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1.
Urol Pract ; 10(5): 501-510, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37594033

RESUMO

INTRODUCTION: A manufacturer's benefit verification database was evaluated to ascertain United States health plan insurance coverage for implantable penile prostheses for erectile dysfunction. METHODS: All-payer and employer-sponsored health plan benefit verification databases were queried to determine implantable penile prosthesis approval status. For the all-payer analysis, data by payer were available and presented for 2019-2021 to assess approval status varied by payer and over time. For the employer-sponsored health plan analysis, data by payer were available from 2018-2021. RESULTS: Benefit verification records for the all-payer database were available for 3,167 patients in 2019, 3,016 in 2020, and 2,837 in 2021. Insurance type was preferred provider organization (27.5%), Medicare Advantage (26.9%), Medicare (15.9%), or point-of-service (10.5%). Most patients were approved or verified for implantable penile prosthesis coverage (79.4% in 2019, 79.6% in 2020, and 78.4% in 2021). Coverage was most extensive for government-based insurance (Medicare 98.7%, Medicare Advantage 97.1%, Tricare 100%, and Veterans Affairs 80.0%) but was also favorable for commercial insurance (75.0%). The most common reason for lack of coverage was employer exclusion; the proportion of patients with no coverage due to exclusion increased from 13.5% in 2019 to 17.5% in 2021. Analyses of the employer-sponsored health plan database (n=3,083 patients) showed that 63.1% of patients were approved or verified for coverage and 34.2% did not have coverage due to health plan exclusions. CONCLUSIONS: Approximately 80% of patients had implantable penile prosthesis coverage. Employer exclusion was the most common reason for lagging coverage; rates of employer exclusion increased 29.3% from 2019-2021.


Assuntos
Disfunção Erétil , Prótese de Pênis , Idoso , Masculino , Humanos , Estados Unidos , Disfunção Erétil/cirurgia , Medicare , Cobertura do Seguro , Bases de Dados Factuais
2.
Asian J Urol ; 10(1): 27-32, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36721684

RESUMO

Objective: The clinical grading system for varicoceles is subjective and dependent on clinician experience. Color Doppler ultrasound (US) has not been standardized in the diagnosis of varicoceles. We aimed to determine if US measurement of varicocele could be predictive of World Health Organization (WHO) varicocele grade. Methods: Men who presented for either scrotal pain or infertility to a tertiary men's health clinic underwent physical examination, and varicoceles were graded following WHO criteria (0=subclinical, 1, 2, 3). US was used to measure largest venous diameter in the pampiniform plexus bilaterally at rest and during Valsalva maneuver. Receiver operator characteristic curve analysis was used to determine if resting diameter, diameter during Valsalva, or change in diameter between at rest and during Valsalva provided the highest sensitivity and specificity for determining clinical grade. Threshold values for diameter were determined from these receiver operator characteristic curves. Results: A total of 102 men (50 with clinical varicocele and 52 with subclinical varicocele) were included. Diameter at rest was the best ultrasonographic discriminator between subclinical and clinical varicoceles (area under the curve [AUC]=0.67) with a diameter threshold of 3.0 mm (sensitivity 79%, specificity 42%). Diameter during Valsalva had the greatest AUC for determining clinical Grades 1 versus 2 (AUC=0.57) with diameter threshold of 5.7 mm (sensitivity 71%, specificity 33%). For differentiating between Grades 2 and 3, diameter at rest had the greatest AUC of 0.65 with a threshold of 3.6 mm (sensitivity 71%, specificity 58%). Conclusion: Our results corroborate other studies that have shown a weak correlation between US and clinical grading. The use of diameter during Valsalva was less predictive than diameter at rest and was only clinically significant in differentiating between Grade 1 and 2 varicocele. A standardized method for determining clinically relevant varicoceles on US would allow for improved patient counseling and clinical decision-making.

