Health-related quality of life 90 days after stroke assessed by the International Consortium for Health Outcome Measurement standard set.

BACKGROUND AND PURPOSE: Stroke has detrimental effects in multiple health domains not captured by routine scales. The International Consortium for Health Outcome Measurement has developed a standardized set for self-reported assessment to overcome this limitation. The aim was to assess this set in acute stroke care. METHODS: Consecutive patients with acute ischaemic stroke, transient ischaemic attack or intracerebral hemorrhage were enrolled. Demographics, living situation and cardiovascular risk factors were collected from medical records and interviews. The Patient-reported Outcomes Measurement Information System 10-Question Short Form (PROMIS-10) and the Patient Health Questionnaire-4 (PHQ-4) were conducted 90 days after admission. Linear and logistic regression analyses were used to identify predictors of outcome. The study is registered at ClinicalTrials.gov, NCT03795948. RESULTS: In all, 1064 patients were enrolled; mean age was 71.6 years, 51% were female, and median National Institutes of Health Stroke Scale (NIHSS) on admission was 3. Diagnosis was acute ischaemic stroke in 74%, transient ischaemic attack in 20% and intracerebral hemorrhage in 6%. 673 patients were available for outcome evaluation at 90 days; of these 90 (13%) had died. In survivors, t scores of PROMIS-10 physical and mental health were 40.3 ± 6.17 and 44.3 ± 8.63, compared to 50 ± 10 in healthy populations. 16% reported symptoms indicating depression or anxiety on the PHQ-4. Higher NIHSS, prior stroke and requiring help pre-stroke predicted lower values in physical and mental health scores. Higher NIHSS and diabetes were associated with anxiety or depression. CONCLUSIONS: Integrated in the routine of acute stroke care, systematic assessment of patient-reported outcomes reveals impairments in physical and mental health. Main predictors are severity of stroke symptoms and comorbidities such as hypertension and diabetes.

Prevalence of problem drinking and associated factors in a representative German sample of adolescents and young adults.

BACKGROUND: Alcohol use in youth is regarded as an important public health concern and in a recent survey in 35 European countries, every third student reported heavy episodic drinking. While prevalence estimates for problem drinking in adults from representative population samples are available, corresponding numbers for adolescents in Germany are currently lacking. METHODS: A representative sample of 1531 12-25 years old in Germany was investigated with a standardized questionnaire concerning problem drinking (assessed with the AUDIT-C) and psychosocial aspects (anxiety with the GAD-2, depressive symptoms with the PHQ-2 and smoking behavior). Due to missing values, we could calculate prevalence estimates, chi-square tests and logistic regression analyses for 1490 cases. RESULTS: The 1-year prevalence of problem drinking in 12-25 years old in Germany was 18.2%. Overall, 5.0% of the adolescents (aged 12-17 years) and 27.7% of the young adults (aged 18-25 years) reported problem drinking in the last year. Young adult males more often showed problem drinking than females, while no gender differences in adolescents were observed. Problem drinking was associated with male gender, higher age, smoking behavior and depressive symptoms. CONCLUSIONS: According to the study findings, problem drinking is widespread in 12-25 years old in Germany.

GEneSTATION 1.0: a synthetic resource of diverse evolutionary and functional genomic data for studying the evolution of pregnancy-associated tissues and phenotypes.

