Dropout from exercise trials among cancer survivors-An individual patient data meta-analysis from the POLARIS study.

INTRODUCTION: The number of randomized controlled trials (RCTs) investigating the effects of exercise among cancer survivors has increased in recent years; however, participants dropping out of the trials are rarely described. The objective of the present study was to assess which combinations of participant and exercise program characteristics were associated with dropout from the exercise arms of RCTs among cancer survivors. METHODS: This study used data collected in the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) study, an international database of RCTs investigating the effects of exercise among cancer survivors. Thirty-four exercise trials, with a total of 2467 patients without metastatic disease randomized to an exercise arm were included. Harmonized studies included a pre and a posttest, and participants were classified as dropouts when missing all assessments at the post-intervention test. Subgroups were identified with a conditional inference tree. RESULTS: Overall, 9.6% of the participants dropped out. Five subgroups were identified in the conditional inference tree based on four significant associations with dropout. Most dropout was observed for participants with BMI >28.4 kg/m2 , performing supervised resistance or unsupervised mixed exercise (19.8% dropout) or had low-medium education and performed aerobic or supervised mixed exercise (13.5%). The lowest dropout was found for participants with BMI >28.4 kg/m2 and high education performing aerobic or supervised mixed exercise (5.1%), and participants with BMI ≤28.4 kg/m2 exercising during (5.2%) or post (9.5%) treatment. CONCLUSIONS: There are several systematic differences between cancer survivors completing and dropping out from exercise trials, possibly affecting the external validity of exercise effects.

Regioselective Hydroxylation of Unsymmetrical Ketones Using Cu, H2O2, and Imine Directing Groups via Formation of an Electrophilic Cupric Hydroperoxide Core.

Herein, we describe the regioselective functionalization of unsymmetrical ketones using imine directing groups, Cu, and H2O2. The C-H hydroxylation of the substrate-ligands derived from 2-substituted benzophenones occurred exclusively at the γ-position of the unsubstituted ring due to the formation of only one imine stereoisomer. Conversely, the imines derived from 4-substituted benzophenones produced E/Z mixtures that upon reacting with Cu and H2O2 led to two γ-C-H hydroxylation products. Contrary to our initial hypothesis, the ratio of the hydroxylation products did not depend on the ratio of the E/Z isomers but on the electrophilicity of the reactive [LCuOOH]1+. A detailed mechanistic analysis suggests a fast isomerization of the imine substrate-ligand binding the CuOOH core before the rate-determining electrophilic aromatic hydroxylation. Varying the benzophenone substituents and/or introducing electron-donating and electron-withdrawing groups on the 4-position of pyridine of the directing group allowed for fine-tuning of the electrophilicity of the mononuclear [LCuOOH]1+ to reach remarkable regioselectivities (up to 91:9 favoring the hydroxylation of the electron-rich arene ring). Lastly, we performed the C-H hydroxylation of alkyl aryl ketones, and like in the unsymmetrical benzophenones, the regioselectivity of the transformations (sp3 vs sp2) could be controlled by varying the electronics of the substrate and/or the directing group.

Physical fitness moderates the association between brain network impairment and both motor function and cognition in progressive multiple sclerosis.

BACKGROUND: Neurodegeneration leads to continuous accumulation of disability in progressive Multiple Sclerosis (MS). Exercise is considered to counteract disease progression, but little is known on the interaction between fitness, brain networks and disability in MS. OBJECTIVE: The aim of this study to explore functional and structural brain connectivity and the interaction between fitness and disability based on motor and cognitive functional outcomes in a secondary analysis of a randomised, 3-month, waiting group controlled arm ergometry intervention in progressive MS. METHODS: We modelled individual structural and functional brain networks based on magnetic resonance imaging (MRI). We used linear mixed effect models to compare changes in brain networks between the groups and explore the association between fitness, brain connectivity and functional outcomes in the entire cohort. RESULTS: We recruited 34 persons with advanced progressive MS (pwMS, mean age 53 years, females 71%, mean disease duration 17 years and an average walking restriction of < 100 m without aid). Functional connectivity increased in highly connected brain regions of the exercise group (p = 0.017), but no structural changes (p = 0.817) were observed. Motor and cognitive task performance correlated positively with nodal structural connectivity but not nodal functional connectivity. We also found that the correlation between fitness and functional outcomes was stronger with lower connectivity. CONCLUSIONS: Functional reorganisation seems to be an early indicator of exercise effects on brain networks. Fitness moderates the relationship between network disruption and both motor and cognitive outcomes, with growing importance in more disrupted brain networks. These findings underline the need and opportunities associated with exercise in advanced MS.

