Four-year follow-up on fatigue and sleep quality of a three-armed partly randomized controlled study in breast cancer survivors with cancer-related fatigue.

Cancer-related fatigue (CRF) is a frequent long-term symptom in non-metastasized breast cancer patients (BC). This 4-year follow-up intended to compare the long-term effects of a 10-week multimodal therapy (MT: sleep education, psychoeducation, eurythmy- and painting therapy) and combination therapy [CT: MT plus aerobic training (AT)] to AT-control. BC-patients were randomized or allocated by preference to three arms in a comprehensive cohort study. Primary outcome was a composite score including Pittsburgh Sleep Quality Index (PSQI) and Cancer Fatigue Scale (CFS-D), captured at baseline, after 10 weeks of intervention (T1), 6 months later (T2), and after 4 years (T3). We exploratively tested for superiority of MT and CT versus AT after 4 years (T3) based on the statistical model of the main analysis. Of 126 (65 randomized) BC-patients included, 105 started treatments and 79 were re-assessed for long-term effects (T3). MT and CT were superior over AT after 4 years regarding PSQI/CFS-D and PSQI sum-score, respectively (all p < 0.05), but not for CFS-D. The multimodal and combination treatment for breast cancer patients with CRF indicates sustainable long-term superiority over aerobic training for the outcomes sleep quality and combined sleep quality/fatigue. A confirmative randomized controlled trial is warranted.

A comprehensive analysis of attempted and fatal suicide cases involving frequently used psychotropic medications.

OBJECTIVES: Self-poisoning is the most common suicide method in non-lethal suicide attempts and the third most frequent in fatal suicides. Psychoactive drugs are often used for intentional self-poisoning. While poisons centre data typically focus on survived suicide attempts and underrepresent fatal self-poisoning, medical examiner reports give insight into suicide deaths. To close this gap, we combined and compared data sets from both sources, assessing the mortality of psychotropic drugs used for self-poisoning. METHODS: Anonymized cases of self-poisoning with suicidal intention from 2000 to 2010 were extracted from the national poisons centre case database and compared with cases of suicide documented in the project "Suicides, a national survey". All cases with single substance exposure to a psychoactive drug (antidepressants, mood stabilizers, antipsychotics, sedatives) were included in the analyses. Opioids, over-the-counter- and illicit- drugs were excluded from the analysis. A mortality index was calculated by the ratio of the number of suicides and the sum of all (lethal and non-lethal) suicide attempts. RESULTS: Tricyclics had a higher mortality rate than other antidepressants. Among the sedatives, zolpidem was found to have a higher mortality index compared to benzodiazepines. Clozapine and levomepromazine were found to be the most lethal antipsychotics. Non-lethal suicide cases with single substance exposure (n = 4697) diminished as age increased, while the rate of suicide cases (n = 165) was higher in elderly subjects (>65 years of age, p < 0.001). CONCLUSION: In summary, our findings confirm previous study results on the relative toxicity of distinct classes of psychotropic drugs. In this comprehensive analysis of a national cohort lorazepam had a lower mortality rate compared to other sedatives.

Acute and chronic alcohol use correlated with methods of suicide in a Swiss national sample.

OBJECTIVES: Chronic and acute alcohol use are highly associated risk factors for suicides worldwide. Therefore, we examined suicide cases with and without alcohol use disorder (AUD) using data from the SNSF project "Suicide in Switzerland: A detailed national survey". Our investigations focus on correlations between acute and chronic alcohol use with reference to suicide and potential interactions with the methods of suicide. METHODS: We used data from the SNSF project in which all cases of registered completed suicide in Switzerland reported to any of the seven Swiss institutes of legal and forensic medicine between 2000 and 2010 were collected. We extracted cases that were tested for blood alcohol to use in our analysis. We compared clinical characteristics, blood alcohol concentrations, and methods of suicide in cases with and without AUD. RESULTS: Out of 6497 cases, 2946 subjects were tested for acute alcohol use and included in our analysis. Of the latter, 366 (12.4%) persons had a medical history of AUD. Subjects with AUD significantly had higher blood alcohol concentrations and were more often in medical treatment before suicide. Drug intoxication as method of suicide was more frequent in cases with AUD compared to NAUD. CONCLUSION: Overall, we found a high incidence of acute alcohol use at the time of death in chronic alcohol misusers (AUD). The five methods of suicide most commonly used in Switzerland differed considerably between individuals with and without AUD. Blood alcohol concentrations varied across different methods of suicide independently from the medical history in both groups.

