The societal costs of problem gambling in Sweden.

BACKGROUND: Problem gambling is a public health issue affecting both the gamblers, their families, their employers, and society as a whole. Recent law changes in Sweden oblige local and regional health authorities to invest more in prevention and treatment of problem gambling. The economic consequences of gambling, and thereby the potential economic consequences of policy changes in the area, are unknown, as the cost of problem gambling to society has remained largely unexplored in Sweden and similar settings. METHODS: A prevalence-based cost-of-illness study for Sweden for the year 2018 was conducted. A societal approach was chosen in order to include direct costs (such as health care and legal costs), indirect costs (such as lost productivity due to unemployment), and intangible costs (such as reduced quality of life due to emotional distress). Costs were estimated by combining epidemiological and unit cost data. RESULTS: The societal costs of problem gambling amounted to 1.42 billion euros in 2018, corresponding to 0.30% of the gross domestic product. Direct costs accounted only for 13% of the total costs. Indirect costs accounted for more than half (59%) of the total costs, while intangible costs accounted for 28%. The societal costs were more than twice as high as the tax revenue from gambling in 2018. Direct and indirect costs of problem gambling combined amounted to one third of the equivalent costs of smoking and one sixth of the costs of alcohol consumption in Sweden. CONCLUSIONS: Problem gambling is increasingly recognized as a public health issue. The societal costs of it are not negligible, also in relation to major public health issues of an addictive nature such as smoking and alcohol consumption. Direct costs for prevention and treatment are very low. A stronger focus on prevention and treatment might help to reduce many of the very high indirect and intangible costs in the future.

Measuring the end-of-life premium in cancer using individual ex ante willingness to pay.

For the assessment of value of new therapies in healthcare, Health Technology Assessment (HTA) agencies often review the cost per quality-adjusted life-year (QALY) gained. Some HTA agencies accept a higher cost per QALY gained when treatment is aimed at prolonging survival for patients with a short expected remaining lifetime, a so-called end-of-life (EoL) premium. The objective of this study is to elicit the existence and size of an EoL premium in cancer. Data was collected from 509 individuals in the Swedish general population 20-80 years old using a web-based questionnaire. Preferences were elicited using subjective risk estimation and the contingent valuation (CV) method. A split-sample design was applied to test for order bias. The mean value of a QALY was MSEK4.8 (€528,000), and there was an EoL premium of 4-10% at 6 months of expected remaining lifetime. Using subjective risk resulted in more robust and valid estimates of the value of a QALY. Order of scenarios did not have a significant impact on the WTP and the result showed scale sensitivity. Our result provides some support for the use of an EoL premium based on individual preferences when expected remaining lifetime is short and below 24 months. Furthermore, we find support for a value of a QALY that is above the current threshold of several HTA agencies.

Real-world outcomes in 2646 psoriasis patients: one in five has PASI ≥10 and/or DLQI ≥10 under ongoing systemic therapy.

BACKGROUND: Although biologics introduced a new era in psoriasis care when available a decade ago, it is unclear to what extent the available systemic treatments treat patients adequately. OBJECTIVE: To analyse the clinical severity and quality of life of the psoriasis population in Sweden treated with systemics. METHODS: Data included 2646 patients from the Swedish Registry for Systemic Treatment of Psoriasis. Average Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI) and EQ-5D were reported. A subgroup of persisting moderate-to-severe psoriasis as defined by PASI ≥10 and/or DLQI ≥10 after >12 weeks treatment was analysed. RESULTS: Mean (SD) PASI, DLQI and EQ-5D were 4.12 (4.57), 4.11 (5.24) and 0.79 (0.22). Eighteen percent had persisting moderate-to-severe psoriasis (n = 472). These patients were younger, had higher BMI, had psoriasis arthritis and were smoking to a larger extent (p < 0.01) compared with lower-severity patients (n = 2174). Mean (SD) EQ-5D was also considerably lower 0.63 (0.29) vs. 0.82 (0.19) (p < 0.01). CONCLUSION: Almost one in every five patients had persisting moderate-to-severe psoriasis, despite ongoing systemic treatment. Both comorbidities and life style factors were associated with persisting moderate-to-severe psoriasis. The considerably lower generic quality of life in these patients demonstrates an unmet need. Subsequently, improved access to biologics and continuous drug development is needed in psoriasis.

