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HEALTHCARE
ANALYTICS
Wiley Series in
Operations Research and Management Science

A complete list of the titles in this series appears at the end of this volume.
HEALTHCARE
ANALYTICS
From Data to Knowledge to Healthcare
Improvement

HUI YANG
Florida, USA

EVA K. LEE
Atlanta, USA
Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved

Published by John Wiley & Sons, Inc., Hoboken, New Jersey

Published simultaneously in Canada

No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or
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Library of Congress Cataloging-in-Publication Data:

Names: Yang, Hui, 1981- author. | Lee, Eva K., author.

Title: Healthcare analytics : from data to knowledge to healthcare
improvement / Hui Yang, Eva K. Lee.
Description: Hoboken, New Jersey : John Wiley & Sons, 2016. | Includes
bibliographical references and index.
Identifiers: LCCN 2015047966| ISBN 9781118919392 (cloth) | ISBN 9781118919408
(online) | ISBN 9781119374664 (ePDF) | ISBN 9781119374640 (ePub)
Subjects: LCSH: Medical care–Data processing. | Medical care–Information
services.
Classification: LCC R858.A1 Y36 2016 | DDC 362.10285–dc23 LC record available at
http://lccn.loc.gov/2015047966

Typeset in 10/12pt TimesLTStd by SPi Global, Chennai, India

Printed in the United States of America

CONTENTS

LIST OF CONTRIBUTORS xvii

PREFACE xxi

PART I ADVANCES IN BIOMEDICAL AND HEALTH

INFORMATICS 1

1 Recent Development in Methodology for Gene Network Problems

and Inferences 3
Sung W. Han and Hua Zhong
1.1 Introduction 3
1.2 Background 5
1.3 Genetic Data Available 7
1.4 Methodology 7
1.4.1 Structural Equation Model 8
1.4.2 Score Function Formulation 9
1.4.3 Two-Stage Learning 12
1.4.4 Further Issues 13
1.5 Search Algorithm 13
1.5.1 Global Optimal Solution Search 13
1.5.2 Heuristic Algorithm for a Local Optimal Solution 14
1.6 PC Algorithm 15
vi CONTENTS

1.7 Application/Case Studies 16

1.7.1 Skin Cutaneous Melanoma (SKCM) Data from the
TCGA Data Portal Website 16
1.7.2 The CCLE (Cancer Cell Line Encyclopedia) Project 20
1.7.3 Cellular Signaling Network in Flow Cytometry Data 20
1.8 Discussion 23
1.9 Other Useful Softwares 23
Acknowledgments 24
References 24

2 Biomedical Analytics and Morphoproteomics: An Integrative

Approach for Medical Decision Making for Recurrent or
Refractory Cancers 31
Mary F. McGuire and Robert E. Brown
2.1 Introduction 31
2.2 Background 32
2.2.1 Data 33
2.2.2 Tools 33
2.2.3 Algorithms 34
2.2.4 Literature Review 35
2.3 Methodology 37
2.3.1 Morphoproteomics (Fig. 2.1(1–3)) 39
2.3.2 Biomedical Analytics (Fig. 2.1(4–10)) 40
2.3.3 Integrating Morphoproteomics and Biomedical
Analytics 44
2.4 Case Studies 46
2.4.1 Clinical: Therapeutic Recommendations for Pancreatic
Adenocarcinoma 46
2.4.2 Clinical: Biology Underlying Exceptional Responder
in Refractory Hodgkin’s Lymphoma 48
2.4.3 Research: Role of the Hypoxia Pathway in Both
Oncogenesis and Embryogenesis 50
2.5 Discussion 51
2.6 Conclusions 52
Acknowledgments 53
References 53

3 Characterization and Monitoring of Nonlinear Dynamics and Chaos

in Complex Physiological Systems 59
Hui Yang, Yun Chen, and Fabio Leonelli
3.1 Introduction 59
3.2 Background 61
3.3 Sensor-Based Characterization and Modeling of Nonlinear
Dynamics 65
CONTENTS vii

3.3.1 Multifractal Spectrum Analysis of Nonlinear Time

Series 65
3.3.2 Recurrence Quantification Analysis 75
3.3.3 Multiscale Recurrence Quantification Analysis 78
3.4 Healthcare Applications 80
3.4.1 Nonlinear Characterization of Heart Rate Variability 81
3.4.2 Multiscale Recurrence Analysis of Space–Time
Physiological Signals 85
3.5 Summary 88
Acknowledgments 90
References 90

4 Statistical Modeling of Electrocardiography Signal for Subject

Monitoring and Diagnosis 95
Lili Chen, Changyue Song, and Xi Zhang
4.1 Introduction 95
4.2 Basic Elements of ECG 96
4.3 Statistical Modeling of ECG for Disease Diagnosis 99
4.3.1 ECG Signal Denoising 100
4.3.2 Waveform Detection 105
4.3.3 Feature Extraction 106
4.3.4 Disease Classification and Diagnosis 111
4.4 An Example: Detection of Obstructive Sleep Apnea from
a Single ECG Lead 115
4.4.1 Introduction to Obstructive Sleep Apnea 115
4.5 Materials and Methods 115
4.5.1 Database 115
4.5.2 QRS Detection and RR Correction 116
4.5.3 R Wave Amplitudes and EDR Signal 117
4.5.4 Feature Set 117
4.5.5 Classifier Training with Feature Selection 118
4.6 Results 118
4.6.1 QRS Detection and RR Correction 118
4.6.2 Feature Selection 118
4.6.3 OSA Detection 120
4.7 Conclusions and Discussions 121
References 121

5 Modeling and Simulation of Measurement Uncertainty in Clinical

Laboratories 127
Varun Ramamohan, James T. Abbott, and Yuehwern Yih
5.1 Introduction 127
5.2 Background and Literature Review 129
viii CONTENTS

5.2.1 Measurement Uncertainty: Background and Analytical

Estimation 130
5.2.2 Uncertainty in Clinical Laboratories 134
5.2.3 Uncertainty in Clinical Laboratories: A System
Approach 136
5.3 Model Development Guidelines 138
5.3.1 System Description and Process Phases 138
5.3.2 Modeling Guidelines 139
5.4 Implementation of Guidelines: Enzyme Assay Uncertainty
Model 141
5.4.1 Calibration Phase 142
5.4.2 Sample Analysis Phase 149
5.4.3 Results and Analysis 150
5.5 Discussion and Conclusions 152
References 154

6 Predictive Analytics: Classification in Medicine and Biology 159

Eva K. Lee
6.1 Introduction 159
6.2 Background 161
6.3 Machine Learning with Discrete Support Vector Machine
Predictive Models 163
6.3.1 Modeling of Reserved-Judgment Region for
General Groups 164
6.3.2 Discriminant Analysis via Mixed-Integer Programming 165
6.3.3 Model Variations 167
6.3.4 Theoretical Properties and Computational Strategies 170
6.4 Applying DAMIP to Real-World Applications 170
6.4.1 Validation of Model and Computational Effort 171
6.4.2 Applications to Biological and Medical Problems 171
6.5 Summary and Conclusion 182
Acknowledgments 183
References 183

7 Predictive Modeling in Radiation Oncology 189

Hao Zhang, Robert Meyer, Leyuan Shi, Wei Lu, and Warren D’Souza
7.1 Introduction 189
7.2 Tutorials of Predictive Modeling Techniques 191
7.2.1 Feature Selection 191
7.2.2 Support Vector Machine 192
7.2.3 Logistic Regression 193
7.2.4 Decision Tree 193
7.3 Review of Recent Predictive Modeling Applications in Radiation
Oncology 194
7.3.1 Machine Learning for Medical Image Processing 194
CONTENTS ix

7.3.2 Machine Learning in Real-Time Tumor Localization 196

7.3.3 Machine Learning for Predicting Radiotherapy
Response 197
7.4 Modeling Pathologic Response of Esophageal Cancer to
Chemoradiotherapy 199
7.4.1 Input Features 200
7.4.2 Feature Selection and Predictive Model Construction 200
7.4.3 Results 202
7.4.4 Discussion 204
7.5 Modeling Clinical Complications after Radiation Therapy 205
7.5.1 Dose-Volume Thresholds: Relationship to OAR
Complications 205
7.5.2 Modeling the Radiation-Induced Complications via
Treatment Plan Surface 206
7.5.3 Modeling Results 208
7.6 Modeling Tumor Motion with Respiratory Surrogates 211
7.6.1 Cyberknife System Data 211
7.6.2 Modeling for the Prediction of Tumor Positions 212
7.6.3 Results of Tumor Positions Modeling 212
7.6.4 Discussion 214
7.7 Conclusion 215
References 215

