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Coral polyps are composed of four tissues; however, their characteristics are largely unexplored. Here we report biological characteristics of tentacles (Te), mesenterial filaments (Me), body wall (Bo), and mouth with pharynx (MP), using comparative genomic, morpho-histological, and transcriptomic analyses of the large-polyp coral, Fimbriaphyllia ancora. A draft F. ancora genome assembly of 434 Mbp was created. Morpho-histological and transcriptomic characterization of the four tissues showed that they have distinct differences in structure, primary cellular composition, and transcriptional profiles. Tissue-specific, highly expressed genes (HEGs) of Te are related to biological defense, predation, and coral-algal symbiosis. Me expresses multiple digestive enzymes, whereas Bo expresses innate immunity and biomineralization-related molecules. Many receptors for neuropeptides and neurotransmitters are expressed in MP. This dataset and new insights into tissue functions will facilitate a deeper understanding of symbiotic biology, immunology, biomineralization, digestive biology, and neurobiology in corals.
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Antozoos , Genoma , Transcriptoma , Antozoos/genética , Antozoos/metabolismo , Animales , Simbiosis/genética , Pólipos/genética , Pólipos/patología , Perfilación de la Expresión Génica , Especificidad de ÓrganosRESUMEN
OBJECTIVES: The impact of rheumatic diseases, long-term medication, and vaccination on COVID-19 severity remain insufficiently understood, hindering effective patient management. This study aims to investigate factors influencing COVID-19 severity in Chinese rheumatic patients and to provide real-world evidence for patient care. METHODS: We conducted a retrospective observational study consisting of two cohorts, followed by a nested case-control analysis. The outpatient cohort included non-severe COVID-19 patients, while the inpatient cohort included consecutive severe COVID-19 inpatients. Additionally, rheumatic patients from both cohorts were included for the nested case-control study. Clinical information was obtained from electronic medical records and surveys. RESULTS: A total of 749 outpatients and 167 inpatients were enrolled. In the outpatient cohort, rheumatic diseases were identified as a risk factor for the severity of dyspnea (No rheumatic disease: OR = 0.577, 95% CI = 0.396-0.841, p = .004), but not for mortality, length of hospitalization, or hospitalization costs in the inpatient cohort. Long-term glucocorticoids use was identified as an independent risk factor for severity of dyspnea in rheumatic patients (OR = 1.814, 95% CI = 1.235-2.663, p = .002), while vaccination and immunosuppressant treatment showed no association. Vaccination was identified as a protective factor against hospitalization due to COVID-19 in patients with rheumatic diseases (OR = 0.031, 95% CI = 0.007-0.136, p < .001), whereas long-term glucocorticoids and immunosuppressant treatment showed no association. CONCLUSIONS: Rheumatic diseases and long-term glucocorticoids use are significant risk factors for COVID-19 severity in the Chinese population, whereas emphasizing the protective effects of vaccines against COVID-19 severity is crucial. Additionally, the investigation provides preliminary support for the concept that long-term immunosuppressant therapy does not necessarily require additional prescription adjustments.