Mammalian gestation and pregnancy are fast evolving processes that involve the interaction of the fetal, maternal and paternal genomes. Version 1.0 of the GEneSTATION database (http://genestation.org) integrates diverse types of omics data across mammals to advance understanding of the genetic basis of gestation and pregnancy-associated phenotypes and to accelerate the translation of discoveries from model organisms to humans. GEneSTATION is built using tools from the Generic Model Organism Database project, including the biology-aware database CHADO, new tools for rapid data integration, and algorithms that streamline synthesis and user access. GEneSTATION contains curated life history information on pregnancy and reproduction from 23 high-quality mammalian genomes. For every human gene, GEneSTATION contains diverse evolutionary (e.g. gene age, population genetic and molecular evolutionary statistics), organismal (e.g. tissue-specific gene and protein expression, differential gene expression, disease phenotype), and molecular data types (e.g. Gene Ontology Annotation, protein interactions), as well as links to many general (e.g. Entrez, PubMed) and pregnancy disease-specific (e.g. PTBgene, dbPTB) databases. By facilitating the synthesis of diverse functional and evolutionary data in pregnancy-associated tissues and phenotypes and enabling their quick, intuitive, accurate and customized meta-analysis, GEneSTATION provides a novel platform for comprehensive investigation of the function and evolution of mammalian pregnancy.

[Psychotherapy of depressive disorders : Procedures, evidence and perspectives]. / Psychotherapie depressiver Störungen : Verfahren, Evidenz und Perspektiven.

BACKGROUND: Depressive disorders are associated with a high burden of suffering and significantly reduce the well-being and the self-esteem of affected patients. Psychotherapy is one of the main treatment options for depressive disorders. OBJECTIVE: The aim of this article is to present the current evidence for antidepressive psychotherapeutic treatments. MATERIAL AND METHODS: During the revision of the German S3- and National Disease Management Guideline (NDMG) on unipolar depression in 2015, a comprehensive and systematic evidence search was conducted. The results of this search along with a systematic update are summarized. RESULTS: The most intensively investigated psychotherapeutic method is cognitive behavioral therapy (CBT), which proved to be effective in many trials. Evidence also exists for psychodynamic psychotherapy and interpersonal therapy (IPT), followed by systemic therapy and client-centered psychotherapy; however, the evidence is less robust. CONCLUSION: Psychotherapy alone or in combination with pharmacotherapy was shown to be an effective treatment option. Psychotherapy represents a key element in the treatment of depressive disorders.

[Psychotherapy of depressive disorders: Evidence in chronic depression and comorbidities]. / Psychotherapie depressiver Störungen: Evidenz bei chronischer Depression und bei Komorbidität.

BACKGROUND: Psychotherapy has been shown to be an effective treatment option for depressive disorders; however, its effectiveness varies depending on patient and therapist characteristics and the individual form of the depressive disorder. OBJECTIVES: The aim of this article is to present the current evidence for psychotherapeutic antidepressive treatments for patients with chronic and treatment-resistant depression as well as for patients with mental and somatic comorbidities. MATERIAL AND METHODS: During the revision of the currently valid German S3- and National Disease Management Guideline (NDMG) on unipolar depression published in 2015, a comprehensive and systematic evidence search including psychotherapy for specific patient groups was conducted. The results of this search along with a systematic update are summarized. RESULTS: Psychotherapy has been shown to be effective in reducing depressive symptoms in patients suffering from chronic and treatment-resistant depression and in patients with mental and somatic comorbidities. The evidence is insufficient particularly for patients with mental comorbidities. CONCLUSION: Based on the current evidence and clinical expertise the NDMG recommends psychotherapy alone or in combination with pharmacotherapy to treat most of these depressive patient groups. Evidence gaps were identified, which highlight the need for further research.

Shared Selective Pressures on Fungal and Human Metabolic Pathways Lead to Divergent yet Analogous Genetic Responses.

