Two Years of Experience and Methodology of Korean COVID-19 Living Clinical Practice Guideline Development.

BACKGROUND: In Korea, during the early phase of the coronavirus disease 2019 (COVID-19) pandemic, we responded to the uncertainty of treatments under various conditions, consistently playing catch up with the speed of evidence updates. Therefore, there was high demand for national-level evidence-based clinical practice guidelines for clinicians in a timely manner. We developed evidence-based and updated living recommendations for clinicians through a transparent development process and multidisciplinary expert collaboration. METHODS: The National Evidence-based Healthcare Collaborating Agency (NECA) and the Korean Academy of Medical Sciences (KAMS) collaborated to develop trustworthy Korean living guidelines. The NECA-supported methodological sections and 8 professional medical societies of the KAMS worked with clinical experts, and 31 clinicians were involved annually. We developed a total of 35 clinical questions, including medications, respiratory/critical care, pediatric care, emergency care, diagnostic tests, and radiological examinations. RESULTS: An evidence-based search for treatments began in March 2021 and monthly updates were performed. It was expanded to other areas, and the search interval was organized by a steering committee owing to priority changes. Evidence synthesis and recommendation review was performed by researchers, and living recommendations were updated within 3-4 months. CONCLUSION: We provided timely recommendations on living schemes and disseminated them to the public, policymakers and various stakeholders using webpages and social media. Although the output was successful, there were some limitations. The rigor of development issues, urgent timelines for public dissemination, education for new developers, and spread of several new COVID-19 variants have worked as barriers. Therefore, we must prepare systematic processes and funding for future pandemics.

Use of evidence during the COVID-19 pandemic in Peru, contributions from the National Institute of Health

The COVID-19 pandemics required the countries to take decisions rapidly. Consequently, the National Institute of Health (INS) developed a series of documents of scientific evidence synthesis according to the Ministry of Health's requirements. Based on these reports, the INS developed recommendations to update normative documents related to COVID-19's management. This article describes the construction of a new methodology applied by the INS to synthesize scientific evidence during the COVID-19 pandemic. Moreover, it emphasizes the efforts and strategies used to guarantee the methodological quality and the implementation of the GRADE approach. Finally, it provides a short reflection on the limitations and challenges of using evidence to design national public policies in the future. © 2022 Publicado por Cuerpo Médico Hospital Nacional Almanzor Aguinaga Asenjo.

How to recognize a trustworthy clinical practice guideline.

Trustworthy clinical practice guidelines represent a fundamental tool to summarize relevant evidence regarding a set of clinical choices and provide guidance for making optimal clinical decisions. Clinicians must differentiate between guidelines that provide trustworthy evidence guidance and those that do not. We present six questions clinicians should ask when evaluating a guideline's trustworthiness. (1) Are the recommendations clear?; (2) Have the panelists considered all alternatives?; (3) Have the panelists considered all patient-important outcomes?; (4) Is the recommendation based on an up-to-date systematic review?; (5) Is the strength of the recommendation compatible with the certainty of the evidence?; (6) Might conflicts of interest influence the recommendations? If yes, were they managed? Once the conclude they are dealing with a trustworthy guideline, clinicians must gain an understanding of the transparent evidence summary that the guideline will offer, and judge the applicability of trustworthy recommendations to their patients and settings. Consideration of the circumstances and values and preferences of patients will be crucial for all weak or conditional recommendations.

