The influence of acetylcholine (ACh) on cardiac performance of larval (Taylor Kollros [TK] stages... more The influence of acetylcholine (ACh) on cardiac performance of larval (Taylor Kollros [TK] stages 11-XVIII) and postmetamorphic (3-609 g) Rana catesbeiana was analyzed in situ (circulatory system intact) and in vitro (isolated heart or ventricular strip preparations). Topical application of ACh to the heart in situ resulted in a dose-dependent decrease in heart rate and in a slight decrease in systolic ventricular pressure in all developmental stages. Injection of acetylcholine into the ventricle lumen in situ caused a dose-dependent transient decrease in systolic ventricular pressure, with little heart rate effect. Intraventricular ACh injection also changed the hemodynamic coupling between ventricle and conus arteriosus, generating a biphasic pressure profile in the conus due to sequential contractions of the ventricle and of the conus. In situ the sensitivity of the ventricle to ACh decreased during larval development, with the lowest sensitivity in small postmetamorphic adults. ACh applied in vitro to cardiac muscle strips or small hearts produced a negative inotropic effect. The ACh dose necessary to induce a 50% reduction in muscle strip contraction force in vitro decreased substantially during larval development, indicating an increase in ACh sensitivity with development. The effects of ACh both in vitro and in situ were diminished or eliminated by topical application or injection of atropine, suggesting the presence of muscarinic cholinergic receptors. After preincubation with the acetylcholinesterase blocker eserine, injection of ACh into the conus arteriosus decreased systolic ventricular pressure with a delay of 4-10 seconds, probably representing the minimum blood circulation time. The observed inotropic and chronotropic responses result from the action of ACh on cardiac muscle, primarily affecting systolic ventricular pressure, and on the cardiac pacemaker, mainly influencing heart rate. These responses occur as early as TK, stage 11, indicating a well-developed set of mechanisms to regulate cardiovascular performance early in development. o 1993 WiIey-Liss, Inc. Heart rate and cardiac contractility in vertebrates is determined via a complex system of neuronal and humoral control mechanisms (Nilsson, '83). These control mechanisms have long been known for the adult amphibian heart (Loewi, '21; Nilsson, '83; Axelsson and Nilsson, '85). For example, vagal cholinergic fibers and acetylcholine represent a powerful inhibitory control mechanism for cardiac activity in frogs and most other vertebrates by exerting a negative chronotropic effect. Usually acetylcholine also has a negative inotropic effect (Nilsson, '83). Far less is known about cardiac control mechanisms in amphibian larvae, although an understanding of some developmental changes is
Genetic variation in SLC12A5 which encodes KCC2, the neuronspecific cation-chloride cotransporter... more Genetic variation in SLC12A5 which encodes KCC2, the neuronspecific cation-chloride cotransporter that is essential for hyperpolarizing GABAergic signaling and formation of cortical dendritic spines, has not been reported in human disease. Screening of SLC12A5 revealed a co-segregating variant (KCC2-R952H) in an Australian family with febrile seizures. We show that KCC2-R952H reduces neuronal Cl À extrusion and has a compromised ability to induce dendritic spines in vivo and in vitro. Biochemical analyses indicate a reduced surface expression of KCC2-R952H which likely contributes to the functional deficits. Our data suggest that KCC2-R952H is a bona fide susceptibility variant for febrile seizures.
A major challenge in understanding complex idiopathic generalized epilepsies has been the charact... more A major challenge in understanding complex idiopathic generalized epilepsies has been the characterization of their underlying molecular genetic basis. Here, we report that genetic variation within the GABRD gene, which encodes the GABA A receptor subunit, affects GABA ...
Expert review of pharmacoeconomics & outcomes research, 2014
Economic evaluations that measure the benefits of health interventions in terms of units of healt... more Economic evaluations that measure the benefits of health interventions in terms of units of health gain inevitably require decision-makers to make judgments about the 'value for money' of those health gains. Decision-making bodies have also commonly returned to the position that a unit of health gain, such as an additional quality-adjusted life year, is of equal value regardless of the characteristics of the recipient. This paper focuses on whether and how health gains in economic evaluation should be differentially weighted by age of recipient. The paper presents a structured overview of evidence from the revealed preference and stated preference literature in this area. It discusses a number of methodological issues raised by differential weighting of health gains by age of recipient. These include identifying appropriate samples for the derivation of age-related weights, methodological issues surrounding the application of the quality-adjusted life year measure, the relat...