Reduced metabolic efficiency, toxic intermediate accumulation, and deficits of molecular building blocks, which all stem from disruptions of flux through metabolic pathways, reduce organismal fitness. Although these represent shared selection pressures across organisms, the genetic signatures of the responses to them may differ. In fungi, a frequently observed signature is the physical linkage of genes from the same metabolic pathway. In contrast, human metabolic genes are rarely tightly linked; rather, they tend to show tissue-specific coexpression. We hypothesized that the physical linkage of fungal metabolic genes and the tissue-specific coexpression of human metabolic genes are divergent yet analogous responses to the range of selective pressures imposed by disruptions of flux. To test this, we examined the degree to which the human homologs of physically linked metabolic genes in fungi (fungal linked homologs or FLOs) are coexpressed across six human tissues. We found that FLOs are significantly more correlated in their expression profiles across human tissues than other metabolic genes. We obtained similar results in analyses of the same six tissues from chimps, gorillas, orangutans, and macaques. We suggest that when selective pressures remain stable across large evolutionary distances, evidence of selection in a given evolutionary lineage can become a highly reliable predictor of the signature of selection in another, even though the specific adaptive response in each lineage is markedly different.

Physical linkage of metabolic genes in fungi is an adaptation against the accumulation of toxic intermediate compounds.

Genomic analyses have proliferated without being tied to tangible phenotypes. For example, although coordination of both gene expression and genetic linkage have been offered as genetic mechanisms for the frequently observed clustering of genes participating in fungal metabolic pathways, elucidation of the phenotype(s) favored by selection, resulting in cluster formation and maintenance, has not been forthcoming. We noted that the cause of certain well-studied human metabolic disorders is the accumulation of toxic intermediate compounds (ICs), which occurs when the product of an enzyme is not used as a substrate by a downstream neighbor in the metabolic network. This raises the hypothesis that the phenotype favored by selection to drive gene clustering is the mitigation of IC toxicity. To test this, we examined 100 diverse fungal genomes for the simplest type of cluster, gene pairs that are both metabolic neighbors and chromosomal neighbors immediately adjacent to each other, which we refer to as "double neighbor gene pairs" (DNGPs). Examination of the toxicity of their corresponding ICs shows that, compared with chromosomally nonadjacent metabolic neighbors, DNGPs are enriched for ICs that have acutely toxic LD50 doses or reactive functional groups. Furthermore, DNGPs are significantly more likely to be divergently oriented on the chromosome; remarkably, ∼40% of these DNGPs have ICs known to be toxic. We submit that the structure of synteny in metabolic pathways of fungi is a signature of selection for protection against the accumulation of toxic metabolic intermediates.

Functional divergence for every paralog.

Because genes can be constrained by selection at more than one phenotypic level, the relaxation of constraints following gene duplication allows for functional divergence (FD) along multiple phenotypic axes. Many studies have generated individual measures of FD, but the profile of FD between paralogs across levels of phenotypic space remains largely uncharted. We evaluate paralog pairs that originated via the yeast whole-genome duplication (ohnolog pairs) at three distinct phenotypic levels (properties of proteins, gene expression, and overall organismal growth) using eight complementary measures of FD (protein: evolutionary rates, radical amino acid substitutions, and domain architecture; gene expression: expression differences in a single species and condition, across species in a single condition, and in a single species across conditions; and organismal: genetic interaction profiles and growth profiles in multiple conditions). We find that the majority of ohnolog pairs show FD by multiple phenotypic measures. Within each phenotypic level, measures of FD are strongly correlated but are generally weakly correlated between levels, suggesting that functional constraints exerted on genes from distinct phenotypic levels are largely decoupled. Our results suggest that redundancy is a rare functional fate for retained paralogs and that FD cannot be fully captured by measures at any single phenotypic level.

[Psychometric Testing of a New Scale Assessing the Reasons for Non-Utilisation of Health Care Services by People with Migration Backgrounds]. / Psychometrische Überprüfung eines Fragebogens zur Erfassung der Barrieren der Inanspruchnahme von Gesundheitsleistungen durch Personen mit Migrationshintergrund.

