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Biomedical subjects

S Petrou

Publications and source records attributed to S Petrou.

At least 19 recordsLinked to original sources
PubMed2006

Economic evaluation of alternative management methods of first-trimester miscarriage based on results from the MIST trial.

OBJECTIVES: To compare the cost-effectiveness of alternative management methods of first-trimester miscarriage. DESIGN: Economic evaluation conducted alongside a large randomised controlled trial (the MIST trial). SETTING: Early pregnancy assessment units of seven participating hospitals in southern England. SAMPLE: A total of 1200 women with a confirmed pregnancy of less than 13 weeks of gestation with a diagnosis of incomplete miscarriage or missed miscarriage. METHODS: Random allocation to expectant management, medical management or surgical management. Collection of health service and broader resource use data, unit costs for each resource item and clinical outcomes. MAIN OUTCOME MEASURES: Costs (pounds, 2001-02 prices) to the health service, social services, women, carers and wider society during the first 8 weeks postrandomisation. Cost-effectiveness estimates, expressed in terms of incremental cost per gynaecological infection prevented; cost-effectiveness acceptability curves presented at alternative willingness-to-pay thresholds for preventing gynaecological infection. RESULTS: There was no significant difference in the incidence of gynaecological infection between groups. The net societal cost per woman was estimated at 1086.20 pounds in the expectant group, 1410.40 pounds in the medical group and 1585.30 pounds in the surgical group. Expectant management had a 97.8% probability of being the most cost-effective management method at a willingness-to-pay threshold of 10,000 pounds for preventing one gynaecological infection, while medical management had a 2.2% probability of being the most cost-effective management method. Expectant management retained the highest probability of being the most cost-effective management method at all willingness-to-pay thresholds of less than 70,000 pounds for preventing one gynaecological infection. CONCLUSIONS: Expectant and medical management of first-trimester miscarriage possess significant economic advantages over traditional surgical management.

Abortion, Spontaneous↗
PubMed2004

Cost effectiveness analysis of neonatal extracorporeal membrane oxygenation based on four year results from the UK Collaborative ECMO Trial.

OBJECTIVE: To assess the cost effectiveness of extracorporeal membrane oxygenation (ECMO) for mature newborn infants with severe respiratory failure over a four year time span. DESIGN: Cost effectiveness analysis based on a randomised controlled trial in which infants were individually allocated to ECMO (intervention) or conventional management (control) and then followed up to 4 years of age. SETTING: Infants were recruited from 55 approved recruiting hospitals throughout the United Kingdom. Infants allocated to ECMO were transferred to one of five specialist regional centres. Follow up of surviving infants was performed in the community. SUBJECTS: A total of 185 mature (gestational age at birth >or= 35 weeks, birth weight >or= 2000 g) newborn infants with severe respiratory failure (oxygenation index >or= 40). MAIN OUTCOME MEASURES: Incremental cost per additional life year gained; incremental cost per additional disability-free life year gained. RESULTS: Over four years, the policy of neonatal ECMO was effective at reducing known death or severe disability (relative risk = 0.64; 95% confidence interval 0.47 to 0.86; p = 0.004). After adjustment for censoring and discounting at 6%, the mean additional health service cost of neonatal ECMO was pound 17367 (95% confidence interval pound 12072 to pound 22224) per infant ( pound UK, 2001 prices). Over four years, the incremental cost of neonatal ECMO was pound 16707 ( pound 9828 to pound 37924) per life year gained and pound 24775 ( pound 13106 to pound 69690) per disability-free life year gained. These results remained robust after variations in the values of key variables performed as part of a sensitivity analysis. CONCLUSIONS: The study provides rigorous evidence of the cost effectiveness of ECMO at four years for mature infants with severe respiratory failure.

Child, Preschool↗
PubMed2004

Economic implications of multiple births: inpatient hospital costs in the first 5 years of life.

