Methods in Biostatistics for Medical Students and Research Workers BK Mahajan, Arun Bhadra Khanal
INDEX
A
Abortion 182
Amniocentesis 170, 213, 231
Avidity 71
B
Bilateral chorioretinitis 105
C
Cataract 106, 109
Chorionic villus sampling 171, 214
transabdominal 173
transcervical 172
Clinically apparent disease 131
CMV infection in pregnancy 229
important points 235
management of 229
treatment 234
Congenital CMV infection 231
Congenital infection 2
Congenital TORCH infection and hearing loss 112
audiological assessment 118
cytomegalovirus 113
herpes 117
rubella 115
toxoplasma 116
Congenital TORCH infections 185
general approach 185
systemic approach 186
Cord-blood sampling 174
Cordocentesis 212
Cytomegalovirus 77, 107
investigations 108
ocular manifestations 108
Cytomegalovirus infection 197
antigen detection 201
laboratory diagnosis 198
molecular methods 200
serodiagnosis 199
prevention 203
prognosis 203
D
Dangling choroid plexus 147
Development of high affinity antibodies 64
Disseminated infection 128
E
Early pregnancy loss 182
factors involved 183
Encephalitis 129
F
Fetal damage 73
Fetal TORCH infection 168
clinical features 169
prenatal diagnosis 168, 169
Fetal TORCH syndromes 166
cytomegalovirus 167
herpes simplex virus 168
rubella 167
toxoplasmosis 166
Functional affinity 71
G
German or three-day measles 194
Glaucoma 107
H
Hepatosplenomegaly 149
Herpes simplex virus 79, 108
investigation 109
ocular manifestations 109
Herpes simplex virus infection 49, 203
diagnostic aids 204
diagnosis in mother 51
management 205
neonatal transmission 50
pathogenesis 50
prevention 206
prognosis 205
Human cytomegalovirus 39
diagnosis 44
detection by shell vial culture 46
prenatal 49
primary infection 44
secondary infection 45
infection of the mother 39
consequences 41
outcome of congenital infection 42
pathogenesis 44
Hydranencephaly 148
Hydrocephalus 132
Hydrocephalus/ventriculomegaly 146
Hydrops fetalis 151
Hyperechoic bowel 151
I
IgG-avidity assays in infectious diseases 65
clinical justification 67
theoretical justification 66
Immunocompromised pregnant women and TORCH 250
cytomegalovirus 254
herpes simplex 255
important points 257
rubella 253
toxoplasmosis 251
Infections during pregnancy 73
Intra-abdominal calcification 150
Intracranial calcification 132, 148
Intrauterine rubella infection 224
important points 228
management protocols 224
prenatal diagnosis and management decision 227
woman diagnosed to have rubella during pregnancy 225
woman presenting for prepregnancy counseling 224
K
Keratoconjunctivitis 109
M
Maternal TORCH infections 56
CMV 58
herpes simplex virus 59
rubella 58
toxoplasmosis 56
Meningoencephalitis 124
Mental retardation 99, 133
contribution of TORCH infection 99
cytomegalovirus 101
herpes simplex virus 101
other organisms 101
rubella 100
toxoplasmosis 100
disorders mimicking congenital infections 102
treatment and prognosis 102
Microcephaly 133, 135, 148
Microcornea 107
Microphthalmos 107
N
Necrotizing chorioretinitis 109
Neurological sequelae 121
cytomegalovirus infection 134
asymptomatic infection 134
CNS manifestations 135
pathogenesis 134
perinatal and early postnatal infection 137
symptomatic infection 135
treatment and prognosis 136
herpes simplex 127
cutaneous disease 128
intrauterine infection 127
treatment and prognosis 130
rubella 121
clinical features 124
Indian scene 123
long-term prognosis 126
permanent manifestations 125
transient manifestations 124
toxoplasmosis 130
CNS findings 131
treatment and prognosis 133
P
Perinatal infections 74
Placentomegaly 153
Pregnant woman with genital herpes 237
antiviral medication 239
counseling the patient 242
effect of HSV infection on pregnancy 238
invasive procedures in women with HSV 245
management of first episode of genital herpes 240