Do we have predictors of therapy responsiveness for a multimodal therapy concept and aerobic training in breast cancer survivors with chronic cancer-related fatigue?

Cancer-related fatigue (CRF) is a burdensome symptom for breast cancer (BC) patients. In this pilot study, we tested several questionnaires as predictors for treatment responsiveness, along with the implementation of a multimodal therapy concept consisting of sleep, psycho-education, eurythmy, painting therapy and standard aerobic training. At the Community Hospital Havelhöhe and the Hannover Medical School, 31 BC patients suffering from CRF could be evaluated in a 10-week intervention study. CRF was assessed by the Cancer Fatigue Scale (CFS-D). Further questionnaires were the Pittsburgh Sleep Quality Index, the autonomic regulation scale, Self-Regulation Scale (SRS), the Internal Coherence Scale (ICS) and the European Organization of Research and Treatment Health-Related Quality of Life Core Questionnaire scale. We estimated the regression coefficients of all scales on CFS-D by simple and multiple linear regression analyses and compared regression slopes and variances between the different questionnaires on CFS-D at the end of treatment. We found a significant impact of SRS and ICS at baseline on CFS-D at the end of the intervention [absolute standardised multiple regression coefficient values ranging from 0.319 (SRS) to 0.269 (ICS)] but not for the other questionnaires. In conclusion, this study supports the hypothesis that the SRS or ICS measuring adaptive capacities could be more appropriate as outcome predictors than classical questionnaire measures in complex interventions studies.

Deep brain stimulation of the nucleus basalis of Meynert in Alzheimer's dementia.

Cholinergic neurons of the medial forebrain are considered important contributors to brain plasticity and neuromodulation. A reduction of cholinergic innervation can lead to pathophysiological changes of neurotransmission and is observed in Alzheimer's disease. Here we report on six patients with mild to moderate Alzheimer's disease (AD) treated with bilateral low-frequency deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM). During a four-week double-blind sham-controlled phase and a subsequent 11-month follow-up open label period, clinical outcome was assessed by neuropsychological examination using the Alzheimer's Disease Assessment Scale-cognitive subscale as the primary outcome measure. Electroencephalography and [(18)F]-fluoro-desoxyglucose positron emission tomography were, besides others, secondary endpoints. On the basis of stable or improved primary outcome parameters twelve months after surgery, four of the six patients were considered responders. No severe or non-transitional side effects related to the stimulation were observed. Taking into account all limitations of a pilot study, we conclude that DBS of the NBM is both technically feasible and well tolerated.

[Deep brain stimulation for addiction, anorexia and compulsion. Rationale, clinical results and ethical implications]. / Tiefe Hirnstimulation bei Sucht, Anorexie und Zwang. Rationale, klinische Ergebnisse und ethische Implikationen.

BACKGROUND: As an established treatment for movement disorders, the application of deep brain stimulation (DBS) for psychiatric indications has been investigated for almost 15 years. A CE label (also FDA approval) has recently been obtained for treatment of refractory obsessive-compulsive disorder (OCD). OBJECTIVES: This article aims at illustrating the current state of DBS in the treatment of refractory OCD. In addition, initial experimental approaches to investigate the potential use of DBS in substance addiction and anorexia nervosa (AN) will also be outlined as both disorders share some common features with OCD. MATERIALS AND METHODS: The present review is based on a keyword literature search (PubMed) while taking into account relevant references and own investigations RESULTS: Although the number of clinical trials for treatment of refractory OCD is limited and sample sizes are small, there is some evidence for a substantial improvement, a so-called full response of OCD symptoms under DBS. However, not all patients benefit from the intervention. Regarding substance addiction and AN, data are scarce and are only indicative of a potential benefit at most. DISCUSSION: Present data regarding the clinical benefits of DBS in OCD are encouraging and open up new avenues for the treatment of therapy refractory patients. However, several aspects, such as mechanisms of action, predictors and long-term side effect profiles, are incomplete or even unknown. In the case of addiction and AN, DBS remains purely experimental, at least for the moment. Hence, clinical trials should remain the gold standard for all three indications.