A method for calculating a land-use change carbon footprint (LUC-CFP) for agricultural commodities - applications to Brazilian beef and soy, Indonesian palm oil.

The world's agricultural system has come under increasing scrutiny recently as an important driver of global climate change, creating a demand for indicators that estimate the climatic impacts of agricultural commodities. Such carbon footprints, however, have in most cases excluded emissions from land-use change and the proposed methodologies for including this significant emissions source suffer from different shortcomings. Here, we propose a new methodology for calculating land-use change carbon footprints for agricultural commodities and illustrate this methodology by applying it to three of the most prominent agricultural commodities driving tropical deforestation: Brazilian beef and soybeans, and Indonesian palm oil. We estimate land-use change carbon footprints in 2010 to be 66 tCO2 /t meat (carcass weight) for Brazilian beef, 0.89 tCO2 /t for Brazilian soybeans, and 7.5 tCO2 /t for Indonesian palm oil, using a 10 year amortization period. The main advantage of the proposed methodology is its flexibility: it can be applied in a tiered approach, using detailed data where it is available while still allowing for estimation of footprints for a broad set of countries and agricultural commodities; it can be applied at different scales, estimating both national and subnational footprints; it can be adopted to account both for direct (proximate) and indirect drivers of land-use change. It is argued that with an increasing commercialization and globalization of the drivers of land-use change, the proposed carbon footprint methodology could help leverage the power needed to alter environmentally destructive land-use practices within the global agricultural system by providing a tool for assessing the environmental impacts of production, thereby informing consumers about the impacts of consumption and incentivizing producers to become more environmentally responsible.

Budget impact analysis of surgical treatment for obesity in Sweden.

BACKGROUND: The recent substantial increase in the number of obese surgeries performed in Sweden has raised concerns about the budget impact. OBJECTIVE: Our aim in this paper is to present an assessment of the budgetary impact of different policies for surgical intervention for obese and overweight subjects from a healthcare perspective in Sweden. METHODS: The model simulates the annual expected treatment costs of obesity related diseases and surgery in patients of different sex, age and Body Mass Index (BMI). Costs evaluated are costs of surgery plus the excess treatment costs that an obese patient has over and above the treatment costs of a normal-weight patient. The diagnoses that are included for costs assessment are diabetes and cardiovascular disease since these diagnoses are the principal diagnoses associated with obesity. Four different scenarios over the number of surgical operations performed each year are simulated and compared: (1) no surgical operation, (2) 3 000 surgical operations in persons with BMI > 40, (3) 4 000 (BMI > 40), and (4) 5 000 (expanded to BMI > 38). RESULTS: Comparing Scenario 2 with Scenario 1 results in a net budget impact of on average SEK 121 million per annum or SEK 40 000 per patient. This implies that 55 percent of the cost of surgery, set equal to SEK 90 000 for each patient, has been offset by a reduction in the excess treatment costs of obesity related diseases. Expanding annual surgery from 3000 to 4000 the cost-offset increased to 58%. By expanding annual surgery further from 4000 to 5000 and at the same time expanding the indication for surgery from BMI > 40 to BMI > 38, no cost-offset is obtained. CONCLUSION: A cost-minimization strategy for bariatric surgery in Sweden should not expand indication, but rather increase the number of surgeries within the currently accepted indication.

Costs associated with blood transfusions in Sweden--the societal cost of autologous, allogeneic and perioperative RBC transfusion.

Anaemia is characterised by an insufficient number of red blood cells (RBCs) and might occur for different reasons, e.g. surgical procedures are often with associated blood loss. Patients who suffer from anaemia have the option of treatment with blood transfusion or medical treatment. In this study, the societal cost, for the case of Sweden, of RBC transfusion using three different techniques, i.e. allogeneic, autologous and intraoperative transfusion, was estimated. The analysis was based on information from interviews with hospital staff at large Swedish hospitals and from published data. The average cost for a 2 units transfusion was found to be Swedish kronor (SEK) 6330 (702 Euro) for filtered allogeneic RBCs and SEK 5394 (598 Euro) for autologous RBCs for surgery patients. Transfusion reactions accounted for almost 35 per cent of the costs of allogeneic RBC transfusions. The administration cost was found to be much higher for autologous transfusions compared with allogeneic transfusions. The cost of intraoperative erythrocyte salvage was calculated to be SEK 2567 (285 Euro) per transfusion (>4 units).

