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Background: Rheumatoid arthritis (RA) is a chronic inflammatory disorder primarily targeting joints, significantly impacting patients' quality of life. The introduction of tumor necrosis factor-alpha (TNF-α) inhibitors has markedly improved RA management by reducing inflammation. However, these medications are associated with adverse skin reactions, which can vary greatly among patients due to genetic differences. Objectives: This study aimed to identify risk factors associated with skin adverse events by TNF-α in RA patients. Methods: A cohort study was conducted, encompassing patients with RA who were prescribed TNF-α inhibitors. This study utilized machine learning algorithms to analyze genetic data and identify markers associated with skin-related adverse events. Various machine learning algorithms were employed to predict skin and subcutaneous tissue-related outcomes, leading to the development of a risk-scoring system. Multivariable logistic regression analysis identified independent risk factors for skin and subcutaneous tissue-related complications. Results: After adjusting for covariates, individuals with the TT genotype of rs12551103, A allele carriers of rs13265933, and C allele carriers of rs73210737 exhibited approximately 20-, 14-, and 10-fold higher incidences of skin adverse events, respectively, compared to those with the C allele, GG genotype, and TT genotype. The machine learning algorithms used for risk prediction showed excellent performance. The risk of skin adverse events among patients receiving TNF-α inhibitors varied based on the risk score: 0 points, 0.6%; 2 points, 3.6%; 3 points, 8.5%; 4 points, 18.9%; 5 points, 36.7%; 6 points, 59.2%; 8 points, 90.0%; 9 points, 95.7%; and 10 points, 98.2%. Conclusions: These findings, emerging from this preliminary study, lay the groundwork for personalized intervention strategies to prevent TNF-α inhibitor-associated skin adverse events. This approach has the potential to improve patient outcomes by minimizing the risk of adverse effects while optimizing therapeutic efficacy.
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PURPOSE: This study aimed to perform a nationwide analysis of medication errors (MEs) from hospitals using national reporting system data and to compare the ME patterns among different age groups. METHODS: We analyzed medication-related incidents in acute care hospitals reported to the Korean Patient Safety Reporting and Learning System (KOPS), which is a patient safety reporting system, from July 2016 to December 2020. The stages of the medication use process, type of errors, medication class involved in MEs, and degree of harm were analyzed. RESULTS: Among a total of 5071 medication-related incidents, 37.7% (1911 cases) were incidents that caused patient harm and 1.2% caused long-term, permanent, and fatal harm. The proportion of medication-related incidents that resulted in harm was the highest among the <1-year-old age group (67 cases, 51.5%), followed by the elderly (≥ 65 years) (828 cases, 40.9%). The cases leading to patient death were most frequently reported in patients aged ≥65 years. Medication-related incidents occurred mainly in the administration stage (2954 cases, 58.3%), and wrong dose was the most frequently reported ME type. The most prevalent medication class occurring in the 20-64-year age group (256 cases, 11.7%) was 'antibacterials for systemic use', whereas 'contrast media' (236 cases, 11.6%) and 'blood substitutes and perfusion solutions' (98 cases, 19.3%) were the most prevalent drug classes in the ≥65- and <20-year-old age groups, respectively. CONCLUSIONS: It is necessary to establish guidelines for the prevention of medication-related incidents according to the medication use process and patient age group.
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Erros de Medicação , Segurança do Paciente , Humanos , Erros de Medicação/estatística & dados numéricos , Idoso , República da Coreia/epidemiologia , Pessoa de Meia-Idade , Adulto , Pré-Escolar , Adulto Jovem , Criança , Lactente , Fatores Etários , Segurança do Paciente/estatística & dados numéricos , Adolescente , Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Masculino , Hospitais/estatística & dados numéricos , Feminino , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Idoso de 80 Anos ou maisRESUMO
The prevalence of Alzheimer's disease (AD) and its associated economic and societal burdens are on the rise, but there are no curative treatments for AD. Interestingly, this neurodegenerative disease shares several biological and pathophysiological features with cancer, including cell-cycle dysregulation, angiogenesis, mitochondrial dysfunction, protein misfolding, and DNA damage. However, the genetic factors contributing to the overlap in biological processes between cancer and AD have not been actively studied. In this review, we discuss the shared biological features of cancer and AD, the molecular targets of anticancer drugs, and therapeutic approaches. First, we outline the common biological features of cancer and AD. Second, we describe several anticancer drugs, their molecular targets, and their effects on AD pathology. Finally, we discuss how protein-protein interactions (PPIs), receptor inhibition, immunotherapy, and gene therapy can be exploited for the cure and management of both cancer and AD. Collectively, this review provides insights for the development of AD theragnostics based on cancer drugs and molecular targets.