To examine the effects of designation and volume of neonatal care at the hospital of birth on mor... more To examine the effects of designation and volume of neonatal care at the hospital of birth on mortality and morbidity outcomes in very preterm infants in a managed clinical network setting. A retrospective, population-based analysis of operational clinical data using adjusted logistic regression and instrumental variables (IV) analyses. 165 National Health Service neonatal units in England contributing data to the National Neonatal Research Database at the Neonatal Data Analysis Unit and participating in the Neonatal Economic, Staffing and Clinical Outcomes Project. 20 554 infants born at <33 weeks completed gestation (17 995 born at 27-32 weeks; 2559 born at <27 weeks), admitted to neonatal care and either discharged or died, over the period 1 January 2009-31 December 2011. Tertiary designation or high-volume neonatal care at the hospital of birth. Neonatal mortality, any in-hospital mortality, surgery for necrotising enterocolitis, surgery for retinopathy of prematurity, bro...
A systematic review of recent economic evaluations of antenatal screening was conducted. Relevant... more A systematic review of recent economic evaluations of antenatal screening was conducted. Relevant studies were identified from a number of sources including computerised databases, bibliographies of economic evaluations, and searches of unpublished manuscripts. Each study identified by the literature searches was categorised on the basis of its title and abstract. Studies considered relevant to the systematic review were obtained from libraries. The methodology, results, and policy implications of studies categorised as economic evaluations upon full review were documented. A total of 566 studies were identified by the literature searches, 41 of which were categorised as economic evaluations upon full review. The economic evaluations covered a range of antenatal screening practices, aimed mainly at the prevention of infectious diseases and fetal anomalies. The review highlighted the poor methodological quality of the bulk of economic evaluations of antenatal screening. The study des...
ABSTRACT Several investigators have hypothesized that outpatient preinduction cervical ripening w... more ABSTRACT Several investigators have hypothesized that outpatient preinduction cervical ripening with nitric oxide donors such as isosorbide mononitrate (IMN) would reduce the elapsed time from hospital admission to delivery and improve women&#39;s experience of induction of labor. This double-blind randomized placebo-controlled trial investigated whether vaginal self-administration at home by woman at term would improve the process of induction of labor. The study subjects were 350 nulliparous singleton women with cephalic presentation at ≥37 weeks&#39; gestation, requiring cervical ripening before induction of labor. The participants self-administered IMN (n = 177) or placebo (n = 173) vaginally at home without fetal monitoring at 48, 32, and 16 hours before the scheduled time of admission for induction of labor. The primary study outcome measures were the elapsed time interval from hospital admission to delivery and the women&#39;s experience of home treatment for cervical ripening. Maternal satisfaction was determined with a questionnaire, using a 10 point scale with 1 = extremely good and 10 = not at all good. There was no statistically significant difference between the 2 study groups in the admission to delivery interval; the mean difference was 1.59 hours, with a 95% confidence interval (CI) of −5.08 to 1.89, P = 0.37. Compared to placebo, however, IMN was more effective in inducing a mean change in modified Bishop score from recruitment to hospital admission (mean difference: 0.65 [95% CI, 0.14–1.17, P = 0.013]). With regard to maternal satisfaction, the overall experience of home treatment was positive in both groups. Women in the placebo group reported it to be marginally more positive than those in the IMN group (placebo: 3.23 vs. IMN: 3.84; the mean difference was 0.61, with a 95% CI of 0.02–1.21, P = 0.043). No difference between the 2 groups was reported in either pain or anxiety levels or in the willingness to have the treatment in a subsequent pregnancy. These data show that administration of IMN at home is effective in ripening the cervix but does not shorten the admission to delivery interval or improve maternal satisfaction. The investigators conclude from these findings that IMN in this setting has limited clinical value.
Background: The objective of this study was to investigate the association between ethnicity and ... more Background: The objective of this study was to investigate the association between ethnicity and health related quality of life (HRQoL) in patients with type 2 diabetes.
