Apolipoprotein E controls Dectin-1-dependent development of monocyte-derived alveolar macrophages upon pulmonary ß-glucan-induced inflammatory adaptation.

The lung is constantly exposed to the outside world and optimal adaptation of immune responses is crucial for efficient pathogen clearance. However, mechanisms that lead to lung-associated macrophages' functional and developmental adaptation remain elusive. To reveal such mechanisms, we developed a reductionist model of environmental intranasal ß-glucan exposure, allowing for the detailed interrogation of molecular mechanisms of pulmonary macrophage adaptation. Employing single-cell transcriptomics, high-dimensional imaging and flow cytometric characterization paired with in vivo and ex vivo challenge models, we reveal that pulmonary low-grade inflammation results in the development of apolipoprotein E (ApoE)-dependent monocyte-derived alveolar macrophages (ApoE+CD11b+ AMs). ApoE+CD11b+ AMs expressed high levels of CD11b, ApoE, Gpnmb and Ccl6, were glycolytic, highly phagocytic and produced large amounts of interleukin-6 upon restimulation. Functional differences were cell intrinsic, and myeloid cell-specific ApoE ablation inhibited Ly6c+ monocyte to ApoE+CD11b+ AM differentiation dependent on macrophage colony-stimulating factor secretion, promoting ApoE+CD11b+ AM cell death and thus impeding ApoE+CD11b+ AM maintenance. In vivo, ß-glucan-elicited ApoE+CD11b+ AMs limited the bacterial burden of Legionella pneumophilia after infection and improved the disease outcome in vivo and ex vivo in a murine lung fibrosis model. Collectively these data identify ApoE+CD11b+ AMs generated upon environmental cues, under the control of ApoE signaling, as an essential determinant for lung adaptation enhancing tissue resilience.

Role of contextual factors in health-related quality of life in ankylosing spondylitis.

BACKGROUND: In the bio-psycho-social model of health, the role of contextual factors, either environmental or personal, is recognised. OBJECTIVE: To assess the impact of a number of contextual factors on self-reported disease-specific and generic health-related quality of life in patients with ankylosing spondylitis (AS). METHODS: 522 patients with AS from Canada and Australia completed a postal questionnaire including sociodemographic variables, disease activity (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)) function (Bath Ankylosing Spondylitis Functional Index (BASFI)) health-related quality of life (ASQoL and EQ-5D) and Rheumatoid Attitudes Index Helplessness Subscale. The contribution of contextual factors (nationality, ethnicity, marital status, education, employment and helplessness) in addition to functioning and disability (BASDAI and BASFI) to health-related quality of life was analysed using multivariate regression analyses. Interactions between contextual variables were explored. RESULTS: Contextual factors explained 37% and 47% of the variance in EQ-5D and ASQoL, respectively. Helplessness and employment were the most important contextual factors. Their role was independent of the strong effect of disease activity (BASDAI) and functional limitations (BASFI). When ASQoL was the outcome, an interaction was seen between employment and education and when EQ-5D was the outcome, an interaction was seen between helplessness and education. CONCLUSIONS: Of the contextual factors explored in this study, helplessness and employment had an important and independent contribution to health-related quality of life. In patients with lower education, the effect of not being employed on ASQoL and the effect of helplessness on EQ-5D were stronger. Contextual factors, especially helplessness and employment, should receive more attention when interpreting data on health-related quality of life.

Cost-of-illness of rheumatoid arthritis and ankylosing spondylitis.

OBJECTIVE: To assess, quantify and summarise the cost of illness of rheumatoid arthritis (RA) and ankylosing spondylitis (AS) from the societal perspective. METHODS: Original studies reporting costs of RA or AS were searched systematically. Both cost-of-illness studies and economic evaluations of therapies were included. Studies were appraised for patient and study characteristics, type of costs and actual costs. Reported costs were aggregated by cost categories and overall mean costs were summarised by cost domain (healthcare, patient and family, and productivity costs). RESULTS: Overall mean costs of RA (euro14,906 per year) were above that of AS (euro9,374 per year), while the relative distribution of costs over cost domains was approximately similar. For both diseases, productivity costs based on the human cost approach were 3 to 10 times higher than the friction costs and accounted for more than half the total costs of both diseases. CONCLUSION: Productivity costs constitute the largest part of the total cost-off-illness of RA and AS reflecting the high burden of the disease on work participation. Although total and direct costs of illness in RA were higher than in AS, the average age of AS patients was 10 years lower and therefore, lifetime costs associated with AS may actually be equal or higher.

