Copepods drive large-scale trait-mediated effects in marine plankton.

Fear of predation may influence food webs more than actual predation. However, the mechanisms and magnitude of nonconsumptive predator effects are largely unknown in unicellular-dominated food webs such as marine plankton. We report a general mechanism of chemically induced predator effects in marine plankton. Copepods, the most abundant zooplankton in the oceans, imprint seawater with unique polar lipids-copepodamides-which trigger toxin production and bioluminescence in harmful dinoflagellates. We show that copepodamides also elicit defensive traits in other phytoplankton, inducing the harmful algal bloom-forming diatom Pseudo-nitzschia seriata to produce 10 times more toxins, and colony-forming diatoms to decrease colony size by half. A 1-year study in the northeast Atlantic revealed that natural copepodamide concentrations are high enough to induce harmful algal toxins and size reduction in dominant primary producers when copepods are abundant. We conclude that copepodamides will structure marine plankton toward smaller, more defended life forms on basin-wide scales.

Patterns of antiepileptic drug prescription in Sweden: A register-based approach.

OBJECTIVES: To determine drug utilization pathways from the incident healthcare visit due to epilepsy and three years onward. MATERIAL AND METHODS: Anti-epileptic drug utilization was calculated using individual information on inpatient- and outpatient care utilization and drug sales. Throughout, we used national register information pertaining to pharmaceutical sales linked to diagnosis-related healthcare utilization. Information on pharmaceutical sales was collected for the 2007-2013 period. RESULTS: For the entire studied period, a majority of new patients with epilepsy were initiated on anti-epileptic drug treatment with a monotherapy (98%); most of these patients remained on that first treatment (64%). The three most frequently prescribed drugs accounted for 72% of the initiated AED treatments. Patients with epilepsy (ICD-10: G40/41) were most commonly prescribed carbamazepine, lamotrigine and valproate. The most common second-line monotherapy was levetiracetam. About 12% of new patients with epilepsy who were initiated on AED treatment during the period eventually switched to an add-on therapy. The proportion of patients who were initiated on treatment with carbamazepine or valproate decreased, and the proportion of patients who remained on their initial monotherapy increased between 2007 and 2013. CONCLUSIONS: A limited number of anti-epileptic drugs accounted for the treatment of a majority of new patients with epilepsy (carbamazepine, lamotrigine and valproate accounted for more than 70%). Add-on therapies showed the same pattern, as the most frequently prescribed add-on regimens were the same ones that accounted for most of the monotherapies. There was a tendency towards fewer patients being initiated on AED treatment with either carbamazepine or valproate.

Prevalence and cost of epilepsy in Sweden--a register-based approach.

OBJECTIVES: To estimate the prevalence of epilepsy, costs associated with in- and outpatient care, drug utilization and productivity losses due to epilepsy in Sweden for the years 2005 and 2011. METHODS: Cost components were calculated using registry data on inpatient- and outpatient-care utilization, drug sales and early pensions granted due to permanent disability and mortality. Moreover, by cross-identification of information in healthcare and pharmaceutical registries, we were able to distinguish between pharmaceuticals prescribed for epilepsy and non-epilepsy indications. RESULTS: The prevalence of epilepsy was estimated at 0.62% in 2005 and 0.88% in 2011. The total cost of epilepsy increased during the same period, while the per-patient cost decreased from €2929 to €1729. Direct medical costs accounted for about 36% of the estimated total cost in 2005 and 60% in 2011. The estimated healthcare cost due to epilepsy as a share of total healthcare costs for all illnesses was about the same in 2005 as in 2011 (0.2%), while the corresponding pharmaceutical cost increased from about 0.5% in 2005 to almost 1% in 2011. CONCLUSIONS: The per-patient cost of epilepsy is substantial, implying a significant aggregated cost incurred on society (despite a prevalence < 1%). Our results suggest that the per-patient pharmaceutical utilization increased, while the per-patient physician visits and hospitalizations decreased, between 2005 and 2011. Moreover, we demonstrate that the 2005 prevalence measure was underestimated the true prevalence in 2005.

Regional variation in prevalence and healthcare utilization due to epilepsy in Sweden.

OBJECTIVE: To estimate the regional differences in the prevalence of epilepsy and the associated costs due to inpatient and outpatient care and anti-epileptic drug (AED) utilization for the years 2005 and 2011 in Sweden. METHODS: Region-specific estimates of the prevalence of epilepsy were obtained using a method based on a linkage of the healthcare and pharmaceutical registries and the cause of death registry. Regional cost components were estimated using registry data by region on inpatient and outpatient care utilization, AED sales, and mortality. Per-patient utilization and monetary costs were calculated. RESULTS: Estimated prevalence of epilepsy varied substantially across the regions in 2011, from 0.76% in Jämtland to 1.08% in Gotland. The national prevalence was 0.88%. The average number of hospitalizations per patient and year decreased at the national level between 2005 and 2011. At the national level, the per-patient specialized care (outpatient) utilization also decreased between 2005 and 2011. However, at the regional level, the decrease was not uniform, and in some counties, the per-patient utilization increased during the period studied. The per-patient utilization of AEDs increased in all counties, except Kronoberg, between 2005 and 2011. Moreover, between-region differences in healthcare and AED utilization, and significant differences between regions and national averages were revealed. Similarly, regional per-patient costs were shown to deviate from the national average in 13 of 21 regions. CONCLUSIONS: There is significant variation in the prevalence of epilepsy and the provision of health care for patients with epilepsy across the different regions of Sweden.

