Erythrocyte ghost NADH dehydrogenase is inhibited in a competitive fashion by ATP and ADP whereas... more Erythrocyte ghost NADH dehydrogenase is inhibited in a competitive fashion by ATP and ADP whereas other nucleoside di-and triphosphates, cyclic nucleosides, as well as non-phosphorylating ATP analogs are relatively ineffective. In addition, this enzyme, measured with ferricyanide as electron acceptor, is inhibited by uncouplers of oxidative phosphorylation (proton-conducting reagents), the inhibition being competitive in character (i.e., the uncouplers were without influence upon maximum velocity). The effectiveness of the uncouplers was in the order of their hydrophobic character with the presence of the alkyl side chain rendering nonyl-dinitrophenol much more active than 2,6-dinitrophenol itself. Hydrophobic compounds that are not protonophores (e.g., eosin, proflavin or valinomycin) were not inhibitory. Whereas adenine nucleotides probably inhibit NADH oxidation competitively through structural similarity with the substrate, it appears unlikely that uncouplers compete at the NADH site directly. Rather, the apparently-competitive inhibition in the latter case may reflect competition for proton transfer to an acceptor residing in a hydrophobic region of the enzyme complex.
Operations research (OR) is well established in India and is also a prominent feature of the glob... more Operations research (OR) is well established in India and is also a prominent feature of the global and local agendas for tuberculosis (TB) control. India accounts for a quarter of the global burden of TB and of new cases. Multidrug-resistant TB is a significant problem in Mumbai, India's most populous city, and there have been recent reports of totally resistant TB. Much thought has been given to the role of OR in addressing programmatic challenges, by both international partnerships and India's Revised National TB Control Programme. We attempt to summarize the major challenges to TB control in Mumbai, with an emphasis on drug resistance. Specific challenges include diagnosis of TB and defining cure, detecting drug resistant TB, multiple sources of health care in the private, public and informal sectors, co-infection with human immunodeficiency virus (HIV) and a concurrent epidemic of non-communicable diseases, suboptimal prescribing practices, and infection control. We propose a local agenda for OR: modeling the effects of newer technologies, active case detection, and changes in timing of activities, and mapping hotspots and contact networks; modeling the effects of drug control, changing the balance of ambulatory and inpatient care, and adverse drug reactions; modeling the effects of integration of TB and HIV diagnosis and management, and preventive drug therapy; and modeling the effects of initiatives to improve infection control.
Background: Around 86% of births in Mumbai, India, occur in healthcare institutions, but this agg... more Background: Around 86% of births in Mumbai, India, occur in healthcare institutions, but this aggregate figure hides substantial variation and little is known about urban home births. We aimed to explore factors influencing the choice of home delivery, care practices and costs, and to identify characteristics of women, households and the environment which might increase the likelihood of home birth.
Public health interventions usually operate at the level of groups rather than individuals, and c... more Public health interventions usually operate at the level of groups rather than individuals, and cluster randomized controlled trials (RCTs) are one means of evaluating their effectiveness. Using examples from six such trials in Bangladesh, India, Malawi and Nepal, we discuss our experience of the ethical issues that arise in their conduct. We set cluster RCTs in the broader context of
The overwhelming majority of the world's annual 4 million neonatal deaths occur in developing cou... more The overwhelming majority of the world's annual 4 million neonatal deaths occur in developing countries. This review therefore briefly addresses the burden, aetiology, prevention and management of serious neonatal bacterial infections in lowincome settings.
This article describes the critical first steps taken to revitalize the vast public health system... more This article describes the critical first steps taken to revitalize the vast public health system of Mumbai City through the active participation of personnel from within the system. It focuses on one of two components of an ambitious action-research project aimed at improving the survival and health of newborn infants and mothers living in slum communities in Mumbai.
