344 research outputs found

    Biosynthetic Cellulose – Novel barrier against biofilm formation on ventricular assist device drivelines

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    Einleitung: Die chronische Herzinsuffizienz ist eine der häufigsten Erkrankungen weltweit und geht in fortgeschrittenen Stadien mit einer schlechten Prognose einher. Die Utlima-Ratio bleibt weiterhin eine Herztransplantation. Aufgrund des anhaltenden Mangels von Spenderorganen, stellen linksventrikuläre Unterstützungssysteme eine wichtige Alternative dar. Aktuell verfügbare Geräte sind für einen gesicherten Energie- und Informationstransfer auf ein Verbindungskabel zur Controller-Einheit – eine sog. Driveline - angewiesen. Infektionen der Driveline, welche sich entlang des subkutanen Tunnels bis zum Mediastinum und damit zur Pumpeneinheit ausbreiten, sind weiterhin eine Hauptkomplikation während der Unterstützung mit diesen Systemen. Biosynthetische Cellulose zeichnet sich durch seine hohe Biokompatibilität aus und stellt aufgrund seiner geringen Porosität eine theoretische Barriere gegenüber der Durchwanderung von Pathogenen dar. In der vorliegenden Arbeit wurde die Barriere für eine bakterielle Durchwanderung einer oberflächenveränderten biosynthetischen Cellulose und deren Bedeutung in der Prävention einer Driveline-Kontamination durch Pathogene in einem Tiermodell untersucht. Methoden: Primär wurde in vitro die Durchlässigkeit der Cellulose für fluoreszierende Mikropartikel in einem Zwei-Kammer-System untersucht, gefolgt von der Evaluation der Barriere gegenüber bakterieller Permeation. Nach Charakterisierung der Barrierefunktion in vitro, wurden die Außenhüllen von Drivelines mittels derselben Cellulose-Membranen ummantelt und anschließend die in-vivo-Barrierefunktion getestet. Insgesamt wurden 16 Kontrollen und 16 Cellulose-ummantelte Driveline-Außenhüllen in 8 Ziegen implantiert. Nach einer Implantationsdauer von 6 Wochen (4 Tiere) und 12 Wochen (4 Tiere) wurden die implantierten Driveline-Außenhüllen mitsamt umgebendem Gewebe explantiert. Die Driveline-Oberfläche wurde anschließend mittels Sonikation auf bakterielle Kontamination hin untersucht. Die Ergebnisse dieser Studie wurden mittels deskriptiver Statistik ausgewertet. Ergebnisse: Die untersuchte Cellulose stellt eine Barriere für Mikropartikel von 2 µm Größe dar und ist auch für Staph. aureus impermeabel. Auch in-vivo konnte diese Barrierefunktion reproduziert werden. Obwohl die Cellulose-beschichteten Implantate insgesamt häufiger infiziert waren als die Kontrollen, verhinderte die Cellulose-Membran in einer relevanten Anzahl der Fälle die Kolonisation der darunterliegenden Driveline-Außenhülle. Schlussfolgerung: Die durchgeführte Studie liefert erste Hinweisen darauf, dass die verwendete oberflächenmodifizierte Cellulose-Membran eine Barrierefunktion gegenüber der bakteriellen Kolonisation der Driveline-Oberfläche besitzt. Zusammen mit der Möglichkeit, die bio-synthetische Cellulose mit antibiotischen Wirkstoffen zu beladen, stellt die Barrierefunktion der untersuchten Cellulose eine neuartige Möglichkeit dar, in der Zukunft die Infektion von Herzunterstützungssystemen zu verhindern.Introduction: Chronic heart failure is one of the most common health conditions worldwide and is accompanied by a poor prognosis in a more advanced state. Heart transplantation remains the gold standard therapy in patients with terminal heart failure despite optimal medical and device therapy. Due to the ongoing organ donor shortage the use of left ventricular assist devices has been established as a bridge-to-transplant or as an alternative in the treatment of end stage heart failure. Available and approved state of the art systems rely on a continuous power and information transfer via an electrical cable to the controller unit – the so called driveline. Infection of the driveline are a main complication during the support with these systems and continuously endanger the life of the patient, since the pathogens are able to ascend along the driveline to the pump and therefore into the mediastinum. Biosynthesized cellulose is characterized as highly biocompatible and due to its low porosity as impermeable for bacteria. This study evaluates the barrier function against bacterial permeation and furthermore the prevention of driveline contamination in an animal trial. Methods: In a first experiment the permeability of the cellulose for fluorescing microparticles was evaluated with a custom designed two chamber system, followed by evaluation of the barrier against bacterial permeation. After evaluation of the barrier function in vitro, the outer sheaths of drivelines were wrapped with the cellulose membranes and afterwards the in-vivo barrier function tested. In total 16 cellulose covered driveline mantles and 16 control driveline mantles were implanted in 8 goats. After being left in situ for 6- (4 animals) and 12-weeks, the implants and surrounding tissue were explanted. Sonication was used to evaluate the driveline surface for bacterial contamination. Results were analyzed using descriptive statistics. Results: The evaluated biosynthetic cellulose presented to behave as a barrier for microparticles with a size of at least 2 µm and is also impermeable upon inoculation with Staph. aureus. This function as a barrier could be reproduced in-vivo. Despite higher colonization rates upon cellulose-covered driveline mantles, in a relevant number of cases the underlying driveline surface was colonization free while the cellulose was contaminated. Conclusion: The performed study represents first evidence that the surface-modified cellulose acts as an impermeable barrier against bacteria and prevents the colonization of the driveline surface. Taken together with the possibility of loading the biosythesized cellulose with antibiotic substances, the barrier function evaluated in this study presents a novel strategy to reduce the rate of ventricular assist device infections caused by driveline contamination in the future

