Rationale and protocol for a prospective cohort study of respiratory viral infections in patients admitted from emergency departments of community hospitals: Effect of respiratory Virus infection on EmeRgencY admission (EVERY) study.

INTRODUCTION: Respiratory syncytial virus (RSV) is a causative virus for the common cold worldwide and can result in hospitalisations and even death in patients with high-risk conditions and older adults. However, the relationship between RSV or other incidental respiratory infections and acute exacerbations of underlying conditions has not been well investigated. The primary objective of this study is to estimate RSV prevalence, risk factors for adverse outcomes or hospitalisation and their effect on the hospital course of patients with acute respiratory symptoms admitted from emergency departments. Furthermore, we evaluate the prevalence of other respiratory viruses associated with respiratory symptoms. METHODS AND ANALYSIS: We are conducting a multicentre prospective cohort study in Japan. We plan to enrol 3000 consecutive patients admitted from emergency departments with acute respiratory symptoms or signs from 1 July 2023 to 30 June 2024. A nasopharyngeal swab is obtained within 24 hours of admission and the prevalence of RSV and other respiratory viruses is measured using the FilmArray Respiratory 2.1 panel. Paired serum samples are collected from patients with suspected lower respiratory infections to measure RSV antibodies at admission and 30 days later. Information on patients' hospital course is retrieved from the electronic medical records at discharge, death or 30 days after admission. Furthermore, information on readmission to the hospital and all-cause mortality is collected 180 days after admission. We assess the differences in clinical outcomes between patients with RSV or other respiratory viruses and those without, adjusting for baseline characteristics. Clinical outcomes include in-hospital mortality, length of hospital stay, disease progression, laboratory tests and management of respiratory symptoms or underlying conditions. ETHICS AND DISSEMINATION: The study protocol was approved by the institutional review boards of participating hospitals. Our study reports will be published in academic journals as well as international meetings. TRIAL REGISTRATION NUMBER: NCT05913700.

Challenges of using body bags for COVID-19 deaths from the healthcare provider perspective - a qualitative study.

BACKGROUND: During the COVID-19 pandemic, numerous issues regarding end-of-life care for COVID-19 patients have been discussed. Among these issues, challenges related to the use of body bags following the death of COVID-19 patients have been suggested. This study aimed to identify the challenges faced by healthcare professionals (HCPs) when using body bags after the death of patients infected with COVID-19 in medical settings. METHODS: We conducted a qualitative descriptive study with semistructured in-depth interviews using inductive thematic analysis. From August to December 2021, we interviewed nurses and doctors who provided end-of-life care to COVID-19 patients focusing on their experiences with the use of body bags for the deceased. RESULTS: Of the 25 interviewees who mentioned body bag use, 14 were nurses (56%) and 13 were women (52%). The mean interview length was 52.0 min (SD 9.6 min). Challenges associated with body bag use were classified into four themes with eight categories: preserving the dignity of the deceased, consideration for the bereaved saying a final goodbye to a loved one in a body bag, the physical and emotional impact on HCPs, and diverse opinions on body bag use. CONCLUSION: Our findings include ethical concerns about the dignity of the deceased, empathy for the grief of bereaved families, and the emotional and physical distress experienced by HCPs struggling with the recommendation to use body bags based on limited evidence. The diverse perspectives of HCPs in this study highlight potential issues that developers should consider when formulating more appropriate and acceptable guidelines/guidance and policies.

Effectiveness of primary series, first, and second booster vaccination of monovalent mRNA COVID-19 vaccines against symptomatic SARS-CoV-2 infections and severe diseases during the SARS-CoV-2 omicron BA.5 epidemic in Japan: vaccine effectiveness real-time surveillance for SARS-CoV-2 (VERSUS).

