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Activation of pyruvate dehydrogenase (PDH) by inhibition of pyruvate dehydrogenase kinase (PDHK) has the potential for the treatment of diabetes mellitus and its complications, caused by the malfunction of the glycolytic system and glucose oxidation. In this paper, we describe the identification of novel PDHK inhibitors with a fluorene structure. High-throughput screening using our in-house library provided compound 6 as a weak inhibitor that occupied the allosteric lipoyl group binding site in PDHK2. Structure-based drug design (SBDD) while addressing physicochemical properties succeeded in boosting inhibitory activity approximately 700-fold. Thus obtained compound 32 showed favorable pharmacokinetics profiles supported by high membrane permeability and metabolic stability, and exhibited activation of PDH in rat livers and a glucose lowering effect in Zucker fatty rats.
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Desenho de Fármacos , Fluorenos , Inibidores de Proteínas Quinases , Proteínas Serina-Treonina Quinases , Piruvato Desidrogenase Quinase de Transferência de Acetil , Ratos Zucker , Animais , Piruvato Desidrogenase Quinase de Transferência de Acetil/antagonistas & inibidores , Piruvato Desidrogenase Quinase de Transferência de Acetil/metabolismo , Ratos , Fluorenos/química , Fluorenos/síntese química , Fluorenos/farmacologia , Relação Estrutura-Atividade , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/metabolismo , Estrutura Molecular , Humanos , Relação Dose-Resposta a DrogaRESUMO
Osteoporosis is characterized by weakened bone microstructure and loss of bone mass. Current diagnostic criteria for osteoporosis are based on the T-score, which is a measure of bone mineral density. However, osteoporotic fragility fractures can occur regardless of the T-score, underscoring the need for additional criteria for the early detection of patients at fracture risk. To identify indicators of reduced bone strength, we performed serum proteomic analysis using data-independent acquisition mass spectrometry with serum samples from two patient groups, one with osteoporosis but no fractures and the other with osteopenia and fragility fractures. Collective evaluation of the results identified six serum proteins that changed to a similar extent in both patient groups compared with controls. Of these, extracellular matrix protein 1 (ECM1), which contributes to bone formation, showed the most significant increase in serum levels in both patient groups. An ELISA-based assay suggested that ECM1 could serve as a serum indicator of the need for therapeutic intervention; however, further prospective studies with a larger sample size are necessary to confirm these results. The present findings may contribute to the provision of early and appropriate therapeutic strategies for patients at risk of osteoporotic fractures. SIGNIFICANCE: This study aimed to identify objective serum indicators of the need for therapeutic intervention in individuals at risk of osteoporotic fracture. Comprehensive proteome analyses of serum collected from patients with osteoporosis but no fractures, patients with osteopenia and fragility fractures, and controls were performed by data-independent acquisition mass spectrometry. Collective evaluation of the proteome analysis data and ELISA-based assays identified serum ECM1 as a potential objective marker of the risk of fragility fractures in patients with osteoporosis or osteopenia. The findings are an important step toward the development of appropriate bone health management methods to improve well-being and maintain quality of life.
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Biomarcadores , Espectrometria de Massas , Osteoporose , Fraturas por Osteoporose , Humanos , Osteoporose/sangue , Feminino , Idoso , Fraturas por Osteoporose/sangue , Biomarcadores/sangue , Espectrometria de Massas/métodos , Masculino , Pessoa de Meia-Idade , Proteômica/métodos , Densidade Óssea , Doenças Ósseas Metabólicas/sangue , Doenças Ósseas Metabólicas/diagnóstico , Proteínas da Matriz Extracelular/sangue , Proteínas Sanguíneas/análise , Idoso de 80 Anos ou mais , Proteoma/análise , Proteoma/metabolismoRESUMO
Physical inactivity associated with gravity unloading, such as microgravity during spaceflight and hindlimb unloading (HU), can cause various physiological changes. In this study, we attempted to identify serum proteins whose levels fluctuated in response to gravity unloading. First, we quantitatively assessed changes in the serum proteome profiles of spaceflight mice using mass spectrometry with data-independent acquisition. The serum levels of several proteins involved in the responses to estrogen and glucocorticoid, blood vessel maturation, osteoblast differentiation, and ossification were changed by microgravity exposure. Furthermore, a collective evaluation of serum proteomic data from spaceflight and HU mice identified 30 serum proteins, including Mmp2, Igfbp2, Tnc, Cdh5, and Pmel, whose levels varied to a similar extent in both gravity unloading models. These changes in serum levels could be involved in the physiological changes induced by gravity unloading. A collective evaluation of serum, femur, and soleus muscle proteome data of spaceflight mice also showed 24 serum proteins, including Igfbp5, Igfbp3, and Postn, whose levels could be associated with biological changes induced by microgravity. This study examined serum proteome profiles in response to gravity unloading, and may help deepen our understanding of microgravity adaptation mechanisms during prolonged spaceflight missions.
