Investigation of urinary steroid metabolites in calf urine after oral and intramuscular administration of DHEA

DHEA (3ß-hydroxy-androst-5-en-17-one) is a natural steroid prohormone. Despite a lack of information on the effect, DHEA and other prohormones are frequently used as a food supplement by body-builders. DHEA is suspected for growth promoting abuse in cattle as well. Considering the latter, urine samples from a previous exposure study in which calves were exposed to 1 g DHEA per day for 7 days, were used. The calves were divided in three groups: one orally treated, one intramuscularly injected, and a control group. The effect of this treatment on the urinary profile of several precursors and metabolites of DHEA was investigated. Urine samples were collected several days before and during the 7 days of administration and were submitted to a clean-up procedure consisting of a separation of the different conjugates (free, glucuronidated, and sulfated forms) of each compound on a SAX column (Varian). An LC-MS/MS method was developed for the detection and quantification of several metabolites of the pathway of DHEA including 17a- and 17ß-testosterone, 4-androstenedione, 5-androstenediol, pregnenolone, and hydroxypregnenolone. Elevated levels of DHEA, 5-androstenediol, and 17a-testosterone were observed in the free and sulfated fraction of the urine of the treated calves, thus indicating that the administered DHEA is metabolized mainly by the ¿5-pathway with 5-androstenediol as the intermediate. Sulfoconjugates of DHEA and its metabolites were found to constitute the largest proportion of the urinary metabolites. The free form was also present, but in a lesser extent than the sulfated form, while glucuronides were negligible

Symptom complexes in patients with seropositive arthralgia and in patients newly diagnosed with rheumatoid arthritis: a qualitative exploration of symptom development

Objective: The aim of this study was to explore symptoms and symptom development during the earliest phases of rheumatoid arthritis (RA) in patients with seropositive arthralgia and patients newly diagnosed with RA

Intermediate weight changes and follow-up of dietetic treatment in primary healthcare:An observational study

Background Primary health care data have shown that most patients who were treated for overweight or obesity by a dietitian did not accomplish the recommended treatment period. It is hypothesised that a slow rate of weight loss might discourage patients from continuing dietetic treatment. This study evaluated intermediate weight changes during regular dietetic treatment in Dutch primary health care, and examined whether weight losses at previous consultations were associated with attendance at follow-up consultations. Methods This observational study was based on real life practice data of overweight and obese patients during the period 2013–2017, derived from Dutch dietetic practices that participated in the Nivel Primary Care Database. Multilevel regression analyses were conducted to estimate the mean changes in body mass index (BMI) during six consecutive consultations and to calculate odds ratios for the association of weight change at previous consultations with attendance at follow-up consultations. Results The total study population consisted of 25,588 overweight or obese patients, with a mean initial BMI of 32.7 kg/m2. The BMI decreased between consecutive consultations, with the highest weight losses between the first and second consultation. After six consultations, a mean weight loss of − 1.5 kg/m2 was estimated. Patients who lost weight between the two previous consultations were more likely to attend the next consultation than patients who did not lose weight or gained weight. Conclusions Body mass index decreased during consecutive consultations, and intermediate weight losses were associated with a higher attendance at follow-up consultations during dietetic treatment in overweight patients. Dietitians should therefore focus on discussing intermediate weight loss expectations with their patients

Reliably estimating prevalences of atopic children: An epidemiological study in an extensive and representative primary care database

Electronic health records stored in primary care databases might be a valuable source to study the epidemiology of atopic disorders and their impact on health-care systems and costs. However, the prevalence of atopic disorders in such databases varies considerably and needs to be addressed. For this study, all children aged 0-18 years listed in a representative primary care database in the period 2002-2014, with sufficient data quality, were selected. The effects of four different strategies on the prevalences of atopic disorders were examined: (1) the first strategy examined the diagnosis as recorded in the electronic health records, whereas the (2) second used additional requirements (i.e., the patient had at least two relevant consultations and at least two relevant prescriptions). Strategies (3) and (4) assumed the atopic disorders to be chronic based on strategy 1 and 2, respectively. When interested in cases with a higher probability of a clinically relevant disorder, strategy 2 yields a realistic estimation of the prevalence of atopic disorders derived from primary care data. Using this strategy, of the 478,076 included children, 28,946 (6.1%) had eczema, 29,182 (6.1%) had asthma, and 28,064 (5.9%) had allergic rhinitis; only 1251 (0.3%) children had all three atopic disorders. Prevalence rates are highly dependent on the clinical atopic definitions used. The strategy using cases with a higher probability of clinically relevant cases, yields realistic prevalences to establish the impact of atopic disorders on health-care systems. However, studies are needed to solve the problem of identifying atopic disorders that are missed or misclassified