OBJECTIVES: To estimate long term health service costs for hospital stays associated with singleton, twin, and higher order multiple births up to 5 years of age. DESIGN: Costs from specialty based data from the English Department of Health's NHS Trust Financial Returns were applied to admissions recorded in the Oxford record linkage study during 1970-1993. SETTING: Oxfordshire and West Berkshire, United Kingdom. SUBJECTS: A total of 276,897 children, of whom 270,428 were singletons, 6284 were twins, and 185 were higher order multiple births. MAIN OUTCOME MEASURES: Duration of hospital admissions during the first 5 years of life. Costs, expressed in pound sterling and valued at 1998-1999 prices, of hospital inpatient services. RESULTS: The total duration of hospital admissions for twins and triplets were respectively twice and eight times that for singletons, once duration of life had been taken into account. Inpatient costs were significantly higher for multiple births than for singletons, with the cost differences concentrated in the first year of life. Over the first 5 years of life, the adjusted mean cost was estimated at 1532 pounds (95% confidence interval (CI) 1516 pounds to 1548 pounds) for singletons, 3826 pounds (95%CI 3724 pounds to 3929 pounds) for twins, and 8156 pounds (95%CI 7559 pounds to 8754 pounds) for higher order multiple births (p < 0.0001). CONCLUSIONS: Multiple births contribute disproportionately to hospital inpatient costs, especially during the children's first year of life.

Age Factors↗
PubMed2002

Point mutations confer loss of ATP-induced human P2X(7) receptor function.

Residues considered essential for ATP binding to the human P2X(7) receptor (hP2X(7)R) were investigated. HEK293 cells or Xenopus oocytes were transfected with wild-type or site-directed mutants of hP2X(7)R constructs and channel/pore activity measured in the presence of ATP or 2',3'-O-(4-benzoylbenzoyl)-ATP (BzATP). Barium uptake and ethidium influx into HEK293 cells were abolished in cells expressing K193A and K311A mutants, and were partially reduced in cells expressing mutant P210A. K193A and K311A mutations also completely abolished responses to ATP and BzATP in Xenopus oocytes as measured by electrophysiology. These results indicate that K193 and K311 are essential residues in ATP binding in the hP2X(7)R.

Adenosine Triphosphate↗
PubMed2002

Economic implications of assisted reproductive techniques: a systematic review.

BACKGROUND: Approximately one in six couples experiences problems with their fertility at some point in their reproductive lives. The economic implications of the use of assisted reproductive techniques require consideration. Herein, the health economics research in this area are critically appraised. METHODS: Multiple strategies were used to identify relevant studies. Each title and abstract was independently reviewed by two members of the study team and categorized according to perceived relevance. The selected papers were then assessed for quality and data were extracted, converted to UK pounds sterling at 1999/2000 prices, tabulated and critically appraised. RESULTS: A total of 2547 papers was identified through the searches; this resulted in 30 economic evaluations, 22 cost studies and five economic benefit studies that met the selection criteria. The quality of these studies was mixed; many failed to disaggregate costs, discount future costs or conduct sensitivity analyses. Consistent findings included the following: initiating treatment with intrauterine insemination appeared to be more cost-effective than IVF; vasectomy reversal appeared to be more cost-effective than ICSI; factors associated with poor prognosis decreased the cost-effectiveness of interventions. CONCLUSIONS: The cost-effectiveness of different interventions should be considered when making decisions about treatment. Future economic appraisals of assisted reproductive techniques would benefit from more robust methodology than is evident in much of the published literature to date.

Adult↗
PubMed2002

Pore-forming proteins and their application in biotechnology.

Proteins and peptides that form membrane-spanning pores and channels comprise a diverse class of molecules ranging from short peptides that are unregulated and create non-selective pathways to large ion channel proteins that are highly regulated and exhibit exquisite selectivity for particular ions. The diversity of regulation and selectivity, together with recent advances in protein "re-engineering" technology, provide a strong framework on which to build custom molecules with wide-ranging biotechnological application. Here we review a selection of pore-forming peptides and proteins from a number of different species to highlight their structural and functional diversity. The current and potential uses of native and re-engineered molecules are discussed together with a novel strategy to re-engineer alpha-hemolysin to create targeted and regulable cell-killing agents termed proimmunolysins. Numerous pore-forming peptides are currently in development as antimicrobial agents with potential application as anti-tumorigenic agents. In addition to their roles as biotherapeutic agents, pore-forming proteins are also being developed as biosensors for a range of different analytes. Recent examples of this technology include the use of alpha-hemolysin with an adapter molecule to create sensors for organic molecules and gramicidin as a general-purpose sensor for a range of analytes. These approaches promise to deliver a configurable binding site for analytes encoded in a readily measured electrical signal. The number of applications for pore-forming molecules is sure to grow in both quantity and diversity with increased knowledge of the fundamental structure and function of pores.

