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BackgroundThe global pandemic of COVID-19 infections continues to grow worldwide, with rising number of deaths day by day. The hyperinflammation state contributes to the multiorgan failure associated with COVID-19 infections. This study aims to explore the efficacy and safety of anakinra in COVID-19 patients with both respiratory distress and cytokine release syndromes. MethodsThis was an open-label, multicenter, randomized clinical trial. Patients were randomized in 1:1 ratio to receive standard of care (SOC) alone, or anakinra plus SOC. Adults with confirmed COVID-19 infection with evidence of both respiratory distress and cytokine release syndrome were included. The primary outcome was treatment success at day 14, defined as WHO clinical progression score of [≤]3. The primary analysis was based on intention-to-treat population, with p-value of <0.05. ResultsA total of 80 patients were enrolled in the study. The mean age was 49.9 years (SD=11.7), with 82.5% (n=66) male patients. The primary outcome was not statistically different (87.5% (n=35) in anakinra group vs. 92.5% (n=37) in SOC group, p=0.712). The majority of reported adverse events were mild in severity and not related to the study treatment. Increased aspartate aminotransferase was the only significant adverse event (35% (n=14) in anakinra group vs. 15% (n=6) in SOC group, p=0.039); yet, was not associated with treatment discontinuation. ConclusionIn patients with severe COVID-19 infection, the addition of anakinra to SOC treatment was not associated with significant improvement in the WHO clinical progression scale. Further studies investigating patients subgroups that might benefit from anakinra are warranted. The trial was registered at ClinicalTrials.gov (NCT04643678).
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COVID-19 vaccine protection against infection in immunosuppressed solid organ transplant recipients is unknown but possibly weak with the low proportion of these patients mounting a robust humoral and cellular immune response after vaccination. Using a retrospective cohort study design with cross-over, we assessed vaccine effectiveness among 782 kidney transplant recipients registered at Hamad Medical Corporation, the national public healthcare provider in Qatar, where the BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines have been used in the national immunization campaign. Vaccine effectiveness against any SARS-CoV-2 infection was estimated at 46.6% (95% CI: 0.0-73.7%) [≥]14 days after the second dose, 66.0% (95% CI: 21.3-85.3%) [≥]42 days after the second dose, and 73.9% (95% CI: 33.0-89.9%) [≥]56 days after the second dose. Vaccine effectiveness against any severe, critical, or fatal COVID-19 disease was estimated at 72.3% (95% CI: 0.0-90.9%) [≥]14 days after the second dose, 85.0% (95% CI: 35.7-96.5%) [≥]42 days after the second dose, and 83.8% (95% CI: 31.3-96.2%) [≥]56 days after the second dose. Most vaccine breakthrough infections occurred in the first few weeks after receiving the first and/or second dose. Vaccine effectiveness reached considerable levels in kidney transplant recipients, but vaccine protection mounted slowly and did not reach a high level until several weeks after the second dose.
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The number of complicated skin and soft tissue infections (cSSTIs) in the Arabian Gulf region has risen in recent years, particularly those caused by multi-drug resistant (MDR) pathogens. The high prevalence of diabetes, obesity, and associated cardio-metabolic comorbidities in the region renders medical and surgical management of cSSTI patients with MDR infections challenging. An experienced panel of international and regional cSSTI experts (consensus group on cSSTIs) was convened to discuss clinical considerations for MDR infections from societal, antimicrobial stewardship, and cost perspectives, to develop best practice recommendations. This article discusses antibiotic therapies suitable for treating MDR cSSTIs in patients from the Gulf region and recommends that these should be tailored according to the local bacterial ecology by country and region. The article highlights the need for a comprehensive patient treatment pathway and defined roles of each of the multidisciplinary teams involved with managing patients with MDR cSSTIs. Aligned and inclusive definitions of cSSTIs for clinical and research purposes, thorough and updated epidemiological data on cSSTIs and methicillin-resistant Staphylococcus aureus in the region, clearcut indications of novel agents and comprehensive assessment of comparative data should be factored into decision-making are necessary.