Risks for comorbidity in children with atopic disorders: an observational study in Dutch general practices

OBJECTIVE: This study aimed to investigate both atopic and non-atopic comorbid symptoms and diseases in children with physician-diagnosed atopic disorders (atopic eczema, asthma and allergic rhinitis).METHODS: All children aged 0-18 years listed in a nationwide primary care database (the Netherlands Institute for Health Services Research-Primary Care Database) with routinely collected healthcare data in 2014 were selected. Children with atopic disorders were matched on age and gender with non-atopic controls within the same general practice. A total of 404 International Classification of Primary Care codes were examined. Logistic regression analyses were performed to examine the associations between the presence of atopic disorders and (non-)atopic symptoms and diseases by calculating ORs.RESULTS: Having one of the atopic disorders significantly increased the risk of having other atopic-related symptoms, even if the child was not registered as having the related atopic disorder. Regarding non-atopic comorbidity, children with atopic eczema (n=15 530) were at significantly increased risk for (infectious) skin diseases (OR: 1.2-3.4). Airway symptoms or (infectious) diseases (OR: 2.1-10.3) were observed significantly more frequently in children with asthma (n=7887). Children with allergic rhinitis (n=6835) had a significantly distinctive risk of ear-nose-throat-related symptoms and diseases (OR: 1.5-3.9). Neither age nor gender explained these increased risks.CONCLUSION: General practitioners are not always fully aware of relevant atopic and non-atopic comorbidity. In children known to have at least one atopic disorder, specific attention is required to avoid possible insufficient treatment and unnecessary loss of quality of life

A versatile, compartmentalised gut-on-a-chip system for pharmacological and toxicological analyses

A novel, integrated, in vitro gastrointestinal (GI) system is presented to study oral bioavailability parameters of small molecules. Three compartments were combined into one hyphenated, flow-through set-up. In the first compartment, a compound was exposed dynamically to enzymatic digestion in three consecutive microreactors, mimicking the processes of the mouth, stomach, and intestine. The resulting solution (chyme) continued to the second compartment, a flow-through barrier model of the intestinal epithelium allowing absorption of the compound and metabolites thereof. The composition of the effluents from the barrier model were analysed either offline by electrospray-ionisation-mass spectrometry (ESI-MS), or online in the final compartment using chip-based ESI-MS. Two model drugs, omeprazole and verapamil, were used to test the integrated model. Omeprazole was shown to be broken down upon treatment with gastric acid, but reached the cell barrier unharmed when introduced to the system in a manner emulating an enteric-coated formulation. In contrast, verapamil was unaffected by digestion. Finally, a reduced uptake of verapamil was observed when verapamil was introduced to the system dissolved in apple juice, a simple food matrix. It is envisaged that this integrated, compartmentalised GI system has potential for enabling future research in the fields of pharmacology, toxicology, and nutrition

Variation in detected adverse events using trigger tools: A systematic review and meta-analysis

Adverse event (AE) detection is a major patient safety priority. However, despite extensive research on AEs, reported incidence rates vary widely.; This study aimed: (1) to synthesize available evidence on AE incidence in acute care inpatient settings using Trigger Tool methodology; and (2) to explore whether study characteristics and study quality explain variations in reported AE incidence.; Systematic review and meta-analysis.; To identify relevant studies, we queried PubMed, EMBASE, CINAHL, Cochrane Library and three journals in the patient safety field (last update search 25.05.2022). Eligible publications fulfilled the following criteria: adult inpatient samples; acute care hospital settings; Trigger Tool methodology; focus on specialty of internal medicine, surgery or oncology; published in English, French, German, Italian or Spanish. Systematic reviews and studies addressing adverse drug events or exclusively deceased patients were excluded. Risk of bias was assessed using an adapted version of the Quality Assessment Tool for Diagnostic Accuracy Studies 2. Our main outcome of interest was AEs per 100 admissions. We assessed nine study characteristics plus study quality as potential sources of variation using random regression models. We received no funding and did not register this review.; Screening 6,685 publications yielded 54 eligible studies covering 194,470 admissions. The cumulative AE incidence was 30.0 per 100 admissions (95% CI 23.9-37.5; I2 = 99.7%) and between study heterogeneity was high with a prediction interval of 5.4-164.7. Overall studies' risk of bias and applicability-related concerns were rated as low. Eight out of nine methodological study characteristics did explain some variation of reported AE rates, such as patient age and type of hospital. Also, study quality did explain variation.; Estimates of AE studies using trigger tool methodology vary while explaining variation is seriously hampered by the low standards of reporting such as the timeframe of AE detection. Specific reporting guidelines for studies using retrospective medical record review methodology are necessary to strengthen the current evidence base and to help explain between study variation