Many factors aff ect child and adolescent mortality in high-income countries. These factors can b... more Many factors aff ect child and adolescent mortality in high-income countries. These factors can be conceptualised within four domains-intrinsic (biological and psychological) factors, the physical environment, the social environment, and service delivery. The most prominent factors are socioeconomic gradients, although the mechanisms through which they exert their eff ects are complex, aff ect all four domains, and are often poorly understood. Although some contributing factors are relatively fi xed-including a child's sex, age, ethnic origin, and genetics, some parental characteristics, and environmental conditions-others might be amenable to interventions that could lessen risks and help to prevent future child deaths. We give several examples of health service features that could aff ect child survival, along with interventions, such as changes to the physical or social environment, which could aff ect upstream (distal) factors.
Objective: To estimate costs and health utilities associated with extremely preterm birth at appr... more Objective: To estimate costs and health utilities associated with extremely preterm birth at approximately 11 years of age using evidence from a whole population study (the EPICure study). Methods: The study population comprised surviving children born at 20 through 25 completed weeks of gestation in all 276 maternity units in the United Kingdom and Republic of Ireland from March through December 1995 and a control group of classmates born at full term, matched for age, sex, and ethnic group. Estimates of utilization of health, social, and education services were combined with unit costs derived from primary and secondary sources. Generalized liner regression was used to estimate the impact of extremely preterm birth on public sector costs during the 11th year of life. Suboptimal levels of function for each of the eight attributes of the Health Utilities Index Mark III (cognition, vision, hearing, speech, ambulation, dexterity, emotion, and pain) and multiplicative multi-attribute utility scores were compared between the extremely preterm children and their classmates. Tobit regressions were performed to explore the effects of gestational age at birth on the Health Utilities Index Mark III multiattribute utility score. Results: Mean (standard deviation [SD]) public sector costs over the 12-month period were £6484 (£5548) for the combined extremely preterm group and £4007 (£2537) for their classmates, generating a mean cost difference of £2477 (bootstrap 95% confidence interval [CI] £1605, £3360) that was statistically significant (P < 0.001). The generalized linear models revealed that compared to birth at term, birth at Յ23 completed weeks, 24 +0 -24 +6 weeks and 25 +0 -25 +6 weeks gestation increased public sector costs by an average of £2417 (95% CI £60, £4774; P = 0.044), £1528 (95% CI £129, £2927; P = 0.032) and £1501 (95% CI £428, £2574; P = 0.006), respectively. In all eight attributes of the Health Utilities Index Mark III, there were significantly higher proportions of suboptimal levels of function among the extremely preterm children (P Յ 0.05). The mean (SD) multiattribute utility score for the extremely preterm children as a cohort was 0.789 (0.264), compared to 0.956 (0.102) for the classmates born at term, a mean difference in utility score of 0.167 (95% CI 0.124, 0.209) that was statistically significant (P < 0.001). The Tobit regressions revealed that, compared to birth at term, birth at Յ23 completed weeks, 24 +0 -24 +6 weeks and 25 +0 -25 +6 weeks gestation reduced the Health Utilities Index Mark III multi-attribute utility score by an average of 0.312 (95% CI 0.169, 0.455; P < 0.001), 0.337 (95% CI 0.235, 0.439; P < 0.001) and 0.243 (95% CI 0.159, 0.327; P < 0.001), respectively.
