165 research outputs found
Reporting accuracy of packed lunch consumption among Danish 11-year-olds differ by gender.
Background: Packed lunch is the dominant lunch format in many countries including Denmark. School lunch is consumed unsupervised, and self-reported recalls are appropriate in the school setting. However, little is known about the accuracy of recalls in relation to packed lunch. Objective: To assess the qualitative recall accuracy of self-reported consumption of packed lunch among Danish 11-year-old children in relation to gender and dietary assessment method. Design: A cross-sectional dietary recall study of packed lunch consumption. Digital images (DIs) served as an objective reference method to determine food items consumed. Recalls were collected with a lunch recall questionnaire (LRQ) comprising an open-ended recall (OE-Q) and a pre-coded food group prompted recall (PC-Q). Individual interviews (INTs) were conducted successively. The number of food items was identified and accuracy was calculated as match rates (% identified by DIs and reported correctly) and intrusion rates (% not identified by DIs but reported) were determined. Setting and subjects: Three Danish public schools from Copenhagen. A total of 114 Danish 11-year-old children, mean (SE) age=11.1 (0.03), and body mass index=18.2 (0.26). Results: The reference (DIs) showed that girls consumed a higher number of food items than boys [mean (SE) 5.4 (0.25) vs. 4.6 (0.29) items (p=0.05)]. The number of food items recalled differed between genders with OE-Q recalls (p=0.005) only. Girls’ interview recalls were more accurate than boys’ with higher match rates (p=0.04) and lower intrusion rates (p=0.05). Match rates ranged from 67–90% and intrusion rates ranged from 13–39% with little differences between girls and boys using the OE-Q and PC-Q methods. Conclusion: Dietary recall validation studies should not only consider match rates as an account of accuracy. Intrusions contribute to over-reporting in non-validation studies, and future studies should address recall accuracy and inaccuracies in relation to gender and recall method
Heat transfer considerations on the spontaneous triggering of vapor explosions : a review
Vapor explosions have been investigated both theoretically and experimentally for several decades, focusing either on the vapor film, or on mechanical aspects. Where the main interest for industry lies in the safety risks of such an event, fundamental research is focusing on all partial processes that occur during a vapor explosion. In this paper, vapor explosions are discussed from a heat transfer point of view. Generally accepted knowledge of heat transfer between hot surfaces and liquids is compared to early investigations regarding the origin of vapor explosions. Both steady state and transient models are discussed. The review of available literature suggests that vapor explosions trigger spontaneously by the collapse of the boiling film. Better understanding of the fundamental aspects of vapor explosions might give rise to future ideas on how to avoid them
The interaction between stress and chronic pain through the lens of threat learning
Stress and pain are interleaved at multiple levels - interacting and influencing each other. Both are modulated by psychosocial factors including fears, beliefs, and goals, and are served by overlapping neural substrates. One major contributing factor in the development and maintenance of chronic pain is threat learning, with pain as an emotionally-salient threat – or stressor. Here, we argue that threat learning is a central mechanism and contributor, mediating the relationship between stress and chronic pain. We review the state of the art on (mal)adaptive learning in chronic pain, and on effects of stress and particularly cortisol on learning. We then provide a theoretical integration of how stress may affect chronic pain through its effect on threat learning. Prolonged stress, as may be experienced by patients with chronic pain, and its resulting changes in key brain networks modulating stress responses and threat learning, may further exacerbate these impairing effects on threat learning. We provide testable hypotheses and suggestions for how this integration may guide future research and clinical approaches in chronic pain
Parent Responses to Their Child's Pain: Systematic Review and Meta-Analysis of Measures
