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Objective:Common genetic variants in the gene encoding uromodulin (UMOD) have been associated with renal function, blood pressure (BP) and hypertension. We investigated the associations between an important single nucleotide polymorphism (SNP) in UMOD, that is rs12917707-G>T, and estimated glomerular filtration rate (eGFR), BP and cardiac organ damage as determined by echocardiography in patients with arterial hypertension.Methods:A cohort of 1218 treated high-risk patients (mean age 58.5 years, 83% men) with documented cardiovascular disease (81% with coronary heart disease) was analysed.Results:The mean values for 24-h SBP and DBP were 124.714.7 and 73.9 +/- 9.4mmHg; mean eGFR was 77.5 +/- 18.3ml/min per 1.73m(2), mean left ventricular ejection fraction was 59.3 +/- 9.9% and mean left ventricular mass index in men and women was 53.9 +/- 23.2 and 54.9 +/- 23.7g/m(2.7) with 50.4% of patients having left ventricular hypertrophy. A significant association between rs12917707 and eGFR was observed with T-allele carriers showing significantly higher eGFR values (+2.6ml/min per 1.73m(2), P=0.006) than noncarriers. This SNP associated also with left atrial diameter (P=0.007); homozygous carriers of the T-allele had smaller left atrial diameter (-1.5mm) than other genotype groups (P=0.040). No significant associations between rs12917707 and other cardiac or BP phenotypes were observed.Conclusions:These findings extend the previously documented role of UMOD for renal function also to treated high-risk patients with arterial hypertension and reveal a novel association with left atrial remodelling and thus a potential cardiorenal link modulated by UMOD.
Substance-dependent individuals often lack the ability to adjust decisions flexibly in response to the changes in reward contingencies. Prediction errors (PEs) are thought to mediate flexible decision-making by updating the reward values associated with available actions. In this study, we explored whether the neurobiological correlates of PEs are altered in alcohol dependence. Behavioral, and functional magnetic resonance imaging (fMRI) data were simultaneously acquired from 34 abstinent alcohol-dependent patients (ADP) and 26 healthy controls (HC) during a probabilistic reward-guided decision-making task with dynamically changing reinforcement contingencies. A hierarchical Bayesian inference method was used to fit and compare learning models with different assumptions about the amount of task-related information subjects may have inferred during the experiment. Here, we observed that the best-fitting model was a modified Rescorla-Wagner type model, the “double-update” model, which assumes that subjects infer the knowledge that reward contingencies are anti-correlated, and integrate both actual and hypothetical outcomes into their decisions. Moreover, comparison of the best-fitting model's parameters showed that ADP were less sensitive to punishments compared to HC. Hence, decisions of ADP after punishments were loosely coupled with the expected reward values assigned to them. A correlation analysis between the model-generated PEs and the fMRI data revealed a reduced association between these PEs and the BOLD activity in the dorsolateral prefrontal cortex (DLPFC) of ADP. A hemispheric asymmetry was observed in the DLPFC when positive and negative PE signals were analyzed separately. The right DLPFC activity in ADP showed a reduced correlation with positive PEs. On the other hand, ADP, particularly the patients with high dependence severity, recruited the left DLPFC to a lesser extent than HC for processing negative PE signals. These results suggest that the DLPFC, which has been linked to adaptive control of action selection, may play an important role in cognitive inflexibility observed in alcohol dependence when reinforcement contingencies change. Particularly, the left DLPFC may contribute to this impaired behavioral adaptation, possibly by impeding the extinction of the actions that no longer lead to a reward.
Methods: As part of the Potsdam Gait Study (POGS), healthy old adults completed a no-intervention control period (69.1 +/- 4A yrs, n =14) or a power training program followed by detraining (72.9 +/- 5.4 yrs, n = 15).We measured isokinetic knee extensor and plantarflexor power and measured hip, knee and ankle kinetics at habitual, fast and standardized walking speeds. Results: Power training significantly increased isokinetic knee extensor power (25%), plantarflexor power (43%), and fast gait velocity (5.9%). Gait mechanics underlying the improved fast gait velocity included increases in hip angular impulse (29%) and H1 work (37%) and no changes in positive knee (K2) and A2 work. Detraining further improved fast gait velocity (4.7%) with reductions in H1(-35%), and increases in K2 (36%) and A2 (7%). Conclusion: Power training increased fast gait velocity in healthy old adults by increasing the reliance on hip muscle function and thus further strengthened the age-related distal-to-proximal shift in muscle function. (C) 2016 Elsevier B.V. All rights reserved.
