Quantification of Salmonella and Yersinia on pork carcasses by simulation modelling

Stagnation in the success of control programmes in pig production in Denmark has led to an increased interest in the development of alternative control strategies such as decontamination of carcasses to further decrease the attribution of pork meat to human foodborne illness. This project sets out to develop a model for quantitative estimation of slaughterhouse output of Salmonella and Yersinia . Distributions of the occurrence of Salmonefla, Yersinia and E. coli on pork carcasses are based on the analysis of paired faecal samples and carcass swabs from 2880 animals originating from four abattoirs. By combining the estimated quantity of faecal contamination of carcasses with a semi-quantitative distribution of the number of Safmoneffa or Yersinia per gram faeces, an output distribution describing the number of Salmonella or Yersinia bacteria per carcass can be established. In order to validate the model, carcass swabs, analysed for Salmonefla and Yersinia serve as control. After the model has been validated, the effect of various decontamination methods on human exposure to foodborne pathogens in pork will be evaluated in both economic terms as well as with regard to public health impact

Nonuniform Cardiac Denervation Observed by 11C-meta-Hydroxyephedrine PET in 6-OHDA-Treated Monkeys

Parkinson's disease presents nonmotor complications such as autonomic dysfunction that do not respond to traditional anti-parkinsonian therapies. The lack of established preclinical monkey models of Parkinson's disease with cardiac dysfunction hampers development and testing of new treatments to alleviate or prevent this feature. This study aimed to assess the feasibility of developing a model of cardiac dysautonomia in nonhuman primates and preclinical evaluations tools. Five rhesus monkeys received intravenous injections of 6-hydroxydopamine (total dose: 50 mg/kg). The animals were evaluated before and after with a battery of tests, including positron emission tomography with the norepinephrine analog 11C-meta-hydroxyephedrine. Imaging 1 week after neurotoxin treatment revealed nearly complete loss of specific radioligand uptake. Partial progressive recovery of cardiac uptake found between 1 and 10 weeks remained stable between 10 and 14 weeks. In all five animals, examination of the pattern of uptake (using Logan plot analysis to create distribution volume maps) revealed a persistent region-specific significant loss in the inferior wall of the left ventricle at 10 (P<0.001) and 14 weeks (P<0.01) relative to the anterior wall. Blood levels of dopamine, norepinephrine (P<0.05), epinephrine, and 3,4-dihydroxyphenylacetic acid (P<0.01) were notably decreased after 6-hydroxydopamine at all time points. These results demonstrate that systemic injection of 6-hydroxydopamine in nonhuman primates creates a nonuniform but reproducible pattern of cardiac denervation as well as a persistent loss of circulating catecholamines, supporting the use of this method to further develop a monkey model of cardiac dysautonomia

Influenza vaccine effectiveness in adults 65 years and older, Denmark, 2015/16:a rapid epidemiological and virological assessment

In Denmark, both influenza A(H1N1)pdm09 and influenza B co-circulated in the 2015/16 season. We estimated the vaccine effectiveness (VE) of the trivalent influenza vaccine in patients 65 years and older using the test-negative case–control design. The adjusted VE against influenza A(H1N1)pdm09 was 35.0% (95% confidence interval (CI): 11.1–52.4) and against influenza B 4.1% (95% CI: −22.0 to 24.7). The majority of influenza A(H1N1)pdm09 circulating in 2015/16 belonged to the new genetic subgroup subclade 6B.1.</jats:p

Pioglitazone in early Parkinson\u27s disease: a phase 2, multicentre, double-blind, randomised trial

