Barrett's oesophagus and oesophageal cancer following oesophageal atresia repair: a systematic review

BACKGROUND: Concern exists that patients born with oesophageal atresia (OA) may be at high risk for Barrett's oesophagus (BO), a known malignant precursor to the development of oesophageal adenocarcinoma. Screening endoscopy has a role in early BO identification but is not universal in this population. This study aimed to determine prevalence of BO after OA repair surgery, to quantify the magnitude of this association and inform the need for screening and surveillance. METHODS: A systematic review, undertaken according to PRISMA guidelines, was preregistered on PROSPERO (CRD42017081001). PubMed and EMBASE were interrogated using a standardized search strategy on 31 July 2020. Included papers, published in English, reported either: one or more patients with either BO (gastric/intestinal metaplasia) or oesophageal cancer in patients born with OA; or long-term (greater than 2 years) follow-up after OA surgery with or without endoscopic screening or surveillance. RESULTS: Some 134 studies were identified, including 19 case reports or series and 115 single- or multi-centre cohort studies. There were 13 cases of oesophageal cancer (9 squamous cell carcinoma, 4 adenocarcinoma) with a mean age at diagnosis of 40.5 (range 20-47) years. From 6282 patients under long-term follow-up, 317 patients with BO were reported. Overall prevalence of BO was 5.0 (95 per cent c.i. 4.5 to 5.6) per cent, with a mean age at detection of 13.8 years (range 8 months to 56 years). Prevalence of BO in series reporting endoscopic screening or surveillance was 12.8 (95 per cent c.i. 11.3 to 14.5) per cent. CONCLUSION: Despite a limited number of cancers, the prevalence of BO in patients born with OA is relatively high. While limited by the quality of available evidence, this review suggests endoscopic screening and surveillance may be warranted, but uncertainties remain over the design and effectiveness of any putative programme

A Toolkit to assess health needs for congenital disorders in low- and middle-income countries: an instrument for public health action.

BACKGROUND: In 2010 the World Health Assembly called for action to improve the care and prevention of congenital disorders, noting that technical guidance would be required for this task, especially in low- and middle-income countries. Responding to this call, we have developed a freely available web-accessible Toolkit for assessing health needs for congenital disorders. METHODS: Materials for the Toolkit website (http://toolkit.phgfoundation.org) were prepared by an iterative process of writing, discussion and modification by the project team, with advice from external experts. A customized database was developed using epidemiological, demographic, socio-economic and health-services data from a range of validated sources. Document-processing and data integration software combines data from the database with a template to generate topic- and country-specific Calculator documents for quantitative analysis. RESULTS: The Toolkit guides users through selection of topics (including both clinical conditions and relevant health services), assembly and evaluation of qualitative and quantitative information, assessment of the potential effects of selected interventions, and planning and prioritization of actions to reduce the risk or prevalence of congenital disorders. CONCLUSIONS: The Toolkit enables users without epidemiological or public health expertise to undertake health needs assessment as a prerequisite for strategic planning in relation to congenital disorders in their country or region

What do we really know about the appropriateness of radiation emitting imaging for low back pain in primary and emergency care? A systematic review and meta-analysis of medical record reviews