3.
Curr Biol ; 33(1): 86-97.e10, 2023 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-36528024

RESUMO

Color variation is a frequent evolutionary substrate for camouflage in small mammals, but the underlying genetics and evolutionary forces that drive color variation in natural populations of large mammals are mostly unexplained. The American black bear, Ursus americanus (U. americanus), exhibits a range of colors including the cinnamon morph, which has a similar color to the brown bear, U. arctos, and is found at high frequency in the American southwest. Reflectance and chemical melanin measurements showed little distinction between U. arctos and cinnamon U. americanus individuals. We used a genome-wide association for hair color as a quantitative trait in 151 U. americanus individuals and identified a single major locus (p < 10-13). Additional genomic and functional studies identified a missense alteration (R153C) in Tyrosinase-related protein 1 (TYRP1) that likely affects binding of the zinc cofactor, impairs protein localization, and results in decreased pigment production. Population genetic analyses and demographic modeling indicated that the R153C variant arose 9.36 kya in a southwestern population where it likely provided a selective advantage, spreading both northwards and eastwards by gene flow. A different TYRP1 allele, R114C, contributes to the characteristic brown color of U. arctos but is not fixed across the range.


Assuntos
Ursidae , Animais , Fluxo Gênico , Variação Genética , Genoma , Estudo de Associação Genômica Ampla , Ursidae/genética
4.
J Geophys Res Space Phys ; 127(7): e2022JA030374, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36248014

RESUMO

The scale size of the plasma boundary region between the sheath and ionosphere in the Martian system is often similar to the gyro-radii of sheath protons, ∼200 km. As a result, ion energization via kinetic structures may play an important role in modifying the ion trajectories and thus be important when evaluating the large-scale dynamics of the Martian system. In this paper, we report observations made with the MAVEN Langmuir Probe and Waves instrument of solitary bipolar electric field structures, and assess their potential role in ion energization in the Martian system. The observed structures appear as short duration (∼0.5 ms) bipolar electric field pulses of ∼1-25 mV/m, and are frequently observed in the upstream solar wind and inside the sheath. The study presented in this paper suggests that the bipolar electric field structures observed at Mars have an average electrostatic potential drop of ∼0.07 V. The estimated upper rate at which these structures could further energize the protons is estimated, assuming the protons gain the full 0.07 eV, to be ∼0.13 eV per gyration, or a change in proton energy of ∼0.3%, and a corresponding change in the gyroradius of ∼0.3 km. These numbers imply that to first order the bipolar structures are not a significant source of ion energization in the Martian magnetosheath.

5.
J Urol ; 204(3): 562-563, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32574105
6.
Urology ; 143: 165-172, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32535075

RESUMO

OBJECTIVE: To determine comorbidities in young men with erectile dysfunction (ED) who are increasingly targeted by direct-to-consumer (DTC) internet platforms that sell phosphodiesterase-5 (PDE-5) inhibitors without comprehensive clinical evaluation; and, further, to characterize the portrayal of DTC platforms by popular news media. METHODS: We retrospectively reviewed all men age ≤40 evaluated for ED at an andrology clinic during January 2016-March 2019 to obtain demographics, exam and lab findings, and treatments. Five news sources were analyzed during the study period to characterize whether articles about DTC platforms were positive, critical, or balanced/neutral. RESULTS: We identified 388 patients, with age 29.5 ± 5.0 years, 15% rate of obesity, 20% prediabetes or diabetes, 54% dyslipidemia, and 20% hypogonadism. Serum lab findings associated with subfertility were found in 11%. Semen analysis was conducted in 64 men, of whom 40% were abnormal. Varicoceles were found in 35%. PDE-5 inhibitor was prescribed to 328 men (88%). Off-label empiric therapies included clomiphene (32.9%) or aromatase inhibitor (12.1%). Testosterone replacement was initiated in 9.7%. Analysis of news coverage revealed 18 articles, of which 61% portrayed DTC platforms exclusively in a positive light. CONCLUSION: Office consultation identified young men with significant comorbidities that would be missed by DTC platforms, which employ only questionnaires for health screening. DTC platforms present themselves as medical authorities without following AUA Guidelines, yet garner mostly positive press coverage. Patients engaging these platforms may falsely believe they are receiving adequate medical assessment. Urologists may do well to incorporate telemedicine to enfranchise young men with evidence-based evaluation.


