Health and Economic Burden of Seven Foodborne Diseases in Denmark, 2019.

We ranked seven foodborne pathogens in Denmark on the basis of their health and economic impact on society in 2019. We estimated burden of disease of infections with Campylobacter spp., Salmonella spp., Shiga toxin-producing Escherichia coli (STEC), Yersinia enterocolitica, Listeria monocytogenes, norovirus, and hepatitis A virus in terms of incidence, mortality, disability-adjusted life years (DALY), and economic burden in terms of direct and indirect health costs. These seven pathogens accounted for 268,372 cases, 98 deaths, and 3121 DALYs, and led to a total expenditure of 434 million Euro in 1 year in a country with 5.8 million citizens. Foodborne infections by Campylobacter, Salmonella, and norovirus caused the most DALYs, whereas Campylobacter, and norovirus and STEC had the higher costs. A combination of disease burden and cost of illness estimates is useful to inform policymaking and establish food safety priorities at the national level.

Market driven initiatives can improve broiler welfare - a comparison across five European countries based on the Benchmark method.

Two kinds of initiatives exist to ensure welfare in broiler production: welfare legislation, where all broiler production in a country or region must comply with legally defined welfare standards; and market driven initiatives, where part of the production must meet specific welfare standards and is sold with a particular label, typically at a price premium, or as part of minimum welfare standards defined by a retailer, a fast-food chain or the like. While the effects of national legislation may be undermined by price competition from lower welfare imported products, the effects of market driven initiatives may be limited by lack of willingness from consumers to pay the extra cost. To investigate how this works out in practice, we compared broiler welfare requirements in 5 European countries, Denmark, Germany, United Kingdom, the Netherlands, and Sweden, in 2018, by means of the Benchmark method. A number of welfare dimensions, covering the input features typically modified in broiler welfare initiatives, were defined. A total of 27 academic welfare experts (response rate 75%) valued the different levels within each dimension on a 0 to 10 scale, and then weighted the relative contribution of each dimension to overall welfare on a 1 to 5 scale. By combining these values and weights with an inventory of existing welfare initiatives, the additional welfare generated by each initiative was calculated. Together with information on national coverage of each initiative, the Benchmark score for each country's production and consumption of chicken meat was calculated. Sweden achieved a much higher Benchmark for national production due to higher legal standards than any of the four other countries. The Netherlands, on the other hand, achieved a Benchmark for national consumption of chicken at the same level as that found in Sweden, because market driven initiatives complemented more welfare-limited Dutch legislation. So, despite some uncertainties in the Benchmark method, it appears that market driven initiatives can have a strong impact on improving broiler welfare, building on those standards achieved by animal welfare legislation.

Is there a potential international market for Danish welfare pork? - A consumer survey from Denmark, Sweden, and Germany.

This cross-country study investigates the potential to improve pig welfare by exploiting consumer demand, domestically and in export markets, for welfare pork produced in indoor production systems. The analysis is based on questionnaire data collected in 2019 focusing on demand for Danish welfare pork both in Denmark and in two nearby export markets, Sweden and Germany. To reduce hypothetical bias, a willingness-to-pay indicator is combined with an indicator of positive interest in buying a fictive Danish welfare labelled pork. We find that the market potential is relatively weak. Our findings indicate that there is some, albeit limited, potential in Denmark and Germany while demand is practically non-existing in Sweden, probably because the pig welfare guaranteed by Swedish legislation is similar to what is provided by the fictive welfare label employed in the study. Hence, consumer demand alone cannot secure enhanced pig welfare. Moreover, we found national differences in the characteristics of consumers who are interested in Danish welfare pork.

Pig Farmers' Perceptions of Economic Incentives to Control Salmonella Prevalence at Herd Level.

