Compartmental pharmacokinetics of nefopam during mild hypothermia

Background Nefopam is a non-opioid, non-steroidal, centrally acting analgesic which has an opioid-sparing effect. It also reduces the threshold (triggering core temperature) for shivering without causing sedation or respiratory depression. The drug is therefore useful as both an analgesic and to facilitate induction of therapeutic hypothermia. However, compartmental pharmacokinetics during hypothermia are lacking for nefopam. Methods We conducted a prospective, randomized, blinded study in eight volunteers. On two different occasions, one of two nefopam concentrations was administered and more than 30 arterial blood samples were gathered during 12 h. Plasma concentrations were determined using gas chromatography/mass spectrometry to investigate the pharmacokinetics of nefopam with non-linear mixed-effect modelling. Results A two-compartment mammillary model with moderate inter-individual variability and inter-occasional variability independent of covariates was found to best describe the data [mean (se): V1=24.13 (2.8) litre; V2=183.34 (13.5) litre; Clel=0.54 (0.07) litre min−1; Cldist=2.84 (0.42) litre min−1]. Conclusions The compartmental data set describing a two-compartment model was determined and could be implemented to drive automated pumps. Thus, work load could be distributed to a pump establishing and maintaining any desired plasma concentration deemed necessary for a treatment with therapeutical hypothermi

Diabetes Risk Factors, Diabetes Risk Algorithms, and the Prediction of Future Frailty: The Whitehall II Prospective Cohort Study

Objective: To examine whether established diabetes risk factors and diabetes risk algorithms are associated with future frailty. / Design: Prospective cohort study. Risk algorithms at baseline (1997–1999) were the Framingham Offspring, Cambridge, and Finnish diabetes risk scores. / Setting: Civil service departments in London, United Kingdom. / Participants: There were 2707 participants (72% men) aged 45 to 69 years at baseline assessment and free of diabetes. / Measurements: Risk factors (age, sex, family history of diabetes, body mass index, waist circumference, systolic and diastolic blood pressure, antihypertensive and corticosteroid treatments, history of high blood glucose, smoking status, physical activity, consumption of fruits and vegetables, fasting glucose, HDL-cholesterol, and triglycerides) were used to construct the risk algorithms. Frailty, assessed during a resurvey in 2007–2009, was denoted by the presence of 3 or more of the following indicators: self-reported exhaustion, low physical activity, slow walking speed, low grip strength, and weight loss; “prefrailty” was defined as having 2 or fewer of these indicators. / Results: After a mean follow-up of 10.5 years, 2.8% of the sample was classified as frail and 37.5% as prefrail. Increased age, being female, stopping smoking, low physical activity, and not having a daily consumption of fruits and vegetables were each associated with frailty or prefrailty. The Cambridge and Finnish diabetes risk scores were associated with frailty/prefrailty with odds ratios per 1 SD increase (disadvantage) in score of 1.18 (95% confidence interval: 1.09–1.27) and 1.27 (1.17–1.37), respectively. / Conclusion: Selected diabetes risk factors and risk scores are associated with subsequent frailty. Risk scores may have utility for frailty prediction in clinical practice

Cardiovascular disease risk scores in identifying future frailty: the Whitehall II prospective cohort study

Objectives: To examine the capacity of existing cardiovascular disease (CVD) risk algorithms widely used in primary care, to predict frailty. / Design: Prospective cohort study. Risk algorithms at baseline (1997–1999) were the Framingham CVD, coronary heart disease and stroke risk scores, and the Systematic Coronary Risk Evaluation. / Setting: Civil Service departments in London, UK. / Participants: 3895 participants (73% men) aged 45–69 years and free of CVD at baseline. / Main outcome measure: Status of frailty at the end of follow-up (2007–2009), based on the following indicators: self-reported exhaustion, low physical activity, slow walking speed, low grip strength and weight loss. / Results: At the end of the follow-up, 2.8% (n=108) of the sample was classified as frail. All four CVD risk scores were associated with future risk of developing frailty, with ORs per one SD increment in the score ranging from 1.35 (95% CI 1.21 to 1.51) for the Framingham stroke score to 1.42 (1.23 to 1.62) for the Framingham CVD score. These associations remained after excluding incident CVD cases. For comparison, the corresponding ORs for the risk scores and incident cardiovascular events varied between 1.36 (1.15 to 1.61) and 1.64 (1.50 to 1.80) depending on the risk algorithm. / Conclusions: The use of CVD risk scores in clinical practice may also have utility for frailty prediction

Hidromedusas profundas del Mediterráneo: Un estudio que incluye la descripción de dos nuevas especies recolectadas en cañones submarinos del Mediterráneo Occidental