Assuntos
Registros Eletrônicos de Saúde/estatística & dados numéricos , Prescrição Eletrônica/estatística & dados numéricos , Disfunção Erétil/epidemiologia , Internet/estatística & dados numéricos , Inibidores da Fosfodiesterase 5/uso terapêutico , Adulto , Comorbidade , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Disfunção Erétil/diagnóstico , Disfunção Erétil/tratamento farmacológico , Humanos , Hipogonadismo/diagnóstico , Hipogonadismo/epidemiologia , Masculino , Obesidade/diagnóstico , Obesidade/epidemiologia , Uso Off-Label/estatística & dados numéricos , Visita a Consultório Médico/estatística & dados numéricos , Ereção Peniana/efeitos dos fármacos , Estudos Retrospectivos , Análise do Sêmen/estatística & dados numéricos , Varicocele/diagnóstico , Varicocele/epidemiologia , Adulto Jovem
7.
Urology ; 142: 112-118, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32445765

RESUMO

OBJECTIVE: To study disease-specific knowledge and decisional quality in men with varicocele being counseled for infertility. MATERIALS AND METHODS: An instrument designed to measure decisional quality by evaluating disease-specific knowledge, decisional conflict, and the impression that shared decision-making was administered to 92 men identified to have a varicocele seeking their initial infertility consultation. Mean scores on disease-specific knowledge questionnaire, prevalence of decisional conflict, and impact of consultation on preferred infertility treatment were analyzed. RESULTS: Fifty-five percent of patients were found to have decisional conflict. Compared to those with decisional conflict, men without decisional conflict scored higher on the infertility knowledge assessment (63% vs 53% correct) and were more likely to feel that they discussed treatment options with their physician in detail (98% vs 82%) (all P <0.01). Prior to consultation, 28% of all patients preferred assisted reproductive technologies and 2% preferred varicocelectomy as the primary treatment for infertility. Following consultation, 12% and 17% preferred assisted reproductive technologies and varicocelectomy, respectively. The increase in preference for varicocelectomy was greater in men without decisional conflict (5%-31%) than those with conflict (0%-8%) (P = 0.03). CONCLUSION: Infertile men with varicocele have limited knowledge of their disease and high rates of decisional conflict. Before consultation, men with varicoceles showed preference for assisted reproductive technology over varicocele surgery; this trend reversed after consultation. Men with decisional conflict were less likely to prefer varicocelectomy, even after consultation.


Assuntos
Conflito Psicológico , Tomada de Decisão Compartilhada , Conhecimentos, Atitudes e Prática em Saúde , Infertilidade Masculina/terapia , Varicocele/cirurgia , Adulto , Humanos , Infertilidade Masculina/etiologia , Masculino , Pessoa de Meia-Idade , Encaminhamento e Consulta/estatística & dados numéricos , Técnicas de Reprodução Assistida/psicologia , Técnicas de Reprodução Assistida/estatística & dados numéricos , Procedimentos Cirúrgicos Urológicos Masculinos/psicologia , Procedimentos Cirúrgicos Urológicos Masculinos/estatística & dados numéricos , Varicocele/complicações , Adulto Jovem
8.
Int J Impot Res ; 32(3): 323-328, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31474755

RESUMO

To evaluate the efficacy of a novel, multi-modal, preoperative approach to postprostatectomy penile rehabilitation (PR), we performed a retrospective review of patients who underwent nerve-sparing robotic-assisted laparoscopic prostatectomy (NS-RALP). All patients were evaluated at a comprehensive, academic sexual medicine clinic between 2016 and 2017. The "prehabilitation" PR group (n = 106) consisted of men who were seen in the pre-op period and began tadalafil and L-citrulline 2 weeks prior to surgery. Vacuum erectile device (VED) therapy was started at 1-month post-op. These interventions were continued throughout the 12-month follow-up period. Individuals refractory to these therapies could start treatment with intracavernosal injections. The postprostatectomy PR group (n = 25) consisted of men who were not seen in the pre-op period and started the above therapies immediately following their first visit. A higher percentage of men in the prehabilitation group reported return of erectile function within 12 months (56% vs. 24%, P = 0.007). The prehabilitation group also showed better compliance with PR (PDE5i [96% vs. 64%, P < 0.001], L-citrulline [93% vs. 49%, P < 0.001], and VED [55% vs. 20%, P < 0.001]). Seventy-eight percent of men who attended 4-5 follow-up visits reported return of erectile function. Our results suggest that men undergoing a preoperative protocol show superior recovery of erectile function following NS-RALP. Further studies with prospective designs are warranted.