OBJECTIVE: Parent responses can have a major impact on their child's pain. The purpose of this systematic review is to (a) identify and describe measures assessing pain-related cognitive, affective, and behavioral responses in parents of children with chronic pain and (b) meta-analyze reported correlations between parent constructs and child outcomes (i.e., pain intensity, functional disability, and school functioning). Prospero protocol registration ID: CRD42019125496. METHODS: We conducted a systematic search of studies including a measure of parent/caregiver responses to their child's chronic pain. Study characteristics and correlations between parent measures and child outcomes were extracted. Data were summarized and meta-analyzed. RESULTS: Seventy-nine met inclusion criteria using 18 different measures of cognitive/affective (n = 3), behavioral (n = 5), and multidimensional responses (n = 10). Measures were used a median of three times (range 1-48), predominantly completed by mothers (88%), and primarily in mixed pain samples. Psychometrics of measures were generally adequate. Meta-analyses were based on 42 papers across five measures. Results showed that each of the cognitive, affective, and behavioral parent constructs we examined was significantly associated with pain-related functional disability. A small number of measures assessing parent cognitions and affective functioning were associated with higher child pain intensity; however, the majority were not. CONCLUSION: Findings demonstrate that there is a wealth of measures available, with adequate reliability overall but a lack of psychometrics on temporal stability. Synthesizing data across studies revealed small effects between parent responses and child functioning, and even smaller and/or absent effects on child pain intensity.</p
Family-Centeredness in Secure Residential Treatment and Its Relationship With Parental Involvement and Adolescent Behavioural Outcomes
Various Dutch secure residential youth care (SRYC) institutions are implementing a family-centered approach aiming to increase parental involvement and improve treatment outcomes. However, it remains unclear if and how family-centeredness (FC) is related to increased parental involvement and to improved treatment outcomes of adolescents. In this study, we unravelled the relation between FC, parental involvement, and behaviour problems of adolescents in SRYC. Families of 404 adolescents admitted to one of seven participating Dutch SRYC institutions completed a survey (at the start, at the end, and at 6-months follow-up) on problem behaviour of adolescents. In addition, 411 group care workers filled out a questionnaire about their residential group's level of FC every 6 months. Moreover, the mentor of each adolescent filled out a questionnaire about the level of parental involvement. We analysed the data using multiple mediator models. Associations were found between FC and parental involvement. However, no relation was found between FC and adolescent problem behaviour, and no mediation and no moderation effects of parental involvement were found. Overall, results showed that most parents were involved during the residential stay, and, independent of FC, adolescent problem behaviour decreased over time. Implementing FC in SRYC institutions seems to be helpful in involving parents during the residential stay, but was not found to be associated with adolescent behavioural outcomes. Our results indicate that institutions could improve their level of FC by offering more informal contact moments for parents and by addressing barriers to FC among residential staff
Microglia facilitate repair of demyelinated lesions via post-squalene sterol synthesis
The repair of inflamed, demyelinated lesions as in multiple sclerosis (MS) necessitates the clearance of cholesterol-rich myelin debris by microglia/macrophages and the switch from a pro-inflammatory to an anti-inflammatory lesion environment. Subsequently, oligodendrocytes increase cholesterol levels as a prerequisite for synthesizing new myelin membranes. We hypothesized that lesion resolution is regulated by the fate of cholesterol from damaged myelin and oligodendroglial sterol synthesis. By integrating gene expression profiling, genetics and comprehensive phenotyping, we found that, paradoxically, sterol synthesis in myelin-phagocytosing microglia/macrophages determines the repair of acutely demyelinated lesions. Rather than producing cholesterol, microglia/macrophages synthesized desmosterol, the immediate cholesterol precursor. Desmosterol activated liver X receptor (LXR) signaling to resolve inflammation, creating a permissive environment for oligodendrocyte differentiation. Moreover, LXR target gene products facilitated the efflux of lipid and cholesterol from lipid-laden microglia/macrophages to support remyelination by oligodendrocytes. Consequently, pharmacological stimulation of sterol synthesis boosted the repair of demyelinated lesions, suggesting novel therapeutic strategies for myelin repair in MS. Efficient repair of demyelinated CNS lesions involves the resolution of inflammation and induction of remyelination. Berghoff et al. show that sterol synthesis in microglia is key to both processes, which can be supported by squalene therapy
Phenobarbital, midazolam pharmacokinetics, effectiveness, and drug-drug interaction in asphyxiated neonates undergoing therapeutic hypothermia
Background: Phenobarbital and midazolam are commonly used drugs in (near-)term neonates treated with therapeutic hypothermia for hypoxic-ischaemic encephalopathy, for sedation, and/or as anti-epileptic drug. Phenobarbital is an inducer of cytochrome P450 (CYP) 3A, while midazolam is a CYP3A substrate. Therefore, co-treatment with phenobarbital might impact midazolam clearance.
