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1.
Asian Spine J ; 18(1): 32-41, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38379143

RESUMO

STUDY DESIGN: Retrospective analysis of case series. PURPOSE: This study aimed to clarify the effects of full endoscopic posterior cervical foraminotomy (FPCF) on cervical spondylotic amyotrophy (CSA). OVERVIEW OF LITERATURE: The method for decompressing the ventral nerve root and anterior horn (AH) in CSA is controversial. METHODS: Patients without myelopathy who underwent FPCF for proximal CSA between 2017 and 2022 were analyzed. The outcome measure was the results of the manual muscle testing (MMT) of the deltoid and biceps. Preoperative nerve root and AH compression were evaluated by magnetic resonance imaging. The intervertebral foramen morphology and bony decompression extent were evaluated by computed tomography. RESULTS: FPCF was performed at the C4/5 level and at the C4/5 and C5/6 levels in 14 and 11 patients, respectively. The width of the narrowest intervertebral foramen was significantly narrower on the affected side than on the healthy side at the C4/5 (2.5 mm vs. 3.6 mm) and operated C5/6 (1.9 mm vs. 3.1 mm) levels. AH compression occurred at the C4/5 and C5/6 levels in 28% and 21% of the patients, respectively. Bony decompression was performed laterally beyond the narrowest foramen at the C4/5 and C5/6 levels in 96% and 91% of the patients, respectively. Compared with patients without AH compression, in those with AH compression, the lamina was resected medially by an average of >1.7 mm and >3.6 mm at the C4/5 and C5/6 levels, respectively. Furthermore, 76% and 81% of the facet joint surfaces were preserved at the C4/5 and C5/6 levels, respectively. Postoperative MMT grade improvement was excellent, good, and fair in 64%, 20%, and 16% of the patients, respectively. CONCLUSIONS: FPCF was effective for treating proximal CSA.

2.
Sci Rep ; 14(1): 1672, 2024 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-38243054

RESUMO

Numerous COVID-19 diagnostic imaging Artificial Intelligence (AI) studies exist. However, none of their models were of potential clinical use, primarily owing to methodological defects and the lack of implementation considerations for inference. In this study, all development processes of the deep-learning models are performed based on strict criteria of the "KAIZEN checklist", which is proposed based on previous AI development guidelines to overcome the deficiencies mentioned above. We develop and evaluate two binary-classification deep-learning models to triage COVID-19: a slice model examining a Computed Tomography (CT) slice to find COVID-19 lesions; a series model examining a series of CT images to find an infected patient. We collected 2,400,200 CT slices from twelve emergency centers in Japan. Area Under Curve (AUC) and accuracy were calculated for classification performance. The inference time of the system that includes these two models were measured. For validation data, the slice and series models recognized COVID-19 with AUCs and accuracies of 0.989 and 0.982, 95.9% and 93.0% respectively. For test data, the models' AUCs and accuracies were 0.958 and 0.953, 90.0% and 91.4% respectively. The average inference time per case was 2.83 s. Our deep-learning system realizes accuracy and inference speed high enough for practical use. The systems have already been implemented in four hospitals and eight are under progression. We released an application software and implementation code for free in a highly usable state to allow its use in Japan and globally.


Assuntos
COVID-19 , Aprendizado Profundo , Humanos , COVID-19/diagnóstico por imagem , Inteligência Artificial , Tomografia Computadorizada por Raios X/métodos , Software , Teste para COVID-19
3.
Xenobiotica ; 54(2): 45-56, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38265764