Awake Prone Positioning in Covid-19: A Review of Prospective Clinical Trials

PURPOSE/HYPOTHESIS: Coronavirus disease 2019 (COVID-19) may result in hypoxemic respiratory failure and death similar to acute respiratory distress syndrome (ARDS). Based on its known efficacy in ARDS, prone positioning (PP) was used to manage intubated patients with severe COVID-19 lung disease. Though less supported by evidence, awake prone positioning (APP) was also trialed in non-intubated patients with COVID-19 to preserve resources and optimize outcomes. The primary available evidence included in recent reviews on APP in COVID-19 were the resultant retrospective single group studies that showed mixed findings. While such designs expedite results, a risk of bias weakens their application. With emerging research, this focused review evaluated APP in COVID-19 based on prospective trials that included a comparison group. NUMBER OF SUBJECTS: Not applicable. MATERIALS AND METHODS: PubMed and CINAHL databases were searched through June 10, 2022 with the following strategy: [(SARS-COV-2) OR (COVID-19) OR (coronavirus)] AND [(prone) OR (proning) OR (prone positioning)]. Prospective studies investigating APP in non-intubated adults with COVID-19 compared to usual care were included. Quality of evidence was determined by the Cochrane Risk of Bias tool with recommendations made using the GRADE approach. RESULT(S): Seven articles evaluating APP in a combined total of 2604 participants (66% male, mean age: 59.8 yrs, BMI: 29.0) with mild to moderate hypoxemic respiratory failure were included. Participant characteristics were heterogeneous and the duration of proning ranged from 4 to 16 hrs/d. APP was associated with improved oxygenation;however, only one study reported a lower incidence of intubation. No effect was noted on mortality or length of stay (LOS). Adverse events were rare but APP was associated an initial worsening outcome in one instance. Lack of blinding and protocol heterogeneity were identified risks of bias. CONCLUSION(S): APP may improve oxygenation in non-intubated individuals with mild to moderate COVID-19 lung disease as compared to usual care;however, prospective controlled trials do not support a positive effect on intubation, LOS, or mortality. The lack of transference in contrast to PP in intubated patients suggests that the primary benefit of PP may be minimizing ventilator-induced lung injury. Alternatively, benefits of APP may be reserved in select individuals as patient characteristics and proning protocols may influence the response. Though serious adverse events were not reported, the potential for skin breakdown and brachial plexus injuries are noted in ventilated patients with the proning times necessary for benefit. Given these findings, the value of immobilizing awake patients in prone should be questioned and alternate active interventions investigated. CLINICAL RELEVANCE: The routine application of APP in COVID-19 lung disease to improve clinical outcomes is not supported by current literature. Based on the GRADE approach, a weak recommendation against using APP was determined. Future studies should investigate if optimal protocols matched to potential responders improve the value of APP in COVID-19.

Prone Positioning for Nonintubated Covid-19 Patients: A Systematic Review and Meta-Analysis

INTRODUCTION: Since the early pandemic, prone positioning (PP) has been broadly utilized for non-intubated COVID-19 patients, but results from recently published randomized controlled trials (RCTs) are contradictory. We aimed to systematically synthesize the outcomes associated with PP for non-intubated COVID-19 patients. METHOD(S): Two independent groups of researchers searched MEDLINE, Embase, PubMed, Web of Science, Scopus, and ClinicalTrials.gov for RCTs of PP in nonintubated adult patients with COVID-19 and published in English from January 1st, 2020 to July 1st, 2022. The same two independent groups extracted the data and assessed the risk of bias. We used a random-effects meta-analysis to pool individual studies and the GRADE approach to assess certainty/quality of the evidence. The primary outcome was the reported cumulative intubation risk, while secondary outcomes included mortality, need for escalating respiratory support, hospital length of stay, ICU admission, and adverse events. The study protocol was prospectively registered with PROSPERO, CRD42022343625. RESULT(S): 12 RCTs with 2,886 patients were included. For non-intubated COVID-19 patients, PP significantly reduced the intubation risk (risk ratio [RR] 0.85, 95%CI 0.75 to 0.96), compared to supine position. Subgroup analysis showed a significant reduction in intubation risk among patients supported by high-flow nasal cannula (HFNC) or noninvasive ventilation (NIV) (RR 0.83, 95%CI 0.73 to 0.94) but not in patients with conventional oxygen therapy (RR 1.02, 95%CI 0.67 to 1.56). No significant reduction was seen in mortality (RR 0.96, 95%CI 0.82 to 1.13), need for escalating respiratory support (RR 1.03, 95%CI 0.77 to 1.37), hospital length of stay (MD 0.35 days, 95%CI -0.57 to 1.26), ICU admission (RR 0.75, 95%CI 0.51 to 1.10), and adverse events. No obvious risk of bias and publication bias was found for the primary outcome. CONCLUSION(S): In non-intubated COVID-19 patients, PP reduced the need for intubation, in particular among those requiring respiratory support with HFNC or NIV, but did not reduce mortality, need for escalating respiratory support, hospital length of stay, and ICU admission.

