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Intermittent preventive treatment in infancy (IPTi) entails routine administration of antimalarial treatment doses at specified times in at-risk infants. Sulfadoxine-pyrimethamine (SDX/PYR) is a combination that has been used as first-line IPTi. Because of limited pharmacokinetic data and suggestions that higher milligram/kilogram pediatric doses than recommended should be considered, we assessed SDX/PYR disposition, randomized to conventional (25/1.25 mg/kg of body weight) or double (50/2.5 mg/kg) dose, in 70 Papua New Guinean children aged 2 to 13 months. Blood samples were drawn at baseline, 28 days, and three time points randomly selected for each infant at 4 to 8 h or 2, 5, 7, 14, or 21 days. Plasma SDX, PYR, and N 4 -acetylsulfadoxine (NSX, the principal metabolite of SDX) were assayed by high-performance liquid chromatography (HPLC). Using population modeling incorporating hepatic maturation and cystatin C-based renal function, two-compartment models provided best fits for PYR and SDX/NSX plasma concentration profiles. The area under the plasma concentration-time curve from 0 h to infinity (AUC 0-∞ ) was greater with the double dose versus the conventional dose of PYR (4,915 versus 2,844 μg/day/liter) and SDX (2,434 versus 1,460 mg/day/liter). There was a 32% reduction in SDX relative bioavailability with the double dose but no evidence of dose-dependent metabolism. Terminal elimination half-lives (15.6 days for PYR, 9.1 days for SDX) were longer than previously reported. Both doses were well tolerated without changes in hemoglobin or hepatorenal function. Five children in the conventional and three in the double-dose group developed malaria during follow-up. These data support the potential use of double-dose SDX/PYR in infancy, but further studies should examine the influence of hepatorenal maturation in very young infants.

The purpose of this exploratory study was to determine the nature of Australian occupational therapy practice and the factors that make that practice successful in short stay, acute care hospitals. The study used a qualitative methodology in the form of focus group discussions. The primary finding of the study is the reconceptualization of the occupational therapy role, which has occurred as a result of the economic constraints imposed on the health care system that have necessitated shorter bed stays for patients. This role is characterized by an assess/discharge plan cycle rather than the more long-term, rehabilitation approach of assess/treat/discharge. This information is useful for practitioners, department managers, hospital administrators, and occupational therapy educators.

Institutions with the responsibility for making adoption (reimbursement) decisions in health care often lack the remit to demand or commission further research: adoption decisions are their only policy instrument. The decision to adopt a technology also influences the prospects of acquiring further evidence because the incentives to conduct research are reduced and the ethical basis of further clinical trials maybe undermined. In these circumstances the decision maker must consider whether the benefits of immediate access to a technology exceeds the value of the evidence which maybe forgone for future patients. We outline how these expected opportunity losses can be established from the perspective of a societal decision maker with and without the remit to commission research, and demonstrate how these considerations change the appropriate decision rules in cost-effectiveness analysis. Importantly, we identify those circumstances in which the approval of a technology that is expected to be cost-effective should be withheld, i.e. when an 'only in research' recommendation should be made. We demonstrate that a sufficient condition for immediate adoption of a technology can provide incentives for manufacturers to reduce the price or provide additional supporting evidence. However, decisions based solely on expected net benefit provide no such incentives, may undermine the evidence base for future clinical practice and reduce expected net health benefits for the patient population.

Purpose. To investigate the expected value of partial perfect information (EVPPI) and the research decisions it can address. Methods. Expected value of information (EVI) analysis assesses the expected gain in net benefit from further research. Where the expected value of perfect information (EVPI) exceeds the costs of additional research, EVPPI can be used to identify parameters that contribute most to the EVPI and parameters with no EVPPI that may be disregarded as targets for further research. Recently, it was noted that parameters with low EVPPI for a one-off research design may be associated with high EVPPI when considered as part of a sequential design. This article examines the characteristics and role of conditional and sequential EVPPI in EVI analysis. Results. The calculation of EVPPI is demonstrated for single parameters, groups of parameters, and conditional and sequential EVPPI. Conditional EVPPI is the value of perfect information about one parameter, conditional on having obtained perfect information about another. Sequential EVPPI is the value of perfect information for a sequential research design to investigate first one parameter, then another. Conditional EVPPI differs from the individual EVPPI for a single parameter. Sequential EVPPI includes elements from the joint EVPPI for the parameters and the EVPPI for the first parameter in sequence. Sequential designs allow abandonment of research on the second parameter on the basis of additional information obtained on the first. Conclusions. The research decision space addressed by EVI analyses can be widened by incorporating sequential EVPPI to assess sequential research designs.

