RESUMO
Corn silk (Zea mays L.) is the stigma of an annual gramineous plant named corn, which is distributed in many regions worldwide and has a long history of medicinal use. In recent years, with the sustainable development of traditional Chinese medicine, studies of corn silk based on modern technologies, such as GC-MS, LC-MS, and other analytical means, have offered more comprehensive analyses. Phytochemistry studies have shown that the main bioactive components in corn silk include flavonoids, polyphenols, phenolic acids, fatty acids, and terpenoids. Pharmacological studies have shown that corn silk extract has various pharmacological effects, such as reducing blood lipids, lowering blood pressure, regulating blood sugar levels, anti-inflammatory effects, and anti-oxidation effects. In this paper, the related research on corn silk from the past few years is summarized to provide a theoretical reference for the further development and utilization of corn silk.
Assuntos
Extratos Vegetais , Zea mays , Pressão Sanguínea , Medicina Tradicional Chinesa , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologiaRESUMO
OBJECTIVE: To report the effect of surgeon and facility volume on outcomes of transurethral resection of the prostate (TURP) and laser treatment of benign prostatic hyperplasia (BPH). We also investigate disparities in access to care by identifying demographic predictors of receipt of treatment at high-volume facilities. METHODS: We used New York State Department of Health Statewide Planning and Research Cooperative System (SPARCS) data. We included 18,041 (41.4%) and 25,577 (58.6%) adult patients that underwent TURP and laser procedures in the outpatient setting between January 2005 and December 2018, respectively. Average annual surgeon and facility volumes were broken down by tertile. The effect of volume on short-term outcomes (30-day and 90-day readmission) was examined using mixed-effect logistic regression models. Cox-proportional-hazard models were used to assess the association between volume and long-term stricture development and reoperation. Demographic predictors of treatment at high-volume facilities were assessed using multinomial logistic regression. RESULTS: High-volume facilities were more likely to offer laser procedures compared to low-volume facilities. Higher facility and surgeon volume were associated with lower odds of 30 and 90-day readmissions compared to low-volume facilities. There was no difference in reoperation and stricture development between surgeon volume groups. Medicaid insurance, Hispanic ethnicity, and Black race were inversely associated with treatment at high-volume facilities. CONCLUSION: Higher surgeon and facility volumes were associated with lower odds of readmission. Higher facility volume was associated with lower hazards of reoperation and developing strictures. Medicaid insurance and non-white race were associated with lower odds of treatment at high-volume facilities, highlighting racial and socioeconomic disparities in access to high-volume BPH surgery facilities.
Assuntos
Hiperplasia Prostática , Cirurgiões , Ressecção Transuretral da Próstata , Masculino , Humanos , Hiperplasia Prostática/cirurgia , Ressecção Transuretral da Próstata/métodos , Constrição Patológica/cirurgia , Acessibilidade aos Serviços de SaúdeRESUMO
BACKGROUND: There are growing interests for minimally invasive surgical techniques (MISTs) for the treatment of benign prostatic hyperplasia (BPH)-associated lower urinary tract symptoms (LUTS). Prostatic artery embolization (PAE) uses selective angioembolization of prostatic arteries, thereby reducing size to improve LUTS/BPH. However, real-world data comparing surgical outcomes between MISTs and tissue resective techniques are lacking. We assessed the differences in surgical outcomes between PAE, transurethral resection of the prostate (TURP), and prostatic urethral lift (PUL) in a real-world population for LUTS/BPH. METHODS: We present an observational population-based study of 12,902 men with BPH in New York State who received PAE, TURP, and PUL in outpatient and ambulatory surgery settings from 2014 to 2018. For short-term outcomes, we report 30-day and 90-day risks of readmission to inpatient and emergency room (ER) with/without complications and compared them across groups using χ2 tests and mixed-effect logistic regressions. For long-term outcomes, we report surgical retreatment and stricture rates using Kaplan-Meier failure curves and compared them using Log rank tests and Cox regression models. RESULTS: Of 12 902 men, 335 had PAE, 11,205 had TURP, and 1362 had PUL. PAE patients had the highest 30-day (19.9%) and 90-day (35.6%) risks of readmission to inpatient or ER (p < 0.01). Non-specific abdominal pain was the main diagnosis associated with 30-day and 90-day readmissions to inpatient or ER after PAE (14.3% and 26.8%, respectively). After 2 years of follow-up, PAE patients had the highest retreatment rate of 28.5% (95%CI 23.7-34.2%) compared to TURP (3.4% (95%CI 3.1-3.8%)) and PUL (8.5% (95%CI 5.6-12.9%)) (p < 0.001). CONCLUSION: In a real-world population, PAE was associated with the most frequent 30-day and 90-day readmission to inpatient or ER and the highest retreatment rate among all surgical techniques even when controlled for individual patient comorbidities and surgical volume.