RESUMO

In the early stages of drug discovery, adequate evaluation of the potential drug-drug interactions (DDIs) of drug candidates is important. Several CYP3A activators are known to lead to underestimation of DDIs. These compounds affect midazolam 1'-hydroxylation but not midazolam 4-hydroxylation.We used both metabolic reactions of midazolam to evaluate the activation and inhibition of CYP3A activators simultaneously. For our CYP inhibition assay using cocktail probe substrates, simultaneous liquid chromatography-tandem mass spectrometry monitoring of 1'-hydroxymidazolam and 4-hydroxymidazolam for CYP3A was established in addition to monitoring of 4-hydroxydiclofenac and 1'-hydroxybufuralol for CYP2C9 and CYP2D6.The results of our cocktail inhibition assay were well correlated with those of a single inhibition assay, as were the estimated inhibition parameters for typical CYP3A inhibitors. In our assay, a proprietary compound that activated midazolam 1'-hydroxylation and tended to inhibit 4-hydroxylation was evaluated along with known CYP3A activators. All compounds were well characterised by comparison of the results of midazolam 1'- and 4-hydroxylation.In conclusion, our CYP cocktail inhibition assay can detect CYP3A activation and assess the direct and time-dependent inhibition potentials for CYP3A, CYP2C9, and CYP2D6. This method is expected to be very efficient in the early stages of drug discovery.


Assuntos
Citocromo P-450 CYP2D6 , Sistema Enzimático do Citocromo P-450 , Citocromo P-450 CYP2D6/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Citocromo P-450 CYP3A/metabolismo , Citocromo P-450 CYP2C9/metabolismo , Espectrometria de Massas em Tandem/métodos , Midazolam/metabolismo , Microssomos Hepáticos/metabolismo , Cromatografia Líquida/métodos , Interações Medicamentosas
4.
Am J Physiol Regul Integr Comp Physiol ; 326(1): R19-R28, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37867474

RESUMO

The sleep-wake cycle of human subjects was artificially split into two episodes by imposing an 8-h light and 4-h dark cycle (LD 8:4) twice a day for 7 days, which was followed by a 3-day free-running session. Sleep was permitted only in the dark period. The subjects in the ordinary group were exposed to ordinary light (ca. 500 lx) in the 8-h light period, and those in the bright light group to bright (ca. 5,000 lx) and ordinary light alternatively with bright light after the first dark period (2400-400). Split sleeps persisted in the free-running session with the major episode around the first dark period and the minor episode around the second dark period. By contrast, circadian melatonin rhythm in the free-running session significantly phase delayed in the ordinary light group, but phase advanced in the bright light group, keeping the melatonin rhythm unsplit. The length of nocturnal melatonin secretion (NMS) was significantly shortened in the bright light group. Interestingly, the falling phase of NMS advanced significantly further than the rising phase. Such a difference was not detected in the ordinary light group. Similar differences were observed in the body temperature rhythm. These findings indicated oscillatory mechanisms underlying split sleeps distinct from the circadian pacemaker and suggested an involvement of different circadian oscillators in the rising and falling phases of NMS, which is consistent with the dual oscillator model proposed for the circadian system of nocturnal rodents.NEW & NOTEWORTHY The present study demonstrated that human sleep was separated into two essentially identical components, which persisted under constant conditions, suggesting circadian oscillator underlying split-sleep episodes. The study also indicated differential light sensitivities in the rising and falling phases of circadian melatonin rhythm, indicating the involvement of two different oscillators. These results consisted of the evening and morning dual-oscillator hypothesis for the circadian pacemaker and the hierarchical model for the pacemaker and sleep-wake cycle.


Assuntos
Melatonina , Humanos , Ritmo Circadiano/fisiologia , Sono/fisiologia , Temperatura Corporal/fisiologia , Luz
5.
Nurs Health Sci ; 25(4): 712-720, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37987542

RESUMO

This study aimed to explore factors associated with ambulance use and emergency department (ED) visits among people with dementia in the month before death. A web-based survey of bereaved family caregivers of people with dementia was conducted in March 2020. Multivariate logistic regression analyses were conducted with ambulance use and ED visits in the month before death as dependent variables. Age and gender of people with dementia and their family caregivers, home care use, decision-makers, comorbidities, degree of independence in daily living, and caregivers' preparedness for death were independent variables. Data were collected from 817 caregivers of people with dementia who had died at hospitals (52.4%), long-term care facilities (25.0%), or own homes (22.4%). Caregivers' lack of preparedness for death was significantly associated with ambulance use in the month before death. Comorbidites and males with dementia were significantly associated with ED visits in the month before death. Better death preparedness of family caregivers may reduce ambulance use for symptoms that can be more effectively addressed by palliative care than acute care for people with dementia.