BACKGROUND: In Germany live a lot of migrants. Cultural and migration specific aspects seem to have an effect on utilisation of health care. There are no instruments that measure such factors of influence. METHODS: A systematic literature research or article that identify the difficulties of the migrants in using the health care system, was made. The relevant aspects were explored during a health related opinion survey of migrants from former USSR, Turkey, Italy and Spain. The psychometric qualities of this questionnaire were investigated with factor and reliability analyses. RESULTS: There were 24 reasons identified for non-utilisation health care. They were combined in a questionnaire. The factor analysis showed 2-factor structure ("janguage und information related Reasons" Chronbach's α=0.928 and "experience with/attitude toward health care system", Chronbach's α=0.879). Furthermore, there was a total scale with Chronbach's α=0.945. The acceptance was between 80.0 and 96.3%. CONCLUSIONS: The results confirm the psychometric quality of this measuring instrument. For further generalisability more verification will be necessary.

[Transcultural prevention of alcohol-related disorders : effects of a culture- and migration-sensitive approach in elderly migrants with respect to attitudes and behavior: a cluster randomized controlled trial]. / Transkulturelle Prävention von Alkoholerkrankungen : Effekte eines kultur- und migrationssensitiven Ansatzes auf Einstellungen und Verhalten älterer Personen mit Migrationshintergrund - Eine Cluster-randomisierte kontrollierte Studie.

BACKGROUND: For migrants who are older than 50, alcohol frequently becomes a problem. Simultaneously alcohol-related prevention measures only reach this group insufficiently. Therefore, a transcultural concept for preventing alcohol-related disorders in elderly (≥ 45 years) migrants has been developed. METHOD: The transcultural concept, which consisted of a prevention event as well as a cultural and language-sensitive information booklet, was evaluated in a cluster-randomized controlled trial (n = 310 immigrants). As a control condition there was a prevention event with materials from Deutsche Hauptstelle für Suchtfragen (German Centre for Addiction Issues). Data were obtained before and after the event, as well as after 6 months. All materials were available both in German and in Russian, Italian, Spanish and Turkish. RESULTS: Directly after the event, as well as 6 months thereafter, the transcultural approach was rated significantly better than the general prevention event. 73.4 % of the participants read the cultural and migration-sensitive booklet, whereas only 21.2 % in the control condition (p = 0.0001). Furthermore, significantly more participants of the transcultural approach reported a reduced alcohol consumption (49.4 vs. 16.7 %; p = 0.004) after 6 months. CONCLUSION: The consideration of diversity with respect to cultural, migration-related, socio demographic und linguistic aspects improves the effectiveness of prevention measures.

Verbal fluency in focal epilepsy: a systematic review and meta-analysis.

Testing of verbal fluency is currently part of standard presurgical neuropsychological assessment for patients with focal epilepsy. However, to date no systematic review has been conducted on semantic (SVF) and phonemic verbal fluency (PVF) in this patient group. The present review compares verbal fluency between healthy control subjects and subgroups of adult presurgical patients with focal epilepsy according to lateralisation and localisation of the dysfunction. PubMed was searched with a comprehensive search string. Abstracts of all studies and full-texts of potentially relevant studies were screened. Study quality was assessed by independent raters according to predefined criteria. 39 studies were included. Meta-analyses were performed to compare SVF and PVF across groups of patients with temporal (TLE) and frontal lobe epilepsy (FLE) as well as healthy controls (HC). Both patients with left- and right sided TLE were impaired on SVF and PVF compared to HC. Patients with left-sided TLE were slightly more impaired than patients with right-sided TLE. Patients with FLE showed a larger impairment in PVF than patients with TLE, whereas on SVF there was no difference between FLE and TLE. For TLE comparisons the study pool seems to have been sufficient, whereas more studies are needed to verify results for FLE. Semantic verbal fluency might not differentiate between FLE and TLE. While verbal fluency impairment was anticipated, especially in left-sided TLE and FLE patients, the impairment in patients with right-sided TLE was larger than expected. Results are discussed with regard to neuropsychological theory and practice.

[Length of hospitalization for inpatient treatment of depression. Results of a multicentre study on the effects of a new treatment model]. / Verweildauer in der stationären Depressionsbehandlung. Ergebnisse einer Multicenterstudie zum Effekt eines neuen Behandlungsmodells.

