Costs and quality of life in multiple sclerosis: A cross-sectional observational study in Germany

We performed a cross-sectional, bottom-up observational study of resource consumption and quality of life of patients with multiple sclerosis (MS) in Germany. Six centers participated in the study. Patients were asked to complete a questionnaire, and a total of 737 patients returned the questionnaire (the answer rate being 66%). The questionnaire provided information on all resource consumption, medical and non-medical, work absence and informal care related to their MS. Simultaneously, medical charts were also abstracted for a sub sample of 202 patients. For this sub sample, disease scores (Expanded Disability Status Scale, EDSS) were available from the study centers. For the remainder, disease scores were assigned using a matrix of disease (mobility) descriptions and EDSS scores. Mean total cost per patient and year was 65,400 DM, adjusted for usage of interferons, which was higher in this sample than the current average usage in Germany. When this cost is extrapolated to an estimated patient population of 120,000, total costs to society are estimated at 7.85 billion DM. Direct costs represented 57.5%, informal care accounted for 12.1% and indirect costs amounted to 42.5%. An estimated 24,800 DM per patient or 38% of total costs are paid for by public payers. Intangible costs were estimated 16,650 DM per patient and year. The mean age of the cohort was 42 years (disease onset 33), the mean utility measured with EQ-5D was 0.552 (0.919 to -0.429), and the mean EDSS score 4.4 (1.0 to 9.5). All costs (direct, informal care, indirect) increased with increasing EDSS scores, while utilities decreased

Interactions of Gastrointestinal Peptides: Ghrelin and Its Anorexigenic Antagonists

Food intake behaviour and energy homeostasis are strongly regulated by a complex system of humoral factors and nerval structures constituting the brain-gut-axis. To date the only known peripherally produced and centrally acting peptide that stimulates food intake is ghrelin, which is mainly synthesized in the stomach. Recent data indicate that the orexigenic effect of ghrelin might be influenced by other gastrointestinal peptides such as cholecystokinin (CCK), bombesin, desacyl ghrelin, peptide YY (PYY), as well as glucagon-like peptide (GLP). Therefore, we will review on the interactions of ghrelin with several gastrointestinal factors known to be involved in appetite regulation in order to elucidate the interdependency of peripheral orexigenic and anorexigenic peptides in the control of appetite

Activity-Based Anorexia Reduces Body Weight without Inducing a Separate Food Intake Microstructure or Activity Phenotype in Female Rats—Mediation via an Activation of Distinct Brain Nuclei

Anorexia nervosa (AN) is accompanied by severe somatic and psychosocial complications. However, the underlying pathogenesis is poorly understood, treatment is challenging and often hampered by high relapse. Therefore, more basic research is needed to better understand the disease. Since hyperactivity often plays a role in AN, we characterized an animal model to mimic AN using restricted feeding and hyperactivity. Female Sprague-Dawley rats were divided into four groups: no activity/ad libitum feeding (ad libitum, AL, n=9), activity/ad libitum feeding (activity, AC, n=9), no activity/restricted feeding (RF, n=12) and activity/restricted feeding (activity-based anorexia, ABA, n=11). During the first week all rats were fed ad libitum, ABA and AC had access to a running wheel for 24h/d. From week two ABA and RF only had access to food from 9:00-10:30 am. Body weight was assessed daily, activity and food intake monitored electronically, brain activation assessed using Fos immunohistochemistry at the end of the experiment. While during the first week no body weight differences were observed (p>0.05), after food restriction RF rats showed a body weight decrease: -13% vs. day eight (p0.05). Similarly, the daily physical activity was not different between AC and ABA (p>0.05). The investigation of Fos expression in the brain showed neuronal activation in several brain nuclei such as the supraoptic nucleus, arcuate nucleus, locus coeruleus and nucleus of the solitary tract of ABA compared to AL rats. In conclusion, ABA combining physical activity and restricted feeding likely represents a suited animal model for AN to study pathophysiological alterations and pharmacological treatment options. Nonetheless, cautious interpretation of the data is necessary since rats do not voluntarily reduce their body weight as observed in human AN