Lacosamide as treatment of epileptic seizures - cost utility results for Sweden.

OBJECTIVES: To calculate cost per additional quality-adjusted life-year (QALY) for lacosamide as adjunctive treatment for patients with uncontrolled partial-onset seizures as compared to no adjunctive treatment. MATERIALS AND METHODS: A decision-tree simulation model was constructed to calculate the number of seizures and health-care utilization for treated and untreated with lacosamide, respectively. Prices from 2007 were used for all costs. RESULTS: All results were calculated for a 24-, 18-, 12- and 6-months follow-up. The cost per additional QALY was estimated to euro 27,641 (24 months). Using a willingness-to-pay threshold for a QALY of euro 50,000 the net marginal value of using lacosamide was estimated to about euro 850,000 per 1000 patients. CONCLUSIONS: The estimated cost per QALY gained falls within the range of reported estimates of the willingness-to-pay for an additional QALY. The results imply that lacosamide is cost-effective in the treatment of uncontrolled partial-onset seizures (1 euro approximately 9.6 SEK).

Cost-effectiveness of formoterol and salbutamol as asthma reliever medication in Sweden and in Spain.

This study aimed to evaluate the cost-effectiveness of formoterol (Oxis) Turbuhaler 4.5 microg and salbutamol 200 microg as reliever medications in Sweden and Spain. The study used data on effectiveness (exacerbations and symptom-free days) and resource utilisation from an open, 6-month, parallel-group, multicentre randomised trial with 18,124 asthma patients in 24 countries. Country-specific unit costs for Sweden and for Spain were used to transform resource utilisation data into costs. Total healthcare costs were not significantly different between formoterol and salbutamol dry powder inhalers in Sweden, whereas in Spain, the healthcare costs were 20% higher for formoterol vs. salbutamol pressurised metered dose inhalers. Total healthcare costs increased with disease severity, defined according to the Global Initiative for Asthma guidelines. Compared with salbutamol, formoterol produced statistically significant improvements in effectiveness, less reliever and maintenance medication usage, reduced healthcare resource utilisation, with no increase or a limited increase in healthcare cost.

Health economic guidelines--similarities, differences and some implications.

OBJECTIVE: To classify, summarize, and compare the health economic guidelines (HE) issued in Europe, North America, and Australia to clarify similarities and differences between them. MATERIALS AND METHODS: In a literature review HE guidelines were classified according to whether they were 1) formalized, 2) informal, or 3) guidelines for health economic methods. All the guidelines were summarized in a table format according to 15 important methodological aspects. The aspects were compared both within and between the three groups. RESULTS: A total of 25 guidelines were identified, seven formalized, eight informal, and 10 guidelines for HE methods. The levels of agreement for methodological aspects within groups were 40% to 100%, 25% to 100% and 30% to 100% for the formalized, informal, and HE guidelines, respectively. The formal guidelines were slightly more homogenous than the other groups. The between-group comparison showed that the guidelines were in agreement for about 75% of methodological aspects. Disagreement between guidelines was found in choice of perspective, resources, and costs that should be included in the analysis, and in methods of evaluating resources used. CONCLUSION: A harmonization of methodological requirements and recommendations exists both within and between the guideline groups. This review provides information concerning the core of agreements that have been reached. A number of policy implications for various parties, mainly the pharmaceutical industry, were identified.

A cost-effectiveness study comparing the as-needed use of formoterol (Oxis) and terbutaline (Bricanyl) in patients with moderate to severe asthma.

This study evaluated the economic and health-related consequences of the as-needed use of a long-acting beta2-agonist with fast onset (formoterol, Oxis Turbuhaler 4.5 microg) versus a short-acting beta2-agonist (terbutaline, Bricanyl Turbuhaler 0.5 mg) in patients with moderate to severe asthma. A multi-national (Sweden, Norway, The Netherlands and Greece), multi-centre (35 centres), randomized, double-blind clinical trial was conducted using 362 patients on inhaled steroids during a 12-week period. The effectiveness results were pooled and the total costs included estimates for beta2-agonists, inhaled steroids, oral steroids, physician visits and sick-leave. The 182 patients in the formoterol group had 14,404 days of exposure and 29 severe exacerbations, and the 180 patients in the terbutaline group had 13,655 days of exposure and 48 severe exacerbations. The terbutaline group had 62% more severe exacerbations than the formoterol group (P=0.039), based on exposure time. Per patient, the calculated total costs were SEK 3386 for the formoterol group and SEK 3709 for the terbutaline group over the 12-week period. The conclusion is that the use of Oxis Turbuhaler instead of Bricanyl Turbuhaler for as-needed treatment is a more effective treatment generating cost savings from a societal perspective.