journal of the American Medical
Association (JAMA) or the New England Journal of Medicine (NEJM). If this
occurs, the journal requests the code and data from the analyst and hires an
independent statistician to verify the results from the analysis. Following
these coding and documentation conventions can make this transfer of
knowledge accurate and easy. If the programmer finds herself is such a situ-
ation, without much complexity, she can provide the metadata files as well
as an organized compendium of code to the verifying statistician with an air
of professionalism while leaving little room for miscommunication during
the transfer process.
Handling of Data
This section begins with a short description of some issues with SAS data
handling that must be understood to make an informed comparison with
R data handling. Next, features of R data handling will be described and
contrasts between SAS and R data handling will be highlighted. Third, basic
differences in SAS and R code syntax will be explained, followed by a dis-
cussion about how to approach the thought of SAS macros when developing
code in R. Finally, an explanation of approaches in R equivalent to SAS labels
and SAS formats will be described.
A Focus on SAS Data Handling

In order to effectively contrast SAS data handling with R data handling, it
is extremely important to gain at least a working knowledge of the issues
inherent in SAS data handling. This is because SAS data handling is par-
ticularly complex, and therefore is the topic of many SUG-initiated white
papers [6,14].
The main reason SAS data handling is so commonly discussed that it is
more complex than that of other modern programs, and relies on the user
developing extremely efficient code using SAS’s commands. SAS’s current
yet historical “data step” language (which is used for data editing in SAS) is
unnecessarily restrictive and complex simply due to lack of modern innova-
tion which is now possible.* Even in the current version, SAS executes data
* The monopoly status of SAS has relieved much pressure on the company to improve the
product in this way. Also, those who are data step masters may feel their positions threat-
ened by users of simpler data editing software, so they inadvertently collude with SAS by
continuing to study, receive certifications in, and promote the use of SAS data step language.
steps by reading row by row (observation by observation) and executing

code in the data step to that particular row. SAS then walks to the next quali-
fying row and performs the set of code again, being stuck in an implied loop
[20]. This means that any indexing in SAS is most efficiently done by simply
sorting the SAS dataset by the indexing variable before executing a function.
In other words, when executing data step code on records where a field is a
certain value, sorting by that field will make the execution of the SAS code
go faster. Sorting may seem easy, but the sort function itself is inefficient
and can take enormous amounts of time depending on the dataset and SAS
implementation [21].
Aside from the complexity of the data step code, the second main reason
that data step functions are discussed ad nauseum in SAS white papers is
that to overcome the inefficiency of these data step functions, the programmer
needs to craft optimal code to ensure data management functions execute in
a reasonable timeframe as is generally required of a “procedural” language.†
Crafting this optimal code requires much study of data step language and
function. Compare this situation to that with structured query language
(SQL), which is a “declarative” rather than “procedural” language. This
means that the user declares what she wants returned in her query output
with relatively simple code, and a query optimizer running in the back-
ground automatically generates an evidence-based optimized execution
plan based on known dataset information such as the performance of prior,
recent queries. Thus, the query executes according to an optimal plan devel-
oped on-the-fly as a custom algorithm from the query optimizer, taking into
account all information known by the optimizer about the query at the time
(such as location of certain types of data within the dataset being queried).
When the process is described this way, one does not need to make a leap
to realize how much more efficient developing data editing code is in SQL,
which relies on a well-designed optimizer, when compared to programmer-
developed data step language in SAS, which is more prone to inefficiencies.
In reaction to this expanding realization among SAS users, SAS developed
PROC SQL, which is not really a PROC but a “language within a language.”
While adopting the characteristics of SQL and being much more intuitive and
easier to use than SAS data step language, SAS PROC SQL is prohibitively
inefficient in processing and cannot be used on large datasets. This is due
to an inefficient optimizer that results in extremely slow-executing queries,
leading disappointed SAS users back to the data step drawing board [22].
Comparison to R Data Handling

Before making a direct comparison between R’s and SAS’s handling of datas-
ets, it is necessary to take one step back and look at the “forest” of R and SAS
† Note that the nomenclature of “PROCs” in SAS point to its procedural processing feature.
rather than the “trees” of specific functions in R and SAS. SAS was developed
expressly for data analysis, meaning importing large datasets and running sta-
tistical analyses on them. SAS has certainly developed other functions—such
as data editing commands, commands to execute calculations, and commands
to set global variables—but these were all developed with the endgame of a
statistical analysis in mind. For this reason, although SAS can execute functions
like defining global variables, SAS’s core processes largely revolve around the
manipulation of datasets and executing statistical calculations on them.
R, on the other hand, was not designed expressly to handle datasets.
Although it is excellent at this function, it is also used for complex math-
ematical calculations, and is deployed extensively in the field of engineer-
ing. Instead of having the separate, specially-designed functions expressly
for handling datasets that SAS has—data steps, PROCs, macros, and other
SAS functions—R has generic functions for handling not only datasets but
also all the other types of objects in R [20]. Although SAS users tend to think
of programming in terms of dataset editing and analysis, it is important to
adopt a different perspective when approaching R for these functions. It is
more useful to consider R as a multifaceted program with an extensive set
of functions for the user to apply, and the health data analyst chooses to use
the functions helpful for dataset editing and analysis. This book is a guide to
choosing these functions.
Here are examples as to where this difference plays out. In SAS, health
analysts work with datasets and also arrays—which are a defined group of
columns in a SAS dataset. In R, there are other objects. The main R object data
analysts use is a “data frame,” which is similar to a SAS dataset. However, in
R, it is possible to make a “vector,” which is a single column of variables all
of the same type, a “matrix,” and a “list” (collection of objects) [20]. This ulti-
mately is an advantage if the R user learns how to make use of these other
objects to assist in data analysis, as they are not available to the SAS user.
SAS can be used in an object-oriented way, but this is not typically done
in health analytics. However, R is completely object-oriented—which is why
it is so much easier to create and invoke objects in R compared to SAS [20].
This difference also sheds light on how R processes indexes differently than
SAS. When R is used for data analysis, the main object is a dataset—which
should be coerced to be a “data frame” object in R. The first column of the
R data frame needs to be a primary key, or a column where all the numbers
are unique. This column is designated as the “row.names” column in R. In
a published dataset, there is usually a column already existing that has this
attribute that can be used as the row.names column. However, if there is not
one, R generates one on loading, which is similar to the OBS or observation
count generated by SAS when loading a dataset.
These differences are reflected in basic differences in how code is formed
in R versus SAS, and those impact how the programmer should approach
designing code. The next sections will describe some high-level differences
in thought that need to be applied while designing a project in R versus SAS.
Another random document with
no related content on Scribd:
COURSE AND DURATION.—The onset of the disease is sudden. The
symptoms in the first two stages may last only for a few minutes and
pass off, or the disease may pass through all the stages and
terminate in gangrene. It is usual for the first stage of ischæmia to
last several days, varying in severity; for the second stage to last
several days; and for the stage of gangrene to occupy about three
weeks. The shortest duration of a single attack has been ten days,
the longest five months. If the gangrene begins simultaneously in all
the fingers, the duration will be shorter than if it proceeds to one after
another. In one-third of the cases a recurrence of the disease within
a year of the first attack has been observed, and it is probable that
the proportion would have been larger had all the patients been kept
under observation. In some cases three and four attacks have
succeeded each other with some rapidity, some of the attacks being
much less severe and shorter than others. In some cases the
condition of gangrene has developed only in one out of three
attacks. When the condition is one of local erythema the duration
may be indefinite, the state becoming chronic and lasting for several
years.
NATURE.—The nature of the disease is a matter of deduction from the

