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Preoperative medication use and development of postoperative delirium and cognitive dysfunction
(2021)
Postoperative delirium (POD) and postoperative (neuro-)cognitive disorder (POCD) are frequent and serious complications after operations. We aim to investigate the association between pre-operative polypharmacy and potentially inappropriate medications and the development of POD/POCD in elderly patients. This investigation 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 less than or equal to 23 points were excluded. POD was assessed up to 7 days after surgery using the Nursing Delirium Screening Scale, Confusion Assessment Method (for the intensive care unit [ICU]), and a patient chart review. POCD was assessed 3 months after surgery with a neuropsychological test battery. Pre-operative long-term medication was evaluated in terms of polypharmacy (≥5 agents) and potentially inappropriate medication (defined by the PRISCUS and European list of potentially inappropriate medications [EU(7)-PIM] lists), and associations with POD and POCD were analyzed using logistic regression analysis. Eight hundred thirty-seven participants were included for analysis of POD and 562 participants for POCD. Of these, 165 patients (19.7%) fulfilled the criteria of POD and 60 (10.7%) for POCD. After adjusting for confounders, pre-operative polypharmacy and intake of potentially inappropriate medications could not be shown to be associated with the development of POD nor POCD. We found no associations between pre-operative polypharmacy and potentially inappropriate medications and development of POD and POCD. Future studies should focus on the evaluation of drug interactions to determine whether patients benefit from a pre-operative adjustment.
The benzodiazepine, midazolam, is one of the most frequently used sedatives in intensive care medicine, but it has an unfavorable pharmacokinetic profile when continuously applied. As a consequence, patients are frequently prolonged and more deeply sedated than intended. Due to its distinct pharmacological features, including a cytochrome P450-independent metabolization, intravenous lormetazepam might be clinically advantageous compared to midazolam. In this retrospective cohort study, we compared patients who received either intravenous lormetazepam or midazolam with respect to their survival and sedation characteristics. The cohort included 3314 mechanically ventilated, critically ill patients that received one of the two drugs in a tertiary medical center in Germany between 2006 and 2018. A Cox proportional hazards model with mortality as outcome and APACHE II, age, gender, and admission mode as covariates revealed a hazard ratio of 1.75 [95% CI 1.46–2.09; p < 0.001] for in-hospital mortality associated with the use of midazolam. After additionally adjusting for sedation intensity, the HR became 1.04 [95% CI 0.83–1.31; p = 0.97]. Thus, we concluded that excessive sedation occurs more frequently in critically ill patients treated with midazolam than in patients treated with lormetazepam. These findings require further investigation in prospective trials to assess if lormetazepam, due to its ability to maintain light sedation, might be favorable over other benzodiazepines for sedation in the ICU.
Objective:
The cervical mucus plugs are enriched with proteins of known immunological functions. We aimed to characterize the anti-HIV-1 activity of the cervical mucus plugs against a panel of different HIV-1 strains in the contexts of cell-free and cell-associated virus.
Design:
A cohort of consenting HIV-1-negative and HIV-1-positive pregnant women in labour was recruited from Mthatha General Hospital in the Eastern Cape province of South Africa, from whom the cervical mucus plugs were collected in 6 M guanidinium chloride with protease inhibitors and transported to our laboratories at −80 °C.
Methods:
Samples were centrifuged to remove insoluble material and dialysed before freeze--drying and subjecting them to the cell viability assays. The antiviral activities of the samples were studied using luminometric reporter assays and flow cytometry. Time-of-addition and BlaM-Vpr virus-cell fusion assays were used to pin-point the antiviral mechanisms of the cervical mucus plugs, before proteomic profiling using liquid chromatography-tandem mass spectrometry.
Results:
The proteinaceous fraction of the cervical mucus plugs exhibited anti-HIV-1 activity with inter-individual variations and some degree of specificity among different HIV-1 strains. Cell-associated HIV-1 was less susceptible to inhibition by the potent samples whenever compared with the cell-free HIV-1. The samples with high antiviral potency exhibited a distinct proteomic profile when compared with the less potent samples.
Conclusion:
The crude cervical mucus plugs exhibit anti-HIV-1 activity, which is defined by a specific proteomic profile.
Background
In DNA methylation analyses like epigenome-wide association studies, effects in differentially methylated CpG sites are assessed. Two kinds of outcomes can be used for statistical analysis: Beta-values and M-values. M-values follow a normal distribution and help to detect differentially methylated CpG sites. As biological effect measures, differences of M-values are more or less meaningless. Beta-values are of more interest since they can be interpreted directly as differences in percentage of DNA methylation at a given CpG site, but they have poor statistical properties. Different frameworks are proposed for reporting estimands in DNA methylation analysis, relying on Beta-values, M-values, or both.
