AASLD position paper: the management of acute liver failure (特集 救急診療ガイドライン) -- (海外のガイドライン)

Background Scrub typhus is an acute febrile illness caused by intracellular bacteria from the genus Orientia. It is estimated that one billion people are at risk, with one million cases annually mainly affecting rural areas in Asia-Oceania. Relative to its burden, scrub typhus is understudied, and treatment recommendations vary with poor evidence base. These knowledge gaps could be addressed by establishing an individual participant-level data (IPD) platform, which would enable pooled, more detailed and statistically powered analyses to be conducted. This study aims to assess the characteristics of scrub typhus treatment studies and explore the feasibility and potential value of developing a scrub typhus IPD platform to address unanswered research questions. Methodology/principal findings We conducted a systematic literature review looking for prospective scrub typhus clinical treatment studies published from 1998 to 2020. Six electronic databases (Ovid Embase, Ovid Medline, Ovid Global Health, Cochrane Library, Scopus, Global Index Medicus), ClinicalTrials.gov, and WHO ICTRP were searched. We extracted data on study design, treatment tested, patient characteristics, diagnostic methods, geographical location, outcome measures, and statistical methodology. Among 3,100 articles screened, 127 were included in the analysis. 12,079 participants from 12 countries were enrolled in the identified studies. ELISA, PCR, and eschar presence were the most commonly used diagnostic methods. Doxycycline, azithromycin, and chloramphenicol were the most commonly administered antibiotics. Mortality, complications, adverse events, and clinical response were assessed in most studies. There was substantial heterogeneity in the diagnostic methods used, treatment administered (including dosing and duration), and outcome assessed across studies. There were few interventional studies and limited data collected on specific groups such as children and pregnant women. Conclusions/significance There were a limited number of interventional trials, highlighting that scrub typhus remains a neglected disease. The heterogeneous nature of the available data reflects the absence of consensus in treatment and research methodologies and poses a significant barrier to aggregating information across available published data without access to the underlying IPD. There is likely to be a substantial amount of data available to address knowledge gaps. Therefore, there is value for an IPD platform that will facilitate pooling and harmonisation of currently scattered data and enable in-depth investigation of priority research questions that can, ultimately, inform clinical practice and improve health outcomes for scrub typhus patients.

/pdf/systematic-review-of-the-scrub-typhus-treatment-landscape-26cou68kvi.pdf

Systematic review of the scrub typhus treatment landscape: Assessing the feasibility of an individual participant-level data (IPD) platform.