study of the symptoms, no autopsies having as yet been made. As
already stated, the symptoms are explained on the theory of a vaso-
constrictor irritation in the stages of ischæmia and cyanosis—of a
vaso-dilator irritation in the stage of erythema. Whether this irritation
is the direct result of abnormal processes going on in the vaso-motor
centres in the spinal cord, or is the reflex result of irritation arising
elsewhere, is undetermined. Raynaud held that it must be of central
origin, since in his cases galvanization of the spinal cord modified
the arterial spasm. The latter observation has not been confirmed by
other observers. Weiss believes that the condition may occur in
response to irritation arising in the skin, in the viscera, or in the brain,
and thus prefers the theory of reflex origin. This theory is adopted by
several observers, who find a source for such irritation in the female
genital organs in their cases.
ETIOLOGY.—The disease occurs in adult life, only two cases having
been observed in persons fifty years old. It is most frequent between
the ages of fifteen and thirty, although children and adults beyond
the age of thirty are about equally liable. Females are more liable to
it than males, four-fifths of the recorded cases having been in
women. It occurs more frequently in the winter months, exposure to
cold being a common exciting cause. Other exciting causes are
nervous exhaustion, especially occurring in those who are
predisposed to nervous diseases by heredity; general weakness
from anæmia, malnutrition, or the occurrence of acute fever or
exhausting disease; and mental agitation, a fright having preceded
the attack in several cases. In women menstrual disorders and
uterine disease have been considered as etiological factors.
Occupation has something to do with its occurrence, since
washerwomen, waitresses, and chambermaids are the class most
often affected. In many cases, however, no cause of local irritation
can be found.
DIAGNOSIS.—The diagnosis rests upon the development of vaso-

motor symptoms in the extremities, situated symmetrically, going on
to gangrene, in a person not afflicted with cardiac disease or with
endarteritis of any kind, and not having been exposed to frost-bite or
ergot-poisoning. The age of the patient, the symmetrical position of
the symptoms, the persistence of the pulse in the main arteries, and
the limitation of the gangrene to the tips of the extremities distinguish
it readily from senile gangrene. The history of the case, the absence
of itching, and the presence of pain during the arterial spasm which
passes off when the spasm ceases, serve to separate it clearly from
chilblains. Congenital cyanosis is produced by cardiac anomalies,
and the entire body is affected. Ergot-poisoning can be ascertained
by the history.
PROGNOSIS.—Life is not endangered by this disease, no fatal cases

having been recorded. Recovery from an attack is certain, but the
duration cannot be stated, as it will depend in any case on the
character, the extent, and the severity of the symptoms. The
possibility of a recurrence of the attack should be stated to the
patient.
TREATMENT.—The methods of treatment have varied, and none are

wholly satisfactory. If the causes can be met—e.g. anæmia, nervous
exhaustion—they should be treated. If not, the disease itself may be
attacked by means of electricity. Or the symptoms may be treated as
they demand it. Electricity has been used by almost all observers.
The faradic current produces an aggravation of all the symptoms
except in the stage of erythema, and has been discarded. The
galvanic current may be employed in several ways. Two methods
are in use. In the first the positive pole is applied over the cervical
region, and the negative pole over the lumbar region, a descending
current being thus sent through the spinal cord. The current should
be of moderate strength, not above twenty-five milliamperes, few
patients being able to endure the strength implied in Raynaud's
statement that he used sixty-four cells of a Daniel battery. The
duration of the application should be ten minutes, and the electricity
may be applied once daily. In the second method the anode is
applied over the brachial or lumbar plexus, as the case may be, and
the cathode passed over the affected extremity, the current being
constant and care being taken not to break it suddenly. The strength,
duration, and frequency should be the same as in the first method.
From these two methods, separately or combined, Raynaud claimed
to have seen favorable results. His assertions have not been
confirmed by other observers who have followed his directions
closely, and hence considerable doubt at present prevails as to the
efficacy of the electric current. The so-called electrical application to
the cervical sympathetic is certainly useless. In the stage of
erythema a very weak faradic current applied to the hands in a bath
may be of service.
Many observers have found that the progress of the case to recovery
was quite rapid if the limb were put at rest in an elevated position,
were kept warm by cotton batting or similar bandaging, and were
kept clean with antiseptic lotions when the stage of gangrene set in.
Massage is to be used in all cases, the limbs or affected parts being
gently rubbed with the dry hand or with aromatic liniments or oils. All
local injury, however, and especially counter-irritation, are to be
carefully avoided. General tonic treatment, especially iron and cod-
liver oil, is to be used in all cases.
The pain occurring in the early stages is often so severe as to

