Impact of the first COVID lockdown on accident- and injury-related pediatric intensive care admissions in Germany - a multicenter study

Children’s and adolescents’ lives drastically changed during COVID lockdowns worldwide. To compare accident- and injury-related admissions to pediatric intensive care units (PICU) during the first German COVID lockdown with previous years, we conducted a retrospective multicenter study among 37 PICUs (21.5% of German PICU capacities). A total of 1444 admissions after accidents or injuries during the first lockdown period and matched periods of 2017–2019 were reported and standardized morbidity ratios (SMR) were calculated. Total PICU admissions due to accidents/injuries declined from an average of 366 to 346 (SMR 0.95 (CI 0.85–1.05)). Admissions with trauma increased from 196 to 212 (1.07 (0.93–1.23). Traffic accidents and school/kindergarten accidents decreased (0.77 (0.57–1.02 and 0.26 (0.05–0.75)), whereas household and leisure accidents increased (1.33 (1.06–1.66) and 1.34 (1.06–1.67)). Less neurosurgeries and more visceral surgeries were performed (0.69 (0.38–1.16) and 2.09 (1.19–3.39)). Non-accidental non-suicidal injuries declined (0.73 (0.42–1.17)). Suicide attempts increased in adolescent boys (1.38 (0.51–3.02)), but decreased in adolescent girls (0.56 (0.32–0.79)). In summary, changed trauma mechanisms entailed different surgeries compared to previous years. We found no evidence for an increase in child abuse cases requiring intensive care. The increase in suicide attempts among boys demands investigation

Selective targeting of microglia by quantum dots

<p>Abstract</p> <p>Background</p> <p>Microglia, the resident immune cells of the brain, have been implicated in brain injury and various neurological disorders. However, their precise roles in different pathophysiological situations remain enigmatic and may range from detrimental to protective. Targeting the delivery of biologically active compounds to microglia could help elucidate these roles and facilitate the therapeutic modulation of microglial functions in neurological diseases.</p> <p>Methods</p> <p>Here we employ primary cell cultures and stereotaxic injections into mouse brain to investigate the cell type specific localization of semiconductor quantum dots (QDs) in vitro and in vivo. Two potential receptors for QDs are identified using pharmacological inhibitors and neutralizing antibodies.</p> <p>Results</p> <p>In mixed primary cortical cultures, QDs were selectively taken up by microglia; this uptake was decreased by inhibitors of clathrin-dependent endocytosis, implicating the endosomal pathway as the major route of entry for QDs into microglia. Furthermore, inhibiting mannose receptors and macrophage scavenger receptors blocked the uptake of QDs by microglia, indicating that QD uptake occurs through microglia-specific receptor endocytosis. When injected into the brain, QDs were taken up primarily by microglia and with high efficiency. In primary cortical cultures, QDs conjugated to the toxin saporin depleted microglia in mixed primary cortical cultures, protecting neurons in these cultures against amyloid beta-induced neurotoxicity.</p> <p>Conclusions</p> <p>These findings demonstrate that QDs can be used to specifically label and modulate microglia in primary cortical cultures and in brain and may allow for the selective delivery of therapeutic agents to these cells.</p

Study of the discovery potential for an invisibly decaying Higgs boson via the associated ZH production in the ATLAS experiment

The decay of a Higgs boson into invisible particles is well motivated in many extensions of the Standard Model. In this note an evaluation of the discovery potential of the ATLAS experiment for an invisibly decaying Higgs boson, produced in association with a Z boson, is discussed. In particular, the uncertainties related to the normalization of the dominant backgrounds are addressed

Valuing treatment with infliximab for ankylosing spondylitis using a willingness-to-pay approach

OBJECTIVE: To investigate willingness to pay (WTP) for treatment with infliximab by patients with ankylosing spondylitis (AS) and explore factors associated with WTP. METHODS: Data were used from 85 patients participating in the European AS Infliximab Cohort (EASIC) open-label extension of the AS Study for the Evaluation of Recombinant Infliximab Therapy (ASSERT). WTP was included at baseline of EASIC and comprised a hypothetical scenario exploring whether the patient would be willing to pay for beneficial effects of infliximab and, if so, what amount they would be willing to pay per administration. Factors associated with WTP were explored using zero-inflated negative binomial regressions (ZINB). RESULTS: Sixty-three of 85 patients (74.1%) were willing to pay, and among these the mean amount willing to pay was €275 (median €100) [interquartile range €50-200] per administration. Multivariable ZINB analysis showed that Assessment of SpondyloArthritis international Society 20 (ASAS20) response was associated with a 7-fold lower likelihood to pay zero euros (OR=0.14, 95%-confidence interval [95%CI] 0.03-0.71) and a 3-fold increase in the amount willing to pay (exp(B)=3.32, 95%CI 1.44-7.69). In addition, country of residence was associated with lower likelihood to pay zero euros (OR = 0.07, 95% CI 0.02-0.36), while increased age was associated with the amount willing to pay (exp(B)=1.05, 95%CI 1.01-1.09). CONCLUSION: In a hypothetical scenario, three quarter of patients with AS on long-term infliximab stated to be willing to pay an out-of-pocket contribution for this treatment. Treatment response contributed to the willingness as well as to the amount patients are willing to pay. This article is protected by copyright. All rights reserved

