Is neuropathic pain underdiagnosed in musculoskeletal pain conditions? The Danish PainDETECTive study.

UNLABELLED: In all, 19-22% of the adult Danish population suffer from chronic pain - most frequently in the musculoskeletal system. Different pain management strategies depending on pain mechanism (neuropathic/nociceptive) make diagnosing the pain condition especially important. OBJECTIVES: To investigate whether a validated, self-administered questionnaire (PainDETECT) helps specialists and general practitioners in Denmark identify patients with neuropathic pain components (NeP). RESEARCH DESIGN AND METHODS: In a non-interventional study a sample of Danish specialists (rheumatologists and anaesthesiologists) and general practitioners used the PainDETECT questionnaire on 1322 chronic pain patients. PainDETECT was filled in by patients and scored by the physician. A PainDETECT score above 18 indicates the presence of NeP. RESULTS: A total of 87-95% of the included chronic pain patients (702 by specialists (mean age: 56 years) and 620 by general practitioners (mean age: 55 years)) had musculoskeletal pain. In 39-43% of these patients NeP components were present as assessed by PainDETECT (score 21.1-21.7). One-third of the 540 NeP patients (31-36%) had their pain diagnosis reclassified from a non-NeP to a predominant/mixed NeP diagnosis after use of PainDETECT. CONCLUSIONS: Neuropathic pain seems to be underdiagnosed in musculoskeletal pain conditions. Use of the PainDETECT instrument may be of help to general practitioners and specialists when diagnosing NeP in chronic pain patients. However, the fact that no neurologists were included, together with the limited sample size, with large variations in the number of patients each physician included, as well as the lack of a strict consecutive recruitment process are study limitations.

Cost-effectiveness of specific immunotherapy with Grazax in allergic rhinitis co-existing with asthma.

BACKGROUND: In the United Kingdom, approximately 10.8 million people suffer from asthma, placing an economic burden on the society of more than 2 billion pounds sterling per year. For allergic asthma, treatment options consist of allergen avoidance, symptomatic treatment and allergen-specific immunotherapy (SIT). Only SIT addresses the underlying cause of the disease, reducing symptoms and offering the potential for long-term improvement. Grazax--the first tablet-based SIT--is indicated for the treatment of patients with grass pollen-induced rhinoconjunctivitis, including those with co-existing asthma. OBJECTIVE: To assess the cost-effectiveness of Grazax in patients with rhinoconjunctivitis and co-existing asthma. METHODS: A prospective pharmacoeconomic analysis was carried out as part of a multinational clinical trial assessing the efficacy of Grazax (n = 79) compared with placebo (n = 72). Both groups had access to symptomatic medication; thus the placebo group represented current standard care. Pooled data on health resource use, productivity loss because of absence from work and quality of life (Quality Adjusted Life Years, QALYs) were collected in the trial. Reduced productivity at work was estimated from the literature. A societal perspective was adopted with a 9-year time horizon. The NHS price of Grazax of 2.25 pounds sterling per tablet was used. RESULTS: The QALY gain was significantly higher for patients treated with Grazax than the placebo group receiving symptomatic medication alone (0.197 discounted QALYs gained 9 years into the future - equal to an extra 72 days of perfect health over 9 years). The levels of resource use and productivity loss were higher for the placebo group. As a result, the cost per QALY gained with Grazax was 4319 pounds sterling , which is highly cost-effective. Price sensitivity analyses demonstrated that Grazax remained cost-effective up to a tablet price of 5.07 pounds sterling . CONCLUSION: SIT with Grazax is a cost-effective strategy compared with standard management of patients with rhinoconjunctivitis and co-existing asthma.

Cost-effectiveness of GRAZAX for prevention of grass pollen induced rhinoconjunctivitis in Southern Europe.

