A longitudinal follow-up study of parent-reported family impact and quality of life in young patients with traumatic and non-traumatic brain injury

PurposeBrain injuries (traumatic-/nontraumatic, TBI/nTBI) in young patients may lead to problems e.g., decreased health-related quality of life (HRQoL), and causes family impact. Knowledge regarding the family impact and the relationship with patients' HRQoL over time is scarce. This follow-up study describes family impact/HRQoL and their mutual relationship in young patients (5-24 years) after TBI/nTBI.Materials and methodsParents of patients that were referred to outpatient rehabilitation completed the PedsQL (TM) Family-Impact-Module questionnaire to assess the family impact and the parent-reported PedsQL (TM) Generic-core-set-4.0 to assess patients' HRQoL (lower scores: more family impact/worse HRQoL). Questionnaires were completed at the time of referral to rehabilitation (baseline) and one/two years later (T1/T2). Linear-mixed models were used to examine family impact/HRQoL change scores, and repeated-measure correlations (r) to determine longitudinal relationships.ResultsTwo-hundred-forty-six parents participated at baseline, 72 (at T2), median patient's age at baseline was 14 years (IQR:11-16), and 181 (74%) had TBI. Mean (SD) PedsQL (TM) Family-Impact-Module score at baseline was 71.7 (SD:16.4) and PedsQL (TM) Generic-core-set-4.0: 61.4 (SD:17.0). Over time, PedsQL (TM) Family-Impact-Module scores remained stable, while PedsQL (TM) Generic-core-set-4.0 scores improved significantly(p < 0.05). A moderately strong longitudinal correlation was found between family impact&HRQoL (r = 0.51).ConclusionsFamily impact does not tend to decrease over time but remained a considerable problem, although patients' HRQoL improved. Next to focusing on patients' HRQoL, it remains important to consider family impact and offer family support throughout rehabilitation.</p

Fatigue in young patients with acquired brain injury in the outpatient rehabilitation setting: a 2-year follow-up study

Acquired brain injury (ABI) may cause fatigue and participation restrictions in young patients. However, knowledge regarding the course of these problems over time is lacking. This study aims to describe the course of fatigue and participation and their relationship over time in an observational two-year follow-up study among patients(5-24 years) with ABI referred for outpatient rehabilitation and their parents. Patients/parents completed the PedsQL (TM) Multidimensional-Fatigue-Scale(PedsQL (TM) MFS, totalscore/3-domains) and the Child/Adolescent-Scale of Participation(CASP, totalscore/4-domains). Scores ranged from 0-100: lower scores = more fatigue/participation problems. Linear mixed models and repeated measures correlations were used to determine the course over time (change-scores/95%CI) and correlations between fatigue/participation. At baseline, 223 patients/246 parents participated with 94/104 at either T1, T2 or both. Median age was 15 years (IQR:12-17), 74% had a traumatic brain injury. Mean(SD) patient/parent-reported PedsQL (TM) MFS totalscores(baseline) were: 50.3(17.3) and 53.8(19.1), respectively. CASP totalscores were 78.0(16.4) and 87.1(13.6). Over time, patient-reported scores improved significantly (fatigue: + 8.8 (2.9;14.7), p < 0.05)/participation: + 10.5 (6.3;14.7), p < 0.05)). Similar results were found regarding parent-reported fatigue: + 8.7 (3.4;13.9), p < 0.05 but not regarding participation. Two years later, fatigue was still considerable(patients:59.1/parents:62.5). Moderate/fair correlations between fatigue/participation over time were found. Fatigue and participation in young patients with ABI improved two years after referral to rehabilitation. However, fatigue remained a considerable problem

Parent-reported family impact in children and young adults with acquired brain injury in the outpatient rehabilitation setting

Purpose: To increase knowledge/awareness on family impact (FI) after acquired brain injury (ABI) in rehabilitation settings, it is essential to investigate the associations between patient-functioning and impact on families. This has been explored in hospital-based cohorts, but not in rehabilitation settings.Methods: A cross-sectional, multi-center study among parents of children/young adults (aged 57-6 months after onset, diminished patients' mental/emotional health and HRQoL (child/family factors), and premorbid problems were associated with higher FI.Conclusions: In this rehabilitation cohort, pediatric ABI caused considerably higher FI than in hospital-based studies with referral to rehabilitation >6 months, diminished child/family factors and presence of premorbid problems increasing FI. Assessing and monitoring FI and its associated factors enables professionals to individualize treatment, psychoeducation, support and follow-up.Orthopaedics, Trauma Surgery and Rehabilitatio

