A rapid questionnaire assessment of environmental exposures to pregnant women in the INTERGROWTH-21st Project.

Impaired fetal growth and preterm birth are the leading causes of neonatal and infant mortality worldwide and there is a growing scientific literature suggesting that environmental exposures during pregnancy may play a causal role in these outcomes. Our purpose was to assess the environmental exposure of the Fetal Growth Longitudinal Study (FGLS) participants in the multinational INTERGROWTH-21(st) Project. First, we developed a tool that could be used internationally to screen pregnant women for such exposures and administered it in eight countries on a subsample (n = 987) of the FGLS participants. The FGLS is a study of fetal growth among healthy pregnant women living in relatively affluent areas, at low risk of adverse pregnancy outcomes and environmental exposures. We confirmed that most women were not exposed to major environmental hazards that could affect pregnancy outcomes according to the protocol's entry criteria. However, the instrument was able to identify some women that reported various environmental concerns in their homes such as peeling paint, high residential density (>1 person per room), presence of rodents or cockroaches (hence the use of pesticides), noise pollution and safety concerns. This screening tool was therefore useful for the purposes of the project and can be used to ascertain environmental exposures in studies in which the primary aim is not focused on environmental exposures. The instrument can be used to identify subpopulations for more in-depth assessment, (e.g. environmental and biological laboratory markers) to pinpoint areas requiring education, intervention or policy change.

Post-acute assessment programme for patients with traumatic brain injury: measuring the gap between patients' expectations on entering and end of programme recommendations.

OBJECTIVE: To compare the expectations of patients with brain injury (TBI) entering a post-acute programme to the recommendations made at the end. DESIGN: Retrospective study (1997 and 2009). INTERVENTION: This 12-week post-acute programme included ecological multidisciplinary assessment of physical and cognitive disabilities, independence in activities of daily living and work abilities. Recommendations made at the conclusion of the programme included advice regarding the ability to work in an unsheltered or a sheltered environment and possible social activities. RESULTS: Two hundred and forty patients participated. The main objective of 95.8% was return-to-work: 93.7% expected a normal work environment, 2.1% considered a sheltered environment and 4% entered the programme with the aim of improving social abilities and integration in the community. The recommendations included return-to-work in 68.3% of cases, in an unsheltered environment in 44.2% and in a sheltered environment in 24.1% and advice for contact with social services in order to achieve better social integration in 31.7%. There was a discrepancy between expectations and recommendations in half of the cases. CONCLUSION: The discrepancy between patients' expectations and recommendations is in part due to the cognitive disorders; long-term rehabilitation programmes should focus on this issue.

An audit of the cost effectiveness of protocol-driven versus surgeon-directed pre-operative assessment of NHS patients referred to a General Surgeon.

AIMS: Pre-operative assessment (POA) is now commonplace and follows established protocols. This audit compares the cost-effectiveness of surgeon-directed (SD) POA compared to the standard practice of protocol-driven (PD) POA. METHODS: One hundred and fifty-six NHS patients who were referred to a single surgeon during 2009 were allocated to one of three groups. Group 1: SDPOA required no investigations, whereas the PDPOA would have mandated only Methycillin-Resistant Staphylococcus aureus (MRSA) screening and urinalysis; Group 2: SDPOA required no pre-operative investigations, whereas the PDPOA would have required investigations to be performed; Group 3: SDPOA recommended selective investigations, PDPOA required additional tests. For each group the investigations requested and performed, their cost and whether the results affected patient care were recorded. There is no individual PDPOA group, but the cost of the extra tests was calculated where the PDPOA protocols were followed and therefore the cost differed between the SDPOA and PDPOA. RESULTS: The total cost for all investigations for the 156 patients was pound 43,985. A potential cost saving of pound 9,694 (group 2) and pound 8,898 (group 3) was demonstrated. The total potential saving identified for all 3 groups was pound 18,592, which was 42% of the total cost of all the investigations. Patient care was not affected by these additional investigations. CONCLUSIONS: There were no observed peri-operative complications during the study, implying that the additional pre-operative investigations were clinically unnecessary and identifying an additional cost saving of pound 18,592.

Preventing sudden death with n-3 (omega-3) fatty acids and defibrillators.