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COVID-19 , Glucocorticoides , Inmunosupresores , Enfermedades Reumáticas , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Humanos , COVID-19/prevención & control , COVID-19/epidemiología , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Reumáticas/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Glucocorticoides/uso terapéutico , Glucocorticoides/efectos adversos , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Factores de Riesgo , Anciano , Adulto , China/epidemiología , Estudios de Casos y Controles , Vacunas contra la COVID-19/efectos adversos , Vacunación , Factores de Tiempo , Hospitalización/estadística & datos numéricosRESUMEN
OBJECTIVES: To establish a population pharmacokinetics (PopPK) model of nirmatrelvir in Chinese COVID-19 patients and provide reference for refining the dosing strategy of nirmatrelvir in patients confirmed to be infected with SARS-CoV-2. METHODS: A total of 80 blood samples were obtained from 35 mild to moderate COVID-19 patients who were orally administered nirmatrelvir/ritonavir tablets. The PopPK model of nirmatrelvir was developed using a nonlinear mixed effects modelling approach. The stability and prediction of the final model were assessed through a combination of goodness-of-fit and bootstrap method. The exposure of nirmatrelvir across various clinical scenarios was simulated using Monte Carlo simulations. RESULTS: The pharmacokinetics of nirmatrelvir was well characterised by a one-compartment model with first-order absorption, and with creatinine clearance (Ccr) as the significant covariate. Typical population parameter estimates of apparent clearance and distribution volume for a patient with a Ccr of 95.5 mL·min-1were 3.45 L·h-1 and 48.71 L, respectively. The bootstrap and visual predictive check procedures demonstrated satisfactory predictive performance and robustness of the final model. CONCLUSION: The final model was capable of offering an early prediction of drug concentration ranges for different nirmatrelvir dosing regimens and optimise the dose regimen of nirmatrelvir in individuals with confirmed SARS-CoV-2 infection.
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Tratamiento Farmacológico de COVID-19 , Monitoreo de Drogas , Ritonavir , SARS-CoV-2 , Humanos , Masculino , Persona de Mediana Edad , Femenino , Adulto , Ritonavir/farmacocinética , Ritonavir/uso terapéutico , Ritonavir/administración & dosificación , Antivirales/farmacocinética , Antivirales/administración & dosificación , Antivirales/uso terapéutico , Anciano , China , Combinación de Medicamentos , Método de Montecarlo , Adulto Joven , COVID-19 , Pueblos del Este de AsiaAsunto(s)
Combinación Amoxicilina-Clavulanato de Potasio , Amoxicilina , Antibacterianos , Sinusitis , Niño , Humanos , Amoxicilina/uso terapéutico , Combinación Amoxicilina-Clavulanato de Potasio/uso terapéutico , Sinusitis/tratamiento farmacológico , Enfermedad Aguda , Combinación de Medicamentos , Antibacterianos/uso terapéuticoRESUMEN
BACKGROUND: Time-restricted eating (TRE), a feasible form of intermittent fasting, has been proven to benefit metabolic health in animal models and humans. To our knowledge, specific guidance on the appropriate period for eating during TRE has not yet been promoted. Therefore, to compare and assess the relative effectiveness estimates and rankings of TRE with different eating windows on human metabolic health, we conducted a systematic review and network meta-analysis (NMA). METHOD: PubMed, EMBASE and the Cochrane Library were searched for randomized controlled trials that compared different eating windows on human metabolic health for adults. A Bayesian NMA was used to compare direct and indirect effects to determine the best different eating windows, and scientific evidence using GRADE. RESULTS: Twenty-seven RCTs comparing TRE with different eating windows on human metabolic health were reviewed, and all were included in the NMA. Compared with the normal diet group (non-TRE), the TRE group has certain benefits in reducing weight and fasting insulin. In terms of reducing fasting insulin, the 18:6 group (eating time = 6 h) was better than the 14:10 group (eating time = 10 h) and 16:8 group (eating time = 8 h) (P < 0.05); The < 6 group (eating time < 6 h) was better than the 14:10 group (P < 0.05). In terms of reducing fasting glucose, the < 6 group was better than the 14:10 group (P < 0.05). There were no statistical variations in weight, HDL, TG, and LDL across the different modes of TRE (P > 0.05). CONCLUSIONS: Our research showed that no particular metabolic advantages of various eating windows were found. Therefore, our results suggested that different eating windows could promote similar benefits for metabolic parameters.
