The Dutch multidisciplinary guideline osteoporosis and fracture prevention, taking a local guideline to the international arena.

BACKGROUND: In 2018, a grant was provided for an evidence-based guideline on osteoporosis and fracture prevention based on 10 clinically relevant questions. METHODS: A multidisciplinary working group was formed with delegates from Dutch scientific and professional societies, including representatives from the patient's organization and the Dutch Institute for Medical Knowledge. The purpose was to obtain a broad consensus among all participating societies to facilitate the implementation of the updated guideline. RESULTS: Novel recommendations in our guideline are as follows: - In patients with an indication for DXA of the lumbar spine and hips, there is also an indication for VFA. - Directly starting with anabolic drugs (teriparatide or romosozumab) in patients with a very high fracture risk; - Directly starting with zoledronic acid in patients 75 years and over with a hip fracture (independent of DXA); - Directly starting with parenteral drugs (denosumab, teriparatide, zoledronic acid) in glucocorticoid-induced osteoporosis with very high fracture risk; - A lifelong fracture risk management, including lifestyle, is indicated from the start of the first treatment. CONCLUSION: In our new multidisciplinary guideline osteoporosis and fracture prevention, we developed 5 "relatively new statements" that are all a crucial step forward in the optimization of diagnosis and treatment for fracture prevention. We also developed 5 flowcharts, and we suppose that this may be helpful for individual doctors and their patients in daily practice and may facilitate implementation.

PPI use is not associated with bone microarchitecture and strength assessed with HR-pQCT after three-years follow-up in patients visiting the Fracture Liaison Service.

BACKGROUND: The use of proton pump inhibitors (PPIs) has been associated with an increased fracture risk in observational studies. However, the reported association between PPI use and bone mineral density (BMD), bone microarchitecture, and bone strength is inconsistent. This study aims to assess the association between PPI use and bone microarchitecture and strength using high-resolution peripheral quantitative CT (HR-pQCT) in a three-year follow-up study in patients with a recent fracture visiting the Fracture Liaison Service (FLS). METHODS: This three-year prospective cohort study included FLS patients aged ≥ 50 years with a recent fracture (median age 62 [IQR 56-69] years, 68.7 % females) and without anti-osteoporosis treatment indication. HR-pQCT scans (distal radius and tibia) were obtained at baseline (T0) and three-year follow-up (T3). Volumetric bone mineral density and bone area, microarchitecture, and strength (micro-finite element analysis) were determined. The association between three-year continuous PPI use and the percentage change in HR-pQCT parameters between T0 and T3 was assessed using sex-stratified multivariate linear regression analyses. Covariates included age, BMI, vitamin-D deficiency (< 50 nmol/l), glucocorticoid use, and cardiovascular co-morbidity (males and females) fracture type (major/hip vs. all others, only males) and probable sarcopenia (only females). RESULTS: In total, 282 participants had available medication data throughout follow-up, of whom 20.6 % were continuous PPI users. In both males and females with complete HR-pQCT follow-up data (males: N = 69 radius, N = 84 tibia; females: N = 147 radius, N = 168 tibia), PPI use was not associated with the percentage change of any of the bone microarchitecture or strength parameters between T0 and T3 at the radius and tibia as compared to non-use. CONCLUSION: Compared to non-use, PPI use was not associated with the change of bone microarchitecture and strength in FLS patients at three years of follow-up. These results do not support that an altered bone microarchitecture or strength may contribute to the increased fracture risk associated with PPI use, as reported in observational studies.

Physical performance and sarcopenia assessment in patients with a recent fracture visiting the Fracture Liaison Service.