Background A systematic assessment of potential disease-modifying compounds for Parkinson\u27s disease concluded that pioglitazone could hold promise for the treatment of patients with this disease. We assessed the effect of pioglitazone on the progression of Parkinson\u27s disease in a multicentre, double-blind, placebo-controlled, futility clinical trial. Methods Participants with the diagnosis of early Parkinson\u27s disease on a stable regimen of 1 mg/day rasagiline or 10 mg/day selegiline were randomly assigned (1:1:1) to 15 mg/day pioglitazone, 45 mg/day pioglitazone, or placebo. Investigators were masked to the treatment assignment. Only the statistical centre and the central pharmacy knew the treatment name associated with the randomisation number. The primary outcome was the change in the total Unified Parkinson\u27s Disease Rating Scale (UPDRS) score between the baseline and 44 weeks, analysed by intention to treat. The primary null hypothesis for each dose group was that the mean change in UPDRS was 3 points less than the mean change in the placebo group. The alternative hypothesis (of futility) was that pioglitazone is not meaningfully different from placebo. We rejected the null if there was significant evidence of futility at the one-sided alpha level of 0.10. The study is registered at ClinicalTrials.gov, number NCT01280123. Findings 210 patients from 35 sites in the USA were enrolled between May 10, 2011, and July 31, 2013. The primary analysis included 72 patients in the 15 mg group, 67 in the 45 mg group, and 71 in the placebo group. The mean total UPDRS change at 44 weeks was 4.42 (95% CI 2.55-6.28) for 15 mg pioglitazone, 5.13 (95% CI 3.17-7.08) for 45 mg pioglitazone, and 6.25 (95% CI 4.35-8.15) for placebo (higher change scores are worse). The mean difference between the 15 mg and placebo groups was -1.83 (80% CI -3.56 to -0.10) and the null hypothesis could not be rejected (p=0.19). The mean difference between the 45 mg and placebo groups was -1.12 (80% CI -2.93 to 0.69)and the null hypothesis was rejected in favour of futility (p=0.09). Planned sensitivity analyses of the primary outcome, using last value carried forward (LVCF) to handle missing data and using the completers\u27 only sample, suggested that the 15 mg dose is also futile (p=0.09 for LVCF, p= 0.09 for completers) but failed to reject the null hypothesis for the 45 mg dose (p=0.12 for LVCF, p=0.19 for completers). Six serious adverse events occurred in the 15 mg group, nine in the 45 mg group, and three in the placebo group; none were thought to be definitely or probably related to the study interventions. Interpretation These findings suggest that pioglitazone at the doses studied here is unlikely to modify progression in early Parkinson\u27s disease. Further study of pioglitazone in a larger trial in patients with Parkinson\u27s disease is not recommended

Age-specific vaccination coverage estimates for influenza, human papillomavirus and measles containing vaccines from seven population-based healthcare databases from four EU countries – The ADVANCE project

Background: The Accelerated Development of VAccine beNefit-risk Collaboration in Europe (ADVANCE) is a public–private collaboration aiming to develop and test a system for rapid benefit-risk monitoring of vaccines using existing healthcare databases in Europe. We estimated vaccine coverage from electronic healthcare databases as part of a fit-for-purpose assessment for vaccine benefit-risk studies. Methods: A retrospective dynamic cohort study was conducted through a distributed network approach. Coverage with measles-vaccine for birth year 2006, human papillomavirus (HPV)-vaccine for birth years 1990–2000 and influenza-vaccine for birth years 1920–1950 was estimated using period-prevalence and inverse probability weighting methods. Seven databases from four countries participated: Italy (Pedianet, Val Padana), Spain (BIFAP, SIDIAP), UK (RCGP-RSC, THIN), Denmark (SSI/AUH). Database access providers extracted the data, transformed it into a common structure and ran an R-script locally. The created output tables were shared and pooled at a central server. Results: The total study population comprised 274,616 persons for measles-vaccine, 2,011,666 persons for HPV-vaccine and 14,904,033 persons for influenza-vaccine. Measles-vaccine coverage varied from 84.3% (Denmark) to 96.5% (Italy, Val Padana) for the first dose and from 82.8% (Italy, Val Padana) to 90.9% (UK) for the second dose at the age of 7 years. The HPV-vaccine coverage, aggregated over birth years 1997–2000, ranged from 60% (UK) to 88.3% (Denmark) at the age of 15 years. The influenza-vaccine coverage for the influenza seasons from 2009 to 2015 for persons aged 65 years and more was roughly stable around 43% in Denmark and around 68% in the UK while a decrease from 58 to 50% was observed in Catalonia (Spain). Conclusions: We obtained detailed, age-specific coverage estimates though a common procedure. We discussed between database comparability and comparability to published national estimates

Usefulness of health registries when estimating vaccine effectiveness during the influenza A(H1N1)pdm09 pandemic in Norway

