Translation, reliability, and validity of Japanese version of the Respiratory Distress Observation Scale

Dyspnea is a common, distressing symptom of cardiopulmonary and neuromuscular diseases and is defined as “a subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity.” However, Japanese intensive care units (ICUs) do not routinely screen for dyspnea, as no validated Japanese version of the Respiratory Distress Observation Scale (RDOS) is available. Therefore, we aimed to translate the English version of this questionnaire into Japanese and assess its validity and reliability. To translate the RDOS, we conducted a prospective observational study in a 12-bed ICU of a universal hospital that included 42 healthcare professionals, 10 expert panels, and 128 ventilated patients. The English version was translated into Japanese, and several cross-sectional web-based questionnaires were administered to the healthcare professionals. After completing the translation process, a validity and reliability evaluation was performed in the ventilated patients. Inter-rater reliability was evaluated using Cohen’s weighted kappa coefficient. Criterion validity was ascertained based on the correlation between RDOS and the dyspnea visual analog scale. The area under the receiver operating characteristic curve analysis was used to evaluate the ability of the RDOS to identify patients with self-reported dyspnea. The average content validity index at the scale level was 0.95. Data from the 128 patients were collected and analyzed. Cohen’s weighted kappa coefficient and the correlation coefficient between the two scales were 0.76 and 0.443 (95% confidence intervals 0.70–0.82 and 0.23–0.62), respectively. For predicting self-reported dyspnea, the area under the receiver operating characteristic curve was 0.81 (95% confidence interval 0.67–0.97). The optimal cutoff used was 1, with a sensitivity and specificity of 0.89 and 0.61, respectively. Our findings indicated that the Japanese version of the RDOS is acceptable for face validity, understandability, criterion validity, and inter-rater reliability in lightly sedated mechanically ventilated patients, indicating its clinical utility

Impact of adverse events on patient outcomes in a Japanese intensive care unit: a retrospective observational study

AimWe investigated adverse events (AEs) in a Japanese intensive care unit (ICU) and evaluated the impact of cause-specific AEs on mortality and length of stay.DesignA retrospective observational study in the ICU of an academic hospital.MethodsWe reviewed medical records with the Global Trigger Tool.ResultsOf the 246 patients, 126 (51%) experienced one or more AEs with an incidence of 201 per 1000 patient-days and 115 per 100 admissions. A total of 294 AEs were detected with 119 (42%) adverse drug events, 67 (24%) procedural complications, 63 (22%) surgical complications, 26 (9%) nosocomial infections, 5 (2%) therapeutic errors and 4 (1%) diagnostic errors. Adverse event (AE) presence was associated with length of ICU stay (β = 2.85, 95% confidence interval [CI]: 1.09–4.61). Adverse drug events, procedural complications and nosocomial infections were strongly associated with length of ICU stay (β = 2.38, 95% CI: 0.77–3.98; β = 3.75, 95% CI: 2.03–5.48; β = 6.52, 95% CI: 4.07–8.97 respectively)

Development of the Japanese version of the Intensive Care Unit Trigger Tool to detect adverse events in critically ill patients

AimThe Intensive Care Unit Trigger Tool (ICUTT) was developed to detect adverse events (AEs) in intensive care unit (ICU) patients. The purpose of this study was to determine the validity and reliability of the Japanese version of the ICUTT (ICUTT-J).MethodsThe translation of ICUTT was carried out based on the guideline for translation of instruments. Subsequently, two review teams independently reviewed 50 patients\u27 medical records using the ICUTT-J, and agreement regarding the presence and number of AEs was evaluated to ensure reliability.ResultsThe ICUTT-J was submitted to the authors of the original ICUTT, who confirmed it as being equivalent to the original version. The item-content validity index and scale-content validity index were 1.00 and 1.00, respectively. Interrater reliability showed moderate agreement of κ = 0.52 in terms of the presence of AEs and linear weighting of κ = 0.49 (95% confidence interval, 0.28, 0.71) in terms of the number of AEs.ConclusionThis study\u27s findings suggest that the ICUTT-J is valid and moderately reliable for use in ICUs