Moderators of exercise effects on self-reported cognitive functioning in cancer survivors: an individual participant data meta-analysis.

PURPOSE: This individual participant data meta-analysis (IPD-MA) assesses exercise effects on self-reported cognitive functioning (CF) and investigates whether effects differ by patient-, intervention-, and exercise-related characteristics. METHODS: IPD from 16 exercise RCTs, including 1987 patients across multiple types of non-metastatic cancer, was pooled. A one-stage IPD-MA using linear mixed-effect models was performed to assess exercise effects on self-reported CF (z-score) and to identify whether the effect was moderated by sociodemographic, clinical, intervention- and exercise-related characteristics, or fatigue, depression, anxiety, and self-reported CF levels at start of the intervention (i.e., baseline). Models were adjusted for baseline CF and included a random intercept at study level to account for clustering of patients within studies. A sensitivity analysis was performed in patients who reported cognitive problems at baseline. RESULTS: Minimal significant beneficial exercise effects on self-reported CF (ß=-0.09 [-0.16; -0.02]) were observed, with slightly larger effects when the intervention was delivered post-treatment (n=745, ß=-0.13 [-0.24; -0.02]), and no significant effect during cancer treatment (n=1,162, ß=-0.08 [-0.18; 0.02]). Larger effects were observed in interventions of 12 weeks or shorter (ß=-0.14 [-0.25; -0.04]) or 24 weeks or longer (ß=-0.18 [-0.32; -0.02]), whereas no effects were observed in interventions of 12-24 weeks (ß=0.01 [-0.13; 0.15]). Exercise interventions were most beneficial when provided to patients without anxiety symptoms (ß=-0.10 [-0.19; -0.02]) or after completion of treatment in patients with cognitive problems (ß=-0.19 [-0.31; -0.06]). No other significant moderators were identified. CONCLUSIONS: This cross-cancer IPD meta-analysis observed small beneficial exercise effects on self-reported CF when the intervention was delivered post-treatment, especially in patients who reported cognitive problems at baseline. IMPLICATIONS FOR CANCER SURVIVORS: This study provides some evidence to support the prescription of exercise to improve cognitive functioning. Sufficiently powered trials are warranted to make more definitive recommendations and include these in the exercise guidelines for cancer survivors.

Feasibility, acceptability, and behavioral outcomes of a multimodal intervention for prostate cancer patients: Experience from the MARTINI lifestyle program.

BACKGROUND: Prostate cancer (PCa) is the most frequently diagnosed malignant tumor in men. The potential benefit of a healthy lifestyle contrasts sharply with the observed poor adherence to current international lifestyle guidelines. Thus, well-designed sustainable interventions of aftercare that can be translated into routine practice are highly recommended. The present pilot study aimed to evaluate the feasibility and acceptability of a multimodal lifestyle intervention program in PCa patients after radical prostatectomy (RP). METHODS: In a single-arm study, carried out at the Martini-Klinik of the University Medical Center Hamburg-Eppendorf, Germany, 59 eligible men with locally advanced PCa were recruited within 3-6 months after RP and assigned to a multimodal lifestyle program. The program consisted of 10 weekly 6-7 h course days, with a focus on dietary control, physical activity (per World Cancer Research Fund recommendations) and psychological support. Primary objectives were feasibility, acceptability, completion rate, and safety. In addition, changes in lifestyle, psychological well-being, clinical and laboratory values were assessed. The study was registered in the German Clinical Trials Register (No. DRK S00015288 [MARTINI-Lifestyle-cohort] [www.germanctr.de]). RESULTS: A high program acceptance was observed. Only three participants (5%) dropped out of the program prematurely. Personal feedback reflected appreciation for participation, personal gain through new knowledge and through the group experience. Without exception, all participants have taken part in follow-up examinations and no adverse events or incidents occurred. In addition, changes in lifestyle habits, clinical parameters and improved quality of life were detected. CONCLUSION: The MARTINI lifestyle program appears feasible and safe, and acceptance of the multimodal intervention was high among PCa patients. These encouraging results favor conducting a large multicenter trial to implement the program into routine practice and to evaluate the effectiveness of the intervention on survival and quality of life.

