[Complementary and alternative procedures for fibromyalgia syndrome : Updated guidelines 2017 and overview of systematic review articles]. / Komplementäre und alternative Verfahren beim Fibromyalgiesyndrom : Aktualisierte Leitlinie 2017 und Übersicht von systematischen Übersichtsarbeiten.

BACKGROUND: The regular update of the guidelines on fibromyalgia syndrome, AWMF number 145/004, was scheduled for April 2017. METHODS: The guidelines were developed by 13 scientific societies and 2 patient self-help organizations coordinated by the German Pain Society. Working groups (n =8) with a total of 42 members were formed balanced with respect to gender, medical expertise, position in the medical or scientific hierarchy and potential conflicts of interest. A search of the literature for systematic reviews of randomized controlled trials of complementary and alternative therapies from December 2010 to May 2016 was performed in the Cochrane library, MEDLINE, PsycINFO and Scopus databases. Levels of evidence were assigned according to the classification system of the Oxford Centre for Evidence-Based Medicine version 2009. The strength of recommendations was formed by multiple step formalized procedures to reach a consensus. Efficacy, risks, patient preferences and applicability of available therapies were weighed up against each other. The guidelines were reviewed and approved by the board of directors of the societies engaged in the development of the guidelines. RESULTS AND CONCLUSION: Meditative movement therapies (e.g. qi gong, tai chi and yoga) are strongly recommended. Acupuncture and weight reduction in cases of obesity can be considered.

[Pain assessment in elderly nursing home residents: methods paper for the S3-guideline development]. / Schmerzassessment bei älteren Menschen in der vollstationären Altenhilfe : Methodenpapier zur S3-Leitlinie.

In Germany, there is currently no guideline for pain assessment in elderly people. Pain management in nursing home residents is, however, legally required. For this particular group, especially for people with dementia, suitable interdisciplinary orientations for health care are lacking in Germany. The working group "Pain and Age" of the German Pain Society ("Deutschen Schmerzgesellschaft") in conjunction with the German Centre for Neurodegenerative Diseases ("Deutschen Zentrum für Neurodegenerative Erkrankungen"), Witten, has embarked on the development of interdisciplinary S3-Guideline for "Pain Assessment in Elderly People in Nursing Homes", based on the methodology suggested by the Association of the Scientific Medical Societies ("Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V."), the German Agency for Quality in Medicine ("Ärztliche Zentrum für Qualität in der Medizin"), and that described in the DELBI ("Deutschen Leitlinien-Bewertungsinstrument"). Delegates of the 38 scientific societies and interest groups currently participating can contribute to the contents on three different levels. The present article outlines the methods for developing the guideline.

[Company health promotion as a possible preparatory stage of effective rehabilitation]. / Betriebliche Gesundheitsförderung als mögliche Vorstufe wirksamer Rehabilitation.

In Section 20a of Book 5 of the German Social Code (SGB V), the legislator obliged the health insurance funds to carry out company health promotion in cooperation with the accident insurance agency in charge. He thus created a foundation for more health and secure earnings or employment potential in the companies. At the same time company health promotion permits detecting threats to this potential. That helps to identify a possible need for rehabilitation at an earlier stage and to take appropriate action.To verify whether and how this instrument of preventive health policy is being used, an empirical study explored the actual application of that legal provision in small and medium-sized enterprises in particular. The law, administrative measures and company everyday evidence were set against each other under legal and de facto aspects, which showed obvious deficits in applying the law. Proposals for better company health promotion are derived from these findings. In the first place, actors in administration and self-management of the statutory health and accident insurance schemes are addressed to this end, in anticipation of enhanced implementation. A premature reduction of earning capacity could thus be counteracted. Pension insurants could retain gainful employment for a longer time, companies would have a more reliable employee basis. Social insurance carriers, notably the health and pension insurance schemes, would have to spend less in the end. A development like that would be a benefit for all--including the state.

[Use of health insurance data to analyse pain management practices in the nursing-home setting]. / Sekundärdatenanalyse von Routinedaten einer Krankenkasse - Ein Zugangsweg zur Beschreibung schmerzbezogener Versorgungsleistungen von Pflegeheimbewohnern.