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Proteínas Sanguíneas , Proteômica , Voo Espacial , Ausência de Peso , Animais , Camundongos , Proteômica/métodos , Proteínas Sanguíneas/metabolismo , Proteínas Sanguíneas/análise , Espectrometria de Massas/métodos , Elevação dos Membros Posteriores , Proteoma/metabolismo , Proteoma/análise , Masculino , Camundongos Endogâmicos C57BLRESUMO
The molecular mechanisms associated with spaceflight-induced biological adaptations that may affect many healthy tissue functions remain poorly understood. In this study, we analyzed temporal changes in the serum proteome of six astronauts during prolonged spaceflight missions using quantitative comprehensive proteome analysis performed with the data-independent acquisition method of mass spectrometry (DIA-MS). All six astronauts participated in a spaceflight mission for approximately 6 months and showed a decreasing trend in T-scores at almost all sites where dual-energy X-ray absorptiometry scans were performed. DIA-MS successfully identified 624 nonredundant proteins in sera and further quantitative analysis for each sampling point provided information on serum protein profiles closely related to several time points before (pre-), during (in-), and after (post-) spaceflight. Changes in serum protein levels between spaceflight and on the ground suggest that abnormalities in bone metabolism are induced in astronauts during spaceflight. Furthermore, changes in the proteomic profile occurring during spaceflight suggest that serum levels of bone metabolism-related proteins, namely ALPL, COL1A1, SPP1, and POSTN, could serve as highly responsive indicators of bone metabolism status in spaceflight missions. This study will allow us to accelerate research to improve our understanding of the molecular mechanisms of biological adaptations associated with prolonged spaceflight.
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Astronautas , Proteoma , Voo Espacial , Humanos , Proteoma/metabolismo , Proteoma/análise , Masculino , Proteínas Sanguíneas/análise , Proteínas Sanguíneas/metabolismo , Proteômica/métodos , Pessoa de Meia-Idade , Adulto , Espectrometria de Massas/métodosRESUMO
Intestinal perforation and obstruction are known to be one of the adverse events caused by antipsychotics; however, warning information on package inserts varies among antipsychotics. To investigate the risks of gastrointestinal perforation and intestinal obstruction in patients prescribed atypical antipsychotics compared with those in patients prescribed typical antipsychotics, a nested case-control study was conducted utilizing real-world data from the MID-NET® medical information database in Japan. The study period spanned from January 1, 2009, to December 31, 2018. We found that the risks of gastrointestinal perforation and intestinal obstruction in patients prescribed atypical antipsychotics were significantly lower than those in patients prescribed typical antipsychotics (adjusted odds ratio, 0.48; 95% confidence interval, 0.29-0.80). This finding was supported with prolonged periods for the exposure definition in the sensitivity analyses. In addition, no major differences in the risks of atypical antipsychotics, such as risperidone, quetiapine, olanzapine, and aripiprazole, were identified in this study. The safety profile regarding the lower risks of gastrointestinal perforation and intestinal obstruction in patients prescribed atypical antipsychotics should be considered when choosing antipsychotics in clinical practice in terms of the proper use of such drugs.