Randomised controlled trial testing the feasibility of an exercise and nutrition intervention for patients with ovarian cancer during and after first-line chemotherapy (BENITA-study).

OBJECTIVES: Advanced ovarian cancer is a severe disease with major side effects caused by peritoneal carcinomatosis, ascites and gastrointestinal involvement as well as exhaustive treatment like debulking surgery and combination chemotherapy. Two most frequently reported side effects are muscle wasting and malnutrition, leading to frailty, decreased health-related quality of life (HRQoL) and cancer-related fatigue (CRF). As muscle wasting and malnutrition often commence during first-line chemotherapy and develop progressively into a refractory state, an early intervention is warranted. This pilot study aimed to evaluate the safety and acceptance of a combined exercise and nutrition intervention during and after first-line chemotherapy. DESIGN: The pilot study was conducted as a monocentric 1:1 randomised controlled trial (RCT) with an intervention group (IG) and a control group (CG). Participants were divided by chance into IG or CG. Information on group allocation was conveyed to the study coordinator responsible for making an appointment with the patients for the baseline assessment as well as the physiotherapist and nutritionist responsible for the intervention and outcome assessment in both groups. PARTICIPANTS: Eligibility criteria included women ≥18 years of age, diagnosed with ovarian cancer, tubal cancer or peritoneal cancer and primary or interval debulking, scheduled but not started adjuvant or neoadjuvant chemotherapy and sufficient German-language skills. INTERVENTION: The IG received a 12-month exercise and nutrition programme, the CG continued to follow usual care. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes were recruitment rate, adherence to intervention, completion rate and adverse events. In addition, in-person assessments (eg, HRQoL, CRF, muscle quality and function and dietary intake and quality) were conducted at baseline (T0, before chemotherapy), week 9 (T1, mid-chemotherapy), week 19 (T2, after completion of chemotherapy) and after 12 months of intervention (T3). RESULTS: Of 60 eligible patients, 15 patients signed informed consent (recruitment rate=25.0%) and were randomised into IG (n=8) and CG (n=7). Eleven participants completed the study (completion rate, 73.3%), one patient dropped out due to loss of interest, one due to poor health, one was lost to follow-up and one patient died. CONCLUSION: The BENITA (Bewegungs- und Ernährungsintervention bei Ovarialkrebs) study demonstrated the safety and acceptance of an exercise and nutrition intervention integrated into first-line therapy and follow-up care of ovarian cancer. A large multicentre RCT is planned to investigate the effectiveness of the intervention on HRQoL, CRF and survival and to establish means of implementation into oncology guidelines and clinic routine. TRIAL REGISTRATION NUMBER: DRKS00013231.

Optimal mode of delivery in pregnancy: Individualized predictions using national vital statistics data.

Child birth via Cesarean section accounts for approximately 32% of all births each year in the United States. A variety of risk factors and complications can lead caregivers and patients to plan for a Cesarean delivery in advance before onset of labor. However, a non-trivial subset of Cesarean sections (∼25%) are unplanned and occur after an initial trial of labor is attempted. Unfortunately, patients who deliver via unplanned Cesarean sections have increased maternal morbidity and mortality rates and higher rates of neonatal intensive care admissions. In an effort to develop models aimed at improving health outcomes in labor and delivery, this work seeks to explore the use of national vital statistics data to quantify the likelihood of an unplanned Cesarean section based on 22 maternal characteristics. Machine learning techniques are used to ascertain influential features, train and evaluate models, and assess accuracy against available test data. Based on cross-validation results from a large training cohort (n = 6,530,467 births), the gradient-boosted tree algorithm was identified as the best performer and was evaluated on a large test cohort (n = 10,613,877 births) for two prediction scenarios. Area under the receiver operating characteristic curves of 0.77 or higher and recall scores of 0.78 or higher were obtained and the resulting models are well calibrated. Combined with feature importance analysis to explain why certain maternal characteristics lead to a specific prediction in individual patients, the developed analysis pipeline provides additional quantitative information to aid in the decision process on whether to plan for a Cesarean section in advance, a substantially safer option among women at a high risk of unplanned Cesarean delivery during labor.

