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Development of a tool to identify intensive care patients at risk of meropenem therapy failure
(2018)
Low back pain (LBP) is a leading cause of activity limitation. Objective assessment of the spinal motion plays a key role in diagnosis and treatment of LBP. We propose a method that facilitates clinical assessment of lower back motions by means of a wireless inertial sensor network. The sensor units are attached to the right and left side of the lumbar region, the pelvis and the thighs, respectively. Since magnetometers are known to be unreliable in indoor environments, we use only 3D accelerometer and 3D gyroscope readings. Compensation of integration drift in the horizontal plane is achieved by estimating the gyroscope biases from automatically detected initial rest phases. For the estimation of sensor orientations, both a smoothing algorithm and a filtering algorithm are presented. From these orientations, we determine three-dimensional joint angles between the thighs and the pelvis and between the pelvis and the lumbar region. We compare the orientations and joint angles to measurements of an optical motion tracking system that tracks each skin-mounted sensor by means of reflective markers. Eight subjects perform a neutral initial pose, then flexion/extension, lateral flexion, and rotation of the trunk. The root mean square deviation between inertial and optical angles is about one degree for angles in the frontal and sagittal plane and about two degrees for angles in the transverse plane (both values averaged over all trials). We choose five features that characterize the initial pose and the three motions. Interindividual differences of all features are found to be clearly larger than the observed measurement deviations. These results indicate that the proposed inertial sensor-based method is a promising tool for lower back motion assessment.
Purpose:
To test whether the negative relationship between perceived stress and quality of life (Hypothesis 1) can be buffered by perceived social support in patients with dementia as well as in caregivers individually (Hypothesis 2: actor effects) and across partners (Hypothesis 3: partner effects and actor-partner effects).
Method:
A total of 108 couples (N = 216 individuals) comprised of one individual with early-stage dementia and one caregiving partner were assessed at baseline and one month apart. Moderation effects were investigated by applying linear mixed models and actor-partner interdependence models.
Results:
Although the stress-quality of life association was more pronounced in caregivers (beta = -.63, p<.001) compared to patients (beta= -.31, p<.001), this association was equally moderated by social support in patients (beta = .14, p<.05) and in the caregivers (beta =.13, p<.05). From one partner to his or her counterpart, the partner buffering and actor-partner-buffering effect were not present.
Conclusion:
The stress-buffering effect has been replicated in individuals with dementia and caregivers but not across partners. Interventions to improve quality of life through perceived social support should not only focus on caregivers, but should incorporate both partners.
Differences in neuromuscular activity of ankle stabilizing muscles during postural disturbances
(2018)
The purpose was to examine gender differences in ankle stabilizing muscle activation during postural disturbances. Seventeen participants (9 females: 27 +/- 2yrs., 1.69 +/- 0.1 m, 63 +/- 7 kg; 8 males: 29 +/- 2yrs., 1.81 +/- 0.1 m; 83 +/- 7 kg) were included in the study. After familiarization on a split-belt-treadmill, participants walked (1 m/s) while 15 right-sided perturbations were randomly applied 200 ms after initial heel contact. Muscle activity of M. tibialis anterior (TA), peroneus longus (PL) and gastrocnemius medialis (GM) was recorded during unperturbed and perturbed walking. The root mean square (RMS; [%]) was analyzed within 200 ms after perturbation. Co-activation was quantified as ratio of antagonist (GM)/agonist (TA) EMG-RMS during unperturbed and perturbed walking. Time to onset was calculated (ms). Data were analyzed descriptively (mean +/- SD) followed by three-way-ANOVA (gender/condition/muscle; alpha= 0.05). Perturbed walking elicited higher EMG activity compared to normal walking for TA and PL in both genders (p < 0.000). RMS amplitude gender comparisons revealed an interaction between gender and condition (F = 4.6, p = 0.049) and, a triple interaction among gender, condition and muscle (F = 4.7, p = 0.02). Women presented significantly higher EMG-RMS [%] PL amplitude than men during perturbed walking (mean difference = 209.6%, 95% confidence interval = -367.0 to -52.2%, p < 0.000). Co-activation showed significant lower values for perturbed compared to normal walking (p < 0.000), without significant gender differences for both walking conditions. GM activated significantly earlier than TA and PL (p < 0.01) without significant differences between the muscle activation onsets of men and women (p = 0.7). The results reflect that activation strategies of the ankle encompassing muscles differ between genders. In provoked stumbling, higher PL EMG activity in women compared to men is present. Future studies should aim to elucidate if this specific behavior has any relationship with ankle injury occurrence between genders.