BACKGROUND: This study aimed to evaluate VE of primary, first, and second booster ancestral-strain monovalent mRNA COVID-19 vaccination against symptomatic infections and severe diseases in Japan. METHODS: We conducted a test-negative case-control study. We included medically attended episodes and hospitalizations involving individuals aged ≥16 with signs and symptoms from July to November 2022, when Omicron BA.5 was dominant nationwide. To evaluate VE, we calculated adjusted ORs of vaccination among test-positive versus test-negative individuals using a mixed-effects logistic regression. RESULTS: For VE against symptomatic infections among individuals aged 16 to 59, VE of primary vaccination at > 180 days was 26.1% (95% CI: 10.6-38.8%); VE of the first booster was 58.5% (48.4-66.7%) at ≤90 days, decreasing to 41.1% (29.5-50.8%) at 91 to 180 days. For individuals aged ≥60, VE of the first booster was 42.8% (1.7-66.7%) at ≤90 days, dropping to 15.4% (-25.9-43.2%) at 91 to 180 days, and then increasing to 44.0% (16.4-62.5%) after the second booster. For VE against severe diseases, VE of the first and second booster was 77.3% (61.2-86.7%) at ≤90 days and 55.9% (23.4-74.6%) afterward. CONCLUSION: mRNA booster vaccination provided moderate protection against symptomatic infections and high-level protection against severe diseases during the BA.5 epidemic in Japan.

Infected Aortic Aneurysm Secondary to Pyogenic Flexor Tenosynovitis from Streptococcus pyogenes.

Infected aortic aneurysms are rare, and have a high mortality rate. Although not a major pathogen, Streptococcus pyogenes has been reported to cause infected aortic aneurysms. In the present case, the patient was hospitalized for pyogenic flexor tenosynovitis with S. pyogenes bacteremia. Despite drainage of the abscess around the flexor tendon and effective antimicrobial therapy, infected aneurysms developed in the abdomen and ascending aorta. Because of their rapid enlargement, these aneurysms were treated with in situ reconstruction. Although rare, the possibility that S. pyogenes is the causative pathogen of infected aortic aneurysms should be considered.

Effectiveness of mRNA COVID-19 vaccines against symptomatic SARS-CoV-2 infections during the SARS-CoV-2 Omicron BA.1 and BA.2 epidemic in Japan: vaccine effectiveness real-time surveillance for SARS-CoV-2 (VERSUS).

BACKGROUND: Evaluating COVID-19 vaccine effectiveness (VE) domestically is crucial for assessing and determining national vaccination policy. This study aimed to evaluate VE of mRNA COVID-19 vaccines in Japan. METHODS: We conducted a multicenter test-negative case-control study. The study comprised individuals aged ≥16 visiting medical facilities with COVID-19-related signs or symptoms from 1 January to 26 June 2022, when Omicron BA.1 and BA.2 were dominant nationwide. We evaluated VE of primary and booster vaccination against symptomatic SARS-CoV-2 infections and relative VE of booster compared with primary. RESULTS: We enrolled 7,931 episodes, including 3,055 test positive. The median age was 39, 48.0% were male, and 20.5% had underlying medical conditions. In individuals aged 16 to 64, VE of primary vaccination within 90 days was 35.6% (95% CI, 19.0-48.8%). After booster, VE increased to 68.7% (60.6-75.1%). In individuals aged ≥65, VE of primary and booster was 31.2% (-44.0-67.1%) and 76.5% (46.7-89.7%), respectively. Relative VE of booster compared with primary vaccination was 52.9% (41.0-62.5%) in individuals aged 16 to 64 and 65.9% (35.7-81.9%) in individuals aged ≥65. CONCLUSIONS: During BA.1 and BA.2 epidemic in Japan, mRNA COVID-19 primary vaccination provided modest protection. Booster vaccination was necessary to protect against symptomatic infections.

Predictors of delayed wound healing after simultaneous endovascular treatment and minor forefoot amputation for chronic limb-threatening ischemia with wound infection.