BACKGROUND: Patients with depression are treated for a relatively long period as inpatients in Germany. A new treatment model with symptom-orientated release management, post-hospitalization treatment and standardized referral to outpatient therapists could be suitable to specifically shorten the hospital stay of patients who have already profited sufficiently from treatment. MATERIALS AND METHODS: The aim of the present study was to investigate the effects of a new treatment method (intervention group) with hospitalized depressive patients in comparison to a standard protocol (treatment-as-usual control group) on the length of stay as part of a pragmatic randomized, controlled multicentre study. The evaluation was made using covariance analysis. RESULTS: Of the 202 randomized patients 184 could be included in the analysis. The estimated marginal mean of the length of stay (n = 83) was 57.3 days (range 1-305 days, SE = 3.8) in the intervention group and (n = 101) 57.6 days (range: 6-196 days, SE = 3.5) in the control group. There were no significant statistical differences between the groups (p = 0.966). CONCLUSIONS: An effect of the new treatment model on the inpatient length of hospital stay in depressive patients could not be demonstrated.

Prediction of gene-phenotype associations in humans, mice, and plants using phenologs.

BACKGROUND: Phenotypes and diseases may be related to seemingly dissimilar phenotypes in other species by means of the orthology of underlying genes. Such "orthologous phenotypes," or "phenologs," are examples of deep homology, and may be used to predict additional candidate disease genes. RESULTS: In this work, we develop an unsupervised algorithm for ranking phenolog-based candidate disease genes through the integration of predictions from the k nearest neighbor phenologs, comparing classifiers and weighting functions by cross-validation. We also improve upon the original method by extending the theory to paralogous phenotypes. Our algorithm makes use of additional phenotype data--from chicken, zebrafish, and E. coli, as well as new datasets for C. elegans--establishing that several types of annotations may be treated as phenotypes. We demonstrate the use of our algorithm to predict novel candidate genes for human atrial fibrillation (such as HRH2, ATP4A, ATP4B, and HOPX) and epilepsy (e.g., PAX6 and NKX2-1). We suggest gene candidates for pharmacologically-induced seizures in mouse, solely based on orthologous phenotypes from E. coli. We also explore the prediction of plant gene-phenotype associations, as for the Arabidopsis response to vernalization phenotype. CONCLUSIONS: We are able to rank gene predictions for a significant portion of the diseases in the Online Mendelian Inheritance in Man database. Additionally, our method suggests candidate genes for mammalian seizures based only on bacterial phenotypes and gene orthology. We demonstrate that phenotype information may come from diverse sources, including drug sensitivities, gene ontology biological processes, and in situ hybridization annotations. Finally, we offer testable candidates for a variety of human diseases, plant traits, and other classes of phenotypes across a wide array of species.

RFX2 is broadly required for ciliogenesis during vertebrate development.

In Caenorhabditis elegans, the RFX (Daf19) transcription factor is a major regulator of ciliogenesis, controlling the expression of the many essential genes required for making cilia. In vertebrates, however, seven RFX genes have been identified. Bioinformatic analysis suggests that Rfx2 is among the closest homologues of Daf19. We therefore hypothesize that Rfx2 broadly controls ciliogenesis during vertebrate development. Indeed, here we show that Rfx2 in Xenopus is expressed preferentially in ciliated tissues, including neural tube, gastrocoel roof plate, epidermal multi-ciliated cells, otic vesicles, and kidneys. Knockdown of Rfx2 results in cilia-defective embryonic phenotypes and fewer or truncated cilia are observed in Rfx2 morphants. These results indicate that Rfx2 is broadly required for ciliogenesis in vertebrates. Furthermore, we show that Rfx2 is essential for expression of several ciliogenic genes, including TTC25, which we show here is required for ciliogenesis, HH signaling, and left-right patterning.