Background: We sought to develop a standardized protocol for ultrasound (US) measurements of plantar fascia (PF) width and cross-sectional area (CSA), which may serve as additional outcome variables during US examinations of both healthy asymptomatic PF and in plantar fasciopathy and determine its interrater and intrarater reliability. Methods: Ten healthy individuals (20 feet) were enrolled. Participants were assessed twice by two raters each to determine intrarater and interrater reliability. For each foot, three transverse scans of the central bundle of the PF were taken at its insertion at the medial calcaneal tubercle, identified in real time on the plantar surface of the foot, using a fine wire technique. Reliability was determined using intraclass correlation coefficients (ICC), standard errors of measurement (SEM), and limits of agreement (LOA) expressed as percentages of the mean. Reliability of PF width and CSA measurements was determined using PF width and CSA measurements from one sonogram measured once and the mean of three measurements from three sonograms each measured once. Results: Ultrasound measurements of PF width and CSA showed a mean of 18.6 +/- 2.0 mm and 69.20 +/- 13.6 mm(2) respectively. Intra-reliability within both raters showed an ICC. 0.84 for width and ICC. 0.92 for CSA as well as a SEM% and LOA%, 10% for both width and CSA. Inter-rater reliability showed an ICC of 0.82 for width and 0.87 for CSA as well as a SEM% and LOA%, 10% for width and a SEM%, 10% and LOA%, 20% for CSA. Relative and absolute reliability within and between raters were higher when using the mean of three sonographs compared to one sonograph. Conclusions: Using this novel technique, PF CSA and width may be determined reliably using measurements from one sonogram or the mean of three sonograms. Measurement of PF CSA and width in addition to already established thickness and echogenicity measurements provides additional information on structural properties of the PF for clinicians and researchers in healthy and pathologic PF.
We investigated the efficacy of reminiscence therapy (RT) on symptoms of depression in patients with mild to moderate dementia. Out of 227 patients with mild to moderate dementia from a specialized physician’s office, 27 pairs (N = 54; mean age 79.04 ± 6.16 years) who had either received treatment as usual (TAU) or TAU combined with RT, were matched retrospectively according to age as well as cognitive and depressive symptom scores. After controlling for age and sex, symptoms of depression significantly decreased over time in the RT group compared to TAU (F1,52 = 4.36; p < .05). RT is a promising option for the treatment of depression in mild to moderate dementia. Larger randomized-controlled trials are needed.
Background/Aims: The tumor suppressor p53 is rarely mutated in gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) but they frequently show a strong expression of negative regulators of p53, rendering these tumors excellent targets for a p53 recovery therapy. Therefore, we analyzed the mechanisms of a p53 recovery therapy on intestinal neuroendocrine tumors in vitro and in vivo. Methods: By Western blot and immunohistochemistry, we found that in GEP-NEN biopsy material overexpression of MDM2 was present in intestinal NEN. Therefore, we analyzed the effect of a small-molecule inhibitor, nutlin-3a, in p53 wild-type and mutant GEP-NEN cell lines by proliferation assay, flow cytometry, immunofluorescence, Western blot, and by multiplex gene expression analysis. Finally, we analyzed the antitumor effect of nutlin-3a in a xenograft mouse model in vivo. During the study, the tumor volume was determined. Results: The midgut wild-type cell line KRJ-I responded to the treatment with cell cycle arrest and apoptosis. By gene expression analysis, we could demonstrate that nutlins reactivated an antiproliferative p53 response. KRJ-I-derived xenograft tumors showed a significantly decreased tumor growth upon treatment with nutlin-3a in vivo. Furthermore, our data suggest that MDM2 also influences the expression of the oncogene FOXM1 in a p53-independent manner. Subsequently, a combined treatment of nutlin-3a and cisplatin (as chemoresistance model) resulted in synergistically enhanced antiproliferative effects. Conclusion: In summary, MDM2 overexpression is a frequent event in p53 wild-type intestinal neuroendocrine neoplasms and therefore recovery of a p53 response might be a novel personalized treatment approach in these tumors. (c) 2017 S. Karger AG, Basel