Sequencing Effects of Neuromuscular Training on Physical Fitness in Youth Elite Tennis Players
(2018)
Fernandez-Fernandez, J, Granacher, U, Sanz-Rivas, D, Sarabia Marin, JM, Hernandez-Davo, JL, and Moya, M. Sequencing effects of neuromuscular training on physical fitness in youth elite tennis players. J Strength Cond Res 32(3): 849-856, 2018-The aim of this study was to analyze the effects of a 5-week neuromuscular training (NMT) implemented before or after a tennis session in prepubertal players on selected components of physical fitness. Sixteen high-level tennis players with a mean age of 12.9 +/- 0.4 years participated in this study, and were assigned to either a training group performing NMT before tennis-specific training (BT; n = 8) or a group that conducted NMT after tennis-specific training (AT; n = 8). Pretest and posttest included: speed (5, 10, and 20 m); modified 5-0-5 agility test; countermovement jump (CMJ); overhead medicine ball throw (MBT); and serve velocity (SV). Results showed that the BT group achieved positive effects from pretest to posttest measures in speed (d = 0.52, 0.32, and 1.08 for 5, 10, and 20 m respectively), 5-0-5 (d = 0.22), CMJ (d = 0.29), MBT (d = 0.51), and SV (d = 0.32), whereas trivial (10 m, 20 m, CMJ, SV, and MBT) or negative effects (d = -0.19 and -0.24 for 5 m and 5-0-5, respectively) were reported for the AT group. The inclusion of an NMT session before the regular tennis training led to positive effects from pretest to posttest measures in performance-related variables (i.e., jump, sprint, change of direction capacity, as well as upper-body power), whereas conducting the same exercise sessions after the regular tennis training was not accompanied by the same improvements.
Symptoms of anxiety and depression in young athletes using the hospital anxiety and depression scale
(2018)
Elite young athletes have to cope with multiple psychological demands such as training volume, mental and physical fatigue, spatial separation of family and friends or time management problems may lead to reduced mental and physical recovery. While normative data regarding symptoms of anxiety and depression for the general population is available (Hinz and Brahler, 2011), hardly any information exists for adolescents in general and young athletes in particular. Therefore, the aim of this study was to assess overall symptoms of anxiety and depression in young athletes as well as possible sex differences. The survey was carried out within the scope of the study "Resistance Training in Young Athletes" (KINGS-Study). Between August 2015 and September 2016, 326 young athletes aged (mean +/- SD) 14.3 +/- 1.6 years completed the Hospital Anxiety and Depression Scale (HAD Scale). Regarding the analysis of age on the anxiety and depression subscales, age groups were classified as follows: late childhood (12-14 years) and late adolescence (15-18 years). The participating young athletes were recruited from Olympic weight lifting, handball, judo, track and field athletics, boxing, soccer, gymnastics, ice speed skating, volleyball, and rowing. Anxiety and depression scores were (mean +/- SD) 4.3 +/- 3.0 and 2.8 +/- 2.9, respectively. In the subscale anxiety, 22 cases (6.7%) showed subclinical scores and 11 cases (3.4%) showed clinical relevant score values. When analyzing the depression subscale, 31 cases (9.5%) showed subclinical score values and 12 cases (3.7%) showed clinically important values. No significant differences were found between male and female athletes (p >= 0.05). No statistically significant differences in the HADS scores were found between male athletes of late childhood and late adolescents (p >= 0.05). To the best of our knowledge, this is the first report describing questionnaire based indicators of symptoms of anxiety and depression in young athletes. Our data implies the need for sports medical as well as sports psychiatric support for young athletes. In addition, our results demonstrated that the chronological classification concerning age did not influence HAD Scale outcomes. Future research should focus on sports medical and sports psychiatric interventional approaches with the goal to prevent anxiety and depression as well as teaching coping strategies to young athletes.