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Antipsicóticos , Obstrução Intestinal , Humanos , Antipsicóticos/efeitos adversos , Japão , Estudos de Casos e Controles , Benzodiazepinas/efeitos adversos , Obstrução Intestinal/induzido quimicamenteRESUMO
BACKGROUND: Existing knee related patient reported outcome measurements (PROMs) have overwhelmingly been developed and validated in western chair-based societies, suggesting a potential for a western bias in PROMs evaluation of patients with knee conditions. We, therefore, endeavor to evaluate the responsiveness of the previously developed culturally relevant Japanese version of the knee injury and osteoarthritis outcome score (JKOOS+). METHODS: We enrolled 114 patients scheduled for total knee arthroplasty (TKA) across 8 knee clinics in Japan. Patients completed the Oxford Knee Score (OKS) and JKOOS + both at the time of enrollment and again 1-year post-TKA. Responsiveness was evaluated using effect size and standardized response mean (SRM). An effect size or SRM >0.8 is considered adequately responsive. We further tested the difference in responsiveness between the original Japanese language KOOS activities of daily living (ADL) domain and the novel Japanese ADL (JADL) domain using the modified Jacknife test. RESULTS: All domains were adequately responsive with the exception of the KOOS sports and recreation domain, which has previously been ignored by TKA researchers due to its lack of applicability to elderly patients undergoing TKA. The JADL domain outperformed the ADL domain in both effect size (1.51 v. 1.45) and SRM (1.67 v. 1.57) (p < 0.001). The novel Knee Flexion (KF) domain was adequately responsive, though less responsive than other domains except sports and recreation (p < 0.01 v. all other PROMs domains). CONCLUSIONS: The JKOOS+ JADL domain is significantly more responsive than the Europe-developed ADL domain to TKA in Japanese knee patients suffering from knee osteoarthritis (OA). The KF domain, unique to the JKOOS+ and intended to assess difficulty with knee flexion, is adequately responsive to TKA in Japanese patients suffering from OA.
RESUMO
To examine the association between hip fracture and associated factors, including polypharmacy, and develop an optimal predictive model, we conducted a population-based matched case-control study using the health insurance claims data on hip fracture among Japanese patients. We included 34,717 hospitalized Japanese patients aged ≥ 65 years with hip fracture and 34,717 age- and sex- matched controls who were matched 1:1. This study included 69,434 participants. Overall, 16 variable comorbidities and 60 variable concomitant medications were used as explanatory variables. The participants were added to early elderly and late elderly categories for further analysis. The odds ratio of hip fracture increased with the number of medications only in the early elderly. AUC was highest for early elderly (AUC, 0.74, 95% CI 0.72-0.76). Use of anti-Parkinson's drugs had the largest coefficient and was the most influential variable in many categories. This study confirmed the association between risk factors, including polypharmacy and hip fracture. The risk of hip fracture increased with an increase in medication number taken by the early elderly and showed good predictive accuracy, whereas there was no such association in the late elderly. Therefore, the early elderly in Japan should be an active target population for hip fracture prevention.
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População do Leste Asiático , Fraturas do Quadril , Polimedicação , Idoso , Humanos , Estudos de Casos e Controles , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/etiologia , Modelos Logísticos , Fatores de Risco , ComorbidadeRESUMO
Gravity-dependent physical processes strongly affect the ability of elderly people to maintain musculoskeletal health by reducing muscle atrophy and increasing bone mineral density, thereby increasing quality of life. A need therefore exists to identify molecules in the musculoskeletal system that are responsive to gravitational loading and to establish an objective indicator for the maintenance of healthy musculoskeletal systems. Here, we performed an integrated assessment of the results of soleus muscle proteomic analyses in three model mouse experiments under different gravity environments (hypergravity, hindlimb unloading, and spaceflight). Myl6b, Gpd1, Fbp2, Pvalb, and Actn3 were shown to be gravity-responsive muscle proteins, and alterations in the levels of these proteins indicated changes in muscle fiber type to slow-twitch type due to gravity loading. In addition, immunoblotting and enzyme-linked immunosorbent assays revealed that Pvalb levels in the sera of hindlimb-unloaded mice and osteoporosis patients were higher than in control subjects, suggesting that Pvalb levels might be useful to objectively evaluate soleus muscle atrophy and bone loss.
