ORCID Profile
0000-0002-6951-8081
Current Organisation
Yale University
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Publisher: Elsevier BV
Date: 07-06-2021
DOI: 10.51893/2021.2.OA4
Abstract: Objective: Benefit or harm of higher positive end expiratory pressure (PEEP) for acute respiratory distress syndrome (ARDS) is controversial. We aimed to assess the impact of higher levels of PEEP in patients with ARDS under a Bayesian framework. Design: Systematic review and Bayesian meta-analysis of randomised clinical trials comparing higher to lower PEEP in adult patients with ARDS. Data sources: MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials from 1996 to 1 March 2020. Review methods: We extracted data from high quality randomised clinical trials comparing higher to lower levels of PEEP in adult patients, using low tidal volume in both arms, and conducted a Bayesian meta-analysis using aggregate data from these studies. Results: Eight clinical trials including 3703 patients (n = 1833 for higher PEEP, n = 1870 for lower PEEP) were included. Under a minimally informative prior, the posterior probability of benefit with higher PEEP was 65% (relative risk, 0.97 [95% credible interval, 0.78–1.14]). In patients with moderate-to-severe ARDS, the posterior probability of benefit with higher PEEP was 77% (relative risk, 0.94 [95% credible interval, 0.77–1.13]). Down-weighting studies that employed a maximum recruitment strategy by 100% increased the posterior probability of benefit to 92% under a minimally informative prior. Conclusions: The probability of benefit or harm from routine use of higher PEEP for patients with ARDS ranges from 27% to 86%, and from 14% to 73% depending on one’s prior, suggesting continued uncertainty and equipoise regarding the benefit of PEEP. If data from trials using a maximum recruitment strategy is discounted to some extent because of uncertainty over the appropriateness of this approach, the available evidence suggests that higher PEEP could be beneficial for moderate-to-severe ARDS. However, well powered randomised clinical trials are needed to confirm these findings.
Publisher: Cold Spring Harbor Laboratory
Date: 21-01-2023
DOI: 10.1101/2023.01.19.524823
Abstract: In addition to its canonical function in protecting from pathogens, the immune system can also promote behavioural alterations 1–3 . The scope and mechanisms of behavioural modifications by the immune system are not yet well understood. Using a mouse food allergy model, here we show that allergic sensitization drives antigen-specific behavioural aversion. Allergen ingestion activates brain areas involved in the response to aversive stimuli, including the nucleus of tractus solitarius, parabrachial nucleus, and central amygdala. Food aversion requires IgE antibodies and mast cells but precedes the development of gut allergic inflammation. The ability of allergen-specific IgE and mast cells to promote aversion requires leukotrienes and growth and differentiation factor 15 (GDF15). In addition to allergen-induced aversion, we find that lipopolysaccharide-induced inflammation also resulted in IgE-dependent aversive behaviour. These findings thus point to antigen-specific behavioural modifications that likely evolved to promote niche selection to avoid unfavourable environments.
Publisher: Cold Spring Harbor Laboratory
Date: 28-08-2021
DOI: 10.1101/2021.08.24.21262515
Abstract: The choice of intravenous fluid for fluid therapy in critically ill adult patients remains a matter of debate. Currently, crystalloids are used more often than colloids, with ongoing controversy over the relative efficacy and safety of buffered salt solutions (BSS) versus normal saline (0.9% sodium chloride). In 2021 two large pragmatic trials enrolling critically ill patients will add substantial new data to address this controversy. We will conduct a systematic review and meta-analysis of randomised controlled trials (RCTs) that will include the data from these two trials to provide clinicians with the most up to date evidence and robust evidence to guide their choice of crystalloid fluids. We will include RCTs that compare the effect of buffered salt solutions to normal saline for fluid resuscitation and/or fluid therapy in critically ill adults, on all-cause mortality and other patient centred outcomes. We will perform a search that includes the electronic databases MEDLINE and EMBASE, and clinical trial registries. Two reviewers will independently screen titles and abstracts, perform full article reviews and extract study data, with discrepancies resolved by a third reviewer. We will report study characteristics and assess risk of bias using the Cochrane Risk-of-Bias tool. We will perform Hartung-Knapp-Sidik-Jonkman random-effects aggregate data meta-analysis whenever it is feasible to do so. We will evaluate overall certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. This systematic review and meta-analysis does not require ethical approval as it does not involve primary data collection. We will publish our results in a peer-reviewed scientific journal and present them at national and international scientific conferences. CRD42021243399 This systematic review will provide up-to-date evidence to answer the focused clinical question: In adult patients who are critically ill, does administering balanced crystalloid solutions for fluid therapy reduce mortality and other patient-centered outcomes, compared with administering 0.9% sodium chloride? We will conduct a systematic review according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines, searching three electronic databases, clinical trial registries and published conference abstracts, with two independent reviewers evaluating studies and extracting data. A meta-analysis will assess the primary outcome of all-cause mortality at 90 days and secondary outcomes of ventilator and vasopressor free days, renal replacement therapy use, incidence of acute kidney injury, and patient quality of life outcomes. The limitations of this review include the clinical heterogeneity of the included trials, ersity of the targeted population receiving fluid therapy, variability in the composition of balanced crystalloid solutions, and timing of initiation of study crystalloids. We will address all limitations with the Grading of Recommendations, Assessment, Development and Evaluations framework.
Publisher: Springer Science and Business Media LLC
Date: 12-07-2023
DOI: 10.1038/S41586-023-06362-4
Abstract: In addition to its canonical function of protection from pathogens, the immune system can also alter behaviour 1,2 . The scope and mechanisms of behavioural modifications by the immune system are not yet well understood. Here, using mouse models of food allergy, we show that allergic sensitization drives antigen-specific avoidance behaviour. Allergen ingestion activates brain areas involved in the response to aversive stimuli, including the nucleus of tractus solitarius, parabrachial nucleus and central amygdala. Allergen avoidance requires immunoglobulin E (IgE) antibodies and mast cells but precedes the development of gut allergic inflammation. The ability of allergen-specific IgE and mast cells to promote avoidance requires cysteinyl leukotrienes and growth and differentiation factor 15. Finally, a comparison of C57BL/6 and BALB/c mouse strains revealed a strong effect of the genetic background on the avoidance behaviour. These findings thus point to antigen-specific behavioural modifications that probably evolved to promote niche selection to avoid unfavourable environments.
No related grants have been discovered for Andrew Wang.