Impaired physical performance is associated with increased fracture risk. Performance on four physical functioning tests and prevalence of sarcopenia were assessed for 1789 fracture patients and compared to reference data. Performance was low on all tests, especially for patients with a hip, major or ≥ 1 prevalent vertebral fracture. PURPOSE INTRODUCTION: Impaired physical performance and sarcopenia are associated with increased fracture risk. This study aims to assess physical performance and the prevalence of sarcopenia in patients with a recent clinical fracture attending the Fracture Liaison Service (FLS) compared to population means. METHODS: In this cross-sectional study, chair stand test (CST), handgrip strength (HGS), timed-up-and-go (TUG), 6-min walking-test (6MWT), and sarcopenia (following EWGSOP2) were assessed. The proportion of patients with impaired/poor performance compared to reference data was calculated (Z-score: ≥ - 2SD to < - 1 (impaired) and < - 2 SD (poor)). Associations of fracture type, sex, age, and time since fracture with Z-scores were assessed using linear regression analyses. RESULTS: A total of 1789 consecutive FLS patients were included (median age (IQR): 66 (59-74), 70.7% females, 3.9 (± 1.6) months after fracture). The prevalence of impaired/poor performance for CST, HGS, TUG, and 6MWT was 39.2%, 30.4%, 21.9%, and 71.5%, respectively (expected proportion of 16%) and 2.8% had sarcopenia. Lower Z-scores (P < 0.001) were found for hip, major, and ≥ 1 prevalent vertebral fracture (VF) in CST (major: regression coefficient (B) (95%CI) = - 0.25 [- 0.34, - 0.16]; hip: B = - 0.32 [- 0.47, - 0.17], VF: B = - 0.22 [- 0.34, - 0.11]), TUG; (major: B = - 0.54 [- 0.75, - 0.33]; hip: B = - 1.72 [- 2.08, -1.35], VF: B = - 0.61 [- 0.88, - 0.57]), 6MWT (major: B = - 0.34 [- 0.47, - 0.21]; hip: B = - 0.99 [- 1,22, - 0.77], VF: B = - 0.36 [- 0.53, - 0.19]). CONCLUSIONS: Physical performance is significantly lower in FLS patients compared to healthy peers, especially in patients with hip, major or prevalent VF. These findings underline the need to assess and improve the physical performance of FLS patients, despite a low prevalence of sarcopenia.

Physical Functioning in Patients with a Recent Fracture: The "Can Do, Do Do" Framework Applied to Explore Physical Capacity, Physical Activity and Fall Risk Factors.

Physical capacity (PC) and physical activity (PA) are associated physical performance measures, and combined, PC and PA are used to categorize physical performance in the "can do, do do" framework. We aimed to explore physical performance of patients attending the fracture liaison service (FLS). In this cross-sectional study, PC was measured by 6-min-walking-test (can't do/can do) and PA by accelerometer (don't do/do do). Following quadrants were defined based on predefined cut-off scores for poor performance: (1) "can't do, don't do"; (2) "can do, don't do"; (3) "can't do, do do"; (4) "can do, do do". Odds ratios (OR) were calculated and fall and fracture risk factors were assessed between quadrants. Physical performance of 400 fracture patients was assessed (mean age 64; female 70.8%). Patients performed as follows: 8.3% "can't do, don't do"; 3.0% "can do, don't do"; 19.3% "can't do, do do"; 69.5% "can do, do do". For the "can't do" group the OR for low PA was 9.76 (95% CI: 4.82-19.80). Both the "can't do, don't do" and "can't do, do do" group differed significantly compared to the "can do, do do" group on several fall and fracture risk factors and had lower physical performance. The "can do, do do" framework is able to identify fracture patients with an impaired physical performance. Of all FLS patients 20% "can't do, but "do do" while having a high prevalence of fall risk factors compared to persons that "can do, do do", which may indicate this group is prone to fall.

Prospective comparison of three methods for detecting peri-operative neurocognitive disorders in older adults undergoing cardiac and non-cardiac surgery.