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BACKGROUND: Responsiveness to opioid analgesics differs among patients with acute postoperative pain. OBJECTIVE: Our study presents the most recent evidence on the effect of genetic variations on postoperative pain, opioid consumption, nausea, and vomiting in patients treated with opioids. STUDY DESIGN: An updated systematic review and meta-analysis on the association between single-nucleotide polymorphisms and opioids administered to patients with acute postoperative pain. METHODS: PubMed, Embase, ISI Web of Science, and the Cochrane Library databases were searched for articles published from February 1, 2014, through December 31, 2021. RESULTS: Added to the previous meta-analysis, 39 studies (a total of 7,455 patients) were included in the final meta-analysis. Highlights of the findings include: 1) human µ-opioid receptor gene 118G allele carriers required more opioids during the first postoperative 24 hours (standard mean difference [SMD] = -0.27; 95% CI,-0.40 to -0.14; P < 0.0001) and 48 hours (SMD = -0.52; 95% CI, -0.83 to -0.20; P = 0.001), and reported higher pain scores during the first 24 hours but not at the 48-hour postoperative period (SMD = -0.09, 95% CI, -0.15 to -0.03; P = 0.002) compared to homozygous 118AA patients. 2) patients with the CYP3A4 *1G allele required fewer opioids during the first 24-hour postoperative period (SMD = 0.59; 95% CI, 0.05 to 1.14; P = 0.03) compared to patients with the homozygous CYP3A4*1/*1 allele. 3) Adenosine triphosphate-binding cassette subfamily B member-1 (ABCB1) 3435T allele carriers required more opioids during the 48-hour postoperative period (SMD = -0.21; 95% CI, -0.38 to -0.04; P = 0.02) compared to homozygous CC carriers. 4) Catechol-O-methyl transferase 158A allele carriers required fewer opioids during the first 24-hour postoperative period (SMD = 0.33; 95% CI, 0.15 to 0.51; P = 0.0004) compared to homozygous GG carriers. No significant differences were observed in patients with CYP2D6*10 and ABCB1 G2677A/T genetic polymorphisms. LIMITATIONS: Several loci were not analyzed in detail due to insufficient clinical data. Furthermore, nongenetic factors that affected analgesic efficacy and the clinical outcome of postoperative pain were not discussed and were not the aim of this meta-analysis. CONCLUSIONS: In combination with previous systematic reviews and meta-analyses, our results indicate that the A118G allele variant of OPRM1 and the *1*1G allele variant of CYP3A4 have a profound influence on individual differences in opioid reactivity in patients with postoperative pain. Our results, together with the identification of additional single nucleotide polymorphisms in future studies, may provide a theoretical basis for precise clinical analgesia. KEY WORDS: Single nucleotide polymorphism, postoperative pain, opioid, meta-analysis.
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Analgésicos Opioides , Catecol O-Metiltransferasa , Humanos , Analgésicos Opioides/uso terapéutico , Catecol O-Metiltransferasa/genética , Catecol O-Metiltransferasa/uso terapéutico , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/uso terapéutico , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/genética , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
BACKGROUND: Clinical trial evidence is limited to identify better topical non-steroidal anti-inflammatory drugs (NSAIDs) for treating knee osteoarthritis (OA). We aimed to compare the clinical efficacy and safety of flurbiprofen cataplasms (FPC) with loxoprofen sodium cataplasms (LSC) in treating patients with knee OA. METHODS: This is an open-label, non-inferiority randomized controlled trial conducted at Peking University Shougang Hospital. Overall, 250 patients with knee OA admitted from October 2021 to April 2022 were randomly assigned to FPC and LSC treatment groups in a 1:1 ratio. Both medications were administered to patients for 28 days. The primary outcome was the change of pain measured by visual analog scale (VAS) score from baseline to day 28 (range, 0-10 points; higher score indicates worse pain; non-inferiority margin: 1 point; superiority margin: 0 point). There were four secondary outcomes, including the extent of pain relief, the change trends of VAS scores, joint function scores measured by the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and adverse events. RESULTS: Among 250 randomized patients (One patient without complete baseline record in the flurbiprofen cataplasms was excluded; age, 62.8 ± 10.5 years; 61.4% [153/249] women), 234 (93.6%) finally completed the trial. In the intention-to-treat analysis, the decline of the VAS score for the 24-h most intense pain in the FPC group was non-inferior, and also superior to that in the LSC group (differences and 95% confidence interval, 0.414 (0.147-0.681); P <0.001 for non-inferiority; P = 0.001 for superiority). Similar results were observed of the VAS scores for the current pain and pain during exercise. WOMAC scores were also lower in the FPC group at week 4 (12.50 [8.00-22.50] vs . 16.00 [11.00-27.00], P = 0.010), mainly driven by the dimension of daily activity difficulty. In addition, the FPC group experienced a significantly lower incidence of adverse events (5.6% [7/124] vs . 33.6% [42/125], P <0.001), including irritation, rash and pain of the skin, and sticky hair uncovering pain. CONCLUSIONS: This study suggested that FPC is superior to LSC for treating patients with knee OA in pain relief, joint function improvement, and safety profile.