    Nonparametric Identifiability of Causal Representations from Unknown Interventions

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    We study causal representation learning, the task of inferring latent causal variables and their causal relations from high-dimensional functions ("mixtures") of the variables. Prior work relies on weak supervision, in the form of counterfactual pre- and post-intervention views or temporal structure; places restrictive assumptions, such as linearity, on the mixing function or latent causal model; or requires partial knowledge of the generative process, such as the causal graph or the intervention targets. We instead consider the general setting in which both the causal model and the mixing function are nonparametric. The learning signal takes the form of multiple datasets, or environments, arising from unknown interventions in the underlying causal model. Our goal is to identify both the ground truth latents and their causal graph up to a set of ambiguities which we show to be irresolvable from interventional data. We study the fundamental setting of two causal variables and prove that the observational distribution and one perfect intervention per node suffice for identifiability, subject to a genericity condition. This condition rules out spurious solutions that involve fine-tuning of the intervened and observational distributions, mirroring similar conditions for nonlinear cause-effect inference. For an arbitrary number of variables, we show that two distinct paired perfect interventions per node guarantee identifiability. Further, we demonstrate that the strengths of causal influences among the latent variables are preserved by all equivalent solutions, rendering the inferred representation appropriate for drawing causal conclusions from new data. Our study provides the first identifiability results for the general nonparametric setting with unknown interventions, and elucidates what is possible and impossible for causal representation learning without more direct supervision

    Selecting candidate predictor variables for the modelling of post-discharge mortality from sepsis: a protocol development project

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    Background: Post-discharge mortality is a frequent but poorly recognized contributor to child mortality in resource limited countries. The identification of children at high risk for post-discharge mortality is a critically important first step in addressing this problem.Objectives: The objective of this project was to determine the variables most likely to be associated with post-discharge mortality which are to be included in a prediction modelling study.Methods: A two-round modified Delphi process was completed for the review of a priori selected variables and selection of new variables. Variables were evaluated on relevance according to (1) prediction (2) availability (3) cost and (4) time required for measurement. Participants included experts in a variety of relevant fields.Results: During the first round of the modified Delphi process, 23 experts evaluated 17 variables. Forty further variables were suggested and were reviewed during the second round by 12 experts. During the second round 16 additional variables were evaluated. Thirty unique variables were compiled for use in the prediction modelling study.Conclusion: A systematic approach was utilized to generate an optimal list of candidate predictor variables for the incorporation into a study on prediction of pediatric post-discharge mortality in a resource poor setting.Keywords: Candidate predictor variables, pediatrics, prediction, post-discharge mortality, sepsi

    “WAS IT HIS MILK”? A CASE REPORT OF CHLORPYRIFOS AND CYPERMETHRIN MIXED POISONING IN A TODDLER.

