Population-based screening in a municipality after a primary school outbreak of the SARSCoV-2 Alpha variant, the Netherlands, December 2020–February 2021

An outbreak of SARS-CoV-2 Alpha variant (Pango lineage B.1.1.7) was detected at a primary school (School X) in Lansingerland, the Netherlands, in December 2020. The outbreak was studied retrospectively, and population-based screening was used to assess the extent of virus circulation and decelerate transmission. Cases were SARS-CoV-2 laboratory confirmed and were residents of Lansingerland (November 16(th) 2020 until February 22(th) 2021), or had an epidemiological link with School X or neighbouring schools. The SARS-CoV-2 variant was determined using variant PCR or whole genome sequencing. A questionnaire primarily assessed clinical symptoms. A total of 77 Alpha variant cases were found with an epidemiological link to School X, 16 Alpha variant cases linked to the neighbouring schools, and 146 Alpha variant cases among residents of Lansingerland without a link to the schools. The mean number of self-reported symptoms was not significantly different among Alpha variant infected individuals compared to non-Alpha infected individuals. The secondary attack rate (SAR) among Alpha variant exposed individuals in households was 52% higher compared to non-Alpha variant exposed individuals (p = 0.010), with the mean household age, and mean number of children and adults per household as confounders. Sequence analysis of 60 Alpha variant sequences obtained from cases confirmed virus transmission between School X and neighbouring schools, and showed that multiple introductions of the Alpha variant had already taken place in Lansingerland at the time of the study. The alpha variant caused a large outbreak at both locations of School X, and subsequently spread to neighbouring schools, and households. Population-based screening (together with other public health measures) nearly stopped transmission of the outbreak strain, but did not prevent variant replacement in the Lansingerland municipality

Multiproxy analysis of permafrost preserved faeces provides an unprecedented insight into the diets and habitats of extinct and extant megafauna

The study of faecal samples to reconstruct the diets and habitats of extinct megafauna has traditionally relied on pollen and macrofossil analysis. DNA metabarcoding has emerged as a valuable tool to complement and refine these proxies. While published studies have compared the results of these three proxies for sediments, this comparison is currently lacking for permafrost preserved mammal faeces. Moreover, most metabarcoding studies have focused on a single plant-specific DNA marker region. In this study, we target both the commonly used chloroplast trnL P6 loop as well as nuclear ribosomal ITS (nrITS). The latter can increase taxonomic resolution of plant identifications but requires DNA to be relatively well preserved because of the target length (∼300–500 bp). We compare DNA results to pollen and macrofossil analyses from permafrost and ice-preserved faeces of Pleistocene and Holocene megafauna. Samples include woolly mammoth, horse, steppe bison as well as Holocene and extant caribou. Most plant identifications were found using DNA, likely because the studied faeces contained many vegetative remains that could not be identified using macrofossils or pollen. Several taxa were, however, identified to lower taxonomic levels uniquely with macrofossil and pollen analysis. The nrITS marker provides species level taxonomic resolution for commonly encountered plant families that are hard to distinguish using the other proxies (e.g. Asteraceae, Cyperaceae and Poaceae). Integrating the results from all proxies, we are able to accurately reconstruct known diets and habitats of the extant caribou. Applying this approach to the extinct mammals, we find that the Holocene horse and steppe bison were not strict grazers but mixed feeders living in a marshy wetland environment. The mammoths showed highly varying diets from different non-analogous habitats. This confirms the presence of a mosaic of habitats in the Pleistocene ‘mammoth steppe’ that mammoths could fully exploit due to their flexibility in food choice

Voice outcome after unilateral ELS type III or bilateral type II resections for T1-T2 glottic carcinoma: Results after 1 year

Abstract Background: Voice outcome was assessed in patients with extended T1 and limited T2 glottic carcinoma, treated with a unilateral type III or a bilateral type II resection according to the European Laryngological Society (ELS) classification. Methods: Objective evaluation (acoustic and aerodynamic parameters), perceptual evaluation (GRBAS), and patients' self-assessment (voice handicap index [VHI]) were performed before and 1 year after treatment. Results were evaluated according to ELS resection type and the involvement of the anterior commissure. Results: The majority of voice parameters in all resection subgroups showed an improvement of the mean score 1 year postoperatively. Grade of dysphonia varied between 1.15 and 1.66 postoperatively and VHI score varied from 23.3 to 24.5. Conclusion: Voice outcome after ELS unilateral type III or a bilateral type II resection for extended T1 and limited T2 glottic carcinoma is good with mild to very moderate perceptive dysphonia and low self-reported voice impairment