BACKGROUND: Because interventions that prevent and treat events due to cardiovascular disease are applied to different, but overlapping, segments of the population, it can be difficult to estimate their effectiveness if formal calculations are not available. METHODS: Markov chain analysis, including sensitivity analysis, was used with a hypothetical population resembling that of Olmsted County, MN, aged 30 to 84 in the year 2000 to compare the estimated impact of three interventions to prevent sudden death: (1) raising blood levels of n-3 (omega-3) fatty acids, (2) distributing automated external defibrillators (AEDs), and (3) implanting cardioverter defibrillators (ICDs) in appropriate candidates. The analysis was performed in 2004, 2005, and 2006. RESULTS: Raising median n-3 fatty acid levels would be expected to lower total mortality by 6.4% (range from sensitivity analysis = 1.6% to 10.3%). Distributing AEDs would be expected to lower total mortality by 0.8% (0.2% to 1.3%), and implanting ICDs would be expected to lower total mortality by 3.3% (0.6% to 8.7%). Three fourths of the reduction in total mortality due to n-3 fatty acid augmentation would accrue from raising n-3 fatty acid levels in the healthy population. CONCLUSIONS: Based on central values of candidacy and efficacy, raising n-3 fatty acid levels would have about eight times the impact of distributing AEDs and two times the impact of implanting ICDs. Raising n-3 fatty acid levels would also reduce rates of sudden death among the subpopulation that does not qualify for ICDs.

How Philip Morris unlocked the Japanese cigarette market: lessons for global tobacco control.

BACKGROUND: The Framework Convention on Tobacco Control includes tobacco advertising restrictions that are strongly opposed by the tobacco industry. Marketing strategies used by transnational tobacco companies to open the Japanese market in the absence of such restrictions are described. METHODS: Analysis of internal company documents. FINDINGS: Between 1982 and 1987 transnational tobacco companies influenced the Japanese government through the US Trade Representative to open distribution networks and eliminate advertising restrictions. US cigarette exports to Japan increased 10-fold between 1985 and 1996. Television advertising was central to opening the market by projecting a popular image (despite a small actual market share) to attract existing smokers, combined with hero-centred advertisements to attract new smokers. Philip Morris's campaigns featured Hollywood movie personalities popular with young men, including James Coburn, Pierce Brosnan, Roger Moore, and Charlie Sheen. Event sponsorships allowed television access despite restrictions. When reinstatement of television restrictions was threatened in the late 1980s, Philip Morris more than doubled its television advertising budget and increased sponsorship of televised events. By adopting voluntary advertising standards, transnational companies delayed a television advertising ban for over a decade. CONCLUSIONS: Television image advertising was important to establish a market, and it has been enhanced using Hollywood personalities. Television advertising bans are essential measures to prevent industry penetration of new markets, and are less effective without concurrent limits on sponsorship and promotion. Comprehensive advertising restrictions, as included in the Framework Convention for Tobacco Control, are vital for countries where transnational tobacco companies have yet to penetrate the market.

Design and development of a coronary heart disease decision support tool.

We are developing a decision support tool to help clinicians and policy makers estimate the impact of various coronary heart disease (CHD) treatments on disease outcomes for populations. We have created seven modules that correspond to states commonly encountered with CHD, that is, congestive heart failure, tachyarrhythmia, stable angina pectoris, acute coronary syndrome, bradycardia, postmyocardial infarction, and postcoronary artery bypass grafting, and a healthy individual module. Within each module, we created event-decision- intervention-outcome flow pathways to simulate risk of a clinical event and the expected outcome as the result of a particular intervention. We will combine disease state probability estimates based on the experience of the Olmsted County, Minnesota, population and estimates of intervention efficacy based on clinical trial data to estimate the impact of interventions on a population. We plan to make this tool available to the public through the internet.

Experimental assessment of proximal stent-graft (InterVascular) fixation in human cadaveric infrarenal aortas.

OBJECTIVES: This paper investigates the radial deformation load of an aortic endoluminal prosthesis and determines the longitudinal load required to cause migration in a human cadaveric aorta of the endoprosthesis. DESIGN AND METHODS: The endovascular prosthesis under investigation was a 24 mm diameter, nitinol, self-expanding aortoaortic device (InterVascular, Clearwater, Florida, U.S.A.). Initially, a motorised digital force gauge developed an incremental load which was applied to the ends of five stent-grafts, to a maximum of 10 mm (42%) compression. Secondly, using a simple bench model, each ends of four stent-grafts were deployed into 10 cadaveric experimental aneurysm necks and a longitudinal load applied to effect distraction. RESULTS: Increasing load produced increasing percentage deformation of the stent-grafts. The mean longitudinal distraction load for an aneurysm neck of 20 mm was 409 g (200-480 g), for 15 mm was 277 g (130-410 g) and for 10 mm was 218 g (130-340 g). The aneurysm diameter and aortic calcification had p values of 0.002 and 0.047, respectively, while the p value for aneurysm neck length was less than 0.00001. CONCLUSIONS: These results suggest that there is a theoretical advantage of oversizing an aortic prosthesis and that sufficient anchorage is achieved in an aortic neck of 10 mm to prevent migration when fully deployed.