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Doença de Alzheimer , Antineoplásicos , Neoplasias , Humanos , Doença de Alzheimer/terapia , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/metabolismo , Neoplasias/genética , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Imunoterapia , Animais , Terapia de Alvo Molecular , Terapia GenéticaRESUMO
In this study, the recovery of Atrina pectinata posterior adductor polysaccharides (APP-PS) using subcritical water extraction (SWE) was optimized by response surface methodology (RSM) and the physicochemical and biological properties of the recovered APP-PS were evaluated. The optimal extraction conditions, which resulted in a maximum yield of 55.58 ± 1.12 %, were temperature, 152.08 °C; extraction time, 10 min; solid-liquid ratio, 30 g/600 mL. The obtained APP-PS was found to be 88.05 ± 0.17 % total sugar. Fourier transform infrared (FT-IR) and Nuclear magnetic resonance (NMR) analyses confirmed the presence of the α-coordination of D-glucan in the polymer sample. The analysis of monosaccharide composition, along with thermogravimetric analysis, revealed the typical structure of the sample, composed of glucose alone. Total phenolic contents of APP-PS were measured as 5.47 ± 0.01 mg Gallic acid/g of dry sample and total flavonoids contents were determined to be 0.78 ± 0.06 mg Quercetin/g of dry sample. For biological activities, ABTS+, DPPH and FRAP antioxidant activities were measured to be 20.00 ± 0.71, 2.35 ± 0.05 and 4.02 ± 0.07 µg Trolox equivalent/100 g of dry sample, respectively. Additionally ACE inhibitory was confirmed to be 87.02 ± 0.47 %. These results showed that SWE is an effective method to recover biofunctional materials from marine organisms.
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Produtos Biológicos , Água , Água/química , Espectroscopia de Infravermelho com Transformada de Fourier , Extratos Vegetais/química , Antioxidantes/farmacologia , Antioxidantes/química , Polissacarídeos/farmacologia , Polissacarídeos/químicaRESUMO
The primary objective of this study was to investigate the factors contributing to hyperglycemic adverse events (AEs) associated with the administration of remdesivir in hospitalized patients diagnosed with coronavirus disease 2019 (COVID-19). Furthermore, the study aimed to develop a risk score model employing various machine learning approaches. A total of 1262 patients were enrolled in this investigation. The relationship between covariates and hyperglycemic AEs was assessed through logistic regression analysis. Diverse machine learning algorithms were employed for the purpose of forecasting hyperglycemia-related complications. After adjusting for covariates, individuals with a body mass index ≥23 kg/m2 , those using proton pump inhibitors, cholinergic medications, or individuals with cardiovascular diseases exhibited approximately 2.41-, 2.73-, 2.65-, and 1.97-fold higher risks of experiencing hyperglycemic AEs (95% CI 1.271-4.577, 1.223-6.081, 1.168-5.989, and 1.119-3.472, respectively). Multivariate logistic regression, elastic net, and random forest models displayed area under the receiver operating characteristic curve values of 0.65, 0.66, and 0.60, respectively (95% CI 0.572-0.719, 0.640-0.671, and 0.583-0.611, respectively). This study comprehensively explored factors associated with hyperglycemic complications arising from remdesivir administration and, concurrently, leveraged a range of machine learning methodologies to construct a risk scoring model, thereby facilitating the tailoring of individualized remdesivir treatment regimens for patients with COVID-19.