require the use of opium or other narcotics. And when the nervous
symptoms are especially aggravated, and irritability and insomnia
give the patient discomfort, bromide and chloral may be employed.
Diseases of the Cervical Sympathetic.
ETIOLOGY.—Diseases of the cervical sympathetic ganglia or cord may

be of two kinds—either irritative or destructive.61 They are produced
by pressure upon the cervical ganglia or upon the sympathetic cord
between these ganglia, by tumors, especially aneurisms, and
enlarged glands; by abscesses; and by cicatrices of old wounds in
the neck. They are also due to extension of inflammation from a
thickened pleura in phthisis and chronic pleuritis of the apex. They
may be caused by injuries, such as stab-wounds, gunshot wounds,
etc. Any disease which produces marked irritation of peripheral
branches of the sympathetic in the neck, or of the cerebro-spinal
cervical nerves, may cause reflex phenomena resembling the
symptoms of actual disease. From such phenomena it is not
justifiable to conclude that the sympathetic cord and ganglia are the
seat of lesions, and the only cases which will be considered here are
those in which actual disease was proven to be present by an
autopsy.
61 Ogle, Medico-Chirurgical Transactions, xli. 397-440, 1858, 27 cases; Poiteau, “Le
Nerf sympathetique,” Thèse de Paris, 1869, 19 cases; Eulenburg and Guttmann, Die
Pathologie der Sympathicus, 1873; Nicati, Le Paralysie du Nerf sympathique-
cervicale, 1873, 25 cases; Seeligmüller, Inaug. Dissertation, 1876; Mitchell, Injuries of
Nerves; Mobius, “Pathologie der Sympathicus,” Berlin. klin. Woch., 1884, Nos. 15-19.
Inasmuch as the cervical sympathetic is in close anatomical
connection with the spinal cord, especially with the eighth cervical to
the second dorsal segments (the so-called cilio-spinal centre of
Budge), and as the functions of the sympathetic are dependent upon
the integrity of the spinal cord, it is evident that any lesion of the
nerves uniting it with the cord, or any lesion in the cord itself at the
levels mentioned, may produce symptoms which resemble closely
those of disease of the sympathetic. Thus, cervical pachymeningitis,
myelitis (especially from injury of the cord, or hæmato-myelia), and
diseases of the cervical vertebræ which produce either or both
conditions, may cause a train of symptoms somewhat similar to
those to be described.62 A careful distinction must be made between
primary and secondary disease of the sympathetic, between reflex
and direct symptoms, between lesions in its substance and lesions in
its governing centres in the spinal cord. The symptoms produced by
affections of a reflex or central nature are rarely as numerous as
those of disease of the sympathetic itself. An example of such a
secondary affection is the combination of sympathetic symptoms
occurring in progressive muscular atrophy. And, finally, since mental
action of an emotional nature may cause flushing or pallor of the
face, with profuse sweating and variations in the size of the pupil and
prominence of the eyeballs, as well as palpitation or arrest of the
heart, there is reason to believe that symptoms of sympathetic
disease may be produced by cerebral lesions.
62 Ross, Diseases of the Nervous System, 2d ed., i. 686-688.
PATHOLOGY.—The pathological anatomy of the cervical sympathetic

is obscure. This is probably owing to the fact that the ganglia are
rarely examined, and pathologists have not been familiar with their
histology. Lesions of the cervical sympathetic have been described
in almost every imaginable form of disease, and at one time, when
many obscure conditions were blindly termed sympathetic, the
records were filled with descriptions of fatty degeneration or
interstitial inflammation or pigment deposit in the ganglia. As no
actual symptoms of disease of the cervical sympathetic, as now
understood, were present in such cases, it is impossible to believe
that the lesion was other than hypothetical.
The conditions which have been observed in a few carefully-studied

cases of primary disease have been—(1) A parenchymatous
inflammation of the cells of the ganglia, attended by swelling, loss of
nuclei, granular and fatty degeneration, and by atrophy, together with
a degeneration of the fibres issuing from the cells. (2) A sclerotic
process in the connective tissue in and about the ganglia and in the
nerves, resulting in such an increase in the interstitial tissue as to
compress and injure the cells and axis-cylinders. These may be
observed together in the later stages of the disease. (3) In a number
of cases the capillaries within and about the ganglia have been
found dilated, tortuous, and varicose, and hemorrhages from them
are not rare.
SYMPTOMS.—The symptoms of irritation of the cervical sympathetic

are dilatation of the pupil, widening of the palpebral fissure,
protrusion of the eyeball, pallor of the entire side of the face and
head, with slight fall of local temperature and possibly an increased
secretion of perspiration, and an increased frequency of the heart. It
is rarely that these are all observed in any case, dilatation of the
pupil with slight pallor and rapid pulse being the only signs of
irritation as a rule. Such irritation is a less common occurrence than
might be supposed, many lesions which produce pressure even of a
slight degree on the sympathetic having caused symptoms of a
suspension of its function rather than of an increased activity. This is
doubtless due to the non-medullated structure of the fibres, which
thus lack protection from injury.
The symptoms of destructive disease of the cervical sympathetic are