Impact of autonomic and self-regulation on cancer-related fatigue and distress in breast cancer patients--a prospective observational study.

PURPOSE: Cancer-related fatigue (CRF) has a major impact on the quality of life in breast cancer patients (BC). So far, only a few prospective studies have investigated the effect of adaptive salutogenic mechanisms on CRF. The aim of our study was to evaluate the possible prospective influence of autonomic Regulation (aR) and self-regulation (SR) on CRF and distress in long-term survivors. METHODS: 95 BC and 80 healthy female controls (C) had been included in the observational study between 2000 and 2001 and completed the questionnaires on aR, SR and Hospital Anxiety and Depression Scale (HADS). Of these, 62 BC, and 58 C participated in the re-evaluation 6.6 years later: 16 participants were deceased (14 BC and 2 C). During follow-up, participants were requested to answer questions involving (Cancer Fatigue Scales) CFS-D, aR, SR and HADS. Multiple regression analysis was used to evaluate the influence of aR, SR, age, Charlson co-morbidity-index and diagnosis on CFS-D and HADS, and to select further potentially relevant factors. RESULTS: High aR values showed significant effects, namely inverse relationships with CFS-D, cognitive fatigue, anxiety and depression. SR showed a reduced influence on anxiety and depression (all p < 0.05). CONCLUSIONS: Autonomic regulation might have an independent, reductive influence on global fatigue, cognitive fatigue and--together with self-regulation--it seems to have a protective influence on anxiety and depression. The connection between these parameters is still unclear and awaits further evaluation. IMPLICATION FOR CANCER SURVIVORS: AR seems to be a prognostic factor in breast cancer survivors, capable of reducing cancer-related fatigue and self-regulation distress as well. Further research is necessary in order to show how aR can be improved by therapeutic interventions.

[Cystectomy in the elderly patient]. / Zystektomie im Alter.

Bladder cancer is a carcinoma of the elderly population. The highest incidence of bladder cancer is between the ages of 70 and 80 years old. Radical cystectomy remains the gold standard for muscle invasive bladder cancer treatment. In this article different aspects of radical cystectomy in elderly patients are reviewed. The Pubmed-MEDLINE database was searched using the following keywords: radical, cystectomy, elderly and age.

Management and outcome of pallidal deep brain stimulation in severe Huntington's disease.

Neurodegenerative movement disorders, such as Huntington's disease (HD), have become a promising field for Deep Brain Stimulation (DBS). This study aims to contribute to the establishment of a well-grounded database including both expected and unexpected effects of pallidal DBS in HD, and to discuss the ethical and legal restrictions of DBS in cognitively limited patients. Evaluation of the outcome data indicates that pallidal DBS exerted an independent effect on motor symptoms but probably also on the patient's cognitive and affective state. The cognitive decline, however, that characterizes the late stage of neurodegenerative disorders implicates ethical and legal problems given the patients' inability to give informed consent to DBS.

Clinical effectiveness of unilateral deep brain stimulation in Tourette syndrome.

Dysfunctional basal ganglia loops are thought to underlie the clinical picture of Tourette syndrome (TS). By altering dopaminergic activity in the affected neural structures, bilateral deep brain stimulation is assumed to have a modulatory effect on dopamine transmission resulting in an amelioration of tics. While the majority of published case reports deals with the application of bilateral stimulation, the present study aims at informing about the high effectiveness of unilateral stimulation of pallidal and nigral thalamic territories in TS. Potential implications and gains of the unilateral approach are discussed.

Incommensurately modulated lanthanide coinage-metal diarsenides. II. GdCuAs2, GdAu(1-delta)As2 and TbAu(1-delta)As2--new distortion variants of the HfCuSi2 type with irregularly stacked zigzag chains of arsenic atoms.

