Objective
Treatment of congenital adrenal hyperplasia (CAH) patients with glucocorticoids is often challenging since there is a delicate balance between over‐ and undertreatment. Treatment can be ...monitored noninvasively by measuring salivary androstenedione (A4) and 17‐hydroxyprogesterone (17‐OHP). Optimal treatment monitoring requires the establishment of reference values in saliva.
Design
A descriptive study.
Patients
For this study saliva of 255 healthy paediatric and adult volunteers with an age range of 4–75 years old was used.
Measurements
We developed a sensitive liquid chromatography‐tandem mass spectrometry method, assessed salivary A4 and 17‐OHP stability, and measured A4 and 17‐OHP concentrations in saliva collected in the morning, afternoon, and evening.
Results
We quantified A4 and 17‐OHP concentrations in the morning, afternoon, and evening and demonstrated that there is a significant rhythm with the highest levels in the morning and decreasing levels over the day. A4 and 17‐OHP concentrations display an age‐dependent pattern. These steroids remain stable in saliva at ambient temperature for up to 5 days.
Conclusions
Good stability of the steroids in saliva enables saliva collection by the patient at home. Since salivary A4 and 17‐OHP display a diurnal rhythm and age‐dependent pattern, we established reference values for both children and adults at three time points during the day. These reference values support treatment monitoring of children and adults with CAH.
Major Depressive Disorder (MDD) is a heterogeneous disorder with a considerable symptomatic overlap with other psychiatric and somatic disorders. This study aims at providing evidence for association ...of a set of serum and urine biomarkers with MDD. We analyzed urine and serum samples of 40 MDD patients and 47 age- and sex-matched controls using 40 potential MDD biomarkers (21 serum biomarkers and 19 urine biomarkers). All participants were of Caucasian origin. We developed an algorithm to combine the heterogeneity at biomarker level. This method enabled the identification of correlating biomarkers based on differences in variation and distribution between groups, combined the outcome of the selected biomarkers, and calculated depression probability scores (the “bio depression score”). Phenotype permutation analysis showed a significant discrimination between MDD and euthymic (control) subjects for biomarkers in urine (P < .001), in serum (P = .02) and in the combined serum plus urine result (P < .001). Based on this algorithm, a combination of 8 urine biomarkers and 9 serum biomarkers were identified to correlate with MDD, enabling an area under the curve (AUC) of 0.955 in a Receiver Operating Characteristic (ROC) analysis. Selection of either urine biomarkers or serum biomarkers resulted in AUC values of 0.907 and 0.853, respectively. Internal cross-validation (5-fold) confirmed the association of this set of biomarkers with MDD.
•This study investigates biomarker panels for Major Depressive Disorder (MDD).•The biomarker panels were assessed in serum as well as in urine.•A new method was used to combine results of multiple biomarkers into a single score.•This scoring method is based on differences in variation and distribution.•A panel of 9 serum and 8 urine biomarkers was identified to correlate with MDD.
We examined imprecision and limit of quantification (LOQ) of the new Architect 25-hydroxyvitamin D immunoassay in a multicenter setting. Mean intracenter interlot imprecision varied from 22.0 to ...5.0%CV in the concentration range of 16 - 92 nmol/L. LOQs were locally determined as 10.8, 11.2, and 13.5 nmol/L. We conclude that the Architect 25(OH)D assay provides a precise and analytically sensitive method for routine measurement of 25(OH)D.
We studied precision and accuracy of a HPLC method for determination of porphyrins in feces. A commercial standard solution appeared to contain less coproporphyrin (15%) than stated by the ...manufacturer. The between-batch coefficients of variation were often below 15% and were higher than the within-batch coefficients. The precision of porphyrin measurements was not influenced by the type of porphyria. Recoveries of added coproporphyrin and protoporphyrin were 90% and 108%; coefficients of variation were 6% and 19%, respectively.
This study systematically reviewed the evidence pertaining to socioeconomic inequalities in different domains of physical activity (PA) by European region.
Studies conducted between January 2000 and ...December 2010 were identified by a systematic search in Pubmed, Embase, Web of Science, Psychinfo, Sportdiscus, Sociological Abstracts, and Social Service Abstracts. English-language peer-reviewed studies undertaken in the general population of adults (18-65 years) were classified by domain of PA (total, leisure-time including sport, occupational, active transport), indicator of socioeconomic position (education, income, occupation), and European region. Distributions of reported positive, negative, and null associations were evaluated.