the converse of those just mentioned, and they are all present when
the part is seriously involved. The patient will then have a marked
contraction of the pupil, which no longer responds to light or to
irritation of the skin of the neck, but may change slightly in the act of
accommodation. It resists the action of mydriatics. The vessels of the
choroid and retina may be dilated, as well as those of the iris, in
which case the patient will feel a sense of weariness on any long-
continued attempt to use the eyes. There is no actual disturbance of
vision, and the cornea is not usually flattened, as was formerly
supposed. There is a noticeable narrowing of the palpebral fissure,
the upper lid falling slightly as in a mild state of ptosis, and the lower
lid being slightly elevated. This is due to the paralysis of the muscles
of Müller in the eyelids, which are controlled by the sympathetic. It is
present in 90 per cent. of the recorded cases, and in many the
apparent size of the eye is reduced a half. Retraction of the eyeball
is a less constant symptom, and one which develops only after the
disease has existed some time. It is due partly to the paralysis of the
orbital muscle of Müller, and partly to the decrease in the amount of
fat in the orbit behind the eye. A marked symptom, and one which is
constant, is a dilatation of the vessels of the face, conjunctiva, nasal
mucous membrane, ear, and scalp. This is attended by redness, a
subjective sense of heat, and an actual rise of local temperature,
which may exceed that of the other side by 1.5° F., measured in the
auditory meatus or nose. This vascular congestion has persisted in
some cases for three years. In others it has been followed much
earlier (in nine months) by a partial or complete return to the normal
condition, and even when the local temperature remains higher on
the affected side, the visible congestion and the sensation of heat
may have disappeared. The dilatation, succeeded by the contraction
(normal tone), of the vessels has led to a division of the disease into
two stages, and in a few cases the affected side has become paler
than the other in the second stage. In both stages the part affected is
less sensitive to changes in the external temperature.
An increased secretion of tears and of perspiration has been

supposed to accompany dilatation of the vessels of the skin of the
head inevitably. This is not a constant symptom, as the recent cases
have demonstrated. And no definite statement of the effect of
disease of the cervical sympathetic on the occurrence of dryness or
dampness of the face can be made, both conditions having been
observed. A difference between the degree of moisture on the two
sides of the face on exposure to heat is usually present. Palpitation
of the heart has been an annoying symptom to the patient in many
cases, and is usually associated with a marked slowing of the pulse.
This was reduced from 74 to 66 in Möbius' case,63 and remained
slow for some weeks. The frequency of the heart may, however, be
increased after the first period of slowing, but never reaches a very
high rate (88 in the case cited). A slight atrophy of the affected side
of the face has been observed in several cases, appearing after the
disease has existed for some time. The muscles of the cheek feel
flabby and are slightly sunken; but the condition does not approach
in severity true facial hemiatrophy, nor is it sufficiently rapid to be
considered due to a trophic disturbance. Changes in the secretion of
saliva, dryness of the nasal mucous membrane, and symptoms
referable to paralysis of the intracranial vessels, such as might be
expected from the result of physiological division of the sympathetic,
have only been occasionally observed. Glycosuria has been noted in
a few cases.64
63 Berlin. klin. Woch., 1884, No. 16.
64 Gerhardt, Volkmann's Sammlung klin. Vorträge, No. 209, “Ueber Angioneurosen,”

p. 11.
COURSE.—The course of the disease has been divided into two

stages, as already mentioned, the majority of the symptoms
remaining permanently from the onset. The second stage is
characterized by the cessation of the dilatation of the vessels, by the
appearance of retraction of the eyeball, and by the development of
slight facial atrophy. In the cases where the sympathetic is
extensively destroyed by the lesion no recovery is possible. When it
is simply divided by a wound there has been a considerable degree
of recovery, probably due to a spontaneous union of the divided
ends and re-establishment of the function. From these facts the
prognosis can be deduced.
DIAGNOSIS.—The symptoms are so characteristic that there is no

difficulty in reaching a diagnosis. The most important point in any
case is to determine the cause, care being taken to consider all the
possibilities already mentioned in discussing the causation. The
symptoms of lesion are always unilateral.
TREATMENT.—If the cause can be removed, an indication for
treatment is afforded. Sources of reflex irritation are to be eliminated.
If the sympathetic has been divided by a wound, it may be well to
unite the cut ends, as in suture of other nerves, although this has not
yet been attempted; otherwise there is little hope from any method of
treatment. Electricity has been applied in vain, and galvanization of
the sympathetic in the neck is now regarded by all good authorities
as useless.
Diseases of the thoracic and abdominal sympathetic ganglia and

cords have been suspected, but nothing definite is known of their
symptoms or pathology; the statements which have recently been
made regarding visceral neurosis not being based upon any cases in
which post-mortem lesions were found.
Trophic Neuroses.
TROPHIC NERVES AND NERVOUS CENTRES.—The nutrition of the body

depends upon the nutrition of the individual cells of which it is made
up. Each cell has the power of appropriating from the blood such
substances as will preserve its existence, enable it to perform its
functions, and produce a successor. Whether this power is inherent
in the cell or is controlled by the nervous system is a question upon
which authorities are divided. Those who hold the first position deny
the existence of trophic nervous centres and of trophic nerves from
those centres to the organs and elements of the body, claiming that
this hypothetical trophic system has not been demonstrated
anatomically, and that the facts urged in its support are capable of
another interpretation. Those who believe in the existence of a
trophic system have been able to demonstrate the existence of fine
peripheral nerve-fibres passing to and ending in individual cells of
the skin, glands, and other organs,65 and have brought forward a
large collection of facts which merit a careful examination.66 They are
as follows:
65 Bericht der Section für Dermatologie, Versammlung Deutscher aerzte, Strasburg,
1885; Vierteljahrschrift für Dermatologie und Syphilis, 1885, 4 Heft, S. 683.
66 “Tropho-neurosen,” Real Cyclopædie f. d. gesammt. Medicin, vol. xiv., 1883; Erb,