BACKGROUND: Allergic rhinoconjunctivitis is a global health problem. Around 14 million people in Spain, France, Italy, and Austria suffer from grass pollen induced allergic rhinitis. Standard care only provides symptoms relief, while allergen specific immunotherapy (SIT) treats the underlying cause of the disease. Grazax from ALK-Abelló is a new, tablet-based, effective route of SIT for home treatment. The objective was to assess the cost-effectiveness of Grazax in four Southern European countries. METHODS: A prospective pharmacoeconomic analyses was carried out alongside a multinational, clinical trial measuring the efficacy of Grazax. Pooled data on resource use and health outcomes were collected. A societal perspective was adopted, and the analysis had a nine-year time horizon. The primary outcome measure was quality adjusted life years (QALYs). RESULTS: Grazax was superior to standard care for all efficacy endpoints, including QALYs gained, and resulted in significantly less use of rescue medication and fewer hours missed from work. Grazax was cost-effective for all countries for an annual price in the range of 1500 euros - 1900 euros. The result was improved by inclusion of future costs of asthma and exclusion of Spanish trial centers which experienced an exceptionally low pollen season. CONCLUSION: The analysis illustrates that allergen SIT with Grazax for grass pollen induced rhinoconjunctivitis is a cost-effective intervention in Southern Europe.

Cost-effectiveness of grass allergen tablet (GRAZAX) for the prevention of seasonal grass pollen induced rhinoconjunctivitis - a Northern European perspective.

BACKGROUND: The prevalence of allergic rhinoconjunctivitis has increased dramatically. Seventeen million people in the United Kingdom, Germany, the Netherlands, Sweden, Denmark, Norway and Finland suffer from grass pollen induced allergic rhinitis. Symptomatic therapy with antihistamines and topical steroids is partially effective but allergen-specific immunotherapy by injection or sublingual routes is superior. The grass allergen tablet (GRAZAX) is a new allergen-specific immunotherapy for home administration. OBJECTIVE: To assess the cost-effectiveness of the grass allergen tablet compared with symptomatic medication in seven Northern European countries. METHODS: A prospective pharmacoeconomic analysis was carried out alongside a multinational clinical trial. Pooled data on resource use and health outcomes were collected. A societal perspective was adopted, and the analysis had a 9-year time horizon. The outcome measure was Quality Adjusted Life Years (QALYs). RESULTS: The grass allergen tablet was clinically superior to symptomatic treatment, producing statistically significant differences for all efficacy end-points, including the number of QALYs gained - 0.976 vs. 0.947 QALYs gained. There was a significantly higher usage of the rescue medications loratadine and budesonide, and more hours missed from work (production loss), in the symptomatic treatment group. The cost per QALY gained in the grass allergen tablet group was similar in the seven countries (euro 12,930 to euro 18,263 for an annual cost of the grass allergen tablet of euro 1500). The analysis showed that the grass allergen tablet was cost-effective for all countries for an annual treatment cost below euro 2200. CONCLUSION: The pharmacoeconomic analysis illustrated that allergen-specific immunotherapy with the grass allergen tablet is a cost-effective intervention for the prevention of grass pollen induced rhinoconjunctivitis in Northern European countries, for a tablet price below euro 6. In Germany for example the price of the tablet is euro 2.95 corresponding to a yearly treatment cost of euro 358 - based on a 9-year time horizon.

Cost-effectiveness of computed tomographic colonography: a prospective comparison with colonoscopy.

