[An Experience Report on the Evaluation of New Forms of Care for People with Mental Illness: Pros and Cons of the Use of SHI Claims Data]. / Evaluation von neuen Versorgungsformen für Menschen mit psychischen Erkrankungen: Pro & Contra zum Einsatz von GKV-Routinedaten ­ Ein Erfahrungsbericht.

The present article describes the special features of an evaluation of research in mental health services in Germany. The experiences of the evaluation of flexible and integrated treatment options with a global treatment budget in psychiatric hospitals based on routine data of more than 70 statutory health insurance (SHI) funds (EVA64 study) are systematically presented. Using the EVA64 study as an example, recommendations for the use of claims data in the field of mental health services research and in general are derived. (1) First, the study and its use of claims data is described and classified. (2) The individual outcomes of the study are presented and evaluated in order to (3) derive criteria, identify strengths and suggest potential uses of claims data. (4) Finally, recommendations for the further development of claims data from SHI funds as a basis for evaluation are described.

Adipositas Care and Health Therapy (ACHT) after Bariatric-Metabolic Surgery: A Prospective, Non-Randomized Intervention Study.

INTRODUCTION: Almost 25% of German adults have obesity and numbers are rising, making it an important health issue. Bariatric-metabolic surgery reduces body weight and complications for persons with obesity, but therapeutic success requires long-term postoperative care. Since no German standards for follow-up by family physicians exist, follow-up is provided by surgical obesity centers, but they are reaching their limits. The ACHT study, funded by the German Innovation Fund, is designed to establish and evaluate the follow-up program, with local physicians following patients supported remotely by obesity centers. METHODS: ACHT is a multicenter, prospective, non-randomized control group study. The 18-month ACHT follow-up program is a digitally supported, structured, cross-sectoral, and close-to-home program to improve success after bariatric-metabolic surgery. Four groups are compared: intervention group 1 starts the program immediately (3 weeks) after Roux-en-Y gastric bypass or sleeve gastrectomy (months 1-18 postoperatively), intervention group 2 begins the program 18 months after surgery (months 19-36 postoperatively). Intervention groups are compared to respective control groups that had surgery 18 and 36 months previously. In total, 250 patients, enrolled in the intervention groups, are compared with 360 patients in the control groups, who only receive standard care. RESULTS: The primary endpoint to compare intervention and control groups is the adapted King's score, a composite tool evaluating physical, psychological, socioeconomic, and functional health status. Secondary endpoints include changes in care structures and care processes for the intervention groups. Multivariate regression analyses adjusting for confounders (including the type of surgery) are used to compare intervention and control groups and evaluate determinants in longitudinal analyses. The effect of the intervention on healthcare costs will be evaluated based on health insurance billing data of patients who had bariatric-metabolic surgery in the 3 years prior to the start of the study and of patients who undergo bariatric-metabolic surgery during the study period. CONCLUSIONS: ACHT will be the one of the first evaluated structured, close-to-home follow-up programs for bariatric surgery in Germany. It will evaluate the effectiveness of the implemented program regarding improvements in health status, mental health, quality of life, and the feasibility of such a program outside of specialized obesity centers.

[Implementing a Global Treatment Budget for Psychiatric Hospital Services - What are Incentives, Requirements, and Challenges?] / Implementierung eines globalen Behandlungsbudgets in der Psychiatrie ­ Welche Anreize, Voraussetzungen und Herausforderungen gibt es?

OBJECTIVE: Since 2013, flexible and integrative psychiatric treatment models (FIT64b) have been set up in 22 German hospitals. FIT64b is based on a global treatment budget (GTB) covering costs for all psychiatric hospital services and is related to the number of patients treated. As part of the "PsychCare"-study we are examining incentives, requirements and challenges which relate to the introduction of FIT64b. METHODS: Expert interviews and focus groups (n = 29) were led with management and controlling staff from 7 FIT64b adopting hospitals and 3 statutory health insurance funds (SHI). A thematic analysis was conducted. RESULTS: A central component for the introduction of a GTB is a cooperative relation based on mutual trust between hospitals and SHI. Challenging are, above all, performance documentation and performance control of cross-sectoral treatment as well as the parallel structure of FIT64b and standard care. CONCLUSION: Apart from several surmountable obstacles to implementation, the GTB seems to be a strong driver for the future-oriented transformation of psychiatric hospital services in Germany. In the further development of GTB, the obligation to contract with all SHI should be considered.