Assuntos
Embolização Terapêutica , Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Ressecção Transuretral da Próstata , Masculino , Humanos , Próstata/cirurgia , Próstata/irrigação sanguínea , Ressecção Transuretral da Próstata/métodos , Hiperplasia Prostática/complicações , Hiperplasia Prostática/cirurgia , Embolização Terapêutica/efeitos adversos , Resultado do Tratamento , Sintomas do Trato Urinário Inferior/epidemiologia , Sintomas do Trato Urinário Inferior/etiologia , Sintomas do Trato Urinário Inferior/cirurgia , ArtériasRESUMO
OBJECTIVES: To assess the differences in surgical outcomes between the prostatic urethral lift (PUL) and previous thermal energy procedures for the treatment of benign prostatic hyperplasia (BPH). METHODS: We present an observational population-based study of 2694 men with BPH in New York State and California who received PUL, transurethral needle ablation (TUNA), or transurethral microwave therapy (TUMT) in outpatient and ambulatory surgery settings from 2005 to 2018. For these surgical procedures, short-term outcomes were reported and compared using a Chi-square test and mixed-effect logistic regressions. Long-term outcomes were described using Kaplan-Meier failure curves and compared using a Log-rank test and Cox regressions. RESULTS: A significant portion of PUL patients had a comorbidity count ≥ 2 (n = 838, 37.0%). PUL exhibited the lowest 30 day and 90-day inpatient or ER readmission rates among all surgical techniques except for 90-day ER readmission (p < 0.05). No differences were observed for 1- and 3-year risks of reoperation between PUL [5.5% (95% CI 4.4-6.8%) and 14.9% (95% CI 10.9-20.1%)], TUNA [7.4% (95% CI 5.0-10.9%) and 11.3% (95% CI 8.3-15.4%)] and TUMT [8.5% (95% CI 4.7-15.2%) and 15.3% (95% CI 9.5-24.0%)]. 1- and 3-year risks of stricture development for PUL were 0.2% (95% CI 0.0-0.7%) and 0.2% (95% CI 0.0-0.07%), respectively. CONCLUSION: In a patient population with chronic conditions, patients treated with PUL exhibited similar 30- and 90-day inpatient or ER readmission rates when compared to previous reports. However, 1- and 3-year reoperation risks for PUL closely resembled previous thermal energy surgical procedures.
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Hiperplasia Prostática , Ressecção Transuretral da Próstata , Feminino , Humanos , Masculino , Procedimentos Cirúrgicos Minimamente Invasivos , Próstata/cirurgia , Hiperplasia Prostática/cirurgia , Uretra/cirurgiaRESUMO
Lipid nanoparticles have transformed the drug delivery field enhancing the therapeutic drug performance of small molecules and biologics with several approved drug products. However, in industry, these more complex drug delivery systems such as liposomes require more material and time to develop. Here, we report a liposome and lipodisk decision tree with model compounds of diverse physicochemical properties to understand how to resourcefully optimize encapsulation efficiency (EE) for these lipid-based drug delivery systems. We have identified trends with physicochemical properties such as Log P, where higher Log P compounds such as curcumin were able to efficiently load into the lipid bilayer resulting in high EE with altering the drug/lipid (D/L) ratio. Moderate Log P compounds such as cyclosporine A and dexamethasone had significantly higher encapsulation in lipodisks, which contain higher amounts of PEG lipid compared to liposomes. The EE of negative Log P compounds, like acyclovir, remained low regardless of altering the D/L ratio and PEG concentrations. In this study, microfluidic techniques were employed to fabricate liposomes and lipodisks formulations allowing for a reproducible strategy for formulation development. Both liposome and lipodisk of curcumin demonstrated enhanced in vivo performance compared with a conventional formulation in the rat pharmacokinetic study. This combination of approaches with multiple model compounds and lipid-based drug delivery systems provides a systematic guidance to effective strategies to generate higher EE with minimal drug waste and expedite the process for preclinical development when applied to industry compounds.