Assuntos
Disfunção Erétil , Disfunção Erétil/tratamento farmacológico , Disfunção Erétil/etiologia , Humanos , Masculino , Ereção Peniana , Inibidores da Fosfodiesterase 5/uso terapêutico , Estudos Prospectivos , Prostatectomia/efeitos adversos , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
9.
Urology ; 133: 109-115, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31376474

RESUMO

OBJECTIVE: To measure decisional quality, physician loyalty, and treatment preference in patients diagnosed with urolithiasis, a "preference-sensitive" condition, to identify areas of improvement to be addressed by a targeted shared decision-making intervention. METHODS: We identified patients who presented for an initial consultation for urolithiasis from March 2016 to May 2017. Patients completed a 24-item patient experience questionnaire after the consultation which assessed decisional quality domains, physician loyalty, and treatment preference. We summarized treatment preferences before and after the consultation and described the changes. RESULTS: Among the total of 113 patients who met inclusion criteria, 78 (69%) patients chose to participate. Thirty-six (46%) of those patients had evidence of decisional conflict and 42 (54%) did not. Only 1 in 5 patients experiencing decisional conflict reported knowing the benefits and risks of each treatment option. Patients with decisional conflict reported lower perceived shared decision-making, treatment satisfaction, and urolithiasis knowledge. Physician loyalty was lower among patients with decisional conflict as well. Thirty-nine percent of them were 'Promoters' of their urologist, compared to 71% of patients without decisional conflict. Sixty-four percent of patients without decisional conflict identified a treatment preference before consultation, while only 17% of patients who experienced decisional conflict were able to do so. CONCLUSION: Many patients with urolithiasis experience decisional conflict and are unsure of their preferences when making a treatment choice. Uncertainty can correlate with low physician loyalty after consultation. This population may benefit from a shared decision-making intervention that improves decisional quality while incorporating patient-specific preferences.


Assuntos
Tomada de Decisões , Participação do Paciente , Preferência do Paciente , Urolitíase/terapia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autorrelato , Adulto Jovem
10.
MAbs ; 10(4): 664-677, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29436901

RESUMO

TL1A is an attractive therapeutic target for the treatment of mucosal inflammation associated with inflammatory bowel disease (IBD) and asthma. Blockade of the TL1A pathway has been shown to reduce inflammatory responses while leaving baseline immunity intact, and to be beneficial in animal models of colitis and asthma. Given the therapeutic potential of blocking this pathway in IBD and asthma, we developed C03V, a human antibody that binds with high affinity to soluble and membrane-bound TL1A. In an assay measuring apoptosis induced by exogenous TL1A, C03V was 43-fold more potent than the next most potent anti-TL1A antibody analyzed. C03V also potently inhibited endogenous TL1A activity in a primary cell-based assay. This potency was linked to the C03V-binding epitope on TL1A, encompassing the residue R32. This residue is critical for the binding of TL1A to its signaling receptor DR3 but not to its decoy receptor DcR3, and explains why C03V inhibited TL1A-DR3 binding to a much greater extent than TL1A-DcR3 binding. This characteristic may be advantageous to preserve some of the homeostatic functions of DcR3, such as TL1A antagonism. In colitis models, C03V significantly ameliorated microscopic, macroscopic and clinical aspects of disease pathology, and in an asthma model it significantly reduced airways inflammation. Notable in both types of disease model was the reduction in fibrosis observed after C03V treatment. C03V has the potential to address unmet medical needs in asthma and IBD.


Assuntos
Anticorpos Monoclonais/farmacologia , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/antagonistas & inibidores , Animais , Anticorpos Monoclonais/química , Asma/imunologia , Humanos , Doenças Inflamatórias Intestinais/imunologia
11.
Urol Pract ; 5(5): 327-333, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37312364

