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Background
Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are frequent and serious complications after surgery. We aim to investigate the association between genetic variants in cholinergic candidate genes according to the Kyoto encyclopedia of genes and genomes - pathway: cholinergic neurotransmission with the development of POD or POCD in elderly patients.
Methods
This analysis is part of the European BioCog project (www.biocog.eu), a prospective multicenter observational study with elderly surgical patients. Patients with a Mini-Mental-State-Examination score ≤ 23 points were excluded. POD was assessed up to seven days after surgery using the Nursing Delirium Screening Scale, Confusion Assessment Method and a patient chart review. POCD was assessed three months after surgery with a neuropsychological test battery. Genotyping was performed on the Illumina Infinium Global Screening Array. Associations with POD and POCD were analyzed using logistic regression analysis, adjusted for age, comorbidities and duration of anesthesia (for POCD analysis additionally for education). Odds ratios (OR) refer to minor allele counts (0, 1, 2).
Results
745 patients could be included in the POD analysis, and 452 in the POCD analysis. The rate of POD within this group was 20.8% (155 patients), and the rate of POCD was 10.2% (46 patients). In a candidate gene approach three genetic variants of the cholinergic genes CHRM2 and CHRM4 were associated with POD (OR [95% confidence interval], rs8191992: 0.61[0.46; 0.80]; rs8191992: 1.60[1.22; 2.09]; rs2067482: 1.64[1.10; 2.44]). No associations were found for POCD.
Conclusions
We found an association between genetic variants of CHRM2 and CHRM4 and POD. Further studies are needed to investigate whether disturbances in acetylcholine release and synaptic plasticity are involved in the development of POD.
Background
In mucosal barrier interfaces, flexible responses of gene expression to long-term environmental changes allow adaptation and fine-tuning for the balance of host defense and uncontrolled not-resolving inflammation. Epigenetic modifications of the chromatin confer plasticity to the genetic information and give insight into how tissues use the genetic information to adapt to environmental factors. The oral mucosa is particularly exposed to environmental stressors such as a variable microbiota. Likewise, persistent oral inflammation is the most important intrinsic risk factor for the oral inflammatory disease periodontitis and has strong potential to alter DNA-methylation patterns. The aim of the current study was to identify epigenetic changes of the oral masticatory mucosa in response to long-term inflammation that resulted in periodontitis.
Methods and results
Genome-wide CpG methylation of both inflamed and clinically uninflamed solid gingival tissue biopsies of 60 periodontitis cases was analyzed using the Infinium MethylationEPIC BeadChip. We validated and performed cell-type deconvolution for infiltrated immune cells using the EpiDish algorithm. Effect sizes of DMPs in gingival epithelial and fibroblast cells were estimated and adjusted for confounding factors using our recently developed “intercept-method”. In the current EWAS, we identified various genes that showed significantly different methylation between periodontitis-inflamed and uninflamed oral mucosa in periodontitis patients. The strongest differences were observed for genes with roles in wound healing (ROBO2, PTP4A3), cell adhesion (LPXN) and innate immune response (CCL26, DNAJC1, BPI). Enrichment analyses implied a role of epigenetic changes for vesicle trafficking gene sets.
Conclusions
Our results imply specific adaptations of the oral mucosa to a persistent inflammatory environment that involve wound repair, barrier integrity, and innate immune defense.
A comparison study on modeling of clustered and overdispersed count data for multiple comparisons
(2021)
Data collected in various scientific fields are count data. One way to analyze such data is to compare the individual levels of the factor treatment using multiple comparisons. However, the measured individuals are often clustered – e.g. according to litter or rearing. This must be considered when estimating the parameters by a repeated measurement model. In addition, ignoring the overdispersion to which count data is prone leads to an increase of the type one error rate. We carry out simulation studies using several different data settings and compare different multiple contrast tests with parameter estimates from generalized estimation equations and generalized linear mixed models in order to observe coverage and rejection probabilities. We generate overdispersed, clustered count data in small samples as can be observed in many biological settings. We have found that the generalized estimation equations outperform generalized linear mixed models if the variance-sandwich estimator is correctly specified. Furthermore, generalized linear mixed models show problems with the convergence rate under certain data settings, but there are model implementations with lower implications exists. Finally, we use an example of genetic data to demonstrate the application of the multiple contrast test and the problems of ignoring strong overdispersion.