PURPOSE: To estimate the cost-effectiveness of detecting colorectal polyps with computed tomographic colonography (CTC) and subsequent polypectomy with primary colonoscopy (CC), using CC as the alternative strategy. MATERIAL AND METHODS: A marginal analysis was performed regarding 103 patients who had had CTC prior to same-day CC at two hospitals, H-I (n = 53) and H-II (n = 50). The patients were randomly chosen from surveillance and symptomatic study populations (148 at H-I and 231 at H-II). Populations, organizations, and procedures were compared. Cost data on time consumption, medication, and minor equipment were collected prospectively, while data on salaries and major equipment were collected retrospectively. The effect was the (previously published) sensitivities of CTC and CC for detection of colorectal polyps > or = 6 mm (H-I, n = 148) or > or = 5 mm (H-II, n = 231). RESULTS: Thirteen patients at each center had at least one colorectal polyp > or = 6 mm or > or = 5 mm. CTC was the cost-effective alternative at H-I (euro187 vs. euro211), while CC was the cost-effective alternative at H-II (euro239 vs. euro192). The cost-effectiveness (costs per finding) mainly depended on the sensitivity of CTC and CC, but the depreciation of equipment and the staff's use of time were highly influential as well. CONCLUSION: Detection of colorectal polyps > or = 6 mm or > or = 5 mm with CTC, followed by polypectomy by CC, can be performed cost-effectively at some institutions with the appropriate hardware and organization.

The cost-effectiveness of bimatoprost 0.03% in the treatment of glaucoma in adult patients--a European perspective.

Glaucoma is a condition affecting one or both eyes with raised intraocular pressure (IOP). IOP should be reduced to prevent progression of visual field loss. This study investigates the cost-effectiveness of bimatoprost compared with latanoprost as first-line monotherapies in the treatment of glaucoma in Austria, Finland and France. On the basis of a single multicentre, randomised, investigator-masked controlled trial, a 6- and 12-month cost-effectiveness model was designed following the treatment recommendations from the European Glaucoma Society. Treatment changes due to insufficient IOP reduction and adverse events were included. The cost-effectiveness analysis showed that the need for adjunctive therapy was the major cost driver. On the basis of evidence from the randomised, investigator-masked clinical trial (RCT), the cost-effectiveness analysis found that bimatoprost was a cheaper and a more effective treatment strategy compared with latanoprost. This was true for all three countries and all IOP targets between 13 and 20 mmHg. The cost-effectiveness result may be generalised to a European setting and perspective.

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.

[Saving billions with telemedicine--fact or fiction?]. / Milliardbesparelser ved telemedisin--tro eller faktum?

BACKGROUND: Some claim that telemedicine technologies can save "billions" in health care expenditure. This study is a review of economic studies of telemedicine applications. MATERIAL AND METHODS: In economic evaluation resource use (costs) is compared to the health benefits generated. If telemedicine technologies have lower costs and equal or greater benefits than traditional methods, the former should be chosen. If telemedicine is more costly, but generates greater health benefits, society have to judge whether the benefits justify the costs. These issues are explored in cost-effectiveness and cost-utility analyses. We started off with a review published by the International Network of Agencies for Health Technology Assessment (INAHTA). We updated this review to December 1999 by searches in various databases. RESULTS: The INAHTA report included 19 economic analyses of telemedicine applications; in addition we identified 11 studies from last year. Three of the studies had been undertaken in Norway while the majority stemmed from North America. Only three studies made an assessment of health outcome while the others were various types of cost analyses. The majority of the studies were of low to moderate quality. Sixteen studies concluded that telemedicine was a cost-saver, three concluded opposite while the others had more "neutral" conclusions. INTERPRETATION: Telemedicine technologies can save costs, but their impact on health outcome is largely unknown. Whether a specific technology is a cost-saver will depend on its type, the cost structure of the health care system, patient volume, and geographic factors. Taking into account the limitations of the studies, we conclude that the cost-effectiveness of telemedicine methods is not established. The claim that telemedicine can save "billions" is not backed by research.

[Assessment of medical technology in practice]. / Medicinsk teknologivurdering i praksis.

With the establishment of a national institute for Health Technology Assessment (HTA), the interest in HTA is increasing in Denmark. The National Board of Health defines HTA as a comprehensive systematic evaluation of the assumptions for, and consequences of, the application of health technology. The focus is on four elements: the technology, the economy, the patient and the organisation. However, is this broad and comprehensive definition in agreement with the practical use of HTA? This article refers to an international comparison of 124 HTA-projects made by five national HTA-institutions. The article shows that only seventeen HTA-projects can be characterized as broad and comprehensive, focusing on all four elements. The rest are more restricted in their form. The future implication for Danish HTA initiatives might then be to include some partial interpretations in the HTA-definition, besides the broad and comprehensive one used today.

