METHODS: An online international survey of 800 early career researchers (ECRs) was conducted in 2022. A questionnaire was developed based on three rounds of interviews and distributed using multiple channels including publishers, social media, and direct email to ECRs.
RESULTS: The impact of the pandemic on career prospects, morale, job security, productivity, ability to network and collaborate, and quality and speed of peer review has on the whole been more negative than positive. A quarter of ECRs shifted their research focus to pandemic-related topics and half of those who did, benefited largely due to increased productivity and impact. The majority worked remotely/from home and more than two-thirds of those who did so benefitted from it. While virtual or hybrid conferences have been embraced by the majority of ECRs, around a third still preferred face-to-face only conferences. The use of library online platforms, Sci-Hub, ResearchGate, Google Scholar and smartphone to search and access full-text papers increased. ECRs prioritised journals with fast submission procedures for the publishing of their papers and spent more time on increasing the visibility of their research. Fees were a problem for publishing open access.
CONCLUSION: Although, generally, the pandemic negatively impacted many aspects of ECRs' work-life, certain research areas and individuals benefited from being more appreciated and valued, and, in some cases, resulted in increased resources, better productivity and greater impact. Changes, such as the use of digital technologies and remote working created new opportunities for some ECRs. While continuing work flexibility and hybrid conferences might benefit some ECRs, institutions should also take measures to help those ECRs whose career and productivity have been adversely impacted.
METHODS AND ANALYSIS: At least 51 patients with an acute GPP flare will be randomised 2:1 to receive a single 900 mg intravenous dose of spesolimab or placebo and followed for up to 28 weeks. The primary endpoint is a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 (pustule clearance) at Week 1. The key secondary endpoint is a GPPGA score of 0 or 1 (clear or almost clear) at Week 1. Safety will be assessed over the study duration by the occurrence of treatment-emergent adverse events. Blood and skin biopsies will be collected to assess biomarkers. Superiority of spesolimab over placebo in the proportion of patients achieving the primary and key secondary endpoints will be evaluated.
ETHICS AND DISSEMINATION: The study complies with the ethical principles of the Declaration of Helsinki, the International Council for Harmonisation's Good Clinical Practice and local regulations. Ethics committee approvals have been obtained for each centre from all participating countries and are listed in online supplementary file 1. Primary results will be published in a peer-reviewed journal.
TRIAL REGISTRATION DETAILS: ClinicalTrials.gov identifier: NCT03782792; Pre-results.
Methods: Proton nuclear magnetic resonance spectroscopy (1H NMR)-based metabolomics approach was used to investigate fecal and serum metabolome of rat model of IBS-D with and without HPM treatment.
Results: The current results showed that IBS-induced metabolic alterations in fecal and serum sample include higher level of threonine and UDP-glucose together with lower levels of aspartate, ornithine, leucine, isoleucine, proline, 2-hydroxy butyrate, valine, lactate, ethanol, arginine, 2-oxoisovalerate and bile acids. These altered metabolites potentially involve in impaired gut secretory immune system and intestinal inflammation, malabsorption of nutrients, and disordered metabolism of bile acids. Notably, the HPM treatment was found able to normalize the Bristol stool forms scale scores, fecal water content, plasma endotoxin level, and a number of IBS-induced metabolic changes.
Conclusions: These findings may provide useful insight into the molecular basis of IBS and mechanism of the HPM intervention.
METHODS: In a phase 2 trial, we randomly assigned patients with a GPP flare in a 2:1 ratio to receive a single 900-mg intravenous dose of spesolimab or placebo. Patients in both groups could receive an open-label dose of spesolimab on day 8, an open-label dose of spesolimab as a rescue medication after day 8, or both and were followed to week 12. The primary end point was a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 (range, 0 [no visible pustules] to 4 [severe pustulation]) at the end of week 1. The key secondary end point was a GPPGA total score of 0 or 1 (clear or almost clear skin) at the end of week 1; scores range from 0 to 4, with higher scores indicating greater disease severity.
RESULTS: A total of 53 patients were enrolled: 35 were assigned to receive spesolimab and 18 to receive placebo. At baseline, 46% of the patients in the spesolimab group and 39% of those in the placebo group had a GPPGA pustulation subscore of 3, and 37% and 33%, respectively, had a pustulation subscore of 4. At the end of week 1, a total of 19 of 35 patients (54%) in the spesolimab group had a pustulation subscore of 0, as compared with 1 of 18 patients (6%) in the placebo group (difference, 49 percentage points; 95% confidence interval [CI], 21 to 67; P<0.001). A total of 15 of 35 patients (43%) had a GPPGA total score of 0 or 1, as compared with 2 of 18 patients (11%) in the placebo group (difference, 32 percentage points; 95% CI, 2 to 53; P = 0.02). Drug reactions were reported in 2 patients who received spesolimab, in 1 of them concurrently with a drug-induced hepatic injury. Among patients assigned to the spesolimab group, infections occurred in 6 of 35 (17%) through the first week; among patients who received spesolimab at any time in the trial, infections had occurred in 24 of 51 (47%) at week 12. Antidrug antibodies were detected in 23 of 50 patients (46%) who received at least one dose of spesolimab.
CONCLUSIONS: In a phase 2 randomized trial involving patients with GPP, the interleukin-36 receptor inhibitor spesolimab resulted in a higher incidence of lesion clearance at 1 week than placebo but was associated with infections and systemic drug reactions. Longer and larger trials are warranted to determine the effect and risks of spesolimab in patients with pustular psoriasis. (Funded by Boehringer Ingelheim; Effisayil 1 ClinicalTrials.gov number, NCT03782792.).