Donor and liability insurance of donor registries, donor centers, and collection centers--recommendations.

The article presents views and recommendations of the World Marrow Donor Association regarding the need for donor and liability insurance for hematopoietic stem cell donor registries, and donor and collection centers.

Costs for screening, intervention and hospital treatment generated by the Malmö Preventive Project: a large-scale community screening programme.

OBJECTIVES: The purpose of this study was to estimate retrospectively the costs of health care resources used in the Malmö Preventive Project, Sweden and estimate the costs of in-patient care that were avoided because of early intervention. SETTING AND SUBJECTS: A large-scale community intervention programme was conducted from 1974 to 1992 in Malmö, Sweden with the aim of reducing morbidity and mortality of cardiovascular diseases (CVD), alcohol related illnesses, and breast cancer. Between 1974 and 1992, 33 336 male and female subjects were screened for hypertension, hyperlipidaemia, type-2 diabetes and alcohol abuse. Intervention programmes that included life-style modifications, follow-up visits with physicians and nurses and drug therapy were offered to about 25% of screened subjects. METHODS: Recruitment costs were generated through out the screening period. Intervention costs were estimated for 5 years after screening. Excess in-patient care costs were estimated by subtracting hospital consumption for an unscreened, matched cohort from that of the screened cohort over follow-up periods of 13-19 years. Intervention and excess in-patient care costs were estimated until 1996. RESULTS: The net expenditures for recruitment and intervention was SEK253 million and saved costs for in-patient care of SEK143 millions (1998 prices). Considering the opportunity cost of the resources used in the study, the net cost rises to about SEK200 millions. CONCLUSIONS: The results suggest that only part of the intervention costs were offset by reduction in future morbidity health care costs. This is in line with results from prospective analyses of other primary prevention programmes.

Cost effectiveness of Becaplermin in the treatment of diabetic foot ulcers in four European countries.

OBJECTIVE: The primary objective of this study was to estimate the cost effectiveness of treating diabetic foot ulcers with becaplermin (Regranex) plus good wound care (GWC) compared with GWC alone in a variety of European healthcare settings. A secondary objective was to analyse the effect of different treatment practices on the economics of caring for diabetic foot ulcers. DESIGN AND SETTING: Markov-based simulation study from the perspective of a national health system. METHODS: A 12-month Markov computer simulation model was used to assess the cost effectiveness in 4 European countries of treating diabetic foot ulcers with becaplermin plus GWC versus GWC alone. Transition probabilities were taken from a prospective study of 183 patients and becaplermin efficacy was based on 20-week healing rates in a recent meta-analysis of clinical trials involving 449 patients. Country-specific treatment cost data were collected in collaboration with local economic consultations and combined with the disease model to estimate the incremental cost per ulcer-free month gained. The model was then run using hypothetical low- and high-intensity resource usage profiles to investigate the economics of caring for diabetic foot ulcers. RESULTS: Over the course of 1 year, individuals who received becaplermin plus GWC were, on average, predicted to spend an additional 0.81 months (24% longer) free of ulcers and to experience a 9% lower risk of undergoing a lower extremity amputation than individuals who received GWC alone. Consequently, becaplermin plus GWC was estimated to be net cost saving in Sweden, Switzerland and the UK. In France, the addition of becaplermin was estimated to add $US19 (1999 values) for each additional ulcer-free month gained. There were substantial intercountry differences in treatment practices and the costs of treating diabetic foot ulcers. CONCLUSIONS: Becaplermin may be a cost-effective treatment for neuropathic diabetic foot ulcers in a wide range of European settings. In Sweden, Switzerland and the UK, becaplermin may even be cost saving. Substantial intercountry differences in resource patterns appear, at least partly, to be the logical outcome of differences in unit costs.

