Factors Predicting Long-term Outcome and the Need for Surgery in Graves Orbitopathy: Extended Follow-up From the CIRTED Trial

UNLABELLED: Graves Orbitopathy is both disabling and disfiguring. Medical therapies to reduce inflammation are widely used, but there is limited trial data beyond 18 months of follow-up. METHODS: 3 year follow-up of a subset of the CIRTED trial (N=68) which randomized patients to receive high dose oral steroid with azathioprine/placebo and radiotherapy/sham radiotherapy. RESULTS: Data were available at 3 years from 68 of 126 randomised subjects (54%). No additional benefit was seen at 3 years for patients randomized to azathioprine or radiotherapy with regard to a Binary Clinical Composite Outcome Measure, modified EUGOGO score or Ophthalmopathy Index.Clinical Activity Score (CAS), Ophthalmopathy Index and Total Eye Score improved over 3 years (p<0.001). However, quality of life at 3 years remained poor. Of 64 individuals with available surgical outcome data, 24/64 (37.5%) required surgical intervention. Disease duration of greater than 6 months before treatment was associated with increased need for surgery OR=16.8 (95%CI 2.95, 95.0) p=0.001. Higher baseline levels of CAS, Ophthalmopathy Index and Total Eye Score but not early improvement in CAS were associated with increased requirement for surgery. CONCLUSION: In this long-term follow-up from a clinical trial, 3 year outcomes remained suboptimal with ongoing poor quality of life and high numbers requiring surgery. Importantly, reduction in CAS in the first year, a commonly used surrogate outcome measure, was not associated with improved long-term outcomes

5-Hydroxytryptamine receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

oai:ojs.pkp.sfu.ca:article/31555-HT receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on 5-HT receptors [194] and subsequently revised [176]) are, with the exception of the ionotropic 5-HT3 class, GPCRs where the endogenous agonist is 5-hydroxytryptamine. The diversity of metabotropic 5-HT receptors is increased by alternative splicing that produces isoforms of the 5-HT2A (non-functional), 5-HT2C (non-functional), 5-HT4, 5-HT6 (non-functional) and 5-HT7 receptors. Unique amongst the GPCRs, RNA editing produces 5-HT2C receptor isoforms that differ in function, such as efficiency and specificity of coupling to Gq/11 and also pharmacology [40, 482]. Most 5-HT receptors (except 5-ht1e and 5-ht5b) play specific roles mediating functional responses in different tissues (reviewed by [463, 382])

5-Hydroxytryptamine receptors in GtoPdb v.2023.1

5-HT receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on 5-HT receptors [198] and subsequently revised [180]) are, with the exception of the ionotropic 5-HT3 class, GPCRs where the endogenous agonist is 5-hydroxytryptamine. The diversity of metabotropic 5-HT receptors is increased by alternative splicing that produces isoforms of the 5-HT2A (non-functional), 5-HT2C (non-functional), 5-HT4, 5-HT6 (non-functional) and 5-HT7 receptors. Unique amongst the GPCRs, RNA editing produces 5-HT2C receptor isoforms that differ in function, such as efficiency and specificity of coupling to Gq/11 and also pharmacology [40, 491]. Most 5-HT receptors (except 5-ht1e and 5-ht5b) play specific roles mediating functional responses in different tissues (reviewed by [471, 387])

Implementation of child-centred outcome measures in routine paediatric healthcare practice: a systematic review

Background: Person-centred outcome measures (PCOMs) are commonly used in routine adult healthcare to measure and improve outcomes, but less attention has been paid to PCOMs in children’s services. The aim of this systematic review is to identify and synthesise existing evidence of the determinants, strategies, and mechanisms that influence the implementation of PCOMs into paediatric healthcare practice. Methods: The review was conducted and reported in accordance with PRISMA guidelines. Databased searched included CINAHL, Embase, Medline, and PsycInfo. Google scholar was also searched for grey literature on 25th March 2022. Studies were included if the setting was a children’s healthcare service, investigating the implementation or use of an outcome measure or screening tool in healthcare practice, and reported outcomes relating to use of a measure. Data were tabulated and thematically analysed through deductive coding to the constructs of the adapted-Consolidated Framework for Implementation Research (CFIR). Results were presented as a narrative synthesis, and a logic model developed. Results: We retained 69 studies, conducted across primary (n = 14), secondary (n = 13), tertiary (n = 37), and community (n = 8) healthcare settings, including both child self-report (n = 46) and parent-proxy (n = 47) measures. The most frequently reported barriers to measure implementation included staff lack of knowledge about how the measure may improve care and outcomes; the complexity of using and implementing the measure; and a lack of resources to support implementation and its continued use including funding and staff. The most frequently reported facilitators of implementation and continued use include educating and training staff and families on: how to implement and use the measure; the advantages of using PCOMs over current practice; and the benefit their use has on patient care and outcomes. The resulting logic model presents the mechanisms through which strategies can reduce the barriers to implementation and support the use of PCOMs in practice. Conclusions: These findings can be used to support the development of context-specific implementation plans through a combination of existing strategies. This will enable the implementation of PCOMs into routine paediatric healthcare practice to empower settings to better identify and improve child-centred outcomes. Trial registration: Prospero CRD 42022330013

Evidence and rationale for the World Health Organization recommended standards for Japanese encephalitis surveillance

<p>Abstract</p> <p>Background</p> <p>Japanese encephalitis (JE) is the most important form of viral encephalitis in Asia. Surveillance for the disease in many countries has been limited. To improve collection of accurate surveillance data in order to increase understanding of the full impact of JE and monitor control programs, World Health Organization (WHO) Recommended Standards for JE Surveillance have been developed. To aid acceptance of the Standards, we describe the process of development, provide the supporting evidence, and explain the rationale for the recommendations made in the document.</p> <p>Methods</p> <p>A JE Core Working Group was formed in 2002 and worked on development of JE surveillance standards. A series of questions on specific topics was initially developed. A literature review was undertaken and the findings were discussed and documented. The group then prepared a draft document, with emphasis placed on the feasibility of implementation in Asian countries. A field test version of the Standards was published by WHO in January 2006. Feedback was then sought from countries that piloted the Standards and from public health professionals in forums and individual meetings to modify the Standards accordingly.</p> <p>Results</p> <p>After revisions, a final version of the JE surveillance standards was published in August 2008. The supporting information is presented here together with explanations of the rationale and levels of evidence for specific recommendations.</p> <p>Conclusion</p> <p>Provision of the supporting evidence and rationale should help to facilitate successful implementation of the JE surveillance standards in JE-endemic countries which will in turn enable better understanding of disease burden and the impact of control programs.</p