management of recurrent episode of genital herpes 243
neonatal herpes 239
patients with active HSV and preterm premature rupture of membranes 245
patients with active HSV infection and ruptured membranes 244
presentation of infection 237
prevention of acquisition 246
prevention of postnatal HSV
transmission to the neonate 245
role of cesarean section 242
role of HSV serology during pregnancy 241
role of universal screening 246
routes and risk of transmission 238
women with nongenital herpes 244
Prevention of congenital TORCH infection 272
cytomegalovirus 277
general issues 278
herpes simplex 278
recommendations for education and health policy 279
general 279
specific to particular organisms 280
rubella 276
toxoplasmosis 272
guidelines of Center of Disease Control 274
types of 273
Primary CMV infection 232
Principle of antibody affinity and avidity 63
Progressive rubella panencephalitis 125
R
Recurrent infection 233
Retinitis 108
Retinopathy 106
Rubella 32, 105, 194
epidemiology 32
investigations 106
laboratory diagnosis 195
molecular methods 195
serodiagnosis 195
virus isolation 196
management 36
methods of laboratory diagnosis 34
serology 34
viral antigen detection 35
virus isolation 35
ocular manifestations 106
pathogenesis 33
prevention 197
transmission to fetus 33
vaccination 37
S
Screening of TORCH infections in pregnancy 262
cytomegalovirus 267
disease characteristics 267
role of screening 268
herpes simplex virus 269
disease characteristics 269
role of screening 269
rubella 266
disease characteristics 266
role of screening 267
toxoplasmosis 263
disease characteristics 263
magnitude of problem 263
prenatal therapy 265
role of screening 265
T
TORCH 1
approach to clinical management 5
diagnosis 8
fetal therapy 9
identification and screening 7
neonatal management 10
prevention 10
congenital 4
important points 11
incidence 2
CMV 2
HSV 3
rubella 3
toxoplasma 3
maternal fetal transmission 4
TORCH infections 144
3-D ultrasound 159
anomalies detected in relation to 159
Doppler ultrasound 158
evaluating fetal heart disease 158
to study the evolution of hydrops 158
interventional ultrasound 156
diagnosis 157
therapy 157
sonographic findings 146
abdomen 149
brain 146
cardiac abnormalities 152
change in amniotic fluid volume 153
IUGR 153
limb defects 152
ultrasonographic features 155
specific findings 155
cytomegalovirus 156
rubella 155
toxoplasmosis 156
TORCH infections in pregnancy 284, 292
TORCH infections Indian experience 96
Toxoplasma gondii 104
investigations 105
ocular manifestations 105
Toxoplasma infection 17
Toxoplasmosis 17, 75, 186, 208
antigen detection 193
congenital 211
diagnosis 28
serologic tests for demonstration of antibody 28
effect of prenatal treatment 218
efficacy of prenatal treatment 217
epidemiology 22
important points 221
laboratory diagnosis 187
important facts 189
molecular methods 190
parasite isolation 192
serodiagnosis 188
management of toxoplasmosis during pregnancy 220
maternal fetal transmission 209
mode of transmission 20
parasite 18
pathogenesis 21, 24
prenatal diagnosis 211
prenatal treatment 214
pyrimethamine 216
spiramycin 215, 216
sulfadiazine 217
sulfonamide-pyrimethamine 215
prevention 193
screening 208
V
Ventricular septal defect 153
Vertically transmitted infections 82
infant born with congenital cytomegalovirus infection 87
acute fulminant infection 88
diagnosis of congenital CMV infection 90
perinatally acquired cytomegaloviral infection 89
sequelae of congenital CMV infection 88
neonate born to a mother with toxoplasmosis 82
clinical features of some perinatal infections 83
neurological involvement in perinatal infections 84
subclinical congenital toxoplasma infection 85
symptomatic congenital toxoplasma infection 86
neonate born to mother with herpes simplex virus 93