Moving Beyond ERP Components
(2018)
Relationships between neuroimaging measures and behavior provide important clues about brain function and cognition in healthy and clinical populations. While electroencephalography (EEG) provides a portable, low cost measure of brain dynamics, it has been somewhat underrepresented in the emerging field of model-based inference. We seek to address this gap in this article by highlighting the utility of linking EEG and behavior, with an emphasis on approaches for EEG analysis that move beyond focusing on peaks or "components" derived from averaging EEG responses across trials and subjects (generating the event-related potential, ERP). First, we review methods for deriving features from EEG in order to enhance the signal within single-trials. These methods include filtering based on user-defined features (i.e., frequency decomposition, time-frequency decomposition), filtering based on data-driven properties (i.e., blind source separation, BSS), and generating more abstract representations of data (e.g., using deep learning). We then review cognitive models which extract latent variables from experimental tasks, including the drift diffusion model (DDM) and reinforcement learning (RL) approaches. Next, we discuss ways to access associations among these measures, including statistical models, data-driven joint models and cognitive joint modeling using hierarchical Bayesian models (HBMs). We think that these methodological tools are likely to contribute to theoretical advancements, and will help inform our understandings of brain dynamics that contribute to moment-to-moment cognitive function.
Background and objective Optimisation of hydrocortisone replacement therapy in children is challenging as there is currently no licensed formulation and dose in Europe for children under 6 years of age. In addition, hydrocortisone has non-linear pharmacokinetics caused by saturable plasma protein binding. A paediatric hydrocortisone formulation, Infacort (R) oral hydrocortisone granules with taste masking, has therefore been developed. The objective of this study was to establish a population pharmacokinetic model based on studies in healthy adult volunteers to predict hydrocortisone exposure in paediatric patients with adrenal insufficiency. Methods Cortisol and binding protein concentrations were evaluated in the absence and presence of dexamethasone in healthy volunteers (n = 30). Dexamethasone was used to suppress endogenous cortisol concentrations prior to and after single doses of 0.5, 2, 5 and 10 mg of Infacort (R) or 20 mg of Infacort (R)/hydrocortisone tablet/hydrocortisone intravenously. A plasma protein binding model was established using unbound and total cortisol concentrations, and sequentially integrated into the pharmacokinetic model. Results Both specific (non-linear) and non-specific (linear) protein binding were included in the cortisol binding model. A two-compartment disposition model with saturable absorption and constant endogenous cortisol baseline (Baseline (cort),15.5 nmol/L) described the data accurately. The predicted cortisol exposure for a given dose varied considerably within a small body weight range in individuals weighing < 20 kg. Conclusions Our semi-mechanistic population pharmacokinetic model for hydrocortisone captures the complex pharmacokinetics of hydrocortisone in a simplified but comprehensive framework. The predicted cortisol exposure indicated the importance of defining an accurate hydrocortisone dose to mimic physiological concentrations for neonates and infants weighing < 20 kg.
The aim of the study was to determine pre-interventional predictors for all-cause mortality in patients after transcatheter aortic valve implantation (TAVI) with a 12-month follow-up. From 10/2013 to 07/2015, 344 patients (80.9 +/- 5.0 years, 44.5% male) with an elective TAVI were consecutively enrolled prospectively in a multicentre cohort study. Prior to the intervention, sociodemographic parameters, echocardiographic data and comorbidities were documented. All patients performed a 6-min walk test, Short Form 12 and a Frailty Index (score consisting of activities of daily living, cognition, nutrition and mobility). Peri-interventional complications were documented. Vital status was assessed over telephone 12 months after TAVI. Predictors for all-cause mortality were identified using a multivariate regression model. At discharge, 333 patients were alive (in-hospital mortality 3.2%; n = 11). During a follow-up of 381.0 +/- 41.9 days, 46 patients (13.8%) died. The non-survivors were older (82.3 +/- 5.0 vs. 80.6 +/- 5.1 years; p = 0.035), had a higher number of comorbidities (2.6 +/- 1.3 vs. 2.1 +/- 1.3; p = 0.026) and a lower left ventricular ejection fraction (51.0 +/- 13.6 vs. 54.6 +/- 10.6%; p = 0.048). Additionally, more suffered from diabetes mellitus (60.9 vs. 44.6%; p = 0.040). While the global Frailty Index had no predictive power, its individual components, particularly nutrition (OR 0.83 per 1 pt., CI 0.72-0.95; p = 0.006) and mobility (OR 5.12, CI 1.64-16.01; p = 0.005) had a prognostic impact. Likewise, diabetes mellitus (OR 2.18, CI 1.10-4.32; p = 0.026) and EuroSCORE (OR 1.21 per 5%, CI 1.07-1.36; p = 0.002) were associated with a higher risk of all-cause mortality. Besides EuroSCORE and diabetes mellitus, nutrition status and mobility of patients scheduled for TAVI offer prognostic information for 1-year all-cause mortality and should be advocated in the creation of contemporary TAVI risk scores.