More than 9 million neonatal deaths occur each year, 98% of them in developing countries. Neonata... more More than 9 million neonatal deaths occur each year, 98% of them in developing countries. Neonatal deaths account for two-thirds of deaths in infancy and 40% of deaths before age 5 y. The major direct causes of neonatal death are infections, preterm delivery and asphyxia. Important indirect causes include low birth weight and hypothermia. The present body of work on
... Tanja AJ Houweling, Anthony Costello, and David Osrin relation to drug supply), to stimulate ... more ... Tanja AJ Houweling, Anthony Costello, and David Osrin relation to drug supply), to stimulate community awareness of maternal and child health ... Chowdhury, EK, El Arifeen, S., Rahman, M., Hoque, DE, Hossain, MA, Begum, K., Siddik, A., Begum, N., Sadeq-ur Rahman, Q., Akter ...
Background. Body composition is important as a marker of both current and future health. Bioelect... more Background. Body composition is important as a marker of both current and future health. Bioelectrical impedance (BIA) is a simple and accurate method for estimating body composition, but requires population-specific calibration equations. Objectives.
To determine home based newborn care practices in rural Nepal in order to inform strategies to im... more To determine home based newborn care practices in rural Nepal in order to inform strategies to improve neonatal outcome. Cross sectional, retrospective study using structured interviews. Makwanpur district, Nepal. 5411 married women aged 15 to 49 years who had given birth to a live baby in the past year. Attendance at delivery, hygiene, thermal care, and early feeding practices. 4893 (90%) women gave birth at home. Attendance at delivery by skilled government health workers was low (334, 6%), as was attendance by traditional birth attendants (267, 5%). Only 461 (8%) women had used a clean home delivery kit, and about half of attendants had washed their hands. Only 3482 (64%) newborn infants had been wrapped within half an hour of birth, and 4992 (92%) had been bathed within the first hour. 99% (5362) of babies were breast fed, 91% (4939) within six hours of birth. Practices with respect to colostrum and prelacteals were not a cause for anxiety. Health promotion interventions most li...
To describe the prevalence and determinants of births by caesarean section in private and public ... more To describe the prevalence and determinants of births by caesarean section in private and public health facilities in underserved communities in South Asia. Cross-sectional study. 81 community-based geographical clusters in four locations in Bangladesh, India and Nepal (three rural, one urban). 45,327 births occurring in the study areas between 2005 and 2012. Proportion of caesarean section deliveries by location and type of facility; determinants of caesarean section delivery by location. Institutional delivery rates varied widely between settings, from 21% in rural India to 90% in urban India. The proportion of private and charitable facility births delivered by caesarean section was 73% in Bangladesh, 30% in rural Nepal, 18% in urban India and 5% in rural India. The odds of caesarean section were greater in private and charitable health facilities than in public facilities in three of four study locations, even when adjusted for pregnancy and delivery characteristics, maternal ch...
The Healthy Cities movement has been in process for almost 30 years, and the features needed to t... more The Healthy Cities movement has been in process for almost 30 years, and the features needed to transform a city into a healthy one are becoming increasingly understood. What is less well understood, however, is how to deliver the potential health benefits and how to ensure that they reach all citizens in urban areas across the world. This task is becoming increasingly important because most of the world's population already live in cities, and, with high rates of urbanisation, many millions more will soon do so in the coming decades.
Background In 2002-04, we did a randomised controlled trial in southern Nepal, and reported that ... more Background In 2002-04, we did a randomised controlled trial in southern Nepal, and reported that children born to mothers taking multiple micronutrient supplements during pregnancy had a mean birthweight 77 g greater than children born to mothers taking iron and folic acid supplements. Children born to mothers in the study group were a mean 204 g heavier at 2·5 years of age and their systolic blood pressure was a mean 2·5 mm Hg lower than children born to mothers in the control group. We aimed to follow up the same children to mid-childhood (age 8·5 years) to investigate whether these diff erences would be sustained.