Restructuring of the male mice peripheral circadian network after bariatric surgery.

Bariatric surgery is still the most effective long-term weight-loss therapy. Recent data indicate that surgical outcomes may be affected by diurnal food intake patterns. In this study, we aimed to investigate how surgery-induced metabolic adaptations (i.e. weight loss) interact with circadian clock function. For that reason, vertical sleeve gastrectomy (VSG) was performed in obese mice and rhythms in behavior, tissue rhythmicity, and white adipose tissue transcriptome were evaluated. VSG under constant darkness conditions led to a maximum weight loss of 18% compared to a loss of 3% after sham surgery. Post-surgical weight development was characterized by two distinct intervals of catabolic and subsequent anabolic metabolic state. Locomotor activity was not affected. However, VSG significantly increased active phase meal frequency in the anabolic state. No significant effects on clock gene rhythmicity were detected in adrenal and white adipose tissue (WAT) explant cultures. Transcriptome rhythm analyses of subcutaneous WAT revealed a reduction of cycling genes after VSG (sham: 2493 vs VSG: 1013) independent of sustained rhythms in core clock gene expression. This may be a consequence of weight loss-induced morphological reconstruction of WAT that overwrites the direct influence of the local clock machinery on the transcriptome. However, VSG altered rhythmic transcriptional regulation of WAT lipid metabolism pathways. Thus, our data suggest a reorganization of diurnal metabolic rhythms after VSG downstream of the molecular clock machinery.

Randomized clinical trial comparing buprenorphine/naloxone and methadone for the treatment of patients with failed back surgery syndrome and opioid addiction.

Opioid analgesic consumption has led to an unprecedented epidemic of overdose death and opioid addiction in the US history. The treatment of chronic pain in patients with opioid addiction who receive prescriptions for opioid medications presents a clinical dilemma. Continuing opioid medication could result in hyperalgesia rendering opioids ineffective and results in iatrogenic therapeutic damage as evidenced by the worsening of addiction. Discontinuing opioid medications could result in severe pain and cravings that often leads the patient to the illicit market. This study compared methadone and buprenorphine/naloxone in patients with failed back surgery syndrome and opioid addiction. Nineteen participants were randomly assigned to methadone or buprenorphine/naloxone and were followed for 6 months. In an intent-to-treat analysis analgesia, craving, functioning, drug use, depression, and treatment retention were assessed monthly. It was planned to enroll 66 patients with failed back surgery syndrome and opioid addiction; however, enrollment was closed early due to suspected abuse of medications. Patients in both treatment conditions exhibited significantly improved 24-hour pain severity with up to 20% reduction of pain severity at the last follow-up (p < .05). However, patients receiving methadone reported significantly reduced current pain severity, whereas patients receiving buprenorphine/naloxone did not. Patients reported significantly improved functioning, fewer cravings, less opioid use, and depression (p < .05) across the treatment conditions. When given a choice between methadone and buprenorphine/naloxone, buprenorphine/naloxone is recommended due to its superior safety profile. Treatment with either needs to be monitored closely.

Penile cancer - Incidence, mortality, and survival in Saxony, Germany.

OBJECTIVE: Penile cancer is a rare disease in Europe and North America. Cancer registry data were used to estimate the incidence, mortality, and survival of penile cancer in Saxony, Germany. METHODS: Data on incidence were analyzed for the period 1961 to 2012 and mortality for the period 1990 to 2012. Trend analyses of incidence and mortality were performed using joinpoint regression. Survival rates for primary penile cancer (ICD-10 C60) were estimated; overall, by T stage, UICC stage, and by year of diagnosis for the years 1963 to 2012. RESULTS: Age-standardized incidence increased from 1.2 per 100,000 in 1961 to 1.8 per 100,000 in 2012, with a statistically significant increase between 2003 and 2012 (annual percent change: 4.66; 95% confidence interval, CI 0.62-8.86). There was a statistically significant negative trend in mortality between 1990 and 2012 (annual percent change: -3.46, 95% CI -5.21 to -1.67). A total of 430 new cases of penile cancer were registered between 2003 and 2012, with 63% of all penile cancers occurring in men aged 60 to 79 years. Almost half of those cases were located at the glans penis. The overall relative 5-year survival for the years of diagnosis 2003 to 2012 was 72.4% (95% CI 64.8%-80.0%). Relative 5-year survival decreased with higher UICC stages (I: 96%, 95% CI 84.7%-107.3%; II: 86.3%, 95% CI 71.0%-101.5%; III: 39.6%, 95% CI 19.9%-59.3%; IV: 20.3%, 95% CI 2.4%-38.2%). CONCLUSION: The incidence of penile cancer in Saxony has increased in recent years, while mortality has decreased. However, survival rates have remained constant over time.