Hintergrund In den letzten Jahrzehnten führte die leitliniengerechte Therapie des akuten Myokardinfarktes (MI) zu einer Mortalitätsreduktion in Deutschland, wobei zwischen einzelnen Bundesländern erhebliche Unterschiede beschrieben werden. Ziel war es daher, die aktuelle Versorgungssituation von Patienten mit MI in der Region Nordost-Deutschland (Berlin, Brandenburg [BRB] und Mecklenburg-Vorpommern [MV]) zu untersuchen und Prädiktoren der 1-Jahresmortalität unter Berücksichtigung der regionalen Zuordnung zu identifizieren.
Methode Auf Basis pseudonymisierter Abrechnungsdaten einer gesetzlichen Krankenversicherung wurden für das Jahr 2012 anhand des ICD 10-Codes I21 und I22 von 1 387 084 Versicherten insgesamt 6733 Patienten mit stationärer Aufnahme bei MI gefiltert. Neben der Krankenhaus- und 1-Jahresmortalität wurden potenzielle Prognoseprädiktoren unter Berücksichtigung von Komorbiditäten, periinfarziellen Prozeduren und sekundärpräventiver Pharmakotherapie erfasst und im Ländervergleich analysiert.
Ergebnisse Sowohl die Krankenhaus- als auch die 1-Jahresmortalitätsrate der einzelnen Länder (Berlin 13,6 resp. 27,5 %, BRB 13,9 resp. 27,9 %, MV 14,4 resp. 29,0 %) war vergleichbar zur Gesamtrate (13,9 % resp. 28,0 %) und im Ländervergleich weitgehend identisch. Die multiple Analyse der Einflussfaktoren auf die 1-Jahresmortalität identifizierte vor allem die Koronarangiografie (OR 0,42, 95 % KI 0,35 – 0,51, p < 0,001) und die Umsetzung der pharmakologischen Leitlinienempfehlungen (OR 0,14, 95 % KI 0,12 – 0,17, p < 0,001) als wesentliche Maßnahmen zur Risikoreduktion. Bei beiden Einflussfaktoren lagen univariat keine statistischen Unterschiede zwischen den drei Bundesländern vor.
Schlussfolgerung Die vorliegenden Daten lassen auf eine vergleichbare stationäre und poststationäre Versorgung und 1-Jahresprognose von Patienten mit akutem MI in den Bundesländern Berlin, Brandenburg und Mecklenburg-Vorpommern in der untersuchten Population schließen, wobei insbesondere der Durchführung einer Koronarangiografie und der adäquaten Umsetzung einer leitliniengerechten Pharmakotherapie prognostische Bedeutung zukommt.
Surface electromyographic (EMG) signal amplitude is typically used to compare the neural drive to muscles. We experimentally investigated this association by studying the motor unit (MU) behavior and action potentials in the vastus medialis (VM) and vastus lateralis (VL) muscles. Eighteen participants performed isometric knee extensions at four target torques [10. 30. 50, and 70% of the maximum torque (MVC)] while high-density EMG signals were recorded from the VM and VL. The absolute EMG amplitude was greater for VM than VL (P < 0.001), whereas the EMG amplitude normalized with respect to MVC was greater for VL than VM (P < 0.04). Because differences in EMG amplitude can be due to both differences in the neural drive and in the size of the MU action potentials, we indirectly inferred the neural drives received by the two muscles by estimating the synaptic inputs received by the corresponding motor neuron pools. For this purpose. we analyzed the increase in discharge rate from recruitment to target torque for motor units matched by recruitment threshold in the two muscles. This analysis indicated that the two muscles received similar levels of neural drive. Nonetheless, the size of the MU action potentials was greater for VM than VL (P < 0.001), and this difference explained most of the differences in EMG amplitude between the two muscles (similar to 63% of explained variance). These results indicate that EMG amplitude, even following normalization, does not reflect the neural drive to synergistic muscles. Moreover, absolute EMG amplitude is mainly explained by the size of MU action potentials. NEW & NOTEWORTHY Electromyographic (EMG) amplitude is widely used to compare indirectly the strength of neural drive received by synergistic muscles. However, there are no studies validating this approach with motor unit data. Here, we compared between-muscles differences in surface EMG amplitude and motor unit behavior. The results clarify the limitations of surface EMG to interpret differences in neural drive between muscles.