RESUMO

INTRODUCTION: The documented increasing incidence of nephrolithiasis in the United States will likely be associated with significant economic impact. Time-driven activity-based costing is an analytical method that has been successfully adapted from industrial analysis for use in health care. Using this costing approach we characterized the cost of 4 stone treatment modalities at our academic medical center, including trial of passage, semirigid ureteroscopy, flexible ureteroscopy and extracorporeal shock wave lithotripsy. METHODS: We developed process mapping for urological evaluation, treatment and followup of renal or ureteral stones less than 10 mm in size for each treatment method. We calculated cost of resources, equipment, disposables, personnel and space used for each step in the process. Cost was based on the capacity of each resource and the amount of time required for the treatment process. RESULTS: The cost for trial of stone passage, $389, was expectedly lower than for surgical interventions and was mainly driven by clinic visit costs. Extracorporeal shock wave lithotripsy and semirigid and flexible ureteroscopy costs were $4,367, $4,830 and $5,356, respectively. Intraoperative disposables and personnel were the top contributors to overall treatment costs. CONCLUSIONS: Conservative management is less costly than surgical interventions. Flexible ureteroscopy is the most expensive of surgical interventions. We describe the first time-driven activity-based cost analysis of stone management to our knowledge. Identifying the main drivers of cost can help to improve the value of urological care and improve future cost-effectiveness analyses.

12.
Asian J Urol ; 4(1): 37-43, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29264205

RESUMO

OBJECTIVE: Treatment options for metastatic castration resistant prostate cancer (mCRPC) have expanded rapidly in recent years. Given the significant economic burden, we sought perform a cost-effectiveness analysis (CEA) of the contemporary treatment paradigm for mCRPC. METHODS: We devised a treatment protocol consisting of sipuleucel-T, enzalutamide, abiraterone, docetaxel, radium-223, and cabazitaxel. We estimated number and length of treatments for each therapy using dosing schedules or progression free survival data from published clinical trials. We estimated treatment cost using billing data and Medicare reimbursement values and performed a CEA. Our analysis assumed US$100,000 per life year saved (LYS) as the threshold societal willingness to pay. RESULTS: Incremental cost-effectiveness ratios (ICER) for strategies incorporating sipuleucel-T that were not eliminated by extended dominance exceeded the societal threshold willingness-to-pay of US$100,000 per LYS, the lowest of which was sipuleucel-T + enzalutamide + abiraterone + docetaxel at US$207,714 per LYS. Enzalutamide + abiraterone + docetaxel exhibited the most favorable ICER among strategies without sipuleucel-T at US$165,460 per LYS. CONCLUSION: Based on the available survival data and current costs of treatment, all treatment strategies greatly exceed a commonly assumed societal willingness-to-pay threshold of US$100,000 per LYS. Improvements in this regard can only come with a reduction in pricing, better tailoring of treatment or significant enhancements in survival with clinical use of treatment combinations or sequences.

13.
Oncol Res Treat ; 40(9): 508-514, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28796995

RESUMO

AIM: The aim of this study was to clarify and examine the outcomes of prostate cancer patients classified as intermediate risk (IR) using the D'Amico risk classification system, specifically focusing on the influence of primary and secondary biopsy Gleason score (BGS). PATIENTS AND METHODS: An institutional review board-approved database of robotic-assisted radical prostatectomies performed after 2006 was stratified by standard D'Amico criteria. IR patients were then sub-stratified by BGS. Pathologic and intermediate-term biochemical disease-free survival (BDFS) outcomes were analyzed. RESULTS: Overall, 1,090 patients were classified as D'Amico low-risk, 896 as IR, and 240 as high-risk. Of the 896 IR patients, 63 had BGS 6, 630 were 3 + 4 = 7, and 203 4 + 3 = 7. Among IR patients, as the BGS increased, there was an increasing likelihood of extracapsular extension (21, 28, and 38%, respectively; p = 0.005), positive surgical margins (14, 26, 31%; p = 0.048), and worse 3-year BDFS (96, 94, 88%; p = 0.01). Multivariable logistic regression and Cox regression analyses confirmed differences among IR groups. CONCLUSION: D'Amico IR patients demonstrate significant heterogeneity in both pathologic outcomes and BDFS. IR patients with a BGS of 6 appear to have similar intermediate-term BDFS as low-risk patients. An increasing BGS from 3 + 3 to 3 + 4 to 4 + 3 results in a higher likelihood of locally-advanced disease and intermediate-term biochemical failure.