National estimates for the numbers of babies born small for gestational age and the comorbidity w... more National estimates for the numbers of babies born small for gestational age and the comorbidity with preterm birth are unavailable. We aimed to estimate the prevalence of term and preterm babies born small for gestational age (term-SGA and preterm-SGA), and the relation to low birthweight (<2500 g), in 138 countries of low and middle income in 2010. Small for gestational age was defined as lower than the 10th centile for fetal growth from the 1991 US national reference population. Data from 22 birth cohort studies (14 low-income and middle-income countries) and from the WHO Global Survey on Maternal and Perinatal Health (23 countries) were used to model the prevalence of term-SGA births. Prevalence of preterm-SGA infants was calculated from meta-analyses. In 2010, an estimated 32·4 million infants were born small for gestational age in low-income and middle-income countries (27% of livebirths), of whom 10·6 million infants were born at term and low birthweight. The prevalence of ...
Food security exists when people have access at all times to adequate, safe and nutritious food f... more Food security exists when people have access at all times to adequate, safe and nutritious food for a healthy and active life. Food insecurity contributes to poor health and nutritional outcomes (1) . We assessed food security status in a cohort of households in Nepal's central Terai.
Chronic childhood malnutrition remains common in India. As part of an initiative to improve mater... more Chronic childhood malnutrition remains common in India. As part of an initiative to improve maternal and child health in urban slums, we collected anthropometric data from a sample of children followed up from birth. We described the proportions of underweight, stunting, and wasting in young children, and examined their relationships with age. We used two linked datasets: one based on institutional birth weight records for 17 318 infants, collected prospectively, and one based on follow-up of a subsample of 1941 children under five, collected in early 2010. Mean birth weight was 2736 g (SD 530 g), with a low birth weight (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;2500 g) proportion of 22%. 21% of infants had low weight for age standard deviation (z) scores at birth (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;-2 SD). At follow-up, 35% of young children had low weight for age, 17% low weight for height, and 47% low height for age. Downward change in weight for age was greater in children who had been born with higher z scores. Our data support the idea that much of growth faltering was explained by faltering in height for age, rather than by wasting. Stunting appeared to be established early and the subsequent decline in height for age was limited. Our findings suggest a focus on a younger age-group than the children over the age of three who are prioritized by existing support systems. The trial during which the birth weight data were collected was funded by the ICICI Foundation for Inclusive Growth (Centre for Child Health and Nutrition), and The Wellcome Trust (081052/Z/06/Z). Subsequent collection, analysis and development of the manuscript was funded by a Wellcome Trust Strategic Award: Population Science of Maternal and Child Survival (085417ma/Z/08/Z). D Osrin is funded by The Wellcome Trust (091561/Z/10/Z).
Background: Perinatal common mental disorders are a major cause of disability among women and hav... more Background: Perinatal common mental disorders are a major cause of disability among women and have consequences for children's growth and development. We aimed to identify factors associated with psychological distress, a proxy for common mental disorders, among mothers in rural Dhanusha, Nepal. Methods: We used data from 9078 mothers who were screened for distress using the 12-item General Health Questionnaire (GHQ-12) around six weeks after delivery. We assessed the association between GHQ-12 score and socioeconomic, gender-based, cultural and reproductive health factors using a hierarchical analytical framework and multilevel linear regression models. Results: Using a threshold GHQ-12 score of Z6 to indicate caseness, the prevalence of distress was 9.8% (886/9078). Factors that predicted distress were severe food insecurity (β 2.21 (95% confidence interval 1.43, 3.40)), having a multiple birth (2.
European Journal of Obstetrics & Gynecology and Reproductive Biology, 2000
HIV positive women of reproductive age are increasingly treated with a combination of antiretrovi... more HIV positive women of reproductive age are increasingly treated with a combination of antiretroviral agents, with effects on the developing human fetus that are largely unknown. We report two cases of severe spinal malformations in the fetuses of women treated with combination antiretroviral therapy and co-trimoxazole.
