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Head-To-Head Comparison of Biologic Efficacy in Asthma: What Have We Learned?
Get PDFABSTRACTWe performed an in-depth appraisal of indirect head-to-head comparisons of biologics approved for asthma, including anti-IL5/5Rα (mepolizumab, benralizumab), anti-IL4Rα (dupilumab), anti-TSLP (tezepelumab) and anti-IgE (omalizumab), whichwas neither a systematic review nor a meta-analysis. A crude evaluation of 95% CI's for rate ratios which excluded unity revealedgreater overall reductions in annualised exacerbations with dupilumab versus either mepolizumab or benralizumab and alsowith tezepelumab versus benralizumab. Furthermore in patients with eosinophils ≥ 300/μL exacerbation rates were lower fortezepelumab, dupilumab and mepolizumab versus benralizumab; and with eosinophils< 150/μL for tezepelumab versus dupi-lumab. For lung function, no overall differences in FEV1 response were observed between drugs where there was considerableheterogeneity of overlapping 95% CI's. Dupilumab was superior to benralizumab for oscillometry- derived peripheral lung resist-ance and compliance, as well as for attenuation of mannitol airway hyperresponsiveness. There were no differences in asthmacontrol or quality of life scores where the effect sizes were small, along with wide overlaps in 95% CI's. There is an unmet need forprospective pragmatic randomised controlled trials to directly compare biologics, especially to assess clinical remission in bothtype 2 high and low asthma patients. Real-life studies might also evaluate complete remission with different biologics to includeoutcomes such as inhaled corticosteroid sparing, small airways dysfunction using oscillometry, abolition of airway hyperrespon-siveness and to assess mucus plugging and remodelling as wall thickening with imaging performed an in-depth appraisal of indirect head-to-head comparisons of biologics approved for asthma, including anti-IL5/5Rα (mepolizumab, benralizumab), anti-IL4Rα (dupilumab), anti-TSLP (tezepelumab) and anti-IgE (omalizumab), whichwas neither a systematic review nor a meta-analysis. A crude evaluation of 95% CI's for rate ratios which excluded unity revealedgreater overall reductions in annualised exacerbations with dupilumab versus either mepolizumab or benralizumab and alsowith tezepelumab versus benralizumab. Furthermore in patients with eosinophils ≥ 300/μL exacerbation rates were lower fortezepelumab, dupilumab and mepolizumab versus benralizumab; and with eosinophils< 150/μL for tezepelumab versus dupi-lumab. For lung function, no overall differences in FEV1 response were observed between drugs where there was considerableheterogeneity of overlapping 95% CI's. Dupilumab was superior to benralizumab for oscillometry- derived peripheral lung resist-ance and compliance, as well as for attenuation of mannitol airway hyperresponsiveness. There were no differences in asthmacontrol or quality of life scores where the effect sizes were small, along with wide overlaps in 95% CI's. There is an unmet need forprospective pragmatic randomised controlled trials to directly compare biologics, especially to assess clinical remission in bothtype 2 high and low asthma patients. Real-life studies might also evaluate complete remission with different biologics to includeoutcomes such as inhaled corticosteroid sparing, small airways dysfunction using oscillometry, abolition of airway hyperrespon-siveness and to assess mucus plugging and remodelling as wall thickening with imagin
Guidance from the Strasbourg Court and the OSCE on the State Recognition of Religions and the Legal Registration of Religious or Belief Organisations
No full textOver the past two decades, the Strasbourg Court has received more than two dozen cases involving states denying access to legal personality for religious or belief organisations or otherwise misusing the mechanism of registration to impose undue limits on freedom of religion or belief (FoRB). Most of these cases have resulted in the Court ruling in favour of the applicant by determining such policies and practices as violations of Article 9. Moreover, with the publication in 2014 of the Joint Guidelines on the Legal Personality of Religious or Belief Communities by the joint actions of the Venice Commission and the OSCE, one might assume that issues surrounding recognition and registration have been settled but this would be an inaccurate assessment. The complex disputes over registration that continue to reach the ECtHR, combined with guidelines that are either outdated in parts or vague on key issues, demand that the attention of human rights organisations turns again to the discussion of recognition and registration with a view to developing a new standards document. This article looks back at the guidance the Strasbourg Court has dispensed on cases involving the recognition or registration of religious or belief organisations to reflect on the inadequacy of the criteria used by the Court to determine the permissibility of registration laws. This article also analyses the 2014 OSCE Guidelines to form a series of critical judgements intended to confirm the need for updated international guidance so that legal scholars, policymakers and judges can ascertain with greater precision at what specific points recognition and registration policies and practices contravene FoRB
Research on the Causes and Governance Strategies of False News in the Social Media Era
Get PDFThe emergence of social media has provided a platform for the general public to express their opinions, but it has also lowered the threshold for news release, making false news a type of news that is difficult to completely eliminate in social media. False news not only undermines the credibility of the media and hits the news industry, but also misleads public opinion, disrupts social order, and causes serious harm to society. This article selects 100 pieces of news from “Top 10 False News of the Year” released in Journalist from 2013 to 2022 as research samples, and explores the trends in the initial media, topic types, and sources of false news. The emergence of false news lies in the trend of commercial interests, the lack of professional literacy of media personnel, and the inadequate regulatory mechanism. We suggest addressing the phenomenon of false news by introducing advanced algorithms, improving professional literacy, and strengthening laws and regulations
Evolving the Control-Chaos Continuum: Part 2 – Shifting ‘Attention’ to Progress On-Pitch Rehabilitation
Get PDFBACKGROUND: On-pitch rehabilitation is key to supporting return-to-sport in elite soccer (football). The control-chaos continuum (CCC) guides practitioners through the sport-specific components of return-to-sport. There is a need to update the framework with recent research in injury neurophysiology, soccer performance, and coaching science.
