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The presence of trace water impurities in organic solvents can significantly influence chemical reactions and product quality; thus, the accurate detection of water content in these solvents is a critical requirement for industrial applications. Accordingly, an eco-friendly, effective, and economical sensor for detecting trace quantities of miscible water in organic solvents is required for industrial applications. In this study, we synthesized biomass-derived multi-atom-doped carbon dots (MACDs) as fluorescent probes and employed them for the detection of trace amounts of water impurities in several water-miscible organic solvents. The MACDs exhibited stable dual-color fluorescence emission under ultraviolet light irradiation and red and blue emissions in organic solvents and water. The fluorescence quantum yield was approximately 11 %, which indicates an excited intraparticle proton transfer response due to an increase in the water content within a wide response range from 0 % to 100 % (v/v) in organic solvents. The intensity of the red emission signal at 670 nm gradually decreased with an increase in the water content in the organic solvent. The MACDs could detect water with an instant response time of 55 s, a high sensitivity, and low limits of detection of 0.08 %, 1.36 %, 0.03 %, 0.04 %, 0.12 %, and 0.05 % (v/v) in ethanol, acetonitrile, dimethylformamide, methanol, isopropanol, and tetrahydrofuran, respectively. Hence, biomass-derived MACDs can serve as efficient and eco-friendly water sensors in organic solvents.
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Hydroxyapatite (HA) exhibits outstanding biocompatibility, bioactivity, osteoconductivity, and natural anti-inflammatory properties. Pure HA, ion-doped HA, and HA-polymer composites are investigated, but critical limitations such as brittleness remain; numerous efforts are being made to address them. Herein, the novel self-crystallization of a polymeric single-stranded deoxyribonucleic acid (ssDNA) without additional phosphate ions for synthesizing deoxyribonucleic apatite (DNApatite) is presented. The synthesized DNApatite, DNA1Ca2.2(PO4)1.3OH2.1, has a repetitive dual phase of inorganic HA crystals and amorphous organic ssDNA at the sub-nm scale, forming nanorods. Its mechanical properties, including toughness and elasticity, are significantly enhanced compared with those of HA nanorod, with a Young's modulus similar to that of natural bone.
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BACKGROUND: Exacerbation frequency strongly influences treatment choices in patients with severe asthma. RESEARCH QUESTION: What is the extent of the variability of exacerbation rate across countries and its implications in disease management? STUDY DESIGN AND METHODS: We retrieved data from the International Severe Asthma Registry, an international observational cohort of patients with a clinical diagnosis of severe asthma. We identified patients aged ≥ 18 years who did not initiate any biologics prior to baseline visit. A severe exacerbation was defined as the use of oral corticosteroids for ≥ 3 days or asthma-related hospitalization/ED visit. A series of negative binomial models were applied to estimate country-specific severe exacerbation rates during 365 days of follow-up, starting from a naive model with country as the only variable to an adjusted model with country as a random-effect term and patient and disease characteristics as independent variables. RESULTS: The final sample included 7,510 patients from 17 countries (56% from the United States), contributing to 1,939 severe exacerbations (0.27/person-year). There was large between-country variation in observed severe exacerbation rate (minimum, 0.04 [Argentina]; maximum, 0.88 [Saudi Arabia]; interquartile range, 0.13-0.54), which remained substantial after adjusting for patient characteristics and sampling variability (interquartile range, 0.16-0.39). INTERPRETATION: Individuals with similar patient characteristics but coming from different jurisdictions have varied severe exacerbation risks, even after controlling for patient and disease characteristics. This suggests unknown patient factors or system-level variations at play. Disease management guidelines should recognize such between-country variability. Risk prediction models that are calibrated for each jurisdiction will be needed to optimize treatment strategies.