Erythrocyte ghost NADH dehydrogenase is inhibited in a competitive fashion by ATP and ADP whereas... more Erythrocyte ghost NADH dehydrogenase is inhibited in a competitive fashion by ATP and ADP whereas other nucleoside di-and triphosphates, cyclic nucleosides, as well as non-phosphorylating ATP analogs are relatively ineffective. In addition, this enzyme, measured with ferricyanide as electron acceptor, is inhibited by uncouplers of oxidative phosphorylation (proton-conducting reagents), the inhibition being competitive in character (i.e., the uncouplers were without influence upon maximum velocity). The effectiveness of the uncouplers was in the order of their hydrophobic character with the presence of the alkyl side chain rendering nonyl-dinitrophenol much more active than 2,6-dinitrophenol itself. Hydrophobic compounds that are not protonophores (e.g., eosin, proflavin or valinomycin) were not inhibitory. Whereas adenine nucleotides probably inhibit NADH oxidation competitively through structural similarity with the substrate, it appears unlikely that uncouplers compete at the NADH site directly. Rather, the apparently-competitive inhibition in the latter case may reflect competition for proton transfer to an acceptor residing in a hydrophobic region of the enzyme complex.
Operations research (OR) is well established in India and is also a prominent feature of the glob... more Operations research (OR) is well established in India and is also a prominent feature of the global and local agendas for tuberculosis (TB) control. India accounts for a quarter of the global burden of TB and of new cases. Multidrug-resistant TB is a significant problem in Mumbai, India&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s most populous city, and there have been recent reports of totally resistant TB. Much thought has been given to the role of OR in addressing programmatic challenges, by both international partnerships and India&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Revised National TB Control Programme. We attempt to summarize the major challenges to TB control in Mumbai, with an emphasis on drug resistance. Specific challenges include diagnosis of TB and defining cure, detecting drug resistant TB, multiple sources of health care in the private, public and informal sectors, co-infection with human immunodeficiency virus (HIV) and a concurrent epidemic of non-communicable diseases, suboptimal prescribing practices, and infection control. We propose a local agenda for OR: modeling the effects of newer technologies, active case detection, and changes in timing of activities, and mapping hotspots and contact networks; modeling the effects of drug control, changing the balance of ambulatory and inpatient care, and adverse drug reactions; modeling the effects of integration of TB and HIV diagnosis and management, and preventive drug therapy; and modeling the effects of initiatives to improve infection control.
Background: Around 86% of births in Mumbai, India, occur in healthcare institutions, but this agg... more Background: Around 86% of births in Mumbai, India, occur in healthcare institutions, but this aggregate figure hides substantial variation and little is known about urban home births. We aimed to explore factors influencing the choice of home delivery, care practices and costs, and to identify characteristics of women, households and the environment which might increase the likelihood of home birth.
Public health interventions usually operate at the level of groups rather than individuals, and c... more Public health interventions usually operate at the level of groups rather than individuals, and cluster randomized controlled trials (RCTs) are one means of evaluating their effectiveness. Using examples from six such trials in Bangladesh, India, Malawi and Nepal, we discuss our experience of the ethical issues that arise in their conduct. We set cluster RCTs in the broader context of
The overwhelming majority of the world's annual 4 million neonatal deaths occur in developing cou... more The overwhelming majority of the world's annual 4 million neonatal deaths occur in developing countries. This review therefore briefly addresses the burden, aetiology, prevention and management of serious neonatal bacterial infections in lowincome settings.
This article describes the critical first steps taken to revitalize the vast public health system... more This article describes the critical first steps taken to revitalize the vast public health system of Mumbai City through the active participation of personnel from within the system. It focuses on one of two components of an ambitious action-research project aimed at improving the survival and health of newborn infants and mothers living in slum communities in Mumbai.
