Environmental Microbiology Laboratory, Environmental Engineering Institute, School of Architecture, Civil and Environmental Engineering, École Polytechnique Fédérale de Lausanne, 1015, Lausanne, Switzerland. firstname.lastname@example.org.
The deep terrestrial subsurface remains an environment where there is limited understanding of the extant microbial metabolisms. At Olkiluoto, Finland, a deep geological repository is under construction for the final storage of spent nuclear fuel. It is therefore critical to evaluate the potential impact microbial metabolism, including sulfide generation, could have upon the safety of the repository. We investigated a deep groundwater where sulfate is present, but groundwater geochemistry suggests limited microbial sulfate-reducing activity. Examination of the microbial community at the genome-level revealed microorganisms with the metabolic capacity for both oxidative and reductive sulfur transformations. Deltaproteobacteria are shown to have the genetic capacity for sulfate reduction and possibly sulfur disproportionation, while Rhizobiaceae, Rhodocyclaceae, Sideroxydans, and Sulfurimonas oxidize reduced sulfur compounds. Further examination of the proteome confirmed an active sulfur cycle, serving for microbial energy generation and growth. Our results reveal that this sulfide-poor groundwater harbors an active microbial community of sulfate-reducing and sulfide-oxidizing bacteria, together mediating a sulfur cycle that remained undetected by geochemical monitoring alone. The ability of sulfide-oxidizing bacteria to limit the accumulation of sulfide was further demonstrated in groundwater incubations and highlights a potential sink for sulfide that could be beneficial for geological repository safety.
The FACET (Formoterol and Corticosteroid Establishing Therapy) study established that there is a clear clinical benefit in adding formoterol to budesonide therapy in patients who have persistent symptoms of asthma despite treatment with low to moderate doses of an inhaled corticosteroid. We combined the clinical results from the FACET study with an expert survey on average resource use in connection with mild and severe asthma exacerbations in the U.K., Sweden and Spain. The primary objective of this study was to assess the health economics of adding the inhaled long-acting beta2-agonist formoterol to the inhaled corticosteroid budesonide in the treatment of asthma. The extra costs of adding the inhaled beta2-agonist formoterol to the corticosteroid budesonide in asthmatic patients in Sweden were offset by savings from reduced use of resources for exacerbations. For Spain the picture was mixed. Adding formoterol to low dose budesonide generated savings, whereas for moderate doses of budesonide about 75% of the extra formoterol costs could be recouped. In the U.K., other savings offset about half of the extra cost of formoterol. All cost-effectiveness ratios are within accepted cost-effectiveness ranges reported from previous studies. If productivity losses were included, there were net savings in all three countries, ranging from Euro 267-1183 per patient per year. In conclusion, adding the inhaled, long-acting beta2-agonist formoterol to low-moderate doses of the inhaled corticosteroid budesonide generated significant gains in all outcome measures with partial or complete offset of costs. Adding formoterol to budesonide can thus be considered to be cost-effective.
This open, multinational, randomised, parallel-group, six-month extension conducted in the Swedish centres of a previous six-month study compared the costs of a total of 12 months of treatment with budesonide/formoterol in a single inhaler with budesonide plus formoterol separate inhalers in 320 adults with asthma. Patients received budesonide/formoterol (Symbicort Turbuhaler) 160/4.5 mg delivered doses, two inhalations b.i.d., or corresponding doses of budesonide (Pulmicort Turbuhaler) plus formoterol (Oxis Turbuhaler). Direct costs and indirect costs were estimated. Budesonide/formoterol treatment was associated with reduced healthcare service utilisation and statistically significant reductions in direct (SEK1595, p=0.0004) and total costs (SEK1884, p=0.043) per person per year compared with budesonide plus formoterol. Budesonide/formoterol reduced the average annual emergency room admission cost per person by SEK489.7 (31% of direct cost reduction) and physician costs by SEK235.4 (15%).The direct cost of study, relief and other medication was reduced by SEK893.8 (47% of total reduction).There were no statistically significant differences in efficacy and safety parameters following treatment with budesonide/formoterol from single or separate inhalers, other than a significantly lower proportion of withdrawals with the single inhaler (9.2% vs 19.4%, p=0.008). In summary, budesonide/formoterol treatment from a single inhaler reduced 12-month treatment costs compared with separate inhalers, while maintaining at least as good control of asthma.