CLINICAL QUESTION: How do practitioners integrate the insights from injury neurophysiology, soccer performance, and coaching science discussed in part 1 of this two-part series into an updated version of the CCC, to enhance planning and execution of on-pitch rehabilitation for elite soccer players?
KEY RESULTS: The revised CCC framework emphasizes the design and delivery of progressive training in increasingly 'chaotic' conditions. The updated framework supports practitioners to incorporate elements of visual cognition, attention challenges, decision-making, and progressive representation of the game model when players are preparing to return-to-sport.
CLINICAL APPLICATION: The updated CCC outlines training progression from ‘High Control’, which involves returning to on-pitch linear running, to ‘High Chaos’, which simulates the team environment at game speed. The ‘High Chaos’ phase can be tailored to support players during their re-integration into team training. The model is adaptable for both short- and long-term injuries, and integrates physical-cognitive load monitoring, and strength and power diagnostics to enhance decision-making throughout return-to-sport
P1330 The gut microbiome at the onset of inflammatory bowel disease: A systematic review of the literature and unified bioinformatic synthesis of sequencing data from >1000 treatment naïve patients
No full textBackground
There are few studies of the gut microbiome in new-onset IBD. We present a novel secondary bioinformatic re-analysis (BA) of sequence outputs mapped to latest microbial taxonomy derived from systematic review.
Methods
MEDLINE and Embase searches were performed for microbiome studies in pre-treatment IBD. Appraisal was completed with ROBINS-E. Available 16S rRNA sequence datasets were downloaded and missing datasets requested. Integrated datasets were run through a unified pipeline based in QIIME2 supplemented by phyloseq and DESeq2.
Results
From 12,264 studies, 10,804 abstracts and 217 full texts were screened. 31 studies were eligible; 18 met the requirements for BA. Most were low risk for bias, except uncontrolled confounding. Methodology varied extensively. Considering only amplicon data; samples originated from 1,743 unique individuals (including 678 Crohn’s disease (CD), 399 ulcerative colitis (UC), 123 ‘other’ IBD, 130 healthy, 405 symptomatic, and 8 familial controls) derived from 15 countries. DNA was extracted using 15 different kits, sequencing performed on 4 separate platforms targeting 10 different 16S rRNA hypervariable regions. There was a paucity of adult data, particularly mucosal biopsies.
Bacterial alpha diversity was reduced: in faeces in paediatric UC vs symptomatic controls (SC), in adult CD and UC vs HC and in paediatric SC vs HC (Figure 1).
In paediatric biopsies in CD vs SC, CD vs UC, SC vs UC (Figure 2).
Beta-diversity BA by Bray-Curtis demonstrated clear distinctions between faecal and mucosal biopsy communities, least evident in UC. Faecal communities separated by geography, though less evidently in biopsies.
Differential abundance analysis revealed enrichment of oral genera across sample types (Fusobacterium, Peptostreptococcus, Neisseria in CD; Haemophilus, Aggregatibacter, Peptostreptococcus, Porphyromonas, Neisseria, Gemella in UC). Short-chain fatty acid (SCFA) producers were diminished but less consistently across IBD phenotype and sample type.