This paper investigates how perceived costs and benefits of Salmonella control among Danish pig farmers affect the farmers' choice of action toward reducing the prevalence of Salmonella in their herds. Based on data from an online questionnaire involving 163 Danish pig farmers, we find a considerable uncertainty among pig farmers about the perceived effects of the Salmonella reducing actions. The results indicate large variations in the perceived costs of implementing different types of Salmonella reducing actions (management-, hygiene- and feed-related). For some cases, farmers associate net benefits and positive productivity effects with implementation of the actions while studies by the industry indicate net costs to the farmers. Differences among farmers support the idea of an outcome-based Salmonella penalty scheme but the large uncertainties about costs and effects of actions toward Salmonella control might hamper the effectiveness of such a penalty scheme as a regulatory instrument to affect farmer behavior.

Consumer preferences for low-salt foods: a Danish case study based on a comprehensive supermarket intervention.

OBJECTIVE: The objective is to analyse Danish consumers' attitudes to buying food with reduced salt content. DESIGN: The study is based on a comprehensive store intervention that included 114 stores belonging to the same supermarket chain. Three different salt claims were tested for 8 weeks on six test products within the categories bread, cornflakes and frozen pizzas. Scanner data were supplemented with 134 brief interviews with consumers in nine selected stores. SETTING: Stores spread across Denmark. PARTICIPANTS: Consumers who buy food in the stores. RESULTS: Statistical regression analyses of the scanner data indicated that none of the three claims significantly affected demand for any of the test products. The interviews confirmed that many consumers were more focused on other elements of the official dietary advice than reduced salt consumption, such as eating plenty of vegetables, choosing products with whole grains and reducing their intake of sugar and fat. CONCLUSIONS: Overall, both the scanner data and the interviews pointed in the same direction, towards the conclusion that salt content is often a secondary factor when Danish consumers make dietary choices.

Regulation of the expression of human endogenous retroviruses: elements in fetal development and a possible role in the development of cancer and neurological diseases.

Human endogenous retroviruses (HERVs) are remnants of ancient retroviral germline infections. Most HERV sequences are silenced in somatic cells, but interest is emerging on the involvement of HERV derived transcripts and proteins in human physiology and disease. A HERV-W encoded protein, syncytin-1, has been co-opted into fetal physiology, where it plays a role in trophoblast formation. Altered HERV transcription and expression of HERV derived proteins are associated with various cancer types and neurological diseases such as multiple sclerosis (MS). The implication of HERVs as potential mediators of both health and disease suggests important roles of regulatory mechanisms and alterations of these in physiological and pathological processes. The regulation of HERV sequences is mediated by a wide variety of mechanisms, and the focus of this review is on selected aspects of these, including epigenetic mechanisms such as CpG methylation and histone modifications of the HP1-H3K9me axis, viral transactivation events, and regulatory perspectives of transient stimuli in the microenvironment. Increasing knowledge of the regulation of HERV sequences will not only contribute to the understanding of complex pathogeneses, but also may pinpoint potential targets for better diagnosis and treatment in complex diseases as MS.

Consumer preferences for reduced antibiotic use in Danish pig production.

Denmark has a large and intensive pig production sector which accounts for around half of the total use of antimicrobials in Demark. The economic feasibility of alternative strategies involving reduced use of antibiotics depends not only on their effects on productivity but also on consumers' demand, and willingness-to-pay (WTP), for pork from pigs with no or lower antibiotic treatment. This study investigates the various concerns that consumers might have about the use of antibiotics in pig production, and how they affect demand and WTP. We used data from an online questionnaire survey of approximately 1000 Danish consumers. WTP estimates were obtained using payment card data analysed in an ordered probit regression. We found that 41 % of the respondents wanted antibiotic use to be reduced substantially, and that they linked reduced use of antibiotics in pig production primarily with reduced risk of antibiotic residues in pork and a lowered risk of resistant bacteria developing. A considerable share of the consumers we sampled also linked reduced antibiotic use with improved animal welfare, and with price increases for pork. Two thirds of the consumers stated a positive WTP for reduced use of antibiotics, but only one in five were willing to pay more than 10 % for pork produced using antibiotics 20 % less than average. The WTP estimates differed with socio-demographic variables (education, geography, gender and age). In addition, the respondents' perceptions of the effects of reducing antibiotic use and of externalities associated with the pig industry, and the frequency of their pork consumption, were found to affect their WTP for pork produced with lower antibiotic use. As the vast majority of the Danish pork is exported, future studies should examine consumer perceptions of antibiotic use in pig production in importing countries.