Assuntos
Ambulâncias , Demência , Masculino , Humanos , Estudos Transversais , Demência/complicações , Demência/terapia , Cuidadores , Serviço Hospitalar de Emergência
6.
Am J Physiol Regul Integr Comp Physiol ; 325(5): R619-R628, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37694335

RESUMO

Circadian rhythms and sleep-wake cycles were measured in volunteers staying singly in temporal isolation unit where they were exposed to artificial short and long light-dark (LD) cycles for 7 days. The long day consisted of 16-h light and 8-h dark (LD 16:8) and the short day consisted of 8-h light and 16-h dark (LD 8:16). During the light period, bright light of approximately 5,000 lux was given from the ceiling and during the dark period there was no illumination. Sleep was monitored by bed sensors, wrist actiwatch, and polysomnography (PSG) on the first and last nights of the schedule. Sleep length was significantly longer under LD 8:16 than under LD 16:8 and the sleep quality estimated by PSG was worse under LD 8:16 than under LD 16:8, which were comparable to natural seasonality in sleep. The circadian rhythm in plasma melatonin was measured in dim light (10 lux) before and after the LD exposures. The nocturnal melatonin secretion (NMS) was significantly longer after LD 8:16 than after LD 16:8 due to differential phase shifts of the rising and falling phases of NMS. After LD 8:16, the falling phase was much advanced than the rising phase, whereas after LD 16:8 the rising phase was much delayed than the falling phase, resulting in the NMS compression. These results indicate that the light sensitivity in terms of phase shifting is different in the two circadian phases, supporting a dual oscillator hypothesis with different phase-response curves for light in the human circadian system.NEW & NOTEWORTHY The present study demonstrated differential light responsiveness of the rising and falling phases of nocturnal melatonin secretion in human subjects exposed to artificial long (LD 16:8) and short days (LD 8:16) and suggested the involvement of different oscillators under these phases. The findings well mimicked the seasonality of the circadian rhythms in nature and consisted with the evening/morning dual oscillator hypothesis proposed originally for nocturnal rodents, providing a new concept for the human circadian system.

7.
Acute Med Surg ; 10(1): e851, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37261374

RESUMO

Background: Clinical risk scores are widely used in emergency medicine, and some studies have evaluated their use in patients with coronavirus disease 2019 (COVID-19). However, no studies have evaluated their use in patients with the COVID-19 Delta variant. We aimed to study the performance of four different clinical scores (National Early Warning Score [NEWS], quick Sequential Organ Failure Assessment [qSOFA], Confusion, Respiratory rate, Blood pressure, and Age ≥65 [CRB-65], and Kanagawa score) in predicting the risk of severe disease (defined as the need for intubation and in-hospital mortality) in patients with the COVID-19 Delta variant. Methods: This was a retrospective cohort study of patients hospitalized with suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant infection between June 1 and December 31, 2021. The primary outcomes were the sensitivity and specificity of the aforementioned clinical risk scores at admission to predict severe disease. Areas under the receiver operating characteristic curves (AUROCs) were compared between the clinical risk scores and we identified new cut-off points for all four scores. Results: A total of 249 adult patients were included, of whom 18 developed severe disease. A NEWS ≥7 at admission predicted severe disease with 72.2% sensitivity and 86.2% specificity. The NEWS (AUROC 0.88) was superior to both the qSOFA (AUROC 0.74) and the CRB-65 (AUROC 0.67), and there was no significant difference between the NEWS and Kanagawa score (AUROC 0.86). Conclusion: The NEWS at hospital admission predicted the severity of the COVID-19 Delta variant with high accuracy.