Background Since 2000, guidelines have been consistent in recommending when diagnostic imaging for low back pain should be obtained to ensure patient safety and reduce unnecessary tests. This systematic review and meta-analysis was conducted to determine the pooled proportion of CT and x-ray imaging of the lumbar spine that were considered appropriate in primary and emergency care. Methods Pubmed, CINAHL, The Cochrane Database of Systematic Reviews and Embase were searched for synonyms of “low back pain”, “guidelines”, and “adherence” that were published after 2000. Titles, abstracts, and full texts were reviewed for inclusion with forward and backward tracking on included studies. Included studies had data extracted and synthesized. Risk of bias was performed on all studies, and GRADE was performed on included studies that provided data on CT and x-ray separately. A random effect, single proportion meta-analysis model was used. Results Six studies were included in the descriptive synthesis, and 5 studies included in the meta-analysis. Five of the 6 studies assessed appropriateness of x-rays; two of the six studies assessed appropriateness of CTs. The pooled estimate for appropriateness of x-rays was 43% (95% CI: 30%, 56%) and the pooled estimate for appropriateness of CTs was 54% (95% CI: 51%, 58%). Studies did not report adequate information to fulfill the RECORD checklist (reporting guidelines for research using observational data). Risk of bias was high in 4 studies, moderate in one, and low in one. GRADE for x-ray appropriateness was low-quality and for CT appropriateness was very-low-quality. Conclusion While this study determined a pooled proportion of appropriateness for both x-ray and CT imaging for low back pain, there is limited confidence in these numbers due to the downgrading of the evidence using GRADE. Further research on this topic is needed to inform our understanding of x-ray and CT appropriateness in order to improve healthcare systems and decrease patient harms

Leg disorders in broiler chickens : prevalence, risk factors and prevention

Broiler (meat) chickens have been subjected to intense genetic selection. In the past 50 years, broiler growth rates have increased by over 300% (from 25 g per day to 100 g per day). There is growing societal concern that many broiler chickens have impaired locomotion or are even unable to walk. Here we present the results of a comprehensive survey of commercial flocks which quantifies the risk factors for poor locomotion in broiler chickens.We assessed the walking ability of 51,000 birds, representing 4.8 million birds within 176 flocks.We also obtained information on approximately 150 different management factors associated with each flock. At a mean age of 40 days, over 27.6% of birds in our study showed poor locomotion and 3.3% were almost unable to walk. The high prevalence of poor locomotion occurred despite culling policies designed to remove severely lame birds from flocks. We show that the primary risk factors associated with impaired locomotion and poor leg health are those specifically associated with rate of growth. Factors significantly associated with high gait score included the age of the bird (older birds), visit (second visit to same flock), bird genotype, not feeding whole wheat, a shorter dark period during the day, higher stocking density at the time of assessment, no use of antibiotic, and the use of intact feed pellets. The welfare implications are profound. Worldwide approximately 261010 broilers are reared within similar husbandry systems.We identify a range of management factors that could be altered to reduce leg health problems, but implementation of these changes would be likely to reduce growth rate and production. A debate on the sustainability of current practice in the production of this important food source is required

Early Economic Evaluation of Diagnostic Technologies: Experiences of the NIHR Diagnostic Evidence Co-operatives

Diagnostic tests are expensive and time-consuming to develop. Early economic evaluation using decision modeling can reduce commercial risk by providing early evidence on cost-effectiveness. The National Institute for Health Research Diagnostic Evidence Co-operatives (DECs) was established to catalyze evidence generation for diagnostic tests by collaborating with commercial developers; DEC researchers have consequently made extensive use of early modeling. The aim of this article is to summarize the experiences of the DECs using early modeling for diagnostics. We draw on 8 case studies to illustrate the methods, highlight methodological strengths and weaknesses particular to diagnostics, and provide advice. The case studies covered diagnosis, screening, and treatment stratification. Treatment effectiveness was a crucial determinant of cost-effectiveness in all cases, but robust evidence to inform this parameter was sparse. This risked limiting the usability of the results, although characterization of this uncertainty in turn highlighted the value of further evidence generation. Researchers evaluating early models must be aware of the importance of treatment effect evidence when reviewing the cost-effectiveness of diagnostics. Researchers planning to develop an early model of a test should also 1) consult widely with clinicians to ensure the model reflects real-world patient care; 2) develop comprehensive models that can be updated as the technology develops, rather than taking a “quick and dirty” approach that may risk producing misleading results; and 3) use flexible methods of reviewing evidence and evaluating model results, to fit the needs of multiple decision makers. Decision models can provide vital information for developers at an early stage, although limited evidence mean researchers should proceed with caution