GdCuAs2, GdAu(1-delta)As2 and TbAu(1-delta)As2 crystallize as incommensurately modulated variants of the HfCuSi2 type. Structure models have been developed in the monoclinic superspace group P12(1)/m1(alpha0gamma)00 (No. 11.1). The components of the modulation wavevectors q = alphaa* + 0b* + gammac* are alpha = 0.04 (1) and gamma = 0.48 (1) for GdCuAs2, alpha = 0.03 (1) and gamma = 0.48 (1) for GdAu(1-delta)As2 and alpha = 0.02 (1) and gamma = 0.46 (1) for TbAu(1-delta)As2. The predominant effect of the positional modulation is the distortion of a square net of arsenic atoms, which results in planar zigzag chains. Rod groups and layer groups of the respective structure motifs are identified and discussed.

Validation of the German version of the Cancer Fatigue Scale (CFS-D).

Fatigue is a very important factor determining the quality of life in patients with malignancies. Cancer fatigue occurs with anaemia, during and after chemo- or radiotherapy and in patients with advanced tumours. The Cancer Fatigue Scale (CFS) is a three-dimensional inventory with 15 items which was originally developed in Japan. We present the results of a validation study of the German version (CFS-D) of this instrument. The CFS-D was administered to 114 participants in a matched-pair study. In total, 57 (41 women) of the participants had malignant conditions, and 57 (41 women) were healthy volunteers. The Fatigue Numerical Scale was used to test convergence. The physical and performance status of the cancer patients was assessed by the Karnofsky-Index. Criteria for testing multidimensionality were the Hospital Anxiety and Depression Scale, and the questionnaire on autonomic regulation. We generated a three-dimensional inventory of the CFS-D with the subscales physical fatigue/vitality, cognitive and affective fatigue. The reliability results for the complete scale: Cronbach's alpha: r(alpha) = 0.94, retest reliability: r(rt) = 0.82. The convergence criteria correlate between r = 0.44-0.65 (all P < 0.001). The CFS-D is highly reliable and has construct validity in relation to other measures.

Species identification by means of pyrosequencing the mitochondrial 12S rRNA gene.

The aim of this study was to develop a new method for species identification based on the analysis of a very short nucleotide sequence. For this reason, the mitochondrial 12S rRNA gene, together with the new method of pyrosequencing, was used. The detection of only 20 nucleotides, following the sequencing primer within a 149-bp fragment by pyrosequencing, was sufficient to identify the biological origin of the samples by alignment with a reference sequence database. A case example with a piece of skin is presented, and the question whether this piece of skin came from a missing wife or from an animal could be answered.

Post-mortem evaluation of 415 pacemakers: in situ measurements and bench tests.

AIM: The hypothesis was that there is more undetected dysfunction of implanted pacemaker systems than that detected and corrected. This prompted a research project (sponsored by the German Research Foundation) to detect pacemaker abnormalities and evaluate their complications for patients, thus, proving or disproving the hypothesis. METHODS AND RESULTS: Four hundred and fifteen pacemakers of deceased patients were analyzed assessing their functionality by in situ measurements and bench tests including five measurements and one telemetric interrogation. Results were divided into four categories and statistically evaluated. Life-threatening abnormalities were found in 3.8%, potentially life-threatening in 3.7%, probably symptomatic, divided into atrial and ventricular problems, 13.3% and 2.8%, respectively, and premature exhaustion in 1.2%. Three of 179 bipolar ventricular leads and 2 of 131 bipolar atrial leads had insulation defects corresponding to 1.7% and 1.5%, respectively. The bipolar complication rate was 2.8 times higher than unipolar. CONCLUSION: The pacemaker patients investigated, living 4 years with their pacemaker on average, had a post-mortem evaluated complication rate of the category "life-threatening" of 3.8%. This result corresponds to an annual complication rate of 0.94% compared with a rate of only 0.39% in an earlier investigation.

Stretch expanded polytetrafluoroethylene graft with intrawall radial support system: an advance in vascular access graft design.

Vascular access expanded polytetrafluoroethylene (ePTFE) grafts with external support systems consisting of parallel rings or in a spiral configuration are designed to resist kinking and compression at the apex of loop grafts or when crossing a joint. However, during the implantation procedure, the rings or spiral must be removed from the portion of the graft that is cut to allow the graft to be divided at the desired angle and suture the anastomosis. A new ePTFE graft (Intering) with an intrawall radial support system and a smooth lumen permits easy division of the support segments at the chosen angle. Moreover, minimal resistance is encountered during suturing of the graft. The results of early experience with Intering grafts crossing the elbow joint, in short-segment revisions, and in primary forearm loop configurations are encouraging.