9.
J Vet Med Sci ; 85(4): 443-446, 2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-36806247

RESUMO

The geneLEAD VIII is a fully-automated nucleic acid extraction/quantitative PCR equipment developed by Precision System Science Co., Ltd., (PSS). To take advantage of its capability, we developed a quantitative assay system to measure growth of animal viruses. The system was used to assay one of the Chinese herbal extracts whose anti-malarial activities were previously reported and demonstrated its dose-dependent anti-viral activity against feline infectious peritonitis virus (FIPV), a feline coronavirus causing the fatal diseases in cats, and relatively low cell toxicity. The assay developed in this study is useful to screen antiviral drugs and the anti-FIPV activity of the herbal extract identified have a potential to lead to development of new drugs against FIPV and other coronaviruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).


Assuntos
Antineoplásicos , COVID-19 , Doenças do Gato , Coronavirus Felino , Peritonite , Animais , Gatos , Coronavirus Felino/genética , SARS-CoV-2/genética , COVID-19/veterinária , Antivirais/uso terapêutico , Reação em Cadeia da Polimerase/veterinária , Peritonite/veterinária , Teste para COVID-19/veterinária , Doenças do Gato/tratamento farmacológico
10.
Xenobiotica ; 52(5): 488-497, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35913106

RESUMO

Linzagolix is an orally available gonadotropin-releasing hormone antagonist used to treat sex-hormone-dependent diseases in women. This study aimed to investigate drug-drug interactions between linzagolix and iron/calcium ions in the intended clinical setting by conducting pharmacokinetic studies in vitro and in rats.Insoluble precipitate formation with metal ions was evaluated by measuring linzagolix concentrations in four types of bio-relevant dissolution media (fasted/fed state simulated gastric fluid and fasted/fed state simulated gastric fluid version 2), and chelate complex formation with metal ions was evaluated by release of linzagolix from a cellulose membrane sac. In these in vitro studies, linzagolix showed no potential for insoluble precipitate formation under fasted/fed conditions and no chelate complex formation in the presence of metal ions.In rats, the plasma concentration-time profiles of linzagolix and iron ion were similar regardless of whether they were administered with or without ferrous sulphate and linzagolix choline at clinically relevant doses. Thus, linzagolix and iron ion had no effect on each other's absorption in vivo.In conclusion, linzagolix is unlikely to cause clinically relevant drug-drug interactions by chelating metal ions according to the results of in vitro and in vivo studies.


Assuntos
Cálcio , Ferro , Animais , Ácidos Carboxílicos , Feminino , Hormônio Liberador de Gonadotropina , Humanos , Íons , Pirimidinas , Ratos , Solubilidade
11.
J Neurosurg Spine ; 36(2): 185-192, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34598157

RESUMO

OBJECTIVE: Perineural cysts, also called Tarlov cysts, are dilatations of the nerve root sleeves commonly found in the sacrum. The majority of the cysts are asymptomatic and found incidentally on routine spine imaging. Symptomatic sacral perineural cysts (SPCs) that induce intractable low-back pain, radicular symptoms, and bladder/bowel dysfunction require surgery. However, the surgical strategy for symptomatic SPCs remains controversial. The authors hypothesized that the symptoms were caused by an irritation of the adjacent nerve roots caused by SPCs, and developed a wrapping surgery to treat these cysts. METHODS: Seven patients with severe unilateral medial thigh pain and ipsilateral SPCs were included. Preoperative MRI showed that the cysts were severely compressing the adjacent nerve roots in all patients. After a partial laminectomy of the sacrum, the SPCs were punctured and CSF was aspirated to reduce their size, followed by dissection of the adjacent nerve roots from the SPCs. The SPCs were then wrapped with a Gore-Tex membrane to avoid reexpansion. RESULTS: All 7 patients experienced substantial relief of their symptoms. The average numeric rating scale pain score was reduced from an average preoperative value of 7.9 to 0.6 postoperatively. Postoperative MRI showed that all cysts were reduced in size and the adjacent nerve roots were decompressed. Regrowth of the treated cysts or recurrence of the symptoms did not occur during the entire follow-up period, which ranged from 39 to 90 months. No complications were noted. CONCLUSIONS: The authors' new wrapping technique was effective in relieving radicular symptoms for patients with symptomatic SPCs. The results suggested that the symptoms stemmed from compression of the adjacent nerve roots caused by the SPCs, and not from the nerve roots in the cysts.

