Providing care for older adults in the Emergency Department: expert clinical recommendations from the European Task Force on Geriatric Emergency Medicine.

PURPOSE: Despite the rapidly expanding knowledge in the field of Geriatric Emergency Medicine in Europe, widespread implementation of change is still lacking. Many opportunities in everyday clinical care are missed to improve care for this susceptible and growing patient group. The aim was to develop expert clinical recommendations on Geriatric Emergency Medicine to be disseminated across Europe. METHODS: A group of multi-disciplinary experts in the field of Geriatric Emergency Medicine in Europe was assembled. Using a modified Delphi procedure, a prioritized list of topics related to Geriatric Emergency Medicine was created. Next, a multi-disciplinary group of nurses, geriatricians and emergency physicians performed a review of recent guidelines and literature to create recommendations. These recommendations were voted upon by a group of experts and placed on visually attractive posters. The expert group identified the following eight subject areas to develop expert recommendations on: Comprehensive Geriatric Assessment in the Emergency Department (ED), age/frailty adjusted risk stratification, delirium and cognitive impairment, medication reviews in the ED for older adults, family involvement, ED environment, silver trauma, end of life care in the acute setting. RESULTS: Eight posters with expert clinical recommendations on the most important topics in Geriatric Emergency Medicine are now available through https://posters.geriemeurope.eu/ . CONCLUSION: Expert clinical recommendations for Geriatric Emergency Medicine may help to improve care for older patients in the Emergency Department and are ready for dissemination across Europe.

Highly Variable Paracetamol Pharmacokinetics After Multiple Oral Dosing in Frail Older People: A Population Pharmacokinetic Analysis.

INTRODUCTION: Paracetamol pharmacokinetics (PK) is highly variable in older fit adults after intravenous administration. Frailty and oral administration likely result in additional variability. The aim was to determine oral paracetamol PK and variability in geriatric inpatients. METHODS: A population PK analysis, using NONMEM 7.2, was performed on 245 paracetamol samples in 40 geriatric inpatients (median age 87 [range 80-95] years, bodyweight 66.4 [49.3-110] kg, 92.5% frail [Edmonton Frail Scale]). All subjects received paracetamol 1000 mg as tablet (72.5%) or granulate (27.5%) three times daily. Simulations of dosing regimens (1000 mg every 6 hours [q6h] or q8h) were performed to determine target attainment, using mean steady-state concentration (Css-mean) of 10 mg/L as target. RESULTS: A one-compartment model with first order absorption and lag time best described the data. The inter-individual variability was high, with absorption rate constant containing the highest variability. The inter-individual variability could not be explained by covariates. Simulations of 1000 mg q6h and q8h resulted in a Css-mean of 10.8 [25-75th percentiles 8.2-12.7] and 8.13 [6.3-9.6] mg/L, respectively, for the average geriatric inpatient. The majority of the population remained off-target (22.2% [q6h] and 52.2% [q8h] <8 mg/L; 31.3 [q6h] and 7.6% [q8h] >12 mg/L). CONCLUSION: A population of average geriatric inpatients achieved target Css-mean with paracetamol 1000 mg q6h, while q8h resulted in underexposure for the majority of them. Due to high unexplained variability, a relevant proportion remained either above or below the target concentration of 10 mg/L. Research focusing on PK, efficacy and safety is needed to recommend dosing regimens.

A molecular epidemiological perspective of rhinovirus types circulating in Amsterdam from 2007 to 2012.

Rhinoviruses (RVs) are frequently detected respiratory viruses that cause mild common cold symptoms, but may also lead to more severe respiratory tract infections. The large number of RV types, classified into species A, B and C, hampers clear insights into the epidemiology and clinical significance of each RV type. The aim of this study was to map the circulation of RV types in the Amsterdam area. RV-positive nasopharyngeal and oropharyngeal samples, collected from 2007 to 2012 in the Academic Medical Centre (Amsterdam, the Netherlands), were typed based on the sequence of the region coding for capsid proteins VP4 and VP2. RV-A, RV-B and RV-C were found in proportions of of 52.4% (334/637), 11.3% (72/637), and 36.2% (231/637), respectively. We detected 129 of the 167 currently classified types. RVs circulated throughout the entire year with a peak in the autumn and a decline in the summer. Some RV types were observed throughout the entire sampling period and others had a more seasonal pattern. Nine RV-A and four RV-B novel provisionally assigned types were identified. This study provides an insight into the molecular epidemiology of RVs in the Amsterdam area. The RVs circulating are diverse and include several provisionally new types.