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Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , COVID-19 , Hiperglicemia , Humanos , Tratamento Farmacológico da COVID-19 , Fatores de RiscoRESUMO
It is of great significance to develop efficient methods for preparing high-content modified nanoscale lead azide (LA) composites used in microinitiating devices. In this work, a structurally controllable salicylate-intercalated lead hydroxide with a nanoscale mesoporous structure is designed. Using it as a precursor, carbon-based lead azide (LA/C) and salicylate-based lead azide (LA/SA) are fabricated by the gas-solid azidation of the framework (GAF) method within 3 h, greatly reducing the preparation time of nano-LA composites. The characterizations of the composites demonstrate that the Pb in the precursors is transformed into nanoscale LA attached to the salicylate radical or its carbonized skeleton. Due to the unique embedded nanostructures and excellent electrical and thermal conductivity of salicylate-derived carbon materials, LA/C exhibits excellent electrostatic safety (E50 = 0.25 J) and flame sensitivity (H50 = 28 cm). The adjustable organic-inorganic ratio of intercalated hydroxides allows the LA content in LA/C to reach as high as 92.5%, enabling 6.50 mg of LA/C to successfully detonate secondary explosive CL-20 in a microinitiating device, demonstrating an amazing detonation ability superior to other reported LA complexes. The research provides a new perspective for the development of nanoscale LA composites with high LA content and appropriate sensitivity.
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PURPOSE: To date, risk factors affecting abnormal glycemic control have not been investigated. This study aimed to analyze risk factors for hypoglycemia or hyperglycemia in diabetic cancer patients receiving nutritional support by using machine learning methods. METHODS: This retrospective two-center study was performed using medical records. Odds ratios and adjusted odds ratios were estimated from univariate and multivariate analyses, respectively. Machine learning algorithms, including five-fold cross-validated multivariate logistic regression, elastic net, and random forest, were developed to predict risk factors for hypoglycemia and hyperglycemia. RESULTS: Data from 127 patients were analyzed. The use of sulfonylurea (SU) and blood urea nitrogen (BUN) level > 20 mg/dL increased hypoglycemia by 6.3-fold (95% CI 1.30-30.47) and 5.0-fold (95% CI 1.06-23.46), respectively. In contrast, patients who received an actual energy intake/total energy expenditure (TEE) ≥ 120% and used dipeptidyl peptidase-4 (DPP-4) inhibitors had a higher risk of hyperglycemia by 19.3- (95% CI 1.46-254.78) and 3.3-fold (95% CI 1.23-8.61), respectively. An initial blood glucose level ≥ 182.5 mg/dL also increased the risk of hyperglycemia by 15.3-fold. AUROC values for all machine learning methods indicated acceptable and excellent performance for hypoglycemia and hyperglycemia. CONCLUSION: The use of SU and BUN level > 20 mg/dL increased the risk of hypoglycemia, whereas an initial blood glucose level ≥ 182.5 mg/dL, a supplied actual energy intake/ TEE ≥ 120%, and the use of DPP-4 inhibitors increased the risk of hyperglycemia.
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Diabetes Mellitus , Inibidores da Dipeptidil Peptidase IV , Hiperglicemia , Hipoglicemia , Neoplasias , Humanos , Glicemia/análise , Estudos de Casos e Controles , Estudos Retrospectivos , Controle Glicêmico , Diabetes Mellitus/induzido quimicamente , Hipoglicemia/induzido quimicamente , Hiperglicemia/induzido quimicamente , Fatores de Risco , Aprendizado de Máquina , Hipoglicemiantes/efeitos adversosRESUMO
Since SLCO1B1 encodes the uptake transporter OATP1B1, which can influence the pharmacokinetic and pharmacodynamic profiles of edoxaban, polymorphisms in SLCO1B1 may affect the edoxaban response. This study aimed to investigate the association between SLCO1B1 gene polymorphisms and the bleeding risk in patients receiving edoxaban. We genotyped 10 single-nucleotide polymorphisms (SNPs) from the SLCO1B1 gene in patients receiving edoxaban. We also analyzed rs3842 of ABCB1 as a confounder. The odds ratio (OR) and adjusted OR (AOR) were calculated from univariate and multivariable analysis, respectively. The area under the receiver operating characteristic curve (AUROC) was constructed for the discrimination of the model. A total of 159 patients receiving edoxaban were analyzed. Overdose and rs4149056 showed significant association with bleeding complications by around 11- and 5.5-fold, respectively. Additionally, patients with the rs4149057 variant allele (C) had a 3.9-fold increased bleeding risk compared with wild-type homozygote carriers (TT), whereas rs2306283 variant homozygote (GG) carriers had a 0.27-fold reduced bleeding risk compared with wild-type allele (A) carriers. Patients with the variant-type homozygote (CC) of ABCB1 rs3842 had a higher bleeding risk than T allele carriers (AOR = 5.3 and 5.9). The final models for multivariable analyses were acceptable based on the AUROC values (> 0.70). These findings may help predict bleeding risk in patients taking edoxaban and help personalize treatment.