We conducted a systematic review of current evidence on the effectiveness of continuous positive airway pressure (CPAP) for treatment of obstructive sleep apnoea-hypopnoea syndrome (OSAHS). The primary outcomes were subjective sleepiness, using Epworth Sleepiness Scale (ESS) and objective sleepiness using Maintenance of Wakefulness Test (MWT) and Multiple Sleep Latency Test (MSLT). Mean difference (MD) in endpoints was used to compare CPAP to usual care, placebo and dental devices. The analysis was stratified by symptom and disease severity at baseline. CPAP significantly reduced ESS score compared to control (MD -2.7, 95% CI -3.45, -1.96). The benefit was greatest in patients whose symptoms were severe at baseline: severely symptomatic population (MD -5.0, -6.5, -3.5); moderate (MD -2.3, -3.0, -1.6); mild (MD -1.1, -1.8, -0.3). CPAP significantly improved MWT score compared to control (MD 3.3, 1.3, 5.3) but not on the MSLT. There was no statistically significant difference between CPAP and dental devices on the ESS, MWT or MSLT, in a population with moderate symptoms. There was some evidence of benefit for blood pressure with CPAP compared to control. CPAP is an effective treatment for OSAHS in moderate to severe symptomatic patients and there may be benefits for mild symptoms. Dental devices may be a treatment option for moderate symptoms. Crown Copyright © 2009.

Objectives:An important option for the medical treatment of obstructive sleep apnea-hypopnea syndrome (OSAHS) is continuous positive airway pressure (CPAP) during sleep. This study reports on the cost-effectiveness of CPAP compared with dental devices and lifestyle advice. The work was commissioned by the NHS HTA Programme to inform the National Institute of Health and Clinical Excellence's (NICE) appraisal of CPAP.Methods:A Markov model compared the interventions over the expected patient lifetime. The primary measure of cost-effectiveness was the incremental cost per quality-adjusted life-year (QALY) gained. The QALY incorporated the impact of treatments on daytime sleepiness, blood pressure and health-related quality of life (HRQoL).Results:On average, CPAP was associated with higher costs and QALYs compared with dental devices or lifestyle advice. In the base-case analysis, the incremental cost-effectiveness ratio (ICER) for CPAP compared with dental devices was around £4,000 per QALY (2005–06 prices). The probability that CPAP is more cost-effective than dental devices or lifestyle advice at a threshold value of £20,000 per QALY was 0.78 for men and 0.80 for women. Several sensitivity analyses were undertaken and it was found that the ICER for CPAP consistently fell below £20,000 per QALY gained, apart from in a subgroup with mild disease.Conclusions:The model suggests that CPAP is cost-effective compared with dental devices and lifestyle advice for adults with moderate or severe symptomatic OSAHS at the cost-effectiveness thresholds used by NICE. This finding is reflected in the NICE guidance.

Objectives: To determine the clinical effectiveness, safety and cost-effectiveness of continuous positive airway pressure (CPAP) devices for the treatment of obstructive apnoea - hypopnoea syndrome (OSAHS), compared with the best supportive care, placebo and dental devices. Data sources: The main search was of fifteen electronic databases, including MEDLINE, EMBASE and the Cochrane Library, up to November 2006. Review methods: Randomised controlled trials (RCTs) comparing CPAP with best supportive/usual care, placebo, and dental devices in adults with a diagnosis of OSAHS were included. The primary outcomes of interest were subjective daytime sleepiness assessed by the Epworth Sleepiness Scale (ESS) and objective sleepiness assessed by the Maintenance of Wakefulness Test (MWT) and the Multiple Sleep Latency Test (MSLT). A new economic model was developed to assess incremental cost per quality-adjusted life-year (QALY). The cost-effectiveness of CPAP was compared with that of the use of dental devices and conservative management. The costs and QALYs were compared over a lifetime time horizon. Effectiveness was based on the RCT evidence on sleepiness symptoms (ESS), which was 'mapped' to utilities using individual patient data from a subset of studies. Utilities were expressed on the basis of generic HRQoL instruments [the EQ-5D (EuroQoL-5 Dimensions) in the base-case analysis]. The base-case analysis focused on a male aged 50. A series of subgroup and scenario analyses were also undertaken. Results: The searches yielded 6325 citations, from which 48 relevant clinical effectiveness studies were identified, 29 of these providing data on daytime sleepiness. The majority of the included RCTs did not report using an adequate method of allocation concealment or use an intention-to-treat analysis. Only the studies using a sham CPAP comparator were double blinded. There was a statistically significant benefit with CPAP compared with control (placebo and conservative treatment/usual care) on the ESS [mean difference (MD)-2.7 points, 95% CI-3.45 to-1.96]. However, there was statistical heterogeneity, which was reduced when trials were subgrouped by severity of disease. There was also a significant benefit with CPAP compared with usual care on the MWT. There was a non-statistically significant difference between CPAP and dental devices (six trials) in the impact on daytime sleepiness (ESS) among a population with moderate symptom severity at baseline (MD-0.9, 95% CI-2.1 to 0.4). A review of five studies evaluating the cost-effectiveness of CPAP was undertaken. All existing cost-effectiveness studies had limitations; therefore a new economic model was developed, based on which it was found that, on average, CPAP was associated with higher costs and benefits than dental devices or conservative management. The incremental cost per QALY gained of CPAP was below £20,000 in the base-case analysis and most alternative scenarios. There was a high probability of CPAP being more cost-effective than dental devices and conservative management for a cost-effectiveness threshold of £20,000 per QALY gained. Conclusions: CPAP is an effective and cost-effective treatment for OSAHS compared with conservative/usual care and placebo in populations with moderate to severe daytime sleepiness, and there may be benefits when the disease is mild. Dental devices may be a treatment option in moderate disease but some uncertainty remains. Further research would be potentially valuable, particularly investigation of the effectiveness of CPAP for populations with mild sleepiness and further trials comparing CPAP with dental devices. © 2009 Queen's Printer and Controller of HMSO. All rights reserved.