Irritable bowel syndrome and visceral hypersensitivity : risk factors and pathophysiological mechanisms.

Irritable bowel syndrome (IBS) is a common functional gastro-intestinal disorder, characterized by abdominal pain and altered intestinal motility. Visceral hypersensitivity is an important hallmark feature of IBS and is believed to underlie abdominal pain in patients with IBS. The two main risk factors associated with the development of IBS are gastrointestinal inflammation and psychological distress. On a peripheral level, visceral sensitivity seems to be modulated by several mechanisms. Immune cells in the mucosal wall, such as mast cells, and enterochromaffin cells may sensitize afferent nerves by release of their mediators. Furthermore, increased mucosal permeability, altered intestinal microflora and dietary habits may contribute to this feature. On a central level, an increased prevalence of psychiatric comorbidities is demonstrated in IBS patients, alongside alterations in the hormonal brain-gut axis, increased vigilance towards intestinal stimuli and functional and structural changes in the brain. The pathogenesis of IBS is complicated and multifactorial and the treatment remains clinically challenging. Dietary measures and symptomatic control are the cornerstones for IBS treatment and may be sufficient for patients experiencing mild symptoms, alongside education, reassurance and an effective therapeutic physician-patient relationship. New pharmacological therapies are aimed at interfering with mediator release and/or blockade of the relevant receptors within the gut wall, while modulation of the intestinal flora and diet may also be of therapeutic benefit. Tricyclic anti-depressants and serotonin reuptake inhibitors act both on a central and peripheral level by modulating pain signalling pathways.

Interactive effects of elevated CO2, warming, and drought on photosynthesis of Deschampsia flexuosa in a temperate heath ecosystem.

Global change factors affect plant carbon uptake in concert. In order to investigate the response directions and potential interactive effects, and to understand the underlying mechanisms, multifactor experiments are needed. The focus of this study was on the photosynthetic response to elevated CO(2) [CO2; free air CO(2) enrichment (FACE)], drought (D; water-excluding curtains), and night-time warming (T; infrared-reflective curtains) in a temperate heath. A/C(i) curves were measured, allowing analysis of light-saturated net photosynthesis (P(n)), light- and CO(2)-saturated net photosynthesis (P(max)), stomatal conductance (g(s)), the maximal rate of Rubisco carboxylation (V(cmax)), and the maximal rate of ribulose bisphosphate (RuBP) regeneration (J(max)) along with leaf δ(13)C, and carbon and nitrogen concentration on a monthly basis in the grass Deschampsia flexuosa. Seasonal drought reduced P(n) via g(s), but severe (experimental) drought decreased P(n) via a reduction in photosynthetic capacity (P(max), J(max), and V(cmax)). The effects were completely reversed by rewetting and stimulated P(n) via photosynthetic capacity stimulation. Warming increased early and late season P(n) via higher P(max) and J(max). Elevated CO(2) did not decrease g(s), but stimulated P(n) via increased C(i). The T×CO2 synergistically increased plant carbon uptake via photosynthetic capacity up-regulation in early season and by better access to water after rewetting. The effects of the combination of drought and elevated CO(2) depended on soil water availability, with additive effects when the soil water content was low and D×CO2 synergistic stimulation of P(n) after rewetting. The photosynthetic responses appeared to be highly influenced by growth pattern. The grass has opportunistic water consumption, and a biphasic growth pattern allowing for leaf dieback at low soil water availability followed by rapid re-growth of active leaves when rewetted and possibly a large resource allocation capability mediated by the rhizome. This growth characteristic allowed for the photosynthetic capacity up-regulations that mediated the T×CO2 and D×CO2 synergistic effects on photosynthesis. These are clearly advantageous characteristics when exposed to climate changes. In conclusion, after 1 year of experimentation, the limitations by low soil water availability and stimulation in early and late season by warming clearly structure and interact with the photosynthetic response to elevated CO(2) in this grassland species.

