Background
Treatment outside office hours has been associated with increased workflow times for intravenous thrombolysis (IVT) in acute ischemic stroke (AIS). Limited data suggest that this ...“off-hours effect” also exists for endovascular treatment (EVT). We investigated this phenomenon in a well-organized acute stroke care region in the Netherlands.
Methods
Retrospective, observational cohort study of consecutive patients with AIS who received reperfusion therapy in the Greater Amsterdam Area, consisting of 14 primary stroke centers and 1 comprehensive stroke center (IVT: 2009–2015, EVT: 2014–2017). Office hours were defined as presentation during weekdays between 8 AM and 5 PM, excluding National Festive days. Primary outcome was door-to-treatment time (door-to-needle DNT for IVT, door-to-groin DGT for EVT). For DGT, we used the door time of the first hospital. Other outcomes were in-hospital mortality, modified Rankin Scale (mRS) score at 90 days and symptomatic intracranial hemorrhage (sICH). We performed multivariable linear and logistic regression analyses and used multiple imputation to account for missing values.
Results
In total, 59% (2450/4161) and 61% (239/395) of patients treated with IVT and EVT, respectively, presented outside office hours. Median DNT was minimally longer outside office hours (32 vs. 30 min,
p
= 0.024, adjusted difference 2.5 min, 95% CI 0.7–4.2). Presentation outside office hours was not associated with a longer DGT (median 130 min for both groups, adjusted difference 7.0 min, 95% CI − 4.2 to 18.1). Clinical outcome and sICH rate also did not differ.
Conclusion
Presentation outside office hours did not lead to clinically relevant treatment delays for reperfusion therapy in patients with AIS.
In children with anorectal malformations (ARM), additional anomalies can occur within the VACTERL-association. Routine screening is of great importance for early identification and potential ...treatment. However, uniformity in screening protocols is lacking and only small cohorts have been described in literature. The aim of this study was to assess and describe a unique large cohort of ARM patients who underwent VACTERL screening in the neonatal period.
A retrospective mono-center cohort study was performed. Included were all neonates born between January 2000 and December 2020 who were diagnosed with ARM and screened for additional anomalies. Full screening consisted of x-ray and ultrasound of the spine, cardiac and renal ultrasound, and physical examination for limb deformities, esophageal atresia, and ARM. Criteria for VACTERL-classification were predefined according to the EUROCAT-definitions.
In total, 216 patients were included, of whom 167 (77.3%) underwent full VACTERL-screening (66% in 2000–2006 vs. 82% in 2007–2013 vs. 86% in 2014–2020). Median age at follow-up was 7.0 years (IQR 3.0–12.8). In 103/167 patients (61.7%), additional anomalies were identified. Some 35/216 patients (16.2%) fulfilled the criteria of a form of VACTERL-association. In 37/216 patients (17.1%), a genetic cause or syndrome was found.
The majority of ARM patients underwent full screening to detect additional anomalies (77%), which improved over time to 86%. Yet, approximately a quarter of patients was not screened, with the potential of missing important additional anomalies that might have severe consequences in the future. Forms of VACTERL-association or genetic causes were found in 16% and 17% respectively. This study emphasizes the importance of routine screening.
III.
•ARM can occur as isolated anomaly, or as part of VACTERL-association or syndromes. Additional anomalies can occur.•62% of the ARM patients had additional anomalies. VACTERL-association or syndromes were found in 16% and 17% respectively.