OBJECTIVES: To assess wound healing after simultaneous endovascular treatment (EVT) and minor forefoot amputation and identify the predictors of delayed wound healing in patients with chronic limb-threatening ischemia (CLTI) and bacterial infections of the wounds. METHODS: In this single-center retrospective cohort study, we evaluated 79 consecutive limbs with tissue loss from 73 CLTI patients who underwent simultaneous EVT and minor forefoot amputation between November 2017 and May 2020. To estimate the rate of wound healing after the simultaneous procedure, we used the Kaplan-Meier method. To assess the association between baseline characteristics and delayed wound healing, we used the Cox proportional hazard model. RESULTS: All patients who underwent the simultaneous procedure had ischemic wounds with bacterial infection. The rate of wound healing at 6 months reached 82%. The median time for wound healing was 76 days. According to multivariable analysis, Lisfranc/Chopart amputation (hazard ratio (HR) 2.46, 95% confidence interval (CI) 1.09-6.60), absence of above-the-knee (ATK) occlusive lesions (HR 1.89, 95% CI 1.04-3.45), and poor below-the-ankle (BTA) runoff (HR 1.77, 95% CI 1.01-3.11) were independent predictors of delayed wound healing. CONCLUSION: Lisfranc/Chopart amputation, absence of ATK occlusive lesions, and poor BTA runoff were independent predictors of delayed wound healing after simultaneous EVT and minor forefoot amputation in patients with CLTI and bacterial infections of the wound.

Providing End-of-Life Care for Patients Dying of COVID-19 and Their Families in Isolated Death During the Pandemic in Japan: The Providing End-of-life Care for COVID-19 Project.

BACKGROUND: Death resulting from COVID-19 in a hospital during the pandemic has meant death in isolation. Although many health care providers (HCPs) have struggled with end-of-life (EOL) care for these patients, the various strategies across hospitals are not well known. RESEARCH QUESTION: What EOL care did HCPs give patients dying of COVID-19 and their families in hospitals during the COVID-19 pandemic? What were the key themes in care? STUDY DESIGN AND METHODS: This qualitative study used individual, semistructured, internet, and face-to-face interviews. We recruited HCPs who provided EOL care to patients with COVID-19 dying in hospitals and their families. Purposive sampling was used through the academic networks at the School of Public Health, Kyoto University. Anonymized verbatim transcripts were analyzed thematically. RESULTS: Fifteen doctors and 18 nurses from 23 hospitals in 13 regions across Japan participated; 16 participants (48%) were women, with an age range of 20 to 59 years (most were 30-39 years of age). Participants described 51 strategies, including providing physical and psychological-spiritual care, making connections, providing death care, and arranging care environments and bereavement care for patients and their families. Four themes emerged as prominent efforts in COVID-19 EOL care: maintaining relationships with isolated patients, connecting patients and families, sharing decision-making in isolation, and creating humanistic episodes. INTERPRETATION: Proper application and awareness of the four themes may help HCPs to implement better EOL care. To compensate for limited memories resulting from isolation and rapid progression of the disease, communicating and creating humanistic episodes are emphasized. ICU diaries and the HCPs' arrangements based on cultural funerary procedures could be provided as grief care for the family and to build trust. EOL education and building partnerships among palliative care staff and nonmedical personnel on a regular basis may enhance the capacity to deliver the necessary support for EOL care.

Impact of Antimicrobial-Resistant Bacterial and Polymicrobial Infection on Wound Healing After Minor Forefoot Amputation in Chronic Limb-Threatening Ischemia With Infection.