<p>Abstract</p> <p>Background</p> <p>During the 2009-2010 pandemic in Norway, 12 513 laboratory-confirmed cases of pandemic influenza A(H1N1)pdm09, were reported to the Norwegian Surveillance System for Communicable Diseases (MSIS). 2.2 million persons (45% of the population) were vaccinated with an AS03-adjuvanted monovalent vaccine during the pandemic. Most of them were registered in the Norwegian Immunisation Registry (SYSVAK). Based on these registries, we aimed at estimating the vaccine effectiveness (VE) and describing vaccine failures during the pandemic in Norway, in order to evaluate the role of the vaccine as a preventive measure during the pandemic.</p> <p>Methods</p> <p>We conducted a population-based retrospective cohort study, linking MSIS and SYSVAK with pandemic influenza vaccination as exposure and laboratory-confirmed pandemic influenza as outcome. We measured VE by week and defined two thresholds for immunity; eight and 15 days after vaccination.</p> <p>Results</p> <p>The weekly VE ranged from 77% to 96% when considering 15 days or more after vaccination as the threshold of immunity and from 73% to 94% when considering eight days or more. Overall, 157 individuals contracted pandemic influenza eight or more days after vaccination (8.4/100,000 vaccinated), of these 58 had onset 15 days or more after vaccination (3.0/100,000 vaccinated). Most of the vaccine failures occurred during the first weeks of the vaccination campaign. More than 30% of the vaccine failures were found in people below 10 years of age.</p> <p>Conclusions</p> <p>Having available health registries with data regarding cases of specific disease and vaccination makes it feasible to estimate VE in a simple and rapid way. VE was high regardless the immunity threshold chosen. We encourage public health authorities in other countries to set up such registries. It is also important to consider including information on underlying diseases in registries already existing, in order to make it feasible to conduct more complete VE estimations.</p

ADVANCE database characterisation and fit for purpose assessment for multi-country studies on the coverage, benefits and risks of pertussis vaccinations

Introduction: The public-private ADVANCE consortium (Accelerated development of vaccine benefit-risk collaboration in Europe) aimed to assess if electronic healthcare databases can provide fit-for purpose data for collaborative, distributed studies and monitoring of vaccine coverage, benefits and risks of vaccines. Objective: To evaluate if European healthcare databases can be used to estimate vaccine coverage, benefit and/or risk using pertussis-containing vaccines as an example. Methods: Characterisation was conducted using open-source Java-based (Jerboa) software and R scripts. We obtained: (i) The general characteristics of the database and data source (meta-data) and (ii) a detailed description of the database population (size, representatively of age/sex of national population, rounding of birth dates, delay between birth and database entry), vaccinations (number of vaccine doses, recording of doses, pattern of doses by age and coverage) and events of interest (diagnosis codes, incidence rates). A total of nine databases (primary care, regional/national record linkage) provided data on events (pertussis, pneumonia, death, fever, convulsions, injection site reactions, hypotonic hypo-responsive episode, persistent crying) and vaccines (acellular pertussis and whole cell pertussis) related to the pertussis proof of concept studies. Results: The databases contained data for a total population of 44 million individuals. Seven databases had recorded doses of vaccines. The pertussis coverage estimates were similar to those reported by the World Health Organisation (WHO). Incidence rates of ev

ADVANCE system testing: Can coverage of pertussis vaccination be estimated in European countries using electronic healthcare databases: An example

Introduction: The Accelerated Development of VAccine beNefit-risk Collaboration in Europe (ADVANCE) is a public-private collaboration aiming to develop and test a system for rapid benefit-risk (B/R) monitoring of vaccines, using existing healthcare databases in Europe. The objective of this paper was to assess the feasibility of using electronic healthcare databases to estimate dose-specific acellular pertussis (aP) and whole cell pertussis (wP) vaccine coverage. Methods: Seven electronic healthcare databases in four European countries (Denmark (n = 2), UK (n = 2), Spain (n = 2) and Italy (n = 1)) participated in this study. Children were included from birth and followed up to age six years. Vaccination exposure was obtained from the databases and classified by type (aP or wP), and dose 1, 2 or 3. Coverage was estimated using period prevalence. For the 2006 birth cohort, two estimation methods for pertussis vaccine coverage, period prevalence and cumulative incidence were compared for each database. Results: The majority of the 2,575,576 children included had been vaccinated at the country-specific recommended ages. Overall, the estimated dose 3 coverage was 88–97% in Denmark (birth cohorts from 2003 to 2014), 96–100% in the UK (2003–2014), 95–98% in Spain (2004–2014) and 94% in Italy (2006–2007). The estimated dose 3 coverage per birth cohort in Denmark and the UK differed by 1–6% compared with national estimates, with our estimates mostly higher. The estimated dose 3 coverage in Spain differed by 0–2% with no consistent over- or underestimation. In Italy, the estimates were 3% lower compared with the national estimates. Except for Italy, for which the two coverage estimation methods generated the same results, the estimated cumulative incidence coverages were consistently 1–10% lower than period prevalence estimates. Conclusion: Thi