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Flurbiprofeno , Osteoartritis de la Rodilla , Humanos , Femenino , Persona de Mediana Edad , Anciano , Osteoartritis de la Rodilla/tratamiento farmacológico , Flurbiprofeno/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Dolor/tratamiento farmacológico , Resultado del Tratamiento , Método Doble CiegoRESUMEN
To design a treatment plan for patients with epididymal obstruction, we explored the potential impact of factors such as body mass index (BMI) and age on the surgical outcomes of vasoepididymostomy (VE). In this retrospective study, 181 patients diagnosed with obstructive azoospermia (OA) due to epididymal obstruction between September 2014 and September 2017 were reviewed. All patients underwent single-armed microsurgical intussusception VEs with longitudinal two-suture placement performed by a single surgeon (KH) in a single hospital (Peking University Third Hospital, Beijing, China). Six factors that could possibly influence the patency rates were analyzed, including BMI, age, mode of anastomosis, site of anastomosis, and sperm motility and quantity in the intraoperative epididymal fluid. Single-factor outcome analysis was performed via Chi-square test and multivariable analysis was performed using logistic regression. A total of 159 (87.8%, 159/181) patients were followed up. The follow-up time (mean ± standard deviation [s.d.]) was 27.7 ± 9.3 months, ranging from 12 months to 48 months. The overall patency rate was 73.0% (116/159). The multivariable analysis revealed that BMI and age significantly influenced the patency rate (P = 0.008 and 0.028, respectively). Younger age (≤28 years; odds ratio [OR] = 3.531, 95% confidence interval [95% CI]: 1.397-8.924) and lower BMI score (<26.0 kg m-2; OR = 2.352, 95% CI: 1.095-5.054) appeared to be associated with a higher patency rate. BMI and age were independent factors affecting the outcomes of microsurgical VEs depending on surgical expertise and the use of advanced technology.
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Cirujanos , Vasovasostomía , Humanos , Masculino , Adulto , Estudios Retrospectivos , Índice de Masa Corporal , Epidídimo/cirugía , Conducto Deferente/cirugía , Resultado del Tratamiento , Motilidad Espermática , MicrocirugiaRESUMEN
N6-methyladenosine (m6A) is one of the most important RNA modifications, which is involved in many biological activities. Computational methods have been developed to detect m6A sites due to their high efficiency and low costs. As one of the most widely utilized model organisms, many methods have been developed for predicting m6A sites of Saccharomyces cerevisiae. However, the generalization of these methods was hampered by the limited size of the benchmark datasets. On the other hand, over 60,000 low resolution m6A sites and more than 10,000 base resolution m6A sites of Saccharomyces cerevisiae are recorded in RMBase and m6A-Atlas, respectively. The base resolution m6A sites are often obtained from low resolution results by post calibration. In view of these, we proposed a two-stage deep learning method, named MTDeepM6A-2S, to predict RNA m6A sites of Saccharomyces cerevisiae based on RNA sequence information. In the first stage, a multi-task model with convolutional neural network (CNN) and bidirectional long short-term memory (BiLSTM) deep framework was built to not only detect the low resolution m6A sites but also assign a reasonable probability for the predicted site. In the second stage, a transfer-learning strategy was used to build the model to predict the base resolution m6A sites from those low resolution m6A sites. The effectiveness of our model was validated on both training and independent test sets. The results show that our model outperforms other state-of-the-art models on the independent test set, which indicates that our model holds high potential to become a useful tool for epitranscriptomics analysis.
