Delirium represents the most common form of acute cerebral dysfunction in critical illness. The prevention, recognition, and treatment of delirium must become the focus of modern pediatric intensive ...care, as delirium can lead to increased morbidity and mortality. The aim of this study is to evaluate the impact of a delirium bundle consisting of mainly non-pharmacological measures.
This is a pre-/post-implementation study in an interdisciplinary pediatric intensive care unit of a tertiary care university hospital. In the pre-implementation period, pediatric intensive care delirium was monitored using the Sophia Observation withdrawal Symptoms and Pediatric Delirium scale. After introduction of a delirium bundle consisting of non-pharmacological prevention and treatment measures a period of 4 months was interposed to train the PICU staff and ensure that the delirium bundle was implemented consistently before evaluating the effects in the post-implementation period. Data collection included prevalence of delirium and withdrawal, length of PICU stay, duration of mechanical ventilation, and cumulative dose of sedatives and analgesics.
A total of 792 critically ill children aged 0-18 years were included in this study. An overall delirium prevalence of 30% was recorded in the pre-implementation group and 26% in the post-implementation group (
= 0.13). A significant reduction in the prevalence of pediatric delirium from was achieved in the subgroup of patients under 5 years of age (27.9 vs. 35.8%,
= 0.04) and in patients after surgery for congenital heart disease (28.2 vs. 39.5%,
= 0.04). Young age, length of PICU stay, and iatrogenic withdrawal syndrome were found to be risk factors for developing delirium.
Based on a validated delirium monitoring, our study gives new information regarding the prevalence of pediatric delirium and the characteristics of intensive care patients at risk for this significant complication. Especially young patients and patients after surgery for congenital heart disease seem to benefit from the implementation of non-pharmacological delirium bundles. Based on our findings, it is important to promote change in pediatric intensive care-toward a comprehensive approach to prevent delirium in critically ill children as best as possible.
It is a well-known fact that managing schizophrenia patients as early as possible has a positive impact on the psychopathological and psychosocial outcomes of the disorder. Identifying people at risk ...for this serious disorder before its outbreak has become a major research aim in the past decade. Consequently, the intuitive notion that intervening at this early stage, before a diagnosis of schizophrenia is established, could be a preventive measure has been scientifically studied. In this context, a number of interventions, both pharmacological and psychosocial, have been evaluated in prospective controlled clinical trials. Amisulpride, olanzapine, risperidone, omega-3 fatty acids, and antidepressants have been compared to placebo or other control interventions and have been found somewhat helpful. With the exception of omega-3 fatty acids, however, the original positive findings were not maintained in follow-up studies. In addition, the rates of conversion to psychosis, although generally lower in the experimental treatment groups, were also reasonably low in the control groups. Similar findings have been established in psychotherapy trials.All evidence taken together makes it difficult to justify specific interventions at the prodromal stage of schizophrenia from the perspective of preventing or delaying the onset of the disorder. On the other hand, as many of the affected individuals suffer considerably, symptomatic treatment certainly is called for even though the evidence whether it should be pharmacological or psychosocial is not yet available.
Introduction: Newborn sudden infant death syndrome (SIDS) has failed to decrease in the last decades, and a third of the neonatal cases occurred within the first 6 days of life. The long QT syndrome ...(LQTS) is a genetic disease with a prevalence of 1 in 2,000 live births and contributes to almost 10% of SIDS cases. Early identification of LQTS through electrocardiogram (ECG) screening is likely to reduce mortality. Methods and Results: In this ongoing prospective study we evaluated 2,251 ECGs from newborns participating in the KUNO Kids birth cohort study between July 2015 and July 2018. ECGs were recorded at a mean age of 2.0 days (IQR 0 days). The QT interval was corrected for heart rate using Bazett’s formula (QTc). A QTc between 451 and 460, 461–470, and >470 ms was measured in 23 (1.0), 14 (0.6), and 62 (2.8%) participants, respectively. Fourteen neonates (0.62%) were admitted and monitored because their initial QTc was ≥500 ms. In 2 genetically analyzed participants, a mutation was found. One disease-causing for LQTS type 1 and the other of unclear significance. Cascade screening revealed affected members in both families. Conclusion: A standardized neonatal ECG screening in the first days of life is able to identify neonates with a relevant transient form of prolonged QT intervals and to aid diagnosing congenital LQTS.
Abstract Originally identified as antiviral substances produced by infected cells, type I interferons (IFN-I) are now known to have a wide range of additional activities within both the innate and ...adaptive immune response. Here we review properties of IFN-I contributing to their ‘natural immune adjuvant’ character, and their important role for the function of complete Freund's adjuvant (CFA) and the TLR9-dependent immune adjuvant IC31. We show data to demonstrate that treatment with IFN-I boosts the ability of vaccine/adjuvant combinations to induce peptide-specific CTL in both young and old mice. We view these findings in the perspective of previous clinical applications of IFN-I for vaccination.
