Antimicrobial susceptibility of S. aureus strains isolated from a ham plant in France

As MRSA (methicillin resistant Staphylococcus aureus) were recently isolated from pigs in the Netherlands (1), we were incited to evaluate the resistance gene circulation inside S. aureus strains isolated from swine food products. A study, build in 2002, established the biodiversity of S. aureus isolates originated from a single raw ham industrial unit located in western France. Biotypes and pulsotypes from 106 isolates from raw material ham, end product and plant environment were determined. Isolates split up into 7 biotypes and about forty pulsotypes, which delineated a total of 23 sub-groups with 80% of homology and indicated the presence of numerous S. aureus strains in the plant

Consumption patterns and living conditions inside Het Steen, the late medieval prison of Malines (Mechelen, Belgium)

Excavations at the Main Square (Grote Markt) of Malines (Mechelen, Belgium) have unearthed the building remains of a tower, arguably identifiable as the former town prison: Het Steen. When this assumption is followed, the contents of the fills of two cesspits dug out in the cellars of the building illustrate aspects of daily life within the early 14th-century prison. An integrated approach of all find categories, together with the historical context available, illuminates aspects of the material culture of the users of the cesspits, their consumption patterns and the living conditions within the building

De visserskaai te Oostende (prov. West-Vlaanderen): archeologie van een in de 17de eeuw zwaar geteisterde stad

The Institute for the Archaeological Heritage of the Flemish Community (IAP) has, in close collaboration with the town of Ostend, carried out archaeological excavations during the construction works of the car park below the Visserskaai at Ostend from September 1998 till February 1999. This archaeological work mainly produced information on the eastern ramparts of Ostend and their evolution from the 16th century onwards together with information on the material culture of the inhabitants of Ostend during this same period. The town of Ostend had no defences until late in the 16th century as initial construction work for the defences only started in 1572 when the town came into northern hands. In the beginning of the 17th century Ostend managed to withstand successfully, with its newly built ramparts, for three years an overwhelming Spanish army siege. This was only possible thanks to the fact that the Spaniards never managed to seal of Ostend completely from the sea. As a result, victuals and soldiers arrived continuously at Ostend during the siege. It was only after the arrival of Spinola in the besieging camp, at the end of 1603, that Ostend was gradually forced to surrender. At the bottom of the excavated car park trench, some 4 m below the actual street level, wooden structures of the earthen ramparts were preserved (figs. 4-5). The presence of these con- firms historical data about the use of wood to strengthen the earthen ramparts. The excavations however documented mainly features from 2 bastions, the Peckels bastion and the Spanish bastion (fig. 2-3). Human burials and a gunpowder-magazine (figs. 7, 8, 10, 12) were uncovered in the Peckels bastion and human burials and an open-air rainwater reservoir were detected in the Spanish bastion. The human burials are studied elsewhere in this volume together with other post-medieval burials from Ostend recently discovered outside regular cemeteries. Archaeological material found in connection with the gunpowder-magazine in the Peckelf bastion dates from the 2nd half of the 16th /1st half of the 17th century (figs. 6,9,13-15) and suggests that the construction of this gunpowder-magazine? has to be situated somewhere in the middle of the 17th century, in other words in the period when the town defences of Ostend were adapted to new standards after the above- mentioned siege. A typical object related to the siege is a funnel-shaped gunpowder-flask in a copper-alloy (fig. 6). The inner wall of the gunpowder-magazine was erected on a framework of horizontal wooden beams, which were themselves resting on vertically placed and sharpened beams, mainly in oak (fig. 8). A dendrochronological analysis of the vertically placed beams produced a terminus post quem, which is far too early to be of any help in the discussion on the gunpowder-magazine. The technical differences between the inner and outer wall of the gunpowder-magazine suggest at least 2 phases for this building. The above-mentioned ceramics consist of redwares, Rhenish stone- wares a.o. Raeren, maiolicas, Weser slipwares, olive jars from Seville and some whitewares with green or yellow glaze. The archaeological material from the open- air rainwater reservoir in the Spanish bastion dates from the 2nd half of the 17th/1st half of the 19th century but mainly from the 18th century (figs. 16-32). The collection of ceramics from this context is largely dominated by tablewares. Among these stonewares are nearly missing and replaced by faience, china and industrial white- wares (pearl and cream wares). Maiolica has been nearly completely replaced by faience. Maiolicas remain in fact only important as wall-tiles. The collection contains some olive jars from Seville, a bowl from Dèsvres and a few products from Beauvais. The collection of china mainly consists of cups and small dishes in blue and white china. The china has been brought to Ostend in great quantities in the 18th century, first by the Ostend Company and later by mariners from Ostend in Foreign Service, mainly as ship's ballast. Besides ceramics this context also produced several finds in leather, glass, stone and metal. The leather finds mainly consist of shoes. The glass collection is largely dominated by cylindrical and globular bottles of which one was still intact including its cork (fig. 26: 1). Metal is represented by 22 cast iron cannon balls (fig. 28) and by a standard measure for bottles from an unidentified town inspector of measures and weights of Ostend with GS initials (fig. 27: 8). Small quantities of animal remains were found dispersed over many contexts within the site's stratigraphy. Only three of them are meaningful: a deposit found under the floor of the gunpowder-magazine (table 1: context A), an assemblage excavated in leveling layers within the Peckels bastion (table 1: context B), and material found in the water reservoir in the Spanish bastion (table 1: context C). All connections consisted of larger material; sieved samples did not yield meaningful numbers of smaller animal remains. Context A dates from the second half of the 16th to the first half of the 17th century and consists of consumption refuse: marine molluscs, marine fish bones, bird bone and the remains of cattle, sheep and pig. Context B is contemporaneous to context A and also represents consumption refuse with a similar composition. Remarkable are only a series of vertebrae of a large specimen of ling, a fish that must have been caught in northern waters, and a number of skeletal elements of a gurnard species. Context C has a younger date (second half of the 17th century to the first half of the 19th century) and has a mixed origin in terms of the taphonomy of the animal remains. Not only consumption refuse is present but also parts of the skeletons of at least four dogs and a horse. It is possible that all three contexts represent secondary refuse; in any case their provenance remains unknown. The material certainly has limited value for the interpretation of former consumption patterns. A feature of special interest is the presence of a few cowrie shells. Several aspects of the material culture reflect the maritime character of the town: the presence of several imports such as olive jars from Seville and specific objects as a token in lead (fig. 13: 16) probably used by skippers for the payment of fees and/or tolls. The presence of an important percentage of china and of some cowrie shells is probably related to the activities of the Ostend Company in the l8th century. The pottery discovered from both contexts (2nd half 16th century/ 1 st half 17th century and 2nd half 17th century/ 1st half 19th century) follows the general trends described for post-medieval Flanders