Objectives: To measure and assess the economic impact of adherence to a single quality indicator (QI) regarding weaning from invasive ventilation.
Design: Retrospective observational single-centre study, based on electronic medical and administrative records.
Setting: Intensive care unit (ICU) of a German university hospital, reference centre for acute respiratory distress syndrome.
Participants: Records of 3063 consecutive mechanically ventilated patients admitted to the ICU between 2012 and 2017 were extracted, of whom 583 were eligible adults for further analysis. Patients’ weaning protocols were evaluated for daily adherence to quality standards until ICU discharge. Patients with <65% compliance were assigned to the low adherence group (LAG), patients with ≥65% to the high adherence group (HAG).
Primary and secondary outcome measures: Economic healthcare costs, clinical outcomes and patients’ characteristics.
Results: The LAG consisted of 378 patients with a median negative economic results of −€3969, HAG of 205 (−€1030), respectively (p<0.001). Median duration of ventilation was 476 (248; 769) hours in the LAG and 389 (247; 608) hours in the HAG (p<0.001). Length of stay (LOS) in the LAG on ICU was 21 (12; 35) days and 16 (11; 25) days in the HAG (p<0.001). LOS in the hospital was 36 (22; 61) days in the LAG, and within the HAG, respectively, 26 (18; 48) days (p=0.001).
Conclusions: High adherence to this single QI is associated with better clinical outcome and improved economic returns. Therefore, the results support the adherence to QI. However, the examined QI does not influence economic outcome as the decisive factor.
During gestation, the most drastic change in oxygen supply occurs with the onset of ventilation after birth. As the too early exposure of premature infants to high arterial oxygen pressure leads to characteristic diseases, we studied the adaptation of the oxygen sensing system and its targets, the hypoxia-inducible factor- (HIF-) regulated genes (HRGs) in the developing lung. We draw a detailed picture of the oxygen sensing system by integrating information from qPCR, immunoblotting, in situ hybridization, and single-cell RNA sequencing data in ex vivo and in vivo models. HIF1α protein was completely destabilized with the onset of pulmonary ventilation, but did not coincide with expression changes in bona fide HRGs. We observed a modified composition of the HIF-PHD system from intrauterine to neonatal phases: Phd3 was significantly decreased, while Hif2a showed a strong increase and the Hif3a isoform Ipas exclusively peaked at P0. Colocalization studies point to the Hif1a-Phd1 axis as the main regulator of the HIF-PHD system in mouse lung development, complemented by the Hif3a-Phd3 axis during gestation. Hif3a isoform expression showed a stepwise adaptation during the periods of saccular and alveolar differentiation. With a strong hypoxic stimulus, lung ex vivo organ cultures displayed a functioning HIF system at every developmental stage. Approaches with systemic hypoxia or roxadustat treatment revealed only a limited in vivo response of HRGs. Understanding the interplay of the oxygen sensing system components during the transition from saccular to alveolar phases of lung development might help to counteract prematurity-associated diseases like bronchopulmonary dysplasia.
Background
A peripheral venous catheter (PVC) is the most widely used device for obtaining vascular access, allowing the administration of fluids and medication. Up to 25% of adult patients, and 50% of pediatric patients experience a first-attempt cannulation failure. In addition to patient and clinician characteristics, device features might affect the handling and success rates. The objective of the study was to compare the first-attempt cannulation success rate between PVCs with wings and a port access (Vasofix® Safety, B. Braun, abbreviated hereon in as VS) with those without (Introcan® Safety, B. Braun, abbreviated hereon in as IS) in an anesthesiological cohort.
Methods
An open label, multi-center, randomized trial was performed. First-attempt cannulation success rates were examined, along with relevant patient, clinician, and device characteristics with univariate and multivariate analyses. Information on handling and adherence to use instructions was gathered, and available catheters were assessed for damage.