This paper addresses the use of economic evaluation to inform resource allocation decisions within health care systems about which interventions to reimburse and whether additional research should be funded. A social decision-making view of economic evaluation, that is to maximize health gains subject to an exogenous budget constraint, is adopted. A brief overview of the components of an economic evaluation is presented. Particular attention is paid to how uncertainty is inherent to decisions about resource allocation, the consequences of that uncertainty and how it can be incorporated informatively into economic evaluation. A Bayesian approach to uncertainty is used as it meets the needs of social decision-making, allowing analysts to quantify the probability that an intervention is cost-effective given the available evidence and to quantify the expected value of further research. The discussion covers methods to represent parameter and structural uncertainty and considers the role of formal elicitation of expert judgements. The association between decisions to approve interventions for reimbursement and decisions about future research funding, and how value of information analysis can be used to formalize this link, is explained. Recent developments in the UK highlight the evolving policy environment for economic evaluation, such as the Cooksey report on the funding of UK health research, the review of the Pharmaceutical Price Regulation Scheme by the Office of Fair Trading and the update of the methodological guidelines issued by the National Institute for Health and Clinical Excellence. The paper concludes by describing ongoing methodological work designed to meet the challenges of undertaking decision analysis for resource allocation in health care.

The impact of healthcare interventions on health utility values is most frequently measured using a preference-based instrument. Each of the available instruments instructs the respondent to report their health status over different recall periods ranging from the current day to the past month. In an ongoing randomised controlled trial in patients with advanced HIV disease, the impact of using a preference-based instrument with a 1-week recall period vs a 1-day recall period (e.g. today) for capturing recently resolved serious adverse events was measured. The results suggest that the instrument with a 1-week recall period gave lower utility values for recently resolved events in comparison with the instrument with a 1-day recall period. A plausible interpretation of these results is that the recall period was adhered to; for example, patients ignored the impact of recently resolved events in their response if the questionnaire asked them only about their health today. While there are limitations to our study, we believe further consideration should be given to the recall period used for preference-based instruments, and future research should examine other patient groups using a single instrument with multiple recall periods.

OBJECTIVE: To assess the cost-effectiveness of cotrimoxazole prophylaxis in HIV-infected children in Zambia, as implementation at the local health centre level has yet to be undertaken in many resource-limited countries despite recommendations in recent updated World Health Organization (WHO) guidelines. DESIGN: A probabilistic decision analytical model of HIV/AIDS progression in children based on the CD4 cell percentage (CD4%) was populated with data from the placebo-controlled Children with HIV Antibiotic Prophylaxis trial that had reported a 43% reduction in mortality with cotrimoxazole prophylaxis in HIV-infected children aged 1-14 years. METHODS: Unit costs (US$ in 2006) were measured at University Teaching Hospital, Lusaka. Cost-effectiveness expressed as cost per life-year saved, cost per quality adjusted life-year (QALY) saved, cost per disability adjusted life-year (DALY) averted was calculated across a number of different scenarios at tertiary and primary healthcare centres. RESULTS: : Cotrimoxazole prophylaxis was associated with incremental cost-effectiveness ratios (ICERs) of US$72 per life-year saved, US$94 per QALY saved and US$53 per DALY averted, i.e. substantially less than a cost-effectiveness threshold of US$1019 per outcome (gross domestic product per capita, Zambia 2006). ICERs of US$5 or less per outcome demonstrate that cotrimoxazole prophylaxis is even more cost-effective at the local healthcare level. The intervention remained cost-effective in all sensitivity analyses including routine haematological and CD4% monitoring, varying starting age, AIDS status, cotrimoxazole formulation, efficacy duration and discount rates. CONCLUSION: Cotrimoxazole prophylaxis in HIV-infected children is an inexpensive low technology intervention that is highly cost-effective in Zambia, strongly supporting the adoption of WHO guidelines into essential healthcare packages in low-income countries.