Identification and purification of vitamin K-dependent proteins and peptides with monoclonal antibodies specific for gamma -carboxyglutamyl (Gla) residues.

Novel monoclonal antibodies that specifically recognize gamma-carboxyglutamyl (Gla) residues in proteins and peptides have been produced. As demonstrated by Western blot and time-resolved immunofluorescence assays the antibodies are pan-specific for most or all of the Gla-containing proteins tested (factors VII, IX, and X, prothrombin, protein C, protein S, growth arrest-specific protein 6, bone Gla protein, conantokin G from a cone snail, and factor Xa-like proteins from snake venom). Only the Gla-containing light chain of the two-chain proteins was bound. Decarboxylation destroyed the epitope(s) on prothrombin fragment 1, and Ca(2+) strongly inhibited binding to prothrombin. In Western blot, immunofluorescence, and surface plasmon resonance assays the antibodies bound peptides conjugated to bovine serum albumin that contained either a single Gla or a tandem pair of Gla residues. Binding was maintained when the sequence surrounding the Gla residue(s) was altered. Replacement of Gla with glutamic acid resulted in a complete loss of the epitope. The utility of the antibodies was demonstrated in immunochemical methods for detecting Gla-containing proteins and in the immunopurification of a factor Xa-like protein from tiger snake venom. The amino acid sequences of the Gla domain and portions of the heavy chain of the snake protein were determined.

The cost-effectiveness of treating diabetic lower extremity ulcers with becaplermin (Regranex): a core model with an application using Swedish cost data.

OBJECTIVES: The objective of this study was to develop a model capable of assessing the cost-effectiveness in Sweden of treating diabetic neuropathic lower extremity ulcers with becaplermin gel (Regranex) plus good wound care (GWC) relative to treating them with GWC alone. METHODS: A Markov simulation model was developed that includes six health states: Uninfected Ulcer, Infected Ulcer, Gangrene, Healed Ulcer, Healed Ulcer-History of Amputation, and Deceased. To predict clinical outcomes, information was taken from a specially designed prospective 9-month follow-up study of 183 neuropathic patients in the US treated with GWC. Cost of treatment data were taken primarily from a study of a cohort of 314 patients in Sweden. The efficacy of becaplermin was assumed equal to that achieved in a pooled analysis of four randomized clinical trials. A model application provides expected clinical outcomes for a cohort of patients. Annual treatment costs per patient were estimated using treatment practice and unit prices from Sweden. RESULTS: Due to a higher rate of healing and a shorter average healing time, treatment with becaplermin gel was predicted to increase the average number of months spent in the healed state over the first year following development of an ulcer by 24% relative to GWC alone. In addition, the corresponding number of amputations was 9% lower for the becaplermin-treated cohort. The average expected cost of $12,078 US for an individual treated with GWC alone declines to $11,708 US for one treated with becaplermin, in spite of $1262 becaplermin costs. Expenses related to topical treatment and inpatient care account for 83% of the resources conserved. CONCLUSIONS: Our results suggest that in Sweden treatment with becaplermin in conjunction with GWC consumes fewer resources and generates better outcomes than treatment with GWC alone for diabetic neuropathic ulcers. In light of the high and increasing incidence of such ulcers, the potential savings in costs and suffering may be important. Results are difficult to extrapolate internationally because they are strongly related to country-specific treatment practices and price levels.

The economics of preventing revisions in total hip replacement.

We showed that the selection of a cost-effective type of cement and method of prophylaxis against deep infections for patients undergoing total hip replacement depended on the number of arthroplasties performed each year at individual hospitals. When 100 arthroplasties were performed each year, the use of Palacos cement and systemic antibiotics reduced the total costs to the department, i.e., the cost of cement, infection prophylaxis and revisions. The use of gentamicin-impregnated cement in combination with systemic antibiotics will further reduce the risk of revision and is another cost-effective strategy. The most effective infection prophylaxis would be achieved with a combination of gentamicin-impregnated cement, systemic antibiotics and surgical enclosure. However, the additional cost of the surgical enclosure would not be offset by cost savings due to reduced risk of revisions.