Results
We present and discuss four possible approaches of achieving estimands in DNA methylation analysis. In addition, we present the usage of M-values or Beta-values in the context of bioinformatical pipelines, which often demand a predefined outcome. We show the dependencies between the differences in M-values to differences in Beta-values in two data simulations: a analysis with and without confounder effect. Without present confounder effects, M-values can be used for the statistical analysis and Beta-values statistics for the reporting. If confounder effects exist, we demonstrate the deviations and correct the effects by the intercept method. Finally, we demonstrate the theoretical problem on two large human genome-wide DNA methylation datasets to verify the results.
Conclusions
The usage of M-values in the analysis of DNA methylation data will produce effect estimates, which cannot be biologically interpreted. The parallel usage of Beta-value statistics ignores possible confounder effects and can therefore not be recommended. Hence, if the differences in Beta-values are the focus of the study, the intercept method is recommendable. Hyper- or hypomethylated CpG sites must then be carefully evaluated. If an exploratory analysis of possible CpG sites is the aim of the study, M-values can be used for inference.
BACKGROUND:
Intraoperative electroencephalography (EEG) signatures related to the development of postoperative delirium (POD) in older patients are frequently studied. However, a broad analysis of the EEG dynamics including preoperative, postinduction, intraoperative and postoperative scenarios and its correlation to POD development is still lacking. We explored the relationship between perioperative EEG spectra-derived parameters and POD development, aiming to ascertain the diagnostic utility of these parameters to detect patients developing POD.
METHODS:
Patients aged ≥65 years undergoing elective surgeries that were expected to last more than 60 minutes were included in this prospective, observational single center study (Biomarker Development for Postoperative Cognitive Impairment [BioCog] study). Frontal EEGs were recorded, starting before induction of anesthesia and lasting until recovery of consciousness. EEG data were analyzed based on raw EEG files and downloaded excel data files. We performed multitaper spectral analyses of relevant EEG epochs and further used multitaper spectral estimate to calculate a corresponding spectral parameter. POD assessments were performed twice daily up to the seventh postoperative day. Our primary aim was to analyze the relation between the perioperative spectral edge frequency (SEF) and the development of POD.
RESULTS:
Of the 237 included patients, 41 (17%) patients developed POD. The preoperative EEG in POD patients was associated with lower values in both SEF (POD 13.1 ± 4.6 Hz versus no postoperative delirium [NoPOD] 17.4 ± 6.9 Hz; P = .002) and corresponding γ-band power (POD −24.33 ± 2.8 dB versus NoPOD −17.9 ± 4.81 dB), as well as reduced postinduction absolute α-band power (POD −7.37 ± 4.52 dB versus NoPOD −5 ± 5.03 dB). The ratio of SEF from the preoperative to postinduction state (SEF ratio) was ~1 in POD patients, whereas NoPOD patients showed a SEF ratio >1, thus indicating a slowing of EEG with loss of unconscious. Preoperative SEF, preoperative γ-band power, and SEF ratio were independently associated with POD (P = .025; odds ratio [OR] = 0.892, 95% confidence interval [CI], 0.808–0.986; P = .029; OR = 0.568, 95% CI, 0.342–0.944; and P = .009; OR = 0.108, 95% CI, 0.021–0.568, respectively).
CONCLUSIONS:
Lower preoperative SEF, absence of slowing in EEG while transitioning from preoperative state to unconscious state, and lower EEG power in relevant frequency bands in both these states are related to POD development. These findings may suggest an underlying pathophysiology and might be used as EEG-based marker for early identification of patients at risk to develop POD.
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.
The objective of this article is to prepare for the initial certification according to IFS Global Markets Food V3 at the Landshuter Brauhaus AG private brewery at the Ellermühle site, which is expected in August 2025, and to create the basis for a potential follow-up certification according to IFS Food. The IFS Global Markets Food Program V3 is a standardized, voluntary and non-accredited assessment program for food companies, both for retail and manufacturer brand products (IFS 2023, p. 10 f.). It is based on the specifications of the Global Markets Program developed in 2008 (GFSI 2023a; VDOE 2020, p. 620).