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Curcumina/administração & dosagem , Sistemas de Liberação de Medicamentos , Lipossomos , Microfluídica , Nanopartículas , Animais , Curcumina/química , Curcumina/farmacocinética , Desenvolvimento de Medicamentos , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Masculino , Preparações Farmacêuticas/administração & dosagem , Preparações Farmacêuticas/química , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos TestesRESUMO
PURPOSE: To compare the safety and durability of transurethral resection of the prostate (TURP) and Laser prostatectomy (LP) among multi-morbid and elderly patients. METHODS: Using data retrieved from the New York State Department of Health Statewide Planning and Research Cooperative System and the California Office of Statewide Health Planning and Development, we selected cohorts of 1) multi-morbid (Charlson comorbidity index ≥ 3) and 2) elderly (aged ≥ 75) patients with benign prostatic hyperplasia who underwent laser coagulation, vaporization, enucleation, or TURP between January 2005 and December 2016. We assessed the post-operative incidence of hospital readmission and ER visit at 30 days and 90 days, complications at 90 days, and reoperation and the development of urethral stricture at 6 months or longer. RESULTS: We found 12,815 and 29,806 patients in the multi-morbid and elderly cohort, respectively. Compared to LP, TURP was associated with lower odds of 90-day hospital readmission and ER visit in the multi-morbid cohort (OR 0.92, 95% CI 0.85-1.00) and higher odds in the elderly cohort (OR 1.07, 95% CI 1.01-1.14). The multi-morbid cohort showed lower odds of urinary tract infections (Ref: LP, OR 0.83, 95% CI 0.73-0.93). The elderly cohort showed higher odds of experiencing hematuria (OR 1.28, 95% CI 1.03-1.59) post TURP. TURP was associated with a 19% (95% CI 0.66-1.00) and 20% (95% CI 0.71-0.91) reduced hazard of reoperation at 6 months or longer for multi-morbid and elderly cohorts, respectively. CONCLUSION: Compared to LP, TURP was associated with higher complication rates for the multi-morbid and elderly cohorts overall but a lower hazard of reoperation, supporting its durability.
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Prostatectomia/métodos , Hiperplasia Prostática/complicações , Hiperplasia Prostática/cirurgia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Humanos , Terapia a Laser , Masculino , Prostatectomia/efeitos adversos , Estudos Retrospectivos , Ressecção Transuretral da Próstata/efeitos adversos , Resultado do TratamentoRESUMO
GDC-0334 is a novel small molecule inhibitor of transient receptor potential cation channel member A1 (TRPA1), a promising therapeutic target for many nervous system and respiratory diseases. The pharmacokinetic (PK) profile and pharmacodynamic (PD) effects of GDC-0334 were evaluated in this first-in-human (FIH) study. A starting single dose of 25 mg was selected based on integrated preclinical PK, PD, and toxicology data following oral administration of GDC-0334 in guinea pigs, rats, dogs, and monkeys. Human PK and PK-PD of GDC-0334 were characterized after single and multiple oral dosing using a population modeling approach. The ability of GDC-0334 to inhibit dermal blood flow (DBF) induced by topical administration of allyl isothiocyanate (AITC) was evaluated as a target-engagement biomarker. Quantitative models were developed iteratively to refine the parameter estimates of the dose-concentration-effect relationships through stepwise estimation and extrapolation. Human PK analyses revealed that bioavailability, absorption rate constant, and lag time increase when GDC-0334 was administered with food. The inhibitory effect of GDC-0334 on the AITC-induced DBF biomarker exhibited a clear sigmoid-Emax relationship with GDC-0334 plasma concentrations in humans. This study leveraged emerging preclinical and clinical data to enable iterative refinement of GDC-0334 mathematical models throughout the FIH study for dose selection in subsequent cohorts throughout the study. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? GDC-0334 is a novel, small molecule TRPA1 inhibitor and a pharmacokinetic-pharmacodynamic (PK-PD) modeling strategy could be implemented in a systematic and step-wise manner to build and learn from emerging data for early clinical development. WHAT QUESTION DID THIS STUDY ADDRESS? Can noncompartmental and population-based analyses be used to describe the PK and PD characteristics of GDC-0334 in preclinical and clinical studies? WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? GDC-0334 exposure generally increased with dose in rats, dogs, and monkeys. The starting dose (25 mg) in the clinical study was determined based on the preclinical data. GDC-0334 exhibited linear PK in humans and the bioavailability was increased with food. The inhibitory effect of GDC-0334 on dermal blood flow induced by the TRPA1 agonist allyl isothiocyanate in humans indicates a clear PK-PD relationship. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? The models developed based on TRPA1 agonist-induced dermal blood flow inhibition data can be used to predict PK-PD relationships in future preclinical and clinical studies evaluating new drug entities that target TRPA1.