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Asma , Progressão da Doença , Sistema de Registros , Índice de Gravidade de Doença , Humanos , Asma/tratamento farmacológico , Asma/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Hospitalização/estatística & dados numéricos , Corticosteroides/uso terapêuticoRESUMO
BACKGROUND: The management of mild asthma has lacked an over-the-counter (OTC) option aside from inhaled epinephrine, which is available in the United States. However, inhaled epinephrine use without an inhaled corticosteroid may increase the risk of asthma death. OBJECTIVE: To compare the cost-effectiveness of OTC as-needed budesonide-formoterol as a plausible alternative to inhaled epinephrine. METHODS: We developed a probabilistic Markov model to compare OTC as-needed budesonide-formoterol inhaler use vs inhaled epinephrine use in adults with mild asthma from a US societal perspective over a lifetime horizon, with a 3% annual discount rate (2022 US dollars). Inputs were derived from the SYmbicort Given as-needed in Mild Asthma (SYGMA) trials, published literature, and commercial costs. Outcomes were quality-adjusted life-years (QALY), costs, incremental net monetary benefit (INMB), severe asthma exacerbations, well-controlled asthma days, and asthma-related deaths. Microsimulation was used to evaluate underinsured Americans living with mild asthma (n = 5,250,000). RESULTS: Inhaled epinephrine was dominated (with lower QALYs gains at a higher cost) by both as-needed budesonide-formoterol (INMB, $15,541 at a willingness-to-pay of $100,000 per QALY) and the no-OTC inhaler option (INMB, $1023). Adults using as-needed budesonide-formoterol had 145 more well-controlled asthma days, 2.79 fewer severe exacerbations, and an absolute risk reduction of 0.23% for asthma-related death compared with inhaled epinephrine over a patient lifetime. As-needed budesonide-formoterol remained dominant in all sensitivity and scenario analyses, with a 100% probability of being cost-effective compared with inhaled epinephrine in probabilistic sensitivity analysis. CONCLUSION: If made available, OTC as-needed budesonide-formoterol for treating mild asthma in underinsured adults without HCP management improves asthma outcomes, prevents fatalities, and is cost-saving.
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Asma , Combinação Budesonida e Fumarato de Formoterol , Adulto , Humanos , Combinação Budesonida e Fumarato de Formoterol/uso terapêutico , Broncodilatadores/uso terapêutico , Budesonida/uso terapêutico , Análise Custo-Benefício , Fumarato de Formoterol/uso terapêutico , Etanolaminas/uso terapêutico , Asma/tratamento farmacológico , Epinefrina/uso terapêutico , Combinação de Medicamentos , Administração por InalaçãoRESUMO
BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of cardiovascular disease (CVD). The extent to which the excess CVD risk is captured by risk factors in QRISK, a widely used CVD risk scoring tool, is not well studied. METHODS: We created an incidence cohort of diagnosed COPD patients from the United Kingdom (UK) Clinical Practice Research Datalink GOLD database (January 1998-July 2018). The outcome was a composite of fatal or non-fatal CVD events. Sex-specific age-standardised incidence ratios (SIR) were compared with values for the UK primary-care population. The observed 10-year CVD risk was derived using the Kaplan-Meier estimator and was compared with predicted 10-year risk from the QRISK3 tool. RESULTS: 13 208 patients (mean age 64.9 years, 45% women) were included. CVD incidence was 3.53 events per 100 person-years. The SIR of CVD was 1.71 (95% CI 1.61 to 1.75) in women and 1.62 (95%CI 1.54-1.64) in men. SIR was particularly high among patients younger than 65 years (women=2.13 (95% CI 1.94 to 2.19); men=1.86 (95% CI 1.74 to 1.90)). On average, the observed 10-year risk was 52% higher than QRISK predicted score (33.5% vs 22.1%). The difference was higher in patients younger than 65 years (observed risk 82% higher than predicted). CONCLUSION: People living with COPD are at a significantly heightened risk of CVD over and beyond their predicted risk. This is particularly the case for younger people whose 10-year CVD risk can be >80% higher than predicted. Risk scoring tools must be validated and revised to provide accurate CVD predictions in patients with COPD.