Moral Convictions and Meat Consumption-A Comparative Study of the Animal Ethics Orientations of Consumers of Pork in Denmark, Germany, and Sweden.

BACKGROUND: The relationship between animal ethics orientations and consumer demand for meat with high standards of animal welfare, and the way this relationship plays out in different countries, is not well understood. Using pork as a case study, this comparative study aims to identify the animal ethics orientations that drive purchases of welfare meat in Denmark, Germany, and Sweden. METHODS: Cross-sectional questionnaire data from representative samples of approximately 1600 consumers in each country were collected. A segmentation of pork consumers (using latent profile analysis) was carried out. RESULTS: In all three countries, two subgroups were concerned about farm animal welfare: the first subgroup was driven by animal rights values; the second subgroup by animal protection values, where the main principle was that "it is all right to use animals as long as they are treated well". Other consumer groups are less concerned about farm animal welfare and display little or no preference for welfare pork. CONCLUSIONS: In all three countries, dual demand for welfare pork exists. The findings of this study can be used, among others, to understand the marketability of enhanced welfare animal products and the potential for market-driven animal welfare improvements.

Non-phthalate plasticizer DEHT preserves adequate blood component quality during storage in PVC blood bags.

BACKGROUND AND OBJECTIVES: Commercial blood bags are predominantly made of polyvinyl chloride (PVC) plasticized with di(2-ethylhexyl) phthalate (DEHP). DEHP is favourable for storage of red blood cells (RBC). Historically, removal of DEHP from blood bags has been linked to unacceptable haemolysis levels. Oncoming regulatory restrictions for DEHP due to toxicity concerns increase the urgency to replace DEHP without compromising RBC quality. Di(2-ethylhexyl) terephthalate (DEHT) is one suggested substitute. The aim of this study was to compare PVC-DEHT to PVC-DEHP blood bags using additive solutions saline-adenine-glucose-mannitol (SAGM) and phosphate-adenine-glucose-guanosine-saline-mannitol (PAGGSM), to determine whether DEHT can maintain acceptable component quality. MATERIALS AND METHODS: RBC concentrates (N = 64), platelet concentrates (N = 16) and fresh frozen plasma (N = 32) were produced from whole blood collected into either DEHT or DEHP plasticized systems. Using a pool-and-split study design, pairs of identical RBC content were created within each plasticizer arm and assigned either SAGM or PAGGSM. Storage effects were assessed weekly for 49 days (RBC), 7 days (platelets) and before/after freezing (plasma). RESULTS: Though haemolysis was slightly higher in DEHT, all study arms remained below half of the European limit 0·8%. K+ was lower in DEHT than in DEHP independent of additive solution. The metabolic parameters were not influenced by choice of plasticizer. Platelet activation/metabolism and plasma content were similarly preserved. CONCLUSION: Our study demonstrates that the plasticizer DEHT provides adequate blood component quality. We propose DEHT as a strong future candidate for replacement of DEHP in blood bags.

Benchmarking Farm Animal Welfare-A Novel Tool for Cross-Country Comparison Applied to Pig Production and Pork Consumption.