Postoperative neurocognitive disorders occur frequently in older adult patients. Neuropsychological assessment is the gold standard for diagnosis, but the resources required for routine use are significant. Instead, it is common for simplified and unvalidated tests to be used for trials and in clinical practice. We undertook a single-centre prospective observational study in elective surgical patients aged ≥ 65 years recruited between September 2019 and January 2021. Patients underwent neuropsychological assessment, the Modified Telephone Interview for Cognitive Status and Montreal Cognitive Assessment before surgery. Tests were repeated at approximately four to eight postoperative weeks. We included 105 patients and 28 (27%) were lost to follow-up. Pre-operative Modified Telephone Interview for Cognitive Status and cognitive domain scores were very weakly to moderately correlated (r = 0.09-0.41). Pre-operative Montreal Cognitive Assessment and cognitive domain scores were very weakly to weakly correlated (r = 0.17-0.37) Postoperative Modified Telephone Interview for Cognitive Status and cognitive domain scores were very weakly to weakly correlated (r = 0.09-0.36). Postoperative Montreal Cognitive Assessment score and cognitive domain scores were very weakly to weakly correlated (r = 0.07-0.36). Overall, there was limited agreement between tests. We conclude that the Modified Telephone Interview for Cognitive Status and Montreal Cognitive Assessment should not be used in isolation to diagnose postoperative neurocognitive disorders. There seems to be little to no pre-operative, postoperative or pre- to postoperative correlation between these tests and the neuropsychological assessment in older adults without pre-operative cognitive impairment.

Nonoperative versus operative management of frail institutionalized older patients with a proximal femoral fracture: a cost-utility analysis alongside a multicenter prospective cohort study.

Hip fractures are associated with significant healthcare costs. In frail institutionalized patients, the costs of nonoperative management are less than operative management with comparable short-term quality of life. Nonoperative management of hip fractures in patients at the end of life should be openly discussed with SDM. PURPOSE: The aim was to describe healthcare use with associated costs and to determine cost-utility of nonoperative management (NOM) versus operative management (OM) of frail institutionalized older patients with a proximal femoral fracture. METHODS: This study included institutionalized patients with a limited life expectancy aged ≥ 70 years who sustained a proximal femoral fracture in the Netherlands. Costs of hospital- and nursing home care were calculated. Quality adjusted life years (QALY) were calculated based on EuroQol-5D-5L utility scores at day 7, 14, and 30 and at 3 and 6 months. The incremental cost-effectiveness ratio (ICER) was calculated from a societal perspective. RESULTS: Of the 172 enrolled patients, 88 (51%) patients opted for NOM and 84 (49%) for OM. NOM was associated with lower healthcare costs at 6 months (NOM; €2425 (SD 1.030), OM; €9325 (SD 4242), p < 0.001). The main cost driver was hospital stay (NOM; €738 (SD 841) and OM; €3140 (SD 2636)). The ICER per QALY gained in the OM versus NOM was €76,912 and exceeded the threshold of €20,000 per QALY. The gained QALY were minimal in the OM group in patients who died within 14- and 30-day post-injury, but OM resulted in more than triple the costs. CONCLUSION: OM results in significant higher healthcare costs, mainly due to the length of hospital stay. For frail patients at the end of life, NOM of proximal femoral fractures should be openly discussed in SDM conversations due to the limited gain in QoL. TRIAL REGISTRATION: Netherlands Trial Register (NTR7245; date 10-06-2018).

Tranexamic acid to prevent operation in chronic subdural haematoma (TORCH): study protocol for a randomised placebo-controlled clinical trial.