Assuntos
Laparoscopia/métodos , Gradação de Tumores , Prostatectomia/métodos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento , Adulto , Idoso , Biópsia , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Próstata/patologia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/mortalidade , Análise de Regressão , Medição de Risco
14.
MAbs ; 7(3): 638-50, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25751125

RESUMO

CD1d is a receptor on antigen-presenting cells involved in triggering cell populations, particularly natural killer T (NKT) cells, to release high levels of cytokines. NKT cells are implicated in asthma pathology and blockade of the CD1d/NKT cell pathway may have therapeutic potential. We developed a potent anti-human CD1d antibody (NIB.2) that possesses high affinity for human and cynomolgus macaque CD1d (KD ∼100 pM) and strong neutralizing activity in human primary cell-based assays (IC50 typically <100 pM). By epitope mapping experiments, we showed that NIB.2 binds to CD1d in close proximity to the interface of CD1d and the Type 1 NKT cell receptor ß-chain. Together with data showing that NIB.2 inhibited stimulation via CD1d loaded with different glycolipids, this supports a mechanism whereby NIB.2 inhibits NKT cell activation by inhibiting Type 1 NKT cell receptor ß-chain interactions with CD1d, independent of the lipid antigen in the CD1d antigen-binding cleft. The strong in vitro potency of NIB.2 was reflected in vivo in an Ascaris suum cynomolgus macaque asthma model. Compared with vehicle control, NIB.2 treatment significantly reduced bronchoalveolar lavage (BAL) levels of Ascaris-induced cytokines IL-5, IL-8 and IL-1 receptor antagonist, and significantly reduced baseline levels of GM-CSF, IL-6, IL-15, IL-12/23p40, MIP-1α, MIP-1ß, and VEGF. At a cellular population level NIB.2 also reduced numbers of BAL lymphocytes and macrophages, and blood eosinophils and basophils. We demonstrate that anti-CD1d antibody blockade of the CD1d/NKT pathway modulates inflammatory parameters in vivo in a primate inflammation model, with therapeutic potential for diseases where the local cytokine milieu is critical.


Assuntos
Anticorpos Monoclonais/farmacologia , Anticorpos Neutralizantes/farmacologia , Antígenos CD1d/imunologia , Asma/tratamento farmacológico , Pulmão/imunologia , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Asma/imunologia , Asma/patologia , Líquido da Lavagem Broncoalveolar/imunologia , Modelos Animais de Doenças , Humanos , Pulmão/patologia , Macaca fascicularis , Macrófagos/imunologia , Macrófagos/patologia , Células T Matadoras Naturais/imunologia , Células T Matadoras Naturais/patologia
15.
Acta Crystallogr D Biol Crystallogr ; 70(Pt 7): 1954-64, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25004972

RESUMO

The heterodimeric ligand-binding region of the Bovicola ovis ecdysone receptor has been crystallized either in the presence of an ecdysteroid or a synthetic methylene lactam insecticide. Two X-ray crystallographic structures, determined at 2.7 Šresolution, show that the ligand-binding domains of both subunits of this receptor, like those of other nuclear receptors, can display significant conformational flexibility. Thermal melt experiments show that while ponasterone A stabilizes the higher order structure of the heterodimer in solution, the methylene lactam destabilizes it. The conformations of the EcR and USP subunits observed in the structure crystallized in the presence of the methylene lactam have not been seen previously in any ecdysone receptor structure and represent a new level of conformational flexibility for these important receptors. Interestingly, the new USP conformation presents an open, unoccupied ligand-binding pocket.


Assuntos
Iscnóceros/química , Receptores de Esteroides/metabolismo , Animais , Ligantes , Modelos Moleculares , Conformação Proteica , Receptores de Esteroides/química
16.
Urol Oncol ; 32(4): 419-25, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24411791