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Proteômica , Qualidade de Vida , Idoso , Humanos , Animais , Camundongos , Atrofia Muscular , Proteínas Musculares , Fibras Musculares Esqueléticas , ActininaRESUMO
PURPOSE: It is not clear whether or not high-flow nasal oxygenation used in patients with severe respiratory tract infection, or coughing, increases the risk of infection to the healthcare personnel, and whether or not applying a surgical mask to the patient's face or treating the patient in a negative-pressure room can reduce the risk. METHODS: In a randomized crossover design, we compared in 50 participants receiving high-flow nasal oxygenation, the aerosol counts measured at approximately 20 cm above the participant's mouth in 32 different circumstances (with or without coughing, with or without wearing a surgical mask, at four different flow rates of oxygenation, in a positive- or negative-pressure operating room). RESULTS: In a positive-pressure room, a surgical mask significantly decreased the aerosol counts during coughing (P = 0.0005), or during no coughing (P = 0.009), under high-flow nasal oxygenation (at 60 l.min-1). In the negative-pressure room, the aerosol count was significantly lower than in the positive-pressure room, for all the circumstances (all P < 0.001), and a surgical mask significantly decreased the aerosol counts during coughing (P = 0.047) but not during no coughing (P = 0.60). CONCLUSION: In conclusion, treating a patient in a negative-pressure room, or applying a surgical mask, during high-flow nasal oxygenation (with the flow rate of 60 l.min-1) would inhibit, but would not completely prevent, dispersion of aerosols by coughing.
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Oxigênio , Aerossóis e Gotículas Respiratórios , Humanos , Oxigenoterapia , Pulmão , Tosse/prevenção & controle , MáscarasAssuntos
Oxigenação por Membrana Extracorpórea , Doenças Pulmonares Intersticiais , Pneumotórax , Cirurgia Torácica , Procedimentos Cirúrgicos Torácicos , Humanos , Pneumotórax/cirurgia , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/cirurgia , Estudos RetrospectivosRESUMO
Although the microgravity (µ-g) environment that astronauts encounter during spaceflight can cause severe acute bone loss, the molecular mechanism of this bone loss remains unclear. To investigate the gravity-response proteins involved in bone metabolism, it is important to comprehensively determine which proteins exhibit differential abundance associated with mechanical stimuli. However, comprehensive proteomic analysis using small bone samples is difficult because protein extraction in mineralized bone tissue is inefficient. Here, we established a high-sensitivity analysis system for mouse bone proteins using data-independent acquisition mass spectrometry. This system successfully detected 40 proteins in the femoral diaphysis showing differential abundance between mice raised in a µ-g environment, where the bone mass was reduced by gravity unloading, and mice raised in an artificial 1-gravity environment on the International Space Station. Additionally, 22 proteins, including noncollagenous bone matrix proteins, showed similar abundance between the two groups in the mandible, where bone mass was unaltered due to mastication stimuli, suggesting that these proteins are responsive to mechanical stimuli. One of these proteins, SPARCL1, is suggested to promote osteoclastogenesis induced by receptor activator of nuclear factor-κB ligand. We expect these findings to lead to new insights into the mechanisms of bone metabolism induced by mechanical stimuli. SIGNIFICANCE: We aimed to investigate the gravity-response proteins involved in bone metabolism. To this end, we established a comprehensive analysis system for mouse bone proteins using data-independent acquisition mass spectrometry, which is particularly useful in comprehensively analyzing the bone proteome using small sample volumes. In addition, a comprehensive proteomic analysis of the femoral diaphysis and mandible, which exhibit different degrees of bone loss in mice raised on the International Space Station, identified proteins that respond to mechanical stimuli. SPARCL1, a mechanical stimulus-responsive protein, was consequently suggested to be involved in osteoclast differentiation associated with bone remodeling. Our findings represent an important step toward elucidating the molecular mechanism of bone metabolism induced by mechanical stimuli.
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Voo Espacial , Ausência de Peso , Camundongos , Animais , Proteômica , Fêmur , ProteomaRESUMO
INTRODUCTION: Recently, circulating neuroblastoma suppressor of tumorigenicity 1 (NBL1) was shown to be strongly associated with kidney disease progression and histological lesions in patients with diabetic kidney disease. This study aimed to examine whether serum NBL1 level was also associated with kidney function and renal histological findings in patients with IgA nephropathy. METHODS: We evaluated the levels of NBL1 in 109 patients with newly diagnosed biopsy-proven primary IgAN, between 2009 and 2018, at the Nihon University School of Medicine Itabashi Hospital, Tokyo, Japan, using serum obtained immediately before the renal biopsy, and examined the relationship between serum NBL1, renal function and renal histological findings assessed using the Oxford Classification (MEST score). Furthermore, we analyzed the association of serum NBL1 with kidney function decline over time in patients with IgA nephropathy who had follow-up data on the estimated glomerular filtration rate (n = 76). RESULTS: Serum NBL1 levels in patients with newly diagnosed IgA nephropathy were elevated, as compared to those in healthy individuals (n = 93). Logistic regression analysis demonstrated that the serum NBL1 level was independently and significantly associated with tubular atrophy/interstitial fibrosis. Immunohistochemical staining revealed that NBL1 was highly expressed in the tubulointerstitium. Furthermore, Spearman's rank correlation identified a significant correlation between serum NBL1 level and estimated glomerular filtration rate slope. CONCLUSIONS: The serum NBL1 level was significantly associated with the severity of renal interstitial fibrosis and kidney disease progression in patients with newly diagnosed IgA nephropathy. Thus, circulating NBL1 may serve as a good biomarker for evaluating renal interstitial fibrosis and the risk of kidney disease progression.