BACKGROUND: Chronic subdural haematoma (cSDH) occurs mainly in the elderly. Surgical evacuation is effective, but in these old, often frail, patients with multi-comorbidity, surgery carries significant risks for future cognitive functioning and loss of independency. Therefore, a growing interest is noted for a non-surgical treatment with medication such as tranexamic acid (TXA). In five small retrospective series, this antifibrinolytic drug showed a beneficial effect on the spontaneous resolution of the haematoma, and with that, the necessity for surgery. METHODS: For this randomised, placebo-controlled clinical multicentre trial, all cSDH patients, over 50 years old with mild symptoms (Glasgow Coma Score (GCS) ≥ 14, modified National Institutes of Health Stroke Scale (mNIHSS) ≤ 4), a midline shift of ≤ 10 mm and in whom a primary conservative treatment is chosen, are eligible for study participation. After informed consent, 140 patients will be randomised to receive either TXA 500 mg or placebo two times daily for 28 days. The primary outcome is the necessity for surgery within 12 weeks; secondary outcomes are cSDH volume, neurological impairment (mNIHSS), falling incidents, cognitive functioning (Montreal Cognitive Assessment (MOCA)), performance in activities of daily living (Barthel and Lawton score), functional outcome (modified Rankin Scale (mRS)), quality of life (Short Form Health Survey (SF-36) and EuroQol 5-Dimension Health Survey (EQ-5D)), mortality and the use of care and health-related costs (Medical Consumption Questionnaire (iMCQ) and Productivity Cost Questionnaire (iPCQ)) at 12 weeks and 6 months. DISCUSSION: This phase III trial investigating the efficacy of TXA to prevent surgery for cSDH is the first in including patients using anticoagulants and mentally incompetent patients, since these comprise a significant part of the target population. Also, this study is one of the first to prospectively measure functional outcome and quality of life in cSDH patients. Final results of this study are expected in 2024. TRIAL REGISTRATION: Dutch Trial Registry (Nederlands Trial Register) NL6584 . Registered on 11 November 2017 ClinicalTrials.gov NCT03582293 . Registered on 11 July 2018 EU Clinical Trials Register 2017-004311-40 . Registered on 29 March 2018.

The impact and challenges of implementing CTCA according to the 2019 ESC guidelines on chronic coronary syndromes: a survey and projection of CTCA services in the Netherlands.

BACKGROUND: The 2019 ESC-guidelines on chronic coronary syndromes (ESC-CCS) recommend computed tomographic coronary angiography (CTCA) or non-invasive functional imaging instead of exercise ECG as initial test to diagnose obstructive coronary artery disease. Since impact and challenges of these guidelines are unknown, we studied the current utilisation of CTCA-services, status of CTCA-protocols and modeled the expected impact of these guidelines in the Netherlands. METHODS AND RESULTS: A survey on current practice and CTCA utilisation was disseminated to every Dutch hospital organisation providing outpatient cardiology care and modeled the required CTCA capacity for implementation of the ESC guideline, based on these national figures and expert consensus. Survey response rate was 100% (68/68 hospital organisations). In 2019, 63 hospital organisations provided CTCA-services (93%), CTCA was performed on 99 CTCA-capable CT-scanners, and 37,283 CTCA-examinations were performed. Between the hospital organisations, we found substantial variation considering CTCA indications, CTCA equipment and acquisition and reporting standards. To fully implement the new ESC guideline, our model suggests that 70,000 additional CTCA-examinations would have to be performed in the Netherlands. CONCLUSIONS: Despite high national CTCA-services coverage in the Netherlands, a substantial increase in CTCA capacity is expected to be able to implement the 2019 ESC-CCS recommendations on the use of CTCA. Furthermore, the results of this survey highlight the importance to address variations in image acquisition and to standardise the interpretation and reporting of CTCA, as well as to establish interdisciplinary collaboration and organisational alignment.

The Clinical Relevance of Hyperkyphosis: A Narrative Review.

The kyphosis angle of the thoracic spine tends to increase with aging. Hyperkyphosis is a kyphosis angle, exceeding the normal range. This narrative literature review aims to provide an overview of the current literature concerning kyphosis measurement methods, the etiology and adverse health effects of hyperkyphosis. As of yet, a well-defined threshold for hyperkyphosis is lacking. To attain more generalizability and to be able to compare study results in older adults, we propose to define age-related hyperkyphosis as a Cobb angle of 50° or more in standing position. Hyperkyphosis may be a potentially modifiable risk factor for adverse health outcomes, like fall risk and fractures. Additionally, hyperkyphosis may indicate the presence of osteoporosis, which is treatable. Prospective and intervention studies, using a Cobb angle of 50° as a clear and uniform definition of hyperkyphosis, are warranted to investigate the clinical relevance of hyperkyphosis.