Pain is the most common health-related complaint in older persons. International estimations mention up to 80% of nursing home residents suffering from pain. In the meantime, no reliable epidemiological data on pain in nursing home residents are available for Germany, because of restricted access to the nursing-home population. This pilot study aimed to evaluate whether routine data from a German statutory health insurance fund can be used to generate data on pain prevalence and analgesic therapy in nursing home residents. To this end, data of all insured persons of Deutsche BKK who received long-term care insurance benefits for nursing-home care between April and June 2007 were selected anonymously. These data were combined with data on diagnoses and analgesic prescriptions. 3 pain-related diagnoses were selected: R 52 (pain, not elsewhere classified), M 16 (coxarthrosis) and G 53.0 (postherpetic neuralgia) and analysed for corresponding prescriptions. The study sample shows similar characteristics regarding age distribution and care needs in terms of long-term care insurance benefits compared to the official data on nursing-home residents for Germany in 2007. The rate of dementia was within the expected range, too. Therefore, external validity of the sample is assumed. One of the 3 selected diagnoses had been documented in 15% of the sample. About 58% of those received an analgesic prescription. Deficits were discovered regarding the documentation of postherpetic neuralgia, the combination of different analgesics and prescriptions for adjuvant drugs. Prevalence rate and numbers of prescriptions were as frequent as expected. The routine method for this analysis proved to be practicable and reliable. Data quality is deemed sufficient so that the main study will proceed to include a longer period of time and additional data.

[Epidemiological characteristics of the influenza pandemic (H1N1) 2009 in Germany based on the mandatory notification of cases]. / Epidemiologischer Steckbrief der pandemischen Influenza (H1N1) 2009 basierend auf Einzelfallmeldungen nach Infektionsschutzgesetz.

The aim of the investigation is the descriptive analysis of case-based information from mandatory notifications in the first year of the influenza pandemic (H1N1) 2009 in order to identify and describe epidemiological characteristics and risk factors for severe outcome. Four distinct time periods were defined to describe the age distribution of hospitalized and fatal cases. In contrast, stratified (age, sex) analysis of risk factors was carried out for the whole time period of pandemic influenza activity (notification weeks 18/2009 to 17/2010). Characteristic differences in the age distribution of reported cases were observed according to the time period. Among the reported risk factors, immunosuppression exhibited the highest probability for hospitalization or a fatal outcome (OR=8.82; CI95% 7.3-10.6 and OR=37.4; CI95% 25.5-54.8, respectively). The stratified analysis showed that this was especially pronounced for patients in the age group 60 years and above. Single case-based notifications of pandemic influenza have proven to be an invaluable source of information for assessing the epidemiological characteristics of the influenza pandemic 2009 in Germany. In addition, it allows comparative analysis of certain risk groups for severe disease. The information, thus, provides an important contribution for further developing and improving of public health recommendations.

Possible role of MDR1 two-locus genotypes for young-age onset ulcerative colitis but not Crohn's disease.

BACKGROUND: The role of the single nucleotide polymorphisms (SNPs) on positions 2677G>T/A and 3435C>T of the multi-drug-resistance gene 1 (MDR1) in inflammatory bowel disease (IBD) remains unclear. AIMS: To further elucidate the potential impact of MDR1 two-locus genotypes on susceptibility to IBD and disease behaviour. PATIENTS AND METHODS: Three hundred eighty-eight German IBD patients [244 with Crohn's disease (CD), 144 with ulcerative colitis (UC)] and 1,005 German healthy controls were genotyped for the two MDR1 SNPs on positions 2677G>T/A and 3435C>T. Genotype-phenotype analysis was performed with respect to disease susceptibility stratified by age at diagnosis as well as disease localisation and behaviour. RESULTS: Genotype distribution did not differ between all UC or CD patients and controls. Between UC and CD patients, however, we observed a trend of different distribution of the combined genotypes derived from SNPs 2677 and 3435 (chi(2) = 15.997, df = 8, p = 0.054). In subgroup analysis, genotype frequencies between UC patients with early onset of disease and controls showed significant difference for combined positions 2677 and 3435 (chi(2) = 16.054, df = 8, p = 0.034 for age at diagnosis >or=25, lower quartile). Herein the rare genotype 2677GG/3435TT was more frequently observed (odds ratio = 7.0, 95% confidence interval 2.5 - 19.7). In this group severe course of disease behaviour depended on the combined MDR1 SNPs (chi(2) = 16.101, df = 6, p = 0.017 for age at diagnosis >or=25). No association of MDR1 genotypes with disease subgroups in CD was observed. CONCLUSIONS: While overall genotype distribution did not differ, combined MDR1 genotypes derived from positions 2677 and 3435 are possibly associated with young age onset of UC and severe course of disease in this patient group.

Beta1-adrenoceptor gene variations: a role in idiopathic dilated cardiomyopathy?

