Pro: The Illegitimate Crusade against Corticosteroids for Severe H1N1 Pneumonia

American Journal of Respiratory and Critical Care Medicine (Impact Factor: 11.99). 05/2011; 183(9):1125-6. DOI: 10.1164/rccm.201102-0345ED
Source: PubMed
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    ABSTRACT: There are no completed randomised trials of the use of corticosteroids in patients with severe influenza infection. Corticosteroid use in influenza is widespread, non-systematic and marked by controversy. A recent meta-analysis of observational studies of adjuvant corticosteroids in influenza found an association with increased mortality but there were important concerns regarding the risks of bias. To (1) evaluate whether or not low-dose corticosteroids given as an adjunct to standard treatment is beneficial in patients who are hospitalised with severe pandemic influenza and (2) develop an 'off-the-shelf' clinical trial that is ready to be activated in a future pandemic. Multicentre, pragmatic, blinded, randomised placebo-controlled trial. Thirty to 40 hospitals in the UK. Adults (≥ 16 years) admitted to hospital with an influenza-like illness during a pandemic. Five-day course of dexamethasone (Dexsol®, Rosemont Pharmaceuticals Ltd) 6 mg daily, started within 24 hours of admission. Admission to Intensive Care Unit, or death, within 30 days of admission to hospital. This trial has not yet been activated. It is currently set up with full ethics and regulatory approvals in place, ready for rapid activation at the onset of the next pandemic. Hurdles to setting up a pandemic trial include planning for pandemic-level pressures on UK NHS resources and co-enrolment of patients to multiple pandemic studies, ensuring adequate geographical distribution of participating sites, maintaining long-term low-level engagement with site investigators, addressing future trial-specific training needs of local investigators and resilience planning in trial management. Identified threats to trial delivery include changes to research capabilities or policies during the hibernation phase, lack of staff resources during a pandemic and the influence of media at the time of a pandemic. A mismatch in the approach to informed consent required by current regulations to that preferred by patients and the public was identified. This study demonstrates that advance set-up of a trial to be conducted during a pandemic, with full regulatory approvals in place, is possible. Regular review during the hibernation phase will be required. This study serves as a model for the development of other 'off-the-shelf' trials as part of preparedness planning for public health emergencies. Current Controlled Trials ISRCTN72331452. European Union Drug Regulating Authorities Clinical Trials number: 2013-001051-12. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 16. See the NIHR Journals Library website for further project information.
    Health technology assessment (Winchester, England) 02/2015; 19(16):1-78. DOI:10.3310/hta19160 · 5.12 Impact Factor
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    ABSTRACT: Corticosteroids are used empirically in influenza A (H1N1) treatment despite lack of clear evidence for effective treatment. This study aims to assess the efficacy of corticosteroids treatment for H1N1 infection. Systematic review and meta-analysis were used to estimate the efficacy of corticosteroids for the prevention of mortality in H1N1 infection. Databases searched included MEDLINE, EMBASE, PubMed, Cochrane Central Register of Controlled Clinical Trials and so on, and bibliographies of retrieved articles, from April 2009 to October 2014. We included both cohort studies and case-control studies reported in English or Chinese that compared treatment effects between corticosteroids and non-corticosteroids therapy in inpatients with H1N1 virus infection. Cohort studies employed mortality as outcome, and case-control studies employed deaths as cases and survivors as controls; both were assessed in this meta-analysis. In total twenty-three eligible studies were included. Both cohort studies (nine studies, n = 1,405) and case-control studies (14 studies, n = 4,700) showed a similar trend toward increased mortality (cohort studies relative risk was 1.85 with 95% confidence interval (CI) 1.46 to 2.33; case-control studies odds ratio was 4.22 with 95% CI 3.10 to 5.76). The results from both subgroup analyses and sensitive analyses were consistent with each other, showing that steroid treatment is associated with mortality. However, considering the fact that corticosteroids were tend to be used in sickest case-patients and heterogeneity was observed between studies, we cannot make a solid conclusion. Available evidence did not support the use of corticosteroids as standard care for patients with severe influenza. We conclude that further research is required.
    Critical Care 12/2015; 19(1). DOI:10.1186/s13054-015-0764-5 · 5.04 Impact Factor
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    ABSTRACT: It was once believed that host cell injury in various infectious diseases is caused solely by pathogens themselves; however, it is now known that host immune reactions to the substances from the infectious agents and/or from the injured host cells by infectious insults are also involved. All biological phenomena in living organisms, including biochemical, physiological and pathological processes, are performed by the proteins that have various sizes and shapes, which in turn are controlled by an interacting network within the living organisms. The author proposes that this network is controlled by the protein homeostasis system (PHS), and that the immune system is one part of the PHS of the host. Each immune cell in the host may recognize and respond to substances, including pathogenic proteins (PPs) that are toxic to target cells of the host, in ways that depend on the size and property of the PPs. Every infectious disease has its own set of toxic substances, including PPs, associated with disease onset, and the PPs and the corresponding immune cells may be responsible for the inflammatory processes that develop in those infectious diseases.
    03/2015; 47(1):12-26. DOI:10.3947/ic.2015.47.1.12