Objective: To assess whether revascularisation that is considered to be clinically appropriate is also cost effective. Design: Prospective observational study comparing cost effectiveness of coronary artery bypass grafting, percutaneous coronary intervention, or medical management within groups of patients rated as appropriate for revascularisation. Setting: Three tertiary care centres in London. Participants: Consecutive, unselected patients rated as clinically appropriate (using a nine member Delphi panel) to receive coronary artery bypass grafting only (n=815); percutaneous coronary intervention only (n=385); or both revascularisation procedures (n=520). Main outcome measure: Cost per quality adjusted life year gained over six year follow-up, calculated with a National Health Service cost perspective and discounted at 3.5%/year. Results: Coronary artery bypass grafting cost {pound}22 000 ({euro}33 000; $43 000) per quality adjusted life year gained compared with percutaneous coronary intervention among patients appropriate for coronary artery bypass grafting only (59% probability of being cost effective at a cost effectiveness threshold of {pound}30 000 per quality adjusted life year) and {pound}19 000 per quality adjusted life year gained compared with medical management among those appropriate for both types of revascularisation (probability of being cost effective 63%). In none of the three appropriateness groups was percutaneous coronary intervention cost effective at a threshold of {pound}30 000 per quality adjusted life year. Among patients rated appropriate for percutaneous coronary intervention only, the cost per quality adjusted life year gained for percutaneous coronary intervention compared with medical management was {pound}47 000, exceeding usual cost effectiveness thresholds; in these patients, medical management was most likely to be cost effective (probability 54%). Conclusions: Among patients judged clinically appropriate for coronary revascularisation, coronary artery bypass grafting seemed cost effective but percutaneous coronary intervention did not. Cost effectiveness analysis based on observational data suggests that the clinical benefit of percutaneous coronary intervention may not be sufficient to justify its cost

Objective To assess the importance of considering decision uncertainty, the appropriateness of probabilistic sensitivity analysis (PSA), and the use of patient-level simulation (PLS) in appraisals for the National Institute for Health and Clinical Excellence (NICE). Methods Decision-makers require estimates of decision uncertainty alongside expected net benefits (NB) of interventions. This requirement may be difficult in computationally expensive models, for example, those employing PLS. NICE appraisals published up until January 2005 were reviewed to identify those where the assessment group utilized a PLS model structure to estimate NB. After identifying PLS models, all appraisals published in the same year were reviewed. Results Among models using PLS, one out of six conducted PSA, compared with 16 out of 24 cohort models. Justification for omitting PSA was absent in most cases. Reasons for choosing PLS included treatment switching, sampling patient characteristics and dependence on patient history. Alternative modeling approaches exist to handle these, including semi-Markov models and emulators that eliminate the need for two-level simulation. Stochastic treatment switching and sampling baseline characteristics do not inform adoption decisions. Modeling patient history does not necessitate PLS, and can depend on the software used. PLS addresses nonlinear relationships between patient variability and model outputs, but other options exist. Increased computing power, emulators or closed-form approximations can facilitate PSA in computationally expensive models. Conclusions In developing models analysts should consider the dual requirement of estimating expected NB and characterizing decision uncertainty. It is possible to develop models that meet these requirements within the constraints set by decision-makers.

OBJECTIVES: To assess the clinical and cost-effectiveness of oral methylphenidate hydrochloride (MPH), dexamfetaminesulphate (DEX) and atomoxetine (ATX) in children and adolescents (

Methamphetamine production for illicit use occurs in makeshift labs and is associated with the release of numerous chemicals, including methamphetamine residues. These methamphetamine residues may pose a health risk to residents who reoccupy these structures after property seizures. Several states have established technology-based cleanup standards for methamphetamine, but none have examined the health-protectiveness of these standards. In response to Colorado House Bill 04-1182, exposure intakes correlated with three technology-based standards were calculated for various groups of individuals. Intakes were assessed for a 1-year-old infant, 6-year-old child, and a female of childbearing age. Exposure intakes were compared to toxicity reference values developed from developmental endpoints following methamphetamine exposure from the available literature. Uncertainty factors were applied to the lowest adverse effect levels observed in these studies to arrive at the toxicity reference values. These reference values were greater than the calculated intakes from each proposed technology standard, suggesting that all of the proposed standards would be protective of human health exposure. The cost and practicality of attaining each of the proposed standards was also factored into the decision making process. In their final regulation (6 CCR 1014-3), the CDPHE selected 0.5 μg/100 cm 2 as the final cleanup standard for methamphetamine residues.

