A Case Report of Successful Management of Clostridium Difficile Colitis with Antegrade Fidaxomicin Through A Mucous Fistula Obviating the Need for Subtotal Colectomy.

Introduction Clostridium difficile is the most common cause of healthcare-associated infections and can have devastating morbidity and mortality. Traditional treatment algorithms involve intravenous metronidazole and enteric metronidazole or vancomycin. Fidaxomicin (DificidR) targets “switch regions” within RNA polymerases and effectively kills clostridium difficile bacteria and is typically administered orally primarily or through a naso/oro-gastric conduit. Presentation of case 55-year-old with a recent elective surgical procedure was hospitalized with multifocal pneumonia and subsequently developed clostridium difficile colitis. This patient failed the standard medical therapy for clostridium difficile colitis, decompensated and required surgical exploration, partial colectomy and mucous fistula creation. Following her surgery, her clinical condition improved and her colitis resolved with the antegrade administration of fidaxomicin through her mucous fistula. Discussion Fidaxomicin is a newer to market therapeutic agent that has been shown to be effective in the treatment of clostridium difficile colitis. Previously studies have shown benefit of oral fidaxomicin therapy for fulminant clostridium difficile but our study case report describes the index case of topical fidaxomicin through a mucous fistula. Conclusion In our case of fulminant clostridium difficile colitis, Fidaxomicin administered in an antegrade fashion through a mucous fistula may have reduced the need for total colectomy in the treatment of fulminant clostridium difficile colitis

Standardization of electroencephalography for multi-site, multi-platform and multi-investigator studies: Insights from the canadian biomarker integration network in depression

Subsequent to global initiatives in mapping the human brain and investigations of neurobiological markers for brain disorders, the number of multi-site studies involving the collection and sharing of large volumes of brain data, including electroencephalography (EEG), has been increasing. Among the complexities of conducting multi-site studies and increasing the shelf life of biological data beyond the original study are timely standardization and documentation of relevant study parameters. We presentthe insights gained and guidelines established within the EEG working group of the Canadian Biomarker Integration Network in Depression (CAN-BIND). CAN-BIND is a multi-site, multi-investigator, and multiproject network supported by the Ontario Brain Institute with access to Brain-CODE, an informatics platform that hosts a multitude of biological data across a growing list of brain pathologies. We describe our approaches and insights on documenting and standardizing parameters across the study design, data collection, monitoring, analysis, integration, knowledge-translation, and data archiving phases of CAN-BIND projects. We introduce a custom-built EEG toolbox to track data preprocessing with open-access for the scientific community. We also evaluate the impact of variation in equipment setup on the accuracy of acquired data. Collectively, this work is intended to inspire establishing comprehensive and standardized guidelines for multi-site studies

The transition of adolescents with juvenile idiopathic arthritis or epilepsy from paediatric health-care services to adult health-care services: A scoping review of the literature and a synthesis of the evidence

Young people with long-term health conditions (LTCs) can face challenges when making the transition to adult health services. This paper sought to identify studies that assess and explore transitional care for young people with LTCs. Two conditions were used as exemplars: juvenile idiopathic arthritis (JIA) and epilepsy. A scoping review of the literature was conducted by using search terms to search for papers in English between 2001 and 2016 concerning transitional care on four databases. Qualitative papers were reviewed and synthesized using thematic analysis. Quantitative papers using health outcomes were also synthesized. Twenty-eight papers were selected for review. Despite the wealth of literature concerning aspects of transitional care that are key to a successful transition for young people with JIA or epilepsy, there is a paucity of outcomes that define ‘successful’ transition and consequently a lack of reliable research evaluating the effectiveness of transitional care interventions to support young people moving to adult health services

Recombinant anticoccidial vaccines - a cup half full?

Eimeria species parasites can cause the disease coccidiosis, most notably in chickens. The occurrence of coccidiosis is currently controlled through a combination of good husbandry, chemoprophylaxis and/or live parasite vaccination; however, scalable, cost-effective subunit or recombinant vaccines are required. Many antigens have been proposed for use in novel anticoccidial vaccines, supported by the capacity to reduce disease severity or parasite replication, increase body weight gain in the face of challenge or improve feed conversion under experimental conditions, but none has reached commercial development. Nonetheless, the protection against challenge induced by some antigens has been within the lower range described for the ionophores against susceptible isolates or current live vaccines prior to oocyst recycling. With such levels of efficacy it may be that combinations of anticoccidial antigens already described are sufficient for development as novel multi-valent vaccines, pending identification of optimal delivery systems. Selection of the best antigens to be included in such vaccines can be informed by knowledge defining the natural occurrence of specific antigenic diversity, with relevance to the risk of immediate vaccine breakthrough, and the rate at which parasite genomes can evolve new diversity. For Eimeria, such data are now becoming available for antigens such as apical membrane antigen 1 (AMA1) and immune mapped protein 1 (IMP1) and more are anticipated as high-capacity, high-throughput sequencing technologies become increasingly accessible

