Factor VIII alloantibody inhibitors: cost analysis of immune tolerance induction vs. prophylaxis and on-demand with bypass treatment.

Development of inhibitors (alloantibodies to exogenous factor VIII) is the most significant treatment complication in patients with haemophilia A. The only proven way to eradicate inhibitors is through immune tolerance induction (ITI), while bypassing agents are typically employed to treat or prevent bleeds in patients with high titre inhibitors. Costs of these approaches have not been well studied. The aim of this study was to compare lifetime costs of treating patients with severe haemophilia A with inhibitors using on-demand or prophylaxis treatment with bypassing agents and ITI. A decision-analytic model was developed to compare the treatment costs and outcomes. Quantitation of the reduction in bleeding events for patients on prophylaxis and after eradication of inhibitors when on ITI and relapse of inhibitors was derived from published studies. Costs were obtained from standard US costing sources and are reported in 2014 US dollars. Costs and outcomes were discounted 3% per annum. Lifetime costs of treating patients with inhibitors are lower for ITI vs. on-demand or prophylaxis. Patients are also projected to live longer, have greater quality-adjusted life-years, and have fewer bleeding events than patients treated on-demand. Treating patients via ITI to eradicate inhibitors may result in lower lifetime costs and greater life-years and quality-adjusted life-years than treating with bypassing agents.

European Antibiotic Awareness Day: a five-year perspective of Europe-wide actions to promote prudent use of antibiotics.

Following the European Union (EU) Council Recommendation on prudent use of antimicrobial agents in human medicine in 2001, and the success of national campaigns, i.e. Belgium and France, the European Centre for Disease Prevention and Control (ECDC) decided to establish the European Antibiotic Awareness Day (EAAD) on 18 November as platform to support national campaigns across Europe. This article provides an overview of EAAD tools, materials, and activities developed during the first five years. It shows that EAAD has been successful due to good cooperation between ECDC and national institutions, strong political and stakeholder support and evidence-based development of campaign materials. EAAD has provided a platform for pre-existing national campaigns and encouraged similar campaigns to develop where neither political support had been secured, nor financial support had been available. As a result, participating countries have continuously expressed strong support for ECDC to continue its work on EAAD. This has been endorsed by a steadily increasing number of countries participating and the growing interest of varied professional and stakeholder organisations. We conclude that EAAD should continue to act as catalyst for discussion and as mechanism to raise awareness of the public and prescribers about prudent use of antibiotics.

Cost-effectiveness of CT perfusion for selecting patients for intravenous thrombolysis: a US hospital perspective.

BACKGROUND AND PURPOSE: Improved selection of patients with stroke for IV tPA treatment may enhance clinical outcomes. Given the limited availability of MR imaging in hospitals, we examined the cost-effectiveness of adding CTP to the usual CT-based methods for selecting patients on the basis of the presence and extent of penumbra. MATERIALS AND METHODS: A decision-analytic model estimated the costs and outcomes associated with penumbra-based CTP selection in a patient population similar to that enrolled in the IV tPA clinical trials. Model inputs were obtained from published literature, clinical trial data, standard US costing sources, and expert opinion. Cost per life-year saved and cost per QALY gained were estimated from a hospital perspective. RESULTS: Addition of penumbra-based CTP to standard unenhanced CT improved favorable outcome (mRS, ≤1) by 0.59% and reduced cost by $42 compared with selection based on unenhanced CT alone. Life-years and QALYs improved. Multivariate sensitivity analysis predicted cost-effectiveness (≤$50,000 per QALY) in 89.2% of simulation runs. CONCLUSIONS: Using penumbra-based CTP after routine CT to select patients with ischemic stroke for IV tPA is cost-effective compared with the usual CT-based methods for hospitals. With the ease of access of CTP, penumbra-based selection methods may be readily available to hospitals. Thus, this economic analysis may lend further support to the consideration of a paradigm shift in acute stroke evaluation.

Methylnaltrexone bromide for the treatment of opioid-induced constipation in patients with advanced illness--a cost-effectiveness analysis.

BACKGROUND: Opioid-induced constipation is a common adverse event in patients with advanced illness and has a significant negative impact on patients' quality of life and costs. AIM: To examine the cost-effectiveness of treating opioid-induced constipation with methylnaltrexone bromide (MNTX) plus standard care compared with standard care alone in patients with advanced illness who receive long-term opioid therapy from a third-party payer perspective in the Netherlands. METHODS: A decision-analytical model was created in which advanced-illness patients with constipation were treated with MNTX plus standard care or standard care alone. Clinical efficacy in terms of percentage of patients with rescue-free laxation and time to rescue-free laxation were obtained from a randomized, controlled clinical study. Resource use, costs, utilities and mortality were obtained from published literature and supplemented with data from clinical experts. RESULTS: Treatment with MNTX plus standard care results in more days without constipation symptoms. Cost of MNTX was mostly offset by reduction in other constipation-related costs. Thus, treating with MNTX plus standard care is cost-effective, with an incremental cost per QALY of 40,865 euro. Results were robust to changes in all parameters. CONCLUSIONS: Although using MNTX may increase total costs, MNTX plus standard care is cost-effective in treating advanced-illness patients with opioid-induced constipation.