More than 9 million neonatal deaths occur each year, 98% of them in developing countries. Neonata... more More than 9 million neonatal deaths occur each year, 98% of them in developing countries. Neonatal deaths account for two-thirds of deaths in infancy and 40% of deaths before age 5 y. The major direct causes of neonatal death are infections, preterm delivery and asphyxia. Important indirect causes include low birth weight and hypothermia. The present body of work on
... Tanja AJ Houweling, Anthony Costello, and David Osrin relation to drug supply), to stimulate ... more ... Tanja AJ Houweling, Anthony Costello, and David Osrin relation to drug supply), to stimulate community awareness of maternal and child health ... Chowdhury, EK, El Arifeen, S., Rahman, M., Hoque, DE, Hossain, MA, Begum, K., Siddik, A., Begum, N., Sadeq-ur Rahman, Q., Akter ...
Background. Body composition is important as a marker of both current and future health. Bioelect... more Background. Body composition is important as a marker of both current and future health. Bioelectrical impedance (BIA) is a simple and accurate method for estimating body composition, but requires population-specific calibration equations. Objectives.
To determine home based newborn care practices in rural Nepal in order to inform strategies to im... more To determine home based newborn care practices in rural Nepal in order to inform strategies to improve neonatal outcome. Cross sectional, retrospective study using structured interviews. Makwanpur district, Nepal. 5411 married women aged 15 to 49 years who had given birth to a live baby in the past year. Attendance at delivery, hygiene, thermal care, and early feeding practices. 4893 (90%) women gave birth at home. Attendance at delivery by skilled government health workers was low (334, 6%), as was attendance by traditional birth attendants (267, 5%). Only 461 (8%) women had used a clean home delivery kit, and about half of attendants had washed their hands. Only 3482 (64%) newborn infants had been wrapped within half an hour of birth, and 4992 (92%) had been bathed within the first hour. 99% (5362) of babies were breast fed, 91% (4939) within six hours of birth. Practices with respect to colostrum and prelacteals were not a cause for anxiety. Health promotion interventions most li...
To describe the prevalence and determinants of births by caesarean section in private and public ... more To describe the prevalence and determinants of births by caesarean section in private and public health facilities in underserved communities in South Asia. Cross-sectional study. 81 community-based geographical clusters in four locations in Bangladesh, India and Nepal (three rural, one urban). 45,327 births occurring in the study areas between 2005 and 2012. Proportion of caesarean section deliveries by location and type of facility; determinants of caesarean section delivery by location. Institutional delivery rates varied widely between settings, from 21% in rural India to 90% in urban India. The proportion of private and charitable facility births delivered by caesarean section was 73% in Bangladesh, 30% in rural Nepal, 18% in urban India and 5% in rural India. The odds of caesarean section were greater in private and charitable health facilities than in public facilities in three of four study locations, even when adjusted for pregnancy and delivery characteristics, maternal ch...
The Healthy Cities movement has been in process for almost 30 years, and the features needed to t... more The Healthy Cities movement has been in process for almost 30 years, and the features needed to transform a city into a healthy one are becoming increasingly understood. What is less well understood, however, is how to deliver the potential health benefits and how to ensure that they reach all citizens in urban areas across the world. This task is becoming increasingly important because most of the world's population already live in cities, and, with high rates of urbanisation, many millions more will soon do so in the coming decades.
Background In 2002-04, we did a randomised controlled trial in southern Nepal, and reported that ... more Background In 2002-04, we did a randomised controlled trial in southern Nepal, and reported that children born to mothers taking multiple micronutrient supplements during pregnancy had a mean birthweight 77 g greater than children born to mothers taking iron and folic acid supplements. Children born to mothers in the study group were a mean 204 g heavier at 2·5 years of age and their systolic blood pressure was a mean 2·5 mm Hg lower than children born to mothers in the control group. We aimed to follow up the same children to mid-childhood (age 8·5 years) to investigate whether these diff erences would be sustained.