The methodology of the target/actual analysis was used to work on the topic in order to be able to carry out a conformity check with regard to the requirements of IFS Global Markets Food V3 (see Appendix 3; IFS 2023). Observations, document analyses and employee surveys were carried out to obtain the most meaningful information possible. These have been recorded and evaluated within the target-performance analysis. A total of 65 deviations (equivalent to 53.7%) were identified at the basic level, and 60 deviations (equivalent to 82.2%) at the intermediate level. These were either processed as directly implemented corrective actions or formulated as recommendations for continuous improvement in the form of an action plan (see Appendix 15). The presentation of the action plan shows the deviations, the resulting measures, the associated responsibilities, the time period with the starting point and end point of the measures, and the current status. In addition a subdivision into "Basic" and "+Intermediate" was made for a better overview in the subsequent processing by the brewery.
A review as well as assessment of relevant requirements with regard to processes and significant violations after completion of the new building and commissioning at the Ellermühle site with regard to correlation with a potential "major" rating is recommended on the part of the operations manager or brewmaster (IFS 2023, p. 30).
The demands placed on companies in terms of up-to-date quality and sustainability management as well as health and safety measures are high and are becoming increasingly complex. Increased legal requirements, additional industry standards and derived customer requirements constantly present companies and value chains with new challenges. The integrated approach to the implementation of these different requirements has already taken place in companies in recent years. However, small businesses still find it difficult to face the complexity of requirements on their own without an accompanying consultation. Qualint is a support tool, which is currently available in the 3rd version. The tool supports companies in setting up and continuously developing their integrated management system with coordinated hybrid service bundles. The focus is on combining the fields of action of quality, environmental and sustainability management as well as occupational safety and health.The article illustrates how quality management can be used as a basis for building up digital and organizational structures in companies and value chains. The focus is on sustainability aspects and ethical requirements that are closely related to people, such as occupational health and safety. Compliance with human rights is required in ISO 26000 and is also part of occupational safety and health. Furthermore, compliance with human rights and corresponding working conditions is also regulated by the new Supply Chain Duty Act (LkSG). It shows how demands on companies have grown and how the consulting tool Qualint has developed accordingly.
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.
In recent years, ISO, IFS, BRC and FSSC 22000 standards in the areas of quality, environment and occupational health and safety have been increas-ingly implemented in companies in various industries. The main focus of these developed standards are the processes. But the past shows that the factor human is another very important factor, which should be much more in the middle in organization. The new developed guideline has the human factor in the foreground. In particular, the attitude and awareness of occupational safe-ty and health protection in the behaviour of employees at all levels of the or-ganisation are at the centre of consideration.
Inspired by this approach, a group of experts from the fields of quality scienc-es, standardisation and certification as well as consulting for system-relevant companies in the agricultural and food industry came together to form a committee during the Corona crisis in spring 2020. The common goal is to develop a new standard. The first step is to establish criteria for a guideline.
and establish an evaluation system for several pillars of a House of Total Safety Culture (HSC) tailored to the entire value chains of the agri-food sec-tor. In addition, the essential building blocks of the guideline must be defined. The attitude of managers and employees, their behaviour and their compe-tence form the roof of the standard. The integrated management system with a continuous improvement process forms the foundation of the House of To-tal Safety Culture across the company in value chains. Qualification and communication are the main pillars and thus further elements of the HSC. Particular attention is paid to the fields of action of occupational safety and health protection, food safety, animal and environmental protection as well as sustainability and digitisation. They form the four inner pillars of the House of Total Safety Culture. The design of the respective certification levels is con-sidered as a “construction phase”. As part of the standardisation process, the coordination of the respective requirements for safety culture has not yet been completed. This article first provides an overview of the state of knowledge in relation to the established standards and norms of the agri-food industry with special consideration of the Safety Culture Ladder model. The procedure for developing and establishing the new guideline is then ex-plained. For this purpose, the composition of the expert forum is presented before the concrete steps to establish the guideline are presented. The model of the House of Total Culture is presented below. Building on this, the proce-dure for assessing the degree of maturity and possible concepts of continuing training are explained before the conclusion of this article.
This paper investigates four different mobile robots with respect to their drivingcharacteristics and soil preservation properties in an agricultural environment.Thereby, robots of classical design from agriculture as well as systems from spacerobotics with advanced locomotion concepts are considered to determine theindividual advantages of each rover concept with respect to the application domain.Locomotion experiments were conducted to analyze the general driving behavior,tensile force, and obstacle‐surmounting capability and ground interaction of eachrobot. Various soil conditions typical for the area of application are taken intoaccount, which are varied in terms of moisture and density. The presented workcovers the specification of the conducted experiments, documentation of theimplementation as well as analysis and evaluation of the collected data. In theevaluation, particular attention is paid to the change in driving characteristics underdifferent soil conditions, as well as to the soil stress caused by driving, since soilquality is of critical importance for agricultural applications. The analysis shows thatthe advanced locomotion concepts, as used in space robotics, also have positiveimplications for certain requirements in agricultural applications, such as maneuver-ability in wet conditions and soil conservation. The results show potential for designinnovations in agricultural robotics that can be used, to open up new fields ofapplication for instance in the context of precision farming.
