Alveolar echinococcosis: from a deadly disease to a well-controlled infection. Relative survival and economic analysis in Switzerland over the last 35 years

BACKGROUND/AIMS: Alveolar echinococcosis (AE) is a serious liver disease. The aim of this study was to explore the long-term prognosis of AE patients, the burden of this disease in Switzerland and the cost-effectiveness of treatment. METHODS: Relative survival analysis was undertaken using a national database with 329 patient records. 155 representative cases had sufficient details regarding treatment costs and patient outcome to estimate the financial implications and treatment costs of AE. RESULTS: For an average 54-year-old patient diagnosed with AE in 1970 the life expectancy was estimated to be reduced by 18.2 and 21.3 years for men and women, respectively. By 2005 this was reduced to approximately 3.5 and 2.6 years, respectively. Patients undergoing radical surgery had a better outcome, whereas the older patients had a poorer prognosis than the younger patients. Costs amount to approximately Euro108,762 per patient. Assuming the improved life expectancy of AE patients is due to modern treatment the cost per disability-adjusted life years (DALY) saved is approximately Euro6,032. CONCLUSIONS: Current treatments have substantially improved the prognosis of AE patients compared to the 1970s. The cost per DALY saved is low compared to the average national annual income. Hence, AE treatment is highly cost-effective in Switzerland.

Ultrasonographic assessment of umbilical disorders

Umbilical disorders are of great clinical relevance in calves during the early postnatal period. They may be classified as (1) noninfectious disorders such as hernias and urachal cysts, (2) infectious disorders involving extra- and intra-abdominal umbilical structures, or (3) combinations thereof. Supplementing clinical examination, umbilical ultrasonography allows the identification of the structures involved and differentiation of the various disorders with a high diagnostic sensitivity. A specific diagnosis of the umbilical disorder is important, because the treatment regimen, prognosis, and treatment costs completely depend upon the extent of the disease and the structures involved.

Cost-effectiveness of ticagrelor and generic clopidogrel in patients with acute coronary syndrome in Switzerland

QUESTION UNDER STUDY The aim of this study was to evaluate the cost-effectiveness of ticagrelor and generic clopidogrel as add-on therapy to acetylsalicylic acid (ASA) in patients with acute coronary syndrome (ACS), from a Swiss perspective. METHODS Based on the PLATelet inhibition and patient Outcomes (PLATO) trial, one-year mean healthcare costs per patient treated with ticagrelor or generic clopidogrel were analysed from a payer perspective in 2011. A two-part decision-analytic model estimated treatment costs, quality-adjusted life years (QALYs), life years and the cost-effectiveness of ticagrelor and generic clopidogrel in patients with ACS up to a lifetime at a discount of 2.5% per annum. Sensitivity analyses were performed. RESULTS Over a patient's lifetime, treatment with ticagrelor generates an additional 0.1694 QALYs and 0.1999 life years at a cost of CHF 260 compared with generic clopidogrel. This results in an Incremental Cost Effectiveness Ratio (ICER) of CHF 1,536 per QALY and CHF 1,301 per life year gained. Ticagrelor dominated generic clopidogrel over the five-year and one-year periods with treatment generating cost savings of CHF 224 and 372 while gaining 0.0461 and 0.0051 QALYs and moreover 0.0517 and 0.0062 life years, respectively. Univariate sensitivity analyses confirmed the dominant position of ticagrelor in the first five years and probabilistic sensitivity analyses showed a high probability of cost-effectiveness over a lifetime. CONCLUSION During the first five years after ACS, treatment with ticagrelor dominates generic clopidogrel in Switzerland. Over a patient's lifetime, ticagrelor is highly cost-effective compared with generic clopidogrel, proven by ICERs significantly below commonly accepted willingness-to-pay thresholds.

Genetic testing for glucokinase mutations in clinically selected patients with MODY: a worthwhile investment