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Modelos Biológicos , Piridinas/farmacocinética , Pirimidinas/farmacocinética , Fluxo Sanguíneo Regional/efeitos dos fármacos , Canal de Cátion TRPA1/antagonistas & inibidores , Administração Intravenosa , Adulto , Animais , Disponibilidade Biológica , Cães , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Feminino , Absorção Gastrointestinal , Voluntários Saudáveis , Humanos , Isotiocianatos/administração & dosagem , Macaca fascicularis , Masculino , Pessoa de Meia-Idade , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Ratos , Pele/irrigação sanguínea , Pesquisa Translacional Biomédica , Adulto JovemRESUMO
PURPOSE: We compared outcomes of transurethral prostatectomy and laser prostatectomy in a real-world setting. MATERIALS AND METHODS: We present a prospectively collected observational cohort study of 85,682 men with benign prostatic enlargement in New York State and California who received transurethral prostatectomy or laser prostatectomy in outpatient and ambulatory surgery settings from January 2005 to December 2016. We used propensity score matching to adjust for differences in patient characteristics between groups. We analyzed short-term outcomes using mixed-effect logistic regressions and long-term outcomes using Cox regressions with a time-dependent treatment variable to account for nonproportionality. We performed a sensitivity analysis using multivariable regression models. RESULTS: Mean±SD patient age was 70.5±9.7 years, 71% of patients were White, and median followup was 3.8 years (IQR 1.8-6.3). Transurethral prostatectomy recipients had increased risk of 30-day hospital readmission/emergency room visit (OR 1.09, 95% CI 1.04-1.13, p <0.001) and decreased risk of reoperation (HR 0.81, 95% CI 0.76-0.88, p <0.001). Transurethral prostatectomy had a higher rate of urethral stricture (HR 1.47, 95% CI 1.22-1.75, p <0.001). CONCLUSIONS: Transurethral prostatectomy was associated with higher risk of short and long-term complications but a lower rate of long-term reoperation than laser prostatectomy for benign prostatic enlargement.
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Procedimentos Cirúrgicos Ambulatórios , Prostatectomia/métodos , Hiperplasia Prostática/cirurgia , Idoso , California/epidemiologia , Humanos , Terapia a Laser , Masculino , New York/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Pontuação de Propensão , Estudos Prospectivos , Ressecção Transuretral da PróstataRESUMO
BACKGROUND: Fecal incontinence (FI) represents a large source of morbidity and is a challenging clinical problem to manage. InterStim was approved to treat FI in 2011. Little is known about its adoption. We sought to characterize patterns of use of Interstim since Food and Drug Administration approval for FI. METHODS: The New York State SPARCS database was used to evaluate InterStim use for FI from 2011 to 2014. The primary endpoint was the number of successful implantations of InterStim. Secondary endpoints included device removal, median time to removal of device, 90-day infection rates, and percentage of procedures performed by surgeon specialty and geographic location. RESULTS: A total of 369 patients with FI underwent "Stage 1" of InterStim from 2011 to 2014. A total of 302 patients underwent "Stage 2," yielding a trial period failure rate of 18.2%. The majority of patients who underwent successful implantation were female (87.7%) and White (78.8%). Twenty-nine patients underwent device removal after a median duration of 147 days. Estimated risk of removal at median follow-up of 2 years was 11.8%. Colorectal surgeons comprised 51.1% of all providers followed by gynecologic (24.4%) and urologic surgeons (17.8%). A total of 71.7% of providers performed <5 procedures, while 3 of the highest volume providers performed 50.7% of all procedures. CONCLUSIONS: InterStim for FI has been used by a wide variety of providers in New York State although only a few high-volume providers have performed the majority of procedures. White, female patients with Medicare are the most common recipients of InterStim. Further work must be done to develop strategies for improving access to this technology and to determine whether volume relates to outcomes.
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Terapia por Estimulação Elétrica , Eletrodos Implantados/efeitos adversos , Incontinência Fecal/terapia , Idoso , Remoção de Dispositivo/estatística & dados numéricos , Terapia por Estimulação Elétrica/efeitos adversos , Terapia por Estimulação Elétrica/instrumentação , Terapia por Estimulação Elétrica/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , New York/epidemiologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE: To evaluate an alternative in vitro system which can provide more quantitatively accurate drug drug interaction (DDI) prediction for 10 protein kinase inhibitors for which DDI risk was over-predicted by inhibition data generated in human liver microsomes (HLM). METHODS: Three cryopreserved human hepatocyte (hHEP) systems: 1) plated hHEPs; 2) hHEPs suspended in Dulbecco's Modified Eagle Medium (DMEM) and 3) hHEPs suspended in human plasma (plasma hHEPs) were developed to detect CYP3A time dependent inhibition, and the static mechanistic model was used to predict clinical outcomes. RESULTS: A general trend was observed in the CYP3A inactivation potency (k inact /K I, app ) as HLM > plated > DMEM ≥ plasma hHEPs. Using the static mechanistic model, DDIs predicted using parameters estimated from plated, DMEM and plasma hHEPs had 84, 74 and 95% accuracy (out of 19 clinical interaction studies) within 2-fold of the reported interaction, respectively. They demonstrated significant improvement compared to the DDIs predicted using parameters estimated from HLMs where 58% accuracy was obtained. CONCLUSIONS: Based on 19 DDIs, plasma hHEPs demonstrate a more reliable clinical DDI prediction for 10 protein kinase inhibitors and prototypical CYP3A time dependent inhibitors.