The association between chronic kidney disease, falls, and fractures: a systematic review and meta-analysis.

Patients with chronic kidney disease (CKD) are more likely to experience falls and fractures due to renal osteodystrophy and the high prevalence of risk factors for falls. However, it is not well established how great the risk is for falls and fractures for the different stages of CKD compared to the general population. The objective of this systematic review and meta-analysis was to assess whether, and in which degree, CKD was associated with falls and fractures in adults. A systematic search in PubMed, Embase, CINAHL, and The Cochrane Library was performed on 7 September 2018. All retrospective, cross-sectional, and longitudinal studies of adults (18 years of older) that studied the association between CKD, fractures, and falls were included. Additional studies were identified by cross-referencing. A total of 39 publications were included, of which two publications assessed three types of outcome and four publications assessed two types of outcome. Ten studies focused on accidental falling; seventeen studies focused on hip, femur, and pelvis fractures; seven studies focused on vertebral fractures; and thirteen studies focused on any type of fracture without further specification. Generally, the risk of fractures increased when kidney function worsened, with the highest risks in the patients with stage 5 CKD or dialysis. This effect was most pronounced for hip fractures and any type of fractures. Furthermore, results on the association between CKD and accidental falling were contradictory. Compared to the general population, fractures are highly prevalent in patients with CKD. Besides more awareness of timely fracture risk assessment, there also should be more focus on fall prevention.

The prevalence and incidence of vertebral fractures in end-stage renal disease and the role of parathyroid hormone.

The risk of vertebral fracture is unclear in end-stage renal disease. We report a high vertebral fracture prevalence and incidence in transplantation-eligible patients on dialysis, suggesting that these patients may benefit from radiographic screening for vertebral fractures. Parathyroid hormone had a U-shaped association with vertebral fracture risk. INTRODUCTION: Vertebral fractures are often overlooked, but even undiagnosed vertebral fractures negatively impact physical functioning, quality of life, and mortality. The risk of vertebral fractures in end-stage renal disease (ESRD) patients is unclear, and parathyroid hormone (PTH) might play a role in the development of vertebral fractures. We therefore determined vertebral fracture prevalence and incidence in ESRD patients and assessed associations of vertebral trabecular bone mineral density (BMD) and PTH with vertebral fracture. METHODS: In 146 transplantation-eligible patients on dialysis, we determined vertebral fractures on lateral chest radiographs, which image the thoracic and upper lumbar spine. We determined incident vertebral fractures in 70 patients with follow-up radiographs (23 received a kidney transplant) after median 1.8 years. Vertebral trabecular BMD was measured with computed tomography, and PTH measured with 2-site immunoassays, categorized in tertiles with the middle tertile as reference. We used Poisson regression to assess associations of vertebral trabecular BMD and PTH with vertebral fracture. RESULTS: Mean age of the study population was 52 ± 13 years, and 98 (67%) were male. Median dialysis duration was 26 (IQR 13-55) months. Vertebral fractures were present in 50/146 patients (34%) and incident vertebral fractures occurred in 20/70 patients (29%). Vertebral trabecular BMD was not associated with vertebral fracture prevalence (relative risk 0.97, 95% CI 0.89 to 1.04). For the lowest PTH tertile (< 11 pmol/L), the relative risk of vertebral fracture was greater although not significant (2.28, 95% CI 0.97 to 5.97) and was significantly greater for the highest PTH tertile (≥ 30 pmol/L; 2.82, 95% CI 1.22 to 7.27) after adjustment for potential confounders. CONCLUSIONS: The prevalence and incidence of vertebral fractures is high even in relatively young and healthy ESRD patients. Vertebral trabecular BMD is not associated with vertebral fracture, and the association of PTH with vertebral fracture risk appears U-shaped. Nevertheless, our study did not measure vertebral BMD using DXA and assessed vertebral fractures using lateral chest radiographs and not spine radiographs.