Objectives: To assess pharmacokinetics and clinical anti-epileptic effectiveness of phenobarbital and midazolam in asphyxiated neonates and to develop dosing guidelines.
Methods: Data were collected in the prospective multicentre PharmaCool study. In the present study, neonates treated with therapeutic hypothermia and receiving midazolam and/or phenobarbital were included. Plasma concentrations of phenobarbital and midazolam including its metabolites were determined in blood samples drawn on days 2–5 after birth. Pharmacokinetic analyses were performed using non-linear mixed effects modelling; clinical effectiveness was defined as no use of additional anti-epileptic drugs.
Results: Data were available from 113 (phenobarbital) and 118 (midazolam) neonates; 68 were treated with both medications. Only clearance of 1-hydroxy midazolam was influenced by hypothermia. Phenobarbital co-administration increased midazolam clearance by a factor 2.3 (95% CI 1.9–2.9, p < 0.05). Anticonvulsant effectiveness was 65.5% for phenobarbital and 37.1% for add-on midazolam.
Conclusions: Therapeutic hypothermia does not influence clearance of phenobarbital or midazolam in (near-)term neonates with hypoxic-ischaemic encephalopathy. A phenobarbital dose of 30 mg/kg is advised to reach therapeutic concentrations. Phenobarbital co-administration significantly increased midazolam clearance. Should phenobarbital be substituted by non-CYP3A inducers as first-line anticonvulsant, a 50% lower midazolam maintenance dose might be appropriate to avoid excessive exposure during the first days after birth. © 2019 The Author(s) Published by S. Karger AG, Base
Pharmacokinetics of morphine in encephalopathic neonates treated with therapeutic hypothermia
Objective
Morphine is a commonly used drug in encephalopathic neonates treated with therapeutic hypothermia after perinatal asphyxia. Pharmacokinetics and optimal dosing of morphine in this population are largely unknown. The objective of this study was to describe pharmacokinetics of morphine and its metabolites morphine-3-glucuronide and morphine-6-glucuronide in encephalopathic neonates treated with therapeutic hypothermia and to develop pharmacokinetics based dosing guidelines for this population.
Study design
Term and near-term encephalopathic neonates treated with therapeutic hypothermia and receiving morphine were included in two multicenter cohort studies between 2008-2010 (SHIVER) and 2010-2014 (PharmaCool). Data were collected during hypothermia and rewarming, including blood samples for quantification of morphine and its metabolites. Parental informed consent was obtained for all participants.
Results
244 patients (GA mean (sd) 39.8 (1.6) weeks, BW mean (sd) 3,428 (613) g, male 61.5%) were included. Morphine clearance was reduced under hypothermia (33.5 degrees C) by 6.89%/degrees C (95% CI 5.37%/degrees C-8.41%/degrees C, p<0.001) and metabolite clearance by 4.91%/degrees C (95% CI 3.53%/degrees C-6.22%/degrees C, p<0.001) compared to normothermia (36.5 degrees C). Simulations showed that a loading dose of 50 mu g/kg followed by continuous infusion of 5 mu g/kg/h resulted in morphine plasma concentrations in the desired range (between 10 and 40 mu g/L) during hypothermia.