8 Mathematical Modeling of Innate Immunity Responses of Sepsis:

Modeling and Computational Studies 221
Chih-Hang J. Wu, Zhenshen Shi, David Ben-Arieh,
and Steven Q. Simpson

8.1 Background 221

8.2 System Dynamic Mathematical Model (SDMM) 223
8.3 Pathogen Strain Selection 224
8.3.1 Step 1: Kupffer Local Response Model 224
8.3.2 Step 2: Neutrophils Immune Response Model 228
8.3.3 Step 3: Damaged Tissue Model 233
8.3.4 Step 4: Monocytes Immune Response Model 234
8.3.5 Step 5: Anti-inflammatory Immune Response Model 237
8.4 Mathematical Models of Innate Immunity of AIR 239
8.4.1 Inhibition of Anti-inflammatory Cytokines 239
8.4.2 Mathematical Model of Innate Immunity of AIR 239
8.4.3 Stability Analysis 241
8.5 Discussion 247
8.5.1 Effects of Initial Pathogen Load on Sepsis Progression 247
8.5.2 Effects of Pro- and Anti-inflammatory Cytokines
on Sepsis Progression 250
8.6 Conclusion 254
References 254
x CONTENTS

PART II ANALYTICS FOR HEALTHCARE DELIVERY 261

9 Systems Analytics: Modeling and Optimizing Clinic Workflow and

Patient Care 263
Eva K. Lee, Hany Y. Atallah, Michael D. Wright, Calvin Thomas IV,
Eleanor T. Post, Daniel T. Wu, and Leon L. Haley Jr
9.1 Introduction 264
9.2 Background 266
9.3 Challenges and Objectives 267
9.4 Methods and Design of Study 268
9.4.1 ED Workflow and Services 269
9.4.2 Data Collection and Time-Motion Studies 270
9.4.3 Machine Learning for Predicting Patient
Characteristics and Return Patterns 274
9.4.4 The Computerized ED System Workflow Model 277
9.4.5 Model Validation 282
9.5 Computational Results, Implementation, and ED Performance
Comparison 285
9.5.1 Phase I: Results 285
9.5.2 Phase I: Adoption and Implementation 288
9.5.3 Phase II: Results 288
9.5.4 Phase II: Adoption and Implementation 290
9.6 Benefits and Impacts 292
9.6.1 Quantitative Benefits 294
9.6.2 Qualitative Benefits 296
9.7 Scientific Advances 297
9.7.1 Hospital Care Delivery Advances 297
9.7.2 OR Advances 298
Acknowledgments 298
References 299

10 A Multiobjective Simulation Optimization of the Macrolevel Patient

Flow Distribution 303
Yunzhe Qiu and Jie Song
10.1 Introduction 303
10.2 Literature Review 305
10.2.1 Simulation Modeling on Patient Flow 305
10.2.2 Multiobjective Patient Flow Optimization Problems 306
10.2.3 Simulation Optimization 307
10.3 Problem Description and Modeling 308
10.3.1 Problem Description 308
10.3.2 System Modeling 310
CONTENTS xi

10.4 Methodology 312

10.4.1 Simulation Model Description 312
10.4.2 Optimization 313
10.5 Case Study: Adjusting Patient Flow for a Two-Level Healthcare
System Centered on the Puth 316
10.5.1 Background and Data 316
10.5.2 Simulation under Current Situation 318
10.5.3 Model Validation 320
10.5.4 Optimization through Algorithm 1 321
10.5.5 Optimization through Algorithm 2 322
10.5.6 Comparison of the Two Algorithms 327
10.5.7 Managerial Insights and Recommendations 328
10.6 Conclusions and the Future Work 329
Acknowledgments 330
References 331

11 Analysis of Resource Intensive Activity Volumes in US Hospitals 335

Shivon Boodhoo and Sanchoy Das
11.1 Introduction 335
11.2 Structural Classification of Hospitals 337
11.3 Productivity Analysis of Hospitals 339
11.4 Resource and Activity Database for US Hospitals 341
11.4.1 Medicare Data Sources for Hospital Operations 343
11.5 Activity-Based Modeling of Hospital Operations 344
11.5.1 Direct Care Activities 344
11.5.2 The Hospital Unit of Care (HUC) Model 347
11.5.3 HUC Component Results by State 350
11.6 Resource use Profile of Hospitals from HUC Activity Data 351
11.6.1 Comparing the Resource Use Profile of States 353
11.6.2 Application of the Hospital Classification Rules 355
11.7 Summary 357
References 358

12 Discrete-Event Simulation for Primary Care Redesign: Review

and a Case Study 361
Xiang Zhong, Molly Williams, Jingshan Li, Sally A. Kraft,
and Jeffrey S. Sleeth
12.1 Introduction 361
12.2 Review of Relevant Literature 362
12.2.1 Literature on Primary Care Redesign 362
12.2.2 Literature on Discrete-Event Simulation in Healthcare 366
12.2.3 UW Health Improvement Projects 369
xii CONTENTS

12.3 A Simulation Case Study at a Pediatric Clinic 369

12.3.1 Patient Flow 369
12.3.2 Model Development 371
12.3.3 Model Validation 376
12.4 What–If Analyses 376
12.4.1 Staffing Analysis 376
12.4.2 Resident Doctor 377
12.4.3 Schedule Template Change 377
12.4.4 Volume Change 379
12.4.5 Room Assignment 379
12.4.6 Early Start 380
12.4.7 Additional Observations 382
12.5 Conclusions 382
References 382

13 Temporal and Spatiotemporal Models for Ambulance Demand 389

Zhengyi Zhou and David S. Matteson
13.1 Introduction 389
13.2 Temporal Ambulance Demand Estimation 391
13.2.1 Notation 392
13.2.2 Factor Modeling with Constraints and Smoothing 393
13.2.3 Adaptive Forecasting with Time Series Models 395
13.3 Spatiotemporal Ambulance Demand Estimation 398
13.3.1 Spatiotemporal Finite Mixture Modeling 400
13.3.2 Estimating Ambulance Demand 403
13.3.3 Model Performance 405
13.4 Conclusions 409
References 410

14 Mathematical Optimization and Simulation Analyses for Optimal

Liver Allocation Boundaries 413
Naoru Koizumi, Monica Gentili, Rajesh Ganesan, Debasree DasGupta,
Amit Patel, Chun-Hung Chen, Nigel Waters, and Keith Melancon
14.1 Introduction 414
14.2 Methods 416
14.2.1 Mathematical Model: Optimal Locations of Transplant
Centers and OPO Boundaries 416
14.2.2 Discrete-Event Simulation: Evaluation of Optimal OPO
Boundaries 422
14.3 Results 423
14.3.1 New Locations of Transplant Centers 423
14.3.2 New OPO Boundaries 426
14.3.3 Evaluation of New OPO Boundaries 428
CONTENTS xiii

14.4 Conclusions 433

Acknowledgment 435
References 435

15 Predictive Analytics in 30-Day Hospital Readmissions

for Heart Failure Patients 439
Si-Chi Chin, Rui Liu, and Senjuti B. Roy
15.1 Introduction 440
15.2 Analytics in Prediction Hospital Readmission Risk 441
15.2.1 The Overall Prediction Pipeline 441
15.2.2 Data Preprocessing 441
15.2.3 Predictive Models 442
15.2.4 Experiment and Evaluation 444
15.3 Analytics in Recommending Intervention Strategies 447
15.3.1 The Overall Intervention Pipeline 447
15.3.2 Bayesian Network Construction 448
15.3.3 Recommendation Rule Generation 452
15.3.4 Intervention Recommendation 453
15.3.5 Experiments 454
15.4 Related Work 457
15.5 Conclusion 459
References 459

16 Heterogeneous Sensing and Predictive Modeling of Postoperative

Outcomes 463
Yun Chen, Fabio Leonelli, and Hui Yang
16.1 Introduction 463
16.2 Research Background 466
16.2.1 Acute Physiology and Chronic Health Evaluation
(APACHE) 466
16.2.2 Simplified Acute Physiology Score (SAPS) 469
16.2.3 Mortality Probability Model (MPM) 470
16.2.4 Sequential Organ Failure Assessment (SOFA) 472
16.3 Research Methodology 474
16.3.1 Data Categorization 475
16.3.2 Data Preprocessing and Missing Data Imputation 475
16.3.3 Feature Extraction 482
16.3.4 Feature Selection 484
16.3.5 Predictive Model 487
16.3.6 Cross-Validation and Ensemble Voting Processes 489
16.4 Materials and Experimental Design 491
16.5 Experimental Results 491
xiv CONTENTS