Two new species of hydromedusae (Foersteria antoniae and Cunina simplex) are described from plankton collected in sediment traps placed in the Lacaze-Duthiers Submarine Canyon and along Banyuls-sur-Mer coast (northwestern Mediterranean). The Mediterranean hydromedusan deep-water fauna contains 41 species which represent 45.5 % of the world-wide deep-sea hydromedusae fauna (90) and 20% of the total number of Mediterranean hydromedusae (204). The Mediterranean deep-water hydromedusan fauna is characterised by a large percentage of holoplanktonic species (61%), mainly Trachymedusae. Nevertheless, contrary to the general opinion, the percentage of meroplanktonic species is equally high. The most original features of this fauna lies however in the importance of the number of endemic species (22%) and in the fact that the majority of them are meroplanktonic Leptomedusae with a supposed bathybenthic stage. Some of the endemic species could still represent relics of the primitive Tethys fauna having survived to the Messinian crisis. The origin of the Mediterranean deep-water hydromedusan fauna is discussed and a general hypothesis is proposed.Se describen dos especies nuevas a partir de ejemplares recolectados mediante trampas de sedimento del cañón submarino de Lacaze-Duthiers situado en frente de la costa de Banyuls-sur-Mer (Mediterráneo noroccidental). La fauna profunda de hydromedusas en el Mediterráneo contiene 41 especies que representan 45.5 % de la fauna mundial del grupo y el 20% de la fauna de hydromedusas del Mediterráneo. La fauna Mediterránea de hydromedusas profundas se caracteriza por un gran porcentaje de especies holoplanctónicas (61%), fundamentalmente Trachymedusas, sin embargo, contrario a la opinión generalizada, el porcentaje de especies meroplanctónicas es igualmente importante (39%). La característica más interesante de esta fauna es el número de especies endémicas (22%) y el hecho de que la mayoría de estas especies son meroplanctónicas (Leptomedusas) con una supuesta fase bentónica. Algunas de estas especies endémicas, podrían ser especies relictas (endémica insular) de la fauna primitiva del Tetis que sobrevivieron a la crisis Mesiniana. Se discute el origen de la fauna de hydromedusas profundas en el Mediterráneo y se presenta una nueva hipótesis

Validating a widely used measure of frailty: are all sub-components necessary? Evidence from the Whitehall II cohort study

There is growing interest in the measurement of frailty in older age. The most widely used measure (Fried) characterizes this syndrome using five components: exhaustion, physical activity, walking speed, grip strength, and weight loss. These components overlap, raising the possibility of using fewer, and therefore making the device more time- and cost-efficient. The analytic sample was 5,169 individuals (1,419 women) from the British Whitehall II cohort study, aged 55 to 79 years in 2007–2009. Hospitalization data were accessed through English national records (mean follow-up 15.2 months). Age- and sex-adjusted Cox models showed that all components were significantly associated with hospitalization, the hazard ratios (HR) ranging from 1.18 (95 % confidence interval = 0.98, 1.41) for grip strength to 1.60 (1.35, 1.90) for usual walking speed. Some attenuation of these effects was apparent following mutual adjustment for frailty components, but the rank order of the strength of association remained unchanged. We observed a dose–response relationship between the number of frailty components and the risk for hospitalization [1 component—HR = 1.10 (0.96, 1.26); 2—HR = 1.52 (1.26, 1.83); 3–5—HR = 2.41 (1.84, 3.16), P trend <0.0001]. A concordance index used to evaluate the predictive power for hospital admissions of individual components and the full scale was modest in magnitude (range 0.57 to 0.58). Our results support the validity of the multi-component frailty measure, but the predictive performance of the measure is poor

Model‐based control of mechanical ventilation: design and clinical validation

Background. We developed a model‐based control system using end‐tidal carbon dioxide fraction (FE′CO2) to adjust a ventilator during clinical anaesthesia. Methods. We studied 16 ASA I-II patients (mean age 38 (range 20-59) yr; weight 67 (54-87) kg) during i.v. anaesthesia for elective surgery. After periods of normal ventilation the patients were either hyper‐ or hypoventilated to assess precision and dynamic behaviour of the control system. These data were compared with a previous group where a fuzzy‐logic controller had been used. Responses to different clinical events (invalid carbon dioxide measurement, limb tourniquet release, tube cuff leak, exhaustion of carbon dioxide absorbent, simulation of pulmonary embolism) were also noted. Results. The model‐based controller correctly maintained the setpoint. No significant difference was found for the static performance between the two controllers. The dynamic response of the model‐based controller was more rapid (P<0.05). The mean rise time after a setpoint increase of 1 vol% was 313 (sd 90) s and 142 (17) s for fuzzy‐logic and model‐based control, respectively, and after a 1 vol% decrease was 355 (127) s and 177 (36) s, respectively. The new model‐based controller had a consistent response to clinical artefacts. Conclusion. A model‐based FE′CO2 controller can be used in a clinical setting. It reacts appropriately to artefacts, and has a better dynamic response to setpoint changes than a previously described fuzzy‐logic controller. Br J Anaesth 2004; 92: 800-