A substantial body of evidence suggests involvement of the human beta1-adrenoceptor (beta1-AR) gene in the pathophysiology of dilated cardiomyopathy (DCM), a severe heart disease of significant public health impact. Beta1-AR-mediated signal transduction is dramatically altered due to downregulation, resulting in an impairment of myocardial response. The important role of genetic factors in idiopathic dilated cardiomyopathy (IDCM) recently recognized, we analyzed this prime candidate gene for genetic variation in carefully selected patients and controls. In this preliminary study, 18 single nucleotide polymorphisms were observed, 17 of which were located in the N-terminal and C-terminal region of the coding exon, resulting in 7 amino acid exchanges: Ser-49-Gly, Ala-59-Ser, Gly-389-Arg, Arg-399-Cys, His-402-Arg, Thr-404-Ala, and Pro-418-Ala. These mutations resulted in 11 different beta1-AR genotypes. Importantly, the genotypes carrying the Ser-49-Gly mutation in the N-terminus of the molecule in a heterozygous or homozygous form were observed significantly more frequently in the group of IDCM patients. The present results may provide a clue on the molecular mechanisms involved in IDCM, and add moreover interesting information on nature, distribution, and evolutionary aspects of sequence variation in human adrenergic receptor genes.

Clinical and functional outcome of assertive outreach for patients with schizophrenic disorder: Results of a quasi-experimental controlled trial.

BACKGROUND: The majority of studies support modern assertive health service models. However, the evidence is limited for parts of continental Europe, as well as for the pharmacological adherence outcome parameter. METHOD: We conducted a quasi-experimental controlled trial including adult patients with a schizophreniform disorder and a maximum of 60 points on the Global Assessment of Functioning Scale (GAF). Interventions (n=176) and controls (TAU, n=142) were assessed every six-month within one year in 17 study practices in rural areas. Mental and functional state were rated using the Brief Psychiatric Rating Scale (BPRS) and the GAF. Functional limitations and pharmacological adherence were patient-rated using the WHO-Disability Assessment Schedule II (WHODAS-II) and the Medication Adherence Report Scale (MARS). We computed multilevel mixed models. RESULTS: The GAF and BPRS of both groups improved significantly, yet the increase in the intervention group was significantly higher. In contrast, patient-rated variables - WHODAS-II and MARS - neither showed a stable temporal improvement nor a difference between groups. CONCLUSION: Our findings only partly support the investigated AO intervention, because of conflicting results between clinician- and patient-ratings. Accordingly, the benefits of AO need to be further evaluated.

Comparison of two cytochromes P-450 from Candida maltosa: primary structures, substrate specificities and effects of their expression in Saccharomyces cerevisiae on the proliferation of the endoplasmic reticulum.

cDNAs were cloned, sequenced and expressed which encode two different cytochrome P-450 forms of the alkane-assimilating yeast Candida maltosa, designated as P-450Cm1 and P-450Cm2. The amino acid sequences deduced were about 55% identical. Expression in Saccharomyces cerevisiae resulted in the formation of intact microsomal P-450 systems catalyzing the hydroxylation of n-hexadecane and lauric acid with significantly different substrate preferences. A massive proliferation of the endoplasmic reticulum was observed in the S. cerevisiae cells which produced P-450. Depending on the P-450 form expressed, distinctly organized stacks of paired membranes appeared and occupied considerable areas of the cytoplasm. As shown by immunoelectron microscopy for P-450Cm1, the protein expressed was highly concentrated within these newly formed membrane structures.

Comparative sequencing of the human CB1 cannabinoid receptor gene coding exon: no structural mutations in individuals exhibiting extreme responses to cannabis.

Rare but striking individual differences in responsiveness to cannabinoids have been observed that might involve mutations in the gene encoding the brain-expressed cannabinoid receptor. In a preliminary study, the human CB1 cannabinoid receptor coding region was comparatively sequenced in different groups of individuals: one group showed acute psychotic symptoms after cannabis intake, while another group did not develop any psychopathology after long-term heavy cannabis abuse. No evidence for structural mutations was obtained, which might provide some insight into the molecular basis of individually different responsiveness to cannabinoids. Comparison of CB1 cannabinoid receptor amino acid sequences between species substantiated evidence that the protein sequence is relatively well conserved.

[Estimation of the effects of cardenolides. 1. Relation between molecular physical parameters and parameters of action of cardenolides]. / Abschätzung der Wirkstärke von Cardenoliden. 1. Mitteilung: Zusammenhang zwischen molekülphysikalischen Parametern und dem Wirkstärkeparameter von Cardenoliden.