The importance of reducing childhood undernutrition has been enshrined in the United Nations&... more The importance of reducing childhood undernutrition has been enshrined in the United Nations&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; Millennium Development Goals. This study explores the relationship between alternative indicators of poverty and childhood undernutrition in developing countries within the context of a multi-national cohort study (Young Lives). Approximately 2000 children in each of four countries - Ethiopia, India (Andhra Pradesh), Peru and Vietnam - had their heights measured and were weighed when they were aged between 6 and 17 months (survey one) and again between 4.5 and 5.5 years (survey two). The anthropometric outcomes of stunted, underweight and wasted were calculated using World Health Organization 2006 reference standards. Maximum-likelihood probit estimation was employed to model the relationship within each country and survey between alternative measures of living standards (principally a wealth index developed using principal components analysis) and each anthropometric outcome. An extensive set of covariates was incorporated into the models to remove as much individual heterogeneity as possible. The fully adjusted models revealed a negative and statistically significant coefficient on wealth for all outcomes in all countries, with the exception of the outcome of wasted in India (Andhra Pradesh) and Vietnam (survey one) and the outcome of underweight in Vietnam (surveys one and two). In survey one, the partial effects of wealth on the probabilities of stunting, being underweight and wasting was to reduce them by between 1.4 and 5.1 percentage points, 1.0 and 6.4 percentage points, and 0.3 and 4.5 percentage points, respectively, with each unit (10%) increase in wealth. The partial effects of wealth on the probabilities of anthropometric outcomes were larger in the survey two models. In both surveys, children residing in the lowest wealth quintile households had significantly increased probabilities of being stunted in all four study countries and of being underweight in Ethiopia, India (Andhra Pradesh) and Peru in comparison to children residing in the highest wealth quintile households. Random effects probit models confirmed the statistical significance of increased wealth in reducing the probability of being stunted and underweight across all four study countries. We conclude that, although multi-faceted, childhood undernutrition in developing countries is strongly rooted in poverty.
Despite constituting the vast majority of preterm births, relatively little is known about the cl... more Despite constituting the vast majority of preterm births, relatively little is known about the clinical and economic outcomes of children born either moderately or late preterm. This paper outlines the economic consequences of moderate and late preterm birth for the health services, for other sectors of the economy, for families and carers and, more broadly, for society. The paper reviews both the peer-reviewed literature and additional sources for information on the economic consequences of moderate and late preterm birth. It then goes on to present the results of a decision-analytic modeling study that aimed to estimate the societal costs associated with moderate and late preterm birth throughout the childhood years.
Children with conditions requiring neonatal intensive care impose a financial burden on health se... more Children with conditions requiring neonatal intensive care impose a financial burden on health services, on families and carers, and on society generally. A systematic review of the literature identified 81 studies that conducted primary research on the cost of services as a result of conditions requiring neonatal intensive care. The majority of studies estimated costs incurred during the initial hospital stay. Relatively few studies considered health service costs following discharge from the neonatal intensive care unit, costs to other sectors of the economy or costs to families and carers. It is important that these costs are considered more fully.
The influence of acetylcholine (ACh) on cardiac performance of larval (Taylor Kollros [TK] stages... more The influence of acetylcholine (ACh) on cardiac performance of larval (Taylor Kollros [TK] stages 11-XVIII) and postmetamorphic (3-609 g) Rana catesbeiana was analyzed in situ (circulatory system intact) and in vitro (isolated heart or ventricular strip preparations). Topical application of ACh to the heart in situ resulted in a dose-dependent decrease in heart rate and in a slight decrease in systolic ventricular pressure in all developmental stages. Injection of acetylcholine into the ventricle lumen in situ caused a dose-dependent transient decrease in systolic ventricular pressure, with little heart rate effect. Intraventricular ACh injection also changed the hemodynamic coupling between ventricle and conus arteriosus, generating a biphasic pressure profile in the conus due to sequential contractions of the ventricle and of the conus. In situ the sensitivity of the ventricle to ACh decreased during larval development, with the lowest sensitivity in small postmetamorphic adults. ACh applied in vitro to cardiac muscle strips or small hearts produced a negative inotropic effect. The ACh dose necessary to induce a 50% reduction in muscle strip contraction force in vitro decreased substantially during larval development, indicating an increase in ACh sensitivity with development. The effects of ACh both in vitro and in situ were diminished or eliminated by topical application or injection of atropine, suggesting the presence of muscarinic cholinergic receptors. After preincubation with the acetylcholinesterase blocker eserine, injection of ACh into the conus arteriosus decreased systolic ventricular pressure with a delay of 4-10 seconds, probably representing the minimum blood circulation time. The observed inotropic and chronotropic responses result from the action of ACh on cardiac muscle, primarily affecting systolic ventricular pressure, and on the cardiac pacemaker, mainly influencing heart rate. These responses occur as early as TK, stage 11, indicating a well-developed set of mechanisms to regulate cardiovascular performance early in development. o 1993 WiIey-Liss, Inc. Heart rate and cardiac contractility in vertebrates is determined via a complex system of neuronal and humoral control mechanisms (Nilsson, '83). These control mechanisms have long been known for the adult amphibian heart (Loewi, '21; Nilsson, '83; Axelsson and Nilsson, '85). For example, vagal cholinergic fibers and acetylcholine represent a powerful inhibitory control mechanism for cardiac activity in frogs and most other vertebrates by exerting a negative chronotropic effect. Usually acetylcholine also has a negative inotropic effect (Nilsson, '83). Far less is known about cardiac control mechanisms in amphibian larvae, although an understanding of some developmental changes is
Genetic variation in SLC12A5 which encodes KCC2, the neuronspecific cation-chloride cotransporter... more Genetic variation in SLC12A5 which encodes KCC2, the neuronspecific cation-chloride cotransporter that is essential for hyperpolarizing GABAergic signaling and formation of cortical dendritic spines, has not been reported in human disease. Screening of SLC12A5 revealed a co-segregating variant (KCC2-R952H) in an Australian family with febrile seizures. We show that KCC2-R952H reduces neuronal Cl À extrusion and has a compromised ability to induce dendritic spines in vivo and in vitro. Biochemical analyses indicate a reduced surface expression of KCC2-R952H which likely contributes to the functional deficits. Our data suggest that KCC2-R952H is a bona fide susceptibility variant for febrile seizures.