A novel multivariate STeady-state index during general ANesthesia (STAN)

The assessment of the adequacy of general anesthesia for surgery, namely the nociception/anti-nociception balance, has received wide attention from the scientific community. Monitoring systems based on the frontal EEG/EMG, or autonomic state reactions (e.g. heart rate and blood pressure) have been developed aiming to objectively assess this balance. In this study a new multivariate indicator of patients' steady-state during anesthesia (STAN) is proposed, based on wavelet analysis of signals linked to noxious activation. A clinical protocol was designed to analyze precise noxious stimuli (laryngoscopy/intubation, tetanic, and incision), under three different analgesic doses; patients were randomized to receive either remifentanil 2.0, 3.0 or 4.0 ng/ml. ECG, PPG, BP, BIS, EMG and [Formula: see text] were continuously recorded. ECG, PPG and BP were processed to extract beat-to-beat information, and [Formula: see text] curve used to estimate the respiration rate. A combined steady-state index based on wavelet analysis of these variables, was applied and compared between the three study groups and stimuli (Wilcoxon signed ranks, Kruskal-Wallis and Mann-Whitney tests). Following institutional approval and signing the informed consent thirty four patients were enrolled in this study (3 excluded due to signal loss during data collection). The BIS index of the EEG, frontal EMG, heart rate, BP, and PPG wave amplitude changed in response to different noxious stimuli. Laryngoscopy/intubation was the stimulus with the more pronounced response [Formula: see text]. These variables were used in the construction of the combined index STAN; STAN responded adequately to noxious stimuli, with a more pronounced response to laryngoscopy/intubation (18.5-43.1 %, [Formula: see text]), and the attenuation provided by the analgesic, detecting steady-state periods in the different physiological signals analyzed (approximately 50 % of the total study time). A new multivariate approach for the assessment of the patient steady-state during general anesthesia was developed. The proposed wavelet based multivariate index responds adequately to different noxious stimuli, and attenuation provided by the analgesic in a dose-dependent manner for each stimulus analyzed in this study.The first author was supported by a scholarship from the Portuguese Foundation for Science and Technology (FCT SFRH/BD/35879/2007). The authors would also like to acknowledge the support of UISPA—System Integration and Process Automation Unit—Part of the LAETA (Associated Laboratory of Energy, Transports and Aeronautics) a I&D Unit of the Foundation for Science and Technology (FCT), Portugal. FCT support under project PEst-OE/EME/LA0022/2013.info:eu-repo/semantics/publishedVersio

Predictors of 25(OH)D half-life and plasma 25(OH)D concentration in The Gambia and the UK

Summary: Predictors of 25(OH)D3 half-life were factors associated with vitamin D metabolism, but were different between people in The Gambia and the UK. Country was the strongest predictor of plasma 25(OH)D concentration, probably as a marker of UVB exposure. 25(OH)D3 half-life may be applied as a tool to investigate vitamin D expenditure.  Introduction: The aim of this study was to investigate predictors of 25(OH)D3 half-life and plasma 25(OH)D concentration.  Methods: Plasma half-life of an oral tracer dose of deuterated-25(OH)D3 was measured in healthy men aged 24–39 years, resident in The Gambia, West Africa (n = 18) and in the UK during the winter (n = 18), countries that differ in calcium intake and vitamin D status. Plasma and urinary markers of vitamin D, calcium, phosphate and bone metabolism, nutrient intakes and anthropometry were measured.  Results: Normally distributed data are presented as mean (SD) and non-normal data as geometric mean (95 % CI). Gambian compared to UK men had higher plasma concentrations of 25(OH)D (69 (13) vs. 29 (11) nmol/L; P < 0.0001); 1,25(OH)2D (181 (165, 197) vs. 120 (109, 132) pmol/L; P < 0.01); and parathyroid hormone (PTH) (50 (42, 60) vs. 33 (27, 39); P < 0.0001). There was no difference in 25(OH)D3 half-life (14.7 (3.5) days vs. 15.6 (2.5) days) between countries (P = 0.2). In multivariate analyses, 25(OH)D, 1,25(OH)2D, vitamin D binding protein and albumin-adjusted calcium (Caalb) explained 79 % of variance in 25(OH)D3 half-life in Gambians, but no significant predictors were found in UK participants. For the countries combined, Caalb, PTH and plasma phosphate explained 39 % of half-life variability. 1,25(OH)2D, weight, PTH and country explained 81 % of variability in 25(OH)D concentration; however, country alone explained 74 %.  Conclusion: Factors known to affect 25(OH)D metabolism predict 25(OH)D3 half-life, but these differed between countries. Country predicted 25(OH)D, probably as a proxy measure for UVB exposure and vitamin D supply. This study supports the use of 25(OH)D half-life to investigate vitamin D metabolism