Comparison of Alternative Meat Inspection Regimes for Pigs From Non-Controlled Housing – Considering the Cost of Error

Denmark has not had cases of bovine tuberculosis (bovTB) for more than 30 years but is obliged by trade agreements to undertake traditional meat inspection (TMI) of finisher pigs from non-controlled housing to detect bovTB. TMI is associated with higher probability of detecting bovTB but is also more costly than visual-only inspection (VOI). To identify whether VOI should replace TMI of finisher pigs from non-controlled housing, the cost of error – defined here as probability of overlooking infection and associated economic costs - should be assessed and compared with surveillance costs. First, a scenario tree model was set up to assess the ability of detecting bovTB in an infected herd (HSe) calculated for three within-herd prevalences, WHP (1, 5 and 10%), for four different surveillance scenarios (TMI and VOI with or without serological test, respectively). HSe was calculated for six consecutive 4-week surveillance periods until predicted bovTB detection (considered high-risk periods HRP). 1-HSe was probability of missing all positives by each HRP. Next, probability of spread of infection, Pspread, and number of infected animals moved were calculated for each HRP. Costs caused by overlooking bovTB were calculated taking into account Pspread, 1-HSe, eradication costs, and trade impact. Finally, the average annual costs were calculated by adding surveillance costs and assuming one incursion of bovTB in either 1, 10 or 30 years. Input parameters were based on slaughterhouse statistics, literature and expert opinion. Herd sensitivity increased by high-risk period and within-herd prevalence. Assuming WHP=5%, HSe reached median 90% by 2nd HRP for TMI, whereas for VOI this would happen after 6th HRP. Serology had limited impact on HSe. The higher the probability of infection, the higher the probability of detection and spread. TMI resulted in lowest average annual costs, if one incursion of bovTB was expected every year. However, when assuming one introduction in 10 or 30 years, VOI resulted in lowest average costs. It may be more cost-effective to focus on imported high-risk animals coming into contact with Danish livestock, instead of using TMI as surveillance on all pigs from non-controlled housing

Reperfusion therapy for ST elevation acute myocardial infarction 2010/2011: current status in 37 ESC countries

Aims Primary percutaneous coronary intervention (PPCI) is the preferred reperfusion therapy in ST-elevation myocardial infarction (STEMI). We conducted this study to evaluate the contemporary status on the use and type of reperfusion therapy in patients admitted with STEMI in the European Society of Cardiology (ESC) member countries. Methods and results A cross-sectional descriptive study based on aggregated country-level data on the use of reperfusion therapy in patients admitted with STEMI during 2010 or 2011. Thirty-seven ESC countries were able to provide data from existing national or regional registries. In countries where no such registries exist, data were based on best expert estimates. Data were collected on the use of STEMI reperfusion treatment and mortality, the numbers of cardiologists, and the availability of PPCI facilities in each country. Our survey provides a brief data summary of the degree of variation in reperfusion therapy across Europe. The number of PPCI procedures varied between countries, ranging from 23 to 884 per million inhabitants. Primary percutaneous coronary intervention and thrombolysis were the dominant reperfusion strategy in 33 and 4 countries, respectively. The mean population served by a single PPCI centre with a 24-h service 7 days a week ranged from 31 300 inhabitants per centre to 6 533 000 inhabitants per centre. Twenty-seven of the total 37 countries participated in a former survey from 2007, and major increases in PPCI utilization were observed in 13 of these countries. Conclusion Large variations in reperfusion treatment are still present across Europe. Countries in Eastern and Southern Europe reported that a substantial number of STEMI patients are not receiving any reperfusion therapy. Implementation of the best reperfusion therapy as recommended in the guidelines should be encourage

A nationwide analytical and clinical evaluation of 44 rapid antigen tests for SARS-CoV-2 compared to RT-qPCR