16.6 Discussion and Conclusions 498

Acknowledgments 499
References 499

17 Analyzing Patient–Physician Interaction in Consultation

for Shared Decision Making 503
Thembi Mdluli, Joyatee Sarker, Carolina Vivas-Valencia, Nan Kong,
and Cleveland G. Shields
17.1 Introduction 503
17.2 Literature Review 505
17.2.1 Patient–Physician Interaction on Prognosis Discussion 506
17.2.2 Physician–Patient Interaction on Pain Assessment 509
17.3 Our Recent Data Mining Studies 510
17.3.1 Predicting Patient Satisfaction with Survey Data 510
17.3.2 Predicting Patient Satisfaction with Conservation Data 513
17.4 Future Directions 515
17.4.1 Regression Shrinkage and Selection 515
17.4.2 Conversational Characterization 517
17.5 Concluding Remarks 519
References 520

18 The History and Modern Applications of Insurance Claims Data in

Healthcare Research 523
Margrét V. Bjarndóttir, David Czerwinski, and Yihan Guan
18.1 Introduction 523
18.1.1 Advantages and Limitations of Claims Data 525
18.1.2 Application Areas 526
18.1.3 Statistical Methodologies Used in Claims-Based
Studies 528
18.2 Healthcare Cost Predictions 531
18.2.1 Modeling of Healthcare Costs 531
18.2.2 Modeling of Disease Burden and Interactions 533
18.2.3 Performance Measures and Baselines 534
18.2.4 Prediction Algorithms 534
18.2.5 Applying Regression Trees to Cost Predictions 535
18.2.6 Applying Clustering Algorithms to Cost Predictions 537
18.2.7 Identifying High-Cost Members 539
18.2.8 Discussion 539
18.3 Measuring Quality of Care 540
18.3.1 Structure, Process, and Outcomes 540
18.3.2 The Quality of Quality Data 542
18.3.3 Composite Quality Measures 542
CONTENTS xv

18.3.4 Practical Considerations for Constructing Quality

Scores 544
18.3.5 A Statistical Approach to Measuring Quality 545
18.3.6 Quality as a Case Management Tool 546
18.3.7 Discussion 547
18.4 Conclusions 548
References 548

19 Understanding the Role of Social Media in Healthcare via Analytics:

a Health Plan Perspective 555
Sinjini Mitra and Rema Padman
19.1 Introduction 555
19.2 Literature Review 556
19.2.1 Privacy and Security Concerns in Social Media and
Healthcare 559
19.2.2 Analytics in Healthcare and Social Media 561
19.3 Case Study Description 562
19.3.1 Survey Design 563
19.4 Research Methods and Analytics Tools 564
19.4.1 The Logistic Regression Model 564
19.5 Results and Discussions 568
19.5.1 Descriptive Statistics 568
19.5.2 Baseline of Technology Usage 570
19.5.3 Mobile and Social Media Usage 571
19.5.4 Clustering of Member Population by Technology,
Social, and Mobile Media Usage 572
19.5.5 Interest in Adopting Online Tools for Healthcare
Purposes 573
19.5.6 Interest in Adopting Mobile Apps for Healthcare
Purposes 574
19.5.7 Health and Wellness Objectives 577
19.5.8 Privacy and Security Concerns 580
19.5.9 Predictive Models 581
19.6 Conclusions 584
References 585

INDEX 589
LIST OF CONTIBUTORS

James T. Abbott, Roche Diagnostics Corporation, Indianapolis, IN, USA

Hany Y. Atallah, Grady Health System, Atlanta, GA, USA; Department of Emer-
gency Medicine, Emory University School of Medicine, Atlanta, GA, USA
David Ben-Arieh, Department of Industrial and Manufacturing Systems Engineer-
ing, Kansas State University, Manhattan, KS, USA
Margrét V. Bjarndóttir, Robert. H. Smith School of Business, Decision, Operations
& Information Technologies University of Maryland, College Park, MD, USA
Shivon Boodhoo, Albert Dorman Honors College, Mechanical and Industrial Engi-
neering, New Jersey Institute of Technology, Newark, NJ, USA
Robert E. Brown, Department of Pathology and Laboratory Medicine, University of
Texas Medical School at Houston, Houston, TX, USA
Chun-Hung Chen, Department of Operations Research, George Mason University,
Fairfax, VA, USA
Lili Chen, Department of Industrial Engineering and Management, Peking Univer-
sity, Beijing, China
Yun Chen, Complex Systems Monitoring, Modeling and Analysis Laboratory, Uni-
versity of South Florida, Tampa, FL, USA
Si-Chi Chin, University of Washington Tacoma, Tacoma, WA, USA
xviii LIST OF CONTIBUTORS

David Czerwinski, Department of Marketing and Decision Sciences, San Jose State
University, San Jose, CA, USA
Warren D’Souza, Department of Radiation Oncology, University of Maryland
School of Medicine, Baltimore, MD, USA
Sanchoy Das, Healthcare Systems Management Program, Newark College of Engi-
neering, New Jersey Institute of Technology, Newark, NJ, USA
Debasree DasGupta, School of Public Policy, George Mason University, Arlington,
VA, USA
Rajesh Ganesan, Department of Operations Research, George Mason University,
Fairfax, VA, USA
Monica Gentili, Mathematics Department, University of Salerno, Fisciano, Italy
Yihan Guan, Oracle Corporation, Redwood Shores, CA, USA
Leon L. Haley, Jr, Grady Health System, Atlanta, GA, USA; Department of Emer-
gency Medicine, Emory University School of Medicine, Atlanta, GA, USA
Sung W. Han, Division of Biostatistics, School of Medicine, New York University,
New York, NY, USA
Naoru Koizumi, School of Public Policy, George Mason University, Arlington, VA,
USA
Nan Kong, Weldon School of Biomedical Engineering, Purdue University, West
Lafayette, IN, USA
Sally A. Kraft, University of Wisconsin Medical Foundation, Middleton, WI, USA
Eva K. Lee, Center for Operations Research in Medicine and HealthCare, School of
Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, GA,
USA; NSF I/UCRC Center for Health Organization Transformation, Industrial
and Systems Engineering, Atlanta, GA, USA; Georgia Institute of Technology,
Atlanta, GA, USA
Fabio Leonelli, Cardiac Electrophysiology Laboratory, James A. Haley Veterans’
Hospital, Tampa, FL, USA
Jingshan Li, Department of Industrial and Systems Engineering, University of Wis-
consin, Madison, WI, USA
Rui Liu, University of Washington Tacoma, Tacoma, WA, USA
Wei Lu, Department of Radiation Oncology, University of Maryland School of
Medicine, Baltimore, MD, USA
David S. Matteson, Department of Statistical Science, Cornell University, Ithaca,
NY, USA
LIST OF CONTIBUTORS xix

Mary F. McGuire, Department of Pathology and Laboratory Medicine, University

of Texas Medical School at Houston, Houston, TX, USA
Thembi Mdluli, Weldon School of Biomedical Engineering, Purdue University, West
Lafayette, IN, USA
Keith Melancon, George Washington University Hospital, Washington, DC, USA
Robert Meyer, Computer Sciences Department, University of Wisconsin, Madison,
WI, USA
Sinjini Mitra, Information Systems and Decision Sciences Department, California
State University, Fullerton, CA, USA
Rema Padman, The H. John Heinz III College, Carnegie Mellon University, Pitts-
burgh, PA, USA
Amit Patel, School of Public Policy, George Mason University, Arlington, VA, USA
Eleanor T. Post, Rockdale Medical Center, Conyers, GA, USA
Yunzhe Qiu, Department of Industrial Engineering & Management, College of Engi-
neering, Peking University, Beijing, China
Varun Ramamohan, Purdue University, West Lafayette, IN, USA
Senjuti B. Roy, University of Washington Tacoma, Tacoma, WA, USA
Joyatee Sarker, Weldon School of Biomedical Engineering, Purdue University, West
Lafayette, IN, USA
Leyuan Shi, Department of Industrial and Systems Engineering, University of Wis-
consin, Madison, WI, USA
Zhenshen Shi, Department of Industrial and Manufacturing Systems Engineering,
Kansas State University, Manhattan, KS, USA
Cleveland G. Shields, Department of Human Development and Family Studies, Pur-
due University, West Lafayette, IN, USA
Steven Q. Simpson, Division of Pulmonary Diseases and Critical Care Medicine,
University of Kansas, Kansas City, KS, USA
Jeffrey S. Sleeth, University of Wisconsin Medical Foundation, Middleton, WI, USA
Changyue Song, Department of Industrial Engineering and Management, Peking
University, Beijing, China
Jie Song, Department of Industrial Engineering & Management, College of Engi-
neering, Peking University, Beijing, China
Calvin Thomas, IV, Health Ivy Tech Community College, Indianapolis, IN, USA
Carolina Vivas-Valencia, Weldon School of Biomedical Engineering, Purdue Uni-
versity, West Lafayette, IN, USA
xx LIST OF CONTIBUTORS

