Communicating risks at the population level: application of population impact numbers.
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Biomedical subjects
Publications and source records attributed to Richard Edwards.
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BACKGROUND: Primary care organisations are faced with implementing a large number of guideline recommendations. We present methods by which the number of eligible patients requiring treatment, and the relative benefits to the whole population served by a general practice or Primary Care Trust, can be calculated to help prioritise between different guideline recommendations. METHODS: We have developed measures of population impact, "Number to be Treated in your Population (NTP)" and "Number of Events Prevented in your Population (NEPP)". Using literature-based estimates, we have applied these measures to guidelines for pharmacological methods of secondary prevention of myocardial infarction (MI) for a hypothetical general practice population of 10,000. RESULTS: Implementation of the NICE guidelines for the secondary prevention of MI will require 176 patients to be treated with aspirin, 147 patients with beta-blockers and with ACE-Inhibitors and 157 patients with statins (NTP). The benefit expressed as NEPP will range from 1.91 to 2.96 deaths prevented per year for aspirin and statins respectively. The drug cost per year varies from euro 1940 for aspirin to euro 60,525 for statins. Assuming incremental changes only (for those not already on treatment), aspirin post MI will be added for 37 patients and produce 0.40 of a death prevented per year at a drug cost of euro 410 and statins will be added for 120 patients and prevent 2.26 deaths per year at a drug cost of euro 46,150. An appropriate policy might be to reserve the use of statins until eligible patients have been established on aspirin, ACE-Inhibitors and beta blockers. CONCLUSIONS: The use of population impact measures could help the Primary Care Organisation to prioritise resource allocation, although the results will vary according to local conditions which should be taken into account before the measures are used in practice.
BACKGROUND: This study was commissioned by the UK Health Development Agency to provide a snapshot of how, at the outset of the 2002 NHS reorganisation, Primary Care Trust (PCT) staff and Professional Executive Committee (PEC) members perceived their public health roles and functions, the opportunities and barriers to delivering those roles and functions and the development needs in order to fulfill them. METHODS: Taped group interviews were conducted with PECs of eight PCTs (covering a range of settings, size and stage of organisational development), followed up by structured telephone interviews with 35 frontline staff from four of the PCTs. Analysis was through content analysis and counting of themes including a quantitative assessment of the occurrence of themes and comparison between different categories of participants. RESULTS: PEC members and frontline staff (particularly community based staff) were keen to address a broad public health agenda within the new PCTs, however a number of barriers to the ability of the PCT to fulfill its Public Health role were identified. The most important were lack of resources (staff and staff time) in the context of a host of competing agendas and excessive clinical workloads. There was a clear difference among frontline staff between those who were practice or community based-many practice-based frontline staff did not acknowledge any major public health dimensions to their daily work. A number of detailed suggestions for improvement were made. CONCLUSION: At the start of the 2002 NHS reorganisation, PCTs need to improve their organisational capacity to address the public health if they are to deliver health improvement as envisaged. We make recommendations which should allow PCTs to perform their public health functions more effectively.
Often the goal of health and social development agencies is to assess communities and work with them to improve community capacity. Particularly for health promoters working in community settings and to ensure consistency in the definition of health promotion, the evaluation of health promotion programmes should be based on strengths and assets, yet existing information for planning and evaluation purposes usually focuses on problems and deficits. A model and definition of community capacity, grounded in community experience and focusing on strengths and assets, was developed following a 4-year, multi-site, qualitative, action research project in four Toronto neighbourhoods. There was significant community involvement in the four Community Advisory Committees, one for each study site. Semi-structured, open-ended interviews and focus groups were conducted with 161 residents and agency workers identified by the Community Advisory Committees. The data were analyzed with the assistance of NUDIST software. Thematic analysis was undertaken in two stages: (i) within each site and (ii) across sites, with the latter serving as the basis for the development of indicators of community capacity. This paper presents a summary of the research, the model and the proposed indicators. The model locates talents and skills of community members in a larger context of socioenvironmental conditions, both inside and outside the community, which can act to enable or constrain the expression of these talents and skills. The significance of the indicators of community capacity proposed in the study is that they focus on identifying and measuring the facilitating and constraining socioenvironmental conditions.