Ramirez-Campillo, R, Alvarez, C, García-Pinillos, F, Sanchez-Sanchez, J, Yanci, J, Castillo, D, Loturco, I, Chaabene, H, Moran, J, and Izquierdo, M. Optimal reactive strength index: is it an accurate variable to optimize plyometric training effects on measures of physical fitness in young soccer players? J Strength Cond Res 32(4): 885–893, 2018—This study aimed to compare the effects of drop-jump training using a fixed drop-box height (i.e., 30-cm [FIXED]) vs. an optimal (OPT) drop-box height (i.e., 10-cm to 40-cm: generating an OPT reactive strength index [RSI]) in youth soccer players' physical fitness. Athletes were randomly allocated to a control group (n = 24; age = 13.7 years), a fixed drop-box height group (FIXED, n = 25; age = 13.9 years), or an OPT drop-box height group (OPT, n = 24; age = 13.1 years). Before and after 7 weeks of training, tests for the assessment of jumping (countermovement jump [CMJ], 5 multiple bounds), speed (20-m sprint time), change of direction ability (CODA [Illinois test]), strength {RSI and 5 maximal squat repetition test (5 repetition maximum [RM])}, endurance (2.4-km time trial), and kicking ability (maximal kicking distance) were undertaken. Analyses revealed main effects of time for all dependent variables (p < 0.001, d = 0.24–0.72), except for 20-m sprint time. Analyses also revealed group × time interactions for CMJ (p < 0.001, d = 0.51), depth jump (DJ) (p < 0.001, d = 0.30), 20-m sprint time (p < 0.001, d = 0.25), CODA (p < 0.001, d = 0.22), and 5RM (p < 0.01, d = 0.16). Post hoc analyses revealed increases for the FIXED group (CMJ: 7.4%, d = 0.36; DJ: 19.2%, d = 0.49; CODA: −3.1%, d = −0.21; 5RM: 10.5%, d = 0.32) and the OPT group (CMJ: 16.7%, d = 0.76; DJ: 36.1%, d = 0.79; CODA: −4.4%, d = −0.34; 5RM: 18.1%, d = 0.47). Post hoc analyses also revealed increases for the OPT group in 20-m sprint time (−3.7%, d = 0.27). Therefore, to maximize the effects of plyometric training, an OPT approach is recommended. However, using adequate fixed drop-box heights may provide a rational and practical alternative.
Serious knee pain and related disability have an annual prevalence of approximately 25% on those over the age of 55 years. As curative treatments for the common knee problems are not available to date, knee pathologies typically progress and often lead to osteoarthritis (OA). While the roles that the meniscus plays in knee biomechanics are well characterized, biological mechanisms underlying meniscus pathophysiology and roles in knee pain and OA progression are not fully clear. Experimental treatments for knee disorders that are successful in animal models often produce unsatisfactory results in humans due to species differences or the inability to fully replicate disease progression in experimental animals. The use of animals with spontaneous knee pathologies, such as dogs, can significantly help addressing this issue. As microscopic and macroscopic anatomy of the canine and human menisci are similar, spontaneous meniscal pathologies in canine patients are thought to be highly relevant for translational medicine. However, it is not clear whether the biomolecular mechanisms of pain, degradation of extracellular matrix, and inflammatory responses are species dependent. The aims of this review are (1) to provide an overview of the anatomy, physiology, and pathology of the human and canine meniscus, (2) to compare the known signaling pathways involved in spontaneous meniscus pathology between both species, and (3) to assess the relevance of dogs with spontaneous meniscal pathology as a translational model. Understanding these mechanisms in human and canine meniscus can help to advance diagnostic and therapeutic strategies for painful knee disorders and improve clinical decision making.
Background: Life events (LEs) are associated with future physical and mental health. They are crucial for understanding the pathways to mental disorders as well as the interactions with biological parameters. However, deeper insight is needed into the complex interplay between the type of LE, its subjective evaluation and accompanying factors such as social support. The "Stralsund Life Event List" (SEL) was developed to facilitate this research.