Nigel Waters, Department of Geography, George Mason University, Fairfax, VA,

USA
Molly Williams, University of Wisconsin Medical Foundation, Middleton, WI, USA
Michael D. Wright, Grady Health System, Atlanta, GA, USA
Chih-Hang J. Wu, Department of Industrial and Manufacturing Systems Engineer-
ing, Kansas State University, Manhattan, KS, USA
Daniel T. Wu, Grady Health System, Atlanta, GA, USA; Department of Emergency
Medicine, Emory University School of Medicine, Atlanta, GA, USA
Hui Yang, Department of Industrial and Manufacturing Engineering, The Pennsyl-
vania State University, University Park, PA, USA
Yuehwern Yih, Purdue University, West Lafayette, IN, USA
Hao Zhang, Department of Radiation Oncology, University of Maryland School of
Medicine, Baltimore, MD, USA
Xi Zhang, Department of Industrial Engineering and Management, Peking Univer-
sity, Beijing, China
Hua Zhong, Division of Biostatistics, School of Medicine, New York University,
New York, NY, USA
Xiang Zhong, Department of Industrial and Systems Engineering, University of Wis-
consin, Madison, WI, USA
Zhengyi Zhou, Center for Applied Mathematics, Cornell University, Ithaca, NY,
USA
PREFACE

Around the world, people are living longer. Health is rooted in everyday life and is
critical to the well-being and economics of society. Delivering personalized, qual-
ity healthcare in a timely manner and at affordable costs remain major challenges
in the United States and around the world. Fueled by rapid digital media advances,
healthcare systems in the 21st century are investing more in advanced sensors and
robotics, communication technologies, and sophisticated data centers. This facilitates
information and knowledge visibility and delivery standardization and performance
efficiency through big data analytics.
Meaningful information and knowledge extraction from diverse and rich health-
care data sets is an emergent critical area of research and development. In the general
practice of medicine, healthcare providers must be empowered with effective analyt-
ical methods and tools that enable and assist them in (i) handling rich data sets gener-
ated from genetic screening to specimen tests to patient monitoring to large-scale
hospital operations, (ii) extracting useful and meaningful information at different
granularities and across heterogeneous healthcare systems, and (iii) exploiting per-
tinent knowledge for optimization of processes and performance across healthcare
systems and the provision of personalized and effective healthcare services.
This book provides a brief overview of the state of the art in healthcare analyt-
ics development. It covers a collection of recent research advances in data-driven
healthcare analytics from biomedical and health informatics to healthcare simula-
tion and modeling to healthcare service science and medical decision making. The
book intends to serve as a reference for healthcare researchers, practitioners, and
students. In addition, through the chapters, those who are new to healthcare analyt-
ics can learn and understand how to apply analytical methods and tools to diverse
healthcare applications. The intended audience includes researchers, practitioners,
xxii PREFACE

and graduate students in the healthcare/engineering fields of statistics, data science,

system engineering, operations research, and operations management, as well as in
biomedical engineering and computer science.
This book is organized into two parts: Part I covers biomedical and health infor-
matics (Chapters 1–8) and Part II focuses on healthcare delivery systems (Chapters
9–19). Specifically, Chapters 1 and 2 address the analytics of genomic and proteomic
data. Chapters 3 and 4 analyze physiological signals from patient monitoring sys-
tems. Chapter 5 handles data uncertainty in clinical laboratory tests. Chapter 6 covers
predictive modeling and presents its applications to a broad variety of clinical and
translational projects, while Chapter 7 focuses on predictive usage within radiation
oncology. Chapter 8 discusses disease modeling for sepsis.
Part II begins with discussion of system advances for transforming clinic workflow
and patient care (Chapter 9). Chapter 10 covers macroanalysis of patient flow distri-
bution. Chapter 11 covers intensive care units while Chapter 12 covers a case study
in primary care. Chapters 13 and 14 detail demand and resource allocation, while
Chapters 15 and 16 focus on mathematical models for predicting patient readmission
(Chapter 15) and postoperative outcome (Chapter 16). The last three chapters deal
with physician–patient interactions (Chapter 17), insurance claims (Chapter 18), and
the role of social media in healthcare (Chapter 19).
This book focuses primarily on data analytics from the field of Industrial Engineer-
ing and Operations Research methodologies drawing technologies from mathemati-
cal modeling, optimization, simulation, and computational methods that advance and
improve healthcare. Most of the analytic authors are affiliated with the INFORMS
community and are members of the healthcare applications society, data mining,
simulation, optimization, computing, quality, statistics, and reliability societies. The
chapters herein showcase the successful and close collaboration with the healthcare
and clinical experts. A rich source of healthcare analytics can be found in the triannual
INFORMS Healthcare Conference http://meetings.informs.org/healthcare2015.
At the time of the writing, big data analytics has attracted increasing attention in
a broad spectrum of research domains, including biomedical and healthcare areas,
where data arose from “omics”; imaging, laboratory, medical records, and operations
offer invaluable opportunities. We also note that a number of large-scale data repos-
itories have been established to accelerate the initiatives of big data to knowledge,
for example, the Human Connectome Project (www.neuroscienceblueprint.nih.gov/
connectome), the Cancer Genome Atlas (cancergenome.nih.gov), and the Physiome
Project (www.physiome.org), to name a few.
Lastly, we would like to thank all the authors for their contribution that result in a
high-quality book. We also gratefully acknowledge the support in part by the National
Science Foundation under Grants CMMI-1454012, CMMI-1266331, IOS-1146882,
and IIP-1447289 to editor H .Yang, and IIP-0832390, CNS-1138733, IIP-1361532,
and IIP-1516074 to editor E.K. Lee. Finally, we thank the support and encouragement
PREFACE xxiii

of Susanne Steitz-Filler, Wiley editor, toward the completion of this book and her staff
for editorial and production assistance.

Hui Yang
Tampa, FL, USA
May 2015

Eva K. Lee
Atlanta, GA, USA
May 2015
PART I

ADVANCES IN BIOMEDICAL AND

HEALTH INFORMATICS
1
RECENT DEVELOPMENT IN
METHODOLOGY FOR GENE
NETWORK PROBLEMS AND
INFERENCES

Sung W. Han and Hua Zhong

Division of Biostatistics, School of Medicine, Department of Population Health,
New York University, New York, NY, USA

1.1 INTRODUCTION

The cell inside of a human body is similar to a manufacturing system producing an

appropriate protein that functions according to the specific organ or the part of the
body to which it belongs. The nucleus centered at the cell contains the DNA sequence,
which is a designed map for the human body. Each time the cell produces a protein, it
duplicates a certain part of the DNA sequence and generates mRNA sequences. This
is called a transcription process. After leaving the nucleus, the mRNA is attached to a
ribosome, and the ribosome interprets the code in mRNA. This is called a translation
process. After interpretation, the ribosome generates a sequence of amino acids; then
it is folded into a certain type of protein.
The manufacturing system from DNAs to proteins sometimes malfunctions due to
the DNA damage, which is known to be a main cause of cancers, also called malig-
nant neoplasms [1, 2]. The DNA damage can occur naturally, but the damage can also
be caused by two groups of agents: (i) exogenous agents such as radiation, smoke
[3], ultraviolet light [4], and viruses [5]; and (ii) endogenous agents such as diet [6]
and macrophages/neutrophils [5]. Such DNA damage leads to epigenetic alteration

Healthcare Analytics: From Data to Knowledge to Healthcare Improvement, First Edition.

Edited by Hui Yang and Eva K. Lee.
© 2016 John Wiley & Sons, Inc. Published 2016 by John Wiley & Sons, Inc.
Another random document with
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The periods of puberty and early menstruation and of pregnancy
furnish the most favorable opportunities for the development of
cataleptoid seizures in predisposed individuals. In 3 of 10 cases
observed by Landouzy catalepsy appeared to be developed in
consequence of the sudden suppression of menstruation; in a fourth
it occurred in a young girl after a dysmenorrhœa with chronic
phlegmasia of the genitals. Masturbation is sometimes mentioned as
a cause, particularly in boys.