clinical manifestations 94
CNS infection in absence of disseminated disease 94
determinants of fetal transmission 93
diagnosis of neonatal HSV infection 95
skin eye-mouth/mucocutaneous disease 94
neonates born with congenital rubella syndrome 91
diagnosis 92
manifestations 91
×
Chapter Notes

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1Methods in Biostatistics2
3Methods in Biostatistics
For Medical Students and Research Workers
Seventh Edition
BK Mahajan MBBS DPH FCGP FIAPSM Professor of Preventive and Social Medicine At Jamnagar (1960–73) and Sevagram (1973–82) Deputy Director Health Services erstwhile Mumbai State (1958–60) and Sr. Consultant, Integrated Child Development Services Department of Gastroenterology and Human Nutrition Unit AIIMS, Ansari Nagar, New Delhi 110029 (1982–87) Consultant of Delhi Council of Child Welfare Statistical Check by Sh BD Malhotra and Prof KR Sundram Head of Department of Biostatistics, AIIMS, New Delhi, India Revised by Arun Bhadra Khanal Lecturer of Statistics Nobel College, Kathmandu Pokhara University, Nepal Foreword by VP Reddaiah
4Published by
Jitendar P Vij
Jaypee Brothers Medical Publishers (P) Ltd
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Methods in Biostatistics
© 2010, Jaypee Brothers Medical Publishers
All rights reserved. No part of this publication should be reproduced, stored in a retrieval system, or transmitted in any form or by any means: electronic, mechanical, photocopying, recording, or otherwise, without the prior written permission of the author and the publisher.
First Edition: 1967
Seventh Edition: 2010
9788184487138
Typeset at JPBMP typesetting unit
Printed at Ajanta
5“Those whom the gods love die young”
Lalit
(Born on Tuesday, September 12, 1944)
This work is dedicated to the loving memory of Author's only son, LALIT who lost his life on way to USA for higher studies in mechanical engineering, in the Air India Boeing accident near Mont Blanc on January 24, 1966, along with 116 others including the world-renowned Atomic Energy Scientist, Dr Homi Bhabha.6
7About the Author
After a brilliant academic career, Dr BK Mahajan got a wide and rich experience as a Senior Health Administrator for 12 years in old Bombay state and over 22 years as Professor of preventive and Social Medicine. He was Sr. Consultant, ICDS Aug. 1982 to Dec. 1987 and was also Consultant of DCCW.
In 1961–62, he was deputed to visit medical schools, in the UK and Europe to study teaching of Prevention and Social Medicine. He had read several papers at All India Conferences and published many of them in Journals of repute, apart from having written book on his subject. From 1973 to 1982 he had served as Professor of Preventive and Social Medicine at Sevagram (Wardha) where he was continued as life long Professor Emeritus. Since 1982 to 1988 he was selected as Sr. Consultant for ICDS at AIIMS, New Delhi to serve the entire country.
He was honoured to deliver Dhanwantri Oration at IAPSM Conference, Bangalore in 1976, Late Rama Murthi Guest Oration at Hyderabad in 1980 and Dr Rameshwar Sharma Oration at Bikaner in 1983. He was Secretary of IAPSM in 1979–80, first President of IAPSM in 1983 and was President of Ind. Assoc. of Comm. Diseases from 1980.
He was an Indian Delegate to Seminar on Medical Education in SEA Countries, at Pokhra (Nepal) in 1976.
He traveled widely in India, UK, Europe, USA and Japan to study the problems of Medical Education in general and of teaching Preventive and Social Medicine/Community Medicine and Biostatistics in particular.
The very next day after retiring from AIIMS, he was requested to join as Medical Consultant to Delhi Council of Child Welfare where he was in 1997 and DCCW wished him to continue as long as his health permited.