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Background: Dosing strategies of ß-lactams and vancomycin should be optimized according to pharmacokinetic/pharmacodynamic principles. However, there is no available data indicating the implementation of extended infusion (EI) or continuous infusion (CI) administration in the management of neonatal sepsis. Methods: A nationwide cross-sectional survey was conducted and the pediatricians from 31 provinces in China were enrolled. A multidisciplinary team created the questionnaire, which had three sections and a total of 21 questions with open- and closed-ended responses. The survey was then conducted using an internet platform in an anonymous way. The data was eventually gathered, compiled, and examined. To identify the risk factors associated with the implementation of EI/CI, logistic regression was carried out. Results: A total of 1501 respondents answered the questionnaires. The implementation of EI/CI of ß-lactams and vancomycin were only available to one-third of the respondents, and the prolonged strategy was primarily supported by guidelines (71.25%) and advice from medical specialists (55.18%). A significant fraction (72.94%-94.71%) lacked a strong understanding of the infusions' stability. Additionally, it was discovered that more frequent MDT discussions about antibiotic use and the appropriate time pediatricians worked in the neonatal ward were associated with an increase in the use of the EI/CI strategy. Conclusion: The EI/CI strategy in neonatal sepsis was not well recognized in China, and it is necessary to establish a solid MDT team with regularly collaborates. In the near future, guidelines regarding prolonged infusion management in neonatal sepsis should be developed.
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Background: The importance of low-density lipoprotein cholesterol (LDL-C) lowering to reduce atherosclerotic cardiovascular disease (ASCVD) risk is strongly emphasized. If the LDL-C goals are not achieved with statin therapy, combination with ezetimibe is recommended. Studies revealed a substantial gap between obtained LDL-C levels and LDL-C target in ASCVD patients. However, little is known about the achievement of LDL-lowering treatment targets in ASCVD patients receiving ezetimibe in addition to statins. Materials and methods: This was a retrospective cohort study based on EHR data from the regional health information system of Yinzhou, an eastern coastal area of China. ASCVD Patients stratified as very high risk, taking both statin and ezetimibe for lipid control, and had at least one lipid test after ezetimibe initiation were included between January 2013 and July 2020. Descriptive statistics were used to summarize the LDL-C values and target value (1.8 mmol/L according to the Chinese guideline, 1.4 mmol/L according to the European guideline) achievements. Multivariable logistic regression was used to explore the influencing factors of target achievement rate. Results: A total of 1,727 patients were included. The median follow-up time was 15.0 months. Taking 1.8 mmol/L as the target value, the achievement rates of LDL-C over the first 3 follow up years were 50.6, 31.3, and 30.3%, respectively. Taking 1.4 mmol/L as the target value, the achievement rates were 25.6, 15.5, and 16.5%, respectively. Multivariable analysis suggested that male patients (OR = 1.78, 95%CI: 1.27-2.49), combined use of atorvastatin or rosuvastatin with ezetimibe (vs other statins, OR = 4.64, 95% CI: 1.83-11.76), better medication adherence (OR = 1.03, 95% CI: 1.01-1.04) and smoking cessation (vs smoking, OR = 2.26, 95% CI: 1.27-4.02) were associated with a higher achievement rate, while baseline LDL-C level (OR = 0.48, 95% CI: 0.41-0.56) and treatment course of statin before ezetimibe (OR = 0.93, 95% CI: 0.89-0.98) were negatively associated with achievement rate. Conclusion: Long-term follow-up data based on a Chinese regional database shows that in very high-risk ASCVD patients taking ezetimibe in addition to statins, achievement rate of LDL-lowering treatment targets is still low and far from satisfactory in real-world setting. More efforts are needed to achieve optimal LDL-C levels.