OBJECTIVES: This study aimed to evaluate the relationship between bacteriological findings and wound healing after minor amputation in the treatment of chronic limb-threatening ischemia (CLTI) with infection. METHODS: This single-center retrospective study analyzed 135 consecutive limbs with tissue loss and infection from 120 patients who underwent endovascular therapy (EVT) and minor forefoot amputation for CLTI with wound infection between November 2017 and August 2021. The Kaplan-Meier method was used to assess the rate of wound healing after the procedure. The Cox proportional-hazards model was used to examine the impact of bacteriological findings and baseline characteristics on wound healing. RESULTS: The wound healing rate at 6 months was 72.6%. In a multivariate analysis, in addition to hemodialysis (hazard ratio [HR]=1.73; p=0.009) and amputation above the metatarsophalangeal (MP) joint (HR=1.81; p=0.006), antimicrobial-resistant bacterial infection (HR=1.80, p=0.004) and polymicrobial infection (H=1.51; p=0.049) were predictors of delayed wound healing. CONCLUSION: Antimicrobial-resistant bacterial infection, polymicrobial infection, hemodialysis, and amputation above the MP joint were independent predictors of delayed wound healing after EVT and minor forefoot amputation in patients with CLTI and bacterial wound infection. CLINICAL IMPACT: In this single-center retrospective study, we analyzed 136 consecutive limbs with tissue loss and infection from 120 patients who underwent endovascular therapy and minor forefoot amputation for chronic limb-threatening ischemia (CLTI) with wound infection between November 2017 and August 2021. Our main findings were that antimicrobial-resistant bacterial infection, polymicrobial infection, hemodialysis, and amputation above the metatarsophalangeal joint were independent predictors of delayed wound healing after minor amputation. This is the first report of the association between bacteriological studies and wound healing in CLTI with infection, and will be of great help in the future clinical practice.

Tracheostomy decannulation rates in Japan: a retrospective cohort study using a claims database.

Despite the exponential increase in the use of tracheostomy worldwide, rates of tracheostomy decannulation are unknown. We conducted a retrospective cohort study to investigate tracheostomy decannulation rates among adult patients over a two-year period and explored factors associated with prolonged tracheostomy. A health insurance claims database including 3,758,210 people in Japan was used. The primary outcome was time to decannulation. Assessed patient and hospital factors included age, sex, emergency endotracheal intubation, disease, and hospital size. A total of 917 patients underwent tracheostomy, and 752 met the eligibility criteria. Decannulation rates were 40.8% (95% confidence interval 36.8-44.9) at 3 months, 63.9% (58.4-69.0) at 12 months, and 65.0% (59.2-70.3) at 24 months. Hazard ratios of patient and hospital factors for tracheostomy decannulation were 0.44 for age (65-74 years) (95% confidence interval 0.28-0.68), 0.81 (0.63-1.05) for female sex, and 0.59 (0.45-0.76) for emergency endotracheal intubation. Cerebrovascular disease, head injuries, and cardiac arrest had lower hazard ratios compared to other diseases. Decannulation rates among adult patients in Japan increased rapidly up to 3 months after tracheostomy, reaching a plateau after 12 months. Older age, female sex, emergency endotracheal intubation, cerebrovascular disease, head injuries, and cardiac arrest were associated with prolonged tracheostomy.

Pre-emptive antifungal therapy versus empirical antifungal therapy for febrile neutropenia in people with cancer.

