Prevalence of anal fistulas in Europe: Systematic literature reviews and population-based database analysis

Introduction: Despite the fact that perianal fistulas are associated with significant morbidity and impaired quality of life, their prevalence in Europe is unknown. The aim of this study was to estimate the prevalence of perianal fistulas in Europe, overall and according to etiology. Methods: Two independent literature reviews were performed using different search strategies to maximize the identification of potentially relevant studies. Data from relevant articles were used to estimate the prevalence of perianal fistulas in Europe. The robustness of the estimate was evaluated using data from a large population-based database from the UK. Results: A total of 26 studies provided epidemiological data on perianal fistulas, of which 16 provided suitable data to estimate the prevalence. Estimations using these data yielded a total prevalence of 1.69 per 10,000 population. Cryptoglandular infection and Crohn’s disease (CD) were the predominant etiologies, with prevalence rates at 0.86 and 0.76 per 10,000 population, respectively. Comparison of prevalence data from the UK population-based database with the European population resulted in a standardized prevalence estimate of all perianal fistulas of 1.83 per 10,000 population, confirming the robustness of the literaturebased estimate. Conclusion: Although in terms of incidence cryptoglandular fistulas were clearly predominant, the prevalence of fistulas in CD and cryptoglandular infection appeared more balanced. This is due to the longer duration and higher frequency of relapses of fistulas in CD. The estimated prevalence implies that perianal fistulas meet the criteria to be considered as a rare condition in Europe (prevalence less than 5 per 10,000 population).This study was funded by Takeda Pharmaceutical U.S.A., Inc. and TiGenix SA

Cervical high-intensity intramedullary lesions in achondroplasia:Aetiology, prevalence and clinical relevance

In achondroplastic patients with slight complaints of medullary compression the cervical spinal cord regularly exhibits an intramedullary (CHII) lesion just below the craniocervical junction with no signs of focal compression on the cord. Currently, the prevalence of the lesion in the general achondroplastic population is studied and its origin is explored. Eighteen achondroplastic volunteers with merely no clinical signs of medullary compression were subjected to dynamic magnetic resonance imaging (MRI). The presence of a CHII lesion and craniocervical medullary compression in flexed and retroflexed craniocervical positions was explored. Several morphological characteristics of the craniocervical junction, possibly related to compression on the cord, were assessed. A CHII lesion was observed in 39% of the subjects and in only one of these was compression at the craniocervical junction present. Consequently, no correlation between the CHII lesion and compression could be established. None of the morphological characteristics demonstrated a correlation with the CHII lesion, except thinning of the cord at the site of the CHII lesion. CHII lesions are a frequent finding in achondroplasia, and are generally unaccompanied by clinical symptoms or compression on the cord. Further research focusing on the origin of CHII lesions and their clinical implications is warranted. aEuro cent MRI now reveals exquisite detail of the cervical spinal cord. aEuro cent Cervical cord lesions are observed in one third of the achondroplastic population. aEuro cent These lesions yield high signal intensity on T2 weighted MRI. aEuro cent They are generally unaccompanied by clinical symptoms or cord compression. aEuro cent Their aetiology is unclear and seems to be unrelated to mechanical causes

Comparative effectiveness of dipeptidyl peptidase-4 (DPP-4) inhibitors and human glucagon-like peptide-1 (GLP-1) analogue as add-on therapies to sulphonylurea among diabetes patients in the Asia-Pacific region: a systematic review