A major challenge in understanding complex idiopathic generalized epilepsies has been the charact... more A major challenge in understanding complex idiopathic generalized epilepsies has been the characterization of their underlying molecular genetic basis. Here, we report that genetic variation within the GABRD gene, which encodes the GABA A receptor subunit, affects GABA ...
Expert review of pharmacoeconomics & outcomes research, 2014
Economic evaluations that measure the benefits of health interventions in terms of units of healt... more Economic evaluations that measure the benefits of health interventions in terms of units of health gain inevitably require decision-makers to make judgments about the 'value for money' of those health gains. Decision-making bodies have also commonly returned to the position that a unit of health gain, such as an additional quality-adjusted life year, is of equal value regardless of the characteristics of the recipient. This paper focuses on whether and how health gains in economic evaluation should be differentially weighted by age of recipient. The paper presents a structured overview of evidence from the revealed preference and stated preference literature in this area. It discusses a number of methodological issues raised by differential weighting of health gains by age of recipient. These include identifying appropriate samples for the derivation of age-related weights, methodological issues surrounding the application of the quality-adjusted life year measure, the relat...
To examine the effects of designation and volume of neonatal care at the hospital of birth on mor... more To examine the effects of designation and volume of neonatal care at the hospital of birth on mortality and morbidity outcomes in very preterm infants in a managed clinical network setting. A retrospective, population-based analysis of operational clinical data using adjusted logistic regression and instrumental variables (IV) analyses. 165 National Health Service neonatal units in England contributing data to the National Neonatal Research Database at the Neonatal Data Analysis Unit and participating in the Neonatal Economic, Staffing and Clinical Outcomes Project. 20 554 infants born at <33 weeks completed gestation (17 995 born at 27-32 weeks; 2559 born at <27 weeks), admitted to neonatal care and either discharged or died, over the period 1 January 2009-31 December 2011. Tertiary designation or high-volume neonatal care at the hospital of birth. Neonatal mortality, any in-hospital mortality, surgery for necrotising enterocolitis, surgery for retinopathy of prematurity, bro...
A systematic review of recent economic evaluations of antenatal screening was conducted. Relevant... more A systematic review of recent economic evaluations of antenatal screening was conducted. Relevant studies were identified from a number of sources including computerised databases, bibliographies of economic evaluations, and searches of unpublished manuscripts. Each study identified by the literature searches was categorised on the basis of its title and abstract. Studies considered relevant to the systematic review were obtained from libraries. The methodology, results, and policy implications of studies categorised as economic evaluations upon full review were documented. A total of 566 studies were identified by the literature searches, 41 of which were categorised as economic evaluations upon full review. The economic evaluations covered a range of antenatal screening practices, aimed mainly at the prevention of infectious diseases and fetal anomalies. The review highlighted the poor methodological quality of the bulk of economic evaluations of antenatal screening. The study des...