Effectiveness of a multimodal intervention in functionally impaired older people with type 2 diabetes mellitus

Background: Type 2 diabetes, a highly prevalent chronic disease, is associated with increasing frailty and functional decline in older people. We aimed to evaluate the effectiveness of a multimodal intervention on functional performance in frail and pre-frail participants aged >= 70 years with type 2 diabetes mellitus. Methods: The MID-Frail study was a cluster-randomized multicenter clinical trial conducted in 74 trial sites across seven European countries. The trial recruited 964 participants who were aged >70 years [mean age in intervention group, 78.4 (SD 5.6) years, 49.2% male and 77.6 (SD 5.29) years, 52.4% male in usual care group], with type diabetes mellitus and determined to be frail or pre-frail using Fried's frailty phenotype. Participants were allocated by trial site to follow either usual care (UCG) or intervention procedures (IG). Intervention group participants received a multimodal intervention composed of (i) an individualized and progressive resistance exercise programme for 16 weeks; (ii) a structured diabetes and nutritional educational programme over seven sessions; and (iii) Investigator-linked training to ensure optimal diabetes care. Short Physical Performance Battery (SPPB) scores were used to assess change in functional performance at 12 months between the groups. An analysis of the cost-effectiveness of the intervention was undertaken using the incremental cost-effectiveness ratio (ICER). Secondary outcomes included mortality, hospitalization, institutionalization, quality of life, burden on caregivers, the frequency and severity of hypoglycaemia episodes, and the cost-effectiveness of the intervention. Results: After 12 months, IG participants had mean SPPB scores 0.85 points higher than those in the UCG (95% CI, 0.44 to 1.26, P < 0.0001). Dropouts were higher in frail participants and in the intervention group, but significant differences in SPPB between treatment groups remained consistent after sensitivity analysis. Estimates suggest a mean saving following intervention of 428.02 EUR (2016) per patient per year, with ICER analysis indicating a consistent benefit of the described health care intervention over usual care. No statistically significant differences between groups were detected in any of the other secondary outcomes. Conclusions: We have demonstrated that a 12 month structured multimodal intervention programme across several clinical settings in different European countries leads to a clinically relevant and cost-effective improvement in the functional status of older frail and pre-frail participants with type 2 diabetes mellitus

Clinical and organizational factors associated with mortality during the peak of first COVID-19 wave: the global UNITE-COVID study