RESUMO

OBJECTIVES: Longitudinal studies report racial disparities in prostate cancer (PCa) including greater incidence, more aggressive tumor biology, and increased cancer-specific mortality in African American (AA) men. Regret concerning primary treatment selection is underevaluated in patients with PCa. We investigated the relationships between clinicopathologic variables across racial and socioeconomic lines following robotic-assisted laparoscopic prostatectomy. MATERIALS AND METHODS: We assessed treatment decisional regret using a validated questionnaire in a total of 484 white and 72 AA patients with PCa who were followed up for a median of 16.6 months post-robotic-assisted laparoscopic prostatectomy. Socioeconomic status (SES) information was aggregated from 2010 US census zip code data. Perioperative clinicopathologic characteristics and functional outcomes were compared between groups. Univariate and multivariate regression analyses were used to evaluate the influence of race, aggregate SES, and other clinical and demographic characteristics on decisional regret. RESULTS: The majority (87.7%) of the population was not regretful of their decision to undergo treatment. However, a greater proportion of AA vs. white patients were regretful (20.6% vs. 11.2%, respectively; P = 0.03). AA and white men were similar on all functional, clinical, and pathologic features with the exception of younger age among AA men (56 vs. 60 y, respectively; P<0.001). Although there were significant differences in SES by race (P<0.001), regret did not differ by SES (ß =-1.53; P = 0.15). Race, postoperative sexual dysfunction, pad usage, and length of hospital stay, however, were significantly associated with decisional regret. CONCLUSIONS: AA men were more regretful than white men, after adjusting for clinicopathologic characteristics and postoperative functional outcomes.


Assuntos
Negro ou Afro-Americano/psicologia , Tomada de Decisões , Emoções , Laparoscopia/psicologia , Prostatectomia/psicologia , Neoplasias da Próstata/psicologia , Robótica , Adulto , Idoso , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Neoplasias da Próstata/cirurgia , Qualidade de Vida , Inquéritos e Questionários , População Branca/psicologia
17.
Urology ; 82(6): 1451.e1-6, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24139525

RESUMO

OBJECTIVE: To evaluate the degree of urothelial exposure using 3 upper tract delivery techniques in an ex vivo porcine model, to determine the optimal modality to locally deliver topical anticarcinogenic agents in patients with upper tract urothelial carcinoma. MATERIALS AND METHODS: An indigo carmine solution was infused into en bloc porcine urinary tracts to test the 3 techniques: antegrade infusion via nephrostomy tube, reflux via indwelling double-pigtail stent, and retrograde administration via a 5F open-ended ureteral catheter. Nine renal units (3 per delivery method) were used. After a 1-hour dwell time, the urinary tracts were bivalved and photographed. Each renal unit was evaluated by 3 blinded reviewers who estimated the total percentage of stained urothelial surface area using a computer-based area approximation system. In addition, as a surrogate for exposure adequacy, a validated equation was used to calculate the staining intensity at 6 predetermined locations in the upper tract, with lower values representing more efficient staining. RESULTS: Mean percent of surface area stained for the nephrostomy tube, double-pigtail stent, and open-ended ureteral catheter groups was 65.2%, 66.2%, and 83.6%, respectively (P = .002). Mean staining intensities were 40.9, 33.4, and 20.4, respectively (P = .023). CONCLUSION: Our results suggest that retrograde infusion via open-ended ureteral catheter is the most efficient method of upper tract therapy delivery. Larger studies using in vivo models should be performed to further validate these findings and potentially confirm this method as optimal for delivery of topical anticarcinogenic agents in upper tract urothelial carcinoma.


Assuntos
Anticarcinógenos/administração & dosagem , Sistema Urinário , Neoplasias Urológicas/tratamento farmacológico , Administração Tópica , Animais , Corantes , Modelos Animais de Doenças , Rim , Stents , Suínos , Ureter , Cateterismo Urinário/métodos , Urotélio
18.
Curr Opin Urol ; 23(4): 306-11, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23673511

RESUMO

PURPOSE OF REVIEW: Abdominal sacrocolpopexy has been considered the gold standard for vaginal vault prolapse repair for several decades. Although transvaginal approaches gained popularity as minimally invasive alternatives, complications related to the use of vaginal mesh have led surgeons to perform these repairs less frequently. By incorporating laparoscopic and robotic techniques into the traditional open abdominal sacrocolpopexy, surgeons can offer the benefits of minimally invasive surgery while avoiding risks of vaginal mesh. This review article aims to evaluate the efficacy and outcomes of abdominal sacrocolpopexy by comparing open, laparoscopic, and robotic assisted laparoscopic surgery. RECENT FINDINGS: The excellent outcomes of open abdominal sacrocolpopexy have repeatedly been shown in published, randomized data. This has been further validated in minimally invasive techniques through randomized data evaluating the outcomes of laparoscopic sacrocolpopexy. Among the various sacrocolpopexy techniques, outcomes are similar among the open, laparoscopic, and robotic approaches. Minimally invasive surgeries have been shown to have advantages in terms of perioperative morbidity. SUMMARY: The superior outcomes of abdominal sacrocolpopexy are available using minimally invasive techniques for pelvic organ prolapse repair. Further research with randomized data is required to establish how these approaches compare to each other. Given the inherent advantages of minimally invasive surgery, robotic or laparoscopic abdominal sacrocolpopexy may become the preferred approach to abdominal pelvic organ prolapse repair.