Ziemssen's Cyclopædia, xi. pp. 408-423.
ATROPHY.—When a nerve is cut certain changes occur in it which are

known as Wallerian degeneration.67 This affects the peripheral end
of a severed nerve, the peripheral end of a severed anterior nerve-
root, and the central end of a posterior nerve-root. To maintain its
integrity a motor nerve must be in direct continuity with a normal cell
of the anterior cornu of the spinal cord; a sensory nerve must be in
connection with the intervertebral spinal ganglion on the posterior
nerve-root. Nerves which pass between two such ganglia do not
degenerate when cut. The degeneration consists68 in a coagulation
of the myelin in the medullary sheath, a fatty degeneration of the
coagulum, and a gradual absorption of the débris. The axis-cylinder
is compressed, and finally disintegrated, by a mass of protoplasm
which develops about the nuclei of the interannular segments, and
after undergoing fatty degeneration its débris becomes mingled with
that of the myelin, and is also absorbed. The sheath of Schwann,
whose nuclei have in the mean time increased by a process of
subdivision, is partly filled by the protoplasm (from which the new
axis-cylinder develops if regeneration occurs), remaining as a fine
thread of connective tissue when all other traces of the nerve-fibre
have disappeared. There may be a proliferation of cells of the endo-
and perineurium at the same time which aids in the transformation of
the nerve into a connective-tissue strand. This process of
degeneration involves the terminal plates by which the nerves join
the muscles, but the terminations of the sensory nerves—i.e. tactile
corpuscles—do not appear to be affected. The central end of the cut
nerve may display a similar change for a distance not greater than
one centimeter; it usually develops a bulbous swelling of connective
tissue, and retains its conducting power indefinitely.
67 Waller, Philosoph. Transactions, 1850, ii. p. 423; Comptes rendus de l'Acad. de
Sci., 1852-55.
68 Ranvier, Leçons sur l'Histologie de Système nerveux, Paris, 1878; Von
Recklinghausen, Pathologie der Ernahrung, 1883.
Degeneration in the tracts of the spinal cord occurs after various

forms of lesion,69 and is similar in its processes to degeneration in
the peripheral nerves. The increase in the connective-tissue
elements is more noticeable in contrast with the parts unaffected,
and from the density of the tract involved the result has been called
sclerosis. The recent researches of Homen70 have shown that the
process of degeneration begins in the entire length of the affected
tract, and does not proceed from the point of lesion onward, as was
formerly supposed.
69 See Vol. V., “Myelitis—The Secondary Scleroses,” p. 892; Schültze, Arch. für
Psych., xiv. 2.
70 Fortschritte der Medicin, 1885, No. 9.
When a muscle is separated from its connection with the central

nervous system, either by a division of the nerve passing to it or by a
destruction of the cells in the anterior cornu of the spinal cord from
which that nerve arises, it undergoes an atrophy which is peculiar in
being immediate and rapidly progressive, thus contrasting strongly
with the gradual and slighter atrophy from disuse in cases of cerebral
paralysis where the cells mentioned and the nerve-fibres are intact.
There is at first a simple diminution in the number of the fibrillæ of
which the muscular fibre is made up, together with an increase in the
interstitial connective tissue nuclei. Then an albuminoid and fatty
degeneration of the muscular elements occurs, with a proliferation of
muscle-corpuscles or nuclei, and a gradual absorption of the débris.
The interstitial connective tissue then increases rapidly, forming
fibrous bands through the degenerated muscle which compress the
few muscular fibres remaining, until as a result the muscle is
transformed into a mere ribbon of connective tissue without any
power of contractility.71 As these changes go on the electrical
reactions change, the three degrees of reaction of degeneration
corresponding to the three stages of atrophy described.72 These
phenomena of nerve- and muscle-degeneration are observed in
traumatic or idiopathic neuritis, in acute and chronic poliomyelitis
anterior, in general myelitis involving the anterior cornua, and in
bulbar paralysis.
71 Hayem, G., Recherches sur l'Anatomie pathologique des Atrophies musculaires,
Paris, 1873; Ross, Diseases of the Nervous System, vol. i. p. 238.
72 See Vol. V., “Electric Reactions.”
The influence of the nervous system on the nutrition of the bones

has also been ascertained. When a bone is developing, a lesion of
the nerve to it, or of the deeper portion of the anterior cornua of the
spinal cord from which these nerves arise, will modify and partly
arrest its growth. This is often seen in anterior poliomyelitis and in
hemiatrophy of the face occurring in children. In the adult a no less
marked effect is produced, although the results are less noticeable.
A condition known as osteoporosis is caused, consisting of an
enlargement of the Haversian canals and an infiltration of fatty
matter into them and an actual decrease in all the inorganic
constituents of the bone, which loses in weight, becomes thinner and
more fragile, so that spontaneous fractures may occur.73 This
condition has been noticed more frequently in diseases of the spinal
cord than in neuritis; it is said to occur in locomotor ataxia. It has
been found in a few cases of long-standing hemiplegia and also in
dementia paralytica, no explanation of its pathogeny in these
instances, however, being offered. In a case of ataxia with a lesion in
the medulla which involved the nuclei of the fifth, ninth, tenth, and
eleventh nerves on one side, all the teeth of the upper jaw on that
side fell out within a few weeks, those in the lower jaw remaining.74
Changes in the nutrition of the bones have also been recorded in
cases of progressive muscular atrophy in the paralyzed limbs.75
73 Weir Mitchell, Amer. Journ. of the Med. Sci., 1873, p. 113; Charcot, Arch. de Phys.,
1874, p. 166.
74 Demange, Rev. de Médecine, 1882, p. 247.
75 Friedreich, Progressive Muskelatrophie, p. 347, 1873.