Intrathecal baclofen therapy in children with intractable spastic cerebral palsy: a cost-effectiveness analysis.

In a Dutch national study, we recently established the effectiveness and safety of continuous intrathecal baclofen infusion (CITB) in children with intractable spastic cerebral palsy (CP). Because prospective studies on the cost-effectiveness of CITB in children with spastic CP are lacking, we conducted a cost-effectiveness analysis alongside our prospective national study. We compared the costs and health effects of CITB with those of standard treatment only, from the health care perspective for a 1-year period. Health effects were expressed in terms of a visual analogue scale for individual problems and quality-adjusted life years (QALYs). We included eight females and seven males, aged between 7 and 17 years (mean age 13y 8mo [SD 3y]). Eleven children had spastic CP and four had spastic-dyskinetic CP. One child was clsssified on the Gross Motor Function Classification System at Level III, two at Level IV, and 12 at Level V. CITB was more effective and more costly than standard treatment only. Gaining one QALY cost on average 32,737 euros. We conclude that based on the threshold-willingness to pay for one QALY in the Netherlands (80,000 euros), our results confirm the cost-effectiveness of CITB for carefully selected children with intractable spastic CP.

Cost of the meticillin-resistant Staphylococcus aureus search and destroy policy in a Dutch university hospital.

Costs related to a search and destroy policy and treatment for Staphylococcus aureus bacteraemia in the University Hospital Maastricht were calculated for the period 2000 and 2004. The financial cost-benefit break-even point of the search and destroy policy was determined by modelling. On average 22,412 patients were admitted per year for an average of 8.7 days. Each year 246 patients were screened for meticillin-resistant Staphylococcus aureus (MRSA) and 74 patients were decolonised and nursed in preventive isolation. The prevalence of MRSA in the University Hospital Maastricht was 0.7%, as calculated from positive blood cultures, and mean length of stay for all patients with S. aureus bloodstream infections was 39.9 days. The annual cost of pro-active searching for MRSA in the University Hospital Maastricht was euro 1,383,200, and euro 2,736,762 for MRSA prevention and treatment of S. aureus bloodstream infections. Simulation of a variety MRSA/meticillin-susceptible S. aureus (MSSA) ratios showed that even if the MRSA prevalence reaches 8%, prevention costs are still lower than the cost of treating S. aureus infections. In conclusion, the total cost of a search and destroy policy is lower than the cost of treating S. aureus bloodstream infections in the University Hospital Maastricht. At an MRSA prevalence of

Cost-effectiveness of pneumococcal vaccination for prevention of invasive pneumococcal disease in the elderly: an update for 10 Western European countries.

Pneumococcal vaccine is effective in preventing invasive pneumococcal disease in adults >or=65 years of age, but it is not widely used in Western Europe. In this study, data from an earlier (1995) cost-effectiveness study on Belgium, France, Scotland, Spain, and Sweden are updated, and data on five new countries--Denmark, the UK (specifically, England and Wales), Germany, Italy and The Netherlands--are added. Epidemiological and economic variables specific for each country were used, and it was assumed that pneumococcal and influenza vaccines would both be administered during the same physician visit. In the base-case analyses, the cost-effectiveness ratios ranged from euro 9239 to euro 23,657 per quality-adjusted life-year. Because the incidence and mortality of invasive pneumococcal disease were underestimated in most countries, a country-by-country analysis was performed, assuming an incidence of 50 cases per 100,000 population and mortality rates of 20, 30 and 40%. For a mortality of 20%, the cost-effectiveness ratios ranged from euro 4,778 to euro 17,093, and for a mortality of 30%, they ranged from euro 3,186 to euro 11,395. Pneumococcal vaccination to prevent invasive pneumococcal disease in elderly adults was very cost-effective in all 10 countries. This evidence justifies the wider use of the vaccine in Western Europe.

Systematic review of economic evaluations of smoking cessation: standardizing the cost-effectiveness.