The health and living conditions of children in child-headed households in Siteki, Swaziland.

OBJECTIVE: The focus of the study reported on here was to determine the health and living conditions of children living in child-headed households (CHHs) in Swaziland, where it is estimated that approximately 10-15 percent of the entire population will be orphans and other vulnerable children (OVC) by 2010 and that one in ten households in the country today are child-headed because of the impact of HIV and AIDS. METHODS: The population comprised 41 heads of household, caring for 97 siblings among them. Data was collected in a single period between the months of February and April 2007 using the convenience sampling method and employing a semi-structured questionnaire as the data-collection instrument. RESULTS: Children were generally physically healthy, despite not receiving adequate food or balanced diets. Most had access to health facilities or at least to sources of medication. Education assistance exists but is limited and abuse was generally not reported for fear of reprisal. Children generally relied on family and community networks for assistance, but the strain this put on those offering assistance meant that the assistance was not always consistent. Some children also relied on NGOs for food donations, but many of the children were unaware of the services offered by these organisations. CONCLUSIONS: There is a dearth of information on adolescents in Swaziland, the primary caregivers in most child-headed households. Children are not actively consulted and encouraged to participate in helping to solve the problems they are affected by. There is a lack of coordination between caregiver organisations, leading to ineffective and inefficient service provision for this particular vulnerable group.

European Antibiotic Awareness Day, 2008 - the first Europe-wide public information campaign on prudent antibiotic use: methods and survey of activities in participating countries.

Antibiotic resistance is a major European and global public health problem and is, for a large part, driven by misuse of antibiotics. Hence, reducing unnecessary antibiotic use, particularly for the treatment of certain respiratory tract infections where they are not needed, is a public health priority. The success of national awareness campaigns to educate the public and primary care prescribers about appropriate antibiotic use in Belgium and France stimulated a European initiative coordinated by the European Centre for Disease Prevention and Control (ECDC), and named European Antibiotic Awareness Day (EAAD), to take place each year on 18 November. Specific campaign materials, including key messages, logos, slogans and a media toolkit, were developed and made available for use in European countries. The focus of the first EAAD campaign was about not taking antibiotics for viral infections such as colds and flu. A post-campaign survey was conducted in January 2009. Thirty-two European countries participated in the first EAAD, producing information materials and implementing activities to mark EAAD. Media coverage peaked on 18 and 19 November. At EU level, EAAD was launched at a scientific meeting in the European Parliament, Strasbourg. The event received EU political engagement through support from the EU Commissioner for Health, the Slovenian and French EU Presidencies, and Members of the European Parliament. Critical factors that led to the success of the first EAAD were good cooperation and process for building the campaign, strong political and stakeholder support and development of campaign materials based on scientific evidence. Countries indicated wide support for another EAAD in 2009. For this purpose, ECDC is developing several TV spots as well as a second set of EAAD campaign materials targeting primary care prescribers.

Cost-effectiveness of bisphosphonate therapies for women with postmenopausal osteoporosis: implications of improved persistence with less frequently administered oral bisphosphonates.

OBJECTIVE: Studies have shown that weekly bisphosphonate dosing results in improved persistence compared to daily dosing among patients with postmenopausal osteoporosis, yet more than 50% of patients discontinue therapy within a year. An oral, less frequent administration bisphosphonate provides an opportunity to improve persistence, a parameter not well modeled in previous cost-effectiveness analyses of osteoporosis therapies. RESEARCH DESIGN AND METHODS: We developed a Markov model to estimate the effect of improved persistence on the cost-effectiveness of bisphosphonates among postmenopausal women with established osteoporosis (vertebral fracture and bone mineral density T-score

Economic evaluation of Durogesic in moderate to severe, nonmalignant, chronic pain in Germany.