New boundaries for measuring burnout among healthcare professionals: Lessons from the 14-item Shirom-Melamed Burnout Measure

Aims: The prevalence of Occupational Burnout has skyrocketed during the Covid-19 pandemic, especially among healthcare professionals (HCP). Hence, it is crucial to have robust measures for ascertaining burnout in this population. The Maslach Burnout Inventory (MBI) is the most widely used measure in burnout research, but fundamental methodological flaws permeated its development. The Shirom-Melamed Burnout Questionnaire/Measure is a prevalent tool used by the Swedish Health System to diagnose burnout and plan the delivery of mental health services. The 14-item Shirom-Melamed Burnout Measure (SMBM) was developed after a methodological revision of the 22-item Shirom-Melamed Burnout Questionnaire (SMBQ). Studies on the psychometric properties of the SMBM exist, but the assessment of the methodological quality of individual studies is lacking. To address this gap, the purpose of this study is to critically appraise the quality of the measurement properties of the 14-item SMBM among HCP. Method(s): Four databases (PubMed, CINAHL, PsycINFO, and Scopus) were searched for studies on the psychometric properties of the 14-item SMBM among HCP. The methodological quality of the studies was evaluated using the COSMIN Risk of Bias checklist. Evidence supporting the measurement properties of the SMBM was synthesized and graded using the GRADE approach. Result(s): We identified three studies on the psychometric properties of the 14-item SMBM among HCP. One study on the 12-item SMBM was included to estimate content validity. We found a high quality of evidence for internal consistency, moderate quality of evidence for structural and crosscultural validity, and low quality of evidence for hypothesis testing. Most importantly, we found that PROM development and content validity were inadequate. Conclusion(s): Although informed by the Conservation of Resources Theory, the 14-item SMBM warrants revision to engage critical stakeholders for concept elicitation and cognitive interview. Both processes will contribute to the relevance, comprehensiveness, and comprehensibility of the PRO items.

Clinical Practice Guideline for the treatment of COVID-19 in the Social Security of Peru (EsSalud)

Introduction: Since the beginning of the COVID-19 pandemic, different drugs and medications have been used for the prevention and treatment of COVID-19 infection. Likewise, various investigations have been carried out to evaluate the efficacy and safety of these interventions, many of which have been shown to generate more harm than benefit for the patient, for this reason it is necessary to standardize the management of adult patients with COVID-19 in our context. Objective: To provide evidence-based clinical recommendations for the management of adults with COVID-19. Methods: A guideline development group (GEG) was formed that included medical specialists and methodologists. For its elaboration, GEG decided to carry out a rapid adaptation of the Guide for the care of critical adult patients with COVID-19 in the Americas of the Pan American Health Organization (PAHO) as well as to carry out searches for novo questions. For the formulation of the recommendations, the evidence frameworks for the decision (EtD) of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology were developed. Results: This CPG addressed 28 clinical questions, divided into three topics: prevention, diagnosis and management. Based on these questions, 33 recommendations (16 strong and 17 conditional), 26 good clinical practices (GCP) and 2 flowcharts were formulated. This CPG was published in its third version in December 2021 Conclusion: This article summarizes the methodology and evidence-based conclusions of the CPG for the management of adults with COVID 19 in EsSalud. © 2022 Publicado por Cuerpo Médico Hospital Nacional Almanzor Aguinaga Asenjo.