Results
Two thousand three hundred four patients were included in the intention to treat analysis. First-attempt success rate was significantly higher with winged and ported catheters (VS) than with the non-winged, non-ported design (IS) (87.5% with VS vs. 78.2% with IS; PChi < .001). Operators rated the handling of VS as superior (rating of “good” or “very good: 86.1% VS vs. 20.8% IS, PChi < .001). Reinsertion of the needle into the catheter after partial withdrawal—prior or during the catheterization attempt—was associated with an increased risk of cannulation failure (7.909, CI 5.989–10.443, P < .001 and 23.023, CI 10.372–51.105, P < .001, respectively) and a twofold risk of catheter damage (OR 1.999, CI 1.347–2.967, P = .001).
Conclusions
First-attempt cannulation success of peripheral, ported, winged catheters was higher compared to non-ported, non-winged devices. The handling of the winged and ported design was better rated by the clinicians. Needle reinsertions are related to an increase in rates of catheter damage and cannulation failure.
Background
To detect changes in biological processes, samples are often studied at several time points. We examined expression data measured at different developmental stages, or more broadly, historical data. Hence, the main assumption of our proposed methodology was the independence between the examined samples over time. In addition, however, the examinations were clustered at each time point by measuring littermates from relatively few mother mice at each developmental stage. As each examination was lethal, we had an independent data structure over the entire history, but a dependent data structure at a particular time point. Over the course of these historical data, we wanted to identify abrupt changes in the parameter of interest - change points.
Results
In this study, we demonstrated the application of generalized hypothesis testing using a linear mixed effects model as a possible method to detect change points. The coefficients from the linear mixed model were used in multiple contrast tests and the effect estimates were visualized with their respective simultaneous confidence intervals. The latter were used to determine the change point(s). In small simulation studies, we modelled different courses with abrupt changes and compared the influence of different contrast matrices. We found two contrasts, both capable of answering different research questions in change point detection: The Sequen contrast to detect individual change points and the McDermott contrast to find change points due to overall progression. We provide the R code for direct use with provided examples. The applicability of those tests for real experimental data was shown with in-vivo data from a preclinical study.
Conclusion
Simultaneous confidence intervals estimated by multiple contrast tests using the model fit from a linear mixed model were capable to determine change points in clustered expression data. The confidence intervals directly delivered interpretable effect estimates representing the strength of the potential change point. Hence, scientists can define biologically relevant threshold of effect strength depending on their research question. We found two rarely used contrasts best fitted for detection of a possible change point: the Sequen and McDermott contrasts.
Hintergrund
Die Anämie hat eine hohe Prävalenz bei Patienten vor Hüftgelenkrevisionsoperation und ist mit einer erhöhten Komplikationsrate assoziiert. Die vorliegende Arbeit untersucht erstmals den Zusammenhang von Kosten, realen DRG-Erlösen und Falldeckung der präoperativen Anämie bei elektiven Hüftgelenkrevisionsoperationen.
Methoden
Für alle Patienten, die sich von 2010 bis 2017 an 2 Campi der Charité – Universitätsmedizin Berlin einer Hüftgelenkrevisionsoperation unterzogen, wurden Daten zu Patienten sowie Transfusionen, Kosten und Erlösen gesammelt. Subgruppen- und lineare Regressionsanalysen untersuchten die Falldeckung anämischer und nichtanämischer Patienten.
Ergebnisse
Von 1187 eingeschlossenen Patienten waren 354 (29,8 %) präoperativ anämisch. Insgesamt wurden 565 (47,6 %) Patienten, mit einem deutlichen Überwiegen anämischer Patienten (72,6 % vs. 37,0 %, p < 0,001), transfundiert. Kosten (12.318 € [9027;20.044 €] vs. 8948 € [7501;11.339 €], p < 0,001) und Erlöse (11.788 € [8992;16.298 €] vs. 9611 € [8332;10.719 €], p < 0,001) waren für anämische Patienten höher, die Fallkostendeckung defizitär (−1170 € [−4467;1238 €] vs. 591 € [−1441;2103 €] €, p < 0,001). Bei anämischen Patienten nahm die Falldeckung mit zunehmender Transfusionsrate ab (p ≤ 0,001). Komorbiditäten hatten keinen signifikanten ökonomischen Einfluss.