A pluralist approach to farm animal welfare, combining animal welfare legislation with market-driven initiatives, has developed in many countries. To enable cross-country comparisons of pig welfare, a number of welfare dimensions, covering the features typically modified in legislative and market-driven welfare initiatives aimed at pig production, were defined. Five academic welfare experts valued the different welfare states within each dimension on a 0-10 scale, then assessed the relative contribution of each dimension to overall welfare on a 1-5 scale. By combining these values and weights with an inventory of pig welfare initiatives in five countries, the additional welfare generated by each initiative was calculated. Together with information on the national coverage of each initiative, the Benchmark value for each country's production and consumption of pork could be calculated on a scale from 0 to 100. Two (Sweden and the UK) had a much higher Benchmark value than the rest. However, there was a drop in the Benchmark for consumption in Sweden and the UK (indicating imports from countries with lower-Benchmark values for production). Even though the experts differed in the values and weights ascribed to different initiatives, they were largely in agreement in their ranking of the countries.

Activated monocytes and markers of inflammation in newly diagnosed multiple sclerosis.

In multiple sclerosis (MS), the inflammation and demyelination of the central nervous system (CNS) develop in distinct ways. This makes diagnosing patients difficult, imperative to initiating early and proper treatment. Several common features exist, among them a profound infiltration of monocytes into the CNS mediating demyelination and tissue destruction. In the periphery, monocytes are divided into three subsets depending on expression of CD14 and CD16, representing different stages of activation and differentiation. To investigate their involvement in MS, peripheral blood mononuclear cells (PBMCs) from 61 patients with incipient, untreated MS and 22 symptomatic control (SC) patients as well as 6 patients with radiologically isolated syndrome (RIS) were characterized ex vivo. In addition, paired serum and cerebrospinal fluid (CSF) samples were analyzed with a panel of biomarkers. In PBMC samples, we demonstrate decreased levels of nonclassical monocytes with a concomitant significant decrease of human endogenous retrovirus (HERV) H3 envelope epitopes on this monocyte subset compared with SC and RIS. The observed HERV expression is present on nonclassical monocytes irrespective of MS and thus presumably a result of the inflammatory activation. For the other surface markers analyzed, we found significantly decreased expression between classical and nonclassical monocytes. In matched samples of CSF a highly significant increase in levels of soluble markers of activation and inflammation is shown, and notably this is not the case for the serum samples. Of the soluble markers investigated, interleukin (IL)-12/IL-23p40 had the highest discriminatory power in differentiating patients with MS from SC and RIS, almost comparable to the immunoglobulin G index.

Costs and Benefits of Alternative Strategies to Control the Spread of Livestock-Acquired Methicillin-Resistant Staphylococcus Aureus From Pig Production.

BACKGROUND: Livestock-acquired methicillin-resistant Staphylococcus aureus (LA-MRSA) is a concern in healthcare and a political priority in some countries. OBJECTIVE: This study investigates the net societal costs of 2 alternative strategies for controlling LA-MRSA in Denmark: (1) eradicating LA-MRSA in all pig housing units, and (2) containing LA-MRSA within the units. METHODS: Benefits and costs are considered for affected economic sectors: healthcare, pig production, pig-related industries, and public administration. RESULTS: The cost to society of eradication is estimated at €2.3 to €2.5 billion (present value). Containment will cost €55 to €93 million. For both strategies, the main cost lies in primary pig production-for containment this is mainly due to establishing and operating anterooms and shower rooms, and for eradication it is due to production losses, loss of genetic resources, and costs of cleaning and disinfection. CONCLUSION: Compared with these costs, health economic benefits are moderate for both strategies. Containment is superior to eradication when measured by a benefit-cost ratio.

A taste for locally produced food - Values, opinions and sociodemographic differences among 'organic' and 'conventional' consumers.

Local food has received considerable attention in recent years. It is seen as a response to increased demand for authentic foods, just as organic foods have been considered to be. It is unclear whether organic and local are two complementary or competitive trends in food consumption. This study addresses this question with a mixed methods investigation of why Danish consumers of organic products and conventional consumers of local products choose locally produced food, what values and opinions they associate with local food, and whether there are sociodemographic differences between the groups. The results show that the same values and opinions tended to motivate organic consumers and a group of committed conventional consumers of local foods. However, organic consumers were much more likely to include environmental issues in their deliberations. Another group of local-food consumers did not seem to be motivated by values and opinions when purchasing locally produced foods. Some sociodemographic differences between the groups were found: organic consumers were more likely to live in the capital than committed local consumers; to have a lengthy education than consumers of local foods; and committed local-food consumers were more likely than organic consumers to have a vocational education. The article concludes that while it is to some extent the same preference for authentic food that motivates organic and committed conventional local-food consumers to buy locally produced foods, it is at the same time different types of consumers who prefer (conventional) local food and organic food.

Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology: A Systematic Review and Meta-analysis.

IMPORTANCE: Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date. OBJECTIVES: To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions. DATA SOURCES: PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC. STUDY SELECTION: Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex. DATA EXTRACTION AND SYNTHESIS: Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept. MAIN OUTCOME AND MEASURE: The cNfL levels adjusted for age and sex across diagnoses. RESULTS: Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes. CONCLUSIONS AND RELEVANCE: These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.

Are independent agricultural advisors more oriented towards recommending reduced pesticide use than supplier-affiliated advisors?

This paper explores whether agricultural advisors employed by chemical companies or agricultural companies selling pesticides (supplier-affiliated advisors) are more likely to recommend more intensive use of pesticides than advisors employed by companies without an economic interest in selling pesticides (independent advisors). We further test whether potential differences in advice are caused by differences in advisors' perceived demands for advice from farmers, different environmental risk perceptions about pesticide use or different weighing of the purposes of pesticide use. The analysis is based on a survey administered to the whole population of 540 advisors in Denmark; we received 227 valid responses. The main finding is that pesticide advice differs across company type. We find that supplier-affiliated advisors are less likely to recommend lower doses - scoring on average 3.9 on a scale from 1 (never) to 5 (always). Independent advisors employed at Danish Agricultural Advisory Services score an average of 4.3. The difference is statistically significant. The analysis does not offer strong support for the different causal mediators we examined. Advisors across company type tend to weigh different objectives equally; tend to agree on environmental risk perception of using pesticides; and differ only slightly on perceived farmer demand. One possible conclusion, therefore, is that explanation is as simply that differences in economic incentives produce different recommendations between advisory companies. Policy implications of the findings are that the European Union should consider addressing this difference more directly when regulating the use of pesticides in European agriculture through e.g. the Sustainable Use of Pesticides Directive (Directive, 2009/128/EC). More differentiation in the approaches for informing different types of advisors might be needed. Moreover, our results point towards the need for knowledge about whether advisors in other countries than Denmark tend to believe that approved pesticides are innocuous to the environment because such perceptions might hamper initiatives to reduce the doses of approved pesticides.

Nationwide prevalence and incidence study of neuromyelitis optica spectrum disorder in Denmark.

OBJECTIVES: To estimate the nationwide population-based incidence, prevalence, and geographical distribution of neuromyelitis optica (NMO) spectrum disorder (NMOSD) in Denmark based on the 2015 International Panel for NMO Diagnosis (IPND) criteria. METHODS: We conducted a multicentre, historically prospective study. Data were sourced from the Danish National Patient Registry, the Danish Multiple Sclerosis Registry, departments of neurology, and laboratories providing aquaporin-4 antibody test. Cases were selected based on the 2006 Wingerchuk and the 2015 IPND criteria and were individually validated by an expert panel. RESULTS: We confirmed NMO in 30 cases (2006 criteria) and NMOSD in 56 cases (2015 IPND criteria) between 2007 and 2014. Defined by the 2006 criteria, the incidence of NMO was 0.029 per 100,000 person-years (95% confidence interval [CI] 0.014-0.051), and the prevalence (aged 16 years and older) was 0.566 per 100,000 (95% CI 0.370-0.830). Based on the 2015 IPND criteria, the incidence of NMOSD was 0.070 per 100,000 person-years (95% CI 0.046-0.102), and the prevalence (aged 16 years and older) was 1.09 per 100,000 (95% CI 0.808-1.440), without regional differences. CONCLUSIONS: Our estimates of incidence and prevalence are similar to other Caucasian population-based studies using the 2015 IPND criteria. We found no geographical clustering in Denmark.