OBJECTIVES: This study was performed to render cost-effectiveness studies on smoking cessation therapies, utilized until now, more comparable and more useful for medical decision making. METHODS: The cost-effectiveness ratios reported by the studies were recalculated using a societal perspective and guidelines for economic evaluation. RESULTS: The costs of individual interventions generally increased as a result of the standardization procedure, whereas the effect size decreased. This resulted in increases in the cost-effectiveness ratios for individual studies ranging from 120% to 5600%. CONCLUSIONS: The variation between studies in the percentage increase in cost-effectiveness ratios is huge. This means that not following guidelines when calculating cost-effectiveness ratios can result in large errors. Despite the fact that the standardized cost-effectiveness ratios of smoking interventions were higher than the unstandardized cost-effectiveness ratios, interventions aimed at reducing the prevalence of smoking are cost-effective.

Patient satisfaction with out-of-hours primary care in the Netherlands.

BACKGROUND: In recent years out-of-hours primary care in the Netherlands has changed from practice-based to large-scale cooperatives. The purpose of this study is to determine patient satisfaction with current out-of-hours care organised in general practitioner (GP) cooperatives, and gain insight in factors associated with this satisfaction. METHODS: From March to June 2003, 2805 questionnaires were sent to patients within three weeks after they had contacted the GP cooperative in their region. The study was conducted in the province of Limburg in the South of the Netherlands. One-third of these questionnaires was sent to patients who had only received telephone advice, one-third to patients who attended the GP cooperative for consultation, and one-third to patients who received a home visit. Four weeks after the first reminder, a non-respondents telephone interview was performed among a random sample of 100 patients. Analyses were performed with respect to the type of consultation. RESULTS: The total response was 42.4% (1160/2733). Sixty-seven percent of patients who received telephone advice only reported to be satisfied with out-of-hours care. About 80% of patients who went to the GP cooperative for consultation or those receiving a home visit, reported to be satisfied. Factors that were strongly associated with overall satisfaction included, the doctor's assistant's attitude on the phone, opinion on GP's treatment, and waiting time. CONCLUSION: Patients seem generally satisfied with out-of-hours primary care as organised in GP cooperatives. However, patients who received telephone advice only are less satisfied compared to those who attended the GP cooperative or those who received a home visit.

Cost effectiveness of foldable multifocal intraocular lenses compared to foldable monofocal intraocular lenses for cataract surgery.

AIM: To analyse the cost effectiveness of foldable monofocal intraocular lenses (IOLs) compared to foldable multifocal IOLs in cataract surgery alongside a prospective, multicentre randomised clinical trial (RCT). METHODS: Patients underwent cataract surgery with bilateral monofocal (n = 97) or multifocal (n = 93) IOL implantation. Cost data and patient preferences, using the visual analogue scale (VAS), the time trade-off (TTO), and the standard gamble (SG) technique were obtained preoperatively and postoperatively by structured interviews. The incremental costs (multifocal minus monofocal), mean costs per patient, and differences in preferences were computed. RESULTS: Mean costs for glasses per patient in the monofocal group were 41.67 and in the multifocal group 149.58. The difference in costs between the multifocal and monofocal group was -92.09 and was statistically significant (p = 0.008). No significant differences were found in total costs or in effectiveness between the monofocal and multifocal IOL group. CONCLUSION: The cost effectiveness of multifocal IOLs is reduced to a cost minimisation analysis, because of the inability to demonstrate significant differences in effects. The use of multifocal IOLs in cataract surgery resulted in a significant reduction in costs for patient's postoperative spectacles.

Pneumococcal vaccination and pneumonia: even a low level of clinical effectiveness is highly cost-effective.

Most studies of the cost-effectiveness of pneumococcal vaccination show very favorable cost-effectiveness ratios for preventing pneumococcal pneumonia, but they make the controversial assumption that vaccination is equally effective in preventing bacteremic (BPP) and nonbacteremic (NBPP) pneumonia. However, the results of our study showed that, compared with preventing BPP alone, the cost-effectiveness of pneumococcal vaccination increased substantially even when only a small proportion of additional cases of NBPP were prevented.

Estimating the costs of epilepsy: an international comparison of epilepsy cost studies.