12.
Parasitol Int ; 87: 102532, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34933121

RESUMO

Plasmodium falciparum, the most virulent human malaria parasite, causes serious diseases among the infected patients in the world and is particularly important in African regions. Although artemisinin combination therapy is recommended by the WHO for treatment of P. falciparum-malaria, the emergence of artemisinin-resistant parasites has become a serious issue which underscores the importance of sustained efforts to obtain novel chemotherapeutic agents against malaria. As a part of such efforts, thirty-nine herbal extracts from traditional Chinese medicine (TCM) were assayed for their anti-malarial activity using 3D7 strain of P. falciparum. Three herbal supplements appeared to possess higher specific anti-malarial activity than the others. One of them (D3) was separated by two sequential fractionations with reverse-phase (the first step) and normal-phase (the second step) liquid chromatography, in which some fractions resulted in higher specific activities than those of D3 or the previous fractions. Cell toxicity assay was performed with the fractions of the first fractionation and demonstrated no obvious cell toxicity. These results suggest that structure determination of the major compound for the anti-malarial activity in D3 may help the development of more potent chemicals in the future.


Assuntos
Antimaláricos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Inonotus/química , Malária Falciparum/tratamento farmacológico , Panax notoginseng/química , Plasmodium falciparum/efeitos dos fármacos , Antimaláricos/farmacologia , Antimaláricos/toxicidade , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Resistência a Medicamentos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/toxicidade , Células HeLa , Humanos , Concentração Inibidora 50 , Japão
13.
BMJ Case Rep ; 14(1)2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33402370

RESUMO

A 67-year-old man presented with a 2-month history of pain in his right buttock and lower limb. MRI depicted right L5/S1 lateral recess stenosis requiring surgical treatment; however, preoperative CT showed an approximately 7 cm long, thin, rod-shaped structure in the rectum, which was ultimately determined to be an accidentally ingested toothpick. It was removed surgically 6 days after diagnosis, because right leg pain worsened rapidly. The pain disappeared thereafter, and the symptoms have not recurred since. The pain might have been localised to the right buttock and posterior thigh in the early stages because the fine tip of the toothpick was positioned to the right of the anterior ramus of the S2 spinal nerve. Although sacral plexus disorder caused by a rectal foreign body is extremely rare, physicians should be mindful to avoid misdiagnosis.


Assuntos
Corpos Estranhos/diagnóstico por imagem , Corpos Estranhos/cirurgia , Plexo Lombossacral , Doenças do Sistema Nervoso Periférico/diagnóstico por imagem , Doenças do Sistema Nervoso Periférico/etiologia , Reto , Idoso , Corpos Estranhos/complicações , Humanos , Masculino , Doenças do Sistema Nervoso Periférico/cirurgia
14.
Front Cell Infect Microbiol ; 11: 797509, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35004357

RESUMO

Malaria, a disease caused by the protozoan parasites Plasmodium spp., is still causing serious problems in endemic regions in the world. Although the WHO recommends artemisinin combination therapies for the treatment of malaria patients, the emergence of artemisinin-resistant parasites has become a serious issue and underscores the need for the development of new antimalarial drugs. On the other hand, new and re-emergences of infectious diseases, such as the influenza pandemic, Ebola virus disease, and COVID-19, are urging the world to develop effective chemotherapeutic agents against the causative viruses, which are not achieved to the desired level yet. In this review article, we describe existing drugs which are active against both Plasmodium spp. and microorganisms including viruses, bacteria, and fungi. We also focus on the current knowledge about the mechanism of actions of these drugs. Our major aims of this article are to describe examples of drugs that kill both Plasmodium parasites and other microbes and to provide valuable information to help find new ideas for developing novel drugs, rather than merely augmenting already existing drug repurposing efforts.