Adrenomedullin Regulates IL-1β Gene Expression in F4/80+ Macrophages during Synovial Inflammation

Adrenomedullin (AM) plays an important role in the regulation of inflammatory processes; however, the role and expression of AM in synovial inflammation have not been determined. To investigate the expression and role of AM in inflamed synovial tissue (ST), the gene expression profiles of AM in the ST, including synovial macrophages and fibroblasts, of a murine patellar surgical dislocation model were characterized. In addition, the effects of interleukin- (IL-) 1β and AM in cultured synovial cells were also examined. CD11c+ macrophages were found to be elevated in ST of the surgically dislocated patella. Higher gene expression of CD11c, IL-1β, AM, receptor activity-modifying proteins 2 (RAMP2), and 3 (RAMP3) was also observed in ST obtained from the dislocated side. AM expression was also significantly increased in synovial fibroblasts and macrophages in response to IL-1β treatment. Synovial macrophages also highly expressed RAMP3 compared to fibroblasts and this expression was further stimulated by exogenously added IL-1β. Further, the treatment of the F4/80-positive cell fraction obtained from ST with AM inhibited IL-1β expression. Taken together, these findings demonstrated that AM was produced by synovial fibroblasts and macrophages in inflamed ST and that increased levels of AM may exert anti-inflammatory effects on synovial macrophages

Association of a Determinant on Mouse Chromosome 18 with Experimental Severe Plasmodium berghei Malaria

Experimental severe malaria (ESM; also known as experimental cerebral malaria) is an acute lethal syndrome caused by infection with Plasmodium berghei ANKA and associated with coma and other neurological manifestations in mice. Various inbred strains of mice exhibit differences in susceptibility to the development of ESM. For example, C57BL/6 mice are highly susceptible and DBA/2 mice are relatively resistant. We report here the results of a genomewide scan for host genomic regions that control resistance to ESM in DBA/2 mice using an F(2) intercross population of susceptible and resistant strains. A region of mid-chromosome 18 was found to be a major determinant of resistance to ESM

Vascular endothelial growth factor expression and their action in the synovial membranes of patients with painful knee osteoarthritis

Abstract Background Research suggests that vascular endothelial growth factor (VEGF) levels in the synovial fluid of knee osteoarthritis (KOA) patients are positively correlated with KOA severity. The relationship between synovial VEGF levels and pain in human KOA patients is not fully understood, and the role of VEGF in the pain pathway remains unclear. Methods We harvested synovial membrane (SM) from 102 patients with radiographic evidence of KOA (unilateral Kellgren/Lawrence [K/L] grade 2–4) during total knee arthroplasty. Patients scored their pain on a 0 to 10 cm visual analog scale (VAS). VEGF levels in the SM of KOA patients with strong/severe (VAS ≥ 6) and mild/moderate pain (VAS < 6) were compared. Correlations between VAS and VEGF mRNA expression were investigated. To investigate a possible mechanism for VEGF-induced pain, the distribution of VEGF and the neuropeptide apelin was determined by immunohistochemical analyses. To investigate the role of VEGF in regulating apelin expression, SM cells were exposed to VEGF. Results VEGF expression in the VAS ≥ 6 group was significantly greater than expression in the VAS < 6 group. Expression levels of VEGF were also positively correlated with VAS. VEGF-positive cells were identified in the lining of the SM. Expression of apelin mRNA and protein were significantly elevated in SM cells treated with exogenous VEGF compared to those treated with vehicle. Conclusion Synovial VEGF may be involved in pain pathways in KOA and its action may be mediated by apelin

Expression of calcitonin gene-related peptide in the infrapatellar fat pad in knee osteoarthritis patients

