Economic modelling of antenatal screening and ultrasound scanning programmes for identification of fetal abnormalities

Objective Within the framework of a health technology assessment and using an economic model, to determine the most clinically and cost effective policy of scanning and screening for fetal abnormalities in early pregnancy. Design A discrete event simulation model of 50,000 singleton pregnancies. Setting Maternity services in Scotland. Population Women during the first 24 weeks of their pregnancy. Methods The mathematical model was populated with data on uptake of screening, prevalence, detection and false positive rates for eight fetal abnormalities and with costs for ultrasound scanning and serum screening. Inclusion of abnormalities was based on the relative prevalence and clinical importance of conditions and the availability of data. Six strategies for the identification of abnormalities prenatally including combinations of first and second trimester ultrasound scanning and first and second trimester screening for chromosomal abnormalities were compared. Main outcome measures The number of abnormalities detected and missed, the number of iatrogenic losses resulting from invasive tests, the total cost of strategies and the cost per abnormality detected were compared between strategies. Results First trimester screening for chromosomal abnormalities costs more than second trimester screening but results in fewer iatrogenic losses. Strategies which include a second trimester ultrasound scan result in more abnormalities being detected and have lower costs per anomaly detected. Conclusions The preferred strategy includes both first and second trimester ultrasound scans and a first trimester screening test for chromosomal abnormalities. It has been recommended that this policy is offered to all women in Scotland.

From stress to distress: Conceptualizing the British family farming patriarchal way of life

‘Rural stress’ and ‘farming stress’ are terms that have become commonly appropriated by British health-based academic disciplines, the medical profession and social support networks, especially since the agricultural ‘crises’ of B.S.E. and Foot and Mouth Disease. Looking beyond the media headlines, it is apparent that the terms in fact are colloquial catch-alls for visible psychological and physiological outcomes shown by individuals. Seldom have the underlying causes and origins of presentable medical outcomes been probed, particularly within the context of the patriarchal and traditionally patrilineal way of life which family forms of farming business activity in Britain encapsulate. Thus, this paper argues that insufficient attention has been paid to the conceptualization of the terms. They have become both over-used and ill-defined in their application to British family farm individuals and their life situations. A conceptual framework is outlined that attempts to shift the stress research agenda into the unilluminated spaces of the family farming ‘way of life’ and focus instead on ‘distress’. Drawing upon theorization from agricultural and feminist geography together with cultural approaches from rural geography, four distinct clusters of distress originate from the thoughts of individuals and the social practices now required to enact patriarchal family farming gender identities. These are explored using case study evidence from ethnographic repeated life history interviews with members of seven farming families in Powys, Mid Wales, an area dominated by family forms of farming business. Future research agendas need to be based firmly on the distressing reality of patriarchal family farming and also be inclusive of those who, having rejected the associated way of life, now lie beyond the farm gate.

Mothers' antenatal depression and their children's antisocial outcomes

Interviews of 120 British adolescents and their parents (80% of a random sample of antenatal patients drawn from a representative urban population and followed longitudinally) revealed that 40 (33%) had been arrested and/or had a diagnosis of DSM-IV conduct disorder by 16 years of age; of those, 18 (45%) had committed violent acts. Depression in pregnancy significantly predicted violence in adolescence, even after controlling for the family environment, the child's later exposure to maternal depression, the mother's smoking and drinking during pregnancy, and parents' antisocial behavior. Mothers with a history of conduct problems were at elevated risk to become depressed in pregnancy, and the offspring of depressed women had a greater chance of becoming violent by age 16.

Salbutamol up-regulates matrix metalloproteinase-9 in the alveolar space in the acute respiratory distress syndrome.

Objectives: Acute respiratory distress syndrome (ARDS) is characterized by alveolar-capillary barrier damage. Matrix metalloproteinases (MMPs) are implicated in the pathogenesis of ARDS. In the Beta Agonists in Acute Lung Injury Trial, intravenous salbutamol reduced extravascular lung water (EVLW) in patients with ARDS at day 4 but not inflammatory cytokines or neutrophil recruitment. We hypothesized that salbutamol reduces MMP activity in ARDS.

Methods: MMP-1/-2/-3/-7/-8/-9/-12/-13 was measured in supernatants of distal lung epithelial cells, type II alveolar cells, and bronchoalveolar lavage (BAL) fluid from patients in the Beta Agonists in Acute Lung Injury study by multiplex bead array and tissue inhibitors of metalloproteinases (TIMPs)-1/-2 by enzyme-linked immunosorbent assay. MMP-9 protein and activity levels were further measured by gelatin zymography and fluorokine assay.

Measurements and Main Results: BAL fluid MMP-1/-2/-3 declined by day 4, whereas total MMP-9 tended to increase. Unexpectedly, salbutamol augmented MMP-9 activity. Salbutamol induced 33.7- and 13.2-fold upregulation in total and lipocalin-associated MMP-9, respectively at day 4, compared with 2.0- and 1.3-fold increase in the placebo group, p < 0.03. Salbutamol did not affect BAL fluid TIMP-1/-2. Net active MMP-9 was higher in the salbutamol group (4222 pg/mL, interquartile range: 513-7551) at day 4 compared with placebo (151 pg/mL, 124-2108), p = 0.012. Subjects with an increase in BAL fluid MMP-9 during the 4-day period had lower EVLW measurements than those in whom MMP-9 fell (10 vs. 17 mL/kg, p = 0.004): change in lung water correlated inversely with change in MMP-9, r = -.54, p = 0.0296. Salbutamol up-regulated MMP-9 and down-regulated TIMP-1/-2 secretion in vitro by distal lung epithelial cells. Inhibition of MMP-9 activity in cultures of type II alveolar epithelial cells reduced wound healing.

Conclusions: Salbutamol specifically up-regulates MMP-9 in vitro and in vivo in patients with ARDS. Up-regulated MMP-9 is associated with a reduction in EVLW. MMP-9 activity is required for alveolar epithelial wound healing in vitro. Data suggest MMP-9 may have a previously unrecognized beneficial role in reducing pulmonary edema in ARDS by improving alveolar epithelial healing.