Cessation of pulmonary and coronary secretion of adrenomedullin peptides in the progression of human heart failure.

In human heart failure (CHF), adrenomedullin (AM) counteracts vasoconstriction and sodium retention. We investigated circulating levels of proadrenomedullin N-20 peptide (PAMP) and AM, and left ventricular expression of preproAM and calcitonin receptor-like receptor (CRLR) mRNA. Peptide levels were determined from the left ventricle, pulmonary artery, coronary sinus, and antecubital vein in patients demonstrating severe CHF (n = 12; mean +/- SEM cardiac index, 1.9 +/- 0.2 l/min/m(2); pulmonary wedge pressure, 32 +/- 1 mmHg), moderate CHF (n = 11; cardiac index, 2.9 +/- 0.2; pulmonary wedge pressure, 14 +/- 2), and in controls (n = 11). Left ventricular mRNA was quantified using RT-PCR and Southern blot hybridization. Depending on sites of measurement, PAMP and AM in severe CHF were 1.3 - 2.0 and 1.2 - 1.9 times as high as in moderate CHF, and 3.8 - 4.6 and 2.3 - 2.8 times as high as in controls. Only patients with moderate CHF demonstrated pulmonary and coronary net release of both peptides, that is, significant step-ups in concentrations between the pulmonary artery, left ventricle, and coronary sinus. In failing ventricles, preproAM mRNA increased 2.9 times above control, but CRLR mRNA was unchanged. Altogether, the heart and the lungs release AM peptides in moderate CHF. This secretion breaks down in severe CHF: a process that may contribute to and indicate decompensation. Unlike AM, the CRLR is not transcriptionally upregulated in severe CHF.

Chronic exposure to a GSM-like signal (mobile phone) does not stimulate the development of DMBA-induced mammary tumors in rats: results of three consecutive studies.

Certain epidemiological and experimental studies raised concerns about the safety of radiofrequency (RF) electromagnetic fields because of a possible increased risk of leukemia and lymphoma. In this study, an RF field used in mobile telecommunication was tested using 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in female Sprague-Dawley rats as a model for human breast cancer. Three experiments were carried out under strictly standardized conditions and were started on the same day of three consecutive years. The field consisted of a GSM-like signal (900 MHz pulsed at 217 Hz, pulse width 577 micros) of relatively low power flux density (100 microW/cm(2) +/- 3 dB) and was applied continuously throughout each experiment to freely moving animals. The specific absorption rates averaged over the whole body were 17.5-70 mW/kg. The highest values in young animals were at or around the exposure limit permissible for the general public (i.e. 80 mW/kg). The animals were palpated weekly for the presence of mammary tumors and were killed humanely when tumors reached a diameter of 1-2 cm to allow a reliable histopathological classification and a distinction between malignant and benign subtypes. The overall results of the three studies are that there was no statistically significant effect of RF-field exposure on tumor latency and that the cumulative tumor incidence at the end of the experiment was unaffected as well. The risk ratios were 1.08 (95% CI: 0.91-1.29) and 0.96 (95% CI: 0.85-1.07) for benign and malignant tumors, respectively. These observations are in agreement with other published findings. In the first experiment, however, the median latency for the development of the first malignant tumor in each animal was statistically significantly extended for RF-field-exposed animals compared to controls (278 days compared to 145 days, P = 0.009). No such differences were detected in the two subsequent experiments. These results show that low-level RF radiation does not appear to possess carcinogenic or cancer-promoting effects on DMBA-induced mammary tumors. To explain the mechanisms underlying the different results obtained in the three experiments, a hypothesis is presented which is based upon the neuroendocrine control mechanisms involved in the promotion of DMBA-induced mammary tumors. Despite the apparent absence of stimulatory effects of low-level RF-field exposure on the development and growth of solid tumors, it will be necessary to verify these results for leukemias and lymphomas, which may have completely different biological control mechanisms.