BACKGROUND: Intensive cytotoxic chemotherapy for people with cancer can cause severe and prolonged cytopenia, especially neutropenia, a critical condition that is potentially life-threatening. When manifested by fever and neutropenia, it is called febrile neutropenia (FN). Invasive fungal disease (IFD) is one of the serious aetiologies of chemotherapy-induced FN. In pre-emptive therapy, physicians only initiate antifungal therapy when an invasive fungal infection is detected by a diagnostic test. Compared to empirical antifungal therapy, pre-emptive therapy may reduce the use of antifungal agents and associated adverse effects, but may increase mortality. The benefits and harms associated with the two treatment strategies have yet to be determined.  OBJECTIVES: To assess the relative efficacy, safety, and impact on antifungal agent use of pre-emptive versus empirical antifungal therapy in people with cancer who have febrile neutropenia. SEARCH METHODS: We searched CENTRAL, MEDLINE Ovid, Embase Ovid, and ClinicalTrials.gov to October 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared pre-emptive antifungal therapy with empirical antifungal therapy for people with cancer. DATA COLLECTION AND ANALYSIS: We identified 2257 records from the databases and handsearching. After removing duplicates, screening titles and abstracts, and reviewing full-text reports, we included seven studies in the review. We evaluated the effects on all-cause mortality, mortality ascribed to fungal infection, proportion of antifungal agent use (other than prophylactic use), duration of antifungal use (days), invasive fungal infection detection, and adverse effects for the comparison of pre-emptive versus empirical antifungal therapy. We presented the overall certainty of the evidence for each outcome according to the GRADE approach. MAIN RESULTS: This review includes 1480 participants from seven randomised controlled trials. Included studies only enroled participants at high risk of FN (e.g. people with haematological malignancy); none of them included participants at low risk (e.g. people with solid tumours).  Low-certainty evidence suggests there may be little to no difference between pre-emptive and empirical antifungal treatment for all-cause mortality (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.72 to 1.30; absolute effect, reduced by 3/1000); and for mortality ascribed to fungal infection (RR 0.92, 95% CI 0.45 to 1.89; absolute effect, reduced by 2/1000). Pre-emptive therapy may decrease the proportion of antifungal agent used more than empirical therapy (other than prophylactic use; RR 0.71, 95% CI 0.47 to 1.05; absolute effect, reduced by 125/1000; very low-certainty evidence). Pre-emptive therapy may reduce the duration of antifungal use more than empirical treatment (mean difference (MD) -3.52 days, 95% CI -6.99 to -0.06, very low-certainty evidence). Pre-emptive therapy may increase invasive fungal infection detection compared to empirical treatment (RR 1.70, 95% CI 0.71 to 4.05; absolute effect, increased by 43/1000; very low-certainty evidence). Although we were unable to pool adverse events in a meta-analysis, there seemed to be no apparent difference in the frequency or severity of adverse events between groups. Due to the nature of the intervention, none of the seven RCTs could blind participants and personnel related to performance bias. We identified considerable clinical and statistical heterogeneity, which reduced the certainty of the evidence for each outcome. However, the two mortality outcomes had less statistical heterogeneity than other outcomes. AUTHORS' CONCLUSIONS: For people with cancer who are at high-risk of febrile neutropenia, pre-emptive antifungal therapy may reduce the duration and rate of use of antifungal agents compared to empirical therapy, without increasing over-all and IFD-related mortality; but the evidence regarding invasive fungal infection detection and adverse events was inconsistent and uncertain.

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.

Doppler trans-thoracic echocardiography for detection of pulmonary hypertension in adults.