Animals↗
PubMed2001

A Glu-496 to Ala polymorphism leads to loss of function of the human P2X7 receptor.

The P2X(7) receptor is a ligand-gated cation-selective channel that mediates ATP-induced apoptosis of cells of the immune system. We and others have shown that P2X(7) is nonfunctional both in lymphocytes and monocytes from some subjects. To study a possible genetic basis we sequenced DNA coding for the carboxyl-terminal tail of P2X(7). In 9 of 45 normal subjects a heterozygous nucleotide substitution (1513A-->C) was found, whereas 1 subject carried the homozygous substitution that codes for glutamic acid to alanine at amino acid position 496. Surface expression of P2X(7) on lymphocytes was not affected by this E496A polymorphism, demonstrated both by confocal microscopy and immunofluorescent staining. Monocytes and lymphocytes from the E496A homozygote subject expressed nonfunctional receptor, whereas heterozygotes showed P2X(7) function that was half that of germline P2X(7). Results of transfection experiments showed that the mutant P2X(7) receptor was nonfunctional when expressed at low receptor density but regained function at a high receptor density. This density dependence of mutant P2X(7) function was also seen on differentiation of fresh monocytes to macrophages with interferon-gamma, which up-regulated mutant P2X(7) and partially restored its function. P2X(7)-mediated apoptosis of lymphocytes was impaired in homozygous mutant P2X(7) compared with germline (8.6 versus 35.2%). The data suggest that the glutamic acid at position 496 is required for optimal assembly of the P2X(7) receptor.

Alanine↗
PubMed2001

Methodological limitations of economic evaluations of antenatal screening.

A review of recent economic studies of antenatal screening reveals widespread violation of accepted economic evaluation methodology. In particular, the costs and benefits of antenatal screening are often misclassified and conflated, and the non-resource effects of averted costs are often excluded from the evaluation process. The result is a widespread violation of the explicit and systematic approaches taken by economic analysts more generally, and conclusions that may be described as misleading. This letter calls for economic analysts to be consistent in their application of economic evaluation methodology to antenatal screening programmes.

Abortion, Legal↗
PubMed2001

Clinical, provider and sociodemographic determinants of the number of antenatal visits in England and Wales.

The objective of this study was to measure the independent effects of clinical factors and non-clinical factors, such as provider and sociodemographic characteristics, on the number of antenatal visits made by women in England and Wales. The study was based on a survey of the secondary case records of 20,771 women with singleton pregnancies who were delivered between 1 August 1994 and 31 July 1995. The women in the survey attended one of nine maternity units in Northern England and North Wales selected within those areas to reflect geographical variations, as well as variations in the size and teaching status of the institution. A multivariate Poisson regression model was developed to examine differences in the number of antenatal visits made by women with different clinical and non-clinical characteristics. After controlling for non-clinical factors, primiparous women identified as high risk at booking made 1.0% more visits than primiparous women identified as low risk at booking (p = 0.196). Multiparous women identified as high risk at booking made 3.5% more visits than their low risk counterparts (p<0.001). High risk-defining criteria during antenatal care led to a 0.3% weekly increase in the number of antenatal visits amongst primiparous women (p <0.001) and a 0.4% weekly increase in the number of antenatal visits amongst multiparous women (p < 0.001). Several notable results, not reported elsewhere in the literature, were revealed by the regression analyses. After all independent variables were controlled for, women who were booked into urban teaching hospitals made 10% fewer antenatal visits than the women who were booked into the urban non-teaching hospitals. Women of Pakistani origin made 9.1% fewer antenatal visits than women of white British origin. Similar results were revealed for women of Indian origin and women from other ethnic groups. Non-smokers made 6.0% more antenatal visits than smokers. The planned pattern of antenatal care, number of carers seen, gestation at first presentation and maternal age also had significant independent impacts on the number of antenatal visits. The study highlights the sizeable impact of non-clinical factors on the antenatal care delivery process and indicates ways in which variations in antenatal care might be reduced.