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As one of the most important posttranslational modifications (PTMs), protein lysine glycation changes the characteristics of the proteins and leads to the dysfunction of the proteins, which may cause diseases. Accurately detecting the glycation sites is of great benefit for understanding the biological function and potential mechanism of glycation in the treatment of diseases. However, experimental methods are expensive and time-consuming for lysine glycation site identification. Instead, computational methods, with their higher efficiency and lower cost, could be an important supplement to the experimental methods. In this study, we proposed a novel predictor, BERT-Kgly, for protein lysine glycation site prediction, which was developed by extracting embedding features of protein segments from pretrained Bidirectional Encoder Representations from Transformers (BERT) models. Three pretrained BERT models were explored to get the embeddings with optimal representability, and three downstream deep networks were employed to build our models. Our results showed that the model based on embeddings extracted from the BERT model pretrained on 556,603 protein sequences of UniProt outperforms other models. In addition, an independent test set was used to evaluate and compare our model with other existing methods, which indicated that our model was superior to other existing models.
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The voltage-dependent anion channel 1 (VDAC1), a pore protein located in the outer mitochondrial membrane, has been confirmed to be related to cancer in cell or animal evidence. However, there is no available pan-cancer analysis of VDAC1. Herein, we investigated the potential roles of VDAC1 in tumorigenesis and progression based on the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) datasets. The expression of VDAC1 increased in most cancers, and the upregulation of VDAC1 distinctly correlated with the poor prognosis in patients, including breast invasive carcinoma, cervical squamous cell carcinoma, pancreatic adenocarcinoma, lung adenocarcinoma, and skin cutaneous melanoma. We also found VDAC1 S104 phosphorylation raised in various cancers, such as breast cancer, colon cancer, and lung adenocarcinoma. Moreover, the expression of VDAC1 was related to the estimated infiltration value of cancer-associated fibroblasts in bladder urothelial carcinoma, colon adenocarcinoma, kidney renal papillary cell carcinoma, and testicular germ cell tumors. At last, we showed that VDAC1-related oxidative phosphorylation and metabolic regulation may partially explain its association with tumorigenesis and progression. Taken together, this pan-cancer analysis provides relatively comprehensive information on the potential value of VDAC1 as a prognostic biomarker and therapeutic target.
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Adenocarcinoma , Carcinoma de Células Transicionales , Neoplasias del Colon , Melanoma , Neoplasias Pancreáticas , Neoplasias Cutáneas , Neoplasias de la Vejiga Urinaria , Animales , Biomarcadores , Carcinogénesis , Proteómica , Neoplasias Cutáneas/genética , Canales Aniónicos Dependientes del Voltaje , Melanoma Cutáneo MalignoRESUMEN
Objective: Continuous lenalidomide (LEN) therapy is important to achieve a therapeutic effect in patients with multiple myeloma (MM) and non-Hodgkin lymphoma (NHL). However, despite dose adjustment according to kidney function, many patients discontinue LEN therapy because of hematological toxicity. To date, therapeutic drug monitoring (TDM) of LEN has not been performed in oncology, and no target concentration level has been yet defined. The aim of this study was to evaluate the exposure-safety relationship of LEN and determine the target concentration for toxicity. Materials and Methods: A prospective observational study was designed and implemented. Blood samples were collected at 0.5 h (trough concentration, Cmin) before oral administration and 1 h (C1h) thereafter on the day. Clinical data were gathered from patients' medical records and laboratory reports. Outcome measures of hematological toxicity were defined by the Common Terminology Criteria for Adverse Events. The concentration values were dichotomized by receiver operating characteristic (ROC) curve analysis, and the association between exposure and outcome was determined using the logistic regression model. Results: Out of the 61 patients enrolled in this study, 40 (65.57%) had MM, and 21 (34.43%) had NHL. Hematological toxicity was reported in 15 (24.59%) patients. The LEN Cmin showed remarkable differences (p = 0.031) among patients with or without hematological toxicity, while no association between C1h values and toxicity was noted (p>0.05). By ROC analysis, a Cmin threshold of 10.95 ng/mL was associated with the best sensitivity/specificity for toxicity events (AUC = 0.687; sensitivity = 0.40; specificity = 0.935). By multivariate logistic regression, an LEN Cmin below 10.95 ng/mL was associated with a markedly decreased risk of hematological toxicity (<10.95 ng/mL vs. >10.95 ng/mL: OR = 0.023, 95% CI = 0.002-0.269; p = 0.003). Conclusions: We demonstrate that the LEN trough concentration correlates with hematological toxicity, and the Cmin threshold for hematological toxicity (10.95 ng/mL) is proposed. Altogether, LEN TDM appears to be a new approach to improve medication safety and achieve continuous treatment for patients with NHL or MM in routine clinical care.