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: New ischaemic brain lesions on magnetic resonance imaging (MRI) are reported in up to 86% of patients after transcatheter edge-to-edge repair of the mitral valve (TEER-MV). Knowledge of the exact procedural step(s) that carry the highest risk for cerebral embolisation may help to further improve the procedure.
Aims: The aim of this study was to identify the procedural step(s) that are associated with an increased risk of cerebral embolisation during TEER-MV with the MitraClip system. Furthermore, the risk of overt stroke and silent brain ischaemia after TEER-MV was assessed.
Methods: In this prospective, pre-specified observational study, all patients underwent continuous transcranial Doppler examination during TEER-MV to detect microembolic signals (MES). MES were assigned to specific procedural steps: (1) transseptal puncture and placement of the guide, (2) advancing and adjustment of the clip in the left atrium, (3) device interaction with the MV, and (4) removal of the clip delivery system and the guide. Neurological examination using the National Institutes of Health Stroke Scale (NIHSS) and cerebral MRI were performed before and after TEER-MV.
Results: Fifty-four patients were included. The number of MES differed significantly between the procedural steps with the highest numbers observed during device interaction with the MV. Mild neurological deterioration (NIHSS ≤3) occurred in 9/54 patients. New ischaemic lesions were detected in 21/24 patients who underwent MRI. Larger infarct volume was significantly associated with neurological deterioration.
Conclusions: Cerebral embolisation is immanent to TEER-MV and predominantly occurs during device interaction with the MV. Improvements to the procedure may focus on this procedural step.
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.
BACKGROUND: Postoperative delirium (POD) is an acute and common complication after surgery that can increase morbidity and mortality. Few previous studies with inconsistent findings have examined the association of preoperative pain and POD. Our purpose is to investigate the association of preoperative chronic pain and POD.
METHODS: This prospective observational cohort study included 200 patients ≥ 18 years scheduled for elective surgery under general anaesthesia in a tertiary care hospital. POD was defined as meeting diagnostic criteria during the study visits (according to delirium screening tests and the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition), or by diagnosis of the responsible physicians. Chronic pain was defined as pain lasting six months or longer. Features of chronic pain were assessed with the German Pain Questionnaire, including the Depression Anxiety and Stress Scale-21 (DASS-21). Associations with POD were assessed using logistic regression analysis adjusting for confounding factors.
RESULTS: Thirty-nine (22%) out of 176 patients developed POD. Chronic pain was not associated with POD after adjustment for ASA physical status, duration of anesthesia and DASS-21 Anxiety score (Odds ratio [OR], 95%-Confidence Interval [CI], 2.216 [0.968;5.070], P=0.060). A subgroup analysis of chronic pain patients revealed that current pain intensity was higher in patients with POD.
CONCLUSIONS: Preoperative chronic pain was no independent predictor for POD. Current pain intensity was higher in chronic pain patients with POD. This indicates that certain features of pain might be influential. Further research is needed to examine different forms of preoperative pain and their possible influence on POD.
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.
This study reported the impact of electron beam (e-beam) treatment on microbiota and mycotoxins naturally present in red pepper powder and physicochemical quality changes. Treatment at 6 kGy indicated significant (p < 0.05) decontamination of yeasts and molds by 3.0 and 4.4 log CFU/g, respectively. A reduction of 4.5 log CFU/g of total plate counts (TPC) was observed at 10 kGy for 23 s. Fungal inactivation followed first-order kinetics while TPC better fitted with Gompertz function (R2 = 0.9912). E-beam treatment was not efficient for the degradation of aflatoxins but indirectly controlled their production by inactivation of mycotoxigenic molds. Indeed, reduction of 25% ochratoxin A was recorded at 30 kGy retaining >85% of total phenols, carotenoids and antioxidants activity. Moreover, treatment impact on total color difference (ΔE*) indicated ‘slight differences’. Overall, e-beam treatments up to 10 kGy were efficient in decontaminating the natural microbiota without detrimental effects on the physicochemical qualities of red pepper powder.