Methods: The SEL is a standardized interview that assesses the time of occurrence and frequency of 81 LEs, their subjective emotional valence, the perceived social support during the LE experience and the impact of past LEs on present life. Data from 2265 subjects from the general population-based cohort study "Study of Health in Pomerania" (SHIP) were analysed. Based on the mean emotional valence ratings of the whole sample, LEs were categorized as "positive" or "negative". For verification, the SEL was related to lifetime major depressive disorder (MDD; Munich Composite International Diagnostic Interview), childhood trauma (Childhood Trauma Questionnaire), resilience (Resilience Scale) and subjective health (SF-12 Health Survey).
Conclusions: The SEL is a valid instrument that enables the analysis of the number and frequency of LEs, their emotional valence, perceived social support and current impact on life on a global score and on an individual item level. Thus, we can recommend its use in research settings that require the assessment and analysis of the relationship between the occurrence and subjective evaluation of LEs as well as the complex balance between distressing and stabilizing life experiences.
Recently, there has been a proliferation of published articles on the effect of plyometric jump training, including several review articles and meta-analyses. However, these types of research articles are generally of narrow scope. Furthermore, methodological limitations among studies (e.g., a lack of active/passive control groups) prevent the generalization of results, and these factors need to be addressed by researchers. On that basis, the aims of this scoping review were to (1) characterize the main elements of plyometric jump training studies (e.g., training protocols) and (2) provide future directions for research. From 648 potentially relevant articles, 242 were eligible for inclusion in this review. The main issues identified related to an insufficient number of studies conducted in females, youths, and individual sports (~ 24.0, ~ 37.0, and ~ 12.0% of overall studies, respectively); insufficient reporting of effect size values and training prescription (~ 34.0 and ~ 55.0% of overall studies, respectively); and studies missing an active/passive control group and randomization (~ 40.0 and ~ 20.0% of overall studies, respectively). Furthermore, plyometric jump training was often combined with other training methods and added to participants’ daily training routines (~ 47.0 and ~ 39.0% of overall studies, respectively), thus distorting conclusions on its independent effects. Additionally, most studies lasted no longer than 7 weeks. In future, researchers are advised to conduct plyometric training studies of high methodological quality (e.g., randomized controlled trials). More research is needed in females, youth, and individual sports. Finally, the identification of specific dose-response relationships following plyometric training is needed to specifically tailor intervention programs, particularly in the long term.
Background: Optimal antibiotic exposure is a vital but challenging prerequisite for achieving clinical success in ICU patients. Objectives: To develop and externally validate a population pharmacokinetic model for continuous-infusion meropenem in critically ill patients and to establish a nomogram based on a routinely available marker of renal function. Methods: A population pharmacokinetic model was developed in NONMEM (R) 7.3 based on steady-state meropenem concentrations (C-ss) collected during therapeutic drug monitoring. Different serum creatinine-based markers of renal function were compared for their influence on meropenem clearance (the Cockcroft-Gault creatinine clearance CLCRcG, the CLCR bedside estimate according to Jelliffe, the Chronic Kidney Disease Epidemiology Collaboration equation and the four-variable Modification of Diet in Renal Disease equation). After validation of the pharmacokinetic model with independent data, a dosing nomogram was developed, relating renal function to the daily doses required to achieve selected target concentrations (4/8/16 mg/L) in 90% of the patients. Probability of target attainment was determined for efficacy (C-ss >= 8 mg/L) and potentially increased likelihood of adverse drug reactions (C-ss >32 mg/L). Results: In total, 433 plasma concentrations (3.20-48.0 mg/L) from 195 patients (median/P-0.05 - P-0.95 at baseline: weight 77.0/55.0-114 kg, CLCRCG 63.0/19.6-168 mL/min) were used for model building. We found that CLCRCG best described meropenem clearance (CL = 7.71 L/h, CLCRCG = 80 mL/min). The developed model was successfully validated with external data (n = 171, 73 patients). According to the nomogram, daily doses of 910/1480/2050/2800/ 3940 mg were required to reach a target C-ss = 8 mg/L in 90% of patients with CLCRCG = 20/50/80/120/180 mL/min, respectively. A low probability of adverse drug reactions (<0.5%) was associated with these doses. Conclusions: A dosing nomogram was developed for continuous-infusion meropenem based on renal function in a critically ill population.