Longitudinal Analyses of Presenteeism and Its Role as a Predictor of Sick Leave in Patients With Ankylosing Spondylitis

ObjectiveTo investigate, in a cohort of patients with ankylosing spondylitis (AS) adequately treated with infliximab, changes over time in presenteeism and the role of presenteeism relative to that of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Bath Ankylosing Spondylitis Functional Index (BASFI) in predicting sick leave. MethodsData were analyzed from 71 patients with paid work and taking a stable dose of infliximab participating in a 96-week study with 5 assessment points. Covariates included presenteeism, sick leave, time, sex, age, BASDAI, BASFI, Bath Ankylosing Spondylitis Metrology Index, and part- or full-time work. Presenteeism represented the AS impact on productivity (by visual analog scale, range 0-10, where 10=completely unproductive). Sick leave represented the number of days absent from work due to AS in the last 6 months. A linear mixed-effects model for presenteeism, and hurdle and zero-inflated count models for sick leave were explored. ResultsMeanSD presenteeism ranged from 2.2 +/- 2.2 to 3.8 +/- 7.8, and sick leave occurred in 8-17% of the patients during the 6-month period. Presenteeism positively correlated with BASDAI and BASFI, but was not significantly influenced by time. The chance of incurring sick leave was affected by presenteeism but not by BASDAI and BASFI. Conditional on being absent from work, the effect of presenteeism on the length of sick leave (in days) was much stronger than BASDAI and BASFI. For presenteeism 5, an increase of 1 unit in presenteeism yielded an increase by 36-40% (or 2-12 days) in the length of sick leave during the following 6 months. ConclusionPresenteeism, even measured by a simple visual analog scale, was an important factor to explain future sick leave

Diagnostic value of a 3-day course of prednisolone in patients with possible rheumatoid arthritis – the TryCort study

Abstract Background In patients with tender and swollen finger joints, the differential diagnosis between rheumatoid arthritis (RA) and osteoarthritis (OA) of the hands can be initially difficult. This prospective study (the TryCort study) was performed to study the diagnostic value of prednisolone in differentiating between RA and hand OA. We present the results of this potentially diagnostic test in patients with possible RA in daily clinical practice by demonstrating the results of a pilot and a validation part of this ‘prednisolone test’ (pred-test). Methods We investigated the response to a 3-day course of 20 mg of prednisolone in patients with suspicion of RA. All patients received 1 g of paracetamol per day for 5 days for pain relief. On days 3–5, a morning dose of 20 mg of prednisolone was added. Hand pain was quantified on a 0–10 Numerical Rating Scale, and the subjective percentage of improvement (0–100%) was recorded. Thresholds for response to prednisolone were investigated in a pilot phase with differentiation in response between patients with RA and patients with OA of the hands, both with pain in the hands ≥4. In a validation phase, the best differentiating cut-off of the pilot phase was applied to discriminate responders from non-responders in consecutive patients with hand pain ≥4 referred because of suspected RA. Final diagnoses were made by the expert upon re-examination at week 12. Primary outcomes were the sensitivity and specificity of a positive test in relation to the diagnosis. Results A percentage of 40% subjective improvement of pain in the hands on day 3 discriminated best between RA and OA in the pilot phase. Among 95 patients with complete data in the validation phase, RA was diagnosed in about 50%. Patients with RA had more swollen joints, higher C-reactive protein levels and slightly higher Health Assessment Questionnaire scores. The pred-test was positive in 42.1% of all patients (40 of 95). The median percentage of improvement on day 5 was higher in RA than in non-RA: 50% (IQR 30–60%) vs. 20% (IQR 10–30%) (p < 0.001). The sensitivity and specificity of the pred-test were 0.6 (95% CI 0.5–0.8) and 0.8 (95% CI 0.7–0.9), respectively, and the positive and negative predictive values were 0.77 and 0.70, respectively. Conclusions To our knowledge, this is the first evaluation of the widely used pred-test that has ever been performed. The pred-test had a moderate sensitivity and a good specificity. We conclude that rheumatologists may use this test in unclear clinical situations to better differentiate between inflammatory and other conditions. Trial registration ClinicalTrials.gov identifier: NCT01395251 . Registered on 14 Jul 2011. EudraCT number: 2011-002633-19. Registered on 21 Dec 2011