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Glomerulonefrite por IGA , Neuroblastoma , Humanos , Progressão da Doença , Fibrose , Taxa de Filtração Glomerular , Glomerulonefrite por IGA/patologia , Rim , Neuroblastoma/complicações , Neuroblastoma/patologiaRESUMO
PURPOSE: Loss of motor response to thrusting the jaw forward is a useful indicator for uncomplicated insertion of a supraglottic airway. The aim of this study was to assess the suitability of remimazolam for insertion of a supraglottic airway assessed by loss of response to jaw thrusting. METHODS: Seventy patients, who were scheduled for elective surgeries under general anesthesia, were allocated randomly to one of two groups. In one group (remimazolam group), remimazolam was infused 12 mg kg-1 h-1 (50 mg maximum), and in the other (propofol group), propofol was infused at 120 mg kg-1 h-1 (500 mg maximum). Once the eyelash reflex disappeared, response to jaw thrusting was assessed. Primary outcome measure was the proportion of patients with loss of response to jaw thrusting before reaching the maximum dose of the test drug. We planned an interim analysis (of one time) after 40 patients, using the Pocock adjustment method. RESULTS: From the interim analysis results, the study was stopped after recruitment of 40 patients. Loss of response to jaw thrusting was observed in all of 21 patients (100%) in the propofol group, and in 9 of 19 patients (47%) in the remimazolam group. There was a significant difference in the proportion between the groups (P = 0.0001, 95% CI for difference 30-75%). CONCLUSION: Remimazolam frequently does not inhibit response to jaw thrusting, and thus remimazolam is not a suitable induction agent for uncomplicated insertion of a supraglottic airway unless either a neuromuscular blocking agent or an opioid is co-administered.
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Propofol , Humanos , Benzodiazepinas , Procedimentos Cirúrgicos Eletivos , Analgésicos OpioidesRESUMO
BACKGROUND/AIM: Nonalcoholic fatty liver disease (NAFLD) is a wide spectrum of liver disorders ranging from simple steatosis to nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. Recently, the prevalence of NAFLD has dramatically increased, and treatment is urgently needed. Animal models are often used to understand the molecular mechanisms of disease development and progression, but their relevance to human diseases has not been fully understood. This study aimed to establish the usefulness of the animal model for preclinical research, we evaluated its relevance to human disease by gene expression analysis. MATERIALS AND METHODS: We performed weighted gene co-expression network analysis of liver tissues from a choline-deficient L-amino acid-defined (CDAA) diet-induced NAFLD animal model. In addition, module preservation analysis was conducted to evaluate similarity across species. RESULTS: Several modules were identified to be associated with disease severity, and their gene co-expression network was found to be preserved in the human NAFLD datasets. Of note, module brown (immune cell clusters involved in inflammatory responses) was positively associated with disease severity, and its gene co-expression network was highly preserved in the human datasets. Tyrobp, Laptm5 and Lgals3 were identified as hub genes in the brown module, and their increased expression was confirmed in the human datasets. CONCLUSION: CDAA diet-induced NAFLD animal model recaptured key aspects of human pathophysiology (especially immune cell functions) and is thought to be a powerful tool for understanding the molecular mechanisms of NAFLD development and progression.
