Correction to: Impact of a combined multimodal-aerobic and multimodal intervention compared to standard aerobic treatment in breast cancer survivors with chronic cancer-related fatigue - results of a three-armed pragmatic trial in a comprehensive cohort design.

An amendment to this paper has been published and can be accessed via the original article.

Impact of a combined multimodal-aerobic and multimodal intervention compared to standard aerobic treatment in breast cancer survivors with chronic cancer-related fatigue - results of a three-armed pragmatic trial in a comprehensive cohort design.

BACKGROUND: Cancer-related fatigue (CRF) and insomnia are major complaints in breast cancer survivors (BC). Aerobic training (AT), the standard therapy for CRF in BC, shows only minor to moderate treatment effects. Other evidence-based treatments include cognitive behavioral therapy, e.g., sleep education/restriction (SE) and mindfulness-based therapies. We investigated the effectiveness of a 10-week multimodal program (MT) consisting of SE, psycho-education, eurythmy- and painting-therapy, administered separately or in combination with AT (CT) and compared both arms to AT alone. METHODS: In a pragmatic comprehensive cohort study BC with chronic CRF were allocated randomly or by patient preference to (a) MT, (b) CT (MT + AT) or (c) AT alone. Primary endpoint was a composite score of the Pittsburgh Sleep Quality Index and the Cancer Fatigue Scale after 10 weeks of intervention (T1); a second endpoint was a follow-up assessment 6 months later (T2). The primary hypothesis stated superiority of CT and non-inferiority of MT vs. AT at T1. A closed testing procedure preserved the global α-level. The intention-to-treat analysis included propensity scores for the mode of allocation and for the preferred treatment, respectively. RESULTS: Altogether 126 BC were recruited: 65 were randomized and 61 allocated by preference; 105 started the intervention. Socio-demographic parameters were generally balanced at baseline. Non-inferiority of MT to AT at T1 was confirmed (p < 0.05), yet the confirmative analysis stopped as it was not possible to confirm superiority of CT vs. AT (p = 0.119). In consecutive exploratory analyses MT and CT were superior to AT at T1 and T2 (MT) or T2 alone (CT), respectively. CONCLUSIONS: The multimodal CRF-therapy was found to be confirmatively non-inferior to standard therapy and even yielded exploratively sustained superiority. A randomized controlled trial including a larger sample size and a longer follow-up to evaluate multimodal CRF-therapy is highly warranted. TRIAL REGISTER: DRKS-ID: DRKS00003736 . Recruitment period June 2011 to March 2013. Date of registering 19 June 2012.

Validation of the Internal Coherence Scale (ICS) in Healthy Geriatric Individuals and Patients Suffering from Diabetes Mellitus Type 2 and Cancer.

BACKGROUND: With increased life expectancy, the coexistence of functional impairment and multimorbidity can negatively impact life quality and coherence in geriatric individuals. The self-report 10-item Internal Coherence (ICS) measures how individuals cope with and make sense of disease-specific life challenges. The aim of this study was to validate the ICS in a sample of geriatric individuals. METHODS AND PROCEDURE: In a cross-sectional study, geriatric individuals with and without chronic diseases were recruited. A factor analysis with principal component extraction (PCA) and a structural equation model (SEM) was conducted to assess the ICS factor structure in a geriatric sample. To measure convergent validity, the following scales were used: Short Health Survey (SF-12), Karnofsky Performance Index (KPI), Trait autonomic regulation (Trait aR), Sense of Coherence Scale (SOC), and Geriatric Depression Scale (GDS). RESULTS: A sample of n = 104 (70-96 years of age) patients with Diabetes Mellitus Type 2 (n = 22), cancer diseases (n = 31) and healthy controls (n = 51) completed the ICS. PCA and SEM yielded the original two-factor solution: 1. Inner resilience and coherence and 2. Thermo coherence. Overall internal consistency for this cohort was satisfying (Cronbach's α with rα = 0.72), and test-retest reliability was moderate (rrt = 0.53). ICS scores were significantly correlated to all convergent criteria ranging between r = 0.22 * and 0.49 ** (p < 0.05 *; p < 0.01 **). CONCLUSION: Study results suggest that the ICS appears to be a reliable and valid tool to measure internal coherence in a geriatric cohort (70-96 years). However, moderate test-retest reliability prompts the consideration of potential age-effects that may bias the reliability for this specific cohort.