Circadian clock-gastrointestinal peptide interaction in peripheral tissues and the brain.

Food intake and sleep are two mutually exclusive behaviors and both are normally confined to opposing phases of the diurnal cycle. The temporal coordination of behavior and physiology along the 24-h day-night cycle is organized by a network of circadian clocks that orchestrate transcriptional programs controlling cellular physiology. Many of the peptide hormones of the gastrointestinal tract are not only secreted in a circadian fashion, they can also affect circadian clock function in peripheral metabolic tissues and the brain, thus providing metabolic feedback to metabolic and neurobehavioral circuits. In this review, we summarize the current knowledge on this gastrointestinal peptide crosstalk and its potential role in the coordination of nutrition and the maintenance of metabolic homeostasis.

Invitation to cervical cancer screening does increase participation in Germany: Results from the MARZY study.

The effect of different invitation models on participation in cervical cancer screening (CCS) was investigated in a randomized population-based cohort study in Germany. Participants were randomly selected via population registries and randomized into intervention Arm A (invitation letter) and Arm B (invitation letter and information brochure) or control Arm C (no invitation). The intervention and control arms were compared with regard to 3-year participation and the two invitation models were compared between intervention arms. Of the 7,758 eligible women aged 30-65 years, living in the city of Mainz and in the rural region of Mainz-Bingen, 5,265 were included in the analysis. Differences in proportions of women attending CCS were investigated and logistic regression was performed to analyze various factors influencing participation. In the intervention group, 91.8% participated in CCS compared to 85.3% in the control group (p < 0.0001), with a 6.6 percentage point increase in participation [95% confidence interval (CI) 4.6-8.6] and an adjusted odds ratio (OR) of 2.69 (95% CI 2.15-3.37). Effect estimators increased to 21.9 percentage points (95% CI 16.7-27.1) and an OR of 3.64 (95% CI 2.74-4.82), respectively, when women who participated in screening annually were excluded from the analysis. The invitation letter was particularly effective among women with lower school education, migrant women and older women. No difference in participation was found between the intervention Arm A and Arm B. An accompanying information brochure did not motivate more women to undergo CCS. However, a written invitation statistically significantly increased participation in CCS in Germany.

Nanoporous silica nanoparticles as biomaterials: evaluation of different strategies for the functionalization with polysialic acid by step-by-step cytocompatibility testing.

Nanoporous silica materials have become a prominent novel class of biomaterials which are typically applied as nanoparticles or thin films. Their large surface area combined with the rich surface chemistry of amorphous silica affords the possibility to equip this material with variable functionalities, also with several different ones on the same particle or coating. Although many studies have shown that nanoporous silica is apparently non-toxic and basically biocompatible, any surface modification may change the surface properties considerably and, therefore, the modified materials should be checked for their biocompatibility at every step. Here we report on different silane-based functionalization strategies, firstly a conventional succinic anhydride-based linker system and, secondly, copper-catalyzed click chemistry, to bind polysialic acid, a polysaccharide important in neurogenesis, onto nanoporous silica nanoparticles (NPSNPs) of MCM-41 type. At each of the different modification steps, the materials are characterized by cell culture experiments. The results show that polysialic acid can be immobilized on the surface of NPSNPs by using different strategies. The cell culture experiments show that the kind of surface immobilization has a strong influence on the toxicity of the material versus the cells. Whereas most modifications appear inoffensive, NPSNPs modified by click reactions are toxic, probably due to residues of the Cu catalyst used in these reactions.

Immunosuppressive capabilities of mesenchymal stromal cells are maintained under hypoxic growth conditions and after gamma irradiation.