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Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Animais , Humanos , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/complicações , Colina/metabolismo , Fígado/patologia , Dieta/efeitos adversos , Neoplasias Hepáticas/patologia , Modelos Animais de Doenças , Aminoácidos/metabolismoRESUMO
BACKGROUND: Videolaryngoscopes may not be as effective in small children as they are in older children and in adults. The size 1 blade is commercially available for the McGRATH®MAC videolaryngoscope (Covidien, Medtronic, Tokyo, Japan), but its efficacy in comparison with a Macintosh laryngoscope blade 1 is not known. AIM: The main aim of this study was to assess the efficacy of McGrath®MAC blade 1 in comparison with a conventional Macintosh laryngoscope blade 1, in children aged less than 24 months. METHODS: Thirty-eight children aged less than 24 months were randomly allocated to one of two groups, and tracheal intubation was attempted using either a direct laryngoscope with a Macintosh blade 1 or a videolaryngoscope with a McGRATH®MAC blade 1. In another 12 children aged 2-4 years, the same comparisons were made with blade 2. The primary outcome measure was time to tracheal intubation using a size 1 blade. RESULTS: Tracheal intubation took significantly longer with a McGRATH®MAC blade 1 (median (interquartile range): 38.0 (31.8-43.5) s) than with the Macintosh blade 1(27.4 (25.9-29.2) s) (p < 0.0001; median difference (95% CI for the median difference): 10.6 (6.4-14.0) s), mainly due to difficulty in advancing a tube into the trachea. No significant difference was observed for the size 2. CONCLUSIONS: In small children without predicted difficult airways, time to intubate the trachea was significantly longer for a McGRATH®MAC blade 1 than a Macintosh blade 1. CLINICAL TRIAL REGISTRATION: jRCT1032220366.
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Intubação Intratraqueal , Laringoscópios , Cirurgia Vídeoassistida , Adulto , Criança , Humanos , Intubação Intratraqueal/instrumentação , Intubação Intratraqueal/métodos , Japão , Laringoscopia , Traqueia , Cirurgia Vídeoassistida/métodosRESUMO
AIM: Some clinical trials have shown that sodium-glucose cotransporter-2 (SGLT2) inhibitors are associated with fracture risk. However, this notion remains controversial. This study aimed to evaluate hip fracture risk after the use of SGLT2 inhibitors while controlling for factors that may affect fracture risk. Furthermore, hip fracture risk is evaluated in relation to the SGLT2 inhibitors component and its concomitant use with other antidiabetic agents. METHODS: Using large-scale real-world data, this case-control study investigated hospitalized patients between January 2018 and December 2020. Patients were aged 65-89 years and had been prescribed with SGLT2 inhibitors at least twice. Patients with hip fracture (cases) and those without (controls) were identified via 1:3 matching according to sex, age (±3 years), hospital size classification, and number of concomitant antidiabetic agents. Exposure to SGLT2 inhibitors of the cases and controls was compared with the use of multivariate conditional logistic regression. RESULTS: After matching, 396 cases and 1081 controls were identified. The adjusted odds ratio for patients receiving treatment with SGLT2 inhibitors was 0.83 (95% confidence interval: 0.55-1.26), indicating no increase in hip fracture risk. Additionally, no increased risk was observed with respect to SGLT2 inhibitors by component or concomitant use with other antidiabetic agents. CONCLUSION: Our study showed that SGLT2 inhibitors do not increase hip fractures in older patients. However, because the risk assessment of SGLT2 inhibitors by component and their concomitant use with other antidiabetic agents is based on a limited number of patients, it is important to interpret the results with caution. Geriatr Gerontol Int 2023; 23: 418-425.