A total of 131 studies met the inclusion criteria. Most studies were conducted in Scandinavia (n = 47). Leisure-time PA was the most frequently studied PA outcome (n = 112). Considerable differences in the direction of inequalities were seen for the different domains of PA. Most studies reported that those with high socioeconomic position were more physically active during leisure-time compared to those with low socioeconomic position (68% positive associations for total leisure-time PA, 76% for vigorous leisure-time PA). Occupational PA was more prevalent among the lower socioeconomic groups (63% negative associations). Socioeconomic differences in total PA and active transport PA did not show a consistent pattern (40% and 38% positive associations respectively). Some inequalities differed by European region or socioeconomic indicator, however these differences were not very pronounced.
The direction of socioeconomic inequalities in PA in Europe differed considerably by domain of PA. The contradictory results for total PA may partly be explained by contrasting socioeconomic patterns for leisure-time PA and occupational PA.
The availability of methotrexate and the introduction of multiple biological agents have revolutionized the treatment of juvenile idiopathic arthritis (JIA). Several international and national drug ...registries have been implemented to accurately monitor the long-term safety/efficacy of these agents. This report aims to present the combined data coming from Pharmachild/PRINTO registry and the national registries from Germany (BiKeR) and Sweden.
Descriptive statistics was used for demographic, clinical data, drug exposure, adverse events (AEs) and events of special interest (ESIs). For the Swedish register, AE data were not available.
Data from a total of 15,284 patients were reported: 8274 (54%) from the Pharmachild registry and 3990 (26%) and 3020 (20%) from the German and the Swedish registries, respectively. Pharmachild children showed a younger age (median of 5.4 versus 7.6 years) at JIA onset and shorter disease duration at last available visit (5.3 versus 6.1-6.8) when compared with the other registries. The most frequent JIA category was the rheumatoid factor-negative polyarthritis (range of 24.6-29.9%). Methotrexate (61-84%) and etanercept (24%-61.8%) were the most frequently used synthetic and biologic disease-modifying anti-rheumatic drugs (DMARDs), respectively. There was a wide variability in glucocorticoid use (16.7-42.1%). Serious AEs were present in 572 (6.9%) patients in Pharmachild versus 297 (7.4%) in BiKeR. Infection and infestations were the most frequent AEs (29.4-30.1%) followed by gastrointestinal disorders (11.5-19.6%). The most frequent ESIs were infections (75.3-89%).
This article is the first attempt to present a very large sample of data on JIA patients from different national and international registries and represents the first proposal for data merging as the most powerful tool for future analysis of safety and effectiveness of immunosuppressive therapies in JIA.
The Pharmachild registry is registered at ClinicalTrials.gov ( NCT01399281 ) and at the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) ( http://www.encepp.eu/encepp/viewResource.htm?id=19362 ). The BiKeR registry is registered at ENCePP ( http://www.encepp.eu/encepp/viewResource.htm?id=20591 ).
The current ecological approach in health behaviour research recognises that health behaviour needs to be understood in a broad environmental context. This has led to an exponential increase in the ...number of studies on this topic. It is the aim of this systematic review to summarise the existing empirical evidence pertaining to environmental influences on fruit and vegetable (FV) consumption. The environment was defined as 'all factors external to the individual'. Scientific databases and reference lists of selected papers were systematically searched for observational studies among adults (18-60 years old), published in English between 1 January 1980 and 31 December 2004, with environmental factor(s) as independent factor(s), and fruit intake, vegetable intake or FV intake combined as one outcome measure as dependent factor(s). Findings showed there was a great diversity in the environmental factors studied, but that the number of replicated studies for each determinant was limited. Most evidence was found for household income, as people with lower household incomes consistently had a lower FV consumption. Married people had higher intakes than those who were single, whereas having children showed mixed results. Good local availability (e.g. access to one's own vegetable garden, having low food insecurity) seemed to exert a positive influence on intake. Regarding the development of interventions, improved opportunities for sufficient FV consumption among low-income households are likely to lead to improved intakes. For all other environmental factors, more replicated studies are required to examine their influence on FV intake.