Ligation of the BCR induces a complex signaling network that involves activation of Akt, a family of serine/threonine protein kinases associated with B‐cell development, proliferation, and tumor ...formation. Here, we analyzed the effect of enhanced Akt1 signals on B‐cell maturation and function. Unexpectedly, we found that peripheral B cells overexpressing Akt1 were less responsive to BCR stimuli. This correlated with a decrease in Ca2+‐mobilization and proliferation, in an impaired activation of Erk1/2 and mammalian target of rapamycin (mTOR) kinases and poor mobilization of NFATc1 and NF‐κB/p65 factors. In contrast, activation of STAT5 and migration of B cells toward the chemokine SDF1α was found to be enhanced. Akt1 Tg mice showed an altered maturation of peritoneal and splenic B1 B cells and an enhanced production of IgG1 and IgG3 upon immunization with the T‐cell independent Ag TNP‐Ficoll. Furthermore, mice homo‐zygous for Tg Akt1 showed a severe block in the maturation of B‐cell precursors in BM and a strong enrichment of plasma cells in spleen. Altogether, our data reveal that enhanced Akt1 signals modify BCR signaling strength and, thereby, B‐cell development and effector function.
Ligation of the
BCR
induces a complex signaling network that involves activation of
A
kt, a family of serine/threonine protein kinases associated with
B
‐cell development, proliferation, and tumor ...formation. Here, we analyzed the effect of enhanced
A
kt1 signals on
B
‐cell maturation and function. Unexpectedly, we found that peripheral
B
cells overexpressing
A
kt1 were less responsive to
BCR
stimuli. This correlated with a decrease in
C
a
2+
‐mobilization and proliferation, in an impaired activation of
E
rk1/2 and mammalian target of rapamycin (m
TOR
) kinases and poor mobilization of
NFAT
c1 and
NF
‐κ
B
/p65 factors. In contrast, activation of
STAT
5 and migration of
B
cells toward the chemokine
SDF
1α was found to be enhanced.
A
kt1
T
g mice showed an altered maturation of peritoneal and splenic
B
1
B
cells and an enhanced production of
I
g
G
1 and
I
g
G
3 upon immunization with the
T
‐cell independent
A
g
TNP
‐
F
icoll. Furthermore, mice homo‐zygous for
T
g
A
kt1 showed a severe block in the maturation of
B
‐cell precursors in
BM
and a strong enrichment of plasma cells in spleen. Altogether, our data reveal that enhanced
A
kt1 signals modify
BCR
signaling strength and, thereby,
B
‐cell development and effector function.
Phosphorylation of transcription factor STAT-1 on Y701 regulates subcellular localization whereas phosphorylation of the transactivating domain at S727 enhances transcriptional activity. In this ...study, we investigate the impact of STAT-1 and the importance of transactivating domain phosphorylation on the induction of peptide-specific CTL in presence of the TLR9-dependent immune adjuvant IC31. STAT-1 deficiency completely abolished CTL induction upon immunization, which was strongly reduced in animals carrying the mutation of the S727 phospho-acceptor site. A comparable reduction of CTL was found in mice lacking the type I IFN (IFN-I) receptor, whereas IFN-gamma-deficient mice behaved like wild-type controls. This finding suggests that S727-phosphorylated STAT-1 supports IFN-I-dependent induction of CTL. In adoptive transfer experiments, IFN-I- and S727-phosphorylated STAT-1 were critical for the activation and function of dendritic cells. Mice with a T cell-specific IFN-I receptor ablation did not show impaired CTL responses. Unlike the situation observed for CTL development S727-phosphorylated STAT-1 restrained proliferation of naive CD8(+) T cells both in vitro and following transfer into Rag-deficient mice. In summary, our data reveal a dual role of S727-phosphorylated STAT-1 for dendritic cell maturation as a prerequisite for the induction of CTL activity and for T cell autonomous control of activation-induced or homeostatic proliferation.
Zwischenbericht 2007 der FH Frankfurt, Institut für Stadt- und Regionalentwicklung, und des Instituts für angewandte Sozialwissenschaft (infas) zur Implementations- und Governanceanalyse im Rahmen ...der Evalouation der Experimentierklausel nach § 6c SGB II. Die Implementations- und Governanceanalyse untersucht die Umsetzung der durch das SGB II definierten Leistungsprozesse anhand einer Stichprobe von 154 regionalen Einheiten aus allen Arbeitsgemeinschaften (ARGEn), zugelassenen kommunalen Trägern und Fällen getrennter Aufgabenwahrnehmung. Der Bericht analysiert im ersten Teil überregionale Governance-Strukturen (z. B. rechtliche und finanzielle Vorgaben, Zielvereinbarungen), die Auswirkungen auf die Leistungserbringung der SGB II-Einheiten haben. Im zweiten Teil werden die lokalen Steuerungs- und Organisationsstrukturen in den Formen der Aufgabenwahrnehmung untersucht und wird eine Typologie der Organisation des Leistungsprozesses entwickelt. Der dritte Teil beschäftigt sich mit der Ausgestaltung der Schnittstellen zwischen SGB II, SGB III und SGB VIII, insbesondere im Hinblick auf Eingliederungsleistungen für Jugendliche und junge Erwachsene sowie die Organisation der Arbeitsvermittlung.
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