Saturable elimination of piperacillin in critically ill patients: implications for continuous infusion.

The study aimed to evaluate saturation of piperacillin elimination in critically ill adult patients. Seventeen critically ill adult patients received continuous and intermittent infusion of piperacillin/tazobactam. Piperacillin plasma concentrations (n = 217) were analysed using population pharmacokinetic (PopPK) modelling. Post-hoc simulations were performed to evaluate the type I error rate associated with the study. Unseen data were used to validate the final model. The mean error (ME) and root mean square error (RMSE) were calculated as a measure of bias and imprecision, respectively. A PopPK model with parallel linear and non-linear elimination best fitted the data. The median and 95% confidence interval (CI) for the model parameters drug clearance (CL), volume of central compartment (V), volume of peripheral compartment (Vp) and intercompartmental clearance (Q) were 9 (7.69-11) L/h, 6.18 (4.93-11.2) L, 11.17 (7.26-12) L and 15.61 (12.66-23.8) L/h, respectively. The Michaelis-Menten constant (Km) and the maximum elimination rate for Michaelis-Menten elimination (Vmax) were estimated without population variability in the model to avoid overfitting and inflation of the type I error rate. The population estimates for Km and Vmax were 37.09 mg/L and 353.57 mg/h, respectively. The bias (ME) was -20.8 (95% CI -26.2 to -15.4) mg/L, whilst imprecision (RMSE) was 49.2 (95% CI 41.2-56) mg/L. In conclusion, piperacillin elimination is (partially) saturable. Moreover, the population estimate for Km lies within the therapeutic window and therefore saturation of elimination should be accounted for when defining optimum dosing regimens for piperacillin in critically ill patients.

Thoracic vertebral fractures and hyperkyphosis in elderly patients with end-stage kidney disease; do these patients have different clinical outcomes?

BACKGROUND AND OBJECTIVES: Elderly patients with end-stage kidney disease (ESKD) are at high risk for fractures. However, the prevalence of vertebral fractures and hyperkyphosis is not studied well. This is relevant, because in the general population, both vertebral fractures and hyperkyphosis are associated with poor outcome. Therefore, the primary aim of our study was to assess the prevalence of vertebral fractures and hyperkyphosis in the ESKD population. The secondary aim was to assess if patients with vertebral fractures and/or hyperkyphosis more often have poor outcome after starting dialysis, such as accidental falling, functional decline and mortality compared to the patients without vertebral fractures and/or hyperkyphosis. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS: This study included patients ≥65 years with ESKD who were enrolled in the Geriatric assessment in Older patients starting Dialysis (GOLD) study of whom a lateral chest radiograph was available. Chest radiographs were scored independently by two observers for vertebral fractures (Genant ≥1) and hyperkyphosis (≥50 degrees). The relation between vertebral fractures and hyperkyphosis with clinical outcomes (falls, decline in ADL and IADL, mortality) was studied using the Chi-square test. RESULTS: Of the 196 enrolled patients, chest radiographs were available for 160 patients. Mean age was 75.3 (SD ±6.9), and 35% were female. The prevalence of vertebral fractures was 43% and of hyperkyphosis 22%. Patients with hyperkyphosis had a higher one-year mortality compared to patients without hyperkyphosis (20% vs. 8%, p = 0.04). No differences were observed between patients with and without hyperkyphosis, vertebral fractures and the remaining outcomes after six months of follow-up. CONCLUSIONS: In patients ≥65 years old with ESKD starting dialysis, vertebral fractures are highly prevalent. In contrast to the general population, patients with vertebral fractures did experience poor outcome as often as patients without vertebral fractures. Remarkably, patients with hyperkyphosis did have a higher one-year mortality. However, these patients did not experience more functional decline or accidental falls.