Abstract Background The infrapatellar fat pad (IPFP) has been implicated as a possible source of osteoarthritis (OA) development and knee pain due to the production of inflammatory mediators and the existence of nerve fibers within this structure. Calcitonin gene-related peptide (CGRP) is a vasodilatory neuropeptide that is localized to joint tissues and has recently been implicated in the development of knee OA and OA pain. To date, however, the expression levels of CGRP in the IPFP of human knee OA patients have not been examined. Methods IFFP and synovial (SYN) tissues were harvested from 100 individuals with radiographic knee OA (unilateral Kellgren/Lawrence [K/L] grades 2–4) during total knee arthroplasty and subjected to immunohistochemical analysis for CGRP localization. In addition, the messenger RNA (mRNA) expression levels of CGRP and cyclooxygenase-2 (COX-2) in the collected tissues were evaluated and compared using real-time PCR analysis of total RNA extracts. CGRP and COX-2 mRNA expression were also compared among individuals with K/L grades 2–4. Results CGRP-positive cells were detected in the capillaries within the IPFP and lining layer of SYN tissue. The expression levels of CGRP in the IPFP were positively correlated with COX-2 and were significantly higher than those in SYN tissue. CGRP expression in tissue from the KL4 group was twofold higher than that from the KL2 group. Conclusions The IPFP of knee OA patients produces relatively high levels of CGRP, which may be regulated by COX-2 at the transcriptional level. Further studies are needed to determine if CGRP levels are directly linked to OA pathology

Regulation of calcitonin gene-related peptide expression through the COX-2/mPGES-1/PGE2 pathway in the infrapatellar fat pad in knee osteoarthritis

Abstract Background The infrapatellar fat pad (IFP) is implicated in knee osteoarthritis (KOA). Calcitonin gene-related peptide (CGRP), a vasoactive neuropeptide expressed in joint tissues and synovial tissues (ST), was recently found to be associated with KOA progression and pain. CGRP is expressed in the IFPs of human KOA patients; however, its regulation has not been elucidated. Methods IFPs and STs were harvested from 138 KOA patients during total knee replacement (TKR) and analyzed for CGRP, cycloxygenase-2 (COX-2), and microsomal prostaglandin E synthase-1 (mPGES-1) expression using real-time polymerase chain reaction (PCR). To investigate CGRP regulation by prostaglandin E2 (PGE2), adipocytes (Ad) and the stromal vascular fraction (SVF) were harvested from IFPs using collagenase. Synovial cells (SYC) were also harvested from ST and stimulated with vehicle (serum-free culture medium), PGE2, or CGRP. Results CGRP, COX-2, and mPGES-1 expression levels were significantly higher in IFPs than STs. PGE2 stimulation increased CGRP expression in Ad, the SVF, and SYC; however, CGRP expression was significantly higher in PGE2-stimulated SVF than PGE2-stimulated SYC. CGRP stimulation had no effect on COX-2 or mPGES-1 expression. Conclusions CGRP expression in the IFP of KOA patients is regulated by the COX-2/mPGES-1/PGE2 pathway

Nerve Growth Factor Regulation by TNF-α and IL-1β in Synovial Macrophages and Fibroblasts in Osteoarthritic Mice

To investigate the role of macrophages as a regulator and producer of nerve growth factor (NGF) in the synovial tissue (ST) of osteoarthritis (OA) joints, the gene expression profiles of several inflammatory cytokines in the ST, including synovial macrophages and fibroblasts, of OA mice (STR/Ort) were characterized. Specifically, real-time polymerase chain reaction analysis was used to evaluate the expression of tumor necrosis factor- (TNF-) α, interleukin- (IL-) 1β, IL-6, and NGF in CD11b+ and CD11b– cells isolated from the ST of a murine OA model. The effects of TNF-α, IL-1β, and IL-6 on the expression of NGF in cultured synovial cells were also examined. The expression of TNF-α, IL-1β, IL-6, and NGF in the ST of STR/Ort was higher than that in C57/BL6J mice. Compared to the CD11b– cell fraction, higher expression levels of TNF-α, IL-1β, and IL-6 were detected in the CD11b+ cell fraction, whereas no differences in the expression of NGF were detected between the two cell fractions. Notably, TNF-α upregulated NGF expression in synovial fibroblasts and macrophages and IL-1β upregulated NGF expression in synovial fibroblasts. IL-1β and TNF-α may regulate NGF signaling in OA joints and be suitable therapeutic targets for treating OA pain