PURPOSE: To compare systematically the national and per capita estimates of the cost of epilepsy in different countries. METHODS: Studies for this literature review were selected by conducting a Medline literature search from January 1966 to March 2000. Key methodologic, country-related, and monetary issues of the selected epilepsy cost studies were evaluated to compare their direct cost estimates and to explore their distribution. The results of the selected studies were made comparable by converting them with different types of conversion factors and expressing them as a proportion of the national expenditure on health care. RESULTS: Ten epilepsy cost studies were reviewed. The proportion of national health care expenditure on epilepsy shows a range of 0.12-1.12% or 0.12-1.05% depending on the type of conversion factor. The list of cost components included in the estimation of the direct costs of epilepsy differs from study to study. A comprehensive list is associated with a decrease in the contribution of drug and hospital costs to the total direct costs of epilepsy. CONCLUSIONS: This study highlights the importance of studying the economic consequences of epilepsy and of interpreting the results on the international level. The results of epilepsy cost studies can provide insight into the distribution of the costs of epilepsy and the impact of epilepsy on the national expenditure on health care.

Timing of adoption of laparoscopic cholecystectomy in Denmark and in The Netherlands: a comparative study.

Laparoscopic cholecystectomy (LC) has diffused rapidly in most industrialised countries. The aim of this study has been to analyse the impact of different hospital characteristics on the hospital adoption of LC in Denmark and The Netherlands. Data on the timing of the adoption of LC and hospital characteristics (hospital size, teaching status and location) were retrieved in both countries. Proportional hazard regression was used to analyse different multivariate models. A total of 59 Danish and 109 Dutch hospitals adopting LC were identified. The multivariate analyses showed that increased hospital size was associated with relatively early adoption of LC in Denmark. Neither this nor other hospital characteristics influenced the timing of adoption in The Netherlands. As in other countries studied, hospital size is identified as an important factor in hospital adoption, whereas teaching status and location play a more limited role. The study shows that a multivariate method, such as the proportional hazard regression, can be used to elucidate differences among countries of the impact of different factors on the adoption of medium-ticket technologies like LC. Such multinational comparisons provide valuable information for health policy and planning.

Economic evaluation in stroke research. An introduction.

BACKGROUND AND PURPOSE: Before developing new medical facilities or adapting existing facilities in the field of stroke, it is desirable to assess not only the medical, but also the economic consequences of such facilities. Economic evaluation studies differ from other outcome studies in the way that costs are compared with effects. The purpose of this paper is to give an insight into economic evaluation studies in the field of stroke, so that these studies become easier for neurologists to understand and to apply. SUMMARY OF THE ARTICLE: Crucial aspects in economic evaluation research are addressed successively, such as the techniques used and how the results can be influenced by the perspective of the study. The article also considers the inclusion of costs and consequences in economic evaluation research. At the end of this article, special issues in economic evaluation studies are presented such as discounting, sensitivity analysis, incremental analyses and ratios. CONCLUSIONS: Although neurologists have no direct responsibility for allocating scarce resources in the field of stroke, they are confronted with the results of these decisions in their everyday work. Because of this, it might be useful to have clear understanding of economic evaluation studies and their caveats.

[Vaccination of the elderly against pneumococcal disease is cost-efficient. Mass vaccination of all aged 65 and over is recommended]. / Det lönar sig att vaccinera de äldre mot pneumokocksjukdom. Generell vaccination av åldersgruppen över 65 rekommenderas.

The pneumococcal vaccine has been shown to be about 70 percent efficacious in preventing invasive pneumococcal disease in elderly persons. In a European multicenter study, pneumococcal vaccination was moderately cost-effective in preventing hospital admission due to invasive pneumococcal disease in persons 65 years of age or above. In Sweden the cost was approximately 300,000 SEK per quality adjusted life years (QALY) gained, but only about 60,000 SEK per QALY in a two-way sensitivity analysis making reasonable assumptions regarding the incidence and mortality of invasive pneumococcal disease in this age group. On the basis of these findings, pneumococcal vaccination should be recommended for all persons 65 years of age or older.

[Cost effectiveness of vaccination against pneumococcal bacteremia in the elderly: the results in Belgium]. / Kosteneffectiviteit van vaccinatie tegen pneumokokkenbacteriëmie bij bejaarden: resultaten voor België.