Expression of TGF-beta related Smad proteins in human epithelial skin tumors.

Members of the transforming growth factor (TGF)-beta family regulate cell growth and differentiation activating intracellular Smad proteins. Their role in skin and skin tumorigenesis is not well understood. Therefore we investigated the expression of TGF-beta type I receptor (TbetaR-I) and Smad-proteins involved in the TGF-beta-pathway, e.g. Smad2, Smad3, Smad4, Smad6 and Smad7. We examined the effects of TGF-beta1, -beta2, BMP2, BMP7 on five epithelial cell lines in vitro. TGF-beta1-mediated growth inhibition of HaCaT and HSC4 were observed with half maximal effects at approximately 7 pg ml-1 and 20 pg ml-1, respectively. However, malignant HSC2 and A431 cells were unresponsive to TGF-beta1. A differentiation was seen after 5 days in HaCaT and HSC4 cells only. We compared the reactivity with specific antisera against TbetaR-I and Smad proteins among the different skin tumors: seborrheic keratoses (SK), actinic keratoses (AK), basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). There were statistically significant differences of the ratio between the expression in tumor and that in non-tumorous epithelial cells in each tissue specimen. There was a tendency for the lower level of TbetaR-I expression of SCC compared with SK (p=0.08). This was accompanied by the decreased expression of the TbetaR-I. We found a markedly decreased expression of all antigens in BCC. conversion of normal keratinocytes to tumorigenic cells may in part be due to an acquisition of resistance to TGF-beta and loss of expression of intracellular signalling Smad proteins.

C3 and C4 allotypes in anti-neutrophil cytoplasmic autoantibody (ANCA)-positive vasculitis.

In ANCA-associated small vessel vasculitis few genetic factors have proven to be of importance for disease susceptibility, an exception being deficiency of alpha1-anti-trypsin, the main inhibitor of proteinase 3 (PR3). Alerted by our finding that myeloperoxidase has affinity for C3, and the finding of an increased frequency of the C3F allele in systemic vasculitis in a British cohort, we examined polymorphism of C3 and C4 in patients with ANCA+ small vessel vasculitis. After identification of all patients at our department with a positive ANCA test during the period 1991-95 and a diagnosis of small vessel vasculitis, blood samples were collected after informed consent. The 67 included patients were grouped according to ANCA serology and disease phenotype using the Chapel Hill nomenclature. The gene frequency of C3F was found to be increased (0. 32) compared with controls (0.20; P < 0.05) in the PR3-ANCA+ subgroup. The frequency of C4A3 was increased in the group as a whole, but no increase of C4 null alleles was seen. The findings imply a role for the complement system in the pathogenesis of ANCA-associated small vessel vasculitis.

Cost-effectiveness analysis of pegylated-liposomal doxorubicin and liposomal daunorubicin treatments in patients with Kaposi's sarcoma.

Economic evaluations of new AIDS treatment drugs are important. For physicians treating patients with Kaposi's sarcoma, these issues are especially meaningful since cancer treatment costs for this group of patients are high. Kaposi's sarcoma is the most frequently occurring neoplasm in AIDS patients, affecting about 15% of this population. In our study, a retrospective economic evaluation has been made based on data from two randomized phase III clinical studies of severely immune-compromised HIV-infected individuals and which compares liposomal doxorubicin with liposomal daunorubicin. We have estimated the cost and cost effectiveness of the two drugs. The costs per complete or partial response are USS 18340 for daunorubicin and USS 8871 for doxorubicin. The incremental cost per additional responder by using liposomal doxorubicin instead of liposomal daunorubicin is USS 1910. Sensitivity analysis shows that these results hold over a wide range of assumptions.

Painful bone metastases in hormone-refractory prostate cancer: economic costs of strontium-89 and/or external radiotherapy.