There are few data demonstrating the specific extent to which surgical intervention for vocal fold nodules (VFN) improves vocal function in professional (PVU) and non-professional voice users (NVU). The objective of this study was to compare and quantify results after phonomicrosurgery for VFN in these patient groups. METHODS: In a prospective clinical study, surgery was performed via microlaryngoscopy in 37 female patients with chronic VFN manifestations (38±12 yrs, mean±SD). Pre- and postoperative evaluations of treatment efficacy comprised videolaryngostroboscopy, auditory-perceptual voice assessment, voice range profile (VRP), acoustic-aerodynamic analysis, and voice handicap index (VHI-9i). The dysphonia severity index (DSI) was compared with the vocal extent measure (VEM). RESULTS: PVU (n=24) and NVU (n=13) showed comparable laryngeal findings and levels of suffering (VHI-9i 16±7 vs 17±8), but PVU had a better pretherapeutic vocal range (26.8±7.4 vs 17.7±5.1 semitones, p<0.001) and vocal capacity (VEM 106±18 vs 74±29, p<0.01). Three months postoperatively, all patients had straight vocal fold edges, complete glottal closure, and recovered mucosal wave propagation. The mean VHI-9i score decreased by 8±6 points. DSI increased from 4.0±2.4 to 5.5±2.4, and VEM from 95±27 to 108±23 (p<0.001). Both parameters correlated significantly (rs=0.82). The average vocal range increased by 4.1±5.3 semitones, and the mean speaking pitch lowered by 0.5±1.4 semitones. CONCLUSIONS: These results confirm that phonomicrosurgery for VFN is a safe therapy for voice improvement in both PVU and NVU who do not respond to voice therapy alone. Top-level artistic capabilities in PVU were restored, but numeric changes of most vocal parameters were considerably larger in NVU.
The integration of balance and plyometric training has been shown to provide significant improvements in sprint, jump, agility, and other performance measures in young athletes. It is not known if a specific within session balance and plyometric exercise sequence provides more effective training adaptations. The objective of the present study was to investigate the effects of using a sequence of alternating pairs of exercises versus a block (series) of all balance exercises followed by a block of plyometric exercises on components of physical fitness such as muscle strength, power, speed, agility, and balance. Twenty-six male adolescent soccer players ( 13.9 +/- 0.3 years) participated in an 8-week training program that either alternated individual balance (e. g., exercises on unstable surfaces) and plyometric (e. g., jumps, hops, rebounds) exercises or performed a block of balance exercises prior to a block of plyometric exercises within each training session. Pre- and post-training measures included proxies of strength, power, agility, sprint, and balance such as countermovement jumps, isometric back and knee extension strength, standing long jump, 10 and 30-m sprints, agility, standing stork, and Y-balance tests. Both groups exhibited significant, generally large magnitude (effect sizes) training improvements for all measures with mean performance increases of approximately > 30%. There were no significant differences between the training groups over time. The results demonstrate the effectiveness of combining balance and plyometric exercises within a training session on components of physical fitness with young adolescents. The improved performance outcomes were not significantly influenced by the within session exercise sequence.
Background: The aim of the present study was to investigate the psychometric characteristics of the Perceived Stress Scale (PSS) in a sample of dementia patients and their spousal caregivers. Methods: We investigated the reliability and validity of the 14-item PSS in a sample of 80 couples, each including one spouse who had been diagnosed with mild to moderate dementia (mean age 75.55, SD = 5.85, 38.7% female) and one spousal caregiver (mean age 73.06, SD = 6.75, 61.3% female). We also examined the factor structure and sensitivity of the scale with regard to gender differences. Results: Exploratory factor analysis of the PSS revealed a two-factor solution for the scale; the first factor reflected general stress while the second factor consisted of items reflecting the perceived ability to cope with stressors. A confirmatory factor analysis verified that the data were a better fit for the two-factor model than a one-factor model. The two factors of the PSS showed good reliability for patients as well as for caregivers ranging between alpha = 0.73 and alpha = 0.82. Perceived stress was significantly positively correlated with depressive symptomatology in both caregivers and patients. Mean PSS scores did not significantly differ between male and female patients nor did they differ between male and female caregivers. Conclusion: The present data indicate that the PSS provides a reliable and valid measure of perceived stress in dementia patients and their caregivers.