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Background and Objectives: Acute cholangitis may be fatal, particularly in elderly patients. According to the Tokyo Guidelines 2018, those aged ≥75 years are classified as moderate (Grade II) severity. However, it has not been established whether age itself is the deciding factor of poor outcomes. We studied the impact of old age (≥75 years) on the mortality and morbidity of acute cholangitis due to choledocholithiasis. Materials and Methods: We retrospectively examined 260 patients with calculous acute cholangitis who had undergone biliary drainage. Patients were divided into two groups: elderly (≥75 years) and non-elderly (<75 years). We aimed to compare organ dysfunction, in-hospital mortality, intensive care unit (ICU) hospitalization, and the severity of acute cholangitis. Results: Of 260 patients, 134 (51.5%) were in the elderly group and 126 (48.5%) were in the non-elderly group. The mean age was 72.3 ± 14.4 years, and 152 (58.5%) were men. The elderly patients showed a higher incidence of shock (12.7% vs. 4.8%, p = 0.029), respiratory dysfunction (7.5% vs. 0%, p = 0.002), and renal dysfunction (8.2% vs. 0.8%, p = 0.006) than the non-elderly patients. The overall in-hospital mortality rate was 2.7%, with no significant differences between the elderly and the non-elderly (4.5% vs. 0.8%, p = 0.121). The incidence of severe acute cholangitis was significantly higher in the elderly group (26.9% vs. 9.5%, p < 0.001). However, there was no significant difference in the rates of ICU hospitalization (9.7% vs. 4%, p = 0.088) and lengths of hospital stay (LOS) (8.3 d vs. 7.1 d, p = 0.086). Conclusions: No difference was observed in the in-hospital mortality, ICU hospitalization, or LOS between the elderly (≥75 years) and the non-elderly (<75 years) with calculous acute cholangitis. However, severe acute cholangitis was significantly more frequent in elderly patients.
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Colangite , Coledocolitíase , Idoso , Masculino , Humanos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Feminino , Coledocolitíase/complicações , Estudos Retrospectivos , Colangiopancreatografia Retrógrada Endoscópica , Doença Aguda , Colangite/complicaçõesRESUMO
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an ambulatory care-sensitive condition, and the rate of hospital admissions for COPD is an indicator of the quality of outpatient care. We sought to determine long-term trends in hospital admissions for COPD in Canada. METHODS: Using a comprehensive national database of hospital admissions in Canada, we identified those with a main discharge diagnosis of COPD for patients aged 40 years and older between 2002 and 2017. We calculated sex-specific, age-standardized trends in annual rates of hospital admissions for COPD separately for younger (40-64 yr) and older adults (≥ 65 yr). We used spline regression to examine changes in the admissions trends for each sex and age group. RESULTS: Over 16 years, 1 134 359 hospital admissions were for COPD. Between 2002 and 2017, the total number of admissions increased by 68.8%, from 52 937 to 89 384. The overall crude admission rate increased by 30.0%, from 368 to 479 per 100 000 population, and the sex-and age-standardized admission rate increased by 9.6%, from 437 to 479 per 100 000 population. Age-standardized rates increased by 12.2% among younger females, by 24.4% among younger males and by 29.8% among older females, but decreased by 9.0% among older males. Over the same period, the all-cause sex-and age-standardized admission rate declined by 23.0%. INTERPRETATION: Hospital admissions for COPD have increased since 2010, even after adjusting for population growth and aging, and despite declining rates of all-cause hospital admissions. The secular increase in COPD admissions indicates that the burden of COPD on Canadian health care systems is increasing.
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Hospitalização , Doença Pulmonar Obstrutiva Crônica , Feminino , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Canadá/epidemiologia , Alta do Paciente , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/terapia , HospitaisRESUMO
BACKGROUND: A previously developed risk prediction model needs to be validated before being used in a new population. The finite size of the validation sample entails that there is uncertainty around model performance. We apply value-of-information (VoI) methodology to quantify the consequence of uncertainty in terms of net benefit (NB). METHODS: We define the expected value of perfect information (EVPI) for model validation as the expected loss in NB due to not confidently knowing which of the alternative decisions confers the highest NB. We propose bootstrap-based and asymptotic methods for EVPI computations and conduct simulation studies to compare their performance. In a case study, we use the non-US subsets of a clinical trial as the development sample for predicting mortality after myocardial infarction and calculate the validation EVPI for the US subsample. RESULTS: The computation methods generated similar EVPI values in simulation studies. EVPI generally declined with larger samples. In the case study, at the prespecified threshold of 0.02, the best decision with current information would be to use the model, with an incremental NB of 0.0020 over treating all. At this threshold, the EVPI was 0.0005 (relative EVPI = 25%). When scaled to the annual number of heart attacks in the US, the expected NB loss due to uncertainty was equal to 400 true positives or 19,600 false positives, indicating the value of further model validation. CONCLUSION: VoI methods can be applied to the NB calculated during external validation of clinical prediction models. While uncertainty does not directly affect the clinical implications of NB findings, validation EVPI provides an objective perspective to the need for further validation and can be reported alongside NB in external validation studies. HIGHLIGHTS: External validation is a critical step when transporting a risk prediction model to a new setting, but the finite size of the validation sample creates uncertainty about the performance of the model.In decision theory, such uncertainty is associated with loss of net benefit because it can prevent one from identifying whether the use of the model is beneficial over alternative strategies.We define the expected value of perfect information for external validation as the expected loss in net benefit by not confidently knowing if the use of the model is net beneficial.The adoption of a model for a new population should be based on its expected net benefit; independently, value-of-information methods can be used to decide whether further validation studies are warranted.