Arm Ergometry to Improve Mobility in Progressive Multiple Sclerosis (AMBOS)-Results of a Pilot Randomized Controlled Trial.

Background: Walking disability is one of the most frequent and burdening symptoms of progressive multiple sclerosis (MS). Most of the exercise intervention studies that showed an improvement in mobility performance were conducted in low to moderately disabled relapsing-remitting MS patients with interventions using the legs. However, MS patients with substantial walking disability hardly can perform these tasks. Earlier work has indicated that aerobic arm training might also improve walking performance and could therefore be a therapeutic option in already moderately disabled progressive MS patients. Methods: Patients with progressive MS and EDSS 4-6.5 were randomized using a computer-generated algorithm list to either a waitlist control group (CG) or an intervention group (IG). The IG performed a 12-week home-based, individualized arm ergometry exercise training program. Maximum walking distance as measured by the 6-min walking test (6MWT) was the primary endpoint. Secondary endpoints included aerobic fitness, other mobility tests, cognitive functioning, as well as fatigue and depression. Results: Of n = 86 screened patients, 53 with moderate disability (mean EDSS 5.5, SD 0.9) were included and data of 39 patients were analyzed. Patients in the IG showed strong adherence to the program with a mean of 67 (SD 26.4) training sessions. Maximum work load (P max) increased in the training group while other fitness indicators did not. Walking distance in the 6MWT improved in both training and waitlist group but not significantly more in trained patients. Similarly, other mobility measures showed no differential group effect. Cognitive functioning remained unchanged. No serious events attributable to the intervention occurred. Conclusion: Although maximum work load improved, 3 months of high-frequency arm ergometry training of low to moderate intensity could not show improved walking ability or cognitive functioning in progressive MS compared to a waitlist CG. The study was registered at www.clinicaltrials.gov (NCT03147105) and funded by the local MS self-help organization.

Computational medicine, present and the future: obstetrics and gynecology perspective.

Medicine is, in its essence, decision making under uncertainty; the decisions are made about tests to be performed and treatments to be administered. Traditionally, the uncertainty in decision making was handled using expertise collected by individual providers and, more recently, systematic appraisal of research in the form of evidence-based medicine. The traditional approach has been used successfully in medicine for a very long time. However, it has substantial limitations because of the complexity of the system of the human body and healthcare. The complex systems are a network of highly coupled components intensely interacting with each other. These interactions give those systems redundancy and thus robustness to failure and, at the same time, equifinality, that is, many different causative pathways leading to the same outcome. The equifinality of the complex systems of the human body and healthcare system demand the individualization of medical care, medicine, and medical decision making. Computational models excel in modeling complex systems and, consequently, enabling individualization of medical decision making and medicine. Computational models are theory- or knowledge-based models, data-driven models, or models that combine both approaches. Data are essential, although to a different degree, for computational models to successfully represent complex systems. The individualized decision making, made possible by the computational modeling of complex systems, has the potential to revolutionize the entire spectrum of medicine from individual patient care to policymaking. This approach allows applying tests and treatments to individuals who receive a net benefit from them, for whom benefits outweigh the risk, rather than treating all individuals in a population because, on average, the population benefits. Thus, the computational modeling-enabled individualization of medical decision making has the potential to both improve health outcomes and decrease the costs of healthcare.

Aerobic Exercise Induces Functional and Structural Reorganization of CNS Networks in Multiple Sclerosis: A Randomized Controlled Trial.

