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.

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.

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.

[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.

[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.

Anterior vertical mini-incision vs. retroperitoneoscopic nephrectomy in living kidney donation: a prospective study on donors' quality of life and clinical outcome.

BACKGROUND: A fundamental goal in living kidney donation (LKD) is to maximize donor safety while minimizing post-operative impairments. We evaluated clinical outcome and health-related quality of life (QOL) comparing anterior vertical mini-incision donor nephrectomy (MIDN) and retroperitoneoscopic donor nephrectomy (RPDN). METHODS: Thirty-eight MIDN and 45 RPDN donors were analyzed. In a subsample (n = 18 MIDN; n = 32 RPDN), QOL was prospectively assessed with the WHOQOL-Bref questionnaire before and three months after LKD. RESULTS: Skin-to-skin time (169 vs. 116 min, p < 0.001) and hospital stay (6.6 vs. 4.9 d, p < 0.001) were significantly shorter in RPDN. In total, 26% of MIDN patients and 13% of RPDN patients developed post-operative complications (p = 0.14). While in MIDN the QOL domains physical health (p = 0.03) and psychological (p = 0.03) and the overall QOL facet (p = 0.003) were significantly lower three months post-LKD compared to baseline, there were no significant QOL decreases in RPDN. However, no significant post-operative QOL differences were found between groups. RPDN donors retrospectively reported significantly less post-operative pain (p = 0.007) and physical strain (p = 0.05) caused by LKD than MIDN donors. CONCLUSIONS: It may be possible to further reduce the surgical burden of LKD by introducing RPDN. Post-operative QOL was not significantly different between groups, but the QOL decrease appeared to be less pronounced in RPDN.

Determination of ethyl glucuronide in hair improves evaluation of long-term alcohol abstention in liver transplant candidates.

BACKGROUND & AIMS: Prior to listing patients for Orthotopic liver transplantation (OLT) an abstention period of 6 months is required. Ethyl glucuronide in the hair is a new reliable marker for the assessment of alcohol consumption. Here, the diagnostic value of determining the ethyl glucuronide concentration in the hair of liver transplant candidates was evaluated. METHODS: In 63 transplant candidates with alcoholic liver cirrhosis and 25 control patients with cirrhosis of other aetiologies alcohol markers, i.e. hEtG, urine EtG, blood ethanol, methanol and carbohydrate deficient transferrin were determined in parallel to an interview with a psychologist. RESULTS: A total of 19 (30%) transplant candidates admitted alcohol consumption within the last 6 months, while 39/63 (62%) were positive for at least one alcohol marker. In 52% of the 44 candidates denying alcohol consumption, abstention was disproved by detecting at least one positive alcohol marker, in 83% of cases by a positive hEtG result. In the control patients stating abstention from alcohol all hEtG tests were negative. No impact of renal or liver function on hEtG results was detected. A specificity of 98% and a positive predictive value of 92% were calculated for testing hEtG in proximal hair segment and applying a cut-off of 30 pg/mg. CONCLUSIONS: In 52% of patients denying alcohol consumption within the last 6 months, alcohol abstention was disproved, in 83% of cases by hEtG testing. Therefore, hEtG is a promising new marker for the evaluation of long-term alcohol abstention in liver transplant candidates.

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.

Influence of kinship on donors' mental burden in living donor liver transplantation.

In the context of living donor liver transplantation (LDLT), German transplantation law stipulates that donor candidates should primarily be relatives of the recipients or persons with distinct and close relationships. In this study, we investigated the influence of the relationship between the donor and the recipient on the donor's emotional strain before transplantation. Donors were categorized according to the following subgroups: (1) parents donating for their children, (2) children donating for their parents, (3) siblings, (4) spouses, (5) other relatives, and (6) nonrelatives. The sample consisted of 168 donor candidates. Anxiety (F = 2.8, P = 0.02), depression (F = 2.6, P = 0.03), and emotional quality of life (F = 3.1, P = 0.01) differed significantly according to the relationship between the donor and the recipient. In comparison with healthy controls, parents donating for their children were significantly less stressed before LDLT and demonstrated fewer anxiety (P < 0.01) and depression symptoms (P < 0.05). Adult children donating for their parents demonstrated the highest mental burden and the lowest emotional quality of life. However, this was not due to the responsibility of these children for their own families because differences between donors with children and donors without children could not be ascertained. This group should be given special attention before LDLT and during follow-up visits, and psychological help should be provided when it is necessary.

A prospective study on living related kidney donors' quality of life in the first year: choosing appropriate reference data.

Prospective studies on living kidney donors' quality of life (QoL) are still rare. Most existing studies compare healthy donors with the general population, including subjects with diseases. This is the first prospective study comparing living donors' QoL with reference data of both the general population and healthy individuals. We investigated QoL, anxiety, and depression in living kidney donors (n = 79) before donation and at two post-operative data points (three months and one yr). Subsequently, data from the donors were compared with the reference data. Our results show an impaired physical QoL three months post-donation. One yr after surgery, physical QoL had returned to the pre-operative level. Neither mental QoL nor anxiety or depression showed major changes across time. Pre-operative QoL was comparable to that of healthy individuals and higher than that in the general population. Donors' perception of the recipient's health showed moderate correlations with donors' mental outcome three months after donation. In conclusion, the impact on physical QoL seems to persist for at least three months after kidney donation. It could be demonstrated that in the context of living donation, healthy individuals provide more adequate reference data. Future research needs to determine the length and the nature of the post-operative QoL impairment and further explore possible influencing factors.