Reflex irritation undoubtedly often acts as an exciting cause of

catalepsy. Preputial irritation, relieved in part by circumcision, was
present in the case of Lloyd, and has been noted by others.
Handfield Jones mentions a case, recorded by Austen in his work on
General Paralysis, in which the cataleptic seizure was, to all
appearances, due to fecal accumulations. The attack disappeared
promptly after an enema had thoroughly operated.

Briquet believed that catalepsy, when it did not follow upon organic
disease, was ordinarily the result of moral causes, such as vivid and
strong emotions—fear, chagrin, indigestion, anger, or profound and
prolonged meditation. He refers to the able and curious thesis of
Favrot,6 who states that in twenty cases in which the causes of the
malady were indicated it had been always the result of a moral
affection. A magistrate insulted at his tribunal, seized with
indignation, is suddenly taken with catalepsy, etc. According to Puel,
its causes are always depressing moral affections, as chagrin,
hatred, jealousy, and terror at bad treatment. Unrequited love is set
down as a cause, but what has not unrequited love produced? Jones
mentions a case which occurred in a man sixty years old on the
sudden death of his wife.
6 “De la Catalepsie”—Mémoire couronné par l'Académie de Médecine, Mémoires de
l'Académie de Médecine, Paris, 1856, t. xx. p. 409, A. 526.

Cullen believed that catalepsy was always a simulated disease; he

preferred, therefore, to place it as a species of apoplexy. Temporary
catalepsy may, according to Rosenthal, be produced in hysterical
patients by covering their eyes with their hands or a cloth. Malaria
has been charged with the production of catalepsy, and apparently
properly. Traumatism is another of its well-authenticated causes.
Blows upon the head have been particularly recorded as having an
etiological relation to this disorder.

Partial catalepsy has been observed after typhoid fever with severe
cerebral symptoms, and also associated with meningitis and
intermittent fever. Mancini7 relates a case of cerebral rheumatism
complicated or causing catalepsy. A blacksmith, aged thirty-three,
had nearly recovered from a rheumatic attack when he became
melancholic, complaining also of severe headache. When admitted
to the hospital he was found to be imperfectly nourished. He lay on
his back, his face without expression, speechless, motionless, pupils
insensible to the light, smell impaired, sensation of heat and pain
and reflexes absent, galvanic and faradic contractility increased, the
rectum and bladder paralyzed. He presented the phenomena of
waxen flexibility, the trunk and limbs remaining in whatever position
was given them. Considering the previous attack of articular
rheumatism and the sudden appearance of nervous disorder during
the convalescence of this disease, Mancini believed that the case
was probably one of cerebral rheumatism. The man recovered under
diaphoretics and counter-irritation.
7 Lo Sperimentale, March, 1878.

Among the important causes of catalepsy bad nutrition may

undoubtedly be placed. In the case of De Schweinitz the cataleptoid
phenomena rapidly improved, and eventually disappeared as the
child's general health was restored by tonics and good diet. Hovey's
case was insufficiently clad and badly fed. One of Laségue's cases,
quoted by Handfield Jones, died of gradual marasmus, another of
pulmonary phthisis. Attacks of catalepsy have sometimes resulted
from a combination of excitement, fatigue, and want of food. They
occur also in diseases or conditions like phthisis, anæmia, and
chlorosis, affections which practically gives us the same cause—
namely, bad nutrition. In these cases the nervous system, like other
parts of the body, takes part in the general exhaustion.
Rosenthal refers to the production of symptoms of temporary
catalepsy by the administration of narcotics and the inhalation of
ether and chloroform. In a somewhat ancient American medical
periodical8 Charles D. Meigs of Philadelphia gives an interesting
account of a case of catalepsy produced by opium in a man twenty-
seven years of age. The man had taken laudanum. His arms when in
a stuporous condition remained in any posture in which they
happened to be left; his head was lifted off the pillow, and so
remained. “If he were made of wax,” says Meigs, “he could not more
steadily preserve any given attitude.” The patient recovered under
purging, emetics, and bleeding. Darwin, quoted by Meigs, mentions
a case of catalepsy which occurred after the patient had taken
mercury. He recovered in a few weeks.
8 The North American Medical and Surgical Journal, vol. i. p. 74, 1826.

That imitation is an exciting cause of catalepsy has been shown by

the often-told story of epidemic hysteria, but more especially by
accounts given of certain peculiar endemics of catalepsy. Handfield
Jones9 gives an account of an endemic which prevailed at
Billinghausen near Wurzburg: “The population consists of peasants
who are well off, but who intermarry very much, and are small and
deformed. The affected individuals constitute half of the number,
males as well as females. They are called there the stiff ones
(starren). A chill is commonly said to be the exciting cause of the
attacks. The patients are suddenly seized by a peculiar sensation in
their limbs, upon which all their muscles become tense, their
countenances deadly pale; they retain the posture which they first
assume; their fingers are bent and quiver slightly, and the eyeballs in
the same way, the visual axis converging; their intellects and senses
are normal, but their speech consists only of broken sounds. The
attack ceases in from one to five minutes, and the body becomes
warm.”
9 Op. cit., quoted from Schmidt's Jahrbuch.

SYMPTOMATOLOGY.—The cataleptic seizure, when it is not the result of

some hypnotizing procedure, usually takes place in the following
manner: The patient usually, after some patent exciting cause,
suddenly ceases whatever she may chance to be doing, becoming
rigid and immobile in the last position which she had been in before
the attack ensued. “She remains,” says Rosenthal, “as if petrified by
the head of Medusa.” The features are composed, the eyes usually
directed forward. She is pale; breathing, pulsation, and temperature
are usually somewhat reduced. At first the limbs may be found to
offer some resistance; soon, however, and sometimes from the
beginning, they can be moulded like wax into any possible position,
where they will remain until again changed by external agency.

Attacks of catalepsy, as a rule, come on suddenly, without special

warning; sometimes, however, special phenomena, which may be
compared to epileptic aura, may precede the attack. Thus,
Rosenthal speaks of two cases that were ushered in, and also
bowed out, by hiccough. The attacks may terminate as suddenly as
they begin, but sometimes the patients come out of the state
gradually. They are quite likely to appear dazed and stupid when
emerging.

Perverted consciousness is another marked symptom of catalepsy.

According to some authors, the loss of consciousness is absolute,
and upon this symptom they base their diagnosis from two or three
other somewhat similar conditions. As I have already indicated in
discussing the general subject of Hysteria, this question of
consciousness or unconsciousness is not one to be decided in
haste. In catalepsy, as in hystero-epilepsy, the conditions as to
consciousness may differ. What might be termed volitional
consciousness is in true catalepsy certainly in abeyance. Flint10
divides catalepsy, according to the condition as to consciousness,
into three kinds—namely, complete, incomplete, and complicated.
He, however, regards trance and day-mare as instances of
incomplete catalepsy, in which the intellectual faculties are not
entirely suspended and the senses are not materially affected, the
patient being unable to move or speak, but conscious of all that is
going on around him. He believes that such cases resemble more
closely the cataleptic condition than they do that of ecstasy. In
genuine catalepsy with waxen flexibility, analgesia, etc. there may be
greater or less depths of unconsciousness, but some degree of
unconsciousness or of obtunded consciousness is necessary to the
existence of true catalepsy.
10 Buffalo Medical Journal, xiii., 1857-58, p. 141.

Catalepsy presents well-marked disturbances of sensation, although

these, like the conditions as to consciousness, differ somewhat in
different cases. Anæsthesia in its different forms, and especially
analgesia, are always present in some degree. Experiments without
number have been tried on cataleptic patients, showing their
insensibility to painful impressions: they have been pinched, pricked,
pounded, burned with heated irons, and rubbed down with blocks of
ice. Skoda reports a case in which general sensibility was abolished,
but a lighted paper rotated rapidly before the eyes gave rise to
tremors of the limbs, and strong odors induced slight movement,
redness of the cheeks, lachrymation, acceleration of the pulse, and
elevation of the temperature.

Hyperæsthesia, although rare, has been noted in a few isolated

cases of catalepsy. Puel records a case in which, during the
cataleptic paroxysm, the slightest touch or noise caused the patient
to grind the teeth and cry out. In some cases sensibility to certain
special impressions, as to a strong current of electricity, has been
retained, while all others were abolished. In a case of hystero-
catalepsy at the Philadelphia Hospital, when all other measures had
failed an attack was aborted and evidence of pain produced by the
application of a strong faradic current with metallic electrodes.