Circulating Spexin Is Associated with Body Mass Index and Fat Mass but Not with Physical Activity and Psychological Parameters in Women across a Broad Body Weight Spectrum

Spexin (SPX) is a novel, widely expressed peptide, with anorexigenic effects demonstrated in animal models and negatively correlated with body mass index (BMI) in humans. It increases locomotor activity in rodents and is elevated in human plasma following exercise. Studies have also shown an effect of stress and anxiety on SPX's expression in different brain structures in animals. The relationships between plasma SPX and physical activity, body composition, and patient-reported outcomes such as perceived stress, depressiveness, anxiety, and eating behaviors are unknown and were examined in this study over a wide BMI range. A total of 219 female (n = 68 with anorexia nervosa; n = 79 with obesity; n = 72 with normal weight) inpatients were enrolled. Perceived stress (PSQ 20), anxiety (GAD 7), depressiveness (PHQ 9), and eating disorder pathology (EDI 2), as well as BMI, bioimpedance analysis, and accelerometry, were measured cross-sectionally at the beginning of treatment and correlated with plasma SPX levels (measured by ELISA) obtained at the same time. Plasma SPX levels were negatively associated with BMI (r = -0.149, p = 0.027) and body fat mass (r = -0.149, p = 0.04), but did not correlate with perceived stress, anxiety, depressiveness, eating behavior, energy expenditure, and physical activity (p > 0.05). The results replicate the negative correlation of SPX with BMI and fat mass, but do not support the hypothesis that peripheral SPX plays a role in the regulation of stress, depressiveness, anxiety, eating behavior, or physical activity

Costs and Quality of Life in Multiple Sclerosis. A Cross-Sectional Observational Study in Germany

We performed a cross-sectional, “bottom-up” observational study of resource consumption and quality of life of patients with multiple sclerosis (MS) in Germany. Six centers participated in the study. Patients were asked to complete a questionnaire, and a total of 737 patients returned the questionnaire (the answer rate being 66%). The questionnaire provided information on all resource consumption, medical and non-medical, work absence and informal care related to their MS. Simultaneously, medical charts were also abstracted for a sub sample of 202 patients. For this sub sample, disease scores (Expanded Disability Status Scale, EDSS) were available from the study centers. For the remainder, disease scores were assigned using a matrix of disease (mobility) descriptions and EDSS scores. Mean total cost per patient and year was 65,400 DM, adjusted for usage of interferons, which was higher in this sample than the current average usage in Germany. When this cost is extrapolated to an estimated patient population of 120,000, total costs to society are estimated at 7.85 billion DM. Direct costs represented 57.5%, informal care accounted for 12.1% and indirect costs amounted to 42.5%. An estimated 24,800 DM per patient or 38% of total costs are paid for by public payers. Intangible costs were estimated 16,650 DM per patient and year. The mean age of the cohort was 42 years (disease onset 33), the mean utility measured with EQ-5D was 0.552 (0.919 to –0.429), and the mean EDSS score 4.4 (1.0 to 9.5). All costs (direct, informal care, indirect) increased with increasing EDSS scores, while utilities decreased.Keywords: multiple sclerosis; cost-of-illness; quality of life; EDSS; utility

Nesfatin-130−59 Injected Intracerebroventricularly Differentially Affects Food Intake Microstructure in Rats Under Normal Weight and Diet-Induced Obese Conditions