Assuntos
COVID-19 , Preparações Farmacêuticas , Plasmodium , Desenvolvimento de Medicamentos , Humanos , Plasmodium falciparum , SARS-CoV-2
15.
BMC Neurol ; 20(1): 402, 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33143678

RESUMO

BACKGROUND: Persistent first intersegmental artery (PFIA) is a rare anatomical variation of vertebral arteries and is an asymptomatic finding in most cases. Here we report a rare case of cervical myelopathy caused by spinal cord compression by the PFIA. CASE PRESENTATION: The patient was a 52-year-old man who complained of numbness and burning sensation around the neck and left shoulder area, partial weakness in the left deltoid muscle, right side thermal hypoalgesia, and disturbance of deep sensation since the past 1 year, and the symptoms had gradually worsened. Magnetic resonance imaging (MRI) and computed tomography (CT) showed spinal cord compression by the left PFIA at the C1/C2 level. Because conservative treatment was ineffective, microvascular decompression (MVD) of the PFIA was performed. The left PFIA was laterally transposed using polytetrafluoroethylene (PTFE) bands and anchored to the dura mater using three PTFE bands. To achieve adequate transposition, the small blood vessels bridging the spinal cord and PFIA and the dorsal root nerve had to be sacrificed. Postoperative T2-weighted MRI showed a small hyperintense region in the lateral funiculus of the spinal cord, but no new neurological deficits were identified. In the early postoperative stage, the patient's deep sensory impairment and motor dysfunction were improved. His numbness and burning sensation almost disappeared, but slight thermal hypoalgesia remained in the lower limb. CONCLUSION: MVD is an effective treatment for spinal cord compression caused by the PFIA, but further studies are necessary to help address technical difficulties and avoid complications.


Assuntos
Cirurgia de Descompressão Microvascular/métodos , Compressão da Medula Espinal/cirurgia , Doenças da Medula Espinal/etiologia , Vértebras Cervicais , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Artéria Vertebral/cirurgia
16.
Dermatol Ther (Heidelb) ; 10(6): 1359-1369, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32975744

RESUMO

INTRODUCTION: Atopic dermatitis (AD) is a chronic, relapsing, inflammatory skin disease characterized by eczema and pruritus, and frequently impairs sleep quality. Although cyclosporine improves symptoms of AD, objective evaluation of sleep in patients with AD treated with cyclosporine has not been reported. This study was conducted to elucidate the effects of cyclosporine on sleep quality for patients with AD. METHODS: Twelve patients with moderate-to-severe AD were recruited. Nocturnal sleep quality was evaluated for 7 days using a sleep analyzer, which patients wore at the waist before and after cyclosporine was administered at 2.0-4.0 mg/kg per day. Seven parameters of sleep quality were measured before and after cyclosporine administration for a period of 7 days for each patient. RESULTS: The administration of cyclosporine significantly improved total sleep time in four cases, sleep latency in two cases, wake after sleep onset in six cases, number of awakenings in two cases, sleep efficiency in seven cases, number of awakenings for more than 8 min in three cases, and number of position changes recorded every 2 min in three cases. The mean values of sleep latency significantly decreased after cyclosporine administration (P = 0.023). The mean value of sleep efficiency significantly increased after the administration (P = 0.002). CONCLUSION: Cyclosporine improves sleep quality in patients with moderate-to-severe AD.