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Piridinas , Tiazóis , Humanos , Alelos , Piridinas/efeitos adversos , Tiazóis/efeitos adversos , Polimorfismo de Nucleotídeo Único , Transportador 1 de Ânion Orgânico Específico do Fígado/genéticaRESUMO
BACKGRUOUND: Fatty liver is associated with increased risk of developing type 2 diabetes. We aimed to evaluate whether the severity of hepatic steatosis is associated with incident diabetes. METHODS: We conducted a longitudinal analysis using data from 1,798 participants who underwent a comprehensive health checkup and abdominal computed tomography (CT). We assessed the association between baseline liver attenuation value on non-contrast CT images and risk of incident diabetes. All the participants were categorized into three groups based on the baseline liver attenuation value on non-contrast CT images: without hepatic steatosis (>57 Hounsfield unit [HU]), mild hepatic steatosis (41-57 HU), and moderate to severe hepatic steatosis (≤40 HU). RESULTS: During a median follow-up period of 5 years, 6.0% of the study participants progressed to diabetes. The incidence of diabetes was 17.3% in the moderate to severe hepatic steatosis group, 9.0% in the mild steatosis group, and 2.9% in those without hepatic steatosis. In a multivariate adjustment model, as compared with participants without hepatic steatosis, those with moderate to severe steatosis had a hazard ratio (HR) of 3.24 (95% confidence interval [CI], 1.64 to 4.2) for the development of diabetes, and those in the mild steatosis group had a HR of 2.33 (95% CI, 1.42 to 3.80). One standard deviation decrease in mean CT attenuation values of the liver was associated with a 40% increase in the development of diabetes (multivariate adjusted HR, 1.40; 95% CI, 1.2 to 1.63). CONCLUSION: We found a positive association between severity of hepatic steatosis and risk of incident diabetes. Greater severity of steatosis was associated with a higher risk of incident diabetes.
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Diabetes Mellitus Tipo 2 , Fígado Gorduroso , Humanos , Estudos Retrospectivos , Estudos Longitudinais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Fígado Gorduroso/complicações , Fígado Gorduroso/diagnóstico por imagem , Fígado Gorduroso/epidemiologiaRESUMO
In this study, we characterized the bioactive properties of three important brown seaweed species, Sargassum thunbergii, Undaria pinnatifida, and Saccharina japonica, by subcritical water extraction (SWE), as these species are well known for their beneficial health effects. Their physiochemical properties, including potential antioxidant, antihypertensive, and α-glucosidase inhibitory activity, and the antibacterial activity of the hydroysates were also analyzed. The highest total phlorotannin, total sugar content, and reducing sugar content in the S. thunbergii hydrolysates were 38.82 ± 0.17 mg PGE/g, 116.66 ± 0.19 mg glucose/g dry sample, and 53.27 ± 1.57 mg glucose/g dry sample, respectively. The highest ABTS+ and DPPH antioxidant activities were obtained in the S. japonica hydrolysates (124.77 ± 2.47 and 46.35 ± 0.01 mg Trolox equivalent/g, respectively) and the highest FRAP activity was obtained in the S. thunbergii hydrolysates (34.47 ± 0.49 mg Trolox equivalent/g seaweed). In addition, the seaweed extracts showed antihypertensive (≤59.77 ± 0.14%) and α-glucosidase inhibitory activity (≤68.05 ± 1.15%), as well as activity against foodborne pathogens. The present findings provide evidence of the biological activity of brown seaweed extracts for potential application in the food, pharmaceutical, and cosmetic sectors.