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Introduction: Xiyanping injection (XYP), a type of Traditional Chinese Medicine, is widely used and often applied in combination with other medications in treating bronchitis, tonsillitis, and bacillary dysentery in China. In recent years, an elevated risk of allergic reactions has been observed following XYP, but whether concomitant medication use contributes to this risk is still unknown. Objective: This study aims to investigate the association between the concomitant use of XYP and the 25 most frequently co-applied medications with suspected allergic reactions for China's patients receiving XYP. Methods: A nested case-control study was conducted using the sampling data from 2015 China's Urban Employees Basic Medical Insurance and Urban Residents Basic Medical Insurance database. Four anti-allergic marker drugs were used to evaluate suspected allergic reactions. Univariate analyses and multivariable conditional logistic regression were conducted, and results were reported as odds ratios (ORs) with a 95% confidence interval (CI). Sensitivity analyses were performed on the expanded sample by including those prescribed with anti-allergic marker drugs on the same day as XYP and then stopped XYP on the next day. Results: Out of 57,612 participants with XYP prescription, we obtained 949 matched case-control pairs. Multivariable conditional logistic regression revealed that seven concomitant medications including gentamicin [OR = 4.29; 95% CI (2.52, 7.30)], cefoperazone-sulbactam [OR = 4.26; 95% CI (1.40, 13.01)], lidocaine [OR = 2.76; 95% CI (1.79, 4.25)], aminophylline [OR = 1.73; 95% CI (1.05, 2.85)], ribavirin [OR = 1.54; 95% CI (1.13, 2.10)], potassium chloride [OR = 1.45; 95% CI (1.10, 1.91)], and vitamin C [OR = 1.32; 95% CI (1.03, 1.70)] were associated with increased risk, while cefathiamidine [OR = 0.29; 95% CI (0.16, 0.51)] was associated with reduced risk. Sensitivity analysis on 2,438 matched pairs revealed similar findings. Conclusion: Increased risks for suspected allergic reactions were found for the concomitant use of XYP with seven medications. Our data suggest that gentamicin, cefoperazone-sulbactam, lidocaine, and ribavirin should be applied with precautions for patients receiving XYP, and further studies on drug interactions and allergy mechanisms are warranted.