Knowing the modell developed by Repke and co-workers for the cardenolide-receptor-interaction the aim of this study was to find quantitative relations between molecular physical properties of cardenolides and their molecular-biologically defined effect, which are fundamentally useful to estimate the effect of still nonsynthesized cardenolide derivatives. The statistically significant relations (alpha = 0.05) between molecular physical parameters, which are derived from the dipole moment vector, and the molecular-biologically defined effect was found by means of regression analysis.

[Estimation of the intensity of effect of cardenolides. 2: Algorithms for the estimation of the intensity of effect]. / Abschätzung der Wirkstärke von Cardenoliden 2. Mitteilung: Algorithmus zur Abschätzung der Wirkstärke.

An algorithm worked on basis of quantitative relations between molecular-biologically defined effects and molecular-physical properties (see part 1) allows the effect estimation of concepted cardenolides before their synthesis. The empirical use of the developed equations for the estimation of molecular-biologically defined effect of compounds produces usable results and justifies therefore the proposed method, as well as it's shown by the experimental proof of estimated values of some cardenolides . An enlargement of the use of the algorithm for effect estimation seems to be successful.

Dynamical control of the dialysis process. Part I: Structural considerations and first mathematical approach.

Individual optimization of the dialysis process requires the (open-loop or closed-loop) control of many different variables, e.g. plasma ion concentrations, acid base state, volemic state and hemodynamic quantities. For this purpose a general concept for multiple-input-multiple-output (MIMO) control of the dialysis process is presented. The controlled variables have been differentiated into variables which can be modeled mechanistically (primary controlled variables, PCVs) and (hemodynamic) variables for which no mechanistic model has been developed up to now (secondary controlled variables, SCVs). Accordingly the controller is decomposed into two stages. Stage 1 contains an expert system which links the PCVs to the SCVs and provides the generation of optimal profiles for the PCVs with respect to maximum hemodynamic stability of the patient. Stage 2 is a tracking controller for the PCVs. An algorithm for the multidimensional tracking problem at stage 2 has been developed. It can be used for open-loop and future closed-loop control. The algorithm has been tested for 4 controlled (plasma Na+, plasma K+, plasma volume and ratio between intra- and extracellular volume) and 3 control variables (dialysate Na+, dialysate K+, ultrafiltration rate) up to now. It renders possible the exact tracking of the prescribed trajectories as long as all points are reachable under consideration of all physical and physiological boundary conditions. If they are not, appropriate weighting of the conflicting optimization goals must be applied. An extension towards more than 4 controlled variables is possible on principle. Main advantages of the method are its mathematical simplicity and the applicability of standard optimization subroutines.

Tools for advanced and targeted genetic manipulation of the ß-lactam antibiotic producer Acremonium chrysogenum.

Acremonium chrysogenum is the major producer of the ß-lactam antibiotic cephalosporin C and therefore of great importance for the pharmaceutical industry. However, this filamentous fungus is known to reproduce solely by asexual means, shows only sporadic conidiospore production, and has gradual fragmentation of the vegetative mycelium into arthrospores. Due to these peculiar growth characteristics and life style, strain improvement by recombinant technologies is much more challenging than for other biotechnologically relevant fungi. Here, we describe several molecular tools for genetic engineering of A. chrysogenum, including a ΔAcku70 deletion strain for homologous recombination. No physiological or morphological changes occurred due to deletion of the ku70 gene or integration of the nat1 cassette in this recipient strain. We also used a xylose-inducible promoter from Sordaria macrospora (Smxyl) to demonstrate induction of the gfp reporter gene in A. chrysogenum. The Smxyl promoter was used for construction of a vector molecule to develop a one-step FLP/FRT recombination system in A. chrysogenum. This system was then used in the ΔAcku70 deletion strain to construct a marker-free recipient strain for targeted DNA insertion into genomic DNA. The applicability of our tools was demonstrated by construction of a marker-free transgenic strain, lacking any foreign genes.

Deficits in pain treatment in nursing homes in Germany: a cross-sectional study.