Ecteinascidin-743 (ET-743) is a novel marine-derived anticancer drug with clinical activity in soft tissue sarcoma and ovarian cancer. Reversible transaminitis and subclinical cholangitis have frequently been described in patients who receive ET-743. To facilitate understanding of this adverse effect and help design suitable therapeutic rescue strategies, we characterized the hepatic effects of ET-743 in rats. Female rats received ET-743 (single dose, 40 microg/kg) i.v., and liver changes were assessed from 6 h up to 3 months after dosing by histopathology, immunohistochemistry, electron microscopy, hepatic and plasma biochemistry, and DNA microarray analysis. At 24 h posttreatment and beyond, livers displayed degeneration and patchy focal necrosis of bile duct epithelial cells associated with mild inflammation followed by fibrosis. Sporadic and focal zones of hepatic necrosis and hemorrhage were observed from day 2 onward, although the majority of hepatocytes appeared normal as judged by electron microscopy. Pathological alterations persisted up to 3 months after dosing. Plasma levels of total bilirubin were elevated up to 7-fold over those in untreated rats from day 2 onward and returned to control values by day 24. Activities of alkaline phosphatase and aspartate aminotransferase in plasma were elevated for 2 and 3 months, respectively. Activities of the hepatic microsomal drug-metabolizing enzymes cytochrome P-450 A1/2, CYP2E1, and CYP3A2 were decreased. DNA microarray analysis of livers from ET-743-treated animals showed a dramatic increase in the expression of ATP binding cassette transport genes Abcb1a and Abcb1b, which impart resistance to anticancer drugs, and of Cdc2a and Ccnd1, the rodent homologues of human cell cycle genes CDC2 and cyclin D1, respectively. The cell cycle gene expression changes mirrored ET-743-induced increases in liver weight and Ki-67 labeling of liver nuclei. The results suggest that the toxicity exerted by ET-743 in the rat liver is a consequence of biliary rather than hepatocellular damage and that it is accompanied by a wave of mitogenic activity, which may be driven by the transcriptional increase in Cdc2a expression.
OBJECTIVE: To examine the contribution of changes in the distribution of social class to the mortality of the whole population between 1970-2 and 1991-3. DESIGN: Examination of routine data at two time points: 1970-2 and 1991-3. DATA SOURCE: Data provided by the Office for National Statistics. MAIN OUTCOME MEASURES: Difference for the total population in the number of deaths between 1971 and 1991. Proportion of difference accounted for by change in population size, change in risk of death within each social class, or change in distribution of population across social classes. RESULTS: Reductions in mortality between 1970-2 and 1991-3 among men in England and Wales were partially (16% of all deaths) attributable to increases in the proportion of men in higher social classes, representing 3943 fewer deaths per year or one less death for every 3056 men in 1991-3 compared with 1970-2. CONCLUSION: Some of the observed reduction in mortality seen between 1970-2 and 1991-3 can be accounted for by improved overall socioeconomic status of the population.
Coronary artery ligation is the standard technique to induce regional myocardial infarction in small animal models. However, opening the chest and incising the pericardium independently influence post-MI remodelling. Our purpose was to develop and characterize a novel closed chest model of regional myocardial infarction (MI) in the rabbit of increased clinical relevance. Coronary angiography was performed percutaneously in New Zealand White Rabbits (NZW) using pre-formed catheters. A 0.36 mm thrombogenic coil was positioned in the circumflex artery to induce closed chest MI. Of rabbits undergoing coil deployment 40 % survived until day 100. Rabbits were classified as small MI (n = 5), moderate MI (n = 6) and large MI (n = 6) < 15 %, 15 - 30 %, > 30 % of LV myocardial volume respectively) or sham controls (n=11). Transthoracic echocardiographic images were obtained 0, 3, 5, 7, 14, 28, 60, 100 days post procedure. At day 100, LVEDP was measured before and after plasma substitute infusion. Hearts were subsequently excised and chamber stiffness (Kc) was derived from the passive pressure-volume relationship. Cardiac weight, dimensions and MI as a percentage of LV volume (MI%) were also recorded. Differences in percentage fractional shortening (%FS) were apparent from day 14. %FS was reduced in rabbits with large and moderate MI compared to controls (day 100, p < 0.005 and p < 0.05, respectively). LVEDP was increased in large and moderate MI compared to small MI and controls (26 mmHg +/- 6 and 21 mmHg +/- 5 vs. 9 mmHg +/- 1 and 7 mmHg +/- 3 p < 0.005); these differences were maintained during plasma substitute infusion. Kc in large MI was significantly less than moderate MI, small MI or control (all p < 0.05). Direct morphometric measurements distinguished between all groups.This study provides the first description of post-infarction remodelling after coronary artery occlusion where the pericardium remains intact in a small animal model. We believe it may provide a more physiologically and clinically relevant in vivo assay system of left ventricular dysfunction after myocardial infarction.
Peliosis hepatis, characterized by the presence of blood-filled spaces within hepatic parenchyma, developed in C57Bl mice implanted subcutaneously with melanoma cells 23 days previously. The peliosis was associated with dilated hepatic sinusoids that were lined by prominent, proliferating endothelial cells. The development of peliosis hepatis was completely abrogated when melanoma growth was inhibited by administration of dexamethasone. These features support the concept that peliosis hepatis can be induced by a circulating tumor-derived endothelial growth factor such as vascular endothelial growth factor.
The C3(1)/SV40 T antigen transgenic mouse model for which rapid mammary and prostate tumor development has been documented uses the FVB/N mouse as a background strain. In this study, where the background strain used was the C57BL/6J mouse, neither mammary nor prostate tumors developed over periods of up to 40 weeks. However, a disturbance of hyaline cartilage in joints was observed similar to that found in synovial chondromatosis in humans. In addition, cartilage thickening in the external ears and cartilaginous metaplasia of the ascending aorta also occurred. This suggests that rearrangement of the transgene occurred in breeding on the C57BL background, thus modifying its expression. It raises the possibility that the genetic changes induced by the SV40 T antigen transforming sequence are important in cartilage homeostasis.
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