The condition of the skin and its appendages is influenced decidedly
by changes in the nervous system, either in the nerves, in the spinal
ganglia, or in the central gray matter. Here it is the sensory nerves
which convey the trophic influence, not the motor nerves, as in the
cases hitherto considered; and when the lesion producing trophic
changes in the skin is central, it is situated in the posterior cornua of
the spinal cord or in the gray matter near the central canal. The
glossy skin seen on the fingers after injuries to the nerves is a type
of such atrophy from disturbance of trophic impulses. Glossy fingers
present a smooth, shining appearance, are dry from the diminution in
the secretion of sweat, feel soft and satin-like to the touch from the
marked thinning of the skin, and frequently show a defective or
irregular growth of the nails, which may be ridged, curved, or
deformed.76 They are red and mottled from accompanying vaso-
motor paralysis, and are usually hot and painful. Changes in the
pigmentation of the skin and hair are recorded as a not infrequent
accompaniment of severe neuralgia and as a result of great mental
anxiety. Thus in several cases of supraorbital neuralgia the eyebrow
on the affected side has turned white; in infraorbital neuralgia the
beard has become gray; and in both the hair has been observed to
fall out.77 The sudden turning white of the hair is ascribed to a
swelling of the hair by air within it.78 In one case, frequently cited, the
hair and nails fell out after a stroke of lightning.
76 Weir Mitchell, Injuries of Nerves. See also Vol. IV. p. 683.
77 Seeligmüller, Lehrbuch der Krankheiten d. Peripheren Nerven, p. 157, 1882.
78 Arch. f. Path. Anat., xxxv. 5, 575, Landois.
When a gland is cut off from its nervous connection with the cord or
cerebral axis by section of its nerves, its function is impaired and its
nutrition suffers, so that after a time it loses weight and undergoes a
progressive total atrophy. This has been proven experimentally in
animals in the submaxillary gland. It has been observed in the
testicle in man after division of the spermatic nerve (Nélaton) and
after destruction of the spinal cord by traumatic and idiopathic
myelitis (Klebs, Föster).79 The sweat-glands are known to be under
the control of a central nervous mechanism, as cases of
hyperidrosis, anidrosis, and chromiodrosis prove;80 and an atrophy of
them and of the sebaceous glands has been observed81 after
nervous lesions.
79 Cited by Samuel, Realcyclop., loc. cit. See also Obolensky, Centralblatt für med.
Wissen., 1867, 5, 497.
80 See Vol. IV. pp. 583-586.
81 See Vol. IV. pp. 683 et seq.
Progressive hemiatrophy of the face is treated elsewhere. The

following case of progressive hemiatrophy of the entire body may be
mentioned here: A boy, aged fourteen, dislocated his ankle, which in
a few days became swollen, red, hot, and painful. The inflammation
extended up the leg, but did not involve the knee, and soon
subsided. After a short time the foot began to atrophy. The atrophy
extended up the leg, and involved the thigh; it then progressed to the
trunk and the arm, and lastly to the face on the affected side, until in
the course of two years there had developed a unilateral atrophy of
the entire body. Muscles, fat, and bones were all affected, but no
difference in the skin or hair of the two sides was noticed. Fibrillary
tremors were present in the muscles. The electric reactions were not
altered, but were gradually lost. There was a hypersensitiveness to
touch and to cold, but no other sensory disturbance. The boy was
alive and fairly well when the case was reported.82 It is unique.
82 Heuschen, Schmidt's Jahrbuch., vol. cxcviii. p. 130.
These various instances of atrophy cannot be ascribed to simple

disuse, since they differ markedly in their pathological changes and
in the rapidity of their progress from such atrophy. Nor are they to be
referred to vaso-motor disturbances, since in many cases no
vascular changes are evident. Their distribution in the body often
corresponds exactly with that of peripheral nerves, and they
accompany nerve lesions too frequently to be explained on any
theory of coincidence. There are many authorities, however, who
refuse to ascribe them to a lesion of trophic nerves.83 In regard to the
degeneration of nerves it is said that each nerve axis-cylinder is a
part of the nerve-cell from which it arises, and hence destruction of
the cell or division of the cylinder, by disturbing the unity of
existence, results in the death of the part. The fibre shares all the
changes of nutrition which the nerve-cell undergoes, and if
separated from it necessarily perishes. To this it is replied that
trophic paths and motor paths are distinct at some points in their
course, at least in the central nervous system, since each can be
affected alone. Erb, who has studied this subject carefully,84 believes
that trophic are distinct from motor centres in the spinal cord, but that
both impulses may be conveyed by the same axis-cylinder in the
peripheral nerves—a middle ground which is widely accepted. It is
now known that each axis-cylinder is made up of several fibrils, so
that this theory gains probability. This would also explain the
occurrence of atrophy in the muscles, the trophic centres being
affected when the muscle atrophies, and unaffected when it is
paralyzed without atrophy. Mayer, however, denies this explanation
of the muscular atrophy, holding that the motor system, cell, nerve,
and muscle-fibre, forms a nutritive as well as functional unit, and that
the simple suspension of function, by interfering with the special
conditions of nutrition attendant upon physiological excitement, is
competent to cause a pathological change. To this it is replied that
the parts of the motor system are not interdependent, since disease
of the muscle does not produce degeneration of the nerve and of the
cell, and the fact of a degeneration in a peripheral direction alone is
evidence of central trophic influence. The attempt to ascribe trophic
changes in the skin, nails, and hair to vaso-motor disturbance has
been equally unsuccessful in covering all the observed cases.
83 See Handfield Jones, St. George's Hospital Reports, 1868, vol. iii. pp. 89-110;
Sigmund Meyer, Hermann's Handbuch d. Physiol., ii. Th. 2, “Trophische Nerven,”
1879; Gowers, Diseases of the Brain, 1885, p. 4.
84 Arch. f. Psych., v. S. 445, 1875; also Ziemssen's Cyclo., vol. xiii. p. 117 (Amer.
trans.); also Deut. Arch. f. klin. Med., v. S. 54.
FIG. 58.
Diagram of the Arrangement and Connection of Motor and Trophic