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    Introduction: The prevalence of organophosphate poisoning has been increasing over the years, with significant hospitalization following the introduction of various pesticides. The inception of different regulating agencies against organophosphate utilization has been effective in developed countries, unlike low- and middle-income countries. Continuous monitoring of vulnerable populations, such as children, and depressed and anxious individuals, is necessary for reducing poisoning cases. Case: We discussed a 2-year and 6-month-old male child who was previously healthy and was brought into our pediatric emergency unit of a general hospital with a history of ingestion of fluid that he thought was milk. We present the sequelae of events from the ingestion of the substance until discharge from the facility. Additionally, we elaborate on the different preparations for managing any toddler with organophosphate poisoning. Conclusion: Appropriate use of these compounds, instruction of the public about their harmful effects, and restriction of their uncontrolled sales by legal regulations can reduce the incidence of organophosphate poisoning. Promoting emergency management strategies among parents concerning the management of acute poisoning is vital in promoting better children’s outcomes. Recommendation: Heath regulation bodies must take an interest in educating health workers and the community concerning organophosphate poisoning and its management, especially in a limited resource setting

    DEGLUTITION SYNCOPE IN A HEALTHY 9-YEAR-OLD BOY: FIRST OF ITS KIND IN AFRICA. A CASE REPORT AND LITERATURE REVIEW.

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    Introduction Deglutition syncope, also known as swallow syncope is a rear form of situation syncope. It’s a neurally-mediated reflex that occurs during swallowing. This condition has been associated with various esophageal disorders such as esophageal spasm, stricture, and esophageal cancer. In other cases, the cause remains unknown. Case Report In this case report, we present the timeline of a healthy 9-year-old boy with deglutition syncope, a rare entity, and the first of its kind in the Sub-Saharan region. Conclusion Despite its rarity, healthcare professionals ought to consider deglutition syncope as a diagnosis of exclusion especially in the face of unexplained syncope. Because of associated life-threatening bradycardia, knowledge of the clinical manifestation is equally important for early diagnosis, and institution of care to avert death

    Pediatric out-of-hospital deaths following hospital discharge: a mixed-methods study.

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    Background: Out-of-hospital death among children living in resource poor settings occurs frequently. Little is known about the location and circumstances of child death following a hospital discharge. Objectives: This study aimed to understand the context surrounding out-of-hospital deaths and the barriers to accessing timely care for Ugandan children recently discharged from the hospital. Methods: This was a mixed-methods sub-study within a larger cohort study of post-discharge mortality conducted in the Southwestern region of Uganda. Children admitted with an infectious illness were eligible for enrollment in the cohort study, and then followed for six months after discharge. Caregivers of children who died outside of the hospital during the six month post-discharge period were eligible to participate in this sub-study. Qualitative interviews and univariate logistic regression were conducted to determine predictors of out-of-hospital deaths. Results: Of 1,242 children discharged, 61 died during the six month post-discharge period, with most (n=40, 66%) dying outside of a hospital. Incremental increases in maternal education were associated with lower odds of out-of-hospital death compared to hospital death (OR: 0.38, 95% CI: 0.19 \u2013 0.81). The qualitative analysis identified health seeking behaviors and common barriers within the post-discharge period which delayed care seeking prior to death. For recently discharged children, caregivers often expressed hesitancy to seek care following a recent episode of hospitalization. Conclusion: Mortality following discharge often occurs outside of a hospital context. In addition to resource limitations, the health knowledge and perceptions of caregivers can be influential to timely access to care. Interventions to decrease child mortality must consider barriers to health seeking among children following hospital discharge

    Selecting candidate predictor variables for the modelling of post-discharge mortality from sepsis: a protocol development project.