BACKGROUND: Pulmonary hypertension (PH) is an important cause of morbidity and mortality, which leads to a substantial loss of exercise capacity. PH ultimately leads to right ventricular overload and subsequent heart failure and early death. Although early detection and treatment of PH are recommended, due to the limited responsiveness to therapy at late disease stages, many patients are diagnosed at a later stage of the disease because symptoms and signs of PH are nonspecific at earlier stages. While direct pressure measurement with right-heart catheterisation is the clinical reference standard for PH, it is not routinely used due to its invasiveness and complications. Trans-thoracic Doppler echocardiography is less invasive, less expensive, and widely available compared to right-heart catheterisation; it is therefore recommended that echocardiography be used as an initial diagnosis method in guidelines. However, several studies have questioned the accuracy of noninvasively measured pulmonary artery pressure. There is substantial uncertainty about the diagnostic accuracy of echocardiography for the diagnosis of PH. OBJECTIVES: To determine the diagnostic accuracy of trans-thoracic Doppler echocardiography for detecting PH. SEARCH METHODS: We searched MEDLINE, Embase, Web of Science Core Collection, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform from database inception to August 2021, reference lists of articles, and contacted study authors. We applied no restrictions on language or type of publication. SELECTION CRITERIA: We included studies that evaluated the diagnostic accuracy of trans-thoracic Doppler echocardiography for detecting PH, where right-heart catheterisation was the reference standard. We excluded diagnostic case-control studies (two-gate design), studies where right-heart catheterisation was not the reference standard, and those in which the reference standard threshold differed from 25 mmHg. We also excluded studies that did not provide sufficient diagnostic test accuracy data (true-positive [TP], false-positive [FP], true-negative [TN], and false-negative [FN] values, based on the reference standard). We included studies that provided data from which we could extract TP, FP, TN, and FN values, based on the reference standard. Two authors independently screened and assessed the eligibility based on the titles and abstracts of records identified by the search. After the title and abstract screening, the full-text reports of all potentially eligible studies were obtained, and two authors independently assessed the eligibility of the full-text reports. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the risk of bias and extracted data from each of the included studies. We contacted the authors of the included studies to obtain missing data. We assessed the methodological quality of studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. We estimated a summary receiver operating characteristic (SROC) curve by fitting a hierarchical summary ROC (HSROC) non-linear mixed model. We explored sources of heterogeneity regarding types of PH, methods to estimate the right atrial pressure, and threshold of index test to diagnose PH. All analyses were performed using the Review Manager 5, SAS and STATA statistical software. MAIN RESULTS: We included 17 studies (comprising 3656 adult patients) assessing the diagnostic accuracy of Doppler trans-thoracic echocardiography for the diagnosis of PH. The included studies were heterogeneous in terms of patient distribution of age, sex, WHO classification, setting, country, positivity threshold, and year of publication. The prevalence of PH reported in the included studies varied widely (from 6% to 88%). The threshold of index test for PH diagnosis varied widely (from 30 mmHg to 47 mmHg) and was not always prespecified. No study was assigned low risk of bias or low concern in each QUADAS-2 domain assessed. Poor reporting, especially in the index test and reference standard domains, hampered conclusive judgement about the risk of bias. There was little consistency in the thresholds used in the included studies; therefore, common thresholds contained very sparse data, which prevented us from calculating summary points of accuracy estimates. With a fixed specificity of 86% (the median specificity), the estimated sensitivity derived from the median value of specificity using HSROC model was 87% (95% confidence interval [CI]: 78% to 96%). Using a prevalence of PH of 68%, which was the median among the included studies conducted mainly in tertiary hospitals, diagnosing a cohort of 1000 adult patients under suspicion of PH would result in 88 patients being undiagnosed with PH (false negatives) and 275 patients would avoid unnecessary referral for a right-heart catheterisation (true negatives). In addition, 592 of 1000 patients would receive an appropriate and timely referral for a right-heart catheterisation (true positives), while 45 patients would be wrongly considered to have PH (false positives). Conversely, when we assumed low prevalence of PH (10%), as in the case of preoperative examinations for liver transplantation, the number of false negatives and false positives would be 13 and 126, respectively. AUTHORS' CONCLUSIONS: Our evidence assessment of echocardiography for the diagnosis of PH in adult patients revealed several limitations. We were unable to determine the average sensitivity and specificity at any particular index test threshold and to explain the observed variability in results. The high heterogeneity of the collected data and the poor methodological quality would constrain the implementation of this result into clinical practice. Further studies relative to the accuracy of Doppler trans-thoracic echocardiography for the diagnosis of PH in adults, that apply a rigorous methodology for conducting diagnostic test accuracy studies, are needed.

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.

A model six-month workshop for developing systematic review protocols at teaching hospitals: action research and scholarly productivity.