Objectives: Evidence from animal studies suggests that aerobic exercise may promote neuroplasticity and could, therefore, provide therapeutic benefits for neurological diseases such as multiple sclerosis (MS). However, the effects of exercise in human CNS disorders on the topology of brain networks, which might serve as an outcome at the interface between biology and clinical performance, remain poorly understood. Methods: We investigated functional and structural networks in patients with relapsing-remitting MS in a clinical trial of standardized aerobic exercise. Fifty-seven patients were randomly assigned to moderate-intensity exercise for 3 months or a non-exercise control group. We reconstructed functional networks based on resting-state functional magnetic resonance imaging (MRI) and used probabilistic tractography on diffusion-weighted imaging data for structural networks. Results: At baseline, compared to 30 healthy controls, patients exhibited decreased structural connectivity that was most pronounced in hub regions of the brain. Vice versa, functional connectivity was increased in hubs. After 3 months, we observed hub independent increased functional connectivity in the exercise group while the control group presented a loss of functional hub connectivity. On a structural level, the control group remained unchanged, while the exercise group had also increased connectivity. Increased clustering of hubs indicates a better structural integration and internal connectivity at the top of the network hierarchy. Conclusion: Increased functional connectivity of hubs contrasts a loss of structural connectivity in relapsing-remitting MS. Under an exercise condition, a further hub independent increase of functional connectivity seems to translate in higher structural connectivity of the whole brain.

Reference-free NOE NMR analysis.

Nuclear Overhauser Effect (NOE) methods in NMR are an important tool for 3D structural analysis of small molecules. Quantitative NOE methods conventionally rely on reference distances, known distances that have to be spectrally separated and are not always available. Here we present a new method for evaluation and 3D structure selection that does not require a reference distance, instead utilizing structures optimized by molecular mechanics, enabling NOE evaluation even on molecules without suitable reference groups.

Moderators of Exercise Effects on Cancer-related Fatigue: A Meta-analysis of Individual Patient Data.

PURPOSE: Fatigue is a common and potentially disabling symptom in patients with cancer. It can often be effectively reduced by exercise. Yet, effects of exercise interventions might differ across subgroups. We conducted a meta-analysis using individual patient data of randomized controlled trials (RCT) to investigate moderators of exercise intervention effects on cancer-related fatigue. METHODS: We used individual patient data from 31 exercise RCT worldwide, representing 4366 patients, of whom 3846 had complete fatigue data. We performed a one-step individual patient data meta-analysis, using linear mixed-effect models to analyze the effects of exercise interventions on fatigue (z score) and to identify demographic, clinical, intervention- and exercise-related moderators. Models were adjusted for baseline fatigue and included a random intercept on study level to account for clustering of patients within studies. We identified potential moderators by testing their interaction with group allocation, using a likelihood ratio test. RESULTS: Exercise interventions had statistically significant beneficial effects on fatigue (ß = -0.17; 95% confidence interval [CI], -0.22 to -0.12). There was no evidence of moderation by demographic or clinical characteristics. Supervised exercise interventions had significantly larger effects on fatigue than unsupervised exercise interventions (ßdifference = -0.18; 95% CI -0.28 to -0.08). Supervised interventions with a duration ≤12 wk showed larger effects on fatigue (ß = -0.29; 95% CI, -0.39 to -0.20) than supervised interventions with a longer duration. CONCLUSIONS: In this individual patient data meta-analysis, we found statistically significant beneficial effects of exercise interventions on fatigue, irrespective of demographic and clinical characteristics. These findings support a role for exercise, preferably supervised exercise interventions, in clinical practice. Reasons for differential effects in duration require further exploration.

Effects and moderators of exercise on muscle strength, muscle function and aerobic fitness in patients with cancer: a meta-analysis of individual patient data.

OBJECTIVE: To optimally target exercise interventions for patients with cancer, it is important to identify which patients benefit from which interventions. DESIGN: We conducted an individual patient data meta-analysis to investigate demographic, clinical, intervention-related and exercise-related moderators of exercise intervention effects on physical fitness in patients with cancer. DATA SOURCES: We identified relevant studies via systematic searches in electronic databases (PubMed, Embase, PsycINFO and CINAHL). ELIGIBILITY CRITERIA: We analysed data from 28 randomised controlled trials investigating the effects of exercise on upper body muscle strength (UBMS) and lower body muscle strength (LBMS), lower body muscle function (LBMF) and aerobic fitness in adult patients with cancer. RESULTS: Exercise significantly improved UBMS (ß=0.20, 95% Confidence Interval (CI) 0.14 to 0.26), LBMS (ß=0.29, 95% CI 0.23 to 0.35), LBMF (ß=0.16, 95% CI 0.08 to 0.24) and aerobic fitness (ß=0.28, 95% CI 0.23 to 0.34), with larger effects for supervised interventions. Exercise effects on UBMS were larger during treatment, when supervised interventions included ≥3 sessions per week, when resistance exercises were included and when session duration was >60 min. Exercise effects on LBMS were larger for patients who were living alone, for supervised interventions including resistance exercise and when session duration was >60 min. Exercise effects on aerobic fitness were larger for younger patients and when supervised interventions included aerobic exercise. CONCLUSION: Exercise interventions during and following cancer treatment had small effects on UBMS, LBMS, LBMF and aerobic fitness. Demographic, intervention-related and exercise-related characteristics including age, marital status, intervention timing, delivery mode and frequency and type and time of exercise sessions moderated the exercise effect on UBMS, LBMS and aerobic fitness.