Diffusion of laparoscopic technologies in Denmark.

It has been predicted that minimally invasive therapy will have dramatic consequences for the specialty of general surgery, as demonstrated by the diffusion of laparoscopic cholecystectomy. To investigate the determinants of the diffusion in Denmark of five laparoscopic technologies (cholecystectomy, appendicectomy, surgery for colon cancer, surgery for inguinal hernia and fundoplication), questionnaires on seventeen factors' influence on the adoption (stimulating or impeding) were sent to fifty-nine hospitals. Fifty hospitals (85%) responded. Overall, 98% adopted laparoscopic cholecystectomy in Denmark between 1991 and 1995, whereas the remainder of the technologies were adopted by 7-65% of hospitals performing these operations. Large and specialized hospitals were the earliest adopters. The factors, nature of technology (minimally invasive versus conventional), training (appropriate training courses), competition (between specialties and between hospitals) and media attention have stimulated the diffusion, whereas three budget factors (budget for investment, budget for operation and public regulation) usually had an impeding effect. Stimulating factors prevail for all laparoscopic technologies indicating that some guidance of the adoption and use of new health technologies might be necessary. In Denmark, one of the suggested health policies to secure timely guidance is the establishment of an early warning system.

Cytological events in allo-stimulated lymphocytes triggered by exposure to stimulatory alloantigens. IV. The influence of prednisolone.

H-2b lymphocytes were sensitized against H-2d alloantigens by mixed lymphocyte culture reaction (MLR) and incubated with H-2d target cells in the presence of prednisolone or without prednisolone (control). The interaction between lymphoid cells and target cells was stopped by fixation with glutaraldehyde. Changes in cell size, in numerical density of the end of plasmic reticulum (ER) and the Golgi apparatus (GA) as well as in areal density of the lysosomes and the mitochondria in the Golgi apparatus (GA) as well as in areal density of the lysosomes and the mitochondria in the lymphoblasts during the first four hours of interaction with target cells were measured with a Hewlett Packard digitizer. The cell size showed no significant change within the first hour of interaction with target cells, but during the second hour a minor increase in cell diameter was observed whereas the diameter of the control lymphocytes increased a great deal during the first half hour as well as from the second to the third hour. The numerical density of the ER decreased throughout the four hour observation period, whereas the control lymphocytes exhibited a decrease in the numerical density of ER within the first hour after which the density increased. During the first hour of interaction with target cells the numerical density of the GA decreased and there was no increase during the rest of the observation period, whereas in the control lymphocytes the density of GA increased from the second to the third hour of interaction with target cells. There was no lysosome formation, and no significant change in the areal density of mitochondria during the four hour observation period, whereas the density of lysosomes as well as mitochondria increased in the control lymphocytes.

Colony formation by subpopulations of human T lymphocytes. II. Characteristics of colony cells and colony suppressor cells.

Phytohaemagglutinin-induced human T-lymphocyte colony formation in semisolid agar culture is the property of erythrocyte rosette-forming cells (E-RFC) negative for the 7S IgG receptor (FcR-). E-RFC positive for the 7S IgG receptor (FcR+), on the other hand, exhibit a limited capacity for colony formation and suppress colonies formed by FcR- E-RFC. T colonies are composed of small lymphocytes and lymphoblasts, the vast majority being negative for the Fc receptor. Most colony cells (86%) carry the Leu 3a antigen, suggesting that they belong to the inducer/helper T-cell subset. FcR+ colony suppressor cells are small, slowly sedimenting cells (sedimentation velocity less than 3.8 mm/h) and are strongly adherent to plastic, and their activity depends on the ability to synthesize DNA.