BACKGROUND: Research engagement contributes to the improvement of patient care. A systematic review is a suitable first scholarly activity because it entails summarization of publicly available data and usually requires neither rigorous ethical review nor research funding. METHODS: This study aimed to develop a model workshop for healthcare staff to acquire skills in creating systematic review protocols based on their own clinical questions at teaching hospitals. We used an action research method to create a model workshop at four hospitals in Japan from April 2015 to March 2017. To improve the program, we solicited reflections using participant questionnaires for each lecture and examined the quality of homework submitted by participants after each lecture. We administered a revised final version of the workshop at five hospitals from April 2016 to March 2017. We evaluated the participants' scholarly productivity related to these workshops. The observation period was a minimum of 2 years following the workshops. RESULTS: Most participants had never developed a formal clinical research protocol and voluntarily participated in the workshop. The action research was developed and implemented at nine teaching hospitals in Japan, including one university hospital. The study developed a model nine-step workshop curriculum: 1) Research question development, 2) Search strategy development, 3) Search strategy brush-up, 4) Exclusion and inclusion criteria development, 5) Risk of bias assessment planning, 6) Meta-analysis planning, 7) Subgroup and sensitivity analysis planning, 8) Planning the presentation of results, and 9) Presentation protocols. A total of 233 participants, including medical doctors and other health professionals, produced 414 research questions. Seventy-nine participants (34%) completed the workshop, and 47 review teams accomplished systematic review protocols. The participants published 13 peer-reviewed articles as a result of the workshop. CONCLUSIONS: We developed a structured scholarly productive model workshop for healthcare staff working at hospitals. We found healthcare staff with clinical subspecialties were able to develop an unexpectedly high number of research questions through this workshop. Medical teachers at hospitals with prior systematic review experience could teach how to develop systematic review protocols using this model. Further research is needed to increase the academic productivity of such workshops. TRIAL REGISTRATION: UMIN (https://www.umin.ac.jp/ctr/), UMIN000017107 (4/15/2015), UMIN000025580 (1/10/2017).

Prolonged versus intermittent ß-lactam antibiotics intravenous infusion strategy in sepsis or septic shock patients: a systematic review with meta-analysis and trial sequential analysis of randomized trials.

BACKGROUND: The prolonged ß-lactam infusion strategy has emerged as the standard treatment for sepsis or septic shock despite its unknown efficacy. This study aimed to assess the efficacy of prolonged versus intermittent ß-lactam antibiotics infusion on outcomes in sepsis or septic shock patients by conducting a systematic review and meta-analysis. METHODS: A thorough search was conducted on MEDLINE, the Cochrane Central Register of Controlled Trials, and the Igaku Chuo Zasshi databases. Randomized controlled trials (RCTs) comparing mortality between prolonged and intermittent infusion in adult patients with sepsis or septic shock were included. The primary outcome was hospital mortality. The secondary outcomes were the attainment of the target plasma concentration, clinical cure, adverse events, and occurrence of antibiotic-resistant bacteria. We performed a subgroup analysis stratified according to the year of publication before or after 2015 and a trial sequential analysis (TSA). The Der Simonian-Laird random-effects models were subsequently used to report the pooled risk ratios (RR) with confidence intervals (CI). RESULTS: We identified 2869 studies from the 3 databases, and 13 studies were included in the meta-analysis. Hospital mortality did not decrease (RR 0.69 [95%CI 0.47-1.02]) in the prolonged infusion group. The attainment of the target plasma concentration and clinical cure significantly improved (RR 0.40 [95%CI 0.21-0.75] and RR 0.84 [95%CI 0.73-0.97], respectively) in the prolonged infusion group. There were, however, no significant differences in the adverse events and the occurrence of antibiotic-resistant bacteria between the groups (RR 1.01 (95%CI 0.95-1.06) and RR 0.53 [95%CI 0.10-2.83], respectively). For the subgroup analysis, a significant improvement in hospital mortality or clinical cure was reported in studies published in or after 2015 (RR 0.66 [95%CI 0.44-0.98] and RR 0.67 [95%CI 0.50-0.90], respectively). The results of the TSA indicated an insufficient number of studies for a definitive analysis. CONCLUSIONS: The prolonged infusion of ß-lactam antibiotics significantly improved upon attaining the target plasma concentration and clinical cure without increasing the adverse event or the occurrence of antibiotic-resistant bacteria. Prolonged infusion could not improve hospital mortality although an improvement was shown for studies published in or after 2015. Further studies are warranted as suggested by our TSA results.

