Performance of four different diagnostic tests for C. difficile infection in piglets

Clostridium difficile is emerging as a pathogen in man as well as in animals. In 2000 it was described as a cause of neonatal enteritis in piglets and it is now the most common cause of neonatal diarrhoea in the USA. In Europe, C. difficile infection (CDI) in neonatal piglets has also been reported. Diagnosis of this infection is based on detection of the bacterium or its toxins A and B

Syndromic Surveillance for Local Outbreaks of Lower-Respiratory Infections: Would It Work?

Background: Although syndromic surveillance is increasingly used to detect unusual illness, there is a debate whether it is useful for detecting local outbreaks. We evaluated whether syndromic surveillance detects local outbreaks of lower-respiratory infections (LRIs) without swamping true signals by false alarms. Methods and Findings: Using retrospective hospitalization data, we simulated prospective surveillance for LRI-elevations. Between 1999–2006, a total of 290762 LRIs were included by date of hospitalization and patients place of residence (>80% coverage, 16 million population). Two large outbreaks of Legionnaires disease in the Netherlands were used as positive controls to test whether these outbreaks could have been detected as local LRI elevations. We used a space-time permutation scan statistic to detect LRI clusters. We evaluated how many LRI-clusters were detected in 1999–2006 and assessed likely causes for the cluster-signals by looking for significantly higher proportions of specific hospital discharge diagnoses (e.g. Legionnaires disease) and overlap with regional influenza elevations. We also evaluated whether the number of space-time signals can be reduced by restricting the scan statistic in space or time. In 1999–2006 the scan-statistic detected 35 local LRI clusters, representing on average 5 clusters per year. The known Legionnaires' disease outbreaks in 1999 and 2006 were detected as LRI-clusters, since cluster-signals were generated with an increased proportion of Legionnaires disease patients (p:<0.0001). 21 other clusters coincided with local influenza and/or respiratory syncytial virus activity, and 1 cluster appeared to be a data artifact. For 11 clusters no likely cause was defined, some possibly representing as yet undetected LRI-outbreaks. With restrictions on time and spatial windows the scan statistic still detected the Legionnaires' disease outbreaks, without loss of timeliness and with less signals generated in time (up to 42% decline). Conclusions: To our knowledge this is the first study that systematically evaluates the performance of space-time syndromic surveillance with nationwide high coverage data over a longer period. The results show that syndromic surveillance can detect local LRI-outbreaks in a timely manner, independent of laboratory-based outbreak detection. Furthermore, since comparatively few new clusters per year were observed that would prompt investigation, syndromic hospital-surveillance could be a valuable tool for detection of local LRI-outbreaks. (aut. ref.

Limited effect of highly active antiretroviral therapy among HIV-positive injecting drug users on the population level

There is evidence that HIV-positive injecting drug users benefit less than other risk groups from highly active antiretroviral therapy that has been available since 1996. In this multicentre European study the impact of the availability of highly active antiretroviral therapy on the progression rates to AIDS and death among injecting drug users with a documented date of HIV seroconversion is studied. After highly active antiretroviral therapy became available the risk of AIDS and death for injecting drug users decreased by 28% and 36%, which is less than has been reported for other risk group

Converging evidence points towards a role of insulin signaling in regulating compulsive behavior.

Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder with childhood onset, and is characterized by intrusive thoughts and fears (obsessions) that lead to repetitive behaviors (compulsions). Previously, we identified insulin signaling being associated with OCD and here, we aim to further investigate this link in vivo. We studied TALLYHO/JngJ (TH) mice, a model of type 2 diabetes mellitus, to (1) assess compulsive and anxious behaviors, (2) determine neuro-metabolite levels by 1 H magnetic resonance spectroscopy (MRS) and brain structural connectivity by diffusion tensor imaging (DTI), and (3) investigate plasma and brain protein levels for molecules previously associated with OCD (insulin, Igf1, Kcnq1, and Bdnf) in these subjects. TH mice showed increased compulsivity-like behavior (reduced spontaneous alternation in the Y-maze) and more anxiety (less time spent in the open arms of the elevated plus maze). In parallel, their brains differed in the white matter microstructure measures fractional anisotropy (FA) and mean diffusivity (MD) in the midline corpus callosum (increased FA and decreased MD), in myelinated fibers of the dorsomedial striatum (decreased FA and MD), and superior cerebellar peduncles (decreased FA and MD). MRS revealed increased glucose levels in the dorsomedial striatum and increased glutathione levels in the anterior cingulate cortex in the TH mice relative to their controls. Igf1 expression was reduced in the cerebellum of TH mice but increased in the plasma. In conclusion, our data indicates a role of (abnormal) insulin signaling in compulsivity-like behavior

Effect of lactate administration on cerebral blood flow during hypoglycemia in people with type 1 diabetes