Purpose: To accommodate the unprecedented number of critically ill patients with pneumonia caused by coronavirus disease 2019 (COVID-19) expansion of the capacity of intensive care unit (ICU) to clinical areas not previously used for critical care was necessary. We describe the global burden of COVID-19 admissions and the clinical and organizational characteristics associated with outcomes in critically ill COVID-19 patients. Methods: Multicenter, international, point prevalence study, including adult patients with SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) and a diagnosis of COVID-19 admitted to ICU between February 15th and May 15th, 2020. Results: 4994 patients from 280 ICUs in 46 countries were included. Included ICUs increased their total capacity from 4931 to 7630 beds, deploying personnel from other areas. Overall, 1986 (39.8%) patients were admitted to surge capacity beds. Invasive ventilation at admission was present in 2325 (46.5%) patients and was required during ICU stay in 85.8% of patients. 60-day mortality was 33.9% (IQR across units: 20%–50%) and ICU mortality 32.7%. Older age, invasive mechanical ventilation, and acute kidney injury (AKI) were associated with increased mortality. These associations were also confirmed specifically in mechanically ventilated patients. Admission to surge capacity beds was not associated with mortality, even after controlling for other factors. Conclusions: ICUs responded to the increase in COVID-19 patients by increasing bed availability and staff, admitting up to 40% of patients in surge capacity beds. Although mortality in this population was high, admission to a surge capacity bed was not associated with increased mortality. Older age, invasive mechanical ventilation, and AKI were identified as the strongest predictors of mortality

Co-infection and ICU-acquired infection in COIVD-19 ICU patients: a secondary analysis of the UNITE-COVID data set

Background: The COVID-19 pandemic presented major challenges for critical care facilities worldwide. Infections which develop alongside or subsequent to viral pneumonitis are a challenge under sporadic and pandemic conditions; however, data have suggested that patterns of these differ between COVID-19 and other viral pneumonitides. This secondary analysis aimed to explore patterns of co-infection and intensive care unit-acquired infections (ICU-AI) and the relationship to use of corticosteroids in a large, international cohort of critically ill COVID-19 patients.Methods: This is a multicenter, international, observational study, including adult patients with PCR-confirmed COVID-19 diagnosis admitted to ICUs at the peak of wave one of COVID-19 (February 15th to May 15th, 2020). Data collected included investigator-assessed co-infection at ICU admission, infection acquired in ICU, infection with multi-drug resistant organisms (MDRO) and antibiotic use. Frequencies were compared by Pearson's Chi-squared and continuous variables by Mann-Whitney U test. Propensity score matching for variables associated with ICU-acquired infection was undertaken using R library MatchIT using the "full" matching method.Results: Data were available from 4994 patients. Bacterial co-infection at admission was detected in 716 patients (14%), whilst 85% of patients received antibiotics at that stage. ICU-AI developed in 2715 (54%). The most common ICU-AI was bacterial pneumonia (44% of infections), whilst 9% of patients developed fungal pneumonia; 25% of infections involved MDRO. Patients developing infections in ICU had greater antimicrobial exposure than those without such infections. Incident density (ICU-AI per 1000 ICU days) was in considerable excess of reports from pre-pandemic surveillance. Corticosteroid use was heterogenous between ICUs. In univariate analysis, 58% of patients receiving corticosteroids and 43% of those not receiving steroids developed ICU-AI. Adjusting for potential confounders in the propensity-matched cohort, 71% of patients receiving corticosteroids developed ICU-AI vs 52% of those not receiving corticosteroids. Duration of corticosteroid therapy was also associated with development of ICU-AI and infection with an MDRO.Conclusions: In patients with severe COVID-19 in the first wave, co-infection at admission to ICU was relatively rare but antibiotic use was in substantial excess to that indication. ICU-AI were common and were significantly associated with use of corticosteroids

Effect of anti-interleukin drugs in patients with COVID-19 and signs of cytokine release syndrome (COV-AID): a factorial, randomised, controlled trial.