ABSTRACT Several investigators have hypothesized that outpatient preinduction cervical ripening w... more ABSTRACT Several investigators have hypothesized that outpatient preinduction cervical ripening with nitric oxide donors such as isosorbide mononitrate (IMN) would reduce the elapsed time from hospital admission to delivery and improve women&#39;s experience of induction of labor. This double-blind randomized placebo-controlled trial investigated whether vaginal self-administration at home by woman at term would improve the process of induction of labor. The study subjects were 350 nulliparous singleton women with cephalic presentation at ≥37 weeks&#39; gestation, requiring cervical ripening before induction of labor. The participants self-administered IMN (n = 177) or placebo (n = 173) vaginally at home without fetal monitoring at 48, 32, and 16 hours before the scheduled time of admission for induction of labor. The primary study outcome measures were the elapsed time interval from hospital admission to delivery and the women&#39;s experience of home treatment for cervical ripening. Maternal satisfaction was determined with a questionnaire, using a 10 point scale with 1 = extremely good and 10 = not at all good. There was no statistically significant difference between the 2 study groups in the admission to delivery interval; the mean difference was 1.59 hours, with a 95% confidence interval (CI) of −5.08 to 1.89, P = 0.37. Compared to placebo, however, IMN was more effective in inducing a mean change in modified Bishop score from recruitment to hospital admission (mean difference: 0.65 [95% CI, 0.14–1.17, P = 0.013]). With regard to maternal satisfaction, the overall experience of home treatment was positive in both groups. Women in the placebo group reported it to be marginally more positive than those in the IMN group (placebo: 3.23 vs. IMN: 3.84; the mean difference was 0.61, with a 95% CI of 0.02–1.21, P = 0.043). No difference between the 2 groups was reported in either pain or anxiety levels or in the willingness to have the treatment in a subsequent pregnancy. These data show that administration of IMN at home is effective in ripening the cervix but does not shorten the admission to delivery interval or improve maternal satisfaction. The investigators conclude from these findings that IMN in this setting has limited clinical value.
Background: The objective of this study was to investigate the association between ethnicity and ... more Background: The objective of this study was to investigate the association between ethnicity and health related quality of life (HRQoL) in patients with type 2 diabetes.
Many factors aff ect child and adolescent mortality in high-income countries. These factors can b... more Many factors aff ect child and adolescent mortality in high-income countries. These factors can be conceptualised within four domains-intrinsic (biological and psychological) factors, the physical environment, the social environment, and service delivery. The most prominent factors are socioeconomic gradients, although the mechanisms through which they exert their eff ects are complex, aff ect all four domains, and are often poorly understood. Although some contributing factors are relatively fi xed-including a child's sex, age, ethnic origin, and genetics, some parental characteristics, and environmental conditions-others might be amenable to interventions that could lessen risks and help to prevent future child deaths. We give several examples of health service features that could aff ect child survival, along with interventions, such as changes to the physical or social environment, which could aff ect upstream (distal) factors.
Objective: To estimate costs and health utilities associated with extremely preterm birth at appr... more Objective: To estimate costs and health utilities associated with extremely preterm birth at approximately 11 years of age using evidence from a whole population study (the EPICure study). Methods: The study population comprised surviving children born at 20 through 25 completed weeks of gestation in all 276 maternity units in the United Kingdom and Republic of Ireland from March through December 1995 and a control group of classmates born at full term, matched for age, sex, and ethnic group. Estimates of utilization of health, social, and education services were combined with unit costs derived from primary and secondary sources. Generalized liner regression was used to estimate the impact of extremely preterm birth on public sector costs during the 11th year of life. Suboptimal levels of function for each of the eight attributes of the Health Utilities Index Mark III (cognition, vision, hearing, speech, ambulation, dexterity, emotion, and pain) and multiplicative multi-attribute utility scores were compared between the extremely preterm children and their classmates. Tobit regressions were performed to explore the effects of gestational age at birth on the Health Utilities Index Mark III multiattribute utility score. Results: Mean (standard deviation [SD]) public sector costs over the 12-month period were £6484 (£5548) for the combined extremely preterm group and £4007 (£2537) for their classmates, generating a mean cost difference of £2477 (bootstrap 95% confidence interval [CI] £1605, £3360) that was statistically significant (P < 0.001). The generalized linear models revealed that compared to birth at term, birth at Յ23 completed weeks, 24 +0 -24 +6 weeks and 25 +0 -25 +6 weeks gestation increased public sector costs by an average of £2417 (95% CI £60, £4774; P = 0.044), £1528 (95% CI £129, £2927; P = 0.032) and £1501 (95% CI £428, £2574; P = 0.006), respectively. In all eight attributes of the Health Utilities Index Mark III, there were significantly higher proportions of suboptimal levels of function among the extremely preterm children (P Յ 0.05). The mean (SD) multiattribute utility score for the extremely preterm children as a cohort was 0.789 (0.264), compared to 0.956 (0.102) for the classmates born at term, a mean difference in utility score of 0.167 (95% CI 0.124, 0.209) that was statistically significant (P < 0.001). The Tobit regressions revealed that, compared to birth at term, birth at Յ23 completed weeks, 24 +0 -24 +6 weeks and 25 +0 -25 +6 weeks gestation reduced the Health Utilities Index Mark III multi-attribute utility score by an average of 0.312 (95% CI 0.169, 0.455; P < 0.001), 0.337 (95% CI 0.235, 0.439; P < 0.001) and 0.243 (95% CI 0.159, 0.327; P < 0.001), respectively.