Background Scrub typhus is an acute febrile illness caused by intracellular bacteria from the genus Orientia. It is estimated that one billion people are at risk, with one million cases annually mainly affecting rural areas in Asia-Oceania. Relative to its burden, scrub typhus is understudied, and treatment recommendations vary with poor evidence base. These knowledge gaps could be addressed by establishing an individual participant-level data (IPD) platform, which would enable pooled, more detailed and statistically powered analyses to be conducted. This study aims to assess the characteristics of scrub typhus treatment studies and explore the feasibility and potential value of developing a scrub typhus IPD platform to address unanswered research questions. Methodology/Principal Findings We conducted a systematic literature review looking for prospective scrub typhus clinical treatment studies published from 1998 to 2020. Six electronic databases (Ovid Embase, Ovid Medline, Ovid Global Health, Cochrane Library, Scopus, Global Index Medicus), ClinicalTrials.gov, and WHO ICTRP were searched. We extracted data on study design, treatment tested, patient characteristics, diagnostic methods, geographical location, outcome measures, and statistical methodology. Among 3,100 articles screened, 127 were included in the analysis. 12,079 participants from 12 countries were enrolled in the identified studies. ELISA, PCR, and eschar presence were the most commonly used diagnostic methods. Doxycycline, azithromycin, and chloramphenicol were the most commonly administered antibiotics. Mortality, complications, adverse events, and clinical response were assessed in most studies. There was substantial heterogeneity in the diagnostic methods used, treatment administered (including dosing and duration), and outcome assessed across studies. There were few interventional studies and limited data collected on specific groups such as children and pregnant women. Conclusions/Significance There were a limited number of interventional trials, highlighting that scrub typhus remains a neglected disease. The heterogeneous nature of the available data reflects the absence of consensus in treatment and research methodologies and poses a significant barrier to aggregating information across available published data without access to the underlying IPD. There is likely to be a substantial amount of data available to address knowledge gaps. Therefore, there is value for an IPD platform that will facilitate pooling and harmonisation of currently scattered data and enable in-depth investigation of priority research questions that can, ultimately, inform clinical practice and improve health outcomes for scrub typhus patients. Author summary Scrub typhus is a febrile illness most commonly found in rural tropical areas. It is caused by a Gram-\negative bacteria belonging to the family Rickettsiaceae and transmitted by mites when they feed on vertebrates. There is an estimate of one million cases annually, with an estimated one billion people at risk, mostly in Asia-Oceania. But relative to the scale of the problem, scrub typhus is largely understudied. Evidence-based treatment recommendations by policymakers vary or are non-existent. We searched databases and registries for prospective scrub typhus clinical treatment studies published from 1998 to 2020 and reviewed them. Data from clinical trials and particularly for specific groups, such as pregnant women and children, were minimal. The methods used to measure treatment efficacy were heterogeneous, making it difficult to directly compare or conduct a meta-analysis based on aggregated data. One way to improve the current level of evidence would be by pooling and analysing individual participant-level data (IPD), i.e. the raw data from individual participants in completed studies. This review demonstrated that there is scope for developing a database for individual participant data to enable more detailed analyses. IPD meta-analyses could be a way to address knowledge gaps such as optimum dosing for children.

/pdf/systematic-review-of-the-scrub-typhus-treatment-landscape-r1pcr53rbq.pdf

Systematic review of the scrub typhus treatment landscape: Assessing the feasibility of an individual participant-level data (IPD) platform

Abstract Background Sequential organ failure assessment score (SOFA) is a score to quantify organ system dysfunction. This study was done to evaluate SOFA as a predictor of outcomes in children in pediatric intensive care unit (PICU). Objective (A) To determine whether initial SOFA, Delta SOFA, and SOFA score at 72 hours are better predictors of outcome in terms of sensitivity and specificity. (B) To compare the initial SOFA, Delta SOFA, and SOFA score at 72 hours. Materials and methods A prospective observational study was conducted on 160 patients aged from 29 days to 12 years admitted in PICU of a Tertiary Care Hospital in a metropolitan city in India for a period of 1 year. Then, the initial SOFA score, 72-hour SOFA, and Delta SOFA (T0 SOFA - T72 SOFA) were calculated and patients were followed up till discharge from PICU or deceased. Results The best threshold to differentiate between discharged and deceased corresponds to as initial SOFA of 7.50 with a sensitivity of 64.71%, and specificity of 89.51%. The similar threshold for 72 hours SOFA is 10.50 which correspond to a sensitivity of 76.47% and specificity of 96.50%. The study showed strong evidence (p-value < 0.05) that, patients whose Delta SOFA values increased from the previous value (–1.5), had a greater chance to succumb to illness. Delta SOFA had the best sensitivity (82.35%) and 72-hour SOFA had the best specificity (96.50%) in predicting the outcome of PICU patients. Conclusion This study emphasizes the use of SOFA score as a prognostic indicator in critically ill children, as variables measured are easily available. How to cite this article Lois A, Save S. Serial Evaluation of Sequential Organ Failure Assessment Score (SOFA) as a Predictor of Outcome in Children Admitted in Pediatric Intensive Care Unit (PICU) at Tertiary Care Hospital. Indian J Crit Care Med 2023;27(8):590–595.