[Autonomy in the individual oral care programme of the care-dependent cognitively impaired older patient]. / Autonomie in het mondzorgplan van de zorgafhankelijke, cognitief beperkte oudere patiënt.

The decision-making process on oral healthcare issues concerning caredependent, frail older people living in nursing homes may be complex if patients are incapable of (adequately) expressing consent or are legally incapacitated. Therefore, oral healthcare professionals providing care to cognitively impaired patients in nursing homes need background knowledge of healthcare legislation and healthcare ethics, concerning the aspects relevant to developing an individual oral care programme. In this article, attention is given to these aspects of healthcare legislation and ethics, and the guideline 'Mondzorg en verzet bij wilsonbekwaamheid ter zake' (oral healthcare and resistance of the legally incapacitated) is described. This can be applied in comparable cases.

Fine-Tuning Covalent Inhibition of Bacterial Quorum Sensing.

Emerging antibiotic resistance among human pathogens has galvanized efforts to find alternative routes to combat bacterial virulence. One new approach entails interfering with the ability of bacteria to coordinate population-wide gene expression, or quorum sensing (QS), thus inhibiting the production of virulence factors and biofilm formation. We have recently developed such a strategy by targeting LasR, the master regulator of QS in the opportunistic human pathogen Pseudomonas aeruginosa, through the rational design of covalent inhibitors closely based on the core structure of the native ligand. We now report several groups of new inhibitors, one of which, fluoro-substituted ITC-12, displayed complete covalent modification of LasR, as well as effective QS inhibition in vitro and promising in vivo results. In addition to their potential clinical relevance, this series of synthetic QS modulators can be used as a tool to further unravel the complicated QS regulation in P. aeruginosa.

Comparison of milk oligosaccharides pattern in colostrum of different horse breeds.

Colostrum oligosaccharides are known to exhibit prebiotic and immunomodulatory properties. Oligosaccharide composition is species-specific, and equine colostrum has been reported to contain unique oligosaccharides. Therefore, equine oligosaccharides (EMOS) from colostrum from different horse breeds were analyzed by CE-LIF, CE-MS(n), HILIC-MS(n), and exoglycosidase degradation. Sixteen EMOS were characterized and quantified, of which half were neutral and half were acidic. EMOS showed about 63% structural overlap with human milk oligosaccharides, known for their bioactivity. Seven EMOS were not reported before in equine oligosaccharides literature: neutral Gal(ß1-4)HexNAc, Gal(ß1-4)Hex-Hex, ß4'-galactosyllactose, and lactose-N-hexaose, as well as acidic 6'-Sialyl-Hex-Ac-HexNAc, sialyllacto-N-tetraose-a, and disialylacto-N-tetraose (isomer not further specified). In all colostrum samples, the average oligosaccharide concentration ranged from 2.12 to 4.63 g/L; with ß 6'and 3'- galactosyllactose, 3'-sialyllactose, and disialyllactose as the most abundant of all oligosaccharides (27-59, 16-37, 1-8, and 1-6%, respectively). Differences in presence and in abundance of specific EMOS were evident not only between the four breeds but also within the breed.

Interpreting biomarker data from the COPHES/DEMOCOPHES twin projects: Using external exposure data to understand biomarker differences among countries.