Schlussfolgerung
Die präoperative Anämie und perioperative Transfusionen bei Hüftgelenkrevisionsoperationen sind mit erhöhten Behandlungskosten und einer finanziellen Unterdeckung für Kostenträger im Gesundheitswesen verbunden. Konzepte zur Behandlung der präoperativen Anämie (z. B. Patient Blood Management) könnten mittelfristig Behandlungskosten senken.
Intensive care units (ICU) are often overflooded with alarms from monitoring devices which constitutes a hazard to both staff and patients. To date, the suggested solutions to excessive monitoring alarms have remained on a research level. We aimed to identify patient characteristics that affect the ICU alarm rate with the goal of proposing a straightforward solution that can easily be implemented in ICUs. Alarm logs from eight adult ICUs of a tertiary care university-hospital in Berlin, Germany were retrospectively collected between September 2019 and March 2021. Adult patients admitted to the ICU with at least 24 h of continuous alarm logs were included in the study. The sum of alarms per patient per day was calculated. The median was 119. A total of 26,890 observations from 3205 patients were included. 23 variables were extracted from patients' electronic health records (EHR) and a multivariable logistic regression was performed to evaluate the association of patient characteristics and alarm rates. Invasive blood pressure monitoring (adjusted odds ratio (aOR) 4.68, 95%CI 4.15–5.29, p < 0.001), invasive mechanical ventilation (aOR 1.24, 95%CI 1.16–1.32, p < 0.001), heart failure (aOR 1.26, 95%CI 1.19–1.35, p < 0.001), chronic renal failure (aOR 1.18, 95%CI 1.10–1.27, p < 0.001), hypertension (aOR 1.19, 95%CI 1.13–1.26, p < 0.001), high RASS (aOR 1.22, 95%CI 1.18–1.25, p < 0.001) and scheduled surgical admission (aOR 1.22, 95%CI 1.13–1.32, p < 0.001) were significantly associated with a high alarm rate. Our study suggests that patient-specific alarm management should be integrated in the clinical routine of ICUs. To reduce the overall alarm load, particular attention regarding alarm management should be paid to patients with invasive blood pressure monitoring, invasive mechanical ventilation, heart failure, chronic renal failure, hypertension, high RASS or scheduled surgical admission since they are more likely to have a high contribution to noise pollution, alarm fatigue and hence compromised patient safety in ICUs.
Red pepper (Capsicum annuum L.) is one of the major spices consumed globally, recognized for its aroma and nutrient properties, and it has a major economic value for high producing countries. However, characterization of its techno-functional properties and in-depth understanding of oxidative stability is needed to produce food of high quality and stability. Thus, this work focused on the chemical, functional, thermal, oxidative stability and rheological properties of red pepper powder and paste. Experiment was designed in a Completely Randomized Design (CRD) fashion. The red pepper powder contained 14.50 g/100 g, 44.00 g/100 g and 7.57 g/100 g of crude fat, crude fiber and ash, respectively. The concentration of total phenols, carotenoids and antioxidants activity of the powder were 1.04 g GAE/100 g, 374 mg βc/100 g and 38.61 μmol TE/g, respectively. Functional properties showed lower bulk density (395.1 kg/m3) and higher tapped density (583.4 kg/m3) indicating the higher compressibility of the powder. In contrast, Hausner ratio (1.48), Carr’s index (32%) and angle of repose (45°) indicated poor flowability of the powder. Particle size distribution also indicated that the volume weighted mean values D[4,3] of the powder and paste were 262.20 and 201.46, respectively. Emulsifying capacity of the powder was 47.5%. Oil and water absorption capacities varied from 1.41 to 1.73 and 0.86 to 2.29 g/g of initial weight, respectively. Higher glass transition temperature was observed for the powder (62.54°C) than the paste (45.64°C). The induction period indicated that red pepper was more stable against oxidation in powder (5.2 h) than in the paste form (3.2 h). Rheological analysis revealed that the paste exhibited shear-thinning behavior. Overall, understanding of the properties of red pepper could contribute to enhance quality.