Objective: To demonstrate the application of a Bayesian mixed treatment comparison (MTC) model to synthesize data from clinical trials to inform decisions based on all relevant evidence. Methods: The value of an MTC model is demonstrated using a probabilistic decision-analytic model developed to assess the cost-effectiveness of second-line chemotherapy in ovarian cancer. Three clinical trials were found that each made a different pair-wise comparison of three treatments of interest in the overall patient population. As no common comparator existed between the three trials, an MTC model was used to assess the combined weight of evidence on survival from all three trials simultaneously. This analysis was compared to an alternative approach that combined two of the trials to make the same comparison of all three treatments using a common comparator, and an informal approach that did not synthesize the available evidence. Results: By including all three trials using an MTC model, the credible intervals around estimated overall survival were reduced compared with making the same comparison using only two trials and a common comparator. Nevertheless, the survival estimates from the MTC model result in greater uncertainty around the optimal treatment strategy at a cost-effectiveness threshold of £30,000 per qualityadjusted life-year. Conclusions: MTC models can be used to combine more data than would typically be included in a traditional metaanalysis that relies on a common comparator. They can formally quantify the combined uncertainty from all available evidence, and can be conducted using the same analytical approaches as standard meta-analyses.

Eureka City, Utah, was the site of mining, milling, and smelting activities that resulted in contamination of soil with lead. The lead is mainly in the form of lead carbonate, which is readily bioavailable. Children in Eureka had elevated blood lead levels (24% above 10 µg/dL). Recreational exposures on waste piles were also associated with increased risk of elevated blood lead. To reduce lead exposures, contaminated residential soils were removed or capped, and homes with contaminated dust were provided HEPA vacuums. Education programs, home visits by the community nurse, and regular blood lead testing programs were developed. Blood lead levels in younger children have decreased in recent years.

OBJECTIVES: To review systematically the clinical effectiveness and the cost-effectiveness of clopidogrel used in combination with standard therapy including aspirin, compared with standard therapy alone for the treatment of non-ST-segment elevation acute coronary syndromes (ACS). DATA SOURCES: Electronic databases. Manufacturers' submissions. REVIEW METHODS: Studies were selected using rigorous criteria. The quality of randomised controlled trials (RCTs) was assessed according to criteria based on NHS CRD Report No. 4, and the quality of systematic reviews was assessed according to the guidelines for the Database of Reviews of Effect (DARE) criteria. The quality of economic evaluations was assessed according to a specifically tailored checklist. The clinical effectiveness and cost-effectiveness of clopidogrel in combination with standard therapy compared with standard therapy alone were synthesised through a narrative review with full tabulation of the results of the included studies. In the economic evaluations, a cost-effectiveness model was constructed using the best available evidence to determine cost-effectiveness in a UK setting. RESULTS: One RCT (the CURE trial) was a randomised, double-blind, placebo-controlled trial of high quality and showed that clopidogrel in addition to aspirin was significantly more effective than placebo plus aspirin in patients with non-ST-segment elevation ACS for the composite outcome of death from cardiovascular causes, non-fatal myocardial infarction or stroke over the 9-month treatment period. However, clopidogrel was associated with a significantly higher number of episodes of both major and minor bleeding. The results from the five systematic reviews that assessed the adverse events associated with long-term aspirin use showed that aspirin was associated with a significantly higher incidence of haemorrhagic stroke, extracranial haemorrhage and gastrointestinal haemorrhage compared with placebo. Of the cost-effectiveness evidence reviewed, only the manufacturer's submission was considered relevant from the perspective of the NHS. The review of this evidence highlighted potential limitations within the submission in its use of data and in the model structure used. These limitations led to the development of a new model with the aim of providing a more reliable estimate of the cost-effectiveness from the perspective of the UK NHS. This model indicated that clopidogrel appears cost-effective compared with standard care alone in patients with non-ST-elevation ACS as long as the NHS is willing to pay GBP6078 per quality of life year (QALY). The results were most sensitive to the inclusion of additional strategies that assessed alternative treatment durations with clopidogrel. Although treatment with clopidogrel for 12 months remained cost-effective for the overall cohort, provisional findings indicate that the shorter treatment durations may be more cost-effective in patients at low risk. CONCLUSIONS: The results of the CURE trial indicate that clopidogrel in combination with aspirin was significantly more effective than placebo combined with aspirin in a wide range of patients with ACS. This benefit was largely related to a reduction in Q-wave myocardial infarction. There was no statistically significant benefit in relation to mortality. The trial data suggested that a substantial part of the benefit derived from clopidogrel is achieved by 3 months, with a further small benefit over the remaining 9 months of chronic treatment. The results from the base-case model suggest that treatment with clopidogrel as an adjunct to standard therapy (including aspirin) for 12 months, compared with standard therapy alone, is cost-effective in non-ST elevation ACS patients as long as the health service is willing to pay GBP6078 per additional QALY. However, although treatment with clopidogrel for 12 months remained cost-effective for the overall cohort, provisional findings indicate that the shorter treatment durations may be more cost-effective in patients at low risk. To estimate the exact length of time that clopidogrel in addition to standard therapy should be prescribed for patients with non-ST-segment ACS would require a prospective trial that randomised patients to various durations of therapy. This would accurately assess whether a 'rebound' phenomenon occurs in patients if clopidogrel were stopped after 3 months of treatment.