Evaluation of Current Evidence on the Use of Oral Antiseptics Against SARS-CoV-2: A Narrative Review.

Aims and Objectives: The detection of SARS-COV-2 in the oral cavity has generated endless claims about the efficacy of using oral mouthwashes to reduce viral load. This review aims to assess the current evidence on the use of oral antiseptics against SARS-CoV-2 and to assess the certainty of the evidence according to the GRADE system. The question this study focussed on was what is the efficacy of oral antiseptics against SARS-CoV-2? Materials and Methods: A bibliographic search was performed in Medline databases through PubMed, Science Direct, and Google Scholar (until February 2022), using search terms related to COVID-19 and oral antiseptics. Two independent researchers extracted the information from the articles included in an excel form. The identification and selection of the studies was carried out from August 2021 to February 2022. Results: It was found that oral antiseptics can have a potential beneficial effect on COVID-19, mainly in reducing viral load. However, these potential benefits are mainly based on in-vitro studies or clinical studies with various methodological limitations. At present, the certainty of the evidence is very low due to inconsistency (heterogeneity), moderate-to-high risk of bias, and imprecision of the results. Conclusion: The certainty of the current evidence on the efficacy of oral antiseptics against SARS-CoV-2 is very low, mainly due to the methodological limitations of the studies. Therefore, for evidence-based decision-making about this intervention, clinical studies with greater methodological rigor are required. Oral antiseptics could present potential benefits in patients with COVID-19 mainly by reducing viral load. However, a careful and conscious evaluation of the evidence is required for decision-making in clinical practice.

Japanese rapid/living recommendations on drug management for COVID-19: updated guidelines (July 2022).

Background: Coronavirus disease (COVID-19), an infectious disease caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide since early 2020, and there are still no signs of resolution. The Japanese Clinical Practice Guidelines for the Management of Sepsis and Septic Shock (J-SSCG) 2020 Special Committee created the Japanese Rapid/Living recommendations on drug management for COVID-19 using the experience of creating the J-SSCG. Methods: The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach was used to determine the certainty of the evidence and strength of recommendations. The first edition of this guideline was released on September 9, 2020, and this is the revised edition (version 5.0; released on July 15, 2022). Clinical questions (CQs) were set for the following 10 drugs: favipiravir (CQ1), remdesivir (CQ2), corticosteroids (CQ4), tocilizumab (CQ5), anticoagulants (CQ7), baricitinib (CQ8), casirivimab/imdevimab (CQ9-1), sotrovimab (CQ9-2), molnupiravir (CQ10), and nirmatrelvir/ritonavir (CQ11). Recommendations: Favipiravir is not suggested for all patients with COVID-19 (GRADE 2C). Remdesivir is suggested for patients with mild COVID-19 who do not require oxygen, and patients with moderate COVID-19 requiring supplemental oxygen/hospitalization (both GRADE 2B). Corticosteroids are recommended for moderate and severe COVID-19 (GRADE 1B, 1A). However, their administration is not recommended for mild COVID-19 (GRADE 1B). Tocilizumab is suggested for moderate and severe COVID-19 (GRADE 2B, 2C). Anticoagulant administration is recommended for moderate and severe COVID-19 (Good Practice Statement). Baricitinib is suggested for moderate and severe COVID-19 (both GRADE 2C). Casirivimab/imdevimab and sotrovimab are recommended for mild COVID-19 (both GRADE 2C). Molnupiravir and nirmatrelvir/ritonavir are recommended for mild COVID-19 (both GRADE 2C). SARS-CoV-2 mutant strains emerge occasionally, and each time, the treatment policy at clinics is forced to change drastically. We ask health-care professionals in the field to refer to the recommendations in these guidelines and use these to keep up to date with COVID-19 epidemiological information.