BACKGROUND: Several studies have shown that pneumococcal vaccination of older persons would be cost-effective in preventing pneumococcal pneumonia, but evidence of clinical protection for this condition is uncertain. Given much better evidence of vaccination effectiveness against invasive disease, studies showing that vaccination is cost-effective in preventing invasive disease alone could provide strong support for public policies to vaccinate older persons. METHODS: We examined the cost-effectiveness of preventing invasive pneumococcal infection by vaccination with the 23-valent pneumococcal polysaccharide vaccine of persons > or = 65 years in age in Belgium. The direct medical costs expressed per quality adjusted life year (QALYs) of a cohort of vaccinated persons was compared with the costs per QALY in a cohort of persons who are not vaccinated. RESULTS: Preventing invasive pneumococcal infections by vaccinating elderly persons clearly benefits people's health. By vaccinating 10,000 persons over 65 years of age, approximately eight QALYs can be gained compared with no vaccination. Achieving these health benefits however requires additional costs,: 30,000 ECU per QALY gained. The cost-effectiveness ratio is slightly better (i.e. 25,000 ECU per QALY) for the age group 65-75 years, and slightly worse (i.e. 35,000 ECU per QALY) for the age group 75-84 years. It increases sharply to 77,000 ECU per QALY for the persons over 85 years of age. An extensive one-dimensional sensitivity analysis did not greatly affect these results. If vaccination is also clinically effective in preventing pneumococcal pneumonia, vaccinating all elderly persons is cost saving. CONCLUSION: Using empirical epidemiological data, pneumococcal vaccination to prevent invasive pneumococcal disease is acceptably to moderately cost-effective in Belgium. On the basis of our findings, we believe public health authorities should consider policies for encouraging pneumococcal vaccination for all persons > or = 65 years in age.

Cost-effectiveness of pneumococcal vaccination of older people: a study in 5 western European countries.

Pneumococcal vaccination of older persons is thought to be cost-effective in preventing pneumococcal pneumonia, but evidence of clinical protection is uncertain. Because there is better evidence of vaccination effectiveness against invasive pneumococcal disease, we determined the cost-effectiveness of pneumococcal vaccination of persons aged > or =65 years in preventing hospital admission for both invasive pneumococcal disease and pneumococcal pneumonia in 5 western European countries. In the base case analyses, the cost-effectiveness ratios for preventing invasive disease varied from approximately 11,000 to approximately 33,000 European currency units (ecu) per quality-adjusted life year (QALY). Assuming a common incidence (50 cases per 100,000) and mortality rate (20%-40%) for invasive disease, the cost-effectiveness ratios were <12,000 ecu per QALY in all 5 countries. For preventing pneumococcal pneumonia, vaccinating all elderly persons would be highly cost-effective to cost saving. Public health authorities should consider policies for encouraging pneumococcal vaccination for all persons aged > or =65 years.

The usefulness of ratios for allocation decisions: the case of stroke.

Economic evaluation is becoming increasingly important in the field of stroke as well. The results of economic evaluation can be expressed in cost per quality-adjusted life years (QALY) gained, which enables policy makers to compare the relative efficiency of different interventions regarding different diseases. Although using the concept of QALY is preferable from a theoretical point of view, in medical practice more often cost-effectiveness analysis (CEA), and not cost-utility analysis, is applied for practical reasons. One of the main limitations of CEA is that the results may be compared only with results of other CEAs, using the same effect parameter. The calculation of cost-effectiveness ratios (CERs) in many cases is misleading for resource allocation. Effects should be expressed in interval or ratio scales in order to calculate CERs, which is rarely the case. The calculation of a CER in a CEA should only be performed if, and only if, the investigator is convinced that there is a constant relation between the specific effect parameter and the ultimate gain in health.

Economic evaluation in stroke research : a systematic review.

BACKGROUND AND PURPOSE: The purpose of this review is to provide insight into the quality of economic evaluation in the field of cerebrovascular diseases (CVD) on the basis of a systematic analysis. METHODS: A literature search was performed using several sources. Trial-based full economic evaluation studies, were included in this review. The quality of the studies was independently assessed by 2 reviewers using a checklist. RESULTS: Twenty-three articles were found to comply with our inclusion and exclusion criteria. Only a few studies mentioned the perspective of the study, and in these cases it was always the societal perspective. The majority of the studies were cost-minimization and cost-effectiveness analyses based on cohort studies. All studies included healthcare costs, and in some instances patient and family costs were considered. Costs were usually measured by tariffs. Clinical end points and mortality were used to measure effects. Cost and effect measurements were based on hospital records. CONCLUSIONS: Only a few full economic evaluations have been undertaken in the domain of CVD. In most of the studies, the technical execution and methodology were limited.