Influence of Multimodal Treatment on Rest/Activity and Autonomic Regulation in Breast Cancer Patients with Cancer-Related Fatigue: Results of a Tri-Centre Trial with a Comprehensive Cohort Design.

INTRODUCTION: Breast cancer patients with cancer-related fatigue (BC-CRF) often have lower physical activity. To investigate how this could be improved, we evaluated a multimodal treatment (MT) and a combination of MT with aerobic training (CT) and compared these with aerobic training (AT) regarding rest/activity rhythm and state autonomic regulation (State aR). METHODS: In this pragmatic comprehensive cohort design study, the explorative analysis focused on actigraphy and State aR including the rest/activity regulation subscale (State aR-R/A) which were assessed at baseline (T0), after 10 weeks of intervention (T1), and State aR additionally 6 months later (T2). STATISTICS: General linear modelling including propensity scores. RESULTS: 65 BC-CRF were randomized, and 61 were allocated by preference to the treatment arms. 105 patients started the intervention. At T1, State aR-R/A improved the most in MT (+3.49, CI [2.42; 4.55]) compared to AT (+1.59, CI [0.13; 3.06]) and CT (+1.68, CI [0.83; 2.52]), showing superiority of MT to AT (p = 0.048). At T2 MT was sustainably superior to AT regarding State aR-R/A (+3.61, CI [2.38; 4.83] p < 0.01) and State aR also showed superiority of MT to AT (p = 0.006). AT T1 24-h activity was higher in MT compared to AT (p = 0.029). CONCLUSIONS: MT was superior to AT regarding State aR total score after 6 months, State aR-R/A after 10 weeks, and after 6 months. Actigraphically measured total activity also improved after 10 weeks.

Does self-regulation and autonomic regulation have an influence on survival in breast and colon carcinoma patients? results of a prospective outcome study.

BACKGROUND: Cancer Related Fatigue (CRF) and circadian rhythm have a great impact on the quality of life (HRQL) of patients with breast (BC) and colon cancer (CRC). Other patient related outcomes in oncology are measured by new instruments focusing on adaptive characteristics such as sense of coherence or self-regulation, which could be more appropriate as a prognostic tool than classical HRQL. The aim of this study was to assess the association of autonomic regulation (aR) and self-regulation (SR) with survival. METHODS: 146 cancer patients and 120 healthy controls took part in an initial evaluation in 2000/2001. At a median follow up of 5.9 years later, 62 of 95 BC, 17 of 51 CRC patients, and 85 of 117 healthy controls took part in the follow-up study. 41 participants had died. For the follow-up evaluation, participants were requested to complete the standardized aR and SR questionnaires. RESULTS: On average, cancer patients had survived for 10.1 years with the disease. Using a Cox proportional hazard regression with stepwise variables such as age, diagnosis group, Charlson co-morbidity index, body mass index (BMI)) aR and SR. SR were identified as independent parameters with potential prognostic relevance on survival While aR did not significantly influence survival, SR showed a positive and independent impact on survival (OR = 0.589; 95%-CI: 0.354 - 0.979). This positive effect persisted significantly in the sensitivity analysis of the subgroup of tumour patients and in the subscale 'Achieve satisfaction and well-being' and by tendency in the UICC stages nested for the different diagnoses groups. CONCLUSIONS: Self-regulation might be an independent prognostic factor for the survival of breast and colon carcinoma patients and merits further prospective studies.