Global transcriptome changes underlying colony growth in the opportunistic human pathogen Aspergillus fumigatus.

Aspergillus fumigatus is the most common and deadly pulmonary fungal infection worldwide. In the lung, the fungus usually forms a dense colony of filaments embedded in a polymeric extracellular matrix. To identify candidate genes involved in this biofilm (BF) growth, we used RNA-Seq to compare the transcriptomes of BF and liquid plankton (PL) growth. Sequencing and mapping of tens of millions sequence reads against the A. fumigatus transcriptome identified 3,728 differentially regulated genes in the two conditions. Although many of these genes, including the ones coding for transcription factors, stress response, the ribosome, and the translation machinery, likely reflect the different growth demands in the two conditions, our experiment also identified hundreds of candidate genes for the observed differences in morphology and pathobiology between BF and PL. We found an overrepresentation of upregulated genes in transport, secondary metabolism, and cell wall and surface functions. Furthermore, upregulated genes showed significant spatial structure across the A. fumigatus genome; they were more likely to occur in subtelomeric regions and colocalized in 27 genomic neighborhoods, many of which overlapped with known or candidate secondary metabolism gene clusters. We also identified 1,164 genes that were downregulated. This gene set was not spatially structured across the genome and was overrepresented in genes participating in primary metabolic functions, including carbon and amino acid metabolism. These results add valuable insight into the genetics of biofilm formation in A. fumigatus and other filamentous fungi and identify many relevant, in the context of biofilm biology, candidate genes for downstream functional experiments.

Systematic discovery of nonobvious human disease models through orthologous phenotypes.

Biologists have long used model organisms to study human diseases, particularly when the model bears a close resemblance to the disease. We present a method that quantitatively and systematically identifies nonobvious equivalences between mutant phenotypes in different species, based on overlapping sets of orthologous genes from human, mouse, yeast, worm, and plant (212,542 gene-phenotype associations). These orthologous phenotypes, or phenologs, predict unique genes associated with diseases. Our method suggests a yeast model for angiogenesis defects, a worm model for breast cancer, mouse models of autism, and a plant model for the neural crest defects associated with Waardenburg syndrome, among others. Using these models, we show that SOX13 regulates angiogenesis, and that SEC23IP is a likely Waardenburg gene. Phenologs reveal functionally coherent, evolutionarily conserved gene networks-many predating the plant-animal divergence-capable of identifying candidate disease genes.

[Barriers in the attendance of health care interventions by immigrants]. / Subjektiv erlebte Barrieren von Personen mit Migrationshintergrund bei der Inanspruchnahme von Gesundheitsmaßnahmen.

AIM: Analysis of barriers regarding attendance at the health care system under consideration of cultural and migration-related factors. METHOD: Cross-sectional survey with immigrants from Turkey (n = 77), Spain (n = 67), Italy (n = 95) and German resettlers from the former Soviet Union (n = 196), recruited on migration and addiction services of the German Caritasverband, the Arbeiterwohlfahrt and migrant organizations. RESULTS: Spanish and Italian immigrants mainly search for help within their families and social environment. Immigrants from the former Soviet Union use home remedies and experience more linguistic difficulties as barriers for the use of health services, just like Turkish immigrants. Turkish immigrants reported feeling misunderstood regarding their cultural peculiarities by the expert staff as another main barrier. Other major influencing factors were German language proficiency and the subjective wellbeing in Germany. CONCLUSION: The consideration of cultural-related as well as linguistic factors in health care services is an essential contribution for improving health care of immigrants.

[Patient participation in medical decision making within an integrated health care system in Germany: results of a controlled cohort study]. / Patientenbeteiligung bei medizinischen Entscheidungen in der Integrierten Versorgung Gesundes Kinzigtal: Ergebnisse einer kontrollierten Kohortenstudie.