We carried out a cost-effectiveness evaluation of transdermal fentanyl compared to three other widely used opioids: transdermal buprenorphine, sustained-release morphine, and controlled-release oxycodone from a third-party-payers perspective. A decision analytic model with data from a structured database search and from panel data and assumptions was used to derive both cost and utility results. Probabilistic sensitivity analysis was performed to ensure the findings. Transdermal fentanyl patients gain more quality adjusted life-days or quality-adjusted life-years per euro. The incremental cost per quality-adjusted life-year is 1,625.65 euro for transdermal fentanyl compared to sustained-release morphine and 1,003.03 euro compared to CO, and it is cost-saving compared to transdermal buprenorphine (-203.38 euro per patient). Transdermal fentanyl is thus cost-effective compared to both sustained-release morphine and CO and dominant compared to transdermal buprenorphine in the treatment of adults with nonmalignant moderate to severe chronic pain.

Closed reduction of colles fractures: comparison of manual manipulation and finger-trap traction: a prospective, randomized study.

BACKGROUND: An optimal outcome of closed treatment of a Colles fracture may depend on accurate reduction and adequate immobilization. It has been suggested that the use of finger-trap traction results in a better reduction and a lower rate of redisplacement than manual manipulation does, but to our knowledge these concepts have never been evaluated scientifically. We compared these two methods in a prospective, randomized controlled trial. METHODS: Two hundred and twenty-three patients with 225 displaced Colles-type fractures were randomized to treatment with closed reduction with either finger-trap traction (112 patients) or manual manipulation (111 patients). The fractures were assessed radiographically by measurement of the radial angle, dorsal tilt, and radial shortening before reduction, immediately after reduction, and at one and five weeks after reduction. RESULTS: The groups were comparable with regard to age, sex, side of injury, fracture grade, and amount of displacement at presentation. No significant differences were found between the alignment of the fractures in the two treatment groups at any time. With dorsal tilt of <10 degrees and radial shortening of <5 mm considered acceptable, the two techniques both produced an 87% rate of satisfactory reductions. However, the percentages of fractures in an acceptable alignment were only 57% and 50% at one week after finger-trap traction and manual manipulation, respectively, and only 27% and 32% at five weeks. The failure rates did not differ significantly between the two groups. CONCLUSIONS: The two methods of fracture reduction did not differ with regard to the eventual position of the fracture or the rate of failure. Although closed reduction was successful for the majority of fractures, most redisplaced substantially during the period of cast immobilization.

Tooth counts do not predict bone mineral density in early postmenopausal Caucasian women. EPIC study group.

BACKGROUND: It has been suggested that poor dental status may be a suitable criterion for bone densitometry referral in early postmenopausal women. We evaluated this hypothesis in a cohort of 1365 Caucasian women aged between 45 and 59 years, who were enrolled into an international multi-centre trial. METHODS: Subjects were recruited at four study centres, using population-based techniques. Bone mineral density (BMD) at the lumbar spine and proximal femur was measured by dual energy x-ray absorptiometry (DXA) (Hologic QDR 2000). A full physical examination was performed including a tooth count. RESULTS: Baseline tooth counts ranged from 0 to 32 (median 26): 84 (6%) subjects were edentulous. When classified according to the WHO criteria 445 (33%) of the subjects were osteoporotic at one or more of the skeletal sites analysed; 694 (51%) were osteopenic, and 226 (16%) were normal. Adjusting for confounding variables, there was no significant correlation between tooth count and BMD at any skeletal site. Subjects were divided into tertiles of tooth count, and chi2 tests used to compare the two 'extreme' groups against the WHO criteria for BMD. At each of the six BMD regions the proportion of subjects with normal, osteopenic or osteoporotic BMD was similar for both tertiles. CONCLUSIONS: We found no relationship between tooth count and BMD in early postmenopausal women. This may be because in younger women dental status is a reflection more of dietary habits and past dental surgery than of age-related bone loss. Tooth counts therefore cannot be used to identify individuals at risk of osteoporosis.

Colles' fracture of the wrist as an indicator of underlying osteoporosis in postmenopausal women: a prospective study of bone mineral density and bone turnover rate.

Colles' fracture has been shown to be associated with an increased risk of hip fracture. The incidence of low bone mineral density (BMD) and high bone turnover in such patients is uncertain. The aim of this study was to prospectively assess BMD and bone turnover in a cohort of consecutive postmenopausal Colles' fracture patients. BMD (spine, hip and contralateral radius) was measured by dual-energy X-ray absorptiometry (DXA) within 2 weeks of fracture. Bone turnover was assessed within 4 days by measurement of serum osteocalcin, total alkaline phosphatase (TALP), bone-specific alkaline phosphatase (BSAP) and urine hydroxyproline. We recruited 106 (71%) of 149 consecutive patients. Fifty-one per cent of subjects had a history of previous fracture, and 25% a past history of wrist, hip or vertebral body fracture. The incidence of osteoporosis was 21%, 42% and 22% at the spine, hip and radius respectively. Fifty per cent of subjects had osteoporosis of at least one of these sites. When compared with the values expected for their age the patients were found to have higher BMD than expected at the spine, and slightly lower BMD at the hip and distal radius. Patients aged 65 years or less had lower hip BMD than expected from the age-matched normal range (p < 0.01). Osteocalcin and TALP levels did not differ from the normal ranges, but BSAP and hydroxyproline levels were significantly elevated (p < 0.001), with 37% and 25% of patients having levels above the respective normal ranges. We conclude that osteoporosis is common in patients with Colles' fracture; however, in older patients BMD is not lower than would be expected in the normal population. In patients aged 65 years or less BMD is lower than expected at the hip. Bone turnover rate is high in many such patients. Intervention to prevent future fracture would be appropriate in women aged 65 years or less with Colles' fracture.