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Diabetes Mellitus Tipo 2 , Fraturas do Quadril , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Idoso , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Estudos de Casos e Controles , Japão/epidemiologia , Hipoglicemiantes/efeitos adversos , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/induzido quimicamente , Glucose , SódioRESUMO
BACKGROUND AND OBJECTIVE: The use of benzodiazepines and nonbenzodiazepines increases the risk for hip fracture, but the effect of suvorexant, an orexin receptor antagonist, is not clear. The objective of this study was to investigate the association between suvorexant use and hip fractures in older adults. METHODS: A case-control study was conducted using real-world data (RWD) from Medical Data Vision Co., Ltd. with patients hospitalized between January 2019 and December 2020. Patients were aged 65-84 years and had been prescribed suvorexant at least once. Patients with hip fracture (cases) and those without (controls) were identified by matching up to 1:4 for sex, age (± 2 years), and hospital size category. Suvorexant exposure was identified the day before hospitalization. Hip fracture risk associated with suvorexant was presented as adjusted odds ratios (aOR) with 95% confidence intervals (CI) using conditional logistic regression analysis. RESULTS: Matching identified 389 cases and 1509 controls. The risk of hip fracture was not increased in patients treated with suvorexant [aOR: 0.86, 95% confidence interval (CI) 0.61-1.20]. Additionally, concomitant use of suvorexant with other hypnotics did not increase the risk. Benzodiazepines (1.01, 0.46-2.22), nonbenzodiazepines (1.16, 0.57-2.34), and melatonin (1.80, 0.82-3.94) were combined with suvorexant. The risk was increased for the use of benzodiazepine without suvorexant (1.88, 1.10-3.21). CONCLUSIONS: Using RWD in Japanese older adults, we showed that sleep therapy with suvorexant was not associated with an increased risk of hip fracture. The results provide evidence-based drug safety information for the selection of hypnotics for sleep disorders, which increase with age.
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Fraturas do Quadril , Humanos , Idoso , Estudos de Casos e Controles , Japão/epidemiologia , Fraturas do Quadril/induzido quimicamente , Fraturas do Quadril/epidemiologia , Hipnóticos e Sedativos/efeitos adversos , Benzodiazepinas/efeitos adversosAssuntos
Laringoscópios , Humanos , Criança , Laringoscopia , Intubação Intratraqueal , Gravação em VídeoRESUMO
PURPOSE: The healthcare workers are at the greatest risk of being exposed to viral infection during airway management of a patient with coronavirus disease 2019 (COVID-19). An air extractor which suctions air around the patient's face would reduce the spread of viral aerosols during coughing, but no study has confirmed this. We assessed whether or not an air extractor reduces the amount of aerosols spreading toward the operator's face, during coughing of simulated patients. METHODS: After obtained approval of the study by a research ethics committee and written informed consent from 20 volunteers (and additional 20 volunteers), we asked each volunteer to lie supine on a table in a positive-pressure management operating room. As a cross-over design, we used an airborne particle counter (Handheld 3016, SGY company, Tokyo) to measure the aerosols approximately 30 cm above the participant's mouth, while the volunteer was coughing, with and without the use of an air extractor Free-100 M (Forest-one, Funabashi), facing the participant's mouth. In another 20 volunteers, the aerosols were measured, while each volunteer was lying supine, without coughing, and without the use of the air extractor. RESULTS: The aerosol count during coughing was significantly lower when the air extractor was used [median: 55 (interquartile range: 15-128)] than when it was not used [73 (44-201)] [p = 0.001, difference: 19 (95%CI: 4-70)]. CONCLUSIONS: The Free-100 M air extractor would reduce, but do not remove all, aerosols produced by coughing of a patient, and thus may reduce the risk of infection of COVID-19.
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COVID-19 , Humanos , Manuseio das Vias Aéreas , Aerossóis e Gotículas Respiratórios , Sucção , Estudos Cross-OverRESUMO
PURPOSE: We studied whether a newly available gastric tube insertion guide (Fuji Medical, Tokyo, Japan) was effective in insertion of a nasogastric tube. METHODS: Sixty anesthetized patients were randomly allocated to three groups, and we attempted to insert a nasogastric tube with a blind technique (Group B), with the lateral neck pressure (Group L), or with the tube guide (Group G). If the insertion failed in Group B or L, its insertion was attempted with the tube guide. Primary outcome measure was the insertion success rate within 300 s. RESULTS: The success rate in Group G (19 of 20 patients) was significantly higher than Group L (13 of 20 patients) (P = 0.04; 95% confidence intervals for difference: 16-44%), and than Group B (11 of 19 patients) (P = 0.008; 23-50%). In the 15 patients of Groups B and L, in whom insertion had failed, insertion with the tube guide was successful in 14 patients. There was no significant difference in insertion time between the groups, but in patients in whom insertion was successful, it was significantly longer in Group G (median of 147 s) than in Group L (66 s) (P < 0.01) and Group B (46 s) (P < 0.01). Minor complications occurred in 2 patients in Group B, 1 in Group L, and 5 in Group G (P > 0.05). CONCLUSION: We conclude that the gastric tube insertion guide (Fuji Medical, Tokyo, Japan) may be useful when the conventional method of insertion has failed.