Conclusion
This work demonstrates the utility of a combined systematic review/secondary data analysis approach to published microbiome datasets. Whilst synthesis remains challenging due to the methodological inconsistencies within these studies, this approach better accounts for these variations and presents a new way to consider this data. A reduction in bacterial diversity remains core to the IBD microbiome, though with more complexity than previously considered (SC<UC in paediatric biopsies). Microbial community structure changes by sample type and geography. Enrichment of oral bacteria is consistent across IBD subtypes and sample types suggesting their importance in the disease. A deficit in SCFA producers may also be important
Primary task demands modulate background speech disruption during reading of Chinese tongue twisters: an eye-tracking study
No full textThis study investigated how the semantic and phonological properties of background speech affect reading, depending on primary task processing. Chinese participants were randomly assigned to two groups and read Chinese tongue twisters while exposed to meaningful, meaningless, spectrally-rotated speech (acoustically similar to normal speech but without linguistic information), or silence. One group engaged in a semantic task, comprehending sentences and responding to “yes-no” questions, while the other performed a phonological task, identifying the most frequent initial phoneme in sentences and selecting a corresponding character. Although background speech did not significantly influence accuracy for either task, it differentially impacted eye movements and reading rates. Semantic properties disrupted the semantic task without significantly affecting the phonological task, while phonological properties influenced both tasks, particularly the phonological one. These findings indicate that the nature of the reading task modulates the disruptive effects of background speech, supporting the interference-by-process account
Ensuring Effectiveness and Credibility: The Conceptual Foundation of the PREPARED Code
Get PDFThis chapter explains the conceptual foundations of the PREPARED Code, which together provide the credibility required to justify adding yet another ethics code to the thousands that already exist. The code is built on real-world risks identified in nine languages rather than, for instance, on drafters’ expertise, thereby making it as precisely honed an instrument as possible to cope with the real-world ethics and integrity challenges experienced during a pandemic. The code is values-driven, focused on the values of fairness, respect, care and honesty, to harness the motivational power of moral values and to provide an easily understandable, globally applicable moral framework. Unlike most other ethics codes, the PREPARED Code unites research ethics and research integrity guidance into one, to ensure that a culture of integrity rather than a box-ticking mentality is fostered. The short, jargon-free code text addresses all research disciplines and, most importantly, it is based on extensive input from a wide range of stakeholders, including highly marginalised populations, to ensure that it is fit for purpose
Hearing the Voice of God: The Supernatural Phenomenon of Interior Locution
No full textHearing a divine voice is a type of supernatural experience recognised in religions the world over. In Catholicism, a handful of saints and blesseds have reported experiencing locutions while some mystics have conducted theological inquiry into these divine communications. Locutions are not confined to the history books but continue as private revelation, a recent example being the locutions of Derrick Taylor which acted as the case study in this research. An English convert and post-conciliar traditionalist, Mr Taylor claimed to experience two sessions of locution during his lifetime (first in 1971 and again in 1978), both addressing his disillusionment with the Church hierarchy during the implementation of reforms to the Tridentine liturgy after the Second Vatican Council. The first was a locution brought about by the intermediation of the Sacred Heart while the second was spoken by the voice of a deceased priest who had been Mr Taylor’s confessor. Deconstructing each of Mr Taylor’s locutionary accounts and comparing them to past reports of locution tested them according to criteria established by mystics to help ascertain their authenticity
Non-Invasive Detection of Landmines, Unexploded Ordnances and Improvised Explosive Devices Using Bespoke Unmanned Aerial Vehicles
Get PDFFinding and removing legacy landmines, Unexploded Ordnances (UXO), and Improvised Explosive Devices (IED) with a team of people or animals is very dangerous and requires a lot of effort and time. A small-scale customised drone was created in this research to automate the processes of cleaning explosive devices. Field tests were conducted to evaluate its performance. The outcomes of the benchmark evaluations and open-air minefields confirm the feasibility of the technologies, procedures, and strategies used in this study to identify landmines/UXO/IDE effectively
Exploring the Use of Robotics in Reconstructive and Plastic Surgery: A Comprehensive Perspective
No full textRapid advancements have revolutionized robot-assisted surgery (RAS) in the healthcare field, owing to substantial investments in the technology. The development of RAS progressed alongside advancements in microscopes and instruments, enabling microsurgeons to perform supermicrosurgical procedures in a more precise and efficient manner. This paper critically appraises the contemporary literature on RAS, exploring the risks and benefits of integrating and investing in emerging robotic technologies within plastic and reconstructive surgery, along with its limitations and challenges. This narrative review includes systematic reviews, case series, and prospective and retrospective reviews retrieved from PubMed published within the last 10 years, written in English, and conducted in live human subjects. Studies addressed applications of RAS in microsurgery, head and neck reconstruction, breast reconstruction, lymphovenous anastomosis, and aesthetic procedures. The review emphasized clinical outcomes, ergonomic impacts, patient satisfaction, safety, complication rates, and technological innovations. The current literature suggests that RAS is comparable, if not superior, to conventional techniques with respect to safety and effectiveness in specific reconstructive procedures. Reported benefits encompass shorter hospital stays, fewer complications, improved cosmetic outcomes, and enhanced surgeon dexterity. However, challenges persist, such as steep learning curves, high acquisition and maintenance costs, and a lack of tactile feedback, although these limitations are slowly being overcome through continued research and technological innovations. RAS is revolutionizing plastic and reconstructive surgery by enhancing surgical precision, ergonomics, and patient recovery. However, widespread adoption is constrained by substantial costs and the pace of technological evolution. Evidence has shown how it has become an essential component of modern surgical practice. Future research should prioritize high-quality comparative trials, cost-effectiveness analyses, and training programs to facilitate broader clinical integration