OBJECTIVES: To examine the clinical effectiveness and cost-effectiveness of two alternative antiplatelet agents, clopidogrel and modified-release (MR)-dipyridamole, relative to prophylactic doses of aspirin for the secondary prevention of occlusive vascular events. DATA SOURCES: Electronic databases. REVIEW METHODS: A total of 2906 titles and abstracts were rigorously screened and 441 studies were assessed in detail. Two RCTs were identified. For the assessment of cost-effectiveness, eight reviews were identified. The results were presented in structured tables and as a narrative summary. No additional clinical effectiveness data were presented in either of two company submissions. All economic evaluations (including accompanying models) included in the company submissions were assessed. Following this analysis, if the existing models (company or published) were not sufficient, a de novo model or modified versions of the models were developed. RESULTS: In the CAPRIE trial the point estimate for the primary outcome, i.e. ischaemic stroke, myocardial infarction (MI) or vascular death, favoured clopidogrel over aspirin, but the boundaries of the confidence intervals raise the possibility that clopidogrel is not more beneficial than aspirin. In terms of the secondary outcomes reported, there was a non-significant trend in favour of clopidogrel over aspirin but the boundaries of the confidence intervals on the relative risks all crossed unity. There was no difference in the number of patients ever reporting any bleeding disorder in the clopidogrel group compared with the aspirin group. The incidences of rash and diarrhoea were statistically significantly higher in the clopidogrel group than the aspirin group. Patients in the aspirin group had a higher incidence of indigestion/nausea/vomiting than patients in the clopidogrel group. Haematological adverse events were rare in both the clopidogrel and aspirin groups. No cases of thrombotic thrombocytopenic purpura were reported in either group. Treatment with MR-dipyridamole alone did not significantly reduce the risk of any of the primary outcomes reported in ESPS-2 compared with treatment with aspirin. ASA-MR-dipyridamole was significantly more effective than aspirin alone in patients with stroke or transient ischaemic attacks (TIAs) at reducing the outcome of stroke and marginally more effective at reducing stroke and/or death. Treatment with ASA-MR-dipyridamole did not statistically significantly reduce the risk of death compared to treatment with aspirin. The number of strokes was statistically significantly reduced in the ASA-MR-dipyridamole group compared with the MR-dipyridamole group. In terms of the other primary outcomes, stroke and/or death and death, the results favoured treatment with ASA-MR-dipyridamole but the findings were not statistically significant. There was no difference in the number of bleeding complications between the ASA-MR-dipyridamole and aspirin groups. The incidence of bleeding complications was significantly lower in the MR-dipyridamole treatment group. More patients in the MR-dipyridamole treatment groups experienced headaches compared to patients receiving treatment with aspirin alone. The York model assessed the cost-effectiveness of differing combinations of treatment strategies in four patient subgroups, under a number of different scenarios. The results of the model were sensitive to the assumptions made in the alternative scenarios, in particular the impact of therapy on non-vascular deaths. CONCLUSIONS: Clopidogrel was marginally more effective than aspirin at reducing the risk of ischaemic stroke, MI or vascular death in patients with atherosclerotic vascular disease, however, it did not statistically significantly reduce the risk of vascular death or death from any cause compared with aspirin. There was no statistically significant difference in the number of bleeding complications experienced in the clopidogrel and aspirin groups. MR-dipyridamole in combination with aspirin was superior to aspirin alone at reducing the risk of stroke and marginally more effective at reducing the risk of stroke and/or death. Compared with treatment with MR-dipyridamole alone, MR-dipyridamole in combination with aspirin significantly reduced the risk of stroke. Treatment with MR-dipyridamole in combination with aspirin did not statistically significantly reduce the risk of death compared with aspirin. Compared with treatment with MR-dipyridamole alone, bleeding complications were statistically significantly higher in patients treated with aspirin and MR-dipyridamole in combination with aspirin. Due to the assumptions that have to be made, no conclusions could be drawn about the relative effectiveness of MR-dipyridamole, alone or in combination with aspirin, and clopidogrel from the adjusted indirect comparison. The following would apply for a cost of up to GBP20,000-40,000 per additional quality-adjusted life-year. For the stroke and TIA subgroups, ASA-MR-dipyridamole would be the most cost-effective therapy given a 2-year treatment duration as long as all patients were not left disabled by their initial (qualifying) stroke. For a lifetime treatment duration, ASA-MR-dipyridamole would be considered more cost-effective than aspirin as long as treatment effects on non-vascular deaths are not considered and all patients were not left disabled by their initial stroke. In patients left disabled by their initial stroke, aspirin is the most cost-effective therapy. Clopidogrel and MR-dipyridamole alone would not be considered cost-effective under any scenario. For the MI and peripheral arterial disease subgroups, clopidogrel would be considered cost-effective for a treatment duration of 2 years. For a lifetime treatment duration, clopidogrel would be considered more cost-effective than aspirin as long as treatment effects on non-vascular deaths are not considered. It is suggested that the combination of clopidogrel and aspirin should be evaluated for the secondary prevention of occlusive vascular events. Also randomised, direct comparisons of clopidogrel and MR-dipyridamole in combination with aspirin are required to inform the treatment of patients with a history of stroke and TIA, plus trials that compare treatment with clopidogrel and MR-dipyridamole for the secondary prevention of vascular events in patients who demonstrate a genuine intolerance to aspirin.