Abstract A double-blind, placebo-controlled phase II trial (e-Track 444563-014/ NCT00346892 ) was conducted in South Africa to evaluate the co-administration of RIX4414 (live-attenuated human G1P8 ...rotavirus vaccine) and oral poliovirus vaccine (OPV) administered simultaneously. Healthy infants ( n = 450) were randomized into three groups (RIX4414 + OPV, RIX4414 + IPV or Placebo + OPV) to receive two oral doses of RIX4414/placebo with OPV or IPV using two vaccination schedules (6–10 weeks and 10–14 weeks). Serum anti-rotavirus IgA antibodies (ELISA) and neutralizing antibodies (micro-neutralization assay) to poliovirus serotypes 1, 2 and 3 were measured. Co-administration of RIX4414 with OPV did not result in a decrease in the high sero-protection rates against poliovirus serotypes 1, 2 and 3 detected after the third OPV dose (98–100%). The anti-rotavirus IgA antibody sero-conversion rates were higher for the 10–14 weeks schedule (55–61%) compared to the 6–10 weeks schedule (36–43%). Solicited symptoms were reported at similar rates between RIX4414 and placebo groups and no serious adverse events related to RIX4414 were reported. This study provided evidence that RIX4414 can be co-administered with routine EPI immunizations including OPV and that two doses of RIX4414 were well tolerated and immunogenic in South African infants.
In the current concept of bacterial infections, pathogen-associated molecular patterns (PAMPs) derived from pathogens and damage-associated molecular patterns (DAMPs) released from damaged/necrotic ...host cells are crucial factors in induction of innate immune responses. However, the implication of DAMPs in apical and marginal periodontitis is unknown. Serum amyloid A (SAA) is a DAMP that is involved in the development of various chronic inflammatory diseases, such as rheumatoid arthritis. In the present study, we tested whether SAA is involved in the pathogenesis of periapical lesions, using human periapical surgical specimens and mice deficient in SAA and Toll-like receptors (TLR). SAA1/2 was locally expressed in human periapical lesions at the mRNA and protein levels. The level of SAA protein appeared to be positively associated with the inflammatory status of the lesions. In the development of mouse periapical inflammation, SAA1.1/2.1 was elevated locally and systemically in wild-type (WT) mice. Although SAA1.1/2.1 double-knockout and SAA3 knockout mice had redundant attenuation of the extent of periapical lesions, these animals showed strikingly improved inflammatory cell infiltration versus WT. Recombinant human SAA1 (rhSAA1) directly induced chemotaxis of WT neutrophils in a dose-dependent manner in vitro. In addition, rhSAA1 stimulation significantly prolonged the survival of WT neutrophils as compared with nonstimulated neutrophils. Furthermore, rhSAA1 activated the NF-κB pathway and subsequent IL-1α production in macrophages in a dose-dependent manner. However, TLR2/TLR4 double deficiency substantially diminished these SAA-mediated proinflammatory responses. Taken together, the SAA-TLR axis plays an important role in the chronicity of periapical inflammation via induction of inflammatory cell infiltration and prolonged cell survival. The interactions of PAMPs and DAMPs require further investigation in dental/oral inflammation.
Abstract The socio-relational focus of youth peer support workers (YPSWs) poses a challenge when YPSWs are embedded in medical oriented contexts common to child and adolescent mental health services ...(CAMHS); as it requires YPSWs to find a balance between being a peer on one hand, and adhering to professional boundaries and medical standards set out by CAMHS on the other. To create a suitable position for YPSWs in CAMHS, this study investigated the unique socio-relational contributions YPSWs can make to CAMHS in addition to clinicians, and identified how these contributions can be embedded within CAMHS. This study reports on 37 semi-structured interviews conducted in the Netherlands with youth (n = 10), YPSWs (n = 10), and clinicians (n = 17). Overall, the unique socio-relational contributions YPSWs can make include: their ability to build authentic trusting relationships with youth by providing empowerment, promoting autonomy, valuing stillness in recovery, reducing isolation, recognizing strengths, and navigating life inside and outside of (residential) mental healthcare and beyond classification. Moreover, prerequisites to safeguard the integration of YPSWs and these socio-relational contributions were also identified, including YPSWs achieving stability in recovery, recent lived experiences with mental health challenges, and organizational support in terms of suitable treatment climate, resources to enhance flexibility of YPSWs, and shared goals regarding youth peer support work. Overall, YPSWs view youth holistically and foster a connection with youth based on youthfulness and recent lived experience. Involving YPSWs is an important step forward to drive positive transformation in CAMHS.