Honeybee Products for the Treatment and/ or Recovery of COVID-19 and Other Coronavirus-Related Respiratory Tract Infections: A Rapid Systematic Review

Methods: A protocol applying Cochrane rapid review methods was registered with PROSPERO: (CRD42020193847) in July 2020. Four English databases plus preprint servers and trial registries were searched for randomised controlled trials (RCTs). The evidence was appraised using RoB 2.0 and GRADE-approach. Results: 27 results, derived from 9 RCTs, included 674 adults and 781 children. In Hospitalized patients with confirmed SARS-CoV-2 infections, propolis plus usual care compared to usual care alone, reduced the risk of shock, (RR:0.36;95%CI:0.15, 0.88), respiratory failure (RR:0.32;95%CI:0.11, 0.92), and kidney injury (RR:0.36: 95% CI:0.15, 0.88) (all low-certainty) and duration of hospital admission (MD:-3.81 days, 95%CI:-6.19, -1.44) (moderate-certainty). Compared to coffee, honey plus coffee and honey alone, reduced the severity of post-infectious cough of a least 3-weeks duration in adults (MD:-1.40, 95%CI:-1.67, -1.13) (low-certainty) and (MD:-0.40, 95%CI:-0.75, 0.05) (very low-certainty) respectively. Honey was less effective than Guaifenesin in reducing cough severity at 60-minutes in adults with non-specific acute RTIs (MD:0.20 points, 95%CI: 0.05, 0.35) (very low-certainty). Honey compared to placebo reduced the duration of cough in children (MD:-0.71 days 95% CI:-1.15, -0.28) and compared to salbutamol (MD:-0.54 days 95%CI:-0.99, -0.09) (low-certainty);and the global impact of paediatric nocturnal cough was reduced by honey plus usualcare compared to usual-care alone (SMD:-0.80, 95%CI:-1.28, -0.32) (very low-certainty) and pharmaceutical cough medicines (SMD:-0.75 95%CI:-1.13, -0.36) (low-certainty). Background: This rapid review systematically evaluated the effects of honeybee products compared to controls for the duration, severity, and recovery of acute viral respiratory tract infections (RTIs), including SARS-CoV-2, in adults and children. Conclusion: More RCTs are needed to robustly inform the role of honey and propolis for treatment of SARS-CoV-2 and related respiratory infections.

Efficacy and Safety of COVID-19 Vaccines in Children Aged 5 to 11 Years: A Systematic Review

Purpose: To evaluate the efficacy and safety of coronavirus disease 2019 (COVID-19) vaccines in children aged 5–11 years, a rapid systematic review was conducted on published clinical trials of COVID-19 vaccines and studies that analyzed real-world data on adverse events after COVID-19 vaccination. Methods: A systematic search was conducted on medical literature in international (Ovid-MEDLINE) and pre-published literature databases (medRxiv), followed by handsearching up to January 4, 2022. We used terms including COVID-19, severe acute respiratory syndrome coronavirus 2, and vaccines, and the certainty of evidence was graded using the GRADE approach. Results: A total of 1,675 studies were identified, of which five were finally selected. Among the five studies, four consisted of data from clinical trials of each of the four types of COVID-19 vaccines (BNT162b2, mRNA-1273, CoronaVac, and BBIBP-CorV). The remaining study consisted of real-world data on the safety of the BNT162b2 vaccine in children aged 5–11 years. This systematic review identified that COVID-19 vaccines in recipients aged 5–11 years produced a favorable immune response, and were vaccines were effective against COVID-19. The safety findings for the BNT162b2 vaccine in children and early adolescents aged 5–11 years were similar to those data noted in the clinical trial. Conclusions: There is limited data on COVID-19 vaccines in children aged 5–11 years. Consequently continuous and comprehensive monitoring is necessary for the evaluation of the safety and effectiveness of the COVID-19 vaccines.

Japanese rapid/living recommendations on drug management for COVID-19: updated guidelines (September 2021).