Impact of a Multimodal and Combination Therapy on Self-Regulation and Internal Coherence in German Breast Cancer Survivors With Chronic Cancer-Related Fatigue: A Mixed-Method Comprehensive Cohort Design Study.

Background: Recent studies have proved the relevance of salutogenetic variables for fatigue management in breast cancer survivors with cancer-related fatigue (CRF). This comprehensive cohort design study is the first to examine the impact of 2 multimodal therapies, multimodal therapy (MT) and combined therapy (CT), compared with standard aerobic training (AT) on salutogenetic variables (self-regulation and internal coherence) and distress in breast cancer survivors with CRF. Methods: A total of 105 patients started the therapies and n = 84 completed the Self-regulation Scale, the Internal Coherence Scale, the Cancer Fatigue Scale, and the Hospital Anxiety and Depression Scale at baseline, 10 weeks after treatment (T1) and n = 81 after 6 months (T2). Patient satisfaction and qualitative feedback regarding therapy quality was assessed at T1. A general linear model including allocation type, therapy arm (MT/CT/AT), and bias-adjusting propensity scores tested the superiority of both multimodal therapies versus AT for all questionnaires at T1 and T2. Results: MT and CT were superior to AT to improve self-regulation and patients' satisfaction at T1. Additionally, CT showed superiority for self-regulation at T2 (all P < .05). Compared with AT, internal coherence was significantly higher for patients in the MT arms at T2, respectively (all P < .01). Pearson's correlations between self-regulation, internal coherence, and CRF improved from baseline to T2 (Mean r = -0.60). Qualitative feedback confirmed patients' benefits in several health-related categories. Conclusions: Self-regulation and internal coherence are manipulable variables with relevant CRF associations. They can be positively affected by multimodal therapies. Alongside patients' satisfaction and qualitative feedback they help refine treatment.

Influence of a Multimodal and Multimodal-Aerobic Therapy Concept on Health-Related Quality of Life in Breast Cancer Survivors.

CONTEXT: Cancer-related fatigue (CRF) is one of the most burdensome symptoms in breast cancer survivors (BCSs), accompanied by reduced health-related quality of life (HRQOL). OBJECTIVES: This study investigated the influence of a multimodal therapy (MT; psychoeducation, eurythmy therapy, painting therapy, and sleep education/restriction), or a combination therapy (CT; MT plus aerobic training [AT]) on HRQOL in BCS with chronic CRF in comparison with AT alone. METHODS: One hundred and twenty-six BCSs with CRF were included in a pragmatic comprehensive cohort study and allocated either per randomization or by preference to MT, CT, or AT. The EORTC QLQ-C30 core questionnaire was used to measure HRQOL. All analyses on HRQOL parameters were done in an explorative intention. RESULTS: Patients were assigned to MT (n = 44), CT (n = 54), or AT (n = 28). CT was significantly superior to AT after 10 weeks of intervention (T1) in improving physical function. MT was found to have significant superiority over AT at T1 and T2 for physical functioning, emotional functioning, insomnia, and financial problems as well as role functioning, cognitive, social functioning, and fatigue 6 months later (T2). CONCLUSION: A multimodal approach appears to be a suitable concept for BCS with chronic CRF. A confirmatory study with larger samples should demonstrate the superiority of MT and adapted CT in HRQOL compared with the current treatment AT found in these explorative analyses.

The questionnaire on autonomic regulation: a useful concept for integrative medicine?

The concept of autonomic regulation (aR) reflects the relevance of the function of different autonomic systems for health. aR can be captured by questionnaires. We differentiate between a trait or constitutional aR questionnaire version including 12 (short-version) or 18 items, respectively, with three subscales (orthostatic-circulatory, rest/activity and digestive regulation), and an 18-item state aR questionnaire on the preceding week with four subscales (rest/activity, orthostatic-circulatory, thermo- and digestive regulation). The validated questionnaires show satisfying to good reliability and robust validity with clear construct validity. In this article, we summarized the actually available literature on aR and the use of aR questionnaires in clinical and observational studies. We described the relationship of high aR with health and in case of low aR or loss of regulation with disease and functional disorder in the three (four) different subscales and functional systems, such as rest/activity, orthostatic-circulatory or digestive regulation (thermoregulation) with the consecutive therapeutic need. Finally, we gave perspectives of its further application in clinical research.