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Alga Marinha , Água , Água/química , alfa-Glucosidases , Antioxidantes/química , Anti-Hipertensivos/análise , Alga Marinha/química , Glucose , Extratos Vegetais/farmacologiaRESUMO
Pharmacogenomics, which is defined as the study of changes in the properties of DNA and RNA associated with drug response, enables the prediction of the efficacy and adverse effects of drugs based on patients' specific genetic mutations. For the safe and effective use of drugs, it is important that pharmacogenomic information is easily accessible to clinical experts and patients. Therefore, we examined the pharmacogenomic information provided on drug labels in Korea, Europe, Japan, and the United States (US). The selection of drugs that include pharmacogenomic information was based on the drug list that includes genetic information from the Korea Ministry of Food and Drug Safety (MFDS) and US Food and Drug Administration (FDA) websites. Drug labels were retrieved from the sites of MFDS, FDA, European Medicines Agency, and Japanese Pharmaceuticals and Medical Devices Agency. Drugs were classified as per the Anatomical Therapeutic Chemical code, and the biomarkers, labeling sections, and necessity of genetic tests were determined. In total, 348 drugs were selected from 380 drugs with available pharmacogenomic information in Korea and the US after applying the inclusion and exclusion criteria. Of these drugs, 137, 324, 169, and 126 were with pharmacogenomics information in Korea, the US, Europe, and Japan, respectively. The most commonly represented drug class was antineoplastic and immunomodulating agents. Regarding the classification as per the mentioned biomarkers, the cytochrome P450 enzyme was the most frequently mentioned information, and the targeted anticancer drugs most commonly required genetic biomarker testing. The reasons for differences in drug labeling information based on country include differences in mutant alleles according to ethnicity, frequencies at which drug lists are updated, and pharmacogenomics-related guidelines. Clinical experts must continuously strive to identify and report mutations that can explain drug efficacy or side effects for safe drug use.
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Gelatin/carrageenan (Ge/Car) active packaging films incorporated with turmeric essential oil (TEO) encapsulated in zein nanoparticles (ZNP) were developed. The efficacy of these active packaging films and their antimicrobial properties were also investigated to ensure their practical application. Three different types of nanocomposite films (Ge/Car, Ge/Car/TEO, and Ge/Car/ZNP) were prepared. The characterization of the films was elucidated using Fourier transform infrared (FTIR), X-ray diffraction analyses (XRD), and scanning electron microscope (SEM). Physicochemical and mechanical properties of the films were enhanced, owing to the application of TEO-containing nanocomposites. Supercritical-CO2 extracted TEO showed excellent biological activities, alongside GC-MS analysis identified that TEO contained 33 bioactive compounds where the major constituent was Zingiberene. ZNP proved an excellent carrier of TEO. The nanocomposite film sustainably released TEO, improving the shelf life of the chicken meat by reducing bacterial colonies from 3.08 log CFU/g to 2.81 log CFU/g after 14 days incubation against Salmonella enterica compared with 6.66 log CFU/g observed in the control film. The overall results of this study suggest that the nanocomposite active film is an excellent candidate for food packaging to ensure a better world.
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Nanocompostos , Óleos Voláteis , Zeína , Animais , Carragenina , Galinhas , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Gelatina/química , Curcuma , Embalagem de Alimentos/métodos , Nanocompostos/química , CarneRESUMO
AIMS: This study evaluated the efficacy and safety of enavogliflozin, a novel sodium-glucose cotransporter 2 inhibitor, versus dapagliflozin in Korean patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin and gemigliptin. METHODS: In this multicenter, double-blind, randomized study, patients with inadequate response to metformin (≥ 1000 mg/day) plus gemigliptin (50 mg/day) were randomized to receive enavogliflozin 0.3 mg/day (n = 134) or dapagliflozin 10 mg/day (n = 136) in addition to the metformin plus gemigliptin therapy. The primary endpoint was change in HbA1c from baseline to week 24. RESULTS: Both treatments significantly reduced HbA1c at week 24 (-0.92% in enavogliflozin group, -0.86% in dapagliflozin group). The enavogliflozin and dapagliflozin groups did not differ in terms of changes in HbA1c (between-group difference: -0.06%, 95% confidence interval [CI]: -0.19, 0.06) and fasting plasma glucose (between-group difference: -3.49 mg/dl [-8.08;1.10]). An increase in urine glucose-creatinine ratio was significantly greater in the enavogliflozin group than in the dapagliflozin group (60.2 g/g versus 43.5 g/g, P < 0.0001). The incidence of treatment-emergent adverse events was similar between the groups (21.64% versus 23.53%). CONCLUSIONS: Enavogliflozin, added to metformin plus gemigliptin, was well tolerated and as effective as dapagliflozin in the treatment of patients with T2DM.