Assuntos
Laparoscopia , Prolapso de Órgão Pélvico/cirurgia , Robótica , Cirurgia Assistida por Computador , Procedimentos Cirúrgicos Urológicos/métodos , Feminino , Humanos , Laparoscopia/efeitos adversos , Cirurgia Assistida por Computador/efeitos adversos , Resultado do Tratamento , Procedimentos Cirúrgicos Urológicos/efeitos adversos
19.
Female Pelvic Med Reconstr Surg ; 18(6): 340-3, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23143427

RESUMO

OBJECTIVES: Few studies on health literacy and disease understanding among women with pelvic floor disorders have been published. We conducted a pilot study to explore the relationship between disease understanding and health literacy, age, and diagnosis type among women with urinary incontinence and pelvic organ prolapse. METHODS: The study subjects were recruited from urology and urogynecology specialty clinics based on a chief complaint suggestive of urinary incontinence or pelvic prolapse. Subjects completed questionnaires to assess symptom severity, and health literacy was measured using the Test of Functional Health Literacy in Adults. Patient-physician interactions were audiotaped during the office visit. Immediately afterward, patients were asked to describe diagnoses and treatments discussed by the physician and record them on a checklist, with follow-up phone call, where the same checklist was administered 2 to 3 days later. RESULTS: A total of 36 women with pelvic floor disorders, aged 42 to 94 years, were enrolled. We found that health literacy scores decreased with increasing age. However, all patients had low percentage recall of their pelvic floor diagnoses and poor understanding of their pelvic floor condition despite high health literacy scores. Patients with pelvic prolapse seemed to have worse recall and disease understanding than patients with urinary incontinence. CONCLUSIONS: High health literacy as assessed by the Test of Functional Health Literacy in Adults may not correlate with patients' ability to comprehend complex functional conditions such as pelvic floor disorders. Lack of understanding may lead to unrealistic treatment expectations, inability to give informed consent for treatment, and dissatisfaction with care. Better methods to improve disease understanding are needed.


Assuntos
Compreensão , Letramento em Saúde/estatística & dados numéricos , Distúrbios do Assoalho Pélvico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Satisfação do Paciente , Distúrbios do Assoalho Pélvico/psicologia , Projetos Piloto , Inquéritos e Questionários
20.
Australas Med J ; 5(4): 239-42, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22848318

RESUMO

BACKGROUND: The use of electronic resources in education, including i- applications used on portable handheld devices, is increasing. Apple® handheld devices are popular, with free applications the most prevalent download form. Many gross anatomy i- applications are available, however no information on the quality of free anatomy products is available. Rating such products could therefore guide product recommendations. AIM: To evaluate the quality and range of free iPod® applications that are applicable for tertiary level gross anatomy education. METHODS: A search of the iTunes® Application Store with keywords anatomy, free, medical, functional, clinical, gross, and human was performed, with inclusion based on free applications containing human gross anatomy usable for tertiary education purposes. Application specification was noted; each was trialled independently and rated for usability, specification, academic level, and quality (image and programme). RESULTS: Sixty-three applications were identified and eleven met inclusion criteria. Two provided gross anatomy of the entire body, nine examined specific regions or systems. Five were judged introductory in academic level, five intermediate, and one advanced. One application was rated low quality, and four excellent. None were considered difficult to use (six easy, five medium). Application size ranged between 1.2MB and 229MB (mean 27MB). CONCLUSIONS: There are few free i-applications for learning gross anatomy and most concentrate on individual body systems, with the academic level and usability of all products well rated. Results suggest some free I- applications could be suitable adjuncts for gross anatomy education at both an undergraduate and graduate level.

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