[Reduction of endogenous regulation in internal medicine patients]. / Verlust von endogener Regulation bei internistischen Patienten.

BACKGROUND: General health-related questionnaires on quality of life do not satisfactorily distinguish between healthy and sick people. One of the reasons cited for this lack is too much mental influence. This is why we developed a questionnaire on endogenous regulation (eR) that reflects the regulatory state of various vegetative functions. OBJECTIVE: The current study examines whether the short version eR questionnaire is able to distinguish between healthy people and internal medicine patients. PATIENTS AND METHODS: 408 participants were included in the study (284 females, 124 males). Among these were patients with colorectal cancer (n = 49), breast cancer (n = 95), diabetes mellitus (type 1: n = 20, type 2: n = 40), coronary disease (n = 39), rheumatoid illnesses (n = 28) and multimorbid patients (n = 22) as well as a healthy control group (n = 115). In addition to the eR questionnaire the study also used the Hospital Anxiety and Depression Scale (HADS), the short questionnaire on self-regulation and questions on the vegetative status. RESULTS: The healthy control group showed the highest eR, with an estimated average of M = 29.8. Patients with breast cancer, diabetes mellitus type 2, coronary disease and rheumatoid illnesses reveal a significantly lowered eR. Multimorbid patients show the lowest eR. Patients with cancer of the colon and diabetes type 1 were measured at M = 27.9 and M = 27.3 respectively and showed no significantly lowered estimated average compared to the control group. A high eR significantly correlates (p < 0.002) with the following parameters: low levels of anxiety (r = 49) and depression (r = 0.36), high self-regulation (r = 0.34), morning type (r = 0.40), less congestive perspiration (r = 0.38), less shivering (r = 0.23), dysmenorrhoea (r = 0.38) and allergies (r = 0.17). CONCLUSION: Healthy people show the highest, multimorbid patients the lowest eR. Consistent relations to health, illness, heat regulation and personality presence have been shown. Further studies to clarify clinical relevance are necessary.

Effects of eurythmy therapy in the treatment of essential arterial hypertension: a pilot study.

INTRODUCTION: Although eurythmy therapy (ET) has been used in the context of anthroposophic medicine (AM) for the treatment of, among other conditions, arterial hypertension (AH) for more than 80 years, there are as yet no studies on its effectiveness on disease entity. However, it has been shown that ET can increase heart rate variability comparably to ergometer training. OBJECTIVE: To determine whether a 10-week course of ET has an impact on AH and if so, to determine the strength of the effect. The impact of ET on state-autonomic regulation, self-regulation, internal coherence, and quality of life is also explored. METHODS: Consecutive inclusion of 9 subjects (6 female, 3 male, mean age of 64 years, SD 8.26) with AH diagnosed by their general practitioners. INCLUSION CRITERIA: no or unchanged antihypertensive medication from 4 weeks prior to the start of the study until the end of the study. ET was carried out with weekly instruction along with a daily, home-based program for 10 weeks with specific exercises. Twenty-four-hour blood pressure (BP) measuring was carried out, and the questionnaires were administered before and after the intervention. In addition, after a further 6 months during which 8 of the 9 patients carried on with the exercises of their own accord, the aforementioned parameters were assessed for a third time. RESULTS: Parameters of the 24-hour BP measurements show a moderate, but not significant, improvement immediately after the intervention and 6 months after the intervention. After the 10-week intervention, we saw an improvement of the State-autonomic Regulation questionnaire, the subscale on "Rest/Activity regulation," of the Self-regulation questionnaire, and the subscale "Initiative and Interest" of the Herdecke Quality of Life Questionnaire (HLQ) (all P < .045). After the 6-month post-study observation period, the aforementioned parameters improved further still, and an additional, significant improvement was seen for the Trait-autonomic Regulation subscale "Rest/Activity regulation," the HLQ-sum score, and the HLQ subscales "social interaction," "mental balance," and "physical ability." CONCLUSION: A 10-week course of ET does not result in a significant improvement in BP. The average BP measurements improved post-intervention by an absolute 3.2/2.0 mmHg and after 6 months of independent continuation of ET by 6.3/4.4 mmHg (systolic/diastolic). Despite the small group size, the regulation and quality-of-life parameters improved significantly after the intervention and further still after the 6-month observation period. The results need to be validated with larger patient collectives and control groups.