National estimates for the numbers of babies born small for gestational age and the comorbidity w... more National estimates for the numbers of babies born small for gestational age and the comorbidity with preterm birth are unavailable. We aimed to estimate the prevalence of term and preterm babies born small for gestational age (term-SGA and preterm-SGA), and the relation to low birthweight (<2500 g), in 138 countries of low and middle income in 2010. Small for gestational age was defined as lower than the 10th centile for fetal growth from the 1991 US national reference population. Data from 22 birth cohort studies (14 low-income and middle-income countries) and from the WHO Global Survey on Maternal and Perinatal Health (23 countries) were used to model the prevalence of term-SGA births. Prevalence of preterm-SGA infants was calculated from meta-analyses. In 2010, an estimated 32·4 million infants were born small for gestational age in low-income and middle-income countries (27% of livebirths), of whom 10·6 million infants were born at term and low birthweight. The prevalence of ...
Food security exists when people have access at all times to adequate, safe and nutritious food f... more Food security exists when people have access at all times to adequate, safe and nutritious food for a healthy and active life. Food insecurity contributes to poor health and nutritional outcomes (1) . We assessed food security status in a cohort of households in Nepal's central Terai.
Chronic childhood malnutrition remains common in India. As part of an initiative to improve mater... more Chronic childhood malnutrition remains common in India. As part of an initiative to improve maternal and child health in urban slums, we collected anthropometric data from a sample of children followed up from birth. We described the proportions of underweight, stunting, and wasting in young children, and examined their relationships with age. We used two linked datasets: one based on institutional birth weight records for 17 318 infants, collected prospectively, and one based on follow-up of a subsample of 1941 children under five, collected in early 2010. Mean birth weight was 2736 g (SD 530 g), with a low birth weight (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;2500 g) proportion of 22%. 21% of infants had low weight for age standard deviation (z) scores at birth (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;-2 SD). At follow-up, 35% of young children had low weight for age, 17% low weight for height, and 47% low height for age. Downward change in weight for age was greater in children who had been born with higher z scores. Our data support the idea that much of growth faltering was explained by faltering in height for age, rather than by wasting. Stunting appeared to be established early and the subsequent decline in height for age was limited. Our findings suggest a focus on a younger age-group than the children over the age of three who are prioritized by existing support systems. The trial during which the birth weight data were collected was funded by the ICICI Foundation for Inclusive Growth (Centre for Child Health and Nutrition), and The Wellcome Trust (081052/Z/06/Z). Subsequent collection, analysis and development of the manuscript was funded by a Wellcome Trust Strategic Award: Population Science of Maternal and Child Survival (085417ma/Z/08/Z). D Osrin is funded by The Wellcome Trust (091561/Z/10/Z).
Background: Perinatal common mental disorders are a major cause of disability among women and hav... more Background: Perinatal common mental disorders are a major cause of disability among women and have consequences for children's growth and development. We aimed to identify factors associated with psychological distress, a proxy for common mental disorders, among mothers in rural Dhanusha, Nepal. Methods: We used data from 9078 mothers who were screened for distress using the 12-item General Health Questionnaire (GHQ-12) around six weeks after delivery. We assessed the association between GHQ-12 score and socioeconomic, gender-based, cultural and reproductive health factors using a hierarchical analytical framework and multilevel linear regression models. Results: Using a threshold GHQ-12 score of Z6 to indicate caseness, the prevalence of distress was 9.8% (886/9078). Factors that predicted distress were severe food insecurity (β 2.21 (95% confidence interval 1.43, 3.40)), having a multiple birth (2.
European Journal of Obstetrics & Gynecology and Reproductive Biology, 2000
HIV positive women of reproductive age are increasingly treated with a combination of antiretrovi... more HIV positive women of reproductive age are increasingly treated with a combination of antiretroviral agents, with effects on the developing human fetus that are largely unknown. We report two cases of severe spinal malformations in the fetuses of women treated with combination antiretroviral therapy and co-trimoxazole.
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Papers by David Osrin