BACKGROUND: Budesonide and sodium cromoglycate are both recommended as maintenance therapy for childhood asthma. OBJECTIVE: To compare the cost-effectiveness of these two treatment strategies in clinical practice, in an open-label, pharmacoeconomic clinical trial. METHODS: Health economics were evaluated in 138 children, ages 5 to 11 years, with unstable asthma not previously treated with corticosteroids or cromones. The asthma was stabilized during 4 to 6 weeks with budesonide 200 to 400 microg twice daily. The children were then randomly allocated to one of the two treatment strategies aiming at maintaining asthma control for 12 months; budesonide 400 microg/day (N = 69) or sodium cromoglycate 60 mg/day (N = 69). If asthma control was judged unsatisfactory, the doses were increased or the children were switched to the alternate treatment. RESULTS: In children continuing on the same treatment, the degree of asthma control was similar in the two groups at study end. To maintain asthma control, 42% of cromoglycate children switched to budesonide, and then experienced a 14% increase in symptom-free days. No budesonide patient had to switch therapy because of lack of asthma control. Although not statistically significant, total annual cost per patient was 24% (Swedish kronor 4195; US $487; Euro 485) lower in the budesonide than the cromoglycate group, mainly due to a lower cost for asthma medication. CONCLUSIONS: A budesonide strategy for continued maintenance treatment, after an initial period of stabilizing treatment with budesonide, resulted in lower costs and less drug switches than did a strategy with sodium cromoglycate.
We estimated the cost effectiveness of adding the ACE inhibitor ramipril to conventional treatment in patients with heart failure after acute myocardial infarction. These estimates were based on the Acute Infarction Ramipril Efficacy (AIRE) study and on complementary Swedish healthcare resource use data for a subset of patients. The average follow-up period was 15 months (minimum 6 months, maximum 3.8 years). The perspective of the analysis was that of the county councils (third-party payers), and we focused on the cost of drugs and hospitalisation. The marginal cost effectiveness of the treatment was estimated over 3 treatment periods: 1, 2 and 3.8 years. The cost-effectiveness ratios varied between SEK14,148 and SEK33,033 per life-year gained ($US1 = SEK7.70. Pounds 1 = SEK12.40) for the 3 treatment periods. Adding ramipril to conventional treatment for heart failure after acute myocardial infarction is therefore cost effective, and compares favourably with the cost effectiveness of other common medical therapies in the cardiovascular field.
We present results from a Swedish retrospective cost-effectiveness analysis of felodipine-metoprolol (Logimax) and enalapril in hypertension. In the 8-week trial, the average reduction of diastolic blood pressure (DBP) and the share of patients reaching target DBP were both significantly greater in the felodipine-metoprolol group. Cost of treatment (costs of drugs and physician visits) was somewhat higher in the felodipine-metoprolol group. After 8 weeks, an extra 4.8 mmHg reduction and an additional 22% of patients reaching target DBP were achieved with felodipine-metoprolol at the extra cost of SEK 19 (Swedish kronor, $US I=SEK 7.90). The incremental cost per mmHg reduction and per patient reaching target DBP was calculated at SEK 4 and SEK 86, respectively. Average cost-effectiveness ratios showed that the costs per mmHg reduction and per patient reaching target DBP after 8 weeks were 40 and 34% lower in the felodipine-metoprolol group, respectively. In conclusion, felodipine-metoprolol is cost-effective in the treatment of hypertension.