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1.In this work we tried to study the effect of the regular use of potent mouthwash in COVID19 cases, on the premise that it may speedup the recovery, through the repeated reduction of microbial load, of both, the 2019-nCOV and oral microbiota; thus slowing the disease progression and lowering the incidence of superinfections. Through a randomized controlled trial, a mixed solution of Hydrogen peroxide 2% and chlorhexidine gluconate, to be used for oral rinsing and gargling three times daily, was tested in cases admitted to COVID treatment facility, versus the standard (only) COVID19-treatment protocol, starting with 46 cases in each group, matched in terms of disease severity, of symptoms, and average cycle threshold value (CT-value) for the COVID PCR test on diagnosis. Our findings showed statistically significant improvement in terms of a higher conversion rate to "COVID19-negative PCR" by five days of treatment (6/46 Vs 0/46), improvement in "symptoms severity" after two days of treatment, and less intubation and mortality (0/46 Vs 3/46) with all P-value < 0.05. There was also a trend of improvement in other outcome variables, though with no statistically significant difference; namely "shorter hospital stays," "less progression in Oxygen requirements", "less rate of plasma transfusion", and better "gross extent of improvement". Our findings support a beneficial role in treating active cases (Disease) and anticipates better outcome should implemented earlier in course of the disease; thus, suggest a role in limiting the spread (Pandemic), as an additional preventive method. Additionally, we think the repeated reduction in the microbial load might have been sufficient to induce a strain in a possible viral-microbial interaction, resulting in slowing down of the disease progress.
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Updates: This is the fourteenth version (thirteenth update) of the living guideline, replacing earlier versions (available as data supplements). New recommendations will be published as updates to this guideline. Clinical question: What is the role of drugs in the treatment of patients with covid-19? Context: The evidence base for therapeutics for covid-19 is evolving with numerous randomised controlled trials (RCTs) recently completed and underway. Emerging SARS-CoV-2 variants and subvariants are changing the role of therapeutics. What is new?: The guideline development group (GDG) defined 1.5% as a new threshold for an important reduction in risk of hospitalisation in patients with non-severe covid-19. Combined with updated baseline risk estimates, this resulted in stratification into patients at low, moderate, and high risk for hospitalisation. New recommendations were added for moderate risk of hospitalisation for nirmatrelvir/ritonavir, and for moderate and low risk of hospitalisation for molnupiravir and remdesivir. New pharmacokinetic evidence was included for nirmatrelvir/ritonavir and molnupiravir, supporting existing recommendations for patients at high risk of hospitalisation. The recommendation for ivermectin in patients with non-severe illness was updated in light of additional trial evidence which reduced the high degree of uncertainty informing previous guidance. A new recommendation was made against the antiviral agent VV116 for patients with non-severe and with severe or critical illness outside of randomised clinical trials based on one RCT comparing the drug with nirmatrelvir/ritonavir. The structure of the guideline publication has also been changed; recommendations are now ordered by severity of covid-19. About this guideline: This living guideline from the World Health Organization (WHO) incorporates new evidence to dynamically update recommendations for covid-19 therapeutics. The GDG typically evaluates a therapy when the WHO judges sufficient evidence is available to make a recommendation. While the GDG takes an individual patient perspective in making recommendations, it also considers resource implications, acceptability, feasibility, equity, and human rights. This guideline was developed according to standards and methods for trustworthy guidelines, making use of an innovative process to achieve efficiency in dynamic updating of recommendations. The methods are aligned with the WHO Handbook for Guideline Development and according to a pre-approved protocol (planning proposal) by the Guideline Review Committee (GRC). A box at the end of the article outlines key methodological aspects of the guideline process. MAGIC Evidence Ecosystem Foundation provides methodological support, including the coordination of living systematic reviews with network meta-analyses to inform the recommendations. The full version of the guideline is available online in MAGICapp and in PDF on the WHO website, with a summary version here in The BMJ. These formats should facilitate adaptation, which is strongly encouraged by WHO to contextualise recommendations in a healthcare system to maximise impact. Future recommendations: Recommendations on anticoagulation are planned for the next update to this guideline. Updated data regarding systemic corticosteroids, azithromycin, favipiravir and umefenovir for non-severe illness, and convalescent plasma and statin therapy for severe or critical illness, are planned for review in upcoming guideline iterations.