A marked change in the state of reflex irritability is another of the

striking symptoms of true catalepsy. Varying conditions as to reflex
irritability have been observed by different authors. So far as I am
aware, few special observations have been made upon the tendon
reflexes in catalepsy. In the case of De Schweinitz the knee-jerk was
apparently absent on one side and present on the other, although
the cataleptic symptoms were not unilateral.
The symptom known as flexibilitas cerea, or wax-like flexibility, to
which I have referred under Synonyms, is, as has been stated, by
some considered pathognomonic of this affection. While I do not
hold to this view, I regard the symptom as the most important
phenomenon of the disease. It is a symptom which from its very
nature can be, up to a certain point, readily shammed, and when
considering Diagnosis some methods of determining its genuineness
will be given.

Careful observation as to the pulse, respiration, and temperature are

lacking in the reported cases of catalepsy. According to Eulenburg,11
“the respiration is generally of normal frequency, sometimes rather
slow, more frequently of diminished or irregular intensity, so that
lighter and deeper inspirations alternate. The pulse may also be
slower, with slight excursion and diminished tension of the arteries.
The temperature generally remains normal, but in certain cases is
decidedly lowered.” The lowering of temperature, and particularly the
presence of extreme coldness of the surface, with exceedingly weak
pulse and respiration, have doubtless always been present in the
cases—a few, at least, authentic—in which catalepsy has been
supposed to be death.
11 Op. cit.

Hypnotic Catalepsy.

The investigations into the subject of hypnotism made in recent

years have given to the profession a series of interesting
phenomena which should be considered, at least briefly, under the
symptomatology of catalepsy. In a general review of the subject of
hypnotism12 by me many of the facts observed and theories
advanced by Braid, Heidenhain, Charcot, Richer, and others were
examined. I will here recall those observations of Heidenhain13 and
of Charcot and Richer14 which relate to the production of a cataleptic
or cataleptoid state, and to the phenomena which take place in this
state.
12 Am. Journ. Med. Science, Jan., 1882.

13 Animal Magnetism: Physiological Observations, by Rudolph Heidenhain, Prof.

Physiology in the University of Breslau, London, 1880.

14 Etudes cliniques sur l'Hystero-epilepsie, ou Grande Hystérie.

The method of Heidenhain was similar to that employed by Braid.

The latter, however, did not make use of passes. In the first place,
the individual was made to gaze fixedly at a shining faceted glass
button for some six or eight minutes, the visual axes being made to
converge as much as possible. Heidenhain, like Braid, found the
most advantageous direction of the visual axes to be that of upward
convergence. According to Carpenter, in the fixation this upward
convergence is very important; it suffices of itself in blind people or in
the night to produce hypnosis. After the fixation of gaze had been
continued for some six or eight minutes, the operator stroked over
the face, without immediately touching the surface, from the
forehead to the chest, after each pass bringing the hands, which
were warm, around in an arc to the forehead again. He either
allowed the eyelids to be closed or gently closed them. After ten or
twelve passes he asked the person to open his eyes. When this
occurred without hesitation or with only slight difficulty, he again
made the person stare at the glass for some six minutes, and then
repeated the passes, which often brought about the hypnotic state
when the simple fixation did not succeed.

The symptoms of the hypnotic state were in the main those which
have just been described as the symptoms of catalepsy—namely,
diminution of consciousness, insensibility, increased reflex irritability,
and fixity of the body or limbs in any position given.

In the slighter forms of hypnotism the subjects were able to

remember what had occurred during their apparent sleep. In more
fully-developed forms they had no remembrance of what had taken
place, but by giving hints and leading questions of their various
actions they were able to call them to mind. In the most complete
forms of hypnotism no remembrance whatever was retained. It can
nevertheless be proved that even during the most completely
developed hypnosis sensory perceptions take place, but they are no
longer converted into conscious ideas, and consequently are not
retained by the memory; and this is undoubtedly because the
hypnotized individuals have lost the power of directing their attention
to their sensations.

A symptom of the hypnotic state in its most complete development

was highly marked insensibility to pain. A pin could be run right into
the hand, and only an indistinct feeling of contact was brought about.
Immediately on awaking the full sense of pain was again present.
The fact that the tactile sense and the sense of pain are distinct was
corroborated.

Increased reflex irritability and tonic spasm of the voluntary muscles

accompanied the hypnotic condition. Stroking the flexible right arm of
a subject, it at once became stiff, since all the muscles were thrown
into a state of reflex spasm. Reflex muscular contraction spread over
the body when certain definite cutaneous surfaces were irritated.
With slight increase of reflex irritability those muscles alone
contracted which lay immediately under the area of the skin which
had been stroked. Stroking the ball of the thumb caused adduction of
the thumb. Stimulating the skin over the sterno-mastoid caused the
head to assume the stiff-neck position. When the irritability was
somewhat more increased, by a continuous irritation of a definite
spot of skin neighboring and even distant groups of muscles could
be set into activity. Heidenhain stroked continuously the ball of the
left thumb of his brother, when the following muscle-groups were
successively affected with spasm: left thumb, left hand, left forearm,
left upper arm and shoulder, right shoulder and arm, right forearm,
right hand, left leg, left thigh, right thigh, right leg, muscles of
mastication, muscles of the neck.
From a study of such phenomena Heidenhain was inclined to
consider that the hypnotic state was nothing more than artificially
produced catalepsy.

The possibility of fixing any part of the body in any given position
constituted an essential factor in the exhibition of Hansen. He made
one of his subjects, for instance, sit before him in a chair, and
adapted the hands to the seat so that his fingers grasped the edges.
After hypnotizing him he stroked along his arms, and his fingers took
convulsive hold of the edges of the seat. Placing himself in front of
the subject, he bent forward; the subject did the same. He then
walked noisily backward, and thereupon the subject followed him
through the hall, carrying his chair with him like a snail its shell.

One of the observations of Richer was on the influence of light on

catalepsy and hysterical lethargy. The patient was placed before a
bright focus of light, as a Drummond or electric light, on which she
was requested to fix her sight. In a short time, usually a few seconds
or several minutes, sometimes instantaneously, she passed into the
cataleptic state. She was as one fascinated—immobile, the wide-
open eye fixed on the light, the conjunctiva injected and humid.
Anæsthesia was complete. If the patient was hemianæsthetic, she
became totally anæsthetic. She did not present contractures. Her
limbs preserved the suppleness of the normal state or nearly this—
sometimes being the seat of a certain stiffness; but they acquired the
singular property of preserving the attitude which one gave them.
One interesting peculiarity was the influence of gesture on
physiognomy. The features reflected the expression of the gesture. A
tragic attitude imprinted a severe air on the physiognomy; the brows
contracted. If one brought the two hands to the mouth, as in the act
of sending a kiss, a smile immediately appeared on the lips. It was
an example of what Braid calls the phenomena of suggestion—of
Heidenhain's imitation. The state of catalepsy endured as long as
the agent which produced it—that is, as long as the light continued to
impress the retina.
The characteristics of the two abnormal states—catalepsy and
lethargy—into which hystero-epileptics may be thrown were
summarized by Richer as follows: (1) Cataleptic state: The eyes
wide open; total and absolute anæsthesia; aptitude of the limbs and
different parts of the body to preserve the situation in which they are
placed; little or no muscular rigidity; impossibility of causing muscular
contraction by mechanical excitation. (2) Lethargic state: The eyes
wide open or half closed; persistent trembling of the upper eyelids;
convulsion of the eyeballs; total and absolute anæsthesia; muscular
hyperexcitability; the limbs, in a condition of resolution, do not
preserve the situation given to them, except the provoked
contracture impressed upon them.

In the experiments at Salpêtrière the hystero-epileptics were

sometimes plunged into the states of catalepsy and lethargy under
the influence of sonorous vibrations instead of frights.

During the state of provoked hysterical catalepsy it was found that

sight and hearing could be affected by various procedures. The eyes
were fixed, and seemed not to see anything. If, however, an object
was slightly oscillated in the axis of the visual rays at a little distance
from the eyes, soon the gaze of the patient followed these
movements. The eyes, and sometimes even the head, seemed to
turn at the will of the operator. Hallucinations were produced. When
the look was directed upward the expression became laughing;
when downward, sombre. The cataleptic state might now cease
completely. The patient walked, followed the object on which her
gaze was fixed, and took attitudes in relation with the hallucination
suggested. Music also caused her to assume positions related with
the various sentiments suggested to her by the music. Sudden
withdrawal of the object from before the eyes or of the sound from
the range of hearing caused a return of the catalepsy. The cataleptic
patient in whom the eye was in such a state as to perceive the
movements of an experimenter placed in front of her reproduced
these movements exactly. At the Philadelphia Hospital I have
repeated most of the experiments of Heidenhain and of Charcot and
Richer.
 Unilateral Catalepsy.