The prevalence of diabetes mellitus is rising globally, and it induces a substantial public health burden to the healthcare systems. Its optimal control is one of the most significant challenges faced by physicians and policy-makers. Whereas some of the established oral hypoglycaemic drug classes like biguanide, sulphonylureas, thiazolidinediones have been extensively used, the newer agents like dipeptidyl peptidase-4 (DPP-4) inhibitors and the human glucagon-like peptide-1 (GLP-1) analogues have recently emerged as suitable options due to their similar efficacy and favorable side effect profiles. These agents are widely recognized alternatives to the traditional oral hypoglycaemic agents or insulin, especially in conditions where they are contraindicated or unacceptable to patients. Many studies which evaluated their clinical effects, either alone or as add-on agents, were conducted in Western countries. There exist few reviews on their effectiveness in the Asia-Pacific region. The purpose of this systematic review is to address the comparative effectiveness of these new classes of medications as add-on therapies to sulphonylurea drugs among diabetic patients in the Asia-Pacific countries. We conducted a thorough literature search of the MEDLINE and EMBASE from the inception of these databases to August 2013, supplemented by an additional manual search using reference lists from research studies, meta-analyses and review articles as retrieved by the electronic databases. A total of nine randomized controlled trials were identified and described in this article. It was found that DPP-4 inhibitors and GLP-1 analogues were in general effective as add-on therapies to existing sulphonylurea therapies, achieving HbA1c reductions by a magnitude of 0.59–0.90% and 0.77–1.62%, respectively. Few adverse events including hypoglycaemic attacks were reported. Therefore, these two new drug classes represent novel therapies with great potential to be major therapeutic options. Future larger-scale research should be conducted among other Asia-Pacific region to evaluate their efficacy in other ethnic groups

Development and measurement of guidelines-based quality indicators of caesarean section care in the Netherlands: A RAND-modified delphi procedure and retrospective medical chart review

Background There is an ongoing discussion on the rising CS rate worldwide. Suboptimal guideline adherence may be an important contributor to this rise. Before improvement of care can be established, optimal CS care in different settings has to be defined. This study aimed to develop and measure quality indicators to determine guideline adherence and identify target groups for improvement of care with direct effect on caesarean section (CS) rates. Method Eighteen obstetricians and midwives participated in an expert panel for systematic CS quality indicator development according to the RAND-modified Delphi method. A multi-center study was performed and medical charts of 1024 women with a CS and a stratified and weighted randomly selected group of 1036 women with a vaginal delivery were analysed. Quality indicator frequency and adherence were scored in 2060 women with a CS or vaginal delivery. Results The expert panel developed 16 indicators on planned CS and 11 indicators on unplanned CS. Indicator adherence was calculated, defined as the number of women in a specific obstetrical situation in which care was performed as recommended in both planned and unplanned CS settings. The most frequently occurring obstetrical situations with low indicator adherence were: 1) suspected fetal distress (frequency 17%, adh

European multicenter study on antimicrobial resistance in bacteria isolated from companion animal urinary tract infections

BACKGROUND: There is a growing concern regarding the increase of antimicrobial resistant bacteria in companion animals. Yet, there are no studies comparing the resistance levels of these organisms in European countries. The aim of this study was to investigate geographical and temporal trends of antimicrobial resistant bacteria causing urinary tract infection (UTI) in companion animals in Europe. The antimicrobial susceptibility of 22 256 bacteria isolated from dogs and cats with UTI was determined. Samples were collected between 2008 and 2013 from 16 laboratories of 14 European countries. The prevalence of antimicrobial resistance of the most common bacteria was determined for each country individually in the years 2012-2013 and temporal trends of bacteria resistance were established by logistic regression. RESULTS: The aetiology of uropathogenic bacteria differed between dogs and cats. For all bacterial species, Southern countries generally presented higher levels of antimicrobial resistance compared to Northern countries. Multidrug-resistant Escherichia coli were found to be more prevalent in Southern countries. During the study period, the level of fluoroquinolone-resistant E. coli isolated in Belgium, Denmark, France and the Netherlands decreased significantly. A temporal increase in resistance to amoxicillin-clavulanate and gentamicin was observed among E. coli isolates from the Netherlands and Switzerland, respectively. Other country-specific temporal increases were observed for fluoroquinolone-resistant Proteus spp. isolated from companion animals from Belgium. CONCLUSIONS: This work brings new insights into the current status of antimicrobial resistance in bacteria isolated from companion animals with UTI in Europe and reinforces the need for strategies aiming to reduce resistance

Kinetic CRAC uncovers a role for Nab3 in determining gene expression profiles during stress