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Incerteza , Humanos , Análise Custo-BenefícioRESUMO
Emerging pharmaceutical pollutants pose a threat to both human and environmental health. The removal and monitoring of such pollutants necessitate the use of practical on-site monitoring devices; however, the designs of such devices are underdeveloped. This study involves the fabrication of a low-cost sensor based on barium-incorporated copper oxide (Ba-CuO) for the on-site monitoring of the cytotoxic drug methotrexate (MTRX) in water and sediment samples. The tenorite structure of CuO was slightly enriched with Ba ions at the td sites, distorting the tetrahedron and enhancing its electrochemical properties. Ba-CuO was obtained from Cu(NO3)2 and Ba(OH)2 by a ligand exchange protocol and was characterized using X-ray diffraction, Raman spectroscopy, X-ray photoelectron spectroscopy, field-emission scanning electron microscopy, transmission electron microscopy, and energy dispersive X-ray analysis. In addition, the Ba-CuO sensor was tested under various conditions, and it could detect MTRX at concentrations as low as 0.4 nM, with a high sensitivity of 1.3567 µA µM-1 cm-2. On-site monitoring yielded recoveries of greater than 93 % from spiked samples, thus exhibiting excellent reproducibility and stability. Therefore, the developed method is practical and has no matrix effect on the MTRX sensor.
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Antineoplásicos , Metotrexato , Humanos , Cobre/química , Bário , Reprodutibilidade dos Testes , ÓxidosRESUMO
INTRODUCTION: Severe asthma is associated with a disproportionally high disease burden, including the risk of severe exacerbations. Accurate prediction of the risk of severe exacerbations may enable clinicians to tailor treatment plans to an individual patient. This study aims to develop and validate a novel risk prediction model for severe exacerbations in patients with severe asthma, and to examine the potential clinical utility of this tool. METHODS AND ANALYSIS: The target population is patients aged 18 years or older with severe asthma. Based on the data from the International Severe Asthma Registry (n=8925), a prediction model will be developed using a penalised, zero-inflated count model that predicts the rate or risk of exacerbation in the next 12 months. The risk prediction tool will be externally validated among patients with physician-assessed severe asthma in an international observational cohort, the NOVEL observational longiTudinal studY (n=1652). Validation will include examining model calibration (ie, the agreement between observed and predicted rates), model discrimination (ie, the extent to which the model can distinguish between high-risk and low-risk individuals) and the clinical utility at a range of risk thresholds. ETHICS AND DISSEMINATION: This study has obtained ethics approval from the Institutional Review Board of National University of Singapore (NUS-IRB-2021-877), the Anonymised Data Ethics and Protocol Transparency Committee (ADEPT1924) and the University of British Columbia (H22-01737). Results will be published in an international peer-reviewed journal. TRIAL REGISTRATION NUMBER: European Union electronic Register of Post-Authorisation Studies, EU PAS Register (EUPAS46088).