A phase II baseline versus treatment study to determine the efficacy of raltegravir (Isentress) in preventing progression of relapsing remitting multiple sclerosis as determined by gadolinium-enhanced MRI: The INSPIRE study.

BACKGROUND: Although the aetiology of multiple sclerosis (MS) remains elusive, it is clear that Epstein Barr virus (EBV) and possibly other viruses play a role in the pathogenesis of MS. Laboratory evidence suggests that human endogenous retroviruses (HERVs) could also have a role, but no interventional therapy has determined what will happen if HERVs are suppressed. Recent epidemiological evidence indicates patients with HIV infection have a significantly lower risk of developing MS and that HIV antiretroviral therapies may be coincidentally inhibiting HERVs, or other retroelements, that could be implicated in MS. OBJECTIVES: To systematically investigate the effects of an HIV integrase strand inhibitor, raltegravir, on the number of gadolinium (Gd)-enhanced MRI lesions in people with active relapsing MS. METHODS: This is a Phase 2a clinical trial where twenty participants were enrolled in a 3 month baseline phase followed by 3 months of treatment with raltegravir 400 mg twice a day. Patients had monthly Gd-enhanced MRI, saliva collection to test for EBV shedding, blood sampling for safety monitoring, virology (including HERVs), measurement of immunological and inflammatory markers; and physical, neurological and quality-of-life assessments. RESULTS: All patients completed the six months trial period.The primary outcome measure of MS disease activity was the number of Gd-enhancing lesions observed, and raltegravir had no significant effect on the rate of development of Gd-enhancing lesions during the treatment phase compared with the baseline phase. Additionally, there was no change in secondary outcomes of either disability or quality-of-life measures that could reasonably be attributed to the intervention. There was a significant positive between HERV-W/MSRV (multiple sclerosis related virus) Gag Flix (Fluorescence index) B cells and the number of Gd-enhanced lesions at any visit (p = 0.029), which was independent of any potential influence of the trial drug administration. Regarding EBV shedding, there was no significant correlation between the amount of EBV shedding and the number of lesions. No change was detected in inflammatory markers (IL-8, IL-1ß, IL-6, IL-10, TNF, IL-12p70 and HCRP), which were all within normal limits both before and after the intervention. Serum CD163 expression was also unchanged by raltegravir. CONCLUSIONS: Raltegravir did not have any impact on MS disease activity. This could be due to the choice of antiretroviral agent used in this study, the need for a combination of agents, as used in treating HIV infection, the short treatment period or dosing regimen, or the lack of a role of HERV expression in MS once the disease is established. Borderline significance for the association between EBV shedding and the total number of lesions, probably driven by new lesion development, may indicate EBV shedding as a marker of inflammatory disease activity. In conclusion, interesting correlations between HERV-W markers, EBV shedding and new MRI lesions, independent from treatment effects, were found.

Cerebrospinal fluid free kappa light chains and kappa index perform equal to oligoclonal bands in the diagnosis of multiple sclerosis.

Background Detection of intrathecal immunoglobulin G (IgG) synthesis by gold standard oligoclonal bands (OCB) or IgG index remains an integral part of multiple sclerosis (MS) diagnostics, although both methods have weaknesses. Emerging evidence suggests that automated detection of free light chains (FLC) in the cerebrospinal fluid (CSF) has diagnostic performance equal to OCB. The objective of this study was to compare the diagnostic performance of CSF FLC with OCB and IgG index in a large cohort of Scandinavian patients referred for MS evaluation. Methods We prospectively included 230 patients suspected for MS. They are composed of patients with MS (n=96), clinically isolated syndrome (n=37), other neurological diseases (OND, n=31) and symptomatic controls (SC, n=66). CSF and serum samples were analyzed for kappa and lambda FLC, OCB and IgG index. Diagnostic performance was evaluated by receiver operating characteristic (ROC) analysis. Results Both the absolute concentration of CSF-kappa and the kappa index had excellent MS diagnostic performances with ROC area under the curve of 0.93 and 0.94 (MS vs. SC+OND). At the 0.42 mg/L cutoff, CSF-kappa had sensitivity and specificity of 93.8% and 85.6%, whereas sensitivity and specificity for OCB was 82.3% and 93.8% (72.9% and 95.9% for IgG index at cutoff 0.64). CSF-lambda and lambda index performed inferior to CSF-kappa and kappa index. Conclusions CSF-kappa and kappa index represent automated, rapid and low-cost alternatives to OCB. Using merely the absolute concentration of CSF-kappa is a logistic advantage in the clinical laboratories.