17.
BMJ Open ; 10(6): e034602, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32546488

RESUMO

OBJECTIVES: The National Early Warning Score (NEWS) was originally developed to assess hospitalised patients in the UK. We examined whether the NEWS could be applied to patients transported by ambulance in Japan. DESIGN: This retrospective study assessed patients and calculated the NEWS from paramedic records. Emergency department (ED) disposition data were categorised into the following groups: discharged from the ED, admitted to the ward, admitted to the intensive care unit (ICU) or died in the ED. The predictive performance of NEWS for patient disposition was assessed using receiver operating characteristic curve analysis. Patient dispositions were compared among NEWS-based categories after adjusting for age, sex and presence of traumatic injury. SETTING: A tertiary hospital in Japan. PARTICIPANTS: Overall, 2847 patients transported by ambulance between April 2017 and March 2018 were included. RESULTS: The mean (±SD) NEWS differed significantly among patients discharged from the ED (n=1330, 3.7±2.9), admitted to the ward (n=1263, 60.3±3.8), admitted to the ICU (n=232, 9.4±4.0) and died in the ED (n=22, 110.7±2.9) (p<0.001). The prehospital NEWS C-statistics (95% CI) for admission to the ward, admission to the ICU or death in the ED; admission to the ICU or death in the ED; and death in the ED were 0.73 (0.72-0.75), 0.81 (0.78-0.83) and 0.90 (0.87-0.93), respectively. After adjusting for age, sex and trauma, the OR (95% CI) of admission to the ICU or death in the ED for the high-risk (NEWS ≥7) and medium-risk (NEWS 5-6) categories was 13.8 (8.9-21.6) and 4.2 (2.5-7.1), respectively. CONCLUSION: The findings from this Japanese tertiary hospital setting showed that prehospital NEWS could be used to identify patients at a risk of adverse outcomes. NEWS stratification was strongly correlated with patient disposition.


Assuntos
Escore de Alerta Precoce , Serviços Médicos de Emergência/estatística & dados numéricos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Centros de Atenção Terciária
18.
J Clin Pharmacol ; 60(10): 1314-1323, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32459872

RESUMO

The effects of itraconazole on the pharmacokinetics of rovatirelin were investigated in an open-label, single-sequence drug-drug interaction study in 16 healthy subjects. Subjects were administered a single oral dose of rovatirelin (1.6 mg) on day 1 and day 15. From day 8 through 16, subjects received daily oral doses of itraconazole (200 mg/day). Concentrations of rovatirelin and (thiazolylalanyl)methylpyrrolidine (TAMP), the major metabolite of rovatirelin formed by cytochrome P450 (CYP) 3A4/5, were determined in plasma and urine. Pharmacokinetic parameters were used to evaluate the drug-drug interaction potential of rovatirelin as a victim. With coadministration, maximum concentration (Cmax ) and area under the concentration-time curve extrapolated to infinity (AUCinf ) of rovatirelin increased 3.05-fold and 2.82-fold, respectively, and the 90% confidence intervals of the ratios for Cmax (2.64-3.52) and AUCinf (2.47-3.23) did not fall within the 0.8-1.25 boundaries. Urinary excretion of rovatirelin increased at almost the same ratio as the AUCinf ratio with coadministration; however, renal clearance did not change. Cmax , AUCinf , and urinary excretion of TAMP were decreased by coadministration. Itraconazole has the potential to inhibit drug transport via intestinal P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP); therefore, substrate assessments of rovatirelin for the 2 transporters were evaluated using Caco-2 cell monolayers. In vitro studies showed that rovatirelin is a substrate for P-gp but not for BCRP. The current study shows that itraconazole's effect on rovatirelin pharmacokinetics is mediated through inhibition of CYP3A4/5 and intestinal P-gp.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Inibidores do Citocromo P-450 CYP3A/farmacocinética , Interações Medicamentosas , Itraconazol/farmacocinética , Oxazolidinonas/farmacocinética , Pirrolidinas/farmacocinética , Hormônio Liberador de Tireotropina/análogos & derivados , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Administração Oral , Adulto , Área Sob a Curva , Povo Asiático , Transporte Biológico/efeitos dos fármacos , Células CACO-2 , Citocromo P-450 CYP3A/metabolismo , Inibidores do Citocromo P-450 CYP3A/administração & dosagem , Inibidores do Citocromo P-450 CYP3A/farmacologia , Vias de Eliminação de Fármacos/efeitos dos fármacos , Voluntários Saudáveis , Hormônios/sangue , Humanos , Itraconazol/administração & dosagem , Itraconazol/farmacologia , Masculino , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/metabolismo , Oxazolidinonas/administração & dosagem , Oxazolidinonas/efeitos adversos , Oxazolidinonas/metabolismo , Permeabilidade/efeitos dos fármacos , Pirrolidinas/administração & dosagem , Pirrolidinas/efeitos adversos , Pirrolidinas/metabolismo , Adulto Jovem
19.
Acute Med Surg ; 7(1): e474, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31988786