BACKGROUND: Infections with SARS-CoV-2 continue to cause significant morbidity and mortality. Interleukin (IL)-1 and IL-6 blockade have been proposed as therapeutic strategies in COVID-19, but study outcomes have been conflicting. We sought to study whether blockade of the IL-6 or IL-1 pathway shortened the time to clinical improvement in patients with COVID-19, hypoxic respiratory failure, and signs of systemic cytokine release syndrome. METHODS: We did a prospective, multicentre, open-label, randomised, controlled trial, in hospitalised patients with COVID-19, hypoxia, and signs of a cytokine release syndrome across 16 hospitals in Belgium. Eligible patients had a proven diagnosis of COVID-19 with symptoms between 6 and 16 days, a ratio of the partial pressure of oxygen to the fraction of inspired oxygen (PaO(2):FiO(2)) of less than 350 mm Hg on room air or less than 280 mm Hg on supplemental oxygen, and signs of a cytokine release syndrome in their serum (either a single ferritin measurement of more than 2000 μg/L and immediately requiring high flow oxygen or mechanical ventilation, or a ferritin concentration of more than 1000 μg/L, which had been increasing over the previous 24 h, or lymphopenia below 800/mL with two of the following criteria: an increasing ferritin concentration of more than 700 μg/L, an increasing lactate dehydrogenase concentration of more than 300 international units per L, an increasing C-reactive protein concentration of more than 70 mg/L, or an increasing D-dimers concentration of more than 1000 ng/mL). The COV-AID trial has a 2 × 2 factorial design to evaluate IL-1 blockade versus no IL-1 blockade and IL-6 blockade versus no IL-6 blockade. Patients were randomly assigned by means of permuted block randomisation with varying block size and stratification by centre. In a first randomisation, patients were assigned to receive subcutaneous anakinra once daily (100 mg) for 28 days or until discharge, or to receive no IL-1 blockade (1:2). In a second randomisation step, patients were allocated to receive a single dose of siltuximab (11 mg/kg) intravenously, or a single dose of tocilizumab (8 mg/kg) intravenously, or to receive no IL-6 blockade (1:1:1). The primary outcome was the time to clinical improvement, defined as time from randomisation to an increase of at least two points on a 6-category ordinal scale or to discharge from hospital alive. The primary and supportive efficacy endpoints were assessed in the intention-to-treat population. Safety was assessed in the safety population. This study is registered online with ClinicalTrials.gov (NCT04330638) and EudraCT (2020-001500-41) and is complete. FINDINGS: Between April 4, and Dec 6, 2020, 342 patients were randomly assigned to IL-1 blockade (n=112) or no IL-1 blockade (n=230) and simultaneously randomly assigned to IL-6 blockade (n=227; 114 for tocilizumab and 113 for siltuximab) or no IL-6 blockade (n=115). Most patients were male (265 [77%] of 342), median age was 65 years (IQR 54-73), and median Systematic Organ Failure Assessment (SOFA) score at randomisation was 3 (2-4). All 342 patients were included in the primary intention-to-treat analysis. The estimated median time to clinical improvement was 12 days (95% CI 10-16) in the IL-1 blockade group versus 12 days (10-15) in the no IL-1 blockade group (hazard ratio [HR] 0·94 [95% CI 0·73-1·21]). For the IL-6 blockade group, the estimated median time to clinical improvement was 11 days (95% CI 10-16) versus 12 days (11-16) in the no IL-6 blockade group (HR 1·00 [0·78-1·29]). 55 patients died during the study, but no evidence for differences in mortality between treatment groups was found. The incidence of serious adverse events and serious infections was similar across study groups. INTERPRETATION: Drugs targeting IL-1 or IL-6 did not shorten the time to clinical improvement in this sample of patients with COVID-19, hypoxic respiratory failure, low SOFA score, and low baseline mortality risk. FUNDING: Belgian Health Care Knowledge Center and VIB Grand Challenges program

Early mobilisation in critically ill COVID-19 patients: a subanalysis of the ESICM-initiated UNITE-COVID observational study

Background Early mobilisation (EM) is an intervention that may improve the outcome of critically ill patients. There is limited data on EM in COVID-19 patients and its use during the first pandemic wave. Methods This is a pre-planned subanalysis of the ESICM UNITE-COVID, an international multicenter observational study involving critically ill COVID-19 patients in the ICU between February 15th and May 15th, 2020. We analysed variables associated with the initiation of EM (within 72 h of ICU admission) and explored the impact of EM on mortality, ICU and hospital length of stay, as well as discharge location. Statistical analyses were done using (generalised) linear mixed-effect models and ANOVAs. Results Mobilisation data from 4190 patients from 280 ICUs in 45 countries were analysed. 1114 (26.6%) of these patients received mobilisation within 72 h after ICU admission; 3076 (73.4%) did not. In our analysis of factors associated with EM, mechanical ventilation at admission (OR 0.29; 95% CI 0.25, 0.35; p = 0.001), higher age (OR 0.99; 95% CI 0.98, 1.00; p ≤ 0.001), pre-existing asthma (OR 0.84; 95% CI 0.73, 0.98; p = 0.028), and pre-existing kidney disease (OR 0.84; 95% CI 0.71, 0.99; p = 0.036) were negatively associated with the initiation of EM. EM was associated with a higher chance of being discharged home (OR 1.31; 95% CI 1.08, 1.58; p = 0.007) but was not associated with length of stay in ICU (adj. difference 0.91 days; 95% CI − 0.47, 1.37, p = 0.34) and hospital (adj. difference 1.4 days; 95% CI − 0.62, 2.35, p = 0.24) or mortality (OR 0.88; 95% CI 0.7, 1.09, p = 0.24) when adjusted for covariates. Conclusions Our findings demonstrate that a quarter of COVID-19 patients received EM. There was no association found between EM in COVID-19 patients' ICU and hospital length of stay or mortality. However, EM in COVID-19 patients was associated with increased odds of being discharged home rather than to a care facility. Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021)