BACKGROUND: The coronavirus disease 2019 (COVID-19) has spread worldwide since early 2020, and there are still no signs of resolution. The Japanese Clinical Practice Guidelines for the Management of Sepsis and Septic Shock (J-SSCG) 2020 Special Committee created the Japanese rapid/living recommendations on drug management for COVID-19 using the experience of creating the J-SSCG. METHODS: The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach was used to determine the certainty of the evidence and strength of the recommendations. The first edition of this guideline was released on September 9, 2020, and this document is the revised edition (version 4.0; released on September 9, 2021). Clinical questions (CQs) were set for the following seven drugs: favipiravir (CQ1), remdesivir (CQ2), corticosteroids (CQ4), tocilizumab (CQ5), anticoagulants (CQ7), baricitinib (CQ8), and casirivimab/imdevimab (CQ9). Two CQs (hydroxychloroquine [CQ3] and ciclesonide [CQ6]) were retrieved in this updated version. RECOMMENDATIONS: Favipiravir is not suggested for all patients with COVID-19 (GRADE 2C). Remdesivir is suggested for patients with moderate COVID-19 requiring supplemental oxygen/hospitalization (GRADE 2B). Corticosteroids are recommended for patients with moderate COVID-19 requiring supplemental oxygen/hospitalization (GRADE 1B) and for patients with severe COVID-19 requiring mechanical ventilation/intensive care (GRADE 1A); however, their administration is not recommended for patients with mild COVID-19 not requiring supplemental oxygen (GRADE 1B). Tocilizumab is suggested for patients with moderate COVID-19 requiring supplemental oxygen/hospitalization (GRADE 2B). Anticoagulant administration is recommended for patients with moderate COVID-19 requiring supplemental oxygen/hospitalization and patients with severe COVID-19 requiring mechanical ventilation/intensive care (good practice statement). Baricitinib is suggested for patients with moderate COVID-19 requiring supplemental oxygen/hospitalization (GRADE 2C). Casirivimab/imdevimab is recommended for patients with mild COVID-19 not requiring supplemental oxygen (GRADE 1B). We hope that these updated clinical practice guidelines will help medical professionals involved in the care of patients with COVID-19.

Japanese rapid/living recommendations on drug management for COVID-19.

The coronavirus disease (COVID-19) has spread worldwide since early 2020, and there are still no signs of resolution. The Japanese Clinical Practice Guidelines for the Management of Sepsis and Septic Shock (J-SSCG) 2020 Special Committee created the Japanese rapid/living recommendations on drug management for COVID-19 using the experience of creating the J-SSCGs. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach was used to determine the certainty of the evidence and strength of the recommendations. The first edition of this guideline was released on 9 September, 2020, and this document is the revised edition (version 3.1) (released 30 March, 2021). Clinical questions (CQs) were set for the following seven drugs: favipiravir (CQ1), remdesivir (CQ2), hydroxychloroquine (CQ3), corticosteroids (CQ4), tocilizumab (CQ5), ciclesonide (CQ6), and anticoagulants (CQ7). Favipiravir is recommended for patients with mild COVID-19 not requiring supplemental oxygen (GRADE 2C); remdesivir for moderate COVID-19 patients requiring supplemental oxygen/hospitalization (GRADE 2B). Hydroxychloroquine is not recommended for all COVID-19 patients (GRADE 1B). Corticosteroids are recommended for moderate COVID-19 patients requiring supplemental oxygen/hospitalization (GRADE 1B) and severe COVID-19 patients requiring ventilator management/intensive care (GRADE 1A); however, their use is not recommended for mild COVID-19 patients not requiring supplemental oxygen (GRADE 1B). Tocilizumab is recommended for moderate COVID-19 patients requiring supplemental oxygen/hospitalization (GRADE 2B). Anticoagulant therapy is recommended for moderate COVID-19 patients requiring supplemental oxygen/hospitalization and severe COVID-19 patients requiring ventilator management/intensive care (GRADE 2C). We hope that these clinical practice guidelines will aid medical professionals involved in the care of COVID-19 patients.