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A multivariate statistical process control (MSPC) strategy was developed for the monitoring of the ConsiGma™-25 continuous tablet manufacturing line. Thirty-five logged variables ...encompassing three major units, being a twin screw high shear granulator, a fluid bed dryer and a product control unit, were used to monitor the process. The MSPC strategy was based on principal component analysis of data acquired under normal operating conditions using a series of four process runs. Runs with imposed disturbances in the dryer air flow and temperature, in the granulator barrel temperature, speed and liquid mass flow and in the powder dosing unit mass flow were utilized to evaluate the model’s monitoring performance. The impact of the imposed deviations to the process continuity was also evaluated using Hotelling’s T2 and Q residuals statistics control charts. The influence of the individual process variables was assessed by analyzing contribution plots at specific time points. Results show that the imposed disturbances were all detected in both control charts. Overall, the MSPC strategy was successfully developed and applied. Additionally, deviations not associated with the imposed changes were detected, mainly in the granulator barrel temperature control.
Evolution of Avian Influenza (AI) viruses--especially of the Highly Pathogenic Avian Influenza (HPAI) H5N1 subtype--is a major issue for the poultry industry. HPAI H5N1 epidemics are associated with ...huge economic losses and are sometimes connected to human morbidity and mortality. Vaccination (either as a preventive measure or as a means to control outbreaks) is an approach that splits the scientific community, due to the risk of it being a potential driving force in HPAI evolution through the selection of mutants able to escape vaccination-induced immunity. It is therefore essential to study how mutations are selected due to immune pressure. To this effect, we performed an in vitro selection of mutants from HPAI A/turkey/Turkey/1/05 (H5N1), using immune pressure from homologous polyclonal sera. After 42 rounds of selection, we identified 5 amino acid substitutions in the Haemagglutinin (HA) protein, most of which were located in areas of antigenic importance and suspected to be prone to selection pressure. We report that most of the mutations took place early in the selection process. Finally, our antigenic cartography studies showed that the antigenic distance between the selected isolates and their parent strain increased with passage number.
Correct classification of the source of infection is important in observational and interventional studies of sepsis. Centers for Disease Control and Prevention criteria are most commonly used for ...this purpose, but the robustness of these definitions in critically ill patients is not known. We hypothesized that in a mixed ICU population, the performance of these criteria would be generally reduced and would vary among diagnostic subgroups.
Prospective cohort.
Data were collected as part of a cohort of 1,214 critically ill patients admitted to two hospitals in The Netherlands between January 2011 and June 2011.
Eight observers assessed a random sample of 168 of 554 patients who had experienced at least one infectious episode in the ICU. Each patient was assessed by two randomly selected observers who independently scored the source of infection (by affected organ system or site), the plausibility of infection (rated as none, possible, probable, or definite), and the most likely causative pathogen. Assessments were based on a post hoc review of all available clinical, radiological, and microbiological evidence. The observed diagnostic agreement for source of infection was classified as partial (i.e., matching on organ system or site) or complete (i.e., matching on specific diagnostic terms), for plausibility as partial (2-point scale) or complete (4-point scale), and for causative pathogens as an approximate or exact pathogen match. Interobserver agreement was expressed as a concordant percentage and as a kappa statistic.
None.
A total of 206 infectious episodes were observed. Agreement regarding the source of infection was 89% (183/206) and 69% (142/206) for a partial and complete diagnostic match, respectively. This resulted in a kappa of 0.85 (95% CI, 0.79-0.90). Agreement varied from 63% to 91% within major diagnostic categories and from 35% to 97% within specific diagnostic subgroups, with the lowest concordance observed in cases of ventilator-associated pneumonia. In the 142 episodes for which a complete match on source of infection was obtained, the interobserver agreement for plausibility of infection was 83% and 65% on a 2- and 4-point scale, respectively. For causative pathogen, agreement was 78% and 70% for an approximate and exact pathogen match, respectively.
Interobserver agreement for classifying sources of infection using Centers for Disease Control and Prevention criteria was excellent overall. However, full concordance on all aspects of the diagnosis between independent observers was rare for some types of infection, in particular for ventilator-associated pneumonia.
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