An integrated health care project called "Gesundes Kinzigtal" was conducted in a rural area in Germany. As part of the project, physicians were trained and other measures were taken to enhance patient involvement in medical decision making. As part of the external evaluation, various effects regarding patient involvement in medical decision making, patient involvement and information preference, decision confidence, patient satisfaction with ambulatory care and patient quality of life were examined. The data were gathered by means of a questionnaire on an annual basis between 2007 and 2009. Effects were compared between patients who were participating in the integrated care project and two control groups. Analyses are based on the data of 1,205 patients. Over time all outcomes decreased slightly, except for information preference and physical quality of life. No statistically significant intervention effects on patient involvement in medical decision making or any other outcome variable could be found. The intensity of the training was presumably too low to establish an enduring change in the physician-patient interaction.

The effects of nonpharmacological interventions on subjective memory complaints: a systematic review and meta-analysis.

BACKGROUND: Subjective memory complaints (SMC) in the absence of psychiatric or neurological disorders are common among older adults. Although increasing numbers of individuals are suffering from SMC, research into interventions alleviating SMC is sparse. The present systematic review was conducted in order to present a clearer picture of the quality, quantity and outcomes of SMC intervention research. METHODS: PubMed and PsychInfo were searched with a comprehensive search string delivering 4,496 hits. Abstracts and - if applicable - full texts of these studies were screened by independent raters according to predefined criteria. Fourteen relevant studies were included in the review. The categories of intervention were: conventional memory training (MT; n = 8), expectancy change (EC: cognitive restructuring, psychoeducation, etc.; n = 5), combined interventions (n = 5), physical training (n = 1), and physical and mental training combined (n = 2). The outcomes were: subjective memory measures, objective memory, depressive symptoms and well-being. RESULTS: EC, followed by combined interventions, was most efficient in influencing subjective memory. MT or physical and mental training combined were not efficient. On objective memory, MT was the only efficient intervention. No effects were found on depressive symptoms and well-being, with low numbers of studies in these comparisons. CONCLUSION: EC seems to be most efficient in influencing SMC, whereas in objective memory MT is the only effective intervention. Depressive symptoms or well-being do not seem to be influenced significantly by any of the interventions. To date, the number of high-quality publications on SMC interventions is relatively low. More randomized controlled trials including measures of depressive symptoms and well-being are needed.

Cluster-randomized controlled trial of dissemination strategies of an online quality improvement programme for alcohol-related disorders.

AIMS: This project investigated different dissemination strategies of an online quality improvement programme for alcohol-related disorders into routine care in South Baden and South Württemberg in Germany. METHODS: In a cluster-randomized controlled trial, 112 general practices were randomized into three groups. The first group (n = 43) received access to the online system and a training programme for the general practitioners (GPs). The second group (n = 42) additionally received education for the whole practice team. The third group (n = 27) acted as control and received only access to the online system. RESULTS: Two thousand six hundred and forty-seven practitioners were asked to take part in the study, and it was possible to randomize 112 (4%) practices. There were no significant differences concerning the use of the system between the groups: 41.9% of the GPs in the first group, 42.9% in the second group and 44.4% in the control group used the system. In terms of only the system users, 55.6% of the GPs in the first group, 33.3% in the second group and 8.3% in the control group used the system six times or more (P = 0.019). Diagnostic assessments made by the GPs in the groups differed substantially: 72.2% of diagnoses in the first group were correct, while this figure lay at 69.7% in the second group and 36.4% in the control group (P = 0.034). CONCLUSIONS: No effect of the additional training on the primary outcome (acceptance) was identified, but on two of the secondary outcomes. Further cost-effectiveness studies should investigate whether the effort involved in providing training additionally to the system is justifiable. The study is registered at ClinicalTrials.gov: NCT00314067. This article conforms to the guidelines in the Consolidated Standards of Reporting Trials (CONSORT) statement (Moher et al., 2001; Campbell et al., 2004).