2 days versus 5 days of postoperative antibiotics for complex appendicitis:a pragmatic, open-label, multicentre, non-inferiority randomised trial

Background: The appropriate duration of postoperative antibiotics for complex appendicitis is unclear. The increasing global threat of antimicrobial resistance warrants restrictive antibiotic use, which could also reduce side-effects, length of hospital stay, and costs. Methods: In this pragmatic, open-label, non-inferiority trial in 15 hospitals in the Netherlands, patients with complex appendicitis (aged ≥8 years) were randomly assigned (1:1) to receive 2 days or 5 days of intravenous antibiotics after appendicectomy. Randomisation was stratified by centre, and treating physicians and patients were not masked to treatment allocation. The primary endpoint was a composite endpoint of infectious complications and mortality within 90 days. The main outcome was the absolute risk difference (95% CI) in the primary endpoint, adjusted for age and severity of appendicitis, with a non-inferiority margin of 7·5%. Outcome assessment was based on electronic patient records and a telephone consultation 90 days after appendicectomy. Efficacy was analysed in the intention-to-treat and per-protocol populations. Safety outcomes were analysed in the intention-to-treat population. This trial was registered with the Netherlands Trial Register, NL5946. Findings: Between April 12, 2017, and June 3, 2021, 13 267 patients were screened and 1066 were randomly assigned, 533 to each group. 31 were excluded from intention-to-treat analysis of the 2-day group and 30 from the 5-day group owing to errors in recruitment or consent. Appendicectomy was done laparoscopically in 955 (95%) of 1005 patients. The telephone follow-up was completed in 664 (66%) of 1005 patients. The primary endpoint occurred in 51 (10%) of 502 patients analysed in the 2-day group and 41 (8%) of 503 patients analysed in the 5-day group (adjusted absolute risk difference 2·0%, 95% CI −1·6 to 5·6). Rates of complications and re-interventions were similar between trial groups. Fewer patients had adverse effects of antibiotics in the 2-day group (45 [9%] of 502 patients) than in the 5-day group (112 [22%] of 503 patients; odds ratio [OR] 0·344, 95% CI 0·237 to 0·498). Re-admission to hospital was more frequent in the 2-day group (58 [12%] of 502 patients) than in the 5-day group (29 [6%] of 503 patients; OR 2·135, 1·342 to 3·396). There were no treatment-related deaths. Interpretation: 2 days of postoperative intravenous antibiotics for complex appendicitis is non-inferior to 5 days in terms of infectious complications and mortality within 90 days, based on a non-inferiority margin of 7·5%. These findings apply to laparoscopic appendicectomy conducted in a well resourced health-care setting. Adopting this strategy will reduce adverse effects of antibiotics and length of hospital stay. Funding: The Netherlands Organization for Health Research and Development.</p

Severe Asthma Standard-of-Care Background Medication Reduction With Benralizumab: ANDHI in Practice Substudy

Background: The phase IIIb, randomized, parallel-group, placebo-controlled ANDHI double-blind (DB) study extended understanding of the efficacy of benralizumab for patients with severe eosinophilic asthma. Patients from ANDHI DB could join the 56-week ANDHI in Practice (IP) single-arm, open-label extension substudy. Objective: Assess potential for standard-of-care background medication reductions while maintaining asthma control with benralizumab. Methods: Following ANDHI DB completion, eligible adults were enrolled in ANDHI IP. After an 8-week run-in with benralizumab, there were 5 visits to potentially reduce background asthma medications for patients achieving and maintaining protocol-defined asthma control with benralizumab. Main outcome measures for non-oral corticosteroid (OCS)-dependent patients were the proportions with at least 1 background medication reduction (ie, lower inhaled corticosteroid dose, background medication discontinuation) and the number of adapted Global Initiative for Asthma (GINA) step reductions at end of treatment (EOT). Main outcomes for OCS-dependent patients were reductions in daily OCS dosage and proportion achieving OCS dosage of 5 mg or lower at EOT. Results: For non-OCS-dependent patients, 53.3% (n = 208 of 390) achieved at least 1 background medication reduction, increasing to 72.6% (n = 130 of 179) for patients who maintained protocol-defined asthma control at EOT. A total of 41.9% (n = 163 of 389) achieved at least 1 adapted GINA step reduction, increasing to 61.8% (n = 110 of 178) for patients with protocol-defined EOT asthma control. At ANDHI IP baseline, OCS dosages were 5 mg or lower for 40.4% (n = 40 of 99) of OCS-dependent patients. Of OCS-dependent patients, 50.5% (n = 50 of 99) eliminated OCS and 74.7% (n = 74 of 99) achieved dosages of 5 mg or lower at EOT. Conclusions: These findings demonstrate benralizumab's ability to improve asthma control, thereby allowing background medication reduction