    Get PDF
    Background: Post-discharge mortality is a frequent but poorly recognized contributor to child mortality in resource limited countries. The identification of children at high risk for post-discharge mortality is a critically important first step in addressing this problem. Objectives: The objective of this project was to determine the variables most likely to be associated with post-discharge mortality which are to be included in a prediction modelling study. Methods: A two-round modified Delphi process was completed for the review of a priori selected variables and selection of new variables. Variables were evaluated on relevance according to (1) prediction (2) availability (3) cost and (4) time required for measurement. Participants included experts in a variety of relevant fields. Results: During the first round of the modified Delphi process, 23 experts evaluated 17 variables. Forty further variables were suggested and were reviewed during the second round by 12 experts. During the second round 16 additional variables were evaluated. Thirty unique variables were compiled for use in the prediction modelling study. Conclusion: A systematic approach was utilized to generate an optimal list of candidate predictor variables for the incorporation into a study on prediction of pediatric post-discharge mortality in a resource poor setting

    The spinal cord injury-induced immune deficiency syndrome: results of the SCIentinel study

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    Infections are prevalent after spinal cord injury (SCI), constitute the main cause of death and are a rehabilitation confounder associated with impaired recovery. We hypothesize that SCI causes an acquired lesion-dependent (neurogenic) immune suppression as an underlying mechanism to facilitate infections. The international prospective multicentre cohort study (SCIentinel; protocol registration DRKS00000122; n = 111 patients) was designed to distinguish neurogenic from general trauma-related effects on the immune system. Therefore, SCI patient groups differing by neurological level, i.e. high SCI [thoracic (Th)4 or higher]; low SCI (Th5 or lower) and severity (complete SCI; incomplete SCI), were compared with a reference group of vertebral fracture (VF) patients without SCI. The primary outcome was quantitative monocytic Human Leukocyte Antigen-DR expression (mHLA-DR, synonym MHC II), a validated marker for immune suppression in critically ill patients associated with infection susceptibility. mHLA-DR was assessed from Day 1 to 10 weeks after injury by applying standardized flow cytometry procedures. Secondary outcomes were leucocyte subpopulation counts, serum immunoglobulin levels and clinically defined infections. Linear mixed models with multiple imputation were applied to evaluate group differences of logarithmic-transformed parameters. Mean quantitative mHLA-DR [ln (antibodies/cell)] levels at the primary end point 84 h after injury indicated an immune suppressive state below the normative values of 9.62 in all groups, which further differed in its dimension by neurological level: high SCI [8.95 (98.3% confidence interval, CI: 8.63; 9.26), n = 41], low SCI [9.05 (98.3% CI: 8.73; 9.36), n = 29], and VF without SCI [9.25 (98.3% CI: 8.97; 9.53), n = 41, P = 0.003]. Post hoc analysis accounting for SCI severity revealed the strongest mHLA-DR decrease [8.79 (95% CI: 8.50; 9.08)] in the complete, high SCI group, further demonstrating delayed mHLA-DR recovery [9.08 (95% CI: 8.82; 9.38)] and showing a difference from the VF controls of -0.43 (95% CI: -0.66; -0.20) at 14 days. Complete, high SCI patients also revealed constantly lower serum immunoglobulin G [-0.27 (95% CI: -0.45; -0.10)] and immunoglobulin A [-0.25 (95% CI: -0.49; -0.01)] levels [ln (g/l × 1000)] up to 10 weeks after injury. Low mHLA-DR levels in the range of borderline immunoparalysis (below 9.21) were positively associated with the occurrence and earlier onset of infections, which is consistent with results from studies on stroke or major surgery. Spinal cord injured patients can acquire a secondary, neurogenic immune deficiency syndrome characterized by reduced mHLA-DR expression and relative hypogammaglobulinaemia (combined cellular and humoral immune deficiency). mHLA-DR expression provides a basis to stratify infection-risk in patients with SCI
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