BACKGROUND: The SARS-CoV-2 pandemic has resulted in massive testing by Rapid Antigen Tests (RAT) without solid independent data regarding clinical performance being available. Thus, decision on purchase of a specific RAT may rely on manufacturer-provided data and limited peer-reviewed data. METHODS: This study consists of two parts. In the retrospective analytical part, 33 RAT from 25 manufacturers were compared to RT-PCR on 100 negative and 204 positive deep oropharyngeal cavity samples divided into four groups based on RT-PCR Cq levels. In the prospective clinical part, nearly 200 individuals positive for SARS-CoV-2 and nearly 200 individuals negative for SARS-CoV-2 by routine RT-PCR testing were retested within 72 h for each of 44 included RAT from 26 manufacturers applying RT-PCR as the reference method. RESULTS: The overall analytical sensitivity differed significantly between the 33 included RAT; from 2.5% (95% CI 0.5–4.8) to 42% (95% CI 35–49). All RAT presented analytical specificities of 100%. Likewise, the overall clinical sensitivity varied significantly between the 44 included RAT; from 2.5% (95% CI 0.5–4.8) to 94% (95% CI 91–97). All RAT presented clinical specificities between 98 and 100%. CONCLUSION: The study presents analytical as well as clinical performance data for 44 commercially available RAT compared to the same RT-PCR test. The study enables identification of individual RAT that has significantly higher sensitivity than other included RAT and may aid decision makers in selecting between the included RAT. FUNDING: The study was funded by a participant fee for each test and the Danish Regions

Genotype-phenotype correlations in SCN8A-related disorders reveal prognostic and therapeutic implications

We report detailed functional analyses and genotype-phenotype correlations in 392 individuals carrying disease-causing variants in SCN8A, encoding the voltage-gated Na+ channel Nav1.6, with the aim of describing clinical phenotypes related to functional effects. Six different clinical subgroups were identified: Group 1, benign familial infantile epilepsy (n = 15, normal cognition, treatable seizures); Group 2, intermediate epilepsy (n = 33, mild intellectual disability, partially pharmaco-responsive); Group 3, developmental and epileptic encephalopathy (n = 177, severe intellectual disability, majority pharmaco-resistant); Group 4, generalized epilepsy (n = 20, mild to moderate intellectual disability, frequently with absence seizures); Group 5, unclassifiable epilepsy (n = 127); and Group 6, neurodevelopmental disorder without epilepsy (n = 20, mild to moderate intellectual disability). Those in Groups 1-3 presented with focal or multifocal seizures (median age of onset: 4 months) and focal epileptiform discharges, whereas the onset of seizures in patients with generalized epilepsy was later (median: 42 months) with generalized epileptiform discharges. We performed functional studies expressing missense variants in ND7/23 neuroblastoma cells and primary neuronal cultures using recombinant tetrodotoxin-insensitive human Nav1.6 channels and whole-cell patch-clamping. Two variants causing developmental and epileptic encephalopathy showed a strong gain-of-function (hyperpolarizing shift of steady-state activation, strongly increased neuronal firing rate) and one variant causing benign familial infantile epilepsy or intermediate epilepsy showed a mild gain-of-function (defective fast inactivation, less increased firing). In contrast, all three variants causing generalized epilepsy induced a loss-of-function (reduced current amplitudes, depolarizing shift of steady-state activation, reduced neuronal firing). Functional effects were known for 170 individuals. All 136 individuals carrying a functionally tested gain-of-function variant had either focal (n = 97, Groups 1-3) or unclassifiable (n = 39) epilepsy, whereas 34 individuals with a loss-of-function variant had either generalized (n = 14), no (n = 11) or unclassifiable (n = 6) epilepsy; only three had developmental and epileptic encephalopathy. Computational modelling in the gain-of-function group revealed a significant correlation between the severity of the electrophysiological and clinical phenotypes. Gain-of-function variant carriers responded significantly better to sodium channel blockers than to other anti-seizure medications, and the same applied for all individuals in Groups 1-3. In conclusion, our data reveal clear genotype-phenotype correlations between age at seizure onset, type of epilepsy and gain- or loss-of-function effects of SCN8A variants. Generalized epilepsy with absence seizures is the main epilepsy phenotype of loss-of-function variant carriers and the extent of the electrophysiological dysfunction of the gain-of-function variants is a main determinant of the severity of the clinical phenotype in focal epilepsies. Our pharmacological data indicate that sodium channel blockers present a treatment option in SCN8A-related focal epilepsy with onset in the first year of life