OBJECTIVES: In a prospective randomized Canadian trial, addition of radionuclide strontium (89Sr) to external radiotherapy (ER) was found to prolong the time to further ER by 15 weeks (35 versus 20, P = 0.006) compared to ER alone in patients with hormone-refractory metastatic prostate cancer (HRMPC). The total direct lifetime costs within the Swedish health care system for the following two treatment strategies was estimated as follows: (a) ER initially and in the event of relapse and (b) ER + 89Sr initially and ER in the event of relapse. METHODS: Calculation of lifetime costs was based on the initial total treatment cost and the probability of future treatment costs. In a retrospective analysis, the average cost of a relapse treated with ER alone was calculated from the actual care consumption of 79 consecutive patients from the south of Sweden who received ER because of skeletal pain due to HRMPC. The costs related to ER included skeletal scintigraphy, ER, outpatient visits, inpatients days, and travel to the treatment center. When 89Sr was added, the cost also included the radionuclide and its administration. Costs in Swedish currency (SEK) were based on the regional tariff for 1993 (U.S. $1 = SEK 8.30). RESULTS: The initial cost for one relapse treated with ER alone was estimated to be SEK 31,011 (U.S. $3736) per patient resident within county (close to hospital) and SEK 48,585 (U.S. $5854) per patient resident out of county (far from hospital). The corresponding figure for initial addition of 89Sr to ER was SEK 43,426 (U.S. $5232) and 61,000 (U.S. $7349), respectively. However, comparison between estimated lifetime cost for the two treatment strategies indicated potential cost savings with initial addition of 89Sr to 3% SEK 2720 (U.S. $328) and 7% SEK 11,290 (U.S. $1360), respectively. CONCLUSIONS: Strontium-89 as initial supplement to ER for palliation of pain in HRMPC is beneficial both from the patient and lifetime health service costs perspectives.

Donor work-up and transport of bone marrow--recommendations and requirements for a standardized practice throughout the world from the Donor Registries and Quality Assurance Working Groups of the World Marrow Donor Association (WMDA).

In October 1995 the World Marrow Donor Association (WMDA) was restructured in order to facilitate its primary function of establishing guidelines in relation to international bone marrow and blood stem cell transplants -- transplants in which the donor is in one country and the patient is in another country. Five new working groups were established -- Donor Registries, Ethics, Quality Assurance, Finances, and Stem Cells. This paper, prepared by members of the Donor Registries Working Group, in consultation with the Quality Assurance Working Group, provides recommendations for the 'donor work-up'. This term covers events that start when the definitive donor has been identified, includes the harvesting (collection) and transportation of the stem cell product and ends when the product reaches the transplant centre. The paper includes examples of the documentation intended to ensure compliance with the recommendations at all key points in the sequence.

Similar incidence of graft-versus-host disease using HLA-A, -B and -DR identical unrelated bone marrow donors as with HLA-identical siblings.

Among 42 consecutive recipients of unrelated marrow were 39 HLA-A, -B, -DR identical, matched unrelated donors (MUD) and three with one HLA antigen mismatch. The majority were genomically typed for DRB, DQA, DQB and DPB. The recipients of MUD marrow were compared with 39 recipients of marrow from HLA-identical siblings with similar diagnoses, disease status and age. Each group included 24 patients with hematological malignancies, 6 with severe aplastic anemia and 9 inherited disorders. Immunosuppression consisted of anti-thymocyte globulin (ATG; pre-BMT mainly to recipients of unrelated marrow), CsA and four doses of MTX. Grade I acute GVHD was treated with prednisolone 2 mg/kg. In a comparison of MUD marrow recipients and HLA-identical siblings 34 of 39 and 36 of 39 of the patients engrafted, respectively. Recipients of MUD marrow and HLA-identical siblings achieved 0.2 x 10(9) WBC/l on day 16 (median) and 14, respectively (P = 0.03). Furthermore, the recipients of MUD marrow needed more platelet transfusions (P = 0.04). The incidence of acute GVHD grade II-III was 15% in the MUD marrow recipients compared with 11% among the HLA-identical siblings. The 2-4 year cumulative incidence of chronic GVHD was 29% and 22% in the two groups, respectively. The overall 2-year survival was 59 and 78%, respectively. Among patients with CML in chronic phase or accelerated phase (n = 26), 2-year relapse-free survival was 79% in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)