Participation restrictions among children and young adults with acquired brain injury in a pediatric outpatient rehabilitation cohort: the patients' and parents' perspective

Improving participation is an important aim in outpatient rehabilitation treatment. Knowledge regarding participation restrictions in children and young adults with acquired brain injury (ABI) is scarce and little is known regarding the differences in perspectives between patients and parents in the outpatient rehabilitation setting. The aims are to describe participation restrictions among children/young adults (5-24 years) with ABI and investigating differences between patients' and parents' perspectives. At admission in 10 rehabilitation centers, patients and parents were asked to complete the Child and Adolescent Scale of Participation (CASP; score 0-100; lower score = more restrictions) and injury/patient/family-related questions. CASP scores were categorized (full/somewhat-limited/limited/very-limited participation). Patient/parent-reported outcomes were compared using the Wilcoxon signed-rank test. 223 patients and 245 parents participated (209 paired-samples). Median patients' age was 14 years (IQR; 11-16), 135 were female (52%), 195 had traumatic brain injury (75%). The median CASP score reported by patients was 82.5 (IQR: 67.5-90) and by parents 91.3 (IQR: 80.0-97.5) (difference = p < 0.05). The score of 58 patients (26%) and 25 parents (10%) was classified as 'very-limited'. Twenty-six percent of children and young adults referred for rehabilitation after ABI had "very-limited" participation. Overall, parents rated their child's participation better than patients themselves. Quantifying participation restrictions after ABI and considering both perspectives is important for outpatient rehabilitation treatment.Orthopaedics, Trauma Surgery and Rehabilitatio

Microglial activation in Alzheimer's disease: an (R)-[11C]PK11195 positron emission tomography study

AbstractInflammatory mechanisms, like microglial activation, could be involved in the pathogenesis of Alzheimer's disease (AD). (R)-[11C]PK11195 (1-(2-chlorophenyl)-N-methyl-N-1(1-methylpropyl)-3-isoquinolinecarboxamide), a positron emission tomography (PET) ligand, can be used to quantify microglial activation in vivo. The purpose of this study was to assess whether increased (R)-[11C]PK11195 binding is present in AD and mild cognitive impairment (MCI), currently also known as “prodromal AD.”MethodsNineteen patients with probable AD, 10 patients with prodromal AD (MCI), and 21 healthy control subjects were analyzed. Parametric images of binding potential (BPND) of (R)-[11C]PK11195 scans were generated using receptor parametric mapping (RPM) with supervised cluster analysis. Differences between subject groups were tested using mixed model analysis, and associations between BPND and cognition were evaluated using Pearson correlation coefficients.ResultsVoxel-wise statistical parametric mapping (SPM) analysis showed small clusters of significantly increased (R)-[11C]PK11195 BPND in occipital lobe in AD dementia patients compared with healthy control subjects. Regions of interest (ROI)-based analyses showed no differences, with large overlap between groups. There were no differences in (R)-[11C]PK11195 BPND between clinically stable prodromal AD patients and those who progressed to dementia, and BPND did not correlate with cognitive function.ConclusionMicroglial activation is a subtle phenomenon occurring in AD

Discovery of early-stage biomarkers for diabetic kidney disease using ms-based metabolomics (FinnDiane study)

Diabetic kidney disease (DKD) is a devastating complication that affects an estimated third of patients with type 1 diabetes mellitus (DM). There is no cure once the disease is diagnosed, but early treatment at a sub-clinical stage can prevent or at least halt the progression. DKD is clinically diagnosed as abnormally high urinary albumin excretion rate (AER). We hypothesize that subtle changes in the urine metabolome precede the clinically significant rise in AER. To test this, 52 type 1 diabetic patients were recruited by the FinnDiane study that had normal AER (normoalbuminuric). After an average of 5.5 years of follow-up half of the subjects (26) progressed from normal AER to microalbuminuria or DKD (macroalbuminuria), the other half remained normoalbuminuric. The objective of this study is to discover urinary biomarkers that differentiate the progressive form of albuminuria from non-progressive form of albuminuria in humans. Metabolite profiles of baseline 24 h urine samples were obtained by gas chromatography–mass spectrometry (GC–MS) and liquid chromatography–mass spectrometry (LC–MS) to detect potential early indicators of pathological changes. Multivariate logistic regression modeling of the metabolomics data resulted in a profile of metabolites that separated those patients that progressed from normoalbuminuric AER to microalbuminuric AER from those patients that maintained normoalbuminuric AER with an accuracy of 75% and a precision of 73%. As this data and samples are from an actual patient population and as such, gathered within a less controlled environment it is striking to see that within this profile a number of metabolites (identified as early indicators) have been associated with DKD already in literature, but also that new candidate biomarkers were found. The discriminating metabolites included acyl-carnitines, acyl-glycines and metabolites related to tryptophan metabolism. We found candidate biomarkers that were univariately significant different. This study demonstrates the potential of multivariate data analysis and metabolomics in the field of diabetic complications, and suggests several metabolic pathways relevant for further biological studies