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.

Endocrine and immune substrates of depressive symptoms and fatigue in multiple sclerosis patients with comorbid major depression.

OBJECTIVE: Depression and fatigue are among the most common symptoms of multiple sclerosis (MS). These symptoms frequently co-occur and partially overlap in MS but their underlying biological substrates are unclear. In this study, the relative role of cytokines and hypothalamic-pituitary-adrenal (HPA) axis activity in depression and fatigue were examined in patients with relapsing-remitting MS (RRMS). METHODS: HPA axis function and frequency of stimulated cytokine (interferon γ (IFNγ) and tumour necrosis factor α (TNFα)) producing T cells was measured cross sectionally in 44 female patients with RRMS. All subjects completed a neurological examination, the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) and self-report questionnaires. RESULTS: 10 patients met diagnostic criteria for major depressive disorder (MDD). MS patients with comorbid MDD showed normal morning but elevated evening salivary cortisol levels, resulting in a flattened slope. While a higher frequency of cytokine producing CD8+ T cells was also seen in MS patients with MDD, these markers were more closely associated with fatigue than depression. CONCLUSIONS: This study supports a role for HPA axis hyperactivity in major depression in MS. In addition, inflammatory and neuroendocrine factors may differentially mediate fatigue and depressive symptoms.

Effects of a physical exercise rehabilitation group program on anxiety, depression, body image, and health-related quality of life among breast cancer patients.

BACKGROUND: Since physical exercise programs have the potential to help cancer patients regain physical fitness and may exert a range of positive consequences for recovery and psychological well-being, the impact of a physical exercise program was investigated in this prospective study. PATIENTS AND METHODS: Women with primary nonmetastatic breast cancer after a minimum 4-week period post chemotherapy and/or radiotherapy completion were randomly assigned to one of 2 groups: intervention group (IG) (n = 30) and waiting group (WG) (n = 28). The 10-week twice weekly exercise group program consisted of gymnastics, movement games, relaxation, walking, and jogging. Anxiety, depression, body image, and quality of life were measured using standardized questionnaires. Maximal oxygen uptake (VO(2)max/kg) was assessed as a measure of physical fitness. RESULTS: Patients in the IG improved significantly over time with regard to anxiety (p = 0.03, d = 0.45), depression (p = 0.05, d = 0.43), individual body image (p = 0.006, d = 0.44), and VO(2)max/kg (p < 0.001, d = 0.50), whereas no improvements were observed in the WG. However, this randomized controlled trial failed to demonstrate significant intervention effects in quality of life and social body image. CONCLUSIONS: This prospective study provided evidence for the effectiveness of a 10-week physical exercise intervention to significantly improve psychosocial wellbeing, individual body image, and physical fitness.

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.

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.

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.

Mental and physical quality of life in actual living liver donors versus potential living liver donors: a prospective, controlled, multicenter study.

In a quasi-experimental design, we investigated the quality of life (QOL) in actual liver donors (n = 43) and potential liver donors (n = 33) before and 3 months after liver transplantation. This is the first study in this field combining a prospective design with an adequate control group. Potential donors served as a control group because they also had a relative in need of a liver transplant and were as emotionally involved with the recipient as actual donors, but they were not subjected to the donor operation. Groups did not differ in age, gender, marital status, donor-recipient relationship, urgency of transplantation, or recipient group (adult versus child). Actual donors showed decreased physical QOL, whereas potential donors were not affected. However, for both groups, a decrease in anxiety was found. Furthermore, actual donors showed a better mental QOL postoperatively than potential donors. The recipients of these 2 groups did not differ with respect to postoperative complications. Furthermore, the groups did not report a different caregiver burden, but actual donors showed higher self-esteem. Because of the surgery, the worsening of physical symptoms in actual donors was expected. It is remarkable, however, that although actual donors still showed a limited physical QOL 3 months after the operation, in both groups, a similar reduction in anxiety could be observed, and actual donors even demonstrated a better mental QOL postoperatively than potential donors. The latter might be due to a psychological benefit that actual donors derived from the fact that they were able to help the recipients.

Sense of coherence and social support predict living liver donors' emotional stress prior to living-donor liver transplantation.

The protection of the donors from physical or emotional harm has been a fundamental principle in living-donor liver donation from the beginning. Psychosomatic donor evaluation aims at the selection of eligible donors and the screening and exclusion of psychiatrically vulnerable donors. As clinical interviews may include subjective biases, efforts should be made to establish objective criteria for donor assessment. In recent research, protective factors have been reported to be a significant force behind healthy adjustment to life stresses and can be investigated as possible predictors of donors' eligibility. Being the central construct of Antonovsky's theory of salutogenesis, the sense of coherence is one of the most surveyed protective factors and a good predictor of individuals' stability when experiencing stress. Furthermore, family support has been shown to be a valuable protective resource in coping with stress. This study surveyed whether sense of coherence and social support predict donors' emotional strain prior to transplantation. Seventy-one donor candidates were included in the study during the donor evaluation prior to living-donor liver transplantation. Sense of coherence proved to be a significant predictor for all criterion variables, namely anxiety, depression and mental quality of life. In addition to this, donor candidates who were classified as eligible for donation in the psychosomatic interview had significantly higher values on sense of coherence total scores compared with rejected donors. In a multiple regression analysis, sense of coherence and social support together yielded a prediction of depression with an explained variance of 22% (R(2) = 0.22). Sense of coherence and social support can be implemented as self-rating instruments in the psychosomatic selection of donors and would help to further objectify donors' eligibility.

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).