Background: Total hip or knee replacement is one of the most frequently performed surgical procedures. Physical rehabilitation following total hip or knee replacement is an essential part of the therapy to improve functional outcomes and quality of life. After discharge from inpatient rehabilitation, a subsequent postoperative exercise therapy is needed to maintain functional mobility. Telerehabilitation may be a potential innovative treatment approach. We aim to investigate the superiority of an interactive telerehabilitation intervention for patients after total hip or knee replacement, in comparison to usual care, regarding physical performance, functional mobility, quality of life and pain. Methods/design: This is an open, randomized controlled, multicenter superiority study with two prospective arms. One hundred and ten eligible and consenting participants with total knee or hip replacement will be recruited at admission to subsequent inpatient rehabilitation. After comprehensive, 3-week, inpatient rehabilitation, the intervention group performs a 3-month, interactive, home-based exercise training with a telerehabilitation system. For this purpose, the physiotherapist creates an individual training plan out of 38 different strength and balance exercises which were implemented in the system. Data about the quality and frequency of training are transmitted to the physiotherapist for further adjustment. Communication between patient and physiotherapist is possible with the system. The control group receives voluntary, usual aftercare programs. Baseline assessments are investigated after discharge from rehabilitation; final assessments 3 months later. The primary outcome is the difference in improvement between intervention and control group in 6-minute walk distance after 3 months. Secondary outcomes include differences in the Timed Up and Go Test, the Five-Times-Sit-to-Stand Test, the Stair Ascend Test, the Short-Form 36, the Western Ontario and McMaster Universities Osteoarthritis Index, the International Physical Activity Questionnaire, and postural control as well as gait and kinematic parameters of the lower limbs. Baseline-adjusted analysis of covariance models will be used to test for group differences in the primary and secondary endpoints. Discussion: We expect the intervention group to benefit from the interactive, home-based exercise training in many respects represented by the study endpoints. If successful, this approach could be used to enhance the access to aftercare programs, especially in structurally weak areas.
Instrumented treadmills offer the potential to generate standardized walking perturbations, which are particularly rapid and powerful. However, technical requirements to release adequate perturbations regarding timing, duration and amplitude are demanding. This study investigated the test-retest reliability and validity of a new treadmill perturbation protocol releasing rapid and unexpected belt perturbations to provoke muscular reflex responses at lower extremities and the trunk. Fourteen healthy participants underwent two identical treadmill walking protocols, consisting of 10 superimposed one-sided belt perturbations (100 ms duration; 2 m/s amplitude), triggered by a plantar pressure insole 200 ms after heel contact. Delay, duration and amplitude of applied perturbations were recorded by 3D-motion capture. Muscular reflex responses (within 200 ms) were measured at lower extremities and the trunk (10-lead EMG). Data was analyzed descriptively (mean +/- SD). Reliability was analyzed using test-retest variability (TRV%) and limits of agreement (LoA, bias +/- 1.96*SD). Perturbation delay was 202 14 ms, duration was 102 +/- 4 ms and amplitude was 2.1 +/- 0.01 m/s. TRV for perturbation delay, duration and amplitude ranged from 5.0% to 5.7%. LoA reached 3 +/- 36 ms for delay, 2 +/- 13 ms for duration and 0.0 +/- 0.3 m/s for amplitude. EMG amplitudes following perturbations ranged between 106 +/- 97% and 909 +/- 979% of unperturbed gait and EMG latencies between 82 +/- 14 ms and 106 +/- 16 ms. Minor differences between preset and observed perturbation characteristics and results of test-retest analysis prove a high validity with excellent reliability of the setup. Therefore, the protocol tested can be recommended to provoke muscular reflex responses at lower extremities and the trunk in perturbed walking. (C) 2017 Elsevier Ltd. All rights reserved.
Background
In health research, indicators of socioeconomic status (SES) are often used interchangeably and often lack theoretical foundation. This makes it difficult to compare results from different studies and to explore the relationship between SES and health outcomes. To aid researchers in choosing appropriate indicators of SES, this article proposes and tests a theory-based selection of SES indicators using chronic back pain as a health outcome.
Methods
Strength of relationship predictions were made using Brunner & Marmot’s model of ‘social determinants of health’. Subsequently, a longitudinal study was conducted with 66 patients receiving in-patient treatment for chronic back pain. Sociodemographic variables, four SES indicators (education, job position, income, multidimensional index) and back pain intensity and disability were obtained at baseline. Both pain dimensions were assessed again 6 months later. Using linear regression, the predictive strength of each SES indicator on pain intensity and disability was estimated and compared to the theory based prediction.