The differential diagnosis for children with diabetes includes a group of monogenic diabetic disorders known as maturity-onset diabetes of the young (MODY). So far, six underlying gene defects have been identified. The most common subtypes are caused by mutations in the genes encoding the transcription factor HNF-1a (MODY 3) and the glycolytic enzyme glucokinase (GCK) (MODY 2). MODY 2 is the most benign form of diabetes as the threshold for glucose sensing is elevated resulting in mild, regulated hyperglycemia. MODY 2 may usually be treated with diet alone without risk of microvascular complications. Patients with MODY usually present as children or young adults. Genetic testing for MODY in diabetic subjects is often not performed because of the costs and its unavailability in Switzerland. We describe the impact of the genetic analysis for MODY 2 on diabetes management and treatment costs in a five-year-old girl. The patient and her diabetic mother were both found to have a heterozygous missense mutation (V203A) in the glucokinase gene. The five-year-old girl was started on insulin therapy for her diabetes but because her HbA1c remained between 5.8-6.4% (reference 4.1-5.7%) and her clinical presentation suggested MODY insulin was discontinued. She is now well controlled on a carbohydrate controlled diet regimen only. Omission of insulin treatment made regular blood glucose monitoring unnecessary and removed her risk of hypoglycemia. Costs for the genetic analysis were 500 Euro. At our centre costs for diabetes care of a patient with type 1 diabetes are approximately 2050 Euro/year compared to 410 Euro/year for the care of a patient with MODY 2. In addition, a diagnosis of MODY 2 may reassure patients and their families, as microvascular complications are uncommon. Thus there are both health and financial benefits in diagnosing MODY 2. We recommend genetic testing for MODY 2 in clinically selected patients even though this analysis is currently not available in Switzerland and costs are not necessarily covered by the health insurances.

Cost-effectiveness analysis of paclitaxel-coated balloons for endovascular therapy of femoropopliteal arterial obstructions.

PURPOSE To explore the cost-effectiveness of using drug-eluting balloon (DEB) angioplasty for the treatment of femoropopliteal arterial lesions, which has been shown to significantly lower the rates of target lesion revascularization (TLR) compared with standard balloon angioplasty (BA). METHODS A simplified decision-analytic model based on TLR rates reported in the literature was applied to baseline and follow-up costs associated with in-hospital patient treatment during 1 year of follow-up. Costs were expressed in Swiss Francs (sFr) and calculated per 100 patients treated. Budgets were analyzed in the context of current SwissDRG reimbursement figures and calculated from two different perspectives: a general budget on total treatment costs (third-party healthcare payer) as well as a budget focusing on the physician/facility provider perspective. RESULTS After 1 year, use of DEB was associated with substantially lower total inpatient treatment costs when compared with BA (sFr 861,916 vs. sFr 951,877) despite the need for a greater investment at baseline related to higher prices for DEBs. In the absence of dedicated reimbursement incentives, however, use of DEB was shown to be the financially less favorable treatment approach from the physician/facility provider perspective (12-month total earnings: sFr 179,238 vs. sFr 333,678). CONCLUSION Use of DEBs may be cost-effective through prevention of TLR at 1 year of follow-up. The introduction of dedicated financial incentives aimed at improving DEB reimbursements may help lower total healthcare costs.

Swiss national guideline for reimbursement of enzyme replacement therapy in late-onset Pompe disease.

Glycogen storage disease type II is a rare multi-systemic disorder characterised by an intracellular accumulation of glycogen due a mutation in the acid alpha glucosidase (GAA) gene. The level of residual enzyme activity, the genotype and other yet unknown factors account for the broad variation of the clinical phenotype. The classical infantile form is characterised by severe muscle hypotonia and cardiomyopathy leading to early death. The late-onset form presents as a limb girdle myopathy with or without pulmonary dysfunction. Enzyme replacement therapy (ERT) with recombinant human GAA (rhGAA) in infants is life saving. In contrast, therapeutic efficacy of rhGAA in the late-onset form is modest. High expenses of rhGAA, on-going infusions and poor pharmacokinetic efficacy raised a discussion of the cost effectiveness of ERT in late-onset Pompe disease in Switzerland. This discussion was triggered by a Swiss federal court ruling which confirmed the reluctance of a health care insurer not to reimburse treatment costs in a 67-year-old female suffering from Pompe disease. As a consequence of this judgement ERT was stopped by all insurance companies in late-onset Pompe patients in Switzerland regardless of their clinical condition. Subsequent negotiations lead to the release of a national guideline of the management of late-onset Pompe disease. Initiation and limitation of ERT is outlined in a national Pompe registry. Reimbursement criteria are defined and individual efficacy of ERT with rhGAA is continuously monitored.