Nesfatin-1 is well-established to induce an anorexigenic effect. Recently, nesfatin-130−59, was identified as active core of full length nesfatin-11−82 in mice, while its role in rats remains unclear. Therefore, we investigated the effects of nesfatin-130−59 injected intracerebroventricularly (icv) on the food intake microstructure in rats. To assess whether the effect was also mediated peripherally we injected nesfatin-130−59 intraperitoneally (ip). Since obesity affects the signaling of various food intake-regulatory peptides we investigated the effects of nesfatin-130−59 under conditions of diet- induced obesity (DIO). Male Sprague–Dawley rats fed ad libitum with standard diet were icv cannulated and injected with vehicle (5 μl ddH2O) or nesfatin-130−59 at 0.37, 1.1, and 3.3 μg (0.1, 0.3, 0.9 nmol/rat) and the food intake microstructure assessed using a food intake monitoring system. Next, naïve rats were injected ip with vehicle (300 μl saline) or nesfatin-130−59 (8.1, 24.3, 72.9 nmol/kg). Lastly, rats were fed a high fat diet for 10 weeks and those developing DIO were icv cannulated. Nesfatin-1 (0.9 nmol/rat) or vehicle (5 μl ddH2O) was injected icv and the food intake microstructure assessed. In rats fed standard diet, nesfatin-130−59 caused a dose-dependent reduction of dark phase food intake reaching significance at 0.9 nmol/rat in the period of 4–8 h post injection (−29%) with the strongest reduction during the fifth hour (−75%), an effect detectable for 24 h (−12%, p < 0.05 vs. vehicle). The anorexigenic effect of nesfatin-130−59 was due to a reduction in meal size (−44%, p < 0.05), while meal frequency was not altered compared to vehicle. In contrast to icv injection, nesfatin-130−59 injected ip in up to 30-fold higher doses did not alter food intake. In DIO rats fed high fat diet, nesfatin-130−59 injected icv reduced food intake in the third hour post injection (−71%), an effect due to a reduced meal frequency (−27%, p < 0.05), while meal size was not altered. Taken together, nesfatin-130−59 is the active core of nesfatin-11−82 and acts centrally to reduce food intake in rats. The anorexigenic effect depends on the metabolic condition with increased satiation (reduction in meal size) under normal weight conditions, while in DIO rats satiety (reduction in meal frequency) is induced

Nesfatin-1(30-59) injected intracerebroventricularly increases anxiety, depression-like behavior, and anhedonia in normal weight rats

Nesfatin-1 is a well-established anorexigenic peptide. Recent studies indicated an association between nesfatin-1 and anxiety/depression-like behavior. However, it is unclear whether this effect is retained in obesity. The aim was to investigate the effect of nesfatin-1(30-59)—the active core of nesfatin-1—on anxiety and depression-like behavior in normal weight (NW) and diet-induced (DIO) obese rats. Male rats were intracerebroventricularly (ICV) cannulated and received nesfatin-1(30-59) (0.1, 0.3, or 0.9 nmol/rat) or vehicle 30 min before testing. Nesfatin-1(30-59) at a dose of 0.3 nmol reduced sucrose consumption in the sucrose preference test in NW rats compared to vehicle (-33%, p 0.05). These results indicate an implication of nesfatin-1(30-59) in the mediation of anxiety and depression-like behavior/anhedonia under normal weight conditions, while in DIO rats, a desensitization might occur

Health-Enabling Technologies for Telerehabilitation of the Shoulder: A Feasibility and User Acceptance Study

BACKGROUND: After discharge from a rehabilitation center the continuation of therapy is necessary to secure already achieved healing progress and sustain (re-)integration into working life. To this end, home-based exercise programs are frequently prescribed. However, many patients do not perform their exercises as frequently as prescribed or even with incorrect movements. The telerehabilitation system AGT-Reha was developed to support patients with shoulder diseases during their home-based aftercare rehabilitation. OBJECTIVES: The presented pilot study AGT-Reha-P2 evaluates the technical feasibility and user acceptance of the home-based telerehabilitation system AGT-Reha. METHODS: A nonblinded, nonrandomized exploratory feasibility study was conducted over a 2-year period in patients' homes. Twelve patients completed a 3-month telerehabilitation exercise program with AGT-Reha. Primary outcome measures are the satisfying technical functionality and user acceptance assessed by technical parameters, structured interviews, and a four-dimensional questionnaire. Secondary endpoints are the medical rehabilitation success measured by the active range of motion and the shoulder function (pain and disability) assessed by employing the Neutral-0 Method and the standardized questionnaire "Shoulder Pain and Disability Index" (SPADI), respectively. To prepare an efficacy trial, various standardized questionnaires were included in the study to measure ability to work, capacity to work, and subjective prognosis of work capacity. The participants have been assessed at three measurement points: prebaseline (admission to rehabilitation center), baseline (discharge from rehabilitation center), and posttherapy. RESULTS: Six participants used the first version of AGT-Reha, while six other patients used an improved version. Despite minor technical problems, all participants successfully trained on their own with AGT-Reha at home. On average, participants trained at least once per day during their training period. Five of the 12 participants showed clinically relevant improvements of shoulder function (improved SPADI score > 11). The work-related parameters suggested a positive impact. All participants would recommend the system, ten participants would likely reuse it, and seven participants would have wanted to continue their use after 3 months. CONCLUSION: The findings show that home-based training with AGT-Reha is feasible and well accepted. Outcomes of SPADI indicate the effectiveness of aftercare with AGT-Reha. A controlled clinical trial to test this hypothesis will be conducted with a larger number of participants