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Diabetes Mellitus Tipo 2 , Metformina , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Metformina/efeitos adversos , Diabetes Mellitus Tipo 2/epidemiologia , Hipoglicemiantes/efeitos adversos , Hemoglobinas Glicadas , Glicemia , Resultado do Tratamento , Compostos Benzidrílicos/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Quimioterapia Combinada , Método Duplo-CegoRESUMO
Background and Objectives: Opioid use in Korea is lower than in other developed countries. However, recent studies have reported an increase in opioid prescriptions and the number of chronic opioid users. The current status of adverse events (AEs) associated with opioid analgesics in Korea is unclear. This nested case-control study aimed to evaluate the influence of opioid analgesic use patterns on all emergency department (ED) visits and opioid-related ED visits after opioid analgesic initiation using the national claims database. Materials and Methods: Adult non-cancer patients who initiated non-injectable opioid analgesics (NIOA) between January 2017 and June 2018 were included. We defined the case group as patients who visited the ED within six months of opioid initiation, and the control group was selected in a 1:1 ratio using an exact matching method. Results: A total of 97,735 patients (13.58%) visited the ED within six months of NIOA initiation. Nearly 32% of cases were linked to opioid-related AEs. The most frequent AEs were falls and fractures (61.27%). After adjusting for covariates, opioid initiation at the ED was associated with all-cause or opioid-related ED visits (adjusted odds ratio (aOR) = 3.19, 95% confidence interval (CI) = 3.09-3.29; aOR = 3.82, 95% CI = 3.62-4.04, respectively). Chronic NIOA use was associated with all-cause and opioid-related ED visits (aOR = 1.32, 95% CI = 1.23-1.40; aOR = 1.56, 95% CI = 1.39-1.76, respectively). Conclusion: This study found that 13% of non-cancer patients visited the ED within six months of NIOA initiation. In addition, the NIOA use pattern was significantly associated with all-cause and opioid-related ED visits.
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Analgésicos não Narcóticos , Analgésicos Opioides , Adulto , Humanos , Analgésicos Opioides/efeitos adversos , Estudos de Casos e Controles , Fatores de Risco , Serviço Hospitalar de Emergência , República da Coreia/epidemiologiaRESUMO
Background and Objectives: Even though low-molecular-weight heparin (LMWH), including dalteparin, has a critical role in portal vein thrombosis (PVT) treatment in liver cirrhosis (LC) patients, the predictive factors and the proper dose of dalteparin for PVT treatment and relapse have not yet been investigated. Materials and Methods: This retrospective study evaluated the records of LC patients receiving dalteparin from July 2013 to June 2019. The odds ratio (OR) and adjusted OR were calculated from univariate and multivariable analyses, respectively. Results: Among data from 121 patients, the overall recanalization rate of all patients was 66.1% (80 patients). No history of variceal bleeding (OR 4.6, 95% CI: 1.88-11.43) and the case of newly developed thrombus before dalteparin treatment (OR 3.2, 95% CI: 1.24-8.08) were predictive factors associated with increased treatment response. Relapse of PVT occurred in 32 out of 80 patients (40%) who showed a recanalization. The risk of relapse was 3.1-3.9 times higher in those who took more than three months or more than six months from the diagnosis of PVT to dalteparin treatment compared to those who took less than these durations, respectively. In the dosing regimen, patients with the kg-based dosing regimen showed 2.6 times better response than those with the fixed dosing regimen. However, no difference in bleeding complications was observed. Conclusion: In the dosing regimen, the kg-based regimen that was the same as the venous thromboembolism regimen was a better option for the efficacy and safety of dalteparin therapy. Additionally, when treating PVT in LC patients, careful monitoring is recommended for patients with predictive factors for treatment response and relapse of PVT.