Background Patients who have undergone the Fontan procedure are at high risk of circulatory failure. In an exploratory analysis we aimed to determine the prognostic value of blood biomarkers in a ...young cohort who have undergone the Fontan procedure. Methods and Results In multicenter prospective studies patients who have undergone the Fontan procedure underwent blood sampling, cardiopulmonary exercise testing, and stress cardiac magnetic resonance imaging. Several biomarkers including NT-proBNP (N-terminal pro-B-type natriuretic peptide), GDF-15 (growth differentiation factor 15), Gal-3 (galectin-3), ST2 (suppression of tumorigenicity 2), DLK-1 (protein delta homolog 1), FABP-4 (fatty acid-binding protein 4), IGFBP-1 (insulin-like growth factor-binding protein 1), IGFBP-7, MMP-2 (matrix metalloproteinase 2), and vWF (von Willebrand factor) were assessed in blood at 9.6 (7.1-12.1) years after Fontan completion. After this baseline study measurement, follow-up information was collected on the incidence of adverse cardiac events, including cardiac death, out of hospital cardiac arrest, heart transplantation (listing), cardiac reintervention (severe events), hospitalization, and cardioversion/ablation for arrhythmias was collected and the relation with blood biomarkers was assessed by Cox proportional hazard analyses. The correlation between biomarkers and other clinical parameters was evaluated. We included 133 patients who have undergone the Fontan procedure, median age 13.2 (25th, 75th percentile 10.4-15.9) years, median age at Fontan 3.2 (2.5-3.9) years. After a median follow-up of 6.2 (4.9-6.9) years, 36 (27.1%) patients experienced an event of whom 13 (9.8%) had a severe event. NT-proBNP was associated with (all) events during follow-up and remained predictive after correction for age, sex, and dominant ventricle (hazard ratio, 1.89; CI, 1.32-2.68). The severe event-free survival was better in patients with low levels of GDF-15 (
=0.005) and vWF (
=0.008) and high levels of DLK-1 (
=0.041). There was a positive correlation (β=0.33,
=0.003) between DLK-1 and stress cardiac magnetic resonance imaging functional reserve. Conclusions NT-proBNP, GDF-15, vWF, DLK-1, ST-2 FABP-4, and IGFBP-7 levels relate to long-term outcome in young patients who have undergone the Fontan procedure.
Despite conventional radiation therapy, 54 Gy in single doses of 1.8 Gy (54/1.8 Gy) over 6 weeks, most children with diffuse intrinsic pontine glioma (DIPG) will die within 1 year after diagnosis. To ...reduce patient burden, we investigated the role of hypofractionation radiation therapy given over 3 to 4 weeks. A 1:1 matched-cohort analysis with conventional radiation therapy was performed to assess response and survival.
Twenty-seven children, aged 3 to 14, were treated according to 1 of 2 hypofractionation regimens over 3 to 4 weeks (39/3 Gy, n=16 or 44.8/2.8 Gy, n=11). All patients had symptoms for ≤3 months, ≥2 signs of the neurologic triad (cranial nerve deficit, ataxia, long tract signs), and characteristic features of DIPG on magnetic resonance imaging. Twenty-seven patients fulfilling the same diagnostic criteria and receiving at least 50/1.8 to 2.0 Gy were eligible for the matched-cohort analysis.
With hypofractionation radiation therapy, the overall survival at 6, 9, and 12 months was 74%, 44%, and 22%, respectively. Progression-free survival at 3, 6, and 9 months was 77%, 43%, and 12%, respectively. Temporary discontinuation of steroids was observed in 21 of 27 (78%) patients. No significant difference in median overall survival (9.0 vs 9.4 months; P=.84) and time to progression (5.0 vs 7.6 months; P=.24) was observed between hypofractionation vs conventional radiation therapy, respectively.
For patients with newly diagnosed DIPG, a hypofractionation regimen, given over 3 to 4 weeks, offers equal overall survival with less treatment burden compared with a conventional regimen of 6 weeks.
Background
Absolute myocardial perfusion imaging (MPI) is beneficial in the diagnosis and prognosis of patients with suspected or known coronary artery disease. However, validation and ...standardization of perfusion estimates across centers is needed to ensure safe and adequate integration into the clinical workflow. Physical myocardial perfusion models can contribute to this clinical need as these can provide ground-truth validation of perfusion estimates in a simplified, though controlled setup. This work presents the design and realization of such a myocardial perfusion phantom and highlights initial performance testing of the overall phantom setup using dynamic single photon emission computed tomography.
Results
Due to anatomical and (patho-)physiological representation in the 3D printed myocardial perfusion phantom, we were able to acquire 22 dynamic MPI datasets in which
99m
Tc-labelled tracer kinetics was measured and analyzed using clinical MPI software. After phantom setup optimization, time activity curve analysis was executed for measurements with normal myocardial perfusion settings (1.5 mL/g/min) and with settings containing a regional or global perfusion deficit (0.8 mL/g/min). In these measurements, a specific amount of activated carbon was used to adsorb radiotracer in the simulated myocardial tissue. Such mimicking of myocardial tracer uptake and retention over time satisfactorily matched patient tracer kinetics. For normal perfusion levels, the absolute mean error between computed myocardial blood flow and ground-truth flow settings ranged between 0.1 and 0.4 mL/g/min.
Conclusion
The presented myocardial perfusion phantom is a first step toward ground-truth validation of multimodal, absolute MPI applications in the clinical setting. Its dedicated and 3D printed design enables tracer kinetic measurement, including time activity curve and potentially compartmental myocardial blood flow analysis.
PDF