Effects of elevated CO2, warming and drought episodes on plant carbon uptake in a temperate heath ecosystem are controlled by soil water status.

The impact of elevated CO2, periodic drought and warming on photosynthesis and leaf characteristics of the evergreen dwarf shrub Calluna vulgaris in a temperate heath ecosystem was investigated. Photosynthesis was reduced by drought in midsummer and increased by elevated CO2 throughout the growing season, whereas warming only stimulated photosynthesis early in the year. At the beginning and end of the growing season, a T × CO2 interaction synergistically stimulated plant carbon uptake in the combination of warming and elevated CO2. At peak drought, the D × CO2 interaction antagonistically down-regulated photosynthesis, suggesting a limited ability of elevated CO2 to counteract the negative effect of drought. The response of photosynthesis in the full factorial combination (TDCO2) could be explained by the main effect of experimental treatments (T, D, CO2) and the two-factor interactions (D × CO2, T × CO2). The interactive responses in the experimental treatments including elevated CO2 seemed to be linked to the realized range of treatment variability, for example with negative effects following experimental drought or positive effects following the relatively higher impact of night-time warming during cold periods early and late in the year. Longer-term experiments are needed to evaluate whether photosynthetic down-regulation will dampen the stimulation of photosynthesis under prolonged exposure to elevated CO2.

Quantitative assessment of the presence of a single leg separation in Björk-Shiley convexoconcave prosthetic heart valves.

RATIONALE AND OBJECTIVES: The authors developed an analytic software package for the objective and reproducible assessment of a single leg separation (SLS) in the outlet strut of Björk-Shiley convexoconcave (BSCC) prosthetic heart valves. METHODS: The radiographic cinefilm recordings of 18 phantom valves (12 intact and 6 SLS) and of 43 patient valves were acquired. After digitization of regions of interest in a cineframe, several processing steps were carried out to obtain a one-dimensional corrected and averaged density profile along the central axis of each strut leg. To characterize the degree of possible separation, two quantitative measures were introduced: the normalized pit depth (NPD) and the depth-sigma ratio (DSR). The group of 43 patient studies was divided into a learning set (25 patients) and a test set (18 patients). RESULTS: All phantom valves with an SLS were detected (sensitivity, 100%) at a specificity of 100%. The threshold values for the NPD and the DSR to decide whether a fracture was present or not were 3.6 and 2.5, respectively. On the basis of the visual interpretations of the 25 patient studies (learning set) by an expert panel, it was concluded that none of the patients had an SLS. To achieve a 100% specificity by quantitative analysis, the threshold values for the NPD and the DSR were set at 5.8 and 2.5, respectively, for the patient data. Based on these threshold values, the analysis of patient data from the test set resulted in one false-negative detection and three false-positive detections. CONCLUSIONS: An analytic software package for the detection of an SLS was developed. Phantom data showed excellent sensitivity (100%) and specificity (100%). Further research and software development is needed to increase the sensitivity and specificity for patient data.

Determinants of end-systolic pressure during different load alterations in the in situ left ventricle.

Because of the strong dependency of the end-systolic pressure-volume relation on the type of transient loading intervention in the in situ left ventricle (LV), experiments in the basal inotropic state in 16 open-chest anesthetized dogs were reanalyzed to find additional variables to model and predict end-systolic pressure (ESP) of both afterloading and preloading interventions by a single equation. Random-coefficients regression analysis was performed on 22 experiments in the basal inotropic state simultaneously, yielding an overall R2 of 0.97. The major part of total variance of ESP was due to linear terms of end-systolic volume (ESV) (74%) and stroke volume (SV) (19%). The SV effect was consistently negative and quantitatively quite important. An average load-independent end-systolic elastance of 6.7 mmHg/ml and an average SV effect of -5.7 mmHg/ml ejected were estimated, separating the "force-length" property from shortening effects in the in situ LV. History-related effects appeared to be only minor.