Associations of multimorbidity with breast, cervical, and colorectal cancer screening delivery: a cross-sectional study of a nationally representative Japanese sample.

BACKGROUND: Multimorbidity is associated with a high mortality rate and low health-related quality of life. Previous studies have indicated that multimorbidity tends to be associated with not receiving cancer screening, although this association remains unclear. This study aimed to investigate the associations between multimorbidity and the delivery of breast, cervical, and colorectal cancer screening in Japan, and to identify subgroups that did not receive cancer screening. METHODS: This study used cross-sectional data from the 2016 Comprehensive Survey of Living Conditions, which used a stratified random sample of the general Japanese population. Multivariable logistic regression models were used to evaluate the associations between the number of chronic conditions and each cancer's screening proportion. The relevant covariates included age, marital status, education level, occupation, and household income. RESULTS: Relative to subjects with no chronic conditions, subjects with two chronic conditions received more screening for breast, cervical, and colorectal cancers (breast cancer, adjusted odds ratio [aOR]: 5.42, 95% confidence interval [CI]: 2.80-10.5; cervical cancer, aOR: 4.59, 95% CI: 2.03-10.4; male colorectal cancer, aOR: 3.26, 95% CI: 1.29-8.24; female colorectal cancer, aOR: 1.05, 95% CI: 0.39-2.81). Low socioeconomic status was associated with not receiving any type of cancer screening consistently. CONCLUSION: Multimorbidity and high socioeconomic status were associated with higher proportions of screening for breast, cervical, and colorectal cancers in the Japanese population. More aggressive strategies may be needed to promote screening among Japanese individuals with no chronic conditions and individuals with low socioeconomic status.

Updates to and quality of clinical practice guidelines for high-priority diseases in Japan.

PURPOSE: To examine the update status of clinical practice guidelines (CPGs) for 24 main diseases in Japan, and to clarify the quality of and issues pertaining to the most recent versions of CPGs for each disease. DATA SOURCES: CPGs were searched in two Japanese guideline databases. STUDY SELECTION: All relevant Japanese CPGs published between January 1999 and July 2016 were selected. DATA EXTRACTION: The developer and issue date were extracted for all target CPGs. The most recent CPGs were assessed using the Appraisal of Guidelines for Research and Evaluation-II (AGREE II) instrument. RESULTS OF DATA SYNTHESIS: Among 106 target CPGs, 24 most recent CPGs were subjected to assessment using the AGREE II instrument. CPGs for 11 diseases (46%) had a mean time interval for update of ≥5 years. Among the 24 CPGs subjected to AGREE II assessment, median domain scores were 74% for "Domain 1: Scope and Purpose," 43% for "Domain 2: Stakeholder Involvement," 46% for "Domain 3: Rigor of Development," 69% for "Domain 4: Clarity of Presentation," 24% for "Domain 5: Applicability" and 27% for "Domain 6: Editorial Independence." CONCLUSIONS: The systematic assessment of CPGs for 24 major diseases in Japan revealed a trend for a delay in timing of update for many CPGs. Moreover, the 24 most recent CPGs had low domain scores for domains 2, 3, 5 and 6. In the future, concrete measures will need to be considered in order to improve the quality of CPGs.

Social vital signs for improving awareness about social determinants of health.

We, Team SAIL, have held sessions introducing social vital signs (SVS). SVS is a useful tool for evaluating patient's social determinants of health (SDH).