Long-term effectiveness of supported employment: 5-year follow-up of a randomized controlled trial

Objective The individual placement and support model of supported employment has been shown to be more effective than other vocational approaches in improving competitive work over 1-2 years in persons with severe mental illness. The authors evaluated the longer-term effects of the model compared with traditional vocational rehabilitation over 5 years. Method A randomized controlled trial compared supported employment to traditional vocational rehabilitation in 100 unemployed persons with severe mental illness. Competitive work and hospital admissions were tracked for 5 years, and interviews were conducted at 2 and 5 years to assess recovery attitudes and quality of life. A cost-benefit analysis compared program and total treatment costs to earnings from competitive employment. Results The beneficial effects of supported employment on work at 2 years were sustained over the 5-year follow-up period. Participants in supported employment were more likely to obtain competitive work than those in traditional vocational rehabilitation (65% compared with 33%), worked more hours and weeks, earned more wages, and had longer job tenures. Reliance on supported employment services for retaining competitive work decreased from 2 years to 5 years for participants in supported employment. Participants were also significantly less likely to be hospitalized, had fewer psychiatric hospital admissions, and spent fewer days in the hospital. The social return on investment was higher for supported employment participants, whether calculated as the ratio of work earnings to vocational program costs or of work earnings to total vocational program and mental health treatment costs. Conclusions The results demonstrate that the greater effectiveness of supported employment in improving competitive work outcomes is sustained beyond 2 years and suggest that supported employment programs contribute to reduced hospitalizations and produce a higher social return on investment.

Cessation and resuming of alglucosidase alfa in Pompe disease: a retrospective analysis.

Enzyme replacement therapy (ERT) with recombinant human alglucosidase alfa (rhGAA) in late-onset Pompe disease is moderately effective. Little is known about the clinical course after treatment termination and the resumption of ERT. In Switzerland, rhGAA therapy for Pompe disease was temporarily withdrawn after the federal court judged that the treatment costs were greatly out of proportion compared to the benefits. Re-treatment was initiated after the therapy was finally licensed. We retrospectively analysed seven Pompe patients, who underwent cessation and resumption of ERT (median age 43 years). The delay from first symptoms to final diagnosis ranged from 4 to 20 years. The demographics, clinical characteristics, assessments with the 6-min walking test (6-MWT), the predicted forced vital capacity (FVC) and muscle strength were analysed. Before initiation of ERT, all patients suffered from proximal muscle weakness of the lower limbs; one was wheelchair-bound and two patients received night-time non-invasive ventilation. Initial treatment stabilised respiratory function in most patients and improved their walking performance. After treatment cessation, upright FVC declined in most and the 6-MWT declined in all patients. Two patients needed additional non-invasive ventilatory support. Twelve months after resuming ERT, the respiratory and walking capacity improved again in most patients. However, aside for one patient, none of the patients reached the same level of respiratory function or distance walked in 6 min, as at the time of ERT withdrawal. We conclude that cessation of ERT in Pompe disease causes a decline in clinical function and should be avoided. Resuming treatment only partially recovers respiratory function and walking capacity.

Bevacizumab continuation versus no continuation after first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer: a randomized phase III non-inferiority trial (SAKK 41/06)

BACKGROUND Chemotherapy plus bevacizumab is a standard option for first-line treatment in metastatic colorectal cancer (mCRC) patients. We assessed whether no continuation is non-inferior to continuation of bevacizumab after completing first-line chemotherapy. PATIENTS AND METHODS In an open-label, phase III multicentre trial, patients with mCRC without disease progression after 4-6 months of standard first-line chemotherapy plus bevacizumab were randomly assigned to continuing bevacizumab at a standard dose or no treatment. CT scans were done every 6 weeks until disease progression. The primary end point was time to progression (TTP). A non-inferiority limit for hazard ratio (HR) of 0.727 was chosen to detect a difference in TTP of 6 weeks or less, with a one-sided significance level of 10% and a statistical power of 85%. RESULTS The intention-to-treat population comprised 262 patients: median follow-up was 36.7 months. The median TTP was 4.1 [95% confidence interval (CI) 3.1-5.4] months for bevacizumab continuation versus 2.9 (95% CI 2.8-3.8) months for no continuation; HR 0.74 (95% CI 0.58-0.96). Non-inferiority could not be demonstrated. The median overall survival was 25.4 months for bevacizumab continuation versus 23.8 months (HR 0.83; 95% CI 0.63-1.1; P = 0.2) for no continuation. Severe adverse events were uncommon in the bevacizumab continuation arm. Costs for bevacizumab continuation were estimated to be ∼30,000 USD per patient. CONCLUSIONS Non-inferiority could not be demonstrated for treatment holidays versus continuing bevacizumab monotheray, after 4-6 months of standard first-line chemotherapy plus bevacizumab. Based on no impact on overall survival and increased treatment costs, bevacizumab as a single agent is of no meaningful therapeutic value. More efficient treatment approaches are needed to maintain control of stabilized disease following induction therapy. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, number NCT00544700.

Cervical spinal locking plate in combination with cortical ring allograft for a one level fusion in dogs with cervical spondylotic myelopathy.

