Fractures in pituitary adenoma patients from the Dutch National Registry of Growth Hormone Treatment in Adults

Purpose: The effects of growth hormone (GH) replacement therapy on fracture risk in adult GH deficient (GHD) patients with different etiologies of pituitary GHD are not well known, due to limited data. The aim of this study was to investigate characteristics and fracture occurrence at start of (baseline) and during long-term GH replacement therapy in GHD adults previously treated for Cushing’s disease (CD) or acromegaly, compared to patients with previous nonfunctioning pituitary adenoma (NFPA). Methods: From the Dutch National Registry of Growth Hormone Treatment in Adults, a nationwide surveillance study in severe GHD adults, all patients using ≥30 days of GH replacement therapy with previous NFPA (n = 783), CD (n = 180) and acromegaly (n = 65) were selected. Patient characteristics, fractures and potential influencing factors were investigated. Results: At baseline, patients with previous CD were younger, more often female and had more often a history of osteopenia or osteoporosis, whereas patients with previous acromegaly had more often received cranial radiotherapy and a longer duration between treatment of their pituitary tumor and start of adult GH replacement therapy. During follow-up, a fracture occurred in 3.8 % (n = 39) of all patients. Compared to patients with previous NFPA, only patients with previous acromegaly had an increased fracture risk after 6 years of GH replacement therapy. Conclusions: During GH replacement therapy, an increased fracture risk was observed in severe GHD adult patients previously treated for acromegaly, but not in those previously treated for CD, compared to severe GHD adult patients using GH replacement therapy because of previous NFPA. Further studies are needed to confirm these findings and to elucidate potential underlying mechanisms

Population Pharmacokinetics and Dosing Optimization of Ceftazidime in Term Asphyxiated Neonates during Controlled Therapeutic Hypothermia

Ceftazidime is an antibiotic commonly used to treat bacterial infections in term neonates undergoing controlled therapeutic hypothermia (TH) for hypoxic-ischemic encephalopathy after perinatal asphyxia. We aimed to describe the population pharmacokinetics (PK) of ceftazidime in asphyxiated neonates during hypothermia, rewarming, and normothermia and propose a population-based rational dosing regimen with optimal PK/pharmacodynamic (PD) target attainment. Data were collected in the PharmaCool prospective observational multicenter study. A population PK model was constructed, and the probability of target attainment (PTA) was assessed during all phases of controlled TH using targets of 100% of the time that the concentration in the blood exceeds the MIC (T.MIC) (for efficacy purposes and 100% T.4×MIC and 100% T.5×MIC to prevent resistance). A total of 35 patients with 338 ceftazidime concentrations were included. An allometrically scaled one-compartment model with postnatal age and body temperature as covariates on clearance was constructed. For a typical patient receiving the current dose of 100 mg/kg of body weight/day in 2 doses and assuming a worst-case MIC of 8 mg/L for Pseudomonas aeruginosa, the PTA was 99.7% for 100% T.MIC during hypothermia (33.7°C; postnatal age [PNA] of 2 days). The PTA decreased to 87.7% for 100% T.MIC during normothermia (36.7°C; PNA of 5 days). Therefore, a dosing regimen of 100 mg/kg/day in 2 doses during hypothermia and rewarming and 150 mg/kg/day in 3 doses during the following normothermic phase is advised. Higher-dosing regimens (150 mg/kg/day in 3 doses during hypothermia and 200 mg/kg/day in 4 doses during normothermia) could be considered when achievements of 100% T.4×MIC and 100% T.5×MIC are desired.</p

Globally invariant metabolism but density-diversity mismatch in springtails.

Soil life supports the functioning and biodiversity of terrestrial ecosystems. Springtails (Collembola) are among the most abundant soil arthropods regulating soil fertility and flow of energy through above- and belowground food webs. However, the global distribution of springtail diversity and density, and how these relate to energy fluxes remains unknown. Here, using a global dataset representing 2470 sites, we estimate the total soil springtail biomass at 27.5 megatons carbon, which is threefold higher than wild terrestrial vertebrates, and record peak densities up to 2 million individuals per square meter in the tundra. Despite a 20-fold biomass difference between the tundra and the tropics, springtail energy use (community metabolism) remains similar across the latitudinal gradient, owing to the changes in temperature with latitude. Neither springtail density nor community metabolism is predicted by local species richness, which is high in the tropics, but comparably high in some temperate forests and even tundra. Changes in springtail activity may emerge from latitudinal gradients in temperature, predation and resource limitation in soil communities. Contrasting relationships of biomass, diversity and activity of springtail communities with temperature suggest that climate warming will alter fundamental soil biodiversity metrics in different directions, potentially restructuring terrestrial food webs and affecting soil functioning

Global fine-resolution data on springtail abundance and community structure

Springtails (Collembola) inhabit soils from the Arctic to the Antarctic and comprise an estimated ~32% of all terrestrial arthropods on Earth. Here, we present a global, spatially-explicit database on springtail communities that includes 249,912 occurrences from 44,999 samples and 2,990 sites. These data are mainly raw sample-level records at the species level collected predominantly from private archives of the authors that were quality-controlled and taxonomically-standardised. Despite covering all continents, most of the sample-level data come from the European continent (82.5% of all samples) and represent four habitats: woodlands (57.4%), grasslands (14.0%), agrosystems (13.7%) and scrublands (9.0%). We included sampling by soil layers, and across seasons and years, representing temporal and spatial within-site variation in springtail communities. We also provided data use and sharing guidelines and R code to facilitate the use of the database by other researchers. This data paper describes a static version of the database at the publication date, but the database will be further expanded to include underrepresented regions and linked with trait data.</p

Controlling complexity: the clinical relevance of mouse complex genetics.