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Asma , Humanos , Estudos Longitudinais , Asma/epidemiologia , Asma/tratamento farmacológico , Efeitos Psicossociais da Doença , Estudos Multicêntricos como AssuntoRESUMO
Background and Objectives: Although laparoscopic cholecystectomy is the preferred treatment method in patients who experience typical biliary pain with or without gallstones, medical treatment has not been extensively studied. Rowachol is a potent choleretic agent, comprising six cyclic monoterpenes. This study aimed to investigate the clinical improvement and changes in gallbladder ejection fraction (GBEF) by Rowachol treatment in patients with typical biliary pain. Materials and Methods: We retrospectively reviewed 138 patients with typical biliary pain who underwent cholescintigraphy from July 2016 to April 2022. We included patients who received Rowachol for more than 2 months and underwent follow-up GBEF measurements. Finally, we analyzed pre- and post-treatment symptoms and GBEF. GBEF was calculated using the fatty meal-stimulated cholescintigraphy. Results: This retrospective observational study included 31 patients; their median age was 46.0 (range, 26.0-72.7) years, and 22 (71.0%) were female. Overall, 9 (29.0%) patients had gallbladder stones or sludges (maximum size: 2 mm) on initial transabdominal ultrasonography. During a median follow-up of 23.3 months, the symptoms of 21 (67.7%) patients were resolved after a median Rowachol treatment of 10.0 months. The mean GBEF was significantly improved after Rowachol treatment (initial cholescintigraphy: 42.6% ± 16.2%; follow-up cholescintigraphy: 53.0% ± 18.1%, p = 0.012). In patients with a GBEF ≤35% (n = 9), Rowachol significantly increased the GBEF from 21.3% ± 8.3% to 49.1% ± 20.7% (p = 0.008). Conclusions: Rowachol may have beneficial medical effects that can improve gallbladder dysfunction and treatment response.
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Doenças da Vesícula Biliar , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Volume Sistólico , Doenças da Vesícula Biliar/tratamento farmacológico , Doenças da Vesícula Biliar/cirurgia , Monoterpenos , DorRESUMO
Chloramphenicol (CAP) is a harmful antibiotic that inevitably enters our food chain through natural or manmade means. Its ineradicable residue pollutes soils and water, accumulates in plants and animal products, and eventually affects human health. An ultrasensitive method for detecting and monitoring CAP is therefore urgently required. Herein, we report an ultrafast extraction and amperometry detection method based on a graphite-sulfate-modified electrode for detecting CAP in soil, water, and food samples. The graphite sulfate is prepared by the oxidation method and its structural properties are comprehensively investigated. The developed sensor electrode showed a wider linear range of 0.3-32.0 µg kg-1 and an ultralow detection limit of 0.1 µg kg-1, both of which meet the European Commission Reg 1871/2019 reference points for action. The method works well with both meat and plant samples, achieving CAP recoveries ranging from 90.8 to 99.1% even at low concentrations. Moreover, the sensor electrode shows more than 95% selectivity toward CAP detection in the soil, water, and food matrices. The developed method exhibits good repeatability and reproducibility in the analysis of real samples.
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Antibacterianos , Grafite , Animais , Humanos , Antibacterianos/análise , Cloranfenicol/análise , Grafite/química , Água/análise , Reprodutibilidade dos Testes , Solo , Limite de DetecçãoRESUMO
PURPOSE: Delayed hemorrhage (DH) is a rare and yet well-known fatal complication associated with postoperative pancreatic fistula (POPF) in pancreatoduodenectomy (PD). The study aimed to investigate whether arterial reinforcement (AR) using polyglycolic acid sheets (PAS) followed by fibrin sealant (FS) to the hepatic artery could prevent DH in the setting of POPF after PD. METHODS: A total of 345 patients underwent PD for periampullary tumors from March 2011 to March 2022. From March 2011 to March 2018, 225 patients underwent PD, and AR was not performed (non-AR group). From April 2018 to March 2022, 120 patients underwent PD, and AR was performed (AR group). AR was achieved by wrapping the proper hepatic artery all the way down to the celiac artery with PAS followed by coating with FS. Demographic profile and various outcomes including DH of these two groups were compared and analyzed retrospectively. RESULTS: In non-AR group, 48 (21.3%) and 12 (5.3%) patients had grade B and C POPF, respectively. In AR group, 26 (21.7%) and four (3.3%) patients had grade B and C POPF, respectively. The incidence of POPF was not statistically significant (p = .702) between the groups. Among the patients with grade B or C POPF, DH occurred in 14 (23.3%) patients in non-AR group and only one patient in AR group (p = .016). Of the 15 patients with DH, four (26.7%) patients died. CONCLUSION: AR using PAS and FS is effective in preventing DH in the setting of POPF.
