Topical clobetasol for the treatment of toxic epidermal necrolysis: study protocol for a randomized controlled trial.

BackgroundToxic epidermal necrolysis (TEN) is a rare systemic allergic drug eruption with high patient mortality. Currently, no established treatments have been shown to be effective for TEN beyond supportive care. Prior studies of systemic corticosteroids have yielded conflicting data, with some showing a possible benefit and others reporting in increased mortality. However, topical steroids have shown promise for treatment of ocular sequelae of TEN, such as scarring and vision loss. We have designed a randomized controlled trial to evaluate topical clobetasol for treatment of the epidermal manifestations of TEN. In addition, we propose genetic studies to characterize the TEN transcriptome and alterations in cutaneous gene expression that might occur following topical steroid treatment.Methods/designThis split-body randomized, double-blind, placebo-controlled Phase IIa proof-of-concept trial will evaluate the safety and efficacy of once-daily topical clobetasol applied to the skin of patients with TEN. This multicenter trial will recruit a total of 15 patients between the ages of 12 and 85 from the University of California Davis Medical Center and Shriners Hospital for Children inpatient burn units. Designated treatment areas on opposite sides of the body will be treated with blinded clobetasol 0.05% ointment or control petrolatum ointment daily for 14 days. On day 3 of therapy, a biopsy will be taken from the treated area for genetic studies. The primary study aims will be to establish the safety of topical clobetasol treatment and determine the time to cessation of skin detachment for the control and clobetasol-treated areas. Secondary endpoints will evaluate efficacy using parameters such as time to 90% re-epithelialization and percentage of affected skin at 0, 3, 6, 9, 12 and 15 days. Genomic DNA and RNA will be obtained from biopsy samples, to characterize the TEN transcriptome and identify changes in gene expression after topical steroid treatment.DiscussionTopical steroids have shown promise for treating ocular complications of TEN, but to date have not been evaluated for cutaneous manifestations of the disease. This trial will investigate clinical and molecular outcomes of topical clobetasol application and hopefully provide insight into the disease pathophysiology.Trial registrationClinicalTrials.gov NCT02319616. https://clinicaltrials.gov/ct2/show/NCT02351037

Dietary supplementation with Bifidobacterium longum subsp. infantis (B. infantis) in healthy breastfed infants: study protocol for a randomised controlled trial.

BackgroundThe development of probiotics as therapies to cure or prevent disease lags far behind that of other investigational medications. Rigorously designed phase I clinical trials are nearly non-existent in the field of probiotic research, which is a contributing factor to this disparity. As a consequence, how to appropriately dose probiotics to study their efficacy is unknown. Herein we propose a novel phase I ascending dose trial of Bifidobacterium longum subsp. infantis (B. infantis) to identify the dose required to produce predominant gut colonisation in healthy breastfed infants at 6 weeks of age.Methods/designThis is a parallel-group, placebo-controlled, randomised, double-blind ascending dose phase I clinical trial of dietary supplementation with B. infantis in healthy breastfed infants. The objective is to determine the pharmacologically effective dose (ED) of B. infantis required to produce predominant (>50 %) gut colonisation in breastfed infants at 6 weeks of age. Successively enrolled infant groups will be randomised to receive two doses of either B. infantis or placebo on days 7 and 14 of life. Stool samples will be used to characterise the gut microbiota at increasing doses of B. infantis.DiscussionProbiotic supplementation has shown promising results for the treatment of a variety of ailments, but evidence-based dosing regimes are currently lacking. The ultimate goal of this trial is to establish a recommended starting dose of B. infantis for further efficacy-testing phase II trials designed to evaluate B. infantis for the prevention of atopic dermatitis and food allergies in at-risk children.Trial registrationClinicaltrials.gov # NCT02286999 , date of trial registration 23 October 2014

Challenges to reduce the ‘10/90 gap’: mental health research in Latin American and Caribbean countries

Razzouk D, Gallo C, Olifson S, Zorzetto R, Fiestas F, Poletti G, Mazzotti G, Levav I, Mari JJ. Challenges to reduce the ‘10/90 gap’: mental health research in Latin American and Caribbean countries

Risk of missing colorectal cancer with COVID-adapted diagnostic pathway using quantitative faecal immunochemical testing