Results
Chronic back pain intensity was best predicted by the multidimensional index (beta = 0.31, p < 0.05), followed by job position (beta = 0.29, p < 0.05) and education (beta = −0.29, p < 0.05); whereas, income exerted no significant influence. Back pain disability was predicted strongest by education (beta = −0.30, p < 0.05) and job position (beta = 0.29, p < 0.05). Here, multidimensional index and income had no significant influence.
Conclusions
The choice of SES indicators influences predictive power on both back pain dimensions, suggesting SES predictors cannot be used interchangeably. Therefore, researchers should carefully consider prior to each study which SES indicator to use. The introduced framework can be valuable in supporting this decision because it allows for a stable prediction of SES indicator influence and their hierarchy on a specific health outcomes.
Background: In health research, indicators of socioeconomic status (SES) are often used interchangeably and often lack theoretical foundation. This makes it difficult to compare results from different studies and to explore the relationship between SES and health outcomes. To aid researchers in choosing appropriate indicators of SES, this article proposes and tests a theory-based selection of SES indicators using chronic back pain as a health outcome. Results: Chronic back pain intensity was best predicted by the multidimensional index (beta = 0.31, p < 0.05), followed by job position (beta = 0.29, p < 0.05) and education (beta = -0.29, p < 0.05); whereas, income exerted no significant influence. Back pain disability was predicted strongest by education (beta = -0.30, p < 0.05) and job position (beta = 0. 29, p < 0.05). Here, multidimensional index and income had no significant influence. Conclusions: The choice of SES indicators influences predictive power on both back pain dimensions, suggesting SES predictors cannot be used interchangeably. Therefore, researchers should carefully consider prior to each study which SES indicator to use. The introduced framework can be valuable in supporting this decision because it allows for a stable prediction of SES indicator influence and their hierarchy on a specific health outcomes.
Objectives: In patients with early-stage dementia and their caregiving partners, reciprocal dyadic coping (DC) is crucial for preventing or reducing depressive symptoms in both partners. This study examines the relationships between ‘own DC’ and ‘perceived partner DC’ with depressive symptoms in couples coping with dementia on individual (actor effects) and cross-person (partner effects) levels.
Method: 164 individuals (82 patients with early-stage dementia and their 82 caregiving partners; ND = 82 dyads) participated in this prospective study with measures (DC, depressive symptoms, and dementia severity) taken at baseline and at six months. Each partner evaluated their own and the perceived partner DC. Actor–partner interdependence models were applied to the resulting four independent evaluations.
Results: Results differed substantially between patients and caregivers. DC was significantly related to patients’ but not to caregivers’ depressive symptoms, when adjustments were made for individual coping. Perceived partner DC showed a negative association with depressive symptoms in patients, whereas own DC was adversely related for actor as well as for partner effects across individuals.
Conclusion: The adverse association between the own DC of the caregiver and the patient on depressive symptoms of the patient might be due to inappropriate efforts or to the loss of autonomy as a care-receiver. DC is important in both patients and caregivers, as shown by the negative association between perceived partner DC and depressive symptoms in the patients, which might inform interventions that target the couple as a whole.
Non-local or crossover (contralateral and non-stretched muscles) increases in range-of-motion (ROM) and balance have been reported following rolling of quadriceps, hamstrings and plantar flexors. Since there is limited information regarding plantar sole (foot) rolling effects, the objectives of this study were to determine if unilateral foot rolling would affect ipsilateral and contralateral measures of ROM and balance in young healthy adults. A randomized within-subject design was to examine non-local effects of unilateral foot rolling on ipsilateral and contralateral limb ankle dorsiflexion ROM and a modified sit-and-reachtest (SRT). Static balance was also tested during a 30 s single leg stance test. Twelve participants performed three bouts of 60 s unilateral plantar sole rolling using a roller on the dominant foot with 60 s rest intervals between sets. ROM and balance measures were assessed in separate sessions at pre-intervention, immediately and 10 minutes post-intervention. To evaluate repeated measures effects, two SRT pre-tests were implemented. Results demonstrated that the second pre-test SRT was 6.6% higher than the first pre-test (p = 0.009, d = 1.91). There were no statistically significant effects of foot rolling on any measures immediately or 10 min post-test. To conclude, unilateral foot rolling did not produce statistically significant increases in ipsilateral or contralateral dorsiflexion or SRT ROM nor did it affect postural sway. Our statistically non-significant findings might be attributed to a lower degree of roller-induced afferent stimulation due to the smaller volume of myofascia and muscle compared to prior studies. Furthermore, ROM results from studies utilizing a single pre-test without a sufficient warm-up should be viewed critically.