Development of the Liverpool Adverse Drug Reaction Avoidability Assessment Tool

Aim To develop and test a new tool to assess the avoidability of adverse drug reactions that is suitable for use in paediatrics but which is also applicable to a variety of other settings. Methods The study involved multiple phases. Preliminary work involved using the Hallas scale and a modification of the existing Hallas scale, to assess two different sets of adverse drug reaction (ADR) case reports. Phase 1 defined, modified and refined a new tool using multidisciplinary teams. Phase 2 involved the assessment of 50 ADR case reports from a prospective study of paediatric inpatients by individual assessors. Phase 3 compared assessments with the new tool for individuals and groups in comparison to the ‘gold standard’ (the avoidability outcome set by a panel of senior investigators: an experienced clinical pharmacologist, paediatrician and pharmacist). Main Outcome Measures Inter-rater reliability (IRR), measure of disagreement and utilization of avoidability categories. Results Preliminary work—Pilot phase: results for the original Hallas cases were fair and pairwise kappa scores ranged from 0.21 to 0.36. Results for the modified Hallas cases were poor, pairwise kappa scores ranged from 0.06 to 0.16. Phase 1: on initial use of the new tool, agreement between the two multidisciplinary groups was found on 13/20 cases with a kappa score of 0.29 (95% CI -0.04 to 0.62). Phase 2: the assessment of 50 ADR case reports by six individual reviewers yielded pairwise kappa scores ranging from poor to good 0.12 to 0.75 and percentage exact agreement (%EA) ranged from 52–90%. Phase 3: Percentage exact agreement ranged from 35–70%. Overall, individuals had better agreement with the ‘gold standard’. Conclusion Avoidability assessment is feasible but needs careful attention to methods. The Liverpool ADR avoidability assessment tool showed mixed IRR. We have developed and validated a method for assessing the avoidability of ADRs that is transparent, more objective than previous methods and that can be used by individuals or groups

Formation of a conceptual framework during the development of a patient-reported outcome measure for early gastrointestinal recovery: Phase I of the PRO-diGi study

Aim: Patients admitted to hospital for abdominal surgery often experience gastrointestinal dysfunction. Many studies have reported outcomes following gastrointestinal dysfunction, yet there is no unified definition of recovery or a validated patient-reported outcome measure (PROM). The first stage of PROM development requires formation of a conceptual framework to identify key themes to patients. The aim of this study was to utilize semistructured interviews to identify core themes and concepts relevant to patients to facilitate development of a conceptual framework. Method: Adult patients admitted to hospital for major gastrointestinal, urological or gynaecological surgery, in an emergency or elective setting, were eligible to participate. Patients treated nonoperatively for small bowel obstruction were also eligible. Interviews were conducted by telephone, audio-recorded, transcribed, coded and analysed using NVivo software by two researchers and reviewed by lay members of the steering group. Interviews continued until data saturation was reached. Ethical approval was gained prior to interviews (21/WA/0231). Results: Twenty nine interviews were completed (17 men, median age 64 years) across three specialties (20 gastrointestinal, six gynaecological, three urological). Two overarching themes of ‘general recovery’ and ‘gastrointestinal symptoms’ were identified. General recovery included three themes: ‘life impact’, ‘mental impact’, including anxiety, and ‘physical impact’, including fatigue. Gastrointestinal symptoms included three themes: ‘abdominal symptoms’ such as pain, ‘diet and appetite’ and ‘expulsory function’, such as stool frequency. A total of 18 gastrointestinal symptoms were identified during patient recovery—many of which lasted several weeks following discharge. Conclusion: This study reports a range of gastrointestinal and nongastrointestinal symptoms experienced by patients during early gastrointestinal recovery. Identified symptoms have been synthesized into a conceptual framework to enable development of a definitive PROM for early gastrointestinal recovery

Genomic epidemiology reveals geographical clustering of multidrug-resistant Escherichia coli ST131 associated with bacteraemia in Wales

Antibiotic resistance is a significant global public health concern. Uropathogenic Escherichia coli sequence type (ST)131, a widely prevalent multidrug-resistant clone, is frequently associated with bacteraemia. This study investigates third-generation cephalosporin resistance in bloodstream infections caused by E. coli ST131. From 2013-2014 blood culture surveillance in Wales, 142 E. coli ST131 genomes were studied alongside global data. All three major ST131 clades were represented across Wales, with clade C/H30 predominant (n = 102/142, 71.8%). Consistent with global findings, Welsh strains of clade C/H30 contain β-lactamase genes from the blaCTX-M-1 group (n = 65/102, 63.7%), which confer resistance to third-generation cephalosporins. Most Welsh clade C/H30 genomes belonged to sub-clade C2/H30Rx (58.3%). A Wales-specific sub-lineage, named GB-WLS.C2, diverged around 1996-2000. An introduction to North Wales around 2002 led to a localised cluster by 2009, depicting limited genomic diversity within North Wales. This investigation emphasises the value of genomic epidemiology, allowing the detection of genetically similar strains in local areas, enabling targeted and timely public health interventions