RESUMO

BACKGROUND: Purpura fulminans secondary to Capnocytophaga canimorsus (C. canimorsus) infection without a wound is rare and often misdiagnosed initially. We report a patient who died due to C. canimorsus bacteremia with purpura fulminans and acute compartment syndrome of all extremities. CARE PRESENTATION: A 38-year-old Japanese man with a history of alcoholism presented with a 2-day history of gastroenteritis. The chief complaints were abdominal pain and diarrhea, and he had abdominal tenderness. Laboratory findings showed multiple organ failure. On day 2, pain in the lower extremities associated with motor and sensory dysfunction developed. On day 3, purpura on the whole body spread to all extremities. All four extremities became rigid, and acute compartment syndrome developed. The patient died due to uncontrolled hyperkalemia and lactic acidosis. CONCLUSIONS: Capnocytophaga canimorsus transmission can occur through licking or even close contact with animals when a risk factor of C. canimorsus infection, such as alcoholism, is present.

20.
Eur J Radiol ; 124: 108817, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31931302

RESUMO

PURPOSE: To clarify the utility of dual energy CT (DECT) virtual non-calcium (VNCa) imaging for investigating lumbar intervertebral disc degeneration. METHOD: Fifty-three patients who underwent both DECT and MR imaging were retrospectively reviewed. Midsagittal T2-weighted imaging findings of all discs were classified based on modified Pfirrmann grade (mPG). Quantitative evaluation of VNCa maps was achieved by setting volumes of interest on each disc. We compared VNCa CT values with mPG using Spearman's rank correlation and one-way ANOVA. VNCa imaging findings of each disc were classified by two neuroradiologists into one of three categories based on the attenuation of nucleus pulposus (NP) compared to that of annulus fibrosus (AF) or muscle. The relationship between the visual categories for each rater and mPGs was analyzed by chi-square test. Statistical significance was established at P < 0.05. RESULTS: Among the included 171 lumbar discs, significant positive correlation was found between VNCa CT values for NP and mPGs (R2 = 0.574, P < 0.05), whereas no significant correlation was found between those for AF and mPGs (R2= -0.015, P = 0.846). Mean VNCa CT values for NP were significantly different among each mPG (P < 0.05 for each), except between grades 3 and 4 (P = 0.111). Mean VNCa CT values for AF were not significantly different among each mPG (P = 0.160-1.000). Statistically significant difference was observed among the visual categories for VNCa maps and mPGs in each rater (P < 0.05 for both). CONCLUSIONS: VNCa imaging acquired by a single DECT scan and post-processing has potential as an imaging biomarker of lumbar intervertebral disc degeneration.


Assuntos
Degeneração do Disco Intervertebral/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Feminino , Humanos , Disco Intervertebral/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Imagem Radiográfica a Partir de Emissão de Duplo Fóton/métodos , Estudos Retrospectivos
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