The purpose of this research was to develop a consensus description of occupational therapy practice in acute care orthopaedics and neurology by Australian therapists. The Delphi technique was used to develop consensus concerning therapists' aims for their patients, the interventions they used, and the factors affecting their practice in acute care. Therapists' primary aim was to conduct a thorough assessment for referral and further treatment purposes. Therapists in acute hospital neurology focus on developing maximal independence in self-care activities and preventing deformities, followed by preparations for discharge or transfer to rehabilitation. Therapists with an orthopaedic caseload state independence in self-care as their second most important aim, but the ranking of intervention methods indicates preparation for discharge in various ways takes precedence over direct self-care retraining. This difference may indicate a disparity between practice ideals and the realities of the acute care setting. The most important factor affecting practice in acute care is early referral for occupational therapy services. Recommendations are made for managers and educators to ensure the most effective practice in acute care are made.

Where was religion in nineteenth-century American women's writing? Everywhere. Especially with the ideological shift from a patriarchal-centered Calvinism to a more “feminized” nonsectarian Protestantism (see works cited below: Cott, Douglas, Sklar), women were given warrant to write on religious matters. At times, this writing took the form of overtly theological texts, some conventionally pious, others, like Mary Baker Eddy's 1875 Science and Health and Elizabeth Cady Stanton's 1895 The Woman's Bible , radical and revolutionary. More widespread was the way that religion as a topic pervaded virtually every genre of women's (and for that matter men's) writing from Sarah Grimke's abolitionist An Epistle to Christian Women of the South (1836) to Emily Dickinson's intensely spiritual - and skeptical - poetry. Perhaps the most striking component of nineteenth-century religious writing was the development and proliferation of religious fiction. In 1871, Harriet Beecher Stowe described the current craze for narratives that “teach[] by parables”: It is now understood that whoever wishes to gain the public ear, and to propound a new theory, must do it in a serial story. Hath any one in our day, as in St. Paul’s, a psalm, a doctrine, a tongue, a revelation, an interpretation – forthwith he wraps it up in a serial story, and presents it to the public . . . We have Romanism and Protestantism, High Church, and Low Church and no Church, contending with each other in serial stories, where each side converts the other, according to the faith of the narrator. ( My Wife and I , 2)