Experimental animal models are essential to obtain basic knowledge of the underlying biological mechanisms in human diseases. Here, we review major contributions to biomedical research and discoveries that were obtained in the mouse model by using forward genetics approaches and that provided key insights into the biology of human diseases and paved the way for the development of novel therapeutic approaches

Cross-sectional and longitudinal associations between different exercise types and food cravings in free-living healthy young adults

Introduction: An increase in energy intake due to alterations in hedonic appetite sensations may, at least in part, contribute to lower-than-expected weight loss in exercise interventions. The aim of this study was to examine cross-sectional and longitudinal associations between habitual exercise participation and food cravings in free-living young adults. Methods: A total of 417 adults (49% male, 28 ± 4 years) reported frequency and duration of walking, aerobic exercise, resistance exercise and other exercise at baseline and every 3 months over a 12-month period. Food cravings were assessed via the Control of Eating Questionnaire at baseline and 12-month follow-up. Results: Cross-sectional analyses revealed more frequent cravings for chocolate and a greater difficulty to resist food cravings in women compared to men (p < 0.01). Only with resistance exercise significant sex by exercise interaction effects were observed with favorable responses in men but not in women. Significant main effects were shown for walking and aerobic exercise with exercisers reporting more frequent food cravings for chocolate and fruits and greater difficulty to resist eating compared to non-exercisers (p < 0.05). Longitudinal analyses revealed significant interaction effects for other exercise (p < 0.05) with favorable results in men but not women. Furthermore, significant main effects were observed for aerobic exercise, resistance exercise and total exercise with an increase in exercise being associated with a reduced difficulty to resist food cravings (p < 0.05). Discussion: The association between exercise participation and hedonic appetite sensations varies by exercise type and sex. Even though exercise was associated with more frequent and greater difficulty to food cravings in the cross-sectional analyses, which may be attributed to greater energy demands, longitudinal results indicate beneficial effects of increased exercise on appetite control, particularly in men

Evaluation of pharmacist clinical interventions in a Dutch hospital setting

OBJECTIVE: Assessing the relevance of a clinically active pharmacist method compared to the traditional working method. METHOD: The study was carried out in a general internal/gastro-enterology unit during two 8-weeks periods in 2004. It was an observational, non-randomized prospective study. Outcome measures were compared before and during the intervention. The intervention was the active presence of a junior hospital pharmacist on the unit. The pharmacist focused on the pharmacotherapy of the individual patient. Patients were included when they used 5 or more medicines on day 1 or 2 of their stay at the ward and/or used at least 1 high-risk drug. Clinical pharmacist interventions were counted and classified. A hospital pharmacist and an internal medicine specialist assessed the clinical relevance of all clinical pharmacist interventions retrospectively. The degree of acceptance of the interventions by physicians was measured. Finally, time associated with the clinical activities was measured. MAIN OUTCOME MEASURES: Number of interventions (related to number of medication orders), clinical relevance and degree of acceptance. RESULTS: In the pre-intervention period 79 patients were included versus 84 in the during-intervention period. About 82 interventions in the pre-intervention period were made compared to 173 during the during-intervention period. There was little agreement between the professional raters (weighted kappa(A-E)=0.30 and weighted kappa(1-5)=0.20). Nevertheless both ratings showed a substantial increase of clinically relevant interventions. The number of interventions accepted by the physician increased from 16 in the pre-intervention period to 75 in the during-intervention period. Working with this method took over 4 h a day. CONCLUSION: Clinical pharmacy services provided by a junior hospital pharmacist on an internal medicine ward contribute to rationalization of drug therapy and are therefore likely to increase medication safety

Impact of a Forced Dose-Equivalent Levothyroxine Brand Switch on Plasma Thyrotropin: A Cohort Study

Background: Patients with primary hypothyroidism are treated with levothyroxine (LT4) to normalize their serum thyrotropin (TSH). Finding the optimal dosage is a long-lasting process, and a small change can have major impact. Currently, limited data are available on the impact of dose-equivalent substitution between brands. This study aimed to determine the effect of the shortage of the LT4 brand Thyrax® in the Netherlands and the resulting dose-equivalent switch to another brand on plasma TSH concentrations in a large cohort of patients. Methods: Observational cohort study. Two registries representative for the Dutch population containing prescription and laboratory test data: the Nivel Primary Care Database and the PHARMO Database Network. Patients using at least 25 μg Thyrax daily for one year or longer were included. Two cohorts were formed: a switch cohort consisting of patients who switched from Thyrax to an alternative brand, and a Thyrax cohort including patients who continued to use Thyrax. Patients in the switch cohort did switch from Thyrax to a different brand of LT4 in 2016 and had two consecutive TSH measurements on the same dose of LT4, one before and one 6 weeks after the switch. Patients in the Thyrax cohort had two consecutive TSH measurements on the same dose of Thyrax that were 6 weeks apart. Results: In the Thyrax cohort, 19% of euthyroid patients using ≤100 μg had a TSH level outside the reference range at the subsequent measurement compared with 24% in the switch cohort (p 100 μg Thyrax, these figures were 24% and 63%, respectively (p 50 μg Thyrax were four to five times more likely to become hyperthyroid after a dose-equivalent switch to a different brand compared with patients who stayed on Thyrax. Conclusions: In euthyroid patients continuing the LT4 product Thyrax at the same dose, TSH was out of range in 19-24% at least 6 weeks later. A dose-equivalent switch from Thyrax to other LT4 brands induced biochemical signs of overdosing in an even larger proportion (24-63%) of patients. The results indicate that a dose-equivalent LT4 brand switch may necessitate a dose adjustment in a large number of patients