Multimodal therapy concept and aerobic training in breast cancer patients with chronic cancer-related fatigue.

UNLABELLED: HYPOTHESE: Cancer-related fatigue (CRF) and sleep disorders are some of the most wearing and common symptoms in disease-free breast cancer patients (BC). Aerobic training (AT) is the treatment with the best available evidence, even though it seems to be insufficient with regards to improvements in cognitive fatigue. We introduced a new multimodal therapy concept (MM) consisting of psycho-, sleep-education and new approaches based on anthroposophic medicine such as eurythmy and painting therapy. STUDY DESIGN: This pilot study will test the implementation of MM and yield first results of the MM and AE in our centres. METHODS: 31 out of 34 patients suffering from BC and CRF were fully assessed in a ten-week intervention study. 21 patients chose MM and 10 decided on AT. CRF was measured with the help of the Cancer Fatigue Scale (CFS-D), and the global quality of sleep was measured with the Pittsburgh Sleep Quality Index (PSQI). We also captured autonomic regulation (aR) and patients' satisfaction with questionnaires. Statistical analysis was done with SAS 9.1.3 for windows. RESULTS: The new MM therapy can be implemented with high satisfaction among patients. Significant improvements were found in the MM group with regards to CFS-D, global quality of sleep, sleep efficiency (PSQI), aR and rest/activity regulation compared to baseline (all p<0.05). In the AT group aR orthostatic-circulatory and rest/activity regulation improved significantly (p<0.05), too. However, no improvement in cognitive fatigue was seen in either group. CONCLUSION: The multimodal therapy concept was feasible and improved cancer fatigue, sleep quality, autonomic and rest-/activity regulation in breast cancer patients. It may therefore constitute a valuable treatment option in addition to aerobic training for BC patients with CRF. A further study with larger sample size needs to be carried out to assess the efficacy of combined multimodal-aerobic therapy.

Comparison of respiratory rates derived from heart rate variability, ECG amplitude, and nasal/oral airflow.

It would often be desirable to obtain the respiratory rate during everyday conditions without obtaining an additional respiratory trace. This study investigates the agreement between respiratory rate assessed from the electrocardiogram (ECG) and the reference respiratory rate derived from a nasal/oral airflow (AF). Nasal/oral airflow and a Holter ECG were recorded in 52 healthy subjects (26 males, age range: 25.4-85.4 years) during everyday conditions for at least 10 h, including night-time sleep. The respiratory rate was assessed for each 5-min epoch (1) using respiratory sinus arrhythmia (RSA), (2) utilizing the respiration induced variations of the R-wave amplitude (ECG derived respiration (EDR)). The agreement with respect to AF was quantified using the average/std and the concordance correlation coefficient rho(c). For RSA and EDR the difference with respect to AF was 0.2 cpm (std: 0.6 cpm) during sleep and -0.2 cpm (std: 1.0 cpm) during wake time. During sleep the RSA-approach performed best for subjects < or =50 years (rho(c) = 0.79) and worst for subjects >50 years (rho(c) = 0.41). The correlation of the EDR-approach was rho(c) = 0.73 for both groups. In conclusion, the respiratory rate may be assessed with reasonable agreement by both methods in younger subjects, but EDR should be preferred in the elderly.