Adult↗
PubMed2001

Mutant GABA(A) receptor gamma2-subunit in childhood absence epilepsy and febrile seizures.

Epilepsies affect at least 2% of the population at some time in life, and many forms have genetic determinants. We have found a mutation in a gene encoding a GABA(A) receptor subunit in a large family with epilepsy. The two main phenotypes were childhood absence epilepsy (CAE) and febrile seizures (FS). There is a recognized genetic relationship between FS and CAE, yet the two syndromes have different ages of onset, and the physiology of absences and convulsions is distinct. This suggests the mutation has age-dependent effects on different neuronal networks that influence the expression of these clinically distinct, but genetically related, epilepsy phenotypes. We found that the mutation in GABRG2 (encoding the gamma2-subunit) abolished in vitro sensitivity to diazepam, raising the possibility that endozepines do in fact exist and have a physiological role in preventing seizures.

Age of Onset↗
PubMed2001

The long-term costs of preterm birth and low birth weight: results of a systematic review.

The high rates of morbidity and mortality arising from preterm birth and low birth weight impose an immense burden on the health, education and social services, and on families. This paper presents the results of a systematic review of the published and unpublished evidence regarding the long-term economic implications of preterm birth and low birth weight for various sectors of the economy and for individuals. The paper highlights the variable methodological quality of the bulk of long-term economic studies of preterm birth and low birth weight and suggests ways in which these methodological limitations can be overcome. The paper reveals that preterm birth and low birth weight can result in substantial costs to the health sector following the infant's initial discharge from hospital. It can also impose a substantial burden on special education and social services, on families and carers of the infants and on society generally. In addition to the costs identified by the literature, preterm birth and low birth weight can have other long-term consequences that require evaluation from an economic perspective.

Cost-Benefit Analysis↗
PubMed2001

Gene transfer: manipulating and monitoring function in cells and tissues.

1. The ectopic expression of genes has proven to be an extremely valuable tool for biologists. The most widely used systems involve electrically or chemically mediated transfer of genes to immortalized cell lines and, at the other end of the spectrum, transgenic animal models. As would be expected, there are compromises to be made when using either of these broad approaches. Immortalized cell lines have limited "physiological relevance" and transgenic approaches are costly and out of the reach of many laboratories. There is also significant time required for the de novo generation of a transgenic animal. 2. As a viable alternative to these approaches, we describe the use of recombinant adenovirus and Sindbis virus to deliver genes to cells and tissues. 3. We exemplify this approach with studies from our laboratories: (i) an investigation of Ca2+ handling deficits in cardiac myocytes of hypertrophied hearts using infection with recombinant adenovirus encoding either green fluorescent protein (GFP) or the sarcoplasmic/endoplasmic reticulum calcium-ATPase (Serca2a); (ii) a study of the mechanism of macrophage/microglial migration by infection of embryonic phagocytes with a GFP-encoding virus and coculture with brain slices to then track the movement of labelled cells; and (iii) we are also exploiting the natural tropism of the Sindbis virus to label neurons in hippocampal brain slices in culture to resolve high-resolution structure and to map neuronal connectivity. 4. Further development of these approaches should open new avenues of investigation for the study of physiology in a range of cells and tissues.

Adenoviridae↗
PubMed2001

Economic aspects of caesarean section and alternative modes of delivery.