Centres and Fibres in the Spinal Cord and Motor Nerve (after Erb): a,
motor fibre of spinal cord from the brain to d, the motor cell, which is
joined to the muscle m by the motor nerve; b, trophic cell in the spinal
cord for the muscle, to which it is joined by the trophic fibre bʹ; c, trophic
cell in the spinal cord for the motor nerve, to which it is joined by the
trophic fibre cʹ; s, a fibre bringing sensory (reflex) impulses to the cell.
If d is destroyed, the fibres from b and c perish with it, and the result is
paralysis and atrophy of the muscle and degeneration in the motor nerve
—e.g. poliomyelitis anterior. If b is destroyed, the muscle atrophies, and
paralysis is a secondary result—e.g. progressive muscular atrophy. If c is
destroyed, the nerve degenerates, and paralysis and atrophy of the
muscle are secondary results—e.g. neuritis with reaction of
degeneration. If a is destroyed, voluntary power is lost, but reflex power
remains, and no atrophic changes occur—e.g. lateral sclerosis. If the
motor nerve is cut between d and m, the result is the same beyond the
division as when the motor cell is destroyed.
HYPERTROPHY.—Trophic changes are not limited to the process of

atrophy. There are conditions of hypertrophy of supposed nervous
origin. Samuel considers the hypertrophy of one testicle which
attends atrophy of the other from section of its nerve as an example
of this. It has been ascertained that one kidney hypertrophies when
the other is atrophied or extirpated. When the spleen is removed the
lymphatic glands increase in size. But these facts are capable of
another explanation—viz. that increased demand upon the organ
leads to its increased growth. Hypertrophy of the skin and of the
tongue is seen in cretins in contrast with the deformity of the body
and atrophy of the limbs. A hemihypertrophy of the face has been
noticed in several cases, the counterpart of hemiatrophy; and in one
case a unilateral hypertrophy of the entire body was observed.85 The
local thickening of the skin known as ichthyosis hystrix, and other
hypertrophies of the skin, certain deposits of pigment, and vitiligo,
have been ascribed to nervous causes. Mitchell has recorded cases
of abnormal growth of the nails and hair after injuries to the nerves,
and similar phenomena have followed central lesions. He has also
described a thickening of the skin of the first three fingers and of the
back of the hand following a wound of the brachial plexus. These
conditions of the skin and its appendages indicate an abnormal
activity in the cells of the affected part, a rapid metabolism and
reproduction, resulting in an undue production of tissue, apparently
dependent on nervous impulses reaching the cells from a distance.
The insane ear may be mentioned in this connection as a trophic
disturbance due to central lesion.
85 Ziel, Virchow's Archiv, xci., S. 92.
MYXŒDEMA (cachexie pachydermique) is a disturbance of nutritive

processes characterized by a production of mucin, which is
deposited in all the tissues of the body, but especially in the
subdermal connective tissue.86 It is considered by the majority of
authors a trophic neurosis, and is therefore considered here.
86 Sir William W. Gull, “On a Cretinoid State supervening in Adult Life,” Trans. Clin.
Soc. London, 1874, vol. vii. p. 170; Ord, “On Myxœdema,” Med.-Chir. Trans., 1878,
vol. lxi. p. 57; Mahomed, Lancet, 1881, ii. No. 26; Hadden, Brain, 1882; W. A.
Hammond, Neurological Contributions, 1881, i. p. 36; Ballet, Archives de Neurologie,
1881, vol. iii. p. 30; Schmidt's Jahrbucher, vol. clxxxix. p. 30, and cxcviii. 264; “The
Brown Lectures,” Victor Horseley, Lancet, Jan., 1886.
PATHOLOGY.—In the few autopsies which have been made an

increase in the connective tissue of all the organs has been found, in
the meshes of which a thick, transparent, slimy substance (called
animal gum), consisting of mucin, is present. This may compress
and destroy the parenchyma of the organs involved. There is also
found a thickening of the coats (adventitia and media) of the vessels.
An atrophy of the thyroid gland has occurred in every case, and
experimental extirpation of the thyroid in animals produces
symptoms so nearly identical with those of myxœdema that this is
considered the chief pathological feature of the disease. Whether
this atrophy is due to a compression by the mucin deposited, or is
due to a disease of the trophic centres of the thyroid in the medulla,
or is a primary affection of the gland, remains to be determined.
ETIOLOGY.—The actual causation is unknown. Cold and mental shock

have been considered exciting causes in some cases. Women are
much more liable to the disease than men, and it develops after the
age of forty in the majority of cases. It may occur in childhood and
result in a cretinoid state. Syphilis and tuberculosis do not appear to
be etiological factors.
SYMPTOMS.—The disease begins gradually, and the nervous
symptoms or the local œdema may appear together or in
succession. The patient notices a thickening of the skin, which
becomes dry, rough, and scaly. The thickening is uniform and
involves the entire body. It is most marked where the subdermal
connective tissue is loose, as in the cheeks, lips, eyelids, and in all
parts where the skin is thrown into folds. The hands and feet do not
escape. The thickened skin is hard, and does not pit on pressure,
thus differing from ordinary œdematous swelling. It appears of a
waxy color, and is free from perspiration, the sweat-glands becoming
atrophied from pressure. The hair may fall out or become woolly and
brittle, and may change its color. In a few cases spots of pigment
have appeared on various regions.87 The nails are brittle. The teeth
are carious. The mucous membranes show similar changes, and the
mouth and tongue, rectum and vagina, may be so swollen as to
impair their respective functions. Digestive disturbances,
constipation alternating with diarrhœa, and uterine hemorrhages,
which occur, are ascribed to this cause. Albumen is occasionally
found in the urine, but is not a constant symptom. The nervous
symptoms are constant. The patients complain of paræsthesiæ and
anæsthesia of the extremities or over the entire body, and the
special senses may be impaired, as well as the tactile sense. They
are very liable to severe attacks of neuralgia. They suffer from
subjective sensations of cold, and are easily affected by changes of
temperature. Motion is interfered with; tremors occur early;
movements become slow and awkward; the gait is unsteady; the
voice is rough and nasal; but no true paralysis or muscular atrophy
has been observed. The patella-tendon reflex is occasionally lost,
but not in all cases.
87 Allan McLane Hamilton, Journ. Nerv. and Ment. Dis., 1885, April, p. 180.
These symptoms have been ascribed to the pressure of the mucin