BACKGROUND: Current knowledge about the quality and appropriateness of pharmacological pain treatment in nursing home residents (NHR), particularly in NHR with moderate to severe cognitive impairment, is poor. METHODS: This observational cross-sectional study assessed pain treatment in a random sample of NHR with or without cognitive impairment from nursing homes in Germany. Prescribed drugs, pain intensity and frequency, diagnoses, and surgical procedures and injuries during the last 4 weeks were documented. Quality and appropriateness of pain medication were assessed by analysis of pain medications and the Pain Medication Appropriateness Scale (PMAS) score (S(PMAS) ), with a cut-off value of >67% indicating appropriate pain treatment. RESULTS: A total of 321 residents (62% women) were studied, including 152 (47%) with severe cognitive impairment. The most frequently prescribed analgesics were dipyrone, fentanyl, tramadol and ibuprofen. The mean S(PMAS) was 48.5 ± 1.5 (range, -33 to +100). Residents with prescribed scheduled analgesics had a significantly better S(PMAS) than patients without such treatment (S(PMAS) 58 ± 1.5 vs. 37 ± 2.5, p < 0.01). NHR without current pain had significantly better S(PMAS) than residents suffering from pain (S(PMAS) 47 ± 1.9 vs. 59 ± 4.2, p = 0.01). With an S(PMAS) of 69 ± 1.5, residents (n = 106) with scheduled pain medication plus PRN analgesics achieved the highest scores in the population. Overall, similar results were found in NHR with and in NHR without cognitive impairment. CONCLUSION: Our study points to a significant deficit in pain treatment in German NHR, including NHR with or without cognitive impairment.

[Upgrade, expand, systematize--an analysis of the status of, the need for reform in, as well as innovative projects for follow-up care in rehabilitation under the German pension insurance scheme]. / Aufwerten, ausbauen und systematisieren -- Eine Analyse von Situation, Reformbedarf und innovativen Projekten zur Nachsorge in der Rehabilitation der Rentenversicherung.

Rehabilitation benefits provided under the German Pension Insurance scheme are of central importance to insureds, in terms of protection in cases of loss or reduction of their earning capacity. Due to this safeguarding effect for the gainfully employed population, rehabilitation benefits at the same time are important to the insured community and to society as a whole. In 2003, some 846 000 insured persons had received medical and other benefits for rehabilitation. Designing these benefits to be as effective as possible is among the pre-eminent goals of the statutory pension insurance scheme. To this end, the statutory pension insurance institutes have initiated a quality assurance programme designed to enable utmost quality of the benefits provided. This programme in the first line covers inpatient medical rehabilitation of, as a rule, three weeks duration. An issue hardly investigated so far is sustainability of the effects achieved by these rehabilitation measures. Among the possibilities for ensuring lasting success are follow-up measures or benefits arranged for already during the in-patient stay, a service field which until recently had hardly been known in Germany. A stock-taking carried out in 2004 by the author and supported by LVA Schleswig-Holstein, a regional pension insurance institute, has for the first time realized an overview of this kind. Its essential findings are presented in this article, supplemented by a partial update vis-à-vis completion of the initial investigation.

Sequence variability and candidate gene analysis in complex disease: association of mu opioid receptor gene variation with substance dependence.

To analyze candidate genes and establish complex genotype-phenotype relationships against a background of high natural genome sequence variability, we have developed approaches to (i) compare candidate gene sequence information in multiple individuals; (ii) predict haplotypes from numerous variants; and (iii) classify haplotypes and identify specific sequence variants, or combinations of variants (pattern), associated with the phenotype. Using the human mu opioid receptor gene (OPRM1) as a model system, we have combined these approaches to test a potential role of OPRM1 in substance (heroin/cocaine) dependence. All known functionally relevant regions of this prime candidate gene were analyzed by multiplex sequence comparison in 250 cases and controls; 43 variants were identified and 52 different haplotypes predicted in the subgroup of 172 African-Americans. These haplotypes were classified by similarity clustering into two functionally related categories, one of which was significantly more frequent in substance-dependent individuals. Common to this category was a characteristic pattern of sequence variants [-1793T-->A, -1699Tins, -1320A-->G, -111C-->T, +17C-->T (A6V)], which was associated with substance dependence. This study provides an example of approaches that have been successfully applied to the establishment of complex genotype-phenotype relationships in the presence of abundant DNA sequence variation.

Molecular cloning and characterization of the primary structure of the alkane hydroxylating cytochrome P-450 from the yeast Candida maltosa.

A cDNA library was established starting from poly(A) RNA of n-alkane-grown Candida maltosa cells and cDNA clones were isolated containing the entire coding sequence for the alkane hydroxylating cytochrome P-450. The deduced protein consists of 521 amino acids, contains two putative transmembrane segments in the N-terminal region and has a characteristic heme-binding sequence in the C-terminal part. Sequence alignments with members of 11 reported cytochrome P-450 families revealed a strong homology to an alkane-inducible cytochrome P-450 from Candida tropicalis.