Short-term interval aerobic exercise training does not improve memory functioning in relapsing-remitting multiple sclerosis-a randomized controlled trial.

BACKGROUND: Only few aerobic exercise intervention trials specifically targeting cognitive functioning have been performed in multiple sclerosis. OBJECTIVE AND METHODS: This randomized controlled trial with 34 patients in the intervention group (IG) (mean: 38.2 years (±9.6)) and 34 patients in the control group (CG) (mean: 39.6 years (±9.7)) aimed to determine the effects of aerobic exercise on cognition in relapsing-remitting multiple sclerosis (RRMS). The primary outcome was verbal learning assessed by the verbal learning and memory test (VLMT). Patients were randomized to an IG or a waitlist CG. Patients in the IG exercised according to an individually tailored training schedule (with two to three sessions per week for 12 weeks). The primary analysis was carried out using the intention-to-treat (ITT) sample with ANCOVA adjusting for baseline scores. RESULTS: A total of 77 patients with RRMS were screened and 68 participants randomized (CG n = 34; IG n = 34). The sample comprised 68% females, had a mean age of 39 years, a mean disease duration of 6.3 years, and a mean expanded disability status scale of 1.8. No significant effects were detected in the ITT analysis for the primary endpoint VLMT or any other cognitive measures. Moreover, no significant treatment effects were observed for quality of life, fatigue, or depressive symptoms. CONCLUSION: This study failed to demonstrate beneficial effects of aerobic exercise on cognition in RRMS. The trial was prospectively registered at clinicaltrials.gov (NCT02005237).

Targeting Exercise Interventions to Patients With Cancer in Need: An Individual Patient Data Meta-Analysis.

Background: Exercise effects in cancer patients often appear modest, possibly because interventions rarely target patients most in need. This study investigated the moderator effects of baseline values on the exercise outcomes of fatigue, aerobic fitness, muscle strength, quality of life (QoL), and self-reported physical function (PF) in cancer patients during and post-treatment. Methods: Individual patient data from 34 randomized exercise trials (n = 4519) were pooled. Linear mixed-effect models were used to study moderator effects of baseline values on exercise intervention outcomes and to determine whether these moderator effects differed by intervention timing (during vs post-treatment). All statistical tests were two-sided. Results: Moderator effects of baseline fatigue and PF were consistent across intervention timing, with greater effects in patients with worse fatigue (Pinteraction = .05) and worse PF (Pinteraction = .003). Moderator effects of baseline aerobic fitness, muscle strength, and QoL differed by intervention timing. During treatment, effects on aerobic fitness were greater for patients with better baseline aerobic fitness (Pinteraction = .002). Post-treatment, effects on upper (Pinteraction < .001) and lower (Pinteraction = .01) body muscle strength and QoL (Pinteraction < .001) were greater in patients with worse baseline values. Conclusion: Although exercise should be encouraged for most cancer patients during and post-treatments, targeting specific subgroups may be especially beneficial and cost effective. For fatigue and PF, interventions during and post-treatment should target patients with high fatigue and low PF. During treatment, patients experience benefit for muscle strength and QoL regardless of baseline values; however, only patients with low baseline values benefit post-treatment. For aerobic fitness, patients with low baseline values do not appear to benefit from exercise during treatment.

[Psychosocial Evaluation of Transplant Patients - Recommendations for the Guidelines for Organ Transplantation]. / Psychosoziale Evaluation von Transplantationspatienten ­ Empfehlungen für die Richtlinien zur Organtransplantation.