Serial Evaluation of Sequential Organ Failure Assessment Score (SOFA) as a Predictor of Outcome in Children Admitted in Pediatric Intensive Care Unit (PICU) at Tertiary Care Hospital

ABSTRACT. In East Asia, severe fever with thrombocytopenia syndrome (SFTS) and scrub typhus, which are common endemic tick- and mite-mediated diseases sharing common clinical manifestations, are becoming public health concerns. However, there are limited data on the comparative immunopathogenesis between the two diseases. We compared the cytokine profiles of SFTS and scrub typhus to further elucidate immune responses that occur during the disease courses. We prospectively enrolled 44 patients with confirmed SFTS and 49 patients with scrub typhus from July 2015 to December 2020. In addition, 10 healthy volunteers were enrolled as healthy controls. A cytometric bead array was used to analyze plasma samples for 16 cytokines. A total of 68 plasma samples, including 31 (45.6%) from patients with SFTS and 37 (54.4%) from patients with scrub typhus, were available for cytokine measurement. There were three cytokine expression patterns: increased levels in both SFTS and scrub typhus (interleukin 6 [IL-6], IL-10, interferon gamma induced protein 10 [IP-10], and granulocyte-macrophage colony-stimulating factor [GM-CSF]), highest levels in SFTS (interferon alpha [IFN-α], IFN-γ, granulocyte-CSF [G-CSF], monocyte chemotactic protein 1 [MCP-1], macrophage inflammatory protein 1α [MIP-1α], and IL-8), and distinct levels in scrub typhus (IL-12p40, tumor necrosis factor alpha [TNFα], IL-1β, regulated on activation and normally T-cell expressed and secreted [RANTES], IL-17A, and vascular endothelial growth factor [VEGF]). Although patients with acute SFTS and scrub typhus exhibited partly shared expression patterns of cytokines related to disease severity, the different profiles of cytokines and chemokines might contribute to higher mortality in SFTS than in scrub typhus. Discrete patterns of helper T cell-related cytokines and VEGF might reflect differences in CD4 T-cell responses and vascular damage between these diseases. 

Cytokine and Chemokine Profiles in Acute Severe Fever with Thrombocytopenia Syndrome and Scrub Typhus in South Korea.

Background and Aim Scrub typhus (ST) is an acute infectious disease of variable severity caused by Orientia (formerly Rickettsia) tsutsugamushi. The disease can be complicated by organ dysfunctions and the case fatality rate (CFR) is approximately 15%, which further rises with the development of severe complications. We studied the clinical features of the ST and the performance of critical illness scoring systems (CISSs) - Acute Physiology and Chronic Health Evaluation (APACHE) II, sequential organ failure assessment (SOFA), and quick SOFA (qSOFA) in predicting the clinical outcomes in complicated ST (cST) patients admitted to the emergency department. Study Design and Methods A prospective observational study was done in 50 patients diagnosed to have cST with one or more organ dysfunctions. Clinical features and laboratory parameters were recorded and the patients were followed up until the end of their stay in the hospital. APACHE II, SOFA, and qSOFA scores at admission were calculated and were analyzed in predicting the clinical outcomes. Results The median SOFA, APACHE II, and qSOFA scores of the cohort were 7 (interquartile range [IQR] = 13-22), 8 (IQR = 5-11), and 2 (IQR = 1-3), respectively. The median duration of in-hospital stay was 9 (IQR 5-11) days and overall CFR was 8%. On bivariate analysis, both SOFA (P = 0.031) and qSOFA (P = 0.001) predicted mortality. However, only SOFA score correlated with the in-hospital stay duration (Pearson's correlation = 0.311, P = 0.028). Conclusion Among the three CISSs studied, the SOFA score correlated with in-hospital stay duration and mortality, whereas the qSOFA score formed a simple as well as a convenient tool in predicting the mortality in patients of cST with organ dysfunction.

/pdf/critical-illness-scoring-systems-sequential-organ-failure-3olr7c11k0.pdf

Critical Illness Scoring Systems: Sequential Organ Failure Assessment, Acute Physiology and Chronic Health Evaluation II, and Quick Sequential Organ Failure Assessment to Predict the Clinical Outcomes in Scrub Typhus Patients with Organ Dysfunctions.

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Critical Illness Scoring Systems: Sequential Organ Failure Assessment, Acute Physiology and Chronic Health Evaluation II, and Quick Sequential Organ Failure Assessment to Predict the Clinical Outcomes in Scrub Typhus Patients with Organ Dysfunctions.