Introduction Impaired awareness of hypoglycemia, clinically reflected by the inability to timely detect hypoglycemia, affects approximately 25% of the people with type 1 diabetes. Both altered brain lactate handling and increased cerebral blood flow (CBF) during hypoglycemia appear to be involved in the pathogenesis of impaired awareness of hypoglycemia. Here we examine the effect of lactate on CBF during hypoglycemia. Research design and methods Nine people with type 1 diabetes and normal awareness of hypoglycemia underwent two hyperinsulinemic euglycemic-hypoglycemic (3.0 mmol/L) glucose clamps in a 3T MR system, once with sodium lactate infusion and once with sodium chloride infusion. Global and regional changes in CBF were determined using pseudocontinuous arterial spin labeling. Results Lactate (3.3±0.6 vs 0.9±0.2 mmol/L during lactate infusion vs placebo infusion, respectively) suppressed the counter-regulatory hormone responses to hypoglycemia. Global CBF increased considerably in response to intravenous lactate infusion but did not further increase during hypoglycemia. Lactate also blunted the hypoglycemia-induced regional redistribution of CBF towards the thalamus. Conclusions Elevated lactate levels enhance global CBF and blunt the thalamic CBF response during hypoglycemia in patients with type 1 diabetes, mimicking observations of impaired awareness of hypoglycemia. These findings suggest that alteration of CBF associated with lactate may play a role in some aspects of the development of impaired awareness of hypoglycemia. Trial registration number NCT03730909

Comparing Pandemic to Seasonal Influenza Mortality: Moderate Impact Overall but High Mortality in Young Children

Background: We assessed the severity of the 2009 influenza pandemic by comparing pandemic mortality to seasonal influenza mortality. However, reported pandemic deaths were laboratory-confirmed - and thus an underestimation - whereas seasonal influenza mortality is often more inclusively estimated. For a valid comparison, our study used the same statistical methodology and data types to estimate pandemic and seasonal influenza mortality. Methods and Findings: We used data on all-cause mortality (1999-2010, 100% coverage, 16.5 million Dutch population) and influenza-like-illness (ILI) incidence (0.8% coverage). Data was aggregated by week and age category. Using generalized estimating equation regression models, we attributed mortality to influenza by associating mortality with ILI-incidence, while adjusting for annual shifts in association. We also adjusted for respiratory syncytial virus, hot/cold weather, other seasonal factors and autocorrelation. For the 2009 pandemic season, we estimated 612 (range 266-958) influenza-attributed deaths; for seasonal influen

Excess mortality among the elderly in european countries, December 2014 to February 2015

Since December 2014 and up to February 2015, the weekly number of excess deaths from all-causes among individuals ≥ 65 years of age in 14 European countries have been significantly higher than in the four previous winter seasons. The rise in unspecified excess mortality coincides with increased proportion of influenza detection in the European influenza surveillance schemes with a main predominance of influenza A(H3N2) viruses seen throughout Europe in the current season, though cold snaps and other respiratory infections may also have had an effect

Pooling European all-cause mortality: methodology and findings for the seasons 2008/2009 to 2010/2011

Several European countries have timely all-cause mortality monitoring. However, small changes in mortality may not give rise to signals at the national level. Pooling data across countries may overcome this, particularly if changes in mortality occur simultaneously. Additionally, pooling may increase the power of monitoring populations with small numbers of expected deaths, e.g. younger age groups or fertile women. Finally, pooled analyses may reveal patterns of diseases across Europe. We describe a pooled analysis of all-cause mortality across 16 European countries. Two approaches were explored. In the ‘summarized' approach, data across countries were summarized and analysed as one overall country. In the ‘stratified' approach, heterogeneities between countries were taken into account. Pooling using the ‘stratified' approach was the most appropriate as it reflects variations in mortality. Excess mortality was observed in all winter seasons albeit slightly higher in 2008/09 than 2009/10 and 2010/11. In the 2008/09 season, excess mortality was mainly in elderly adults. In 2009/10, when pandemic influenza A(H1N1) dominated, excess mortality was mainly in children. The 2010/11 season reflected a similar pattern, although increased mortality in children came later. These patterns were less clear in analyses based on data from individual countries. We have demonstrated that with stratified pooling we can combine local mortality monitoring systems and enhance monitoring of mortality across Europ

European all-cause excess and influenza-attributable mortality in the 2017/18 season: should the burden of influenza B be reconsidered?

Objectives Weekly monitoring of European all-cause excess mortality, the EuroMOMO network, observed high excess mortality during the influenza B/Yamagata dominated 2017/18 winter season, especially among elderly. We describe all-cause excess and influenza-attributable mortality during the season 2017/18 in Europe. Methods Based on weekly reporting of mortality from 24 European countries or sub-national regions, representing 60% of the European population excluding the Russian and Turkish parts of Europe, we estimated age stratified all-cause excess morality using the EuroMOMO model. In addition, age stratified all-cause influenza-attributable mortality was estimated using the FluMOMO algorithm, incorporating influenza activity based on clinical and virological surveillance data, and adjusting for extreme temperatures. Results Excess mortality was mainly attributable to influenza activity from December 2017 to April 2018, but also due to exceptionally low temperatures in February-March 2018. The pattern and extent of mortality excess was similar to the previous A(H3N2) dominated seasons, 2014/15 and 2016/17. The 2017/18 overall all-cause influenza-attributable mortality was estimated to be 25.4 (95%CI 25.0-25.8) per 100,000 population; 118.2 (116.4-119.9) for persons aged 65. Extending to the European population this translates into over-all 152,000 deaths. Conclusions The high mortality among elderly was unexpected in an influenza B dominated season, which commonly are considered to cause mild illness, mainly among children. Even though A(H3N2) also circulated in the 2017/18 season and may have contributed to the excess mortality among the elderly, the common perception of influenza B only having a modest impact on excess mortality in the older population may need to be reconsidered.Peer Reviewe