Conectar
Infections are a major cause of morbidity and mortality among individuals with haematological cancers, but the duration of elevated risk in long-term survivors remains uncertain. Although previous attempts to summarise the existing literature on this topic would have been hampered by the sheer volume of studies on cancer and all-cause infections, emerging artificial intelligence tools now offer the ability to streamline the screening process, allowing for broader and more comprehensive reviews.
This protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols guidelines. Eligible studies will include original observational data reporting long-term (≥1 year follow-up from diagnosis) infection-related outcomes in haematological cancer survivors compared with a general or cancer-free population. Screening will be supported by ASReview, an artificial intelligence-based tool for abstract prioritisation. An internal validation step will be conducted by comparing artificial intelligence-assisted screening results with manual review performed by two independent researchers on a subset of abstracts. The primary outcomes of infection incidence and infection mortality will be summarised by type of infection, type of haematological cancer and time since cancer diagnosis. Information on anti-cancer treatments received will also be described. Data synthesis will be mostly narrative due to the broad scope of the review, though meta-analyses will be performed in cases where studies are sufficiently homogenous. Risk of bias will be assessed using the Newcastle-Ottawa Scale.
Ethical approval is not applicable to this study. The results of the review will be disseminated to clinical audiences and submitted to a peer-reviewed journal.
CRD420251047091.
To determine the safety and efficacy of ruxolitinib (RUX) and fostamatinib (FOS) compared with standard of care (SOC) in patients requiring hospital admission for the treatment of COVID-19 pneumonia.
Adaptive multiarm, multistage, randomised, open-label trial (three arm, two stage).
Five hospitals in England between October 2020 and September 2022.
Hospitalised patients (≥18 years) with COVID-19 pneumonia defined by a modified WHO COVID-19 severity grade of 3 or 4.
Participants were randomly assigned 1:1:1 to receive RUX (10 mg two times per day for 7 days then 5 mg two times per day for 7 days), FOS (150 mg two times per day for 7 days then 100 mg two times per day for 7 days) or SOC.
Primary outcome was development of severe COVID-19 pneumonia (modified WHO severity grade≥5) within 14 days of randomisation. Secondary outcomes included mortality, invasive and non-invasive ventilation, venous thromboembolism, duration of hospital stay, readmissions, inflammatory markers and serious adverse events (SAEs).
At stage 1, 181 patients were randomised, with 4 assessed as ineligible post randomisation. FOS was stopped early for futility with 16 participants (27.6%, n=58) developing severe COVID-19 pneumonia compared with 15 (25.0%, n=60) in the SOC arm (adjusted odds ratio (aOR) compared with SOC: 1.12; 95% CI 0.49 to 2.58; p=0.608). RUX progressed to stage 2 but the trial was stopped early due to slow recruitment. At the final analysis, 10 participants (16.1%, n=62) developed severe COVID-19 pneumonia in the RUX arm compared with 15 (24.6%, n=61) in the SOC arm (aOR: 0.63; 95% CI 0.25 to 1.57; p=0.161). Four (7.4%) participants in the FOS arm, none in the RUX arm and three (5.5%) in the SOC arm died within 14 days of randomisation. Infections were the most frequently reported SAE and were numerically higher in the FOS (10, 17.2%) and RUX (10, 16.1%) arms compared with SOC (7, 11.5%). Two unexpected serious adverse reactions occurred in the RUX arm only.
We found no evidence that FOS was superior to SOC for the treatment of COVID-19 pneumonia in patients requiring hospital admission. Due to early stopping, the trial was underpowered to establish RUX’s effect in this population. Further study is needed.
NCT04581954; EUDRA-CT:
FreshRSS 