Hemi-catalepsy or unilateral catalepsy is sometimes observed, and

has been studied both in hypnotic investigations and as a special
nervous affection. Charcot and Richer found that hemi-catalepsy or
lethargy may be produced on a patient, and that they may both exist
simultaneously in the same subject. When, for instance, a patient
was plunged into the cataleptic state under the influence of a bright
light, shutting with the hand one of the eyes, the patient at once
became lethargic on the same side only; the other side remained
cataleptic. Heidenhain and Gruetzner studied some remarkable
phenomena, which they have recorded under the name of unilateral
hypnosis, in which some surprising sensory disturbances occur.
They also found, among other things, a striking disturbance in the
process of accommodation and in the perception of colors in the eye
of the cataleptic side. In a case of hystero-epilepsy upon which I
performed numerous hypnotic experiments which have been
reported15 the patient nearly always presented unilateral cataleptic
phenomena. These were present on the left side, the patient being
subject to convulsions which were more marked on the right side,
this being also much wasted.
15 Philadelphia Med. Times, Nov. 19, 1881.

I witnessed some curious unilateral cataleptoid phenomena in the

case of a medical friend, who has made a note of his experience.16
He says: “In the course of some experiments on table-tipping, which
were conducted mainly to satisfy the curiosity of persons who had
never seen anything of the kind, I became the subject of a very
peculiar and marked hypnotic influence. The ordinary tricks of
tipping, answering questions, guessing numbers, etc. had been
performed with the table, during the greater part of which I had been
one of the circle, when my right hand began to contract so as to form
an arch, and was then lifted from the table. These movements were
not volitional; I was unable to control them. While my hand was in
this position one of the persons sitting at the table suddenly put his
hand on my forehead, and I sank back in the chair, passing into a
conscious but apparently powerless state, but only for a few
moments. Later in the evening the hypnotic influence in the right
hand was still more distinctly manifested. If allowed to remain a short
time on the table, the fingers began to vibrate vertically and
horizontally, the motion finally extending to the forearm and
becoming so violent as to throw the hand about in a rapid and
forcible manner. While thus affected I found it utterly impossible to
sign my name. I would be able to form the first letter or so, and then
most extraordinary gyrations would be made. In one instance I wrote
very slowly, using all the muscular control at my command, and
succeeded in writing the full name, but in a form wholly different from
my ordinary signature.”
16 Polyclinic, Sept. 15, 1883.

My attention was called to these phenomena, and the experiments

were repeated the next week in my presence, with like results. In
addition, I succeeded in forcibly placing the affected arm in various
positions—bent at right angles, the hand resting on the top of the
head, etc.—from which positions he was unable to move it. He
seemed to have lost the connection between volition and the motor
impulse. The experiments were continued for several hours at each
sitting, but owing to the depressed mental state which was produced
for a short time, apparently by them, they have not been repeated.

Occasionally, cases of unilateral catalepsy associated with rotatory

phenomena are met with, especially in hysterical children. In 1882, I
studied in the nervous dispensary of the hospital of the University of
Pennsylvania an interesting case with rotatory and unilateral
cataleptoid symptoms. This case has been reported by James
Hendrie Lloyd.17 The patient was a boy eight years old. His paternal
grandfather hanged himself. On the mother's side there was a
history of tuberculosis. Two years before coming to the hospital he
had had four attacks of spasms. For two weeks he had been having
from twelve to twenty similar spasms daily; some of these were
observed in the dispensary. “The boy's head was suddenly drawn
upward and to the right to its extreme limits by the action chiefly of
the sterno-cleido-mastoid muscle. The eyes turned also to the
extreme right, with slight convulsive (clonic) action, and became
fixed in that position, with very wide dilatation of the pupils. In a
second or two he began to rotate his whole body to the right, and
turned completely around, perhaps ten or twelve times. On some
occasions he had fallen down, his mother said, toward the end of the
spell. If taken hold of and steadied—which required but little force by
the physician—the rotation could be stopped, though the head and
eyes remained drawn, and the boy's arms could be placed in any
desired position. If now he was once more let loose, his body again
rotated, while his arms were held in true cataleptoid rigidity. The
whole duration of the attack was from one half to one minute. The
boy was intelligent, and said he knew what was taking place about
him while he was in the fit, though he gave no satisfactory evidence
of such knowledge at the time. There was no history of headache or
any disease. His ears were subsequently examined and found
normal. He had taken worm medicine in abundance from the family
physician without results. There were no psychical traits of
importance to suggest foolish or wilful simulation. The only accident
had been a fall from a wagon years previously. As the patient had an
adherent prepuce, Wood advised circumcision, and took pains to
explain the operation to the mother. This evidently made a great
impression on the child's mind, which is worthy of notice in
considering the case. The potassium bromide was continued. At the
third visit, which had been appointed for the operation of
circumcision, the mother reported the patient much better. The boy
had been having great fear of the proposed operation, and now said
that he thought he could control the spells. A psychical element was
thus distinctly indicated, and its likeness to chorea major to some
extent increased. It was thought best, however, instead of
circumcision, to break up adhesions and retract the foreskin, which
was done by J. William White. At the fourth visit, after ten days, a still
greater improvement was noted.”
17 Philada. Med. Times, vol. xii., June 17, 1882.
Lloyd in reporting this case discusses the physiology of the
condition, and refers to other cases in medical literature. According
to Brown-Séquard, the great cause of rotation phenomena is a
convulsive contraction in some of the muscles on one side of the
body. Carpenter believes they are due to weakness of the sensori-
motor apparatus of one side. Laycock holds that the cerebellum is
involved. Lloyd likens the case to chorea major. He refers to cases
reported by Radcliffe18 and J. Andrew Crawford.19
18 Reynolds's System of Medicine, art. “Chorea.”

19 Cycl. of Pract. Medicine, art. “Chorea.”

At the Pennsylvania Training School for Feeble-minded Children at

Elwyn is a little patient familiarly spoken of as the Dervish. I have
examined this boy several times, and have frequently watched his
performances. I. N. Kerlin, superintendent of the institution, has
kindly furnished me with some notes of this case. The antecedents
of the patient are unknown. He is about fifteen years of age, is of
small stature and weight, a demi-microcephalic, epileptic, and mute
idiot. His epilepsy, however, supervened only in 1884, and the
seizures continue now at the rate of three or four a month. At all
times he is subject to certain automatic tricks with his hands, putting
and twisting them into various positions. Periodically almost during
every day he gives exhibitions of the habit which has led him to be
called the Dervish. He commences by tattooing his chin with his left
hand; next he delicately and rapidly touches the fingers of his left
hand to the wrist of the right, makes two or three salaams, and then
impulsively gyrates the body from left to right. The right heel is
pivotal, and the force is maintained by touches of the left toe or heel
upon the floor. He will usually take from three to seven turns at a
time, with a salaam or two between every series. Fifteen minutes or
more will be thus consumed before he darts away toward a window,
where he remains a few moments in a dazed state, from which he
rouses to recommence his hand tricks. Perhaps he will select a
broad belt of light in which to display his hand for visual enjoyment.
He has a cataract of the right lens, and possibly partial amaurosis of
the left eye. A supplemental performance sometimes indulged in is
to stand at one fixed point and throw his head and shoulders from
side to side, describing with the former two-thirds of a circle, the
occiput being flexed backward as far as the neck will permit. These
movements, rapidly made, reach three and four hundred under
favorable conditions.

Kerlin regards the displays made by this boy to be the pure

automatic phenomena of idiocy which have been developed to an
artistic finish, and out of which the patient gets enjoyment. This
enjoyment probably exists in some anæsthetic or stuporous
condition of certain nerve-centres, something like the sensation of
common dizziness. He does not look upon the case, therefore, as
one of genuine catalepsy, but I have recorded it here in connection
with the case just given because it illustrates a phase of automatism
and rotation movements closely allied to cataleptoid conditions.

Catalepsy and Cataleptoid Phenomena among the Insane.

Catalepsy and cataleptoid or cataleptic phenomena are of

comparatively frequent occurrence among the insane. Niemeyer
says20 that they are especially common among persons suffering
from melancholia. Kahlbaum21 has described a form of insanity
which he names katatonia, from the Greek κατατονος, stretching
down. This disease is “characterized by alternate periods,
supervening with more or less regularity, of acute mania,
melancholia, and epileptoid and cataleptoid states, with delusions of
an exalted character and a tendency to dramatism.”22
20 Textbook of Practical Medicine, Felix von Niemeyer, American trans., 1876, vol. ii.
p. 387.

21 Klinische Abhandlungen über psychische Krankheiten, 1 Heft, “Die Katatonie,”

Berlin, 1874.
 22 A Treatise on Insanity in its Medical Relations, by William A. Hammond, M.D., New
York, 1883, p. 576.