Assessment of the bioactivity of human and bovine thyrotrophin preparations using a porcine thyroid cell bioassay.

The biopotency of six preparations of thyrotrophin (TSH) has been compared in a highly sensitive in vitro porcine thyroid cell bioassay using iodide uptake as an endpoint. Three of these preparations were of human origin and three derived from bovine pituitary tissue. One human TSH preparation, the 2nd International Reference Preparation, 80/558, was used to calibrate the other five. The log dose-log response curves for all preparations were sigmoidal in shape. For the purpose of evaluation the central linear portions of the curves were compared. With all preparations the slopes in this region were very similar. The relative biopotencies of the bovine preparations (unit:unit) were at least five times those of the human standards when measured using the porcine thyroid cell bioassay. These findings emphasise the need to control the TSH standards employed in a variety of bioassays, particularly those used for between-laboratory comparison.

Assessment of the biopotency of anti-thyroid drugs using porcine thyroid cells.

The effect of six drugs on the uptake and organification of iodide by porcine thyroid cells stimulated with bovine TSH (10 miU/L) has been investigated. The drugs fall into two categories: the peroxidase inhibitors, methimazole (MMI), 2-thiouracil (2-TU) and 3-amino 1,2,4 triazole (3-ATA) and the ionic inhibitors, lithium chloride (LiCl), potassium perchlorate (KC10(4], and sodium iodide (NaI). All the drugs led to a dose-related inhibition of iodide metabolism. The most potent effect on iodide uptake was seen with NaI which inhibited this function by 20% even at 10(-8) mol/l. In contrast, the most potent effect on iodide organification was observed with methimazole which led to a 25% inhibition at 10(-8) mol/l. The concentrations of drug which gave rise to a 50% inhibition of iodide uptake were (mumol/l) 0.26 (NaI), 3.5 (KClO4), 9.7 (2-TU), 15 (MMI), 26 (3-ATA), and 1500 (LiCl). The comparable figures for organification were 0.13 (MMI), 0.18 (2-TU), 0.23 (NaI), 1.2 (3-ATA), 15 (KClO4) and 1300 (LiCl). We conclude that this in vitro system has considerable potential for the assessment of potency and possible bioassay of anti-thyroid drugs of varying structures and sites of action.

On the assessment of the in vitro biopotency and site(s) of action of drugs affecting adrenal steroidogenesis.

Dispersed guinea-pig adrenal cells have been employed in the in vitro estimation of the biological potency and sites of action of drugs acting against the adrenal. The effect of 12 drugs on cortisol secretion from cells stimulated with adrenocorticotrophin (ACTH, 50 ng/L, a 95% saturating dose) has been tested. All the drugs depressed cortisol output in a dose-related fashion. The concentration of drug which inhibited secretion by 50% was (mumol/L, mean +/- SEM): etomidate 0.1 +/- 0.002; epostane 0.44 +/- 0.02: 17-ketotrilostane 0.55 +/- 0.04: trilostane 1.3 +/- 0.1: metyrapone 3.5 +/- 0.6: cyproterone acetate 4.6 +/- 0.2: megestrol acetate 11 +/- 2: danazol 22 +/- 2: aminoglutethimide 41 +/- 5: stanozolol 50 +/- 4: thiopentone 160 +/- 18: propofol 170 +/- 18. The sites of the anti-steroidogenic effect of seven of these drugs have also been established using a method based upon the sequential stimulation by the exogenous precursor steroids of the various steps leading to the biosynthesis of cortisol by adrenal cells. Propofol acts between ACTH binding and pregnenolone production, trilostane, megestrol acetate and cyproterone acetate are 3 beta-hydroxysteroid dehydrogenase inhibitors whereas metyrapone, etomidate and thiopentone act at 11 beta-hydroxylase.

Life-styles and death-styles: differentials and consequences of mortality trends.

Differentials in mortality in developed countries are examined according to region, sex, age, cause of death, and social class. "Various simulations [using the Odyssey model developed at the Catholic University of Louvain] are presented in order to study the impact of decreasing mortality and mortality differentials on the structure of deaths by cause, and on various economic variables.... The consequences [for] the social security system, among others, are stressed." (summary in FRE, ITA)