Chronology protection in stationary three-dimensional spacetimes

We study chronology protection in stationary, rotationally symmetric spacetimes in 2+1 dimensional gravity, focusing especially on the case of negative cosmological constant. We show that in such spacetimes closed timelike curves must either exist all the way to the boundary or, alternatively, the matter stress tensor must violate the null energy condition in the bulk. We also show that the matter in the closed timelike curve region gives a negative contribution to the conformal weight from the point of view of the dual conformal field theory. We illustrate these properties in a class of examples involving rotating dust in anti-de Sitter space, and comment on the use of the AdS/CFT correspondence to study chronology protection.Comment: 20 pages. V2: minor corrections, Outlook expanded, references added, published versio

The over-reset phenomenon in Ta2O5 RRAM device investigated by the RTN-based defect probing technique

IEEE Despite the tremendous efforts in the past decade devoted to the development of filamentary resistive-switching devices (RRAM), there is still a lack of in-depth understanding of its over-reset phenomenon. At higher reset stop voltages that exceed a certain threshold, the resistance at high resistance state reduces, leading to an irrecoverable window reduction. The over-reset phenomenon limits the maximum resistance window that can be achieved by using a higher Vreset, which also degrades its potential in applications such as multi-level memory and neuromorphic synapses. In this work, the over-reset is investigated by cyclic reset operations with incremental stop voltages, and is explained by defect generation in the filament constriction region of Ta2O5 RRAM devices. This is supported by the statistical spatial defects profile obtained from the random telegraph noise based defect probing technique. The impact of forming compliance current on the over-reset is also evaluated

Takayasu's arteritis associated with Crohn's disease: a case report

<p>Abstract</p> <p>Introduction</p> <p>The simultaneous presence of Takayasu's arteritis and Crohn's disease in a patient seems to be rare. To our knowledge, no patient with the combination of Crohn's disease and Takayasu's arteritis has been reported from our region.</p> <p>Case presentation</p> <p>Herein we present the case of a 22-year-old Iranian woman previously diagnosed as Crohn's disease and who had subsequently developed Takayasu's arteritis.</p> <p>Conclusion</p> <p>Clinical suspicion, proper imaging, and consideration of the differential diagnosis are important for the correct diagnosis and management of patients with this coincidence.</p

Delivery of sTRAIL variants by MSCs in combination with cytotoxic drug treatment leads to p53-independent enhanced antitumor effects

Mesenchymal stem cells (MSCs) are able to infiltrate tumor tissues and thereby effectively deliver gene therapeutic payloads. Here, we engineered murine MSCs (mMSCs) to express a secreted form of the TNF-related apoptosis-inducing ligand (TRAIL), which is a potent inducer of apoptosis in tumor cells, and tested these MSCs, termed MSC.sTRAIL, in combination with conventional chemotherapeutic drug treatment in colon cancer models. When we pretreated human colorectal cancer HCT116 cells with low doses of 5-fluorouracil (5-FU) and added MSC.sTRAIL, we found significantly increased apoptosis as compared with single-agent treatment. Moreover, HCT116 xenografts, which were cotreated with 5-FU and systemically delivered MSC.sTRAIL, went into remission. Noteworthy, this effect was protein 53 (p53) independent and was mediated by TRAIL-receptor 2 (TRAIL-R2) upregulation, demonstrating the applicability of this approach in p53-defective tumors. Consequently, when we generated MSCs that secreted TRAIL-R2-specific variants of soluble TRAIL (sTRAIL), we found that such engineered MSCs, labeled MSC.sTRAIL DR5, had enhanced antitumor activity in combination with 5-FU when compared with MSC.sTRAIL. In contrast, TRAIL-resistant pancreatic carcinoma PancTu1 cells responded better to MSC.sTRAIL DR4 when the antiapoptotic protein XIAP (X-linked inhibitor of apoptosis protein) was silenced concomitantly. Taken together, our results demonstrate that TRAIL-receptor selective variants can potentially enhance the therapeutic efficacy of MSC-delivered TRAIL as part of individualized and tumor-specific combination treatments. © 2013 Macmillan Publishers Limited All rights reserved