A common and functional mineralocorticoid receptor haplotype enhances optimism and protects against depression in females

Mineralocorticoid (MR) and glucocorticoid receptors (GR) are abundantly expressed in the limbic brain and mediate cortisol effects on the stress-response and behavioral adaptation. Dysregulation of the stress response impairs adaptation and is a risk factor for depression, which is twice as abundant in women than in men. Because of the importance of MR for appraisal processes underlying the initial phase of the stress response we investigated whether specific MR haplotypes were associated with personality traits that predict the risk of depression. We discovered a common gene variant (haplotype 2, frequency ∼0.38) resulting in enhanced MR activity. Haplotype 2 was associated with heightened dispositional optimism in study 1 and with less hopelessness and rumination in study 2. Using data from a large genome-wide association study we then established that haplotype 2 was associated with a lower risk of depression. Interestingly, all effects were restricted to women. We propose that common functional MR haplotypes are important determinants of inter-individual variability in resilience to depression in women by differentially mediating cortisol effects on the stress system

Lipidomics Reveals Multiple Pathway Effects of a Multi-Components Preparation on Lipid Biochemistry in ApoE*3Leiden.CETP Mice

Background: Causes and consequences of the complex changes in lipids occurring in the metabolic syndrome are only partly understood. Several interconnected processes are deteriorating, which implies that multi-target approaches might be more successful than strategies based on a limited number of surrogate markers. Preparations from Chinese Medicine (CM) systems have been handed down with documented clinical features similar as metabolic syndrome, which might help developing new intervention for metabolic syndrome. The progress in systems biology and specific animal models created possibilities to assess the effects of such preparations. Here we report the plasma and liver lipidomics results of the intervention effects of a preparation SUB885C in apolipoprotein E3 Leiden cholesteryl ester transfer protein (ApoE*3Leiden.CETP) mice. SUB885C was developed according to the principles of CM for treatment of metabolic syndrome. The cannabinoid receptor type 1 blocker rimonabant was included as a general control for the evaluation of weight and metabolic responses. Methodology/Principal Findings: ApoE*3Leiden.CETP mice with mild hypercholesterolemia were divided into SUB885C-, rimonabant- and non-treated control groups. SUB885C caused no weight loss, but significantly reduced plasma cholesterol (-49%, p <0.001), CETP levels (-31%,

Plasma metabolomics and proteomics profiling after a postprandial challenge reveal subtle diet effects on human metabolic status

We introduce the metabolomics and proteomics based Postprandial Challenge Test (PCT) to quantify the postprandial response of multiple metabolic processes in humans in a standardized manner. The PCT comprised consumption of a standardized 500 ml dairy shake containing respectively 59, 30 and 12 energy percent lipids, carbohydrates and protein. During a 6 h time course after PCT 145 plasma metabolites, 79 proteins and 7 clinical chemistry parameters were quantified. Multiple processes related to metabolism, oxidation and inflammation reacted to the PCT, as demonstrated by changes of 106 metabolites, 31 proteins and 5 clinical chemistry parameters. The PCT was applied in a dietary intervention study to evaluate if the PCT would reveal additional metabolic changes compared to non-perturbed conditions. The study consisted of a 5-week intervention with a supplement mix of anti-inflammatory compounds in a crossover design with 36 overweight subjects. Of the 231 quantified parameters, 31 had different responses over time between treated and control groups, revealing differences in amino acid metabolism, oxidative stress, inflammation and endocrine metabolism. The results showed that the acute, short term metabolic responses to the PCT were different in subjects on the supplement mix compared to the controls. The PCT provided additional metabolic changes related to the dietary intervention not observed in non-perturbed conditions. Thus, a metabolomics based quantification of a standardized perturbation of metabolic homeostasis is more informative on metabolic status and subtle health effects induced by (dietary) interventions than quantification of the homeostatic situation