Increases in caesarean section rates worldwide have raised questions about the economic implications of caesarean section and alternative modes of delivery. This chapter reviews economic aspects of caesarean section and alternative modes of delivery and identifies areas where further research is required. The chapter presents the results of a systematic review of the literature and analyses of three large observational data sets. It provides evidence for the cost of labour and delivery, the cost of the postnatal stay and the cost of the long-term health consequences of alternative modes of delivery. The chapter highlights the paucity of methodologically robust economic analyses in this area of health care and concludes that primary research is required to estimate the cost and utilization of services attributable to caesarean section and alternative modes of delivery. Future research studies should recognize the long-term health service costs and the costs that arise outside the health service, which are likely to vary according to mode of delivery.

Cesarean Section↗
PubMed2001

Restoration of calcium handling properties of adult cardiac myocytes from hypertrophied hearts.

Reductions in cardiac sarcoplasmic reticulum calcium-ATPase (Serca2a) levels are thought to underlie the prolonged calcium (Ca(2+)) transients and consequent reduced contractile performance seen in human cardiac hypertrophy and heart failure. In freshly isolated cardiac myocytes from rats with monocrotaline-induced right ventricular hypertrophy we found reduced sarcoplasmic reticulum Serca2a expression and prolonged Ca(2+)transients, characteristic of hypertrophic cardiac disease. Modulation of intracellular Ca(2+)levels, Ca(2+) kinetics or Ca(2+)sensitivity is the focus of many current therapeutic approaches to improve contractile performance in the hypertrophic or failing heart. However, the functional effects of increasing Serca2a expression on Ca(2+) handling properties in myocytes from an animal model of cardiac hypertrophy are largely unknown. Here, we describe enhancement of the deficient Ca(2+) handling properties evident in myocytes from hypertrophied hearts following adenoviral-mediated transfer of the human Serca2a gene to these myocytes. These results highlight the importance of Serca2a deficiencies in the hypertrophic phenotype of cardiac muscle and suggest a simple, effective approach for manipulation of normal cardiac function.

Adenoviridae Infections↗
PubMed2001

Systematic review of economic aspects of alternative modes of delivery.

OBJECTIVE: To carry out a systematic review of the literature relating to economic aspects of alternative modes of delivery. METHODS: A comprehensive literature search of the years 1990-1999 was conducted of electronic and non-electronic sources using a tested search strategy. Papers considered to contain useful cost or resource use data were read in full and classified according to their relevance to the review and their methodological quality. Relevant cost and resource use data were converted to pound sterling and inflated to 1998-1999 price levels. RESULTS: The literature search resulted in 975 papers, 49 of which met criteria for the review. Thirty-two papers were from the USA where the organisation, structure and costs of health care are significantly different from that of other industrialised countries. The aggregate costs of different modes of delivery reported in these American studies were between four and five times higher than costs reported in other studies. The majority of included studies were of poor quality. Data from the better quality studies demonstrated that caesarean section costs a health service substantially more than other modes of delivery. The range of costs of an uncomplicated vaginal delivery were 629 pound sterling - 1,298 pound sterling compared with1,238 pound sterling - 3,551 pound sterling for a caesarean section. However, papers have so far only considered short term health service costs. CONCLUSIONS: Research is required to estimate the cost and resource use attributable to alternative modes of delivery. Future research should investigate the long term health service costs and the costs that arise outside the health service which are likely to vary according to mode of delivery.

Cesarean Section↗
PubMed2000

Genetically targeted calcium sensors enhance the study of organelle function in living cells.

1. Understanding the regulation of calcium (Ca2+), the most common of the mineral ions within the human body, has always been of extreme interest to physiologists. While the importance of Ca2+ in contributing to physiological events through regulation of levels has been significantly established, seldom is consideration given to the intricacies of this ion and its mechanics in producing such diverse physiological responses in different regions of the cell. 2. The present review will summarize new methodologies used in our laboratories for the study of two major intracellular organelles, mitochondria and the nucleus. These techniques are based predominantly on the use of molecular biological approaches to both create and then target protein-based sensor molecules to specific intracellular locations. 3. The regulation of Ca2+ in the mitochondria and nucleus is of particular interest to us because of the central involvement of these organelles in: (i) cardiac cell responses during ischaemia/reperfusion; and (ii) the control of gene expression, respectively.

Amino Acid Sequence↗
PubMed2000

Economic issues in the follow-up of neonates.

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.

Cost of Illness↗