The importance of reducing childhood undernutrition has been enshrined in the United Nations&... more The importance of reducing childhood undernutrition has been enshrined in the United Nations&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; Millennium Development Goals. This study explores the relationship between alternative indicators of poverty and childhood undernutrition in developing countries within the context of a multi-national cohort study (Young Lives). Approximately 2000 children in each of four countries - Ethiopia, India (Andhra Pradesh), Peru and Vietnam - had their heights measured and were weighed when they were aged between 6 and 17 months (survey one) and again between 4.5 and 5.5 years (survey two). The anthropometric outcomes of stunted, underweight and wasted were calculated using World Health Organization 2006 reference standards. Maximum-likelihood probit estimation was employed to model the relationship within each country and survey between alternative measures of living standards (principally a wealth index developed using principal components analysis) and each anthropometric outcome. An extensive set of covariates was incorporated into the models to remove as much individual heterogeneity as possible. The fully adjusted models revealed a negative and statistically significant coefficient on wealth for all outcomes in all countries, with the exception of the outcome of wasted in India (Andhra Pradesh) and Vietnam (survey one) and the outcome of underweight in Vietnam (surveys one and two). In survey one, the partial effects of wealth on the probabilities of stunting, being underweight and wasting was to reduce them by between 1.4 and 5.1 percentage points, 1.0 and 6.4 percentage points, and 0.3 and 4.5 percentage points, respectively, with each unit (10%) increase in wealth. The partial effects of wealth on the probabilities of anthropometric outcomes were larger in the survey two models. In both surveys, children residing in the lowest wealth quintile households had significantly increased probabilities of being stunted in all four study countries and of being underweight in Ethiopia, India (Andhra Pradesh) and Peru in comparison to children residing in the highest wealth quintile households. Random effects probit models confirmed the statistical significance of increased wealth in reducing the probability of being stunted and underweight across all four study countries. We conclude that, although multi-faceted, childhood undernutrition in developing countries is strongly rooted in poverty.
Despite constituting the vast majority of preterm births, relatively little is known about the cl... more Despite constituting the vast majority of preterm births, relatively little is known about the clinical and economic outcomes of children born either moderately or late preterm. This paper outlines the economic consequences of moderate and late preterm birth for the health services, for other sectors of the economy, for families and carers and, more broadly, for society. The paper reviews both the peer-reviewed literature and additional sources for information on the economic consequences of moderate and late preterm birth. It then goes on to present the results of a decision-analytic modeling study that aimed to estimate the societal costs associated with moderate and late preterm birth throughout the childhood years.
Children with conditions requiring neonatal intensive care impose a financial burden on health se... more Children with conditions requiring neonatal intensive care impose a financial burden on health services, on families and carers, and on society generally. A systematic review of the literature identified 81 studies that conducted primary research on the cost of services as a result of conditions requiring neonatal intensive care. The majority of studies estimated costs incurred during the initial hospital stay. Relatively few studies considered health service costs following discharge from the neonatal intensive care unit, costs to other sectors of the economy or costs to families and carers. It is important that these costs are considered more fully.
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Papers by S. Petrou