Prolonged dilation with an autoperfusion balloon catheter for refractory acute occlusion related to percutaneous transluminal coronary angioplasty.

OBJECTIVES: Efficacy and safety of redilation by an autoperfusion balloon catheter over several hours were investigated in this retrospective and observational study. BACKGROUND: Acute occlusion, refractory to redilation, is a serious complication of coronary angioplasty. METHODS: Of 1,123 patients who underwent angioplasty, 83 had a refractory acute occlusion. Thiry-five patients were treated with extended dilation. Seven had stable, 19 unstable and 6 postinfarction angina and 3 had an acute infarction at the time of angioplasty. The duration of dilation was (mean +/- SD) 17 (+/- 6) h. RESULTS: Angiographically successful redilation, with a mean residual percent diameter stenosis of 13.5% (+/- 11.6%), was achieved in 22 (67.7%) of 34 patients. Five patients underwent bypass surgery. Three patients, who were poor surgical candidates, died. There was one new Q wave infarction and one death that occurred during extended dilation; one death and four operations were related to reocclusion immediately (< or = 30 min) after catheter withdrawal; and one death and one operation were related to in-hospital reocclusion. Overall success, defined as angiographic success and freedom from major events, was obtained in 20 (57%) of 35 patients (95% confidence interval 41% to 73%). Of the variables studied, only multilesion dilation was significantly (p = 0.018) associated with an unfavorable outcome. During a mean follow-up period of 13.8 (+/- 6.1) months, two patients underwent repeat angioplasty, one sustained an infarction and three underwent elective bypass surgery. CONCLUSIONS: In approximately half of the patients (20 [57%] of 35), an initial angioplasty failure due to refractory occlusion could be reverted to a successful procedure by prolonged dilation with an autoperfusion balloon catheter.

Cariogenic changes in dental enamel of boys and girls in relation to salivary properties. II. Radiological examination.

In earlier clinical studies of a group of children subjected to an intense fluoride treatment programme several salivary properties were related to cariogenic changes in the enamel surface, as assessed by mirror and probe. In this study the relationship between salivary parameters and cariogenic changes was investigated on bitewings taken from the same teeth. Inverse correlations were found between the acid producing capacity of the micro-organisms in the saliva (as determined in the Snyder test) and most cariogenic changes detected in bitewings particularly in boys. These radiologically detected changes in enamel were the reverse of those obtained clinically. These discrepancies were explained by differences in sensitivity between clinical and radiological techniques used to diagnose cariogenic changes. In contrast it was confirmed radiologically that for girls the P concentration in saliva and for boys the amount of resting saliva are important for preventing extension of caries into deeper layers of enamel.

The relation between periodontitis and systemic bone mass in women between 46 and 55 years of age.

It has been suggested that periodontitis and systemic bone mass might be related. In order to evaluate this possible relationship, we performed an intra-oral examination and measured lumbar bone mineral density (lumbar BMD) and metacarpal cortical thickness (MCT) in 286 female volunteers between 46 and 55 years of age. In addition, the alveolar bone height was measured on bite wing radiographs of the dentate subjects. Of the subject, n = 60 (21%) were edentulous. Compared to the dentate subjects, the lumbar BMD and MCT of the edentulous women were not significantly different. In the dentate subjects, no significant correlation was observed between the clinical parameters of periodontitis (mean probing depth, occurrence of bleeding after probing and number of missing teeth) and the bone mass parameters (lumbar BMD and MCT); nor was a significant relation observed between the bone mass measurements and alveolar bone height. We therefore suggest that systemic bone mass is not an important factor in the pathogenesis of periodontitis.

Differences between primary and permanent teeth in posteruptive age dependency of radiological changes in enamel during the development of approximal caries.