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Trombose , Trombose Venosa , Humanos , Heparina de Baixo Peso Molecular/uso terapêutico , Anticoagulantes/uso terapêutico , Veia Porta , Dalteparina/uso terapêutico , Estudos Retrospectivos , Cirrose Hepática/complicações , Trombose Venosa/complicações , Trombose/patologia , RecidivaRESUMO
The consumption of fresh produce has led to increase in antibiotic-resistant (AR) Salmonella outbreaks. In this study, indigenous Salmonella was isolated from a total of two hundred-two samples including fresh produce and agricultural environmental samples in Korea. After biochemical confirmation using the Indole, Methyl Red, Voges-Proskauer, Citrate tests, presumable Salmonella isolates were identified by 16S rRNA sequencing. Identified Salmonella isolates were evaluated for antibiotic susceptibility against twenty-two antibiotics. The specificity and the efficiency of plating (EOP) of vB_SalS_KFSSM were evaluated against fifty-three bacterial strains. Twenty-five suspected Salmonella were isolated and confirmed by the positive result for methyl red and citrate, of which ten were identified as Salmonella spp. through 16S rRNA gene sequencing. Eight Salmonella isolates (4.0%, n = 8/202) were resistant to at least one antibiotic, among which five were multi-drug resistant. As a lytic phage against Salmonella spp. CMGS-1, vB_SalS_KFSSM was isolated from cow manure. The phage was observed as a tailed phage belonging to the class Caudoviricetes. It exhibited an intra-broad specificity against four indigenous AR Salmonella isolates, two indigenous Salmonella isolates, and five other Salmonella serotypes with great efficiencies (EOP ≥ 0.75). Thus, this study suggested the potential of vB_SalS_KFSSM to combat indigenous AR Salmonella.
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Antibacterianos , Bacteriófagos , Antibacterianos/farmacologia , Sais , Prevalência , RNA Ribossômico 16S/genética , Salmonella , Cloreto de Sódio , CitratosRESUMO
INTRODUCTION: Although various treatments exist for depression in patients with spinal cord injury (SCI), the comparative effects and relationships between these treatments have not been clearly presented. This study aims to present comprehensive evidence for the treatment of major depressive disorder or dysthymic disorder in patients with SCI by comparing the therapeutic and adverse effects of pharmacological and non-pharmacological treatments through a systematic review and network meta-analysis. METHODS AND ANALYSIS: We will search for studies in five databases (Medline, Central, Embase, PsycINFO and CHINAL) as well as clinical trial registries (US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (www. CLINICALTRIALS: gov), WHO International Clinical Trials Registry Platform (www.who.int/trialsearch)) and grey literature (Google Scholar). The references of the included studies, previous systematic reviews and meta-analyses will be reviewed. Study selection, data extraction and quality and risk of bias assessments will be independently performed by two authors (JMH and WSC), and disagreements will be resolved by discussion with JHK. Moreover, a Bayesian network meta-analysis will be performed using R software. ETHICS AND DISSEMINATION: Our systematic review and network meta-analysis will be performed based on existing studies; thus, we did not seek ethical approval. Our results will be published in a peer-reviewed journal and presented at both domestic and international conferences.