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Context: The role of tumor size in predicting prognosis in upper tract urothelial carcinoma (UTUC) patients remains poorly defined. Objective: To assess the prognostic value of tumor size in patients with UTUC through a systematic review and meta-analysis. Evidence acquisition: A comprehensive literature search of the PubMed and Embase databases were performed to identify all relevant articles published up to December 2021 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Available hazard ratios (HRs) and corresponding 95% confidence intervals (95% CIs) were analyzed to evaluate the association between tumor size and survival outcomes. Evidence synthesis: A total of 35 articles representing 32 292 patients met the eligibility criteria and were finally included for the meta-analysis. Tumor size was significantly associated with poor outcomes in terms of overall survival (HR = 1.42, 95% CI = 1.28-1.58), cancer-specific survival (HR = 1.66, 95% CI = 1.47-1.88), recurrence-free survival (HR = 1.25, 95% CI = 1.13-1.38), and intravesical recurrence (HR = 1.12, 95% CI = 1.04-1.20). There was between-study heterogeneity in the effect of tumor size on all these meta-analyses, with p < 0.10 and I2 generally >50%. Subgroup analyses illustrated that the association of tumor size with adverse prognosis in UTUC patients is not affected by treatment modalities. Segmental resection of ureter, whether receiving lymph node dissection, cutoff of tumor size, and region of population were potential sources of heterogeneity. The funnel plot test indicated no significant publication bias in the meta-analysis of survival outcomes. Conclusions: This study shows that larger tumor size is associated with an increased risk of overall and cancer-specific mortality, and disease recurrence in UTUC. Integration of tumor size with other prognostic indicators may help in risk stratification and individualized treatment of UTUC. Patient summary: Through a systematic review and meta-analysis, this study found that larger tumor size is associated with an increased risk of overall and cancer-specific mortality, and disease recurrence in patients with upper tract urothelial carcinoma.
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Objective: With increasing numbers of biosimilars entering the market or in the approval pipeline in China, understanding the current awareness and attitudes of biosimilars still remains the first step to promote uptake. This study aims to investigate the knowledge, attitudes and practices (KAP) of multiple stakeholders toward biosimilars, including healthcare providers (HCPs), healthcare regulatory practitioners and patients, and to provide practical information for future uptake of biosimilars in China. Methods: This nationwide cross-sectional online survey was conducted in mainland China. The questionnaire with a high level of reliability and validity was designed based on previous studies and clinical questions in the Clinical Practice Guideline for Clinical Application of Biosimilars. Logistic regression model was employed to identify possible impact factors, and Spearman's rank correlation test was used to identify the correlation between knowledge and attitudes. Chi-squared test was used to compare the differences between different stakeholders. Results: Overall, 599 valid respondents were recruited, of whom 77.63%, 7.01% and 15.36% were HCPs, healthcare regulatory practitioners and patients, respectively. A total of 504 respondents who had heard of biosimilars were included in the KAP analysis. 76.70% of HCPs, 90.24% of healthcare regulatory practitioners and 50.98% of patients had good knowledge about the definition, while less familiarity with the development process and regulations on interchangeability and indication extrapolation was found in the former two groups. For attitudes toward biosimilars, an overall lack of positivity was shown, as only 18.20% HCPs, 14.63% healthcare regulatory practitioners and 23.53% patients were classified as having positive attitudes. More specifically, most respondents were positive about the influence of payment policy on the uptake of biosimilars, but they showed a neutral attitude toward the clinical medication and interchangeability of biosimilars. Efficacy, safety, immunogenicity, interchangeability and indication extrapolation are major concerns when utilizing biosimilars. Regarding practice, our study showed an inadequate utilization of biosimilars in China. Several further suggestions on the regulation of biosimilars were proposed by healthcare regulatory practitioners. Conclusions: There is still plenty of room for improvement of knowledge, attitudes and practice toward biosimilars among multiple stakeholders in China, which can be improved through high-quality real world evidence, educational programs and other effective measures directed towards barriers.
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Thrombocytopenia can cause substantial morbidity and mortality in critically ill patients. There are multiple etiology factors and various mechanisms associated with thrombocytopenia, of which drug-induced thrombocytopenia (DITP) deserves attention. Herein, we describe a case of severe thrombocytopenia during intensive care unit (ICU) hospitalization that was likely to be associated with vancomycin. By revealing the process of identifying this case of DITP and reviewing relevant clinical studies, a risk alert of vancomycin-related severe hematotoxicity should be considered.