upon the terminal filaments of the nerves, and also to changes in the
central nervous system. That the latter theory is probably correct is
shown by the occurrence of mental symptoms in the majority of
cases. The patients become apathetic and all mental action is slowly
performed. Indifference to surroundings, loss of memory, and
inability to concentrate the attention may be succeeded by transient
delirium, hallucinations, and occasionally by delusions of
persecution, and the patient finally lapses into a state of imbecility. If
the disease develops in early life, education is impossible, and the
patient remains in an infantile condition.
Whether the changes in the nervous system are due to pressure by

deposit of mucin (Hadden), or are due to an altered nutrition of the
most delicate tissues of the body consequent upon the general
metabolic derangement (Horseley), is undetermined. In experimental
myxœdema the degenerative processes have been found in the
nerve-cells.
There are no symptoms referable to the heart or lungs, and if

cirrhosis of the kidney and liver develop, their symptoms supervene
upon and are secondary to those of myxœdema. High arterial
tension has been noticed in the majority of the cases.
The COURSE of the disease is a chronic one, and is progressive.

There are, however, intermissions in the severity of the symptoms in
some cases. Recovery does not occur.
DIAGNOSIS.—The diagnosis from the accumulation of fat is made by

observing the thickening of the nose, lips, fingers, and tongue, and
the changes in the skin and its appendages. Scleroderma is not
universal like myxœdema. In scleroderma the skin is harder and
more adherent to subjacent parts, is not transparent and waxy, and
the nervous symptoms are wanting. Cretinism seems to be closely
allied to myxœdema, but is only observed before the age of seven
and is accompanied by hypertrophy of the thyroid gland.
TREATMENT.—The treatment is only palliative. Simple nutritious diet,

especially milk diet, with the use of such tonics as iron and quinine,
has been found useful. The progress of the disease is hastened by
exposure to cold, and in a very warm climate the symptoms may
remain stationary for several years. Jaborandi or pilocarpine has
been used in some cases with a moderate degree of success. Nitro-

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Analyzing Health Data in R for SAS

Users 1st Edition Monika Maya Wahi

SAS for R users : a book for budding data scientists

Clinical trial data analysis with R and SAS Second

Analysis of Correlated Data with SAS and R Mohamed M.

Analyzing High-Dimensional Gene Expression and DNA

Analyzing Data through Probabilistic Modeling in

Survival Analysis with Interval Censored Data A

Infographics Powered by SAS:: Data Visualization

Clinical Data Quality Checks for CDISC Compliance Using

© 2018 by Taylor & Francis Group, LLC

No claim to original U.S. Government works

Printed on acid-free paper

International Standard Book Number-13: 978-1-4987-9588-3 (Hardback)

Library of Congress Cataloging‑in‑Publication Data

Names: Wahi, Monika, author. | Seebach, Peter, author

Visit the Taylor & Francis Web site at

and the CRC Press Web site at

1. Differences between SAS and R .................................................................1

2. Preparing Data for Analysis....................................................................... 27

Creating Indicator Variables for Two-Level Categories....................... 61

3. Basic Descriptive Analysis ....................................................................... 133

Making “Table 1”—Continuous Outcome ............................................... 156

4. Basic Regression Analysis ........................................................................ 197

Logistic Regression Model Presentation ............................................. 249

References ........................................................................................................... 287

When I, Monika Wahi, gave a presentation at the Effective Applications of the

Monika Wahi and Peter Seebach

Monika Wahi, MPH, CPH obtained a bachelor of science in costume design

Peter Seebach was raised by mathematicians, and never fully recovered.

Installation of PC Version: SAS versus R

Licensing Differences: SAS versus R

SAS Components versus R Packages

Maintaining Current Versions in SAS versus R

SAS versus R User Communities

SAS versus R User Interfaces

Code Documentation and Metadata: SAS versus R

* A close colleague has referred to this phenomenon as “biostatistics paper hell.”

An analogy can be made to making a movie. Although viewers perceive the

be watched and understood by an outside programmer. This is especially

A Focus on SAS Data Handling

steps by reading row by row (observation by observation) and executing

Comparison to R Data Handling

NATURE.—The nature of the disease is a matter of deduction from the

DIAGNOSIS.—The diagnosis rests upon the development of vaso-

PROGNOSIS.—Life is not endangered by this disease, no fatal cases

TREATMENT.—The methods of treatment have varied, and none are

The pain occurring in the early stages is often so severe as to

Diseases of the Cervical Sympathetic.

ETIOLOGY.—Diseases of the cervical sympathetic ganglia or cord may

PATHOLOGY.—The pathological anatomy of the cervical sympathetic

The conditions which have been observed in a few carefully-studied

SYMPTOMS.—The symptoms of irritation of the cervical sympathetic

The symptoms of destructive disease of the cervical sympathetic are

An increased secretion of tears and of perspiration has been

64 Gerhardt, Volkmann's Sammlung klin. Vorträge, No. 209, “Ueber Angioneurosen,”

COURSE.—The course of the disease has been divided into two

DIAGNOSIS.—The symptoms are so characteristic that there is no

Diseases of the thoracic and abdominal sympathetic ganglia and

TROPHIC NERVES AND NERVOUS CENTRES.—The nutrition of the body

66 “Tropho-neurosen,” Real Cyclopædie f. d. gesammt. Medicin, vol. xiv., 1883; Erb,

ATROPHY.—When a nerve is cut certain changes occur in it which are

Degeneration in the tracts of the spinal cord occurs after various