BACKGROUND AIMS: The discovery of regenerative and immunosuppressive capacities of mesenchymal stromal cells (MSCs) raises hope for patients with tissue-damaging or severe, treatment-refractory autoimmune disorders. We previously presented a method to expand human MSCs in a bioreactor under standardized Good Manufacturing Practice conditions. Now we characterized the impact of critical treatment conditions on MSCs with respect to immunosuppressive capabilities and proliferation. METHODS: MSC proliferation and survival after γ irradiation were determined by 5-carboxyfluorescein diacetate N-succinimidyl ester and annexinV/4',6-diamidino-2-phenylindole (DAPI) staining, respectively. T-cell proliferation assays were used to assess the effect of γ irradiation, passaging, cryopreservation, post-thaw equilibration time and hypoxia on T-cell suppressive capacities of MSCs. Quantitative polymerase chain reaction and ß-galactosidase staining served as tools to investigate differences between immunosuppressive and non-immunosuppressive MSCs. RESULTS: γ irradiation of MSCs abrogated their proliferation while vitality and T-cell inhibitory capacity were preserved. Passaging and long cryopreservation time decreased the T-cell suppressive function of MSCs, and postthaw equilibration time of 5 days restored this capability. Hypoxic culture markedly increased MSC proliferation without affecting their T-cell-suppressive capacity and phenotype. Furthermore, T-cell suppressive MSCs showed higher CXCL12 expression and less ß-galactosidase staining than non-suppressive MSCs. DISCUSSION: We demonstrate that γ irradiation is an effective strategy to abrogate MSC proliferation without impairing the cells' immunosuppressive function. Hypoxia significantly enhanced MSC expansion, allowing for transplantation of MSCs with low passage number. In summary, our optimized MSC expansion protocol successfully addressed the issues of safety and preservation of immunosuppressive MSC function after ex vivo expansion for therapeutic purposes.

Risk equations for the development of worsened glucose status and type 2 diabetes mellitus in a Swedish intervention program.

BACKGROUND: Several studies investigated transitions and risk factors from impaired glucose tolerance (IGT) to type 2 diabetes mellitus (T2D). However, there is a lack of information on the probabilities to transit from normal glucose tolerance (NGT) to different pre-diabetic states and from these states to T2D. The objective of our study is to estimate these risk equations and to quantify the influence of single or combined risk factors on these transition probabilities. METHODS: Individuals who participated in the VIP program twice, having the first examination at ages 30, 40 or 50 years of age between 1990 and 1999 and the second examination 10 years later were included in the analysis. Participants were grouped into five groups: NGT, impaired fasting glucose (IFG), IGT, IFG&IGT or T2D. Fourteen potential risk factors for the development of a worse glucose state (pre-diabetes or T2D) were investigated: sex, age, education, perceived health, triglyceride, blood pressure, BMI, smoking, physical activity, snus, alcohol, nutrition and family history. Analysis was conducted in two steps. Firstly, factor analysis was used to find candidate variables; and secondly, logistic regression was employed to quantify the influence of the candidate variables. Bootstrap estimations validated the models. RESULTS: In total, 29 937 individuals were included in the analysis. Alcohol and perceived health were excluded due to the results of the factor analysis and the logistic regression respectively. Six risk equations indicating different impacts of different risk factors on the transition to a worse glucose state were estimated and validated. The impact of each risk factor depended on the starting or ending pre-diabetes state. High levels of triglyceride, hypertension and high BMI were the strongest risk factors to transit to a worsened glucose state. CONCLUSIONS: The equations could be used to identify individuals with increased risk to develop any of the three pre-diabetic states or T2D and to adapt prevention strategies.

Potential for osteogenic and chondrogenic differentiation of MSC.

The introduction of mesenchymal stem cells (MSC) into the field of tissue engineering for bone and cartilage repair is a promising development, since these cells can be expanded ex vivo to clinically relevant numbers and, after expansion, retain their ability to differentiate into different cell lineages. Mesenchymal stem cells isolated from various tissues have been intensively studied and characterized by many research groups. To obtain functionally active differentiated tissue, tissue engineered constructs are cultivated in vitro statically or dynamically in bioreactors under controlled conditions. These conditions include special cell culture media, addition of signalling molecules, various physical and chemical factors and the application of different mechanical stimuli. Oxygen concentration in the culture environment is also a significant factor which influences MSC proliferation, stemness and differentiation capacity. Knowledge of the different aspects which affect MSC differentiation in vivo and in vitro will help researchers to achieve directed cell fate without the addition of differentiation agents in concentrations above the physiological range.