The EPA uses an exposure assessment model to estimate daily intake to chemicals of potential concern. At the Anaconda Superfund site in Montana, the EPA exposure assessment model was used to predict total and speciated urinary arsenic concentrations. Predicted concentrations were then compared to concentrations measured in children living near the site. When site-specific information on concentrations of arsenic in soil, interior dust, and diet, site-specific ingestion rates, and arsenic absorption rates were used, measured and predicted urinary arsenic concentrations were in reasonable agreement. The central tendency exposure assessment model successfully described the measured urinary arsenic concentration for the majority of children at the site. The reasonable maximum exposure assessment model successfully identified the uppermost exposed population. While the agreement between measured and predicted urinary arsenic is good, it is not exact. The variables that were identified which influenced agreement included soil and dust sample collection methodology, daily urinary volume, soil ingestion rate, and the ability to define the exposure unit. The concentration of arsenic in food affected agreement between measured and predicted total urinary arsenic, but was not considered when comparing measured and predicted speciated urinary arsenic. Speciated urinary arsenic is the recommended biomarker for recent inorganic arsenic exposure. By using site-specific data in the exposure assessment model, predicted risks from exposure to arsenic were less than predicted risks would have been if the EPA's default values had been used in the exposure assessment model. This difference resulted in reduced magnitude and cost of remediation while still protecting human health. Images Figure 1

Despite use of computed tomography, some lung cancer patients are found to have unresectable disease at surgery, or they present early with metastases. We studied whether whole-body positron emission tomography (PET) with 18F-fluorodeoxyglucose (18FDG) would improve the preoperative detection of metastases. We retrospectively analysed 34 patients with "operable" non-small-cell lung cancer who underwent 18FDG PET after routine assessment. Management changes produced by the PET scan and confirmatory tests were reviewed. PET identified unsuspected malignant lesions in 10 (29%) patients. Management changes occurred in 14 (41%), including 6 (18%) patients who were changed to non-surgical therapy. These data suggest that whole-body 18FDG PET improves preoperative assessment of lung cancer patients.

Abstract #6106 Purpose: To use individual patient data from three sequential large UK randomised trials to facilitate an integrated comparison of the cost-effectiveness of three generations of chemotherapy plus a no treatment option. The ABC trial compared CMF versus no chemo (1991 patients), NEAT trial Epirubicin-CMF versus CMF (2391 patients) and TACT FEC-Docetaxel vs FEC or epi-CMF (4162 patients) Methods: The model estimates lifetime costs and Quality-Adjusted Life Years (QALYs). Model inputs include transition probabilities which are estimated from a longitudinal observational study using parametric survival models incorporating characteristics such as number of positive lymph nodes, ER status, grade and tumour size that allow analyses to be conducted for women with differing baseline prognoses. The effects of each chemotherapy regimen on preventing recurrence are taken from the above UK trials and are assumed to be additive on the log scale to facilitate previously untested comparisons. Costs and utility decrements associated with chemotherapy, its toxicity, and type of recurrent disease, are informed from the trial data and published literature. A secondary analysis is performed by basing the effects of each chemotherapy regimen on published meta-analyses based on individual level data that include RCTs conducted in a range of multi-national settings. Results: For a woman aged 50 years with 1 positive node, grade 2 tumour size 2cm, ECMF is expected to be the most cost-effective regimen. However, the cost-effectiveness of the chemotherapy options varies between women with different risk factors. On the basis of the results of the TACT trial, 3rd generation chemotherapy is not cost-effective, but including evidence of the relative risk of recurrence from non-UK trials, particularly those with ER- and HER2+ phenotype, may alter this conclusion. Indicative lifetime costs and QALYs for a woman aged 50 years, with 1 positive node, grade 2 tumor size 2cm, with and without ER+ are shown: Conclusions: Evaluating the cost-effectiveness of chemotherapy regimens in women with early breast cancer who have differing prognoses is feasible using an integrative synthesis and model. Thought does, however, need to be given to how best present cost-effectiveness results when there are differing levels of baseline risk. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6106.

The apparel industry has focused in recent years on improving its responsiveness to the marketplace as a means of increasing the industry's competitiveness with overseas manufacturers. One aspect of efficient market response is the marker making process. This paper reports the results of a 12- month study undertaken at Georgia Tech to determine the technical and economic feasibility of improving the state-of-the-art in marker making systems for the apparel industry. Tech researchers have concentrated on three primary areas in performing this study. The initial effort involved contacting commercial vendors of software systems which address the marker making problem. These vendors participated in a survey designed to determine what capabilities exist in current software packages. In addition to talking with the vendors, researchers visited users of the software of each of the participating vendors. These visits allowed for a more unbiased view of the software packages. The next line of pursuit entailed an extensive literature search and analysis of the optimization problem known as the cutting stock problem. Other pertinent literature was studied for both the technical and economic aspects of the project. The final part of the study was to explore new ideas for future research in the marker making problem. Each of these areas are discussed in detail in this report.