B lymphocyte colony formation in vitro: ultrastructural development of individual colonies.

B lymphocyte colony development in agar culture was studied using an electron microscope, and more than 3,000 colony cells were identified and photographed. In early cultures (day 4) lymphoblasts dominated the colonies. From day 5 onwards plasmablasts and small lymphocytes were present in colonies. From day 6 onward mature plasma cells were observed in increasing numbers. On day 9 culture the colonies started to degenerate and on day 10 of culture approximately 70% of the colony consisted of pyknotic and degenerating cells. Topographically, the degenerating cells were concentrated in the center of the colony whereas proliferation took place in the periphery. Colony growth occurred in an exponential fashion, the number of viable colony cells being maximal on day 8 of culture (400-600 cells/colony). At this time the frequencies of the four B cell categories were: lymphoblasts 72%, plasmablasts 20%, plasma cells 6%, and small lymphocytes 2%. Recloning experiments showed that dispersed colony cells were capable of forming only small cell clusters. It is concluded that B lymphocyte colony formation reflects a series of B cell developmental stages including the formation of the end cell categories o this lymphocyte lineage.

Cytological events in allo-stimulated lymphocytes triggered by exposure to stimulatory alloantigens. III. Changes in the areal density of cytoplasmic vacuoles containing endocytized Thorotrast.

H-2b lymphocytes were sensitized against H-2d alloantigens by a lymphocyte culture reaction (MLR) and incubated with H-2d mastocytoma cells. Thirty minutes before incubation with the mastocytoma cells Thorotrast was added to the lymphocyte culture medium. The interaction between lymphoid cells and mastocytoma cells was stopped by fixation with glutaraldehyde. The areal densities of the cytoplasmic vacuoles were examined by electron microscopy. Two populations of lymphocytes were observed, small lymphocytes with heterochromatic nuclei and larger lymphocytes (lymphoblasts) with euchromatic nuclei. Only the lymphoblasts showed changes following interaction with target cells. The areal density of Thorotrast containing vacuoles in sensitized lymphoblasts increased during the three hour observation period, but the percentage of vacuoles containing Thorotrast in the total area of cytoplasmic vacuoles decreased in the first thirty minutes of interaction with target cells. This observation may indicate greater formation of vacuoles from the Golgi apparatus compared with the formation of vacuoles from the cytoplasmic membrane at the onset of interaction with target cells. In the multivesicular bodies (MVB) the Thorotrast was first observed inside the small vesicles and later on it was also observed in the matrix of the MVB. After three hours of interaction Thorotrast was observed laying "free" in the matrix of phagosomes along with myelin figures.

Cytological events in allo-stimulated lymphocytes triggered by exposure to stimulatory alloantigens. II. Changes in the areal density of cytoplasmic vacuoles and in the subcellular localization of acid phosphatase.

H-2b lymphocytes were sensitized against H-2d alloantigens by lymphocyte culture reaction and incubated with H-2d mastocytoma cells. The interaction between lymphoid cells and mastocytoma cells was stopped by fixation with glutaraldehyde. The areal density of the cytoplasmic vacuoles as well as the subcellular localization of acid phosphatase in lymphocytes were examined by electron microscopy. Two populations of lymphocytes were observed, small lymphocytes with heterochromatic nuclei and larger lymphocytes (lymphoblasts) with euchromatic nuclei. Only the lymphoblasts showed change following interaction with target cells. The vacuole area in percent of cytoplasmic area (vacuole areal density) of sensitized lymphoblasts increased during the first 30 minutes and from the third to fourth hour of interaction with target cells. Acid phosphatase staining was observed in the Golgi apparatus of the lymphoblasts after 30 minutes of interaction. Multivesicular bodies showed acid phosphatase staining within 20 minutes of interaction with target cells. After 20 minutes of interaction, phagosomes containing myelin figures were formed. These phagosomes also showed acid phosphatase staining and during the next hours of interaction their number increased over the number of multivesicular bodies.