Background: COVID-19 has brought an unprecedented challenge to healthcare services. The authors’ COVID-adapted pathway for suspected bowel cancer combines two quantitative faecal immunochemical tests (qFITs) with a standard CT scan with oral preparation (CT mini-prep). The aim of this study was to estimate the degree of risk mitigation and residual risk of undiagnosed colorectal cancer. Method: Decision-tree models were developed using a combination of data from the COVID-adapted pathway (April–May 2020), a local audit of qFIT for symptomatic patients performed since 2018, relevant data (prevalence of colorectal cancer and sensitivity and specificity of diagnostic tools) obtained from literature and a local cancer data set, and expert opinion for any missing data. The considered diagnostic scenarios included: single qFIT; two qFITs; single qFIT and CT mini-prep; two qFITs and CT mini-prep (enriched pathway). These were compared to the standard diagnostic pathway (colonoscopy or CT virtual colonoscopy (CTVC)). Results: The COVID-adapted pathway included 422 patients, whereas the audit of qFIT included more than 5000 patients. The risk of missing a colorectal cancer, if present, was estimated as high as 20.2 per cent with use of a single qFIT as a triage test. Using both a second qFIT and a CT mini-prep as add-on tests reduced the risk of missed cancer to 6.49 per cent. The trade-off was an increased rate of colonoscopy or CTVC, from 287 for a single qFIT to 418 for the double qFIT and CT mini-prep combination, per 1000 patients. Conclusion: Triage using qFIT alone could lead to a high rate of missed cancers. This may be reduced using CT mini-prep as an add-on test for triage to colonoscopy or CTVC

Innovation policies of Cyprus during the global economic crisis: Aligning financial institutions with National Innovation System

Previous research has overlooked the complementarity between National Innovation Systems and financial institutions. This paper extends the literature on National Innovation Systems, arguing that innovation policies should incorporate the particular needs of a nation’s innovation system and the current conditions of that nation’s financial environment. This development is important because the financial environment is malleable and subject to exogenous events, such as the recent global financial crisis. The relationship between a National Innovation System and the financial environment is presented through an analytical framework, which can be used to assess and instigate national innovation policies. The analytical framework is demonstrated using the case of Cyprus, which was on the frontline of the European debt crisis. By integrating the views of leaders from the Cypriot manufacturing and service sectors with widely available reports and indices concerning innovation performance, we demonstrate that the lack of a developed financial environment impedes national innovation performance. This research introduces policy and managerial implications for innovation, especially within the context of underdeveloped national innovation systems, which focus on improving innovation performance by enhancing the availability of financial instruments and the access that entrepreneurs have to them

Repurposing NGO data for better research outcomes: A scoping review of the use and secondary analysis of NGO data in health policy and systems research

Background Non-government organisations (NGOs) collect and generate vast amounts of potentially rich data, most of which are not used for research purposes. Secondary analysis of NGO data (their use and analysis in a study for which they were not originally collected) presents an important but largely unrealised opportunity to provide new research insights in critical areas including the evaluation of health policy and programmes. Methods A scoping review of the published literature was performed to identify the extent to which secondary analysis of NGO data has been used in health policy and systems research (HPSR). A tiered analytic approach provided a comprehensive overview and descriptive analyses of the studies which: 1) used data produced or collected by or about NGOs; 2) performed secondary analysis of the NGO data (beyond use of an NGO report as a supporting reference); 3) used NGO-collected clinical data. Results Of the 156 studies which performed secondary analysis of NGO-produced or collected data, 64% (n=100) used NGO-produced reports (e.g. to critique NGO activities and as a contextual reference) and 8% (n=13) analysed NGO-collected clinical data.. Of the studies, 55% investigated service delivery research topics, with 48% undertaken in developing countries and 17% in both developing and developed. NGO-collected clinical data enabled HPSR within marginalised groups (e.g. migrants, people in conflict-affected areas), with some limitations such as inconsistencies and missing data. Conclusion We found evidence that NGO-collected and produced data are most commonly perceived as a source of supporting evidence for HPSR and not as primary source data. However, these data can facilitate research in under-researched marginalised groups and in contexts that are hard to reach by academics, such as conflict-affected areas. NGO–academic collaboration could help address issues of NGO data quality to facilitate their more widespread use in research. Their use could enable relevant and timely research in the areas of health policy, programme evaluation and advocacy to improve health and reduce health inequalities, especially in marginalised groups and developing countries

Migrant children within Europe: a systematic review of children’s perspectives on their health experiences

Objectives: To review the extant literature in order to explore what is known about children’s own perspectives on the ir health experiences , focusing upon children and young people who have migrated into, and within, Europe. Study Design: A systematic review with narrative synthesis. Methods: A review of English language articles was performed in June 2016 using the following databases: Medline, CINAHL, Coc hrane and Web of Science. Included papers had to report data generated directly with children, up to 18 years of age, who had migrated across national borders into, or within, Europe during their own lifetimes. Extraction from articles was undertaken by a ll authors and quality assessment of included reviews was performed using the Mixed Methods Appraisal Tool ( MMAT ) . Results: The articles in the final dataset included research based on 4 broad areas: alcohol, smoking and substance use; diet, eating disorde rs and overweight; emotional, psychological and mental health issues and; children’s views and experiences of health and health services. The majority of studies were cross - sectional analytic or incidence or prevalence studies. Conclusion: There is a gene ral lack of clarity in the literature regarding the reporting of children’s own migration status. Children’s voices are often subsumed within those of their adult parents or carers. There is a need to promote more child - focussed research which gives voice to migrant children to better understand the complex and multidimensional factors that contribute to their (ill) health