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Transtorno Depressivo Maior , Traumatismos da Medula Espinal , Humanos , Transtorno Depressivo Maior/terapia , Metanálise em Rede , Transtorno Distímico , Teorema de Bayes , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/terapia , Revisões Sistemáticas como Assunto , Metanálise como AssuntoRESUMO
AIMS: This systematic literature review and meta-analysis aimed to evaluate the risk factors for vancomycin-associated acute kidney injury (AKI) incidence. METHODS: This study assessed risk factors for vancomycin-associated AKI in adult patients by searching studies from PubMed, the Cochrane Library and Embase. Random effect models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Fifty-three studies were included in our meta-analysis. For patient factors, black race (OR 1.47, 95% CI: 1.16-1.87), Caucasian (OR 0.72, 95% CI: 0.58-0.90) and obesity (OR 1.46, 95% CI: 1.12-1.90) were associated with an increase in vancomycin-associated AKIs. In terms of vancomycin-related factors, longer treatment duration (>14 d; OR 1.73, 95% CI: 1.06-2.83), serum vancomycin trough level >15 µg/mL (OR 2.10, 95% CI: 1.43-3.07) and vancomycin trough level >20 µg/mL (OR 2.84, 95% CI: 1.48-5.44) increased the risks of vancomycin-associated AKI. For comorbidities and clinical factors, renal disease (OR 2.19, 95% CI: 1.51-3.17) showed the highest odds of vancomycin-associated AKI, followed by hepatic disease, intensive care unit admission, heart failure, sepsis, coronary heart disease and diabetes mellitus. For concomitant nephrotoxic drugs, amphotericin B (OR 5.21, 95% CI: 3.44-7.87) showed the highest odds of vancomycin-associated AKI, followed by acyclovir (OR 3.22, 95% CI: 1.39-7.46), vasopressors, loop diuretics, piperacillin-tazobactam and aminoglycoside. The use of any concomitant nephrotoxic agent (OR 1.74, 95% CI: 1.17-2.58) increased the odds of vancomycin-associated AKI. CONCLUSION: Our results may help predict the risk of vancomycin-associated AKI in the clinical setting.
Assuntos
Injúria Renal Aguda , Vancomicina , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Adulto , Antibacterianos/efeitos adversos , Quimioterapia Combinada , Humanos , Estudos Retrospectivos , Fatores de Risco , Vancomicina/efeitos adversosRESUMO
Copper azide (CA) is one of the preferred primary explosives in the micro-initiating device, and it is of conducive significance to develop high-content CA-modified materials. In this work, we reported two types of CA composites with CA nanorods embedded in carbon nanosheets (CA/C) and CA distributed on salicylic acid (CA/SA) using layered copper hydroxide nanosheets intercalated with salicylic acid as the precursor. The detailed characterizations demonstrated that CA/C exhibits eximious electrostatic sensitivity (1.06 mJ) due to the inherent structural characteristics of CA/C such as the limitation of the free movement of CA by the layered structure and preeminent electrical conductivity of carbon nanosheets. Surprisingly, CA/C with nearly 1.0 mg in the miro-initiating device can reliably detonate Hexanitrohexaazaisowurtzitane (CL-20). CA/C exhibits extremely high CA content (93%), excellent ignition ability, and detonation ability, and its performance is superior to pure CA and most CA-modified materials reported previously. CA/SA also has an excellent detonation ability and its electrostatic sensitivity is as low as 0.92 mJ. These findings provide a new perspective for the development of high-performance primary explosives for the micro-initiating device.
RESUMO
Thyroid dysfunction has been reported to be an extrapulmonary symptom of COVID-19. It is important to identify the tissue subset that expresses angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2), which are essential for host infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in order to understand the viral pathogenesis of COVID-19-related thyroid dysfunction. We investigated the expression and distribution of ACE2- and TMPRSS2-expressing cells in the thyroid gland. RT-PCR and Western blotting were performed on human thyroid follicular cells (Nthy-ori3-1) and rat thyroid tissues to detect the expression levels of ACE and TMPRSS2 mRNA and proteins. We also analyzed the expression patterns of ACE2 and TMPRSS2 in 9 Sprague-Dawley rats and 15 human thyroid tissues, including 5 normal, 5 with Hashimoto's thyroiditis, and 5 with Graves' disease, by immunohistochemistry (IHC) and immunofluorescence. Both ACE2 and TMPRSS2 mRNAs and proteins were detected in the thyroid tissue. However, ACE2 and TMPRSS2 proteins were not expressed in thyroid follicular cells. In IHC, ACE2 and TMPRSS2 were not stained in the follicular cells. No cells co-expressed ACE2 and TMPRSS2. ACE2 was expressed in pericytes between follicles, and TMPRSS2 was mainly stained in the colloid inside the follicle. There was no difference in expression between the normal thyroid, Hashimoto's thyroiditis, and Graves' disease. SARS-CoV-2 does not directly invade the thyroid follicular cells. Whether SARS-CoV-2 infection of pericytes can affect COVID-19-related thyroid dysfunction warrants further study.