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Fístula Pancreática , Pancreaticoduodenectomia , Humanos , Fístula Pancreática/etiologia , Fístula Pancreática/prevenção & controle , Fístula Pancreática/cirurgia , Pancreaticoduodenectomia/efeitos adversos , Estudos Retrospectivos , Pâncreas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND/AIMS: Intrahepatic cholangiocarcinoma (iCCA) is a subgroup of cholangiocarcinoma and is the second- most-common primary hepatic tumor. Several predictive and prognostic factors have been analyzed; however, in this study we focused on the influence of age. Our aim was to use real-world results to determine the influence of age in iCCA patients. METHODS: A retrospective analysis of patients treated between 2005 and 2016 at Konkuk University Medical Center. In total, 133 patients with iCCA were identified. The mass-forming, periductal-infiltrating, and intraductal-growth types were included; patients with extrahepatic or hilar-type cholangiocarcinoma were excluded. We defined two groups: a younger group, age < 65 years, and an older group, age ≥ 65 years. Statistical analyses using univariate and multivariate Cox regression analyses, including the Kaplan-Meier method, were conducted. RESULTS: In total, 114 patients were enrolled. The two groups differed with regard to treatment options such as surgery with adjuvant chemotherapy or palliative chemotherapy (p = 0.012, p < 0.001). The younger group had significantly longer survival than the older group (p = 0.017). In the younger group, patients who received therapy had longer survival than those who did not (hazard ratio, 3.942; 95% confidence interval, 2.053 to 7.569; p < 0.001). Multivariate analysis indicated that younger age, lower bilirubin, low CA 19-9, and no lymph-node involvement were independent factors for improved survival. CONCLUSION: Younger patients and those who underwent surgery with adjuvant chemotherapy had longer survival. The younger the patient, the more treatments received, including palliative chemotherapy.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Tumor de Klatskin , Humanos , Idoso , Ductos Biliares Intra-Hepáticos/patologia , Ductos Biliares Intra-Hepáticos/cirurgia , Resultado do Tratamento , Estudos Retrospectivos , Colangiocarcinoma/terapia , Colangiocarcinoma/patologia , Prognóstico , Neoplasias dos Ductos Biliares/terapia , Neoplasias dos Ductos Biliares/patologia , Taxa de SobrevidaRESUMO
Purpose: In patients who have previously undergone subtotal gastrectomy (STG), the remnant stomach is supplied with arterial blood through the splenic artery. It is currently unclear whether the remnant stomach can be safely preserved when performing distal pancreatosplenectomy (DPS) in these patients. Thus, this study aimed to evaluate the safety and feasibility of performing DPS in patients who had undergone a previous STG. Methods: A multicenter cohort study was performed to identify patients who underwent DPS. Electronic medical data of Clinical Data Warehouse from 7 representative high-volume centers in 5 cities were retrospectively reviewed. A propensity score-matched analysis was performed to match patients who had no history of upper abdominal surgery with patients who had undergone a previous STG. Results: Fourteen DPS patients who had a history of STG (STG group) were studied and matched to 70 patients who underwent DPS without any history of upper abdominal surgery (non-STG group). All patients in the STG group had the remnant stomach preserved. In most patients, the blood vessel supplying blood to the remnant stomach was the left inferior phrenic artery. There was no significant difference in the incidence of stomach-related complications or length of hospital stay between the 2 groups. Conclusion: Our study results suggest that the remnant stomach could be safely preserved when performing DPS in patients with a prior STG. However, it is necessary to carefully evaluate the vascular structure of the remnant stomach through preoperative imaging study and closely observe changes to the blue stomach during the operation.