RNA-binding proteins play a key role in shaping gene expression profiles during stress, however, little is known about the dynamic nature of these interactions and how this influences the kinetics of gene expression. To address this, we developed kinetic cross-linking and analysis of cDNAs (\u3c7CRAC), an ultraviolet cross-linking method that enabled us to quantitatively measure the dynamics of protein\u2013RNA interactions in vivo on a minute time-scale. Here, using \u3c7CRAC we measure the global RNA-binding dynamics of the yeast transcription termination factor Nab3 in response to glucose starvation. These measurements reveal rapid changes in protein\u2013RNA interactions within 1\u2009min following stress imposition. Changes in Nab3 binding are largely independent of alterations in transcription rate during the early stages of stress response, indicating orthogonal transcriptional control mechanisms. We also uncover a function for Nab3 in dampening expression of stress-responsive genes. \u3c7CRAC has the potential to greatly enhance our understanding of in vivo dynamics of protein\u2013RNA interactions

Diabetes self-management arrangements in Europe: a realist review to facilitate a project implemented in six countries

Background: Self-management of long term conditions can promote quality of life whilst delivering benefits to the financing of health care systems. However, rarely are the meso-level influences, likely to be of direct relevance to these desired outcomes, systematically explored. No specific international guidelines exist suggesting the features of the most appropriate structure and organisation of health care systems within which to situate self-management approaches and practices. This review aimed to identify the quantitative literature with regard to diabetes self-management arrangements currently in place within the health care systems of six countries (The United Kingdom, The Netherlands, Norway, Spain, Bulgaria, and Greece) and explore how these are integrated into the broader health care and welfare systems in each country. Methods: The methodology for a realist review was followed. Publications of interest dating from 2000 to 2013 were identified through appropriate MeSH terms by a systematic search in six bibliographic databases. A search diary was maintained and the studies were assessed for their quality and risk of bias. Results: Following the multi-step search strategy, 56 studies were included in the final review (the majority from the UK) reporting design methods and findings on 21 interventions and programmes for diabetes and chronic disease self-management. Most (11/21, 52%) of the interventions were designed to fit within the context of primary care. The majority (11/21, 52%) highlighted behavioural change as an important goal. Finally, some (5/21, 24%) referred explicitly to Internet-based tools. Conclusions: This review is based on results which are derived from a total of at least 5,500 individuals residing in the six participating countries. It indicates a policy shift towards patient-centred self-management of diabetes in a primary care context. The professional role of diabetes specialist nurses, the need for multidisciplinary approaches and a focus on patient education emerge as fundamental principles in the design of relevant programmes. Socio-economic circumstances are relevant to the capacity to self-manage and suggest that any gains and progress will be hard to maintain during economic austerity. This realist review should be interpreted within the wider context of a whole systems approach regarding self-care support and chronic illness management

Cluster Headache Genomewide Association Study and Meta-Analysis Identifies Eight Loci and Implicates Smoking as Causal Risk Factor

Objective: The objective of this study was to aggregate data for the first genomewide association study meta-analysis of cluster headache, to identify genetic risk variants, and gain biological insights. Methods: A total of 4,777 cases (3,348 men and 1,429 women) with clinically diagnosed cluster headache were recruited from 10 European and 1 East Asian cohorts. We first performed an inverse-variance genomewide association meta-analysis of 4,043 cases and 21,729 controls of European ancestry. In a secondary trans-ancestry meta-analysis, we included 734 cases and 9,846 controls of East Asian ancestry. Candidate causal genes were prioritized by 5 complementary methods: expression quantitative trait loci, transcriptome-wide association, fine-mapping of causal gene sets, genetically driven DNA methylation, and effects on protein structure. Gene set and tissue enrichment analyses, genetic correlation, genetic risk score analysis, and Mendelian randomization were part of the downstream analyses. Results: The estimated single nucleotide polymorphism (SNP)-based heritability of cluster headache was 14.5%. We identified 9 independent signals in 7 genomewide significant loci in the primary meta-analysis, and one additional locus in the trans-ethnic meta-analysis. Five of the loci were previously known. The 20 genes prioritized as potentially causal for cluster headache showed enrichment to artery and brain tissue. Cluster headache was genetically correlated with cigarette smoking, risk-taking behavior, attention deficit hyperactivity disorder (ADHD), depression, and musculoskeletal pain. Mendelian randomization analysis indicated a causal effect of cigarette smoking intensity on cluster headache. Three of the identified loci were shared with migraine. Interpretation: This first genomewide association study meta-analysis gives clues to the biological basis of cluster headache and indicates that smoking is a causal risk factor