For the last few years, the German Medical Association's guidelines for transplant medicine have been subject to an extensive revision process. The present contribution presents recommendations regarding the psychosocial evaluation of patients prior to organ transplantation, which were developed by experts from the Psychology/Psychosomatics committee of the German Transplant Society with the aim to incorporate the recommendations into the guidelines. The main objective is to establish a mandatory psychosocial evaluation for all patients prior to their admission to the transplant waiting list. Contents, potential contraindications, and the procedure of the evaluation are described. Furthermore, the qualification deemed necessary for the examiners is addressed in detail. Finally, the future need for action is determined.

[Psychological Foundations of Pediatric Liver Transplantation]. / Psychologische Grundlagen der pädiatrischen Lebertransplantation.

Liver transplantation (LTX) is an established therapy for pediatric patients with liver failure. In recent decades, survival rates have risen continuously. With increased life expectancy, there has been greater attention to children's and adolescents' quality of life following transplantation. This article provides an overview of the tasks of pediatric transplant psychology. We summarize the reviewed literature of research on health-related quality of life in pediatric liver transplant recipients. Furthermore, we present studies on fatigue, mental health, cognitive development and family strain. In adolescents and young adults, the risk of non-adherence is particularly high. Therefore, adherence and transition, i. e. transfer from pediatric to adult-centered transplant care, are discussed separately. Subsequently, studies on long-term survival after LTX are summarized. In conclusion, recommendations for clinical practice are given.

Aberrant peak lactate response in MS.

BACKGROUND: The peak blood lactate response to an exhaustive exercise test in a number of chronic conditions has been shown to differ from that seen in healthy, untrained individuals. However, this has not been investigated for patients with multiple sclerosis (MS). OBJECTIVE: The main objective was to determine and compare the peak blood lactate response to exercise and the maximal workload between two groups of MS patients with different illness severity. METHODS: Twenty-five patients with a relapsing-remitting disease course (Group RR) and 41 patients with a secondary- or primary chronic progressive disease course (group CP) performed an exhaustive incremental bicycle ergometry. Peak blood lactate, maximal workload, peak oxygen consumption and maximal heart rate were measured. RESULTS: The peak blood lactate levels and maximal workload differed significantly between the groups (group CP < group RR; p < 0.001). Furthermore spiroergometric peak performance markers in both groups were significantly lower than predicted for healthy age and sex matched untrained groups. CONCLUSION: A reduced peak blood lactate response to exercise is a novel finding for MS patients. This calls into doubt if the lactate performance tests and lactate thresholds used for healthy individuals can be transferred to MS patients.

Physical condition, nutritional status, fatigue, and quality of life in oncological out-patients.

OBJECTIVE: Early detection of limited physical activity and nutritional deficiencies in cancer survivors could contribute to early treatment and preservation of quality of life. The aim of this study is to describe the association of physical condition and nutritional status with fatigue and quality of life in oncological out-patients. METHODS: Data in this descriptive study was collected on bioelectrical impedance analysis, postural stability (stability index), body mass index, Karnofsky Index, quality of life (Short-Form 36-Item Health Survey) and fatigue (multidimensional fatigue inventory-20) in a consecutive sample of 203 oncological out-patients. Phase angle was calculated from bioelectrical impedance analysis. Values were intercorrelated and compared to appropriate standard values. RESULTS: Phase angle and stability index outcomes were far below the values of a healthy population of similar age (p < 0.001). Quality of life was significantly lower than in the normal population (p < 0.001), and the level of fatigue was significantly higher (p < 0.001). Phase angle correlated with Karnofsky Index (p = 0.002) and Short-Form 36-Item Health Survey Summary physical function (p < 0.001). Furthermore, multidimensional fatigue inventory-20 scales 'physical fatigue' and 'reduced activity' were significantly associated with phase angle (p = 0.04, p = 0.005). Stability indices correlated with Short-Form 36-Item Health Survey physical function. CONCLUSION: The physical condition and the nutritional status are key components determining the individual quality of life of oncological out-patients. These variables also showed an association with the manifestation of fatigue. Results highlight the need for interdisciplinary cooperation to detect physical, nutritional and psychological deficiencies in oncological out-patients.