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Background: The Acute Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Prediction Tool (ACCEPT) was developed for individualised prediction of COPD exacerbations. ACCEPT was well calibrated overall and had a high discriminatory power, but overestimated risk among individuals without recent exacerbations. The objectives of this study were to 1) fine-tune ACCEPT to make better predictions for individuals with a negative exacerbation history, 2) develop more parsimonious models, and 3) externally validate the models in a new dataset. Methods: We recalibrated ACCEPT using data from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE, a three-year observational study, 1,803 patients, 2,117 exacerbations) study by applying non-parametric regression splines to the predicted rates. We developed three reduced versions of ACCEPT by removing symptom score and/or baseline medications as predictors. We examined the discrimination, calibration, and net benefit of ACCEPT 2·0 in the placebo arm of the Towards a Revolution in COPD Health (TORCH, a three-year randomised clinical trial of inhaled therapies in COPD, 1,091 patients, 1,064 exacerbations) study. The primary outcome for prediction was the occurrence of ≥2 moderate or ≥1 severe exacerbation in the next 12 months; the secondary outcomes were prediction of the occurrence of any moderate/severe exacerbation or any severe exacerbation. Findings: ACCEPT 2·0 had an area-under-the-curve (AUC) of 0·76 for predicting the primary outcome. Exacerbation history alone (current standard of care) had an AUC of 0·68. The model was well calibrated in patients with positive or negative exacerbation histories. Changes in AUC in reduced versions were minimal for the primary outcome as well as for predicting the occurrence of any moderate/severe exacerbations (ΔAUC<0·011), but more substantial for predicting the occurrence of any severe exacerbations (ΔAUC<0·020). All versions of ACCEPT 2·0 provided positive net benefit over the use of exacerbation history alone for some range of thresholds. Interpretation: ACCEPT 2·0 showed good calibration regardless of exacerbation history, and predicts exacerbation risk better than current standard of care for a range of thresholds. Future studies need to investigate the utility of exacerbation prediction in various subgroups of patients. Funding: This study was funded by a team grant from the Canadian Institutes of Health Research (PHT 178432).
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BACKGROUND: Asthma hospitalizations declined rapidly in many parts of the world, including Canada, in the 1990s and early 2000s. OBJECTIVE: To examine whether the declining trend of asthma hospitalizations persisted in recent years in Canada. METHODS: Using the Canadian comprehensive nationwide hospitalization data (2002-2017), we identified hospital admissions with the main International Classification of Diseases codes for asthma. We analyzed sex-specific age-standardized trends in annual hospitalization rates among pediatric (< 19 years) and adult (19+ years) patients. We used change-point analysis to evaluate any substantial changes in the trends in the sex-age groups. RESULTS: There were 254,672 asthma-related hospital admissions (59% pediatric, 50% female) during the study period. Among children, age-adjusted annual rates per 100,000 decreased by 55% in females (152-69) and by 60% in males (270-108) from 2002 to 2017. Among adults, the rates decreased by 59% in both sexes (females: 61-25; males: 27-11). Change-point analysis indicated a substantial plateauing of the annual rate in both pediatric (from -15.3 [females] and -25.8 [males] before 2010 to -0.6 [females] and -0.8 [males] after 2010) and adult (from -5.4 [females] and -2.6 [males] before 2008 to -0.6 [females] and -0.2 [males] after 2008) groups. CONCLUSION: After a substantial decline in hospital admissions for acute asthma, there has been minimal further decline since 2010 for children and 2008 for adults. In addition to adhering to the contemporary standards of asthma care, novel, disruptive strategies are likely needed to further reduce the burden of asthma.
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Asma , Hospitalização , Adulto , Asma/epidemiologia , Canadá/epidemiologia , Criança , Feminino , Hospitais , Humanos , Masculino , Adulto JovemRESUMO
The growing population and global food demands have encouraged the use of pesticides to increase agricultural yields; however, the irrational use of pesticides threatens human health and the environment. Carbaryl (CRBL) is the most widespread insecticide and severely affects soil, water systems, and human health. Thus, it is crucial to monitor CRBL residues in the environment and vegetable samples. This study reports the rapid and sensitive electrochemical detection of CRBL based on a pyrochlore-type lanthanum tin oxide (LSO) nanoparticles (NPs)-modified screen-printed carbon electrode (SPCE). A low-temperature hydrothermal method was employed to prepare the LSO NPs. The structural properties of the LSO NPs were characterized by X-ray diffraction, Raman, and X-ray photoelectron spectroscopy analyses. The LSO NPs/SPCE demonstrated good electroanalytical performance for CRBL detection, with a low detection limit of 0.4 nM (0.08 µg/L) and a sensitivity of 1.05 µA/(µM cm2). Furthermore, the LSO NPs/SPCE exhibited high selectivity among highly interfering carbamate and organophosphorus pesticides, which share similar mechanisms of action. Additionally, the LSO NPs/SPCE sensor achieved > 90% recovery for the detection of CRBL in soil, water, and vegetable samples, thus verifying its suitability for the rapid detection of CRBL.