SSA/P and colorectal cancer may not be suitable for CSP adoption.
Objective The aim of this study was to describe the epidemiology, clinical features, antimicrobial treatment, and outcomes of patients with nursing and healthcare-associated pneumonia (NHCAP); a new category of pneumonia proposed by the Japanese Respiratory Society. Methods We conducted a retrospective analysis of a prospectively collected database of patients with NHCAP and community-acquired pneumonia (CAP) hospitalized at a single center between January 2008 and December 2010, and compared their clinical characteristics. The criteria for NHCAP were as follows: (1) residence in a nursing home or an extended-care ward, (2) a discharge from a hospital in the preceding 90 days, (3) an elderly or handicapped patient who needs long-term care, (4) a patient who regularly requires vascular access in an outpatient setting. Results A total of 442 NHCAP patients and 451 CAP patients were evaluated. The NHCAP patients were older and had a higher frequency of underlying diseases. Aspiration was thought to be associated with the NHCAP in 63% of patients. Streptococcus pneumoniae was the leading pathogen in both groups, whereas the frequency of multidrug-resistant pathogens was higher in the NHCAP patients. The most frequently used antimicrobials in NHCAP patients were penicillins with beta-lactamase inhibitors. The in-hospital mortality and recurrence rates were significantly higher in NHCAP patients than in CAP patients (13.1% vs. 5.1%, p<0.001 and 18.8% vs. 5.5%, p<0.001). Conclusion The clinical picture of NHCAP is consistent with that of HCAP described in the past. It is thought to be of benefit to modify the healthcare-associated pneumonia (HCAP) criteria considering the healthcare and social health insurance system in Japan.
BackgroundTo date, only few studies have examined the prognostic factors of community-acquired pneumonia (CAP) defined according to the latest criteria, which excludes healthcare-associated pneumonia (HCAP). Therefore, we aimed to investigate the factors that affect prognosis, and evaluate the usefulness of existing pneumonia severity scores for predicting the prognosis of CAP.MethodsWe retrospectively analyzed patients with CAP, excluding HCAP, who were enrolled prospectively between April 2007 and February 2016. Four patients who used macrolides other than azithromycin (AZM) were excluded. We used age, sex, comorbidities, laboratory findings and antimicrobial therapy as prognostic variables. The primary outcome was 30-day mortality and secondary outcome was ICU admission. We also performed receiver operating characteristic curve analysis of Pneumonia Severity Index (PSI), Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) severe criteria, CURB-65 and A-DROP pneumonia severity scores.ResultsAmong 1834 CAP patients, mean age was 73.5 ± 14.3 years; 1281 (69.8%) were men; and 30-day mortality was 6.7% (122/1834). In total, 1830 patients were analyzed. Multivariate analysis identified age [Odds Ratio (OR): 1.04, 95% Confidence Interval (CI): 1.02–1.07], chronic obstructive pulmonary disease (COPD) [OR: 1.77, 95% CI: 1.13–2.76], malignancy (OR: 2.25, 95% CI: 1.25–4.06), body temperature (OR: 0.81, 95% CI: 0.67–0.99), respiratory rate (OR: 1.04, 95% CI: 1.01–1.07), PaO2/FiO2 ≤ 250 (OR: 3.15, 95% CI: 1.93–5.14), Alb (OR: 0.27, 95% CI: 0.19–0.39), BUN (OR: 1.01, 95% CI: 1.00–1.02), and mechanical ventilation (OR: 2.99, 95% CI: 1.75–5.12) as prognostic factors. AZM and β-lactam combination therapy significantly reduced 30-day mortality (OR: 0.50, 95% CI: 0.26–0.97). Areas under the curve of PSI, IDSA/ATS severe criteria, CURB-65 and A-DROP were 0.759, 0.746, 0.754 and 0.764, respectively.ConclusionsIncreasing age, presence of COPD and malignancy as comorbidities, hypothermia, tachypnea, PaO2/FiO2 ratio ≤250 mmHg, low Alb level, high BUN level and mechanical ventilatory support predict a worse prognosis; AZM combination therapy should be considered for CAP, excluding HCAP. All four pneumonia severity scores are useful for assessing the severity of CAP defined by the latest criteria.Trial registrationUMIN-CTR UMIN000004353. Registered 7 October 2010. Retrospectively registered.Electronic supplementary materialThe online version of this article (doi:10.1186/s12890-017-0424-4) contains supplementary material, which is available to authorized users.
Japan Medical Association Center for Clinical Trials JMA-IIA00146.
Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.
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