Two versus five days of antibiotics after appendectomy for complex acute appendicitis (APPIC): Study protocol for a randomized controlled trial

Background: Acute appendicitis is one of the most common indications for emergency surgery. In patients with a complex appendicitis, prolonged antibiotic prophylaxis is recommended after appendectomy. There is no consensus regarding the optimum duration of antibiotics. Guidelines propose 3 to 7 days of treatment, but shorter courses may be as effective in the prevention of infectious complications. At the same time, the global issue of increasing antimicrobial resistance urges for optimization of antibiotic strategies. The aim of this study is to determine whether a short course (48 h) of postoperative antibiotics is non-inferior to current standard practice of 5 days. Methods: Patients of 8 years and older undergoing appendectomy for acute complex appendicitis - defined as a gangrenous and/or perforated appendicitis or appendicitis in presence of an abscess - are eligible for inclusion. Immunocompromised or pregnant patients are excluded, as well as patients with a contraindication to the study antibiotics. In total, 1066 patients will be randomly allocated in a 1:1 ratio to the experimental treatment arm (48 h of postoperative intravenously administered (IV) antibiotics) or the control arm (5 days of postoperative IV antibiotics). After discharge from the hospital, patients participate in a productivity-cost-questionnaire at 4 weeks and a standardized telephone follow-up at 90 days after appendectomy. The primary outcome is a composite endpoint of infectious complications, including intra-abdominal abscess (IAA) and surgical site infection (SSI), and mortality within 90 days after appendectomy. Secondary outcomes include IAA, SSI, restart of antibiotics, length of hospital stay (LOS), reoperation, percutaneous drainage, readmission rate, and cost-effectiveness. The non-inferiority margin for the difference in the primary endpoint rate is set at 7.5% (one-sided test at α 0.025). Both per-protocol and intention-to-treat analyses will be performed. Discussion: This trial will provide evidence on whether 48 h of postoperative antibiotics is non-inferior to a standard course of 5 days of antibiotics. If non-inferiority is established, longer intravenous administration following appendectomy for complex appendicitis can be abandoned, and guidelines need to be adjusted accordingly

D-Dimer Assessment to Predict Pulmonary Embolism in ICU Patients with COVID-19 Pneumonia

The value of D-dimer assessments in ICU patients with COVID-19 for the prediction of pulmonary embolism (PE) is unclear. The present study had two purposes: 1. To assess the specificity of elevated absolute D-dimer values for PE on admission to the ICU. 2. To assess the specificity of a D-dimer increment for the development of PE during an ICU stay. D-dimer values were paired with the results of a CT pulmonary angiogram (CTPA) and compared in patients with and without PE on admission. In patients without PE on initial imaging and available repeat CTPA during an ICU stay, D-dimer increments between initial and repeat imaging of patients developing PE during an ICU stay were compared with those with persistently no PE. On admission, D-dimers in patients with PE were higher than those in patients without PE (median 850 vs. 6060 μg/L; p p < 0.005). Using a cut-off of 8000 μg/L, specificity was 100% (CI 79.4–100%). Strongly elevated D-dimer values on admission and marked increases in D-dimer during ICU stays have a high specificity for predicting pulmonary embolism in critically ill COVID-19 patients

The potential of near real-time monitoring of β-d-glucuronidase activity to establish effective warning systems in urban recreational waters

Urban water is a crucial element of cities for the purpose of events and recreation, raising concern over the water quality and related hygienic safety. In this study, a near real-time monitoring system of the β-d-glucuronidase activity, the BACTcontrol, was tested in the canals of Breda city in the Netherlands in order to gain insight in its suitability to constitute part of an effective warning system for urban surface waters. Additionally, the qPCR method was also evaluated as a complementary method aiming at determining the E. coli or Bacteroides bacteria, while conventional culture-based measurements aiming at E. coli served as a reference. Analysis of the results obtained via monitoring and sampling during three consecutive bathing seasons revealed that the BACTcontrol demonstrated a timely but short response, implying that it was capable of detecting contamination peaks but not indicating when the water was hygienically safe again. This gap could be filled with qPCR measurements, which proved to provide reliable and fast results. Therefore, the combination of the BACTcontrol with qPCR measurements offers the opportunity to build an effective strategy concerning the use of urban surface waters for recreational purposes, based on timely information on the emergence and duration of contamination events.Sanitary Engineerin