Kiernan23 has written a valuable memoir on this affection. He has

collected fifty cases, a few of which he gives in detail. Hammond and
Spitzka discuss the disorder, giving new cases, in their treatises on
insanity.
23 American Journal of Insanity, July, 1877, and Alienist and Neurologist, October,
1882.

Katatonia may begin in various ways, but it usually pursues a certain

cycle. First appears stuporous melancholia, accompanied or
followed by cataleptoid manifestations; then a period of mania with
illusions, hallucinations, and delusions. Melancholia reappears in
some form, with cataleptoid, waxy condition of the muscles, and a
disposition to talk in a pompous or dramatic manner; convulsions or
choreic movements may be present.24 Sometimes some phase of
the cycle is absent.
24 Hammond.

In some cases in which the peculiar cycle and special phenomena

which characterize katatonia are not present marked cataleptic or
cataleptoid states may be observed among the insane, either as
episodes or as long-continuing conditions.

As cases illustrating cataleptoid phenomena among the insane have

not yet been published in large number, and are not well understood,
I will record here, under the Symptomatology of Catalepsy, some
illustrative cases which have either fallen under my own observation
or have been supplied to me directly by medical friends.

M. A. Avery, assistant physician to the insane department of the

Philadelphia Hospital, has kindly furnished notes of the following
interesting case:
T——, aged twenty, single, dressmaker. The patient was somewhat
below medium height, slender and emaciated, of nervous
temperament, expression melancholy. The attack of insanity for
which she was admitted was her first. It began four months before
admission. No satisfactory history of the attack could be obtained;
she was said to have been depressed in spirits and to have
delusions of poisoning. She had attempted suicide by throwing
herself from the window.

Upon admission, Sept. 20, 1883, she was quiet and gentle in her
manner, but much depressed; she answered questions rationally. No
delusions were detected. Sept. 21st she sat quiet and motionless.
Her eyes were fixed, with marked double, inward squint. She was
apparently insensible to external impressions. This condition lasted
about three hours, when she suddenly sprang up, rushed through
the ward, and made vigorous efforts to escape. On the 22d she lay
in bed in a perfectly passive state, with eyes open and fixed, but the
squint had disappeared. There was a constant slight tremor of the
lids. The conjunctiva was apparently insensible to touch. She
seemed to be unconscious of what was going on around her. Her
arms remained raised in any position in which they were placed.
About three o'clock in the afternoon this condition passed away, and
from that time until she went to bed at eight o'clock she was bright
and cheerful and talked in a rational and intelligent manner. For five
days she was quiet and melancholy, with one spell of a few hours in
which she was in a passive and cataleptic state, as on the 22d.

On the 28th she stood erect with arms extended, whirling rapidly.
She continued this for about half an hour, and then, after a short rest,
began again. She paid no attention to what was said to her, and
seemed unconscious of what took place around her. The next day
she remained in a stupid condition most of the time, but occasionally
sprang up and danced violently or spun round rapidly with arms
extended for a few moments at a time. On the 30th her cataleptic
condition was uninterrupted. She lay motionless, with pulse slow and
feeble, extremities cold; her limbs were easily placed in any desired
position, and remained so for about twenty minutes; then they
returned slowly to a more natural and comfortable position. She
continued for several days in this condition, then aroused and ate
heartily. She seemed brighter and more cheerful, and talked
rationally. She said that she knew all that was said and done when
she seemed unconscious, and that she wanted to speak, but could
not. For several weeks cataleptic symptoms prevailed, with
occasional lucid intervals of a few hours. She eventually settled into
a childish, demented condition.

In the insane department of the Philadelphia Hospital was a middle-

aged man who remained for several years in a stuporous and
cataleptoid state. On several occasions he was before the class in
the clinic-room. He could not be made to speak, but remained
perfectly silent in any condition in which he was placed. His head
and trunk could be bowed forward, sideway, or backward; one foot
could be elevated while he stood; his arms could be placed in
grotesque positions. In whatever attitude he was placed he would
remain for a long time. The only history that could be obtained of this
man was that he had for several months been in a state of
melancholia, after which he was maniacal for three or four months.
He escaped from the hospital, and was brought back in the
stuporous and cataleptoid condition in which he continued. He had
been a masturbator.

A Dane, while on a voyage from Copenhagen, fell and broke his leg,
for which he was treated in a hospital. He recovered and became a
nurse in the institution. He fell in love with a female nurse, and was
to be married, but the lady suddenly fell dead. He became
melancholic, and three weeks afterward tried to hang himself. He
also had hystero-epileptic seizures, and was for a long time in a
condition of extreme stupor with cataleptoid phenomena, from which
he passed into a rather excited condition. He had no special
delusions, but there was a tendency to dramatism.

Another case came into the nervous wards of the Philadelphia

Hospital. No history could be obtained from the patient. Whether or
not he had previously suffered from melancholia could not be
learned. He would retain for a long time any position in which he was
placed. He also had hystero-cataleptic spells, and a peculiarity of
enunciation with a tendency to pose. When asked, “How are you to-
day?” he would reply, “I pre-sume-that-I-am-a-bout-the-same—that-
it-is-likely-that-some-thing-has-dis-ap-peared-in-the-mind.” When
asked, “How long have you been sick?” he would begin in the same
way: “I-pre-sume-that-I-will-have-to-say-that-at-a-time-re-mote-ly-dis-
tant;” and then he would branch off into something else.

Wilks25 speaks of a man whom he saw in the asylum at Morningside

who could be moulded into any position. While in bed on his back his
arms and legs could be arranged in any position, and there they
would remain. He also speaks of a case seen by Savage in Bethlem
—a young man who kept his arms stretched out for two hours, and
stood on one leg for a very long time or until he fell.
25 Lectures on Diseases of the Nervous System, delivered at Guy's Hospital.

William Barton Hopkins of Philadelphia has given me brief details of

a case observed by him at the Pennsylvania Hospital, which would
seem to have been either one of katatonia or one of cataleptoid
attacks occurring in an inebriate. The patient was an habitual
moderate drinker. For three weeks before he was admitted to the
hospital he had been drinking heavily. His family history showed a
tendency to insanity. He showed great mental anxiety; his face was
pale and had a very troubled aspect. He had no hallucinations. Two
days after admission a sudden outbreak of mania occurred, in which
he showed destructive and dangerous tendencies, and mechanical
restraint had to be employed. Under treatment he became quiet, and
was removed by his friends, having been altogether five days in the
hospital. On the day of his departure, while awaiting some of his
friends in the main hall, he suddenly ran up stairs, and was quickly
followed by a nurse, who found him raising a window with the
apparent intention of jumping out. His face at this time had lost its
troubled look, and had rather a pleased but vacant appearance.
While in this condition his limbs were placed in various positions, and
there remained. On another occasion, while lying on the bed, his
limbs and trunk were placed in various grotesque positions, and
there remained. The condition of waxen flexibility was well marked;
many tests were made.

To Wharton Sinkler I am indebted for the unpublished notes of the

case of a woman twenty-seven years of age, who had no family
history of insanity, but whose father was a highly nervous man. She
had always had good health, and was of good physique. Seven
years ago she had an attack of melancholia lasting four or five
months; since then she had no trouble until six months since. At this
time she began to be low-spirited. Then delusions came on—that
she was unworthy to live; that it was wicked for her to eat, because
no one else had food; that those about her were in ill-health. She
refused to eat, and would not talk, and slept badly. When first seen
by Sinkler she was stout and with apparently good nutrition, but was
said to have lost flesh. Her face was expressionless, and she was
unwilling to converse, but said she was quite well, and that her
stepmother was ill and needed treatment. She was undecided in all
her movements, and would stand in one spot until led to a chair,
where she would remain if seated.

The patient was placed under the care of two nurses, and for a week
improved daily—ate food, conversed, read aloud, and sewed. At the
end of this time she was left with one nurse, but became obstinate
about eating, and had an altercation with the nurse, in which she
became violent. After this she gradually got into a cataleptoid state.
At first she would stand for a long time in one place, and if seated in
a chair would remain in any position in which she was placed. She
began to have attacks in which she would lie on the floor motionless
for hours. A sharp faradic current was applied to the forearms on one
occasion, and she soon became relaxed. In the attacks the eyes
were closed or rolled upward and fixed on the ceiling. The muscles
were rigid. The arms and legs could be placed in any attitude, and
would there remain. There was no analgesia: she had decided
objection to pin-pricks. For two or three days she was readily
aroused from the cataleptic state by electricity, but it lost its effect,
and etherization was resorted to. The first time a few whiffs of ether