He had been active member of IMA too and was playing a very vital role in various activities of Delhi Medical Association.8
9Foreword
It is my proud privilege to write the foreword to Methods in Biostatistics by Dr BK Mahajan, who is the grand old man of Preventive and Social Medicine. Most of the Biostatistics books available to Indian students are by foreign nonmedical statisticians who use mathematical formulas which make medical people averse towards statistics. They fail to understand and appreciate the use of statistics in their continuing education by literature review, practice and research.
But this book has been written by an eminent medical person who understands the mentality of the medical people towards statistics. He has written this book from the perspective of medical people in simple language with very little mathematical formulas and Indian examples. This makes medical people accept and master statistics. The fact that this book has come to 7th edition in 43 years is an eloquent testimony to the popularity of the book.
This book is a great boon to medical students both undergraduates and postgraduates who want to be self-significant in statistical analysis. It is a book that every medical person and medical college library must possess. I wish him success in his endeavor and happy to release this edition.
Dr VP Reddaiah
Prof & Head Centre for Community Medicine, AIIMS
New Delhi10
11Preface to the Seventh Edition
Scientific methods of statistical analysis, which were almost unknown a few years ago, today provide very effective data for understanding and in-depth study of any branch of knowledge. It facilitates interpretation of facts and application in medical sciences.
Fruits of any new technique of challenge and different modalities in treatment have to be compared. I am happy to bring the seventh edition in 2010 after the sixth in 1997. After each edition reprints had to be prepared by my publisher Jaypee Brothers in view of everincreasing damand in India and abroad because of its easy and simple understanding. There is no such averseness as existed in the past. All medical research workers too realize application of biostatistics as a science for proper evaluation of the work done—be it thesis or presentation of paper, read or published in journals of repute. There is continuous rising demand for a simple book like this, in which mathematical complexities are avoided and students can easily follow the biostatistics as a science of variation. Simple and familiar examples have been provided abundantly.
Use of computers for which special chapter has been added in brief has greatly facilitated the analysis of the work done in medical field and biosciences too.
Present edition is thoroughly revised and updated. In this context the chapter “Computer Application in Biostatistical Analysis: An SPSS Manual” has been added.
BK Mahajan
12Acknowledgments
I am grateful to Dr Prof Reddaiah for writing Foreword to this edition.
I am very grateful to the experts whose remarks are given at the end of the title of this book. I cannot help mentioning my gratefulness to late Shri BD Malhotra. Statistician, Prof KR Sundaram, Head of Biostatistical Department in AIIMS and Shri DA Shah, Statistician in Medical College, Surat.
I highly appreciate the all long cooperation and genuine support given by Shri Jitendar P Vij, Chairman and Managing Director of Jaypee Brothers Medical Publishers (P) Ltd. who are now the largest medical publishers in India. They render all help to experts in the field of medicine to publish their works. I would be failing in my duty if I don't express my gratitude to Mr PG Bandhu (Director). It is because of their cooperation that I could complete the present volume.
Dr KK Agarwal, Cardiologist at Mool Chand Hospital has given all help despite his busy schedule. A new chapter on computer is due to his help. Dr (Col) BR Chopra, Cardiology Department gave a lot of encouragement by his ever-smiling face.
Dr Bir Singh, Additional Professor of Community Medicine, AIIMS also joined me in updating demography and vital statistics and going through the initial draft but because of his other heavy involvements he did as much as he could.
I am grateful to Dr G Anjneyulu, Prof and Head of PSM, Hyderabad, Maj HS Ratti, MD (PSM), Dy Director (MHS), Dr Nitika Arora and Manu her brother, Shri Praful, Mrs Sapna Bhasin, Shri Jeya Shanker and Km Alpna. I am sincerely thankful to the dedicated team of Jaypee Brothers for their whole hearted cooperation. Dr Sultan Ahmed and Mrs Samina Khan definitely deserve a pat on their back.
Last but not the least I must sincerely thank Smt Anjna Devi Mahajan my wife and Mrs Nandini Churamani my grand daughter for sparing so much time in this dedicated work.