In 2011 and 2012, the COPHES/DEMOCOPHES twin projects performed the first ever harmonized human biomonitoring survey in 17 European countries. In more than 1800 mother-child pairs, individual lifestyle data were collected and cadmium, cotinine and certain phthalate metabolites were measured in urine. Total mercury was determined in hair samples. While the main goal of the COPHES/DEMOCOPHES twin projects was to develop and test harmonized protocols and procedures, the goal of the current paper is to investigate whether the observed differences in biomarker values among the countries implementing DEMOCOPHES can be interpreted using information from external databases on environmental quality and lifestyle. In general, 13 countries having implemented DEMOCOPHES provided high-quality data from external sources that were relevant for interpretation purposes. However, some data were not available for reporting or were not in line with predefined specifications. Therefore, only part of the external information could be included in the statistical analyses. Nonetheless, there was a highly significant correlation between national levels of fish consumption and mercury in hair, the strength of antismoking legislation was significantly related to urinary cotinine levels, and we were able to show indications that also urinary cadmium levels were associated with environmental quality and food quality. These results again show the potential of biomonitoring data to provide added value for (the evaluation of) evidence-informed policy making.

Diagnosis of vertebral fractures on lateral chest X-ray: intraobserver agreement of semi-quantitative vertebral fracture assessment.

BACKGROUND: In clinical practice lateral images of the chest are performed for various reasons. As these lateral chest X rays show the vertebrae of the thoracic and thoraco-lumbar region, we wondered if these X-rays can be used for evaluation of vertebral fractures instead of separate thoracic spine X-rays. METHODS: To evaluate the agreement and intraobserver reliability of the semi-quantitative method for vertebral fractures on the lateral chest X-ray (X-chest) in comparison to the lateral thoracic spine X-ray (X-Tspine), two observers scored vertebral fractures on X-Tspine and twice on X-chest, separately,blinded and in different time periods. Agreement and Cohens' kappa were calculated for a diagnosis of any fracture on patient level and on vertebral body level. The study was done in patients visiting an outpatient geriatric day clinic, with a high prevalence of vertebral fractures. RESULTS: 109 patients were included. The intraobserver agreement for X-chest versus X-Tspine was 95-98%for the two levels of fracturing, with a Cohen's kappa of 0.88-0.91. The intraobserver agreement and reliability of the re-test on the X-chest showed an agreement between 91 and 98% with a Cohen's kappa of 0.81-0.93. More vertebrae were visible on the X-chest, mean 10.2, SD 0.66 versus mean 9.8, SD 0.73 on the X-Tspine (p < 0.001). CONCLUSION: The results show good agreement and intraobserver reliability on the X-chest compared to the X-Tspine for visualizing vertebral fractures. The results of this study emphasizes that the routinely performed X-chest is reliable in order to diagnose vertebral fractures.

A semi-probabilistic modelling approach for the estimation of dietary exposure to phthalates in the Belgian adult population.

In this study, a semi-probabilistic modelling approach was applied for the estimation of the long-term human dietary exposure to phthalates--one of world's most used families of plasticisers. Four phthalate compounds were considered: diethyl phthalate (DEP), di-n-butyl phthalate (DnBP), benzylbutyl phthalate (BBP) and di(2-ethylhexyl) phthalate (DEHP). Intake estimates were calculated for the Belgian adult population and several subgroups of this population for two considered scenarios using an extended version of the EN-forc model. The highest intake rates were found for DEHP, followed by DnBP, BBP and DEP. In the Belgian adult population, men and young adults generally had the highest dietary phthalate intake estimates. Nevertheless, predicted dietary intake rates for all four investigated phthalates were far below the corresponding tolerable daily intake (TDI) values (i.e. P99 intake values were 6.4% of the TDI at most), which is reassuring because adults are also exposed to phthalates via other contamination pathways (e.g. dust ingestion and inhalation). The food groups contributing most to the dietary exposure were grains and grain-based products for DEP, milk and dairy products for DnBP, meat and meat products or grains and grain-based products (depending on the scenario) for BBP and meat and meat products for DEHP. Comparison of the predicted intake results based on modelled phthalate concentrations in food products with intake estimates from other surveys (mostly based on measured concentrations) showed that the extended version of the EN-forc model is a suitable semi-probabilistic tool for the estimation and evaluation of the long-term dietary intake of phthalates in humans.