Current diet does not relate to bone mineral density after the menopause. The Nottingham Early Postmenopausal Intervention Cohort (EPIC) Study Group.

The influence of dietary Ca on peak bone mass and on subsequent bone loss is controversial. Despite this an assessment of nutritional status is often included in the clinical evaluation of osteoporosis risk. To assess the value of this we investigated the relationship between current diet and bone mineral density (BMD) in 426 postmenopausal women, aged 45-59 years, who were enrolled into an international multi-centre trial of alendronate for the prevention of postmenopausal osteoporosis. BMD of the lumbar spine and proximal femur was measured on two occasions approximately 2 weeks apart by dual-energy X-ray absorptiometry. Serum osteocalcin was measured by immunoradiometric assay and serum 25-hydroxycholecalciferol by radioimmunoassay. Dietary assessment was performed by analysis of a 3 d unweighted dietary record, using Salford University's Microdiet software. BMD at both the lumbar spine and femoral neck correlated significantly with BMI, age, and average serum osteocalcin concentration. We therefore corrected for these variables in subsequent analyses. Dietary Ca intake ranged from 223 to 2197 mg/d (median 852 mg/d). Neither dietary Ca intake nor any other nutritional variable correlated significantly with BMD. There was a weak, but significant correlation between Ca intake and serum osteocalcin. We conclude that current diet does not correlate with BMD in early postmenopausal women. However, present diet may affect the rate of change of BMD, and this is supported by the finding of a significant relationship between dietary Ca and serum osteocalcin, a marker of bone formation rate.

Trends in the use of accident and emergency services by the homeless on the Wirral.

OBJECTIVE: To examine the use of accident and emergency (A&E) services by the homeless, with particular reference to the use of psychiatric services generated by this attendance. METHODS: A retrospective study of attendance registers at a large A&E department over an eight year period, during which there were 566 separate attendances by homeless patients out of a total of 421 237 adult attendances (1.3 per 1000). RESULTS: There was no significant change in rates of attendances over the eight year period (P = 0.41), in the broad demographic details of the groups, or in the use of psychiatric services. CONCLUSIONS: There has been no significant increase in the use of A&E services by homeless people in the population studied over the eight year period. Several possible explanations for this are given.

Dangerous monoamine oxidase inhibitor interactions are still occurring in the 1990s.

The clinical course is described of a 28-year-old woman who was severely ill following ingestion of a Do-Do tablet (which consists of ephedrine, caffeine and theophylline), 24 h after discontinuing phenelzine treatment. Signs and symptoms were delayed for 8 h after which she developed encephalopathy, neuromuscular irritability, hypotension, sinus tachycardia, rhabdomyolysis and hyperthermia. Her illness was complicated by pneumonia and adult respiratory distress syndrome (ARDS). The management of monoamine oxidase inhibitor (MAOI) toxicity, which can arise from interactions and overdoses, is discussed. It should be remembered that, despite the increase in use of alternative and safer antidepressants, MAOI interactions still occur and unless they are managed appropriately, are potentially fatal. Patients need to be warned that restrictions apply for up to 2 weeks after stopping the medication, and doctors need to be aware that serious interactions can occur in this time period.

Pressurised aerosol inhalers: the cost of misuse.

Bronchodilator aerosols, if used correctly, have many advantages over other therapies in patients with chronic airflow limitation caused by asthma or chronic bronchitis. The use of pressurized aerosol inhalers was examined in a district general hospital: of 57 patients on these inhalers, 39 were unable to use the inhaler effectively, and 23 had never received any advice on inhaler technique. A single demonstration of correct technique decreased the failures to 21 patients and, after two demonstrations, to ten. The cost of the misused inhalers in this relatively small population was 450 pounds, and obviously this figure escalates when the prescription for these inhalers is repeated monthly. It is also increased when the total numbers of misused inhalers in the country are accounted for. The cost in terms of finance, in these days of medical audit and drug budgets, and, more importantly, in terms of patient health, is unacceptable and can be avoided by repeated tuition of technique.