A longitudinal radiological study of children (N = 549) who participated in a comprehensive preventive maintenance program showed that caries related events in the approximal surfaces of permanent teeth differed from those in deciduous teeth. Changes in the approximal surfaces of the younger permanent teeth were more pronounced than of the older primary teeth and differed significantly from 1 year to 2.5 years. These findings can be explained by posteruptive maturation of tooth enamel.

[Approximal caries in children]. / Approximale cariës. Een longitudinaal röntgenologisch onderzoek bij kinderen van 4-15 jaar.

A longitudinal radiological study in children (N = 549) who participated in a comprehensive maintenance program (they were treated in the clinic of the Department of Pedodontics of the Academic Centre for Dentistry Amsterdam) suggests that changes in the approximal surfaces of deciduous molars may differ from the changes in the approximal surfaces of permanent (pre)molars. Regression and initiation possibly occur more frequently in the deciduous teeth than in permanent teeth.

Comparison between force-velocity and end-systolic pressure-volume characterization of intrinsic LV function.

We reanalyzed experiments in in situ hearts of 16 open-chest anesthetized dogs, in which two different loading interventions were performed, i.e., an occlusion of the descending aorta (InP) and a rapid volume infusion (InV). Previous studies had demonstrated that the end-systolic elastance (Ees) of the InP was substantially larger than the Ees of the InV suggesting either a load dependency of Ees as such, or an increase in contractility during InP. The data were reanalyzed in the light of the muscular pump concept by plotting peak normalized velocity of circumferential shortening versus a global representative force approximating the left ventricle by a sphere. In all but one experiment the points of the two interventions are located on a single relationship over a very broad range of forces (from 397 to 2,461 g between the control states of experiments and from 602 to 3,278 g difference between control and highest load within experiments). The virtual independence of the force-velocity relation (FVR) and the dependence of the end-systolic pressure-volume relation (ESPVR) on the type of loading intervention can be ascribed to the fact that the former is assessed early during ejection and is therefore less influenced by shortening deactivation and internal resistance than the ESPVR. We conclude that the FVR offers a more consistent characterization of intrinsic LV function than the ESPVR.

Parallelism of implants visualised on the orthopantomogram.

Orthopantomography is often used in implantology to determine the position of implants in the bone. Implants, which in fact are parallel, can be projected in a non-parallel position. Considerations inherent to the technique of orthopantomography are responsible for this phenomenon. In this study some experiments were carried out to demonstrate this. It can be concluded that orthopantomography cannot be used to determine whether implants are placed parallel or not.

Parallelism of hollow-cylinder ITI implants: an experimental study.

Site preparation for oral implants is a delicate surgical procedure. In the ITI F-type and Bonefit implant systems, two cylindrical burs are available. Experiments were performed to verify the clinical experience that the longer bur is more accurate in defining the direction of implants. Several preparations were made in six human femur heads. The purpose of the experiments was to investigate the difference in parallelism between preparations made with the standard cylindrical bur and the bur with the long shaft. The results showed that the bur with the longer shaft was preferred for obtaining an accurate direction and parallelism of the implants.

Identifiability of left ventricular end-systolic pressure-volume relationships.

A widely accepted model of the left ventricle (LV) consisting of a time-varying elastance and a nonlinear internal resistance was investigated to make inferences about the identifiability of its parameters by means of simulated experiments. We aimed to retrieve maximum elastance (Emax) and dead volume (Vd) by the usual slope method or end-systolic pressure-volume relations (ESPVR) and by model-based parameter identification. The ESPVR deviated increasingly from the assigned values with increasing internal resistance depending on the type of loading intervention. Model-based parameter identification proved to be hampered by considerable error propagation if applied to single contractions with noise on the data. Better results were obtained by reducing the number of parameters to be estimated or by combining contractions with different loading conditions. The LV model was also matched with experimental data in three open-chest anesthetized dogs when both methods of estimation were used. The trend of ESPVR was in accordance with the model predictions, with larger Emax and larger Vd observed with arterial rather than with venous loading. Inclusion of an internal resistance in the classical elastance model can explain the dependence of the ESPVR on the type of loading intervention. However, application of model-based parameter identification indicates that the model fails to represent the entire systolic pressure-volume time course of the in situ LV.