Background In patients with mild cognitive impairment (MCI), gait instability, particularly in dual-task situations, has been associated with impaired executive function and an increased fall risk. Ginkgo biloba extract (GBE) could be an effective mean to improve gait stability. Aims This study investigated the effect of GBE on spatiotemporal gait parameters of MCI patients while walking under single and dual-task conditions. Methods Fifty patients aged 50-85 years with MCI and associated dual-task-related gait impairment participated in this randomised, double-blind, placebo-controlled, exploratory phase IV drug trial. Intervention group (IG) patients received GBE (Symfona (R) forte 120 mg) twice-daily for 6 months while control group (CG) patients received placebo capsules. A 6-month open-label phase with identical GBE dosage followed. Gait was quantified at months 0, 3, 6 and 12. Results After 6 months, dual-task-related cadence increased in the IG compared to the CG (p = 0.019, d = 0.71). No significant changes, but GBE-associated numerical non-significant trends were found after 6-month treatment for dual-task-related gait velocity and stride time variability. Discussion Findings suggest that 120 mg of GBE twice-daily for at least 6 months may improve dual-task-related gait performance in patients with MCI. Conclusions The observed gait improvements add to the understanding of the self-reported unspecified improvements among MCI patients when treated with standardised GBE.
Background Exercise rehabilitation is highly recommended by current guidelines on prevention of cardiovascular disease, but its implementation is still poor. Many clinicians experience difficulties in prescribing exercise in the presence of different concomitant cardiovascular diseases and risk factors within the same patient. It was aimed to develop a digital training and decision support system for exercise prescription in cardiovascular disease patients in clinical practice: the European Association of Preventive Cardiology Exercise Prescription in Everyday Practice and Rehabilitative Training (EXPERT) tool. Methods EXPERT working group members were requested to define (a) diagnostic criteria for specific cardiovascular diseases, cardiovascular disease risk factors, and other chronic non-cardiovascular conditions, (b) primary goals of exercise intervention, (c) disease-specific prescription of exercise training (intensity, frequency, volume, type, session and programme duration), and (d) exercise training safety advices. The impact of exercise tolerance, common cardiovascular medications and adverse events during exercise testing were further taken into account for optimized exercise prescription. Results Exercise training recommendations and safety advices were formulated for 10 cardiovascular diseases, five cardiovascular disease risk factors (type 1 and 2 diabetes, obesity, hypertension, hypercholesterolaemia), and three common chronic non-cardiovascular conditions (lung and renal failure and sarcopaenia), but also accounted for baseline exercise tolerance, common cardiovascular medications and occurrence of adverse events during exercise testing. An algorithm, supported by an interactive tool, was constructed based on these data. This training and decision support system automatically provides an exercise prescription according to the variables provided. Conclusion This digital training and decision support system may contribute in overcoming barriers in exercise implementation in common cardiovascular diseases.
Knie- und Hüftgelenksarthrose zählen zu den zehn häufigsten Einzeldiagnosen in orthopädischen Praxen. Die Wirksamkeit einer stationären Rehabilitation für Patienten nach Knie- oder Hüft-Totalendoprothese (TEP) ist in mehreren Studien belegt. Dennoch stellt die mittel- und langfristige Nachhaltigkeit zum Erhalt des Therapieerfolges eine große Herausforderung dar. Das Ziel des Projekts ReMove-It ist es, einen Wirksamkeitsnachweis für eintelemedizinisch assistiertes Interventionstraining für Patienten nach einem operativen Eingriff an den unteren Extremitäten zu erbringen.
In dem Beitrag wird anhand von Erfahrungsberichten dargestellt, wie das interaktive Übungsprogramm für Knie- und Hüft-TEP-Patienten entwickelt und das telemedizinische Assistenzsystem MeineReha® in den Behandlungsalltag von drei Rehakliniken integriert wurde. Ebenso werden der Aufbau und Ablauf der klinischen Studie dargestellt und das System aus Sicht der beteiligten Ärzte, und Therapeuten bewertet.