OBJECTIVE To evaluate use of a surgical technique commonly used in humans for treatment of cervical spondylotic myelopathy (CSM) in dogs. DESIGN Prospective case series. ANIMALS Dogs with CSM (n=10). METHODS Dogs weighing >30 kg that had CSM at 1 vertebral articulation were eligible for inclusion. Dogs had vertebral column distraction/fusion performed using a cortical ring allograft, cancellous autograft, and a spinal locking plate. Dogs were evaluated temporally by repeat neurological examinations and by client perception of postsurgical outcome, determined by telephone interview. RESULTS Nine dogs survived the immediate postoperative period. Seven of 8 dogs had moderate to complete improvement without recurrence (mean follow-up, 2.48 years). The most common postsurgical complications were screw loosening (n=4) and plate shifting (2), neither of which required surgical revision. One dog had pseudoarthrosis that may have negatively impacted outcome. CONCLUSION Treatment of single level CSM in dogs with ring allograft and a spinal locking plate system may lead to successful outcomes. The major problems encountered with included cost of the implants and adjusting the system designed for humans to fit the vertebral column of a dog. CLINICAL RELEVANCE For dogs with CSM at a single level, the use of a spinal locking plate in combination with a cortical ring allograft can be an effective surgical treatment. Costs of the implants as well as anatomic differences in dogs make this type of surgery less appealing.

Digital vs. conventional implant prosthetic workflows: a cost/time analysis.

OBJECTIVES The aim of this prospective cohort trial was to perform a cost/time analysis for implant-supported single-unit reconstructions in the digital workflow compared to the conventional pathway. MATERIALS AND METHODS A total of 20 patients were included for rehabilitation with 2 × 20 implant crowns in a crossover study design and treated consecutively each with customized titanium abutments plus CAD/CAM-zirconia-suprastructures (test: digital) and with standardized titanium abutments plus PFM-crowns (control conventional). Starting with prosthetic treatment, analysis was estimated for clinical and laboratory work steps including measure of costs in Swiss Francs (CHF), productivity rates and cost minimization for first-line therapy. Statistical calculations were performed with Wilcoxon signed-rank test. RESULTS Both protocols worked successfully for all test and control reconstructions. Direct treatment costs were significantly lower for the digital workflow 1815.35 CHF compared to the conventional pathway 2119.65 CHF [P = 0.0004]. For subprocess evaluation, total laboratory costs were calculated as 941.95 CHF for the test group and 1245.65 CHF for the control group, respectively [P = 0.003]. The clinical dental productivity rate amounted to 29.64 CHF/min (digital) and 24.37 CHF/min (conventional) [P = 0.002]. Overall, cost minimization analysis exhibited an 18% cost reduction within the digital process. CONCLUSION The digital workflow was more efficient than the established conventional pathway for implant-supported crowns in this investigation.

Cobrança pelo uso da água e escassez de recursos hídricos: proposta de modelo de cobrança e aplicação na bacia do rio Atibaia

No Brasil, a Política Nacional de Recursos Hídricos apresenta a cobrança pelo uso da água como um instrumento de gestão de recursos hídricos de caráter econômico. Considerando esse caráter, a cobrança deve ter como objetivos: racionalizar o uso do recurso baseado na sua escassez; reconhecer a água como um bem de valor econômico, refletindo os custos ambientais advindos de sua utilização; e diminuir os conflitos entre os usos, induzindo uma alocação que considere o gerenciamento da demanda e as prioridades da sociedade. Além dessas metas, como instrumento de gestão de uma política que lista como primeiro objetivo \"assegurar à atual e às futuras gerações a necessária disponibilidade de água, em padrões de qualidade adequados aos respectivos usos\", a cobrança deve ser implementada de maneira que o agente usuário direcione seu comportamento no sentido da sustentabilidade ambiental. Mediante esses fundamentos, o que se pretende desenvolver neste trabalho é a aplicação de um modelo de cobrança sobre o uso da água que considera como princípio base a manutenção da qualidade ambiental medida pela adequada gestão da escassez de água e, compondo a busca dessa qualidade, a racionalização econômica e a viabilização financeira. Essa predominância do ambiente sobre aspectos econômicos vem no sentido de desqualificar argumentos segundo os quais, os impactos advindos dos usos da água serão corrigidos indefinidamente mediante investimentos financeiros em infra estrutura. Admitir que o desenvolvimento tem esse poder é supor equivocadamente que o meio econômico é limitante do meio ambiente e não o contrário. Esta constatação mostra qual é o problema da maioria das propostas de cobrança que valoram a água baseadas em custos de tratamento de resíduos e de obras hidráulicas. Por mais elaborados que sejam essas fórmulas de cobrança, chegando a ponto de se conseguir que fique mais caro, mediante um padrão ambiental corretamente definido, captar água ou lançar poluentes do que racionalizar usos, o preço da água não pode estar baseado em fatores cuja \"sustentabilidade\" pode acabar no curto prazo, dependendo do ritmo de crescimento econômico. A sustentabilidade dos recursos hídricos só será base da cobrança pelo uso da água se o valor cobrado for dificultando esse uso à medida que os recursos tornarem se escassos, e não quando os custos de medidas mitigadoras dessa escassez se tornarem muito elevados. Portanto, o modelo de cobrança proposto neste trabalho procura garantir que o agente econômico que está exaurindo o meio ambiente não possa ter capacidade de pagar por essa degradação, ajudando efetivamente a política de outorga do direito de uso da água na observância da capacidade de suporte do meio.