A survey of 402 Swedish patients with angina pectoris was performed to estimate the annual direct medical costs, and nonmedical costs, of a typical Swedish angina pectoris patient, and to identify those variables having the greatest impact on the direct medical costs. Data regarding the consumption of healthcare services over a 3-month period were collected through telephone interviews conducted by trained nurses at a medical marketing agency. The data were multiplied by 4 to obtain an estimate of the annual resource consumption. The annual direct medical cost of angina pectoris was estimated at 40,052 Swedish krona (SEK; $US1 approximately SEK7.20, March 1995) per patient, comparable with the cost of a myocardial infarction. As expected, however, the severity of angina pectoris was important in determining the direct medical cost. The significant variables explaining variations in direct costs were (in order of importance): (i) whether the patient had undergone cardiovascular surgery; (ii) whether the patient was treated by a general practitioner or an internist; (iii) the number of years since first diagnosis of angina pectoris; and (iv) whether the patient's angina pectoris was characterised as stable or unstable. The annual nonmedical cost of angina pectoris per patient was estimated at SEK38,225. The relatively high costs of angina pectoris underline the importance of health economic evaluations of various diseases and medical interventions.
Exacerbations are the key drivers in the costs of chronic obstructive pulmonary disease (COPD). The objective was to examine the costs of COPD exacerbations in relation to differing degrees of severity of exacerbations and of COPD. We identified 202 subjects with COPD, defined according to the BTS and ERS criteria. Exacerbations were divided into mild (self-managed), mild/moderate (telephone contact with a health-care centre and/or the use of antibiotics/systemic corticosteroids), moderate (health-care centre visits) and severe (emergency care visit or hospital admission). Exacerbations were identified by sending the subjects a letter inquiring whether they had any additional respiratory problems or influenza the previous winter. At least one exacerbation was reported by 61 subjects, who were then interviewed about resource use for these events. The average health-care costs per exacerbation were SEK 120 (95% C=39-246), SEK 354 (252-475), SEK 2111 (1673-2612) and SEK 21852 (14436-29825) for mild, mild/moderate, moderate and severe exacerbations, respectively. Subjects with impaired lung function experienced more severe exacerbations, which was also reflected in the cost of exacerbations per severity of the disease during the 4 1/2 month study period (ranging from SEK 224 for mild to SEK 13708 for severe cases, median SEK 940). Exacerbations account for 35-45% of the total per capita health-care costs for COPD. In conclusion, costs varied considerably with the severity of the exacerbation as well as with the severity of COPD. The prevention of moderate-to-severe exacerbations could be very cost-effective and improve the quality of life.
Early intervention with budesonide is an effective strategy for mild persistent asthma, which has been shown to provide additional clinical benefits at a low incremental cost using USA cost data. The present authors analysed whether this strategy would be cost-effective using cost data for other countries. Based on the 3-yr prospective, randomised, double-blind inhaled Steroid Treatment As Regular Therapy (START) in early asthma study (comparing budesonide and placebo combined with usual asthma therapy), the cost-effectiveness was estimated separately for eight different countries, from both healthcare payer and societal perspectives, of adding budesonide to usual asthma therapy. Local unit costs were applied to data for the total trial population. Incremental cost-effectiveness ratios (ICER) were estimated as cost per symptom-free day (SFD) gained. Budesonide increased SFDs by an average of 14.1 days annually. From a healthcare payer perspective, budesonide would reduce the total cost of asthma care in Australia. In Sweden, Canada, France, Spain, UK, China and the USA, the ICER ranged from US$2.4-11.3 per SFD. From a societal perspective, budesonide would be cost-saving in Australia, Canada and Sweden. In conclusion, for countries where costs with budesonide are higher, the policy implication has to be determined by that health system's willingness to pay for an additional symptom-free day. However, where budesonide therapy increases symptom-free days and reduces total costs, the policy conclusion clearly favours early intervention.