Costs and quality of life in multiple sclerosis: A cross-sectional observational study in the UK

We performed a cross-sectional, bottom-up observational study of resource consumption and quality of life of patients with multiple sclerosis (MS) in the United Kingdom. Three centers participated in the study. Patients received a questionnaire either by mail or during a clinic visit, and a total of 619 patients returned the questionnaire (the answer rate being around 70%). Patients provided information on all resource consumption, medical and non-medical, work absence and informal care related to their MS. Disease scores (Expanded Disability Status Scale, EDSS) were available for a majority of patients from the study centers, and were assigned using a matrix of disease (mobility) descriptions and EDSS scores. Mean total cost per patient and year was 16'717 £. When this cost is extrapolated to an estimated patient population in the UK of 80'000, total costs to society are estimated at 1.34 billion £. Direct costs represented 28%, informal care accounted for 26% and indirect costs amounted to 46%. Of the direct costs, an estimated £ per patient or % of total costs are paid for by the NHS. Intangible costs were estimated at 5000 £ per patient and year. The mean age of the cohort was 44 years (disease onset 34), the mean utility measured with EQ-5D was 0.487 (0.919 to -0.594), and the mean EDSS score 5.1 (1.0 to 9.5). All costs (direct, informal care, indirect) increased with increasing EDSS scores, while utilities decreased

GIPC1 regulates MACC1-driven metastasis

Background: Identification of cancer metastasis-relevant molecular networks is desired to provide the basis for understanding and developing intervention strategies. Here we address the role of GIPC1 in the process of MACC1-driven metastasis. MACC1 is a prognostic indicator for patient metastasis formation and metastasis-free survival. MACC1 controls gene transcription, promotes motility, invasion and proliferation of colon cancer cells in vitro, and causes tumor growth and metastasis in mice. Methods: By using yeast-two-hybrid assay, mass spectrometry, co-immunoprecipitation and peptide array we analyzed GIPC1 protein binding partners, by using the MACC1 gene promoter and chromatin immunoprecipitation and electrophoretic mobility shift assay we probed for GIPC1 as transcription factor. We employed GIPC1/MACC1-manipulated cell lines for in vitro and in vivo analyses, and we probed the GIPC1/MACC1 impact using human primary colorectal cancer (CRC) tissue. Results: We identified MACC1 and its paralogue SH3BP4 as protein binding partners of the protein GIPC1, and we also demonstrated the binding of GIPC1 as transcription factor to the MACC1 promoter (TSS to -60 bp). GIPC1 knockdown reduced endogenous, but not CMV promoter-driven MACC1 expression, and diminished MACC1-induced cell migration and invasion. GIPC1 suppression reduced tumor growth and metastasis in mice intrasplenically transplanted with MACC1-overexpressing CRC cells. In human primary CRC specimens, GIPC1 correlates with MACC1 expression and is of prognostic value for metastasis formation and metastasis-free survival. Combination of MACC1 and GIPC1 expression improved patient survival prognosis, whereas SH3BP4 expression did not show any prognostic value. Conclusions: We identified an important, dual function of GIPC1 - as protein interaction partner and as transcription factor of MACC1 - for tumor progression and cancer metastasis