Time to steroid treatment in severe acute optic neuritis.

OBJECTIVES: Steroid treatment can accelerate visual recovery in patients with optic neuritis (ON), but it is unknown whether the timing of the start of treatment influences the outcome. The main purpose of this observational study was to assess the effect of early onset steroid treatment of ON on visual prognosis and retinal morphology. METHODS: Forty-nine patients with acute mild/moderate (n = 21) or severe (n = 28) ON, and an equal number of healthy controls were enrolled. Patients with severe ON either received early onset steroid treatment (initiated within 1 week of presentation with visual loss) (n = 9), late-onset treatment (initiated after 1 week) (n = 13), or no treatment (n = 6). Visual function and retinal morphology was studied after 6 and 12 months. RESULTS: All measures of visual function had improved after 6 months (p ≤ 0.03) in the three groups with severe ON. This was not the case for Rayleigh match setting range (SR) in the nontreated group (p = 0.24), or for SR (p = 0.08) and latency to P100 of visual evoked potential (p = 0.08) in the late-onset treated group. After 12 months, further improvement occurred in the nontreated and late-treated groups, but not in the early treated group. Macular retinal nerve fiber layer (mRNFL) and ganglion cell plus inner plexiform layer had decreased significantly (p ≤ 0.001) in all three groups with severe ON after 6 months. After 12 months, only mRNFL had further significantly decreased and only in the late-onset treated group (p = 0.02). CONCLUSION: The beneficial effects of early onset steroid treatment of ON is limited to a few months whereas the long-term prognosis is independent of the timing of treatment.

Subsets of activated monocytes and markers of inflammation in incipient and progressed multiple sclerosis.

Multiple sclerosis (MS) is an immune mediated, inflammatory and demyelinating disease of the central nervous system (CNS). Substantial evidence points toward monocytes and macrophages playing prominent roles early in disease, mediating both pro- and anti-inflammatory responses. Monocytes are subdivided into three subsets depending on the expression of CD14 and CD16, representing different stages of inflammatory activation. To investigate their involvement in MS, peripheral blood mononuclear cells from 40 patients with incipient or progressed MS and 20 healthy controls were characterized ex vivo. In MS samples, we demonstrate a highly significant increase in nonclassical monocytes (CD14+CD16++), with a concomitant significant reduction in classical monocytes (CD14++CD16-) compared with healthy controls. Also, a significant reduction in the surface expression of CD40, CD163, and CD192 was found, attributable to the upregulation of the nonclassical monocytes. In addition, significantly increased levels of human endogenous retrovirus (HERV) envelope (Env) epitopes, encoded by both HERV-H/F and HERV-W, were specifically found on nonclassical monocytes from patients with MS; emphasizing their involvement in MS disease. In parallel, serum and cerebrospinal fluid (CSF) samples were analyzed for soluble biomarkers of inflammation and neurodegeneration. For sCD163 versus CD163, no significant correlations were found, whereas highly significant correlations between levels of soluble neopterine and the intermediate monocyte (CD14++CD16+) population was found, as were correlations between levels of soluble osteopontin and the HERV Env expression on nonclassical monocytes. The results from this study emphasize the relevance of further focus on monocyte subsets, particularly the nonclassical monocytes in monitoring of inflammatory diseases.