Hintergrund
Patienten, die nach gescheitertem Weaning von der Intensivstation in die Frührehabilitation (FR) verlegt werden, weisen neben motorischen Einschränkungen oft auch Defizite in ihrer kognitiven Leistungsfähigkeit auf. Welche patientenseitigen Faktoren das kognitive Outcome am Ende der FR beeinflussen, ist noch unzureichend untersucht.
Zielstellung
Ermittlung von Prädiktoren auf das kognitive Leistungsvermögen initial beatmeter FR-Patienten.
Methode
Zwischen 01/2014 und 12/2015 wurden 301 Patienten (68,3 ± 11,4 Jahre, 67 % männlich) einer neurologischen Phase-B-Weaningstation konsekutiv in eine prospektive Beobachtungsstudie eingeschlossen. Zur Ermittlung möglicher Einflussfaktoren auf das kognitive Outcome (operationalisiert mittels Neuromentalindex [NMI]) wurden soziodemografische Daten, kritische Erkrankung, Komorbiditäten, Parameter zu Weaning und Dekanülierung sowie diverse Scores zur Ermittlung funktionaler Parameter erhoben und mittels ANCOVA multivariat ausgewertet.
Ergebnisse
Insgesamt 248 Patienten (82 %) konnten erfolgreich geweant werden, 155 (52 %) dekanüliert, 75 Patienten (25 %) verstarben, davon 39 (13 %) unter Palliativtherapie. Für die überlebenden Patienten (n = 226) konnten im finalen geschlechts- und altersadjustierten statistischen Modell unabhängige Prädiktoren des NMI bei Entlassung aus der FR ermittelt werden: Wachheit und erfolgreiche Dekanülierung waren positiv mit dem NMI assoziiert, während als kritische Erkrankungen hypoxische Hirnschädigungen, Hirninfarkte und Schädel-Hirn-Traumata einen negativen Einfluss auf die kognitive Leistungsfähigkeit hatten. Das berechnete Modell begründet 57 % der Varianz des NMI (R2 = 0,568) und weist damit eine hohe Erklärungsqualität auf.
Schlussfolgerung
Aufgrund des erhöhten Risikos für eine verminderte kognitive Leistungsfähigkeit zum Ende der FR sollten vor allem Patienten nach Hypoxie, Hirninfarkt und Schädel-Hirn-Trauma intensiv neuropsychologisch betreut werden. Da weiterhin eine erfolgreiche Dekanülierung mit verbesserten kognitiven Leistungen assoziiert ist, sollte – vor allem bei wachen Patienten – zudem ein zügiges Trachealkanülenmanagement im therapeutischen Fokus stehen.
Paclitaxel is a commonly used cytotoxic anticancer drug with potentially life-threatening toxicity at therapeutic doses and high interindividual pharmacokinetic variability. Thus, drug and effect monitoring is indicated to control dose-limiting neutropenia. Joerger et al. (2016) developed a dose individualization algorithm based on a pharmacokinetic (PK)/pharmacodynamic (PD) model describing paclitaxel and neutrophil concentrations. Furthermore, the algorithm was prospectively compared in a clinical trial against standard dosing (Central European Society for Anticancer Drug Research Study of Paclitaxel Therapeutic Drug Monitoring; 365 patients, 720 cycles) but did not substantially improve neutropenia. This might be caused by misspecifications in the PK/PD model underlying the algorithm, especially without consideration of the observed cumulative pattern of neutropenia or the platinum-based combination therapy, both impacting neutropenia. This work aimed to externally evaluate the original PK/PD model for potential misspecifications and to refine the PK/PD model while considering the cumulative neutropenia pattern and the combination therapy. An underprediction was observed for the PK (658 samples), the PK parameters, and these parameters were re-estimated using the original estimates as prior information. Neutrophil concentrations (3274 samples) were over-predicted by the PK/PD model, especially for later treatment cycles when the cumulative pattern aggravated neutropenia. Three different modeling approaches (two from the literature and one newly developed) were investigated. The newly developed model, which implemented the bone marrow hypothesis semiphysiologically, was superior. This model further included an additive effect for toxicity of carboplatin combination therapy. Overall, a physiologically plausible PK/PD model was developed that can be used for dose adaptation simulations and prospective studies to further improve paclitaxel/ carboplatin combination therapy.