Illinois Phosphorus Effluent Limits: Minimizing the Impacts Through the Use of Non-point Controls at the Springbrook Water Reclamation Center in Naperville, Illinois

Phosphorus pollution is a major concern in Illinois. Excessive amounts of phosphorus can be detrimental to water bodies. To help control phosphorus, the Illinois Pollution Control Board has proposed phosphorus limits on wastewater treatment facility discharges. If enacted, these limits will have negative impacts on the Springbrook Water Reclamation Center in Naperville, Illinois. To minimize these impacts, Naperville can utilize various non-point controls recommended in this paper to decrease the amount of phosphorus entering into the DuPage River and the Springbrook Water Reclamation Center. While these controls will not reduce levels low enough to totally satisfy limits on phosphorus discharges, they will significantly reduce the treatment costs Naperville will need to expend to meet them and be more environmentally effective.

Poverty and the economic effects of TB in rural China

OBJECTIVE: To investigate the economic effects of illness on individual tuberculosis (TB) cases in rural China and to use a case-control study to show a strong TB-poverty link. SETTING: In 2002-2004 we studied 160 new smear-positive pulmonary tuberculosis (PTB) cases and 320 age- and sex-matched controls living in neighbouring houses in four rural counties of Henan Province. DESIGN: Cases and controls were interviewed 1-3 months after patients were diagnosed. We used matched multivariate logistic regression to compare cases with controls for poverty status using household income, household assets and relative wealth within the village. We conducted follow-up interviews of patients 10-12 months later to assess economic effects by collecting data on treatment costs, income losses, coping strategies and treatment completion. RESULTS: Poverty is strongly associated with TB incidence even after controlling for smoking and other risk factors. Excluding income losses, direct out-of-pocket treatment costs (medical and non-medical) accounted for 55.5 % of average annual household income, and most TB cases fell into heavy debt. The DOTS cure rate was 91 %. When DOTS was incomplete or not done, mortality was high. CONCLUSIONS: Poverty is both a cause and a devastating outcome of TB. Ongoing poverty reduction schemes in China must also include reducing TB.

Análise da expressão dos receptores HER-2 e sua correlação clínica em pacientes com neoplasia gástrica do setor de Oncologia do Hospital de Clínicas da Universidade Federal de Uberlândia-UFU

Introduction: Gastric cancer is currently the fourth higher cancer mortality rate among men in the world and the fifth among women, despite the progressive advances in oncology. The identification of tumor receptors and the development of target-drugs to block them has contributed to increased survival and quality of life of patients, but it becomes important to know the tumor profile of the population being treated, avoiding burdening treatment with examinations and treatments that are not cost-effective. Objective: To evaluate the profile of the population with gastric cancer treated in five years at the Clinical Hospital of the Federal University of Uberlândia and verify the correlation between overexpression of HER-2 receptor with an unfavorable prognosis. Methods: 203 records with gastric cancer were selected through the system database, attending a five-year period, of which 117 paraffin blocks were available for immunohistochemical assessment of HER2 receptor. Results: 2.6% of tumors showed overexpression of HER2, considering for this study two crosses as positive. There was no statistically significant difference in correlation between expression of the HER2 receptor with age, gender, tumor grade, local involvement, Lauren classification, Borrmann classification or staging. Conclusion: For this studied population, we can conclude that there is no need to employ HER2 blockers with high cost as a target-therapy in patients with gastric cancer, since no clinical benefit probably will be obtained due to a low percentage of these patients that demonstrated superexpression of this receptor or even there is no patients with gastric cancer with superexpression of HER2 with more than three crosses of positivity in immunochemistry