Conclusions
Clearance of morphine and its metabolites in neonates is affected by therapeutic hypothermia. The regimen suggested by the simulations will be sufficient in the majority of patients. However, due to the large interpatient variability a higher dose might be necessary in individual patients to achieve the desired effect
Tumoral Ki67 and PSMA Expression in Fresh Pre-PSMA-RLT Biopsies and Its Relation With PSMA-PET Imaging and Outcomes of PSMA-RLT in Patients With mCRPC
INTRODUCTION: Prostate specific membrane antigen (PSMA) directed radioligand therapy (RLT) is a novel therapy for metastatic castration-resistant prostate cancer (mCRPC) patients. However, it is still poorly understood why approximately 40% of the patients does not respond to PSMA-RLT. The aims of this study were to evaluate the pretreatment PSMA expression on immunohistochemistry (IHC) and PSMA uptake on PET/CT imaging in mCRPC patients who underwent PSMA-RLT. We correlated these parameters and a cell proliferation marker (Ki67) to the therapeutic efficacy of PSMA-RLT. PATIENTS AND METHODS: In this retrospective study, mCRPC patients who underwent PSMA-RLT were analyzed. Patients biopsies were scored for immunohistochemical Ki67 expression, PSMA staining intensity and percentage of cells with PSMA expression. Moreover, the PSMA tracer uptake of the tumor lesion(s) and healthy organs on PET/CT imaging was assessed. The primary outcome was to evaluate the association between histological PSMA protein expression of tumor in pre-PSMA-RLT biopsies and the PSMA uptake on PSMA PET/CT imaging of the biopsied lesion. Secondary outcomes were to assess the relationship between PSMA expression and Ki67 on IHC and the progression free survival (PFS) and overall survival (OS) following PSMA-RLT. RESULTS: In total, 22 mCRPC patients were included in this study. Nineteen (86%) patients showed a high and homogenous PSMA expression of >80% on IHC. Three (14%) patients had low PSMA expression on IHC. Although there was limited PSMA uptake on PET/CT imaging, these 3 patients had lower PSMA uptake on PET/CT imaging compared to the patients with high PSMA expression on IHC. Yet, no correlation was found between PSMA uptake on PET/CT imaging and PSMA expression on IHC (SUVmax: R2 = 0.046 and SUVavg: R2 = 0.036). The 3 patients had a shorter PFS compared to the patients with high PSMA expression on IHC (HR: 4.76, 95% CI: 1.14-19.99; P = .033). Patients with low Ki67 expression had a longer PFS and OS compared to patients with a high Ki67 expression (HR: 0.40, 95% CI: 0.15-1.06; P = .013) CONCLUSION: The PSMA uptake on PSMA-PET/CT generally followed the PSMA expression on IHC. However, heterogeneity may be missed on PSMA-PET/CT. Immunohistochemical PSMA and Ki67 expression in fresh tumor biopsies, may contribute to predict treatment efficacy of PSMA-RLT in mCRPC patients. This needs to be further explored in prospective cohorts
Changes in quality of life 1 year after intensive care: a multicenter prospective cohort of ICU survivors
BACKGROUND: With survival rates of critical illness increasing, quality of life measures are becoming an important outcome of ICU treatment. Therefore, to study the impact of critical illness on quality of life, we explored quality of life before and 1 year after ICU admission in different subgroups of ICU survivors. METHODS: Data from an ongoing prospective multicenter cohort study, the MONITOR-IC, were used. Patients admitted to the ICU in one of eleven participating hospitals between July 2016 and June 2021 were included. Outcome was defined as change in quality of life, measured using the EuroQol five-dimensional (EQ-5D-5L) questionnaire, and calculated by subtracting the EQ-5D-5L score 1 day before hospital admission from the EQ-5D-5L score 1 year post-ICU. Based on the minimal clinically important difference, a change in quality of life was defined as a change in EQ-5D-5L score of ≥ 0.08. Subgroups of patients were based on admission diagnosis. RESULTS: A total of 3913 (50.6%) included patients completed both baseline and follow-up questionnaires. 1 year post-ICU, patients admitted after a cerebrovascular accident, intracerebral hemorrhage, or (neuro)trauma, on average experienced a significant decrease in quality of life. Conversely, 11 other subgroups of ICU survivors reported improvements in quality of life. The largest average increase in quality of life was seen in patients admitted due to respiratory disease (mean 0.17, SD 0.38), whereas the largest average decrease was observed in trauma patients (mean -0.13, SD 0.28). However, in each of the studied 22 subgroups there were survivors who reported a significant increase in QoL and survivors who reported a significant decrease in QoL. CONCLUSIONS: This large prospective multicenter cohort study demonstrated the diversity in long-term quality of life between, and even within, subgroups of ICU survivors. These findings emphasize the need for personalized information and post-ICU care. TRIAL REGISTRATION: The MONITOR-IC study was registered at ClinicalTrials.gov: NCT03246334 on August 2nd 2017
- …
