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INTRODUCTION: Expensive oral specialty drugs for advanced prostate cancer can be associated with treatment disparities. The 340B program allows hospitals to purchase medications at discounts, generating savings that can improve care of the socioeconomically disadvantaged. This study assessed the effect of hospital 340B participation on advanced prostate cancer. METHODS: The authors performed a retrospective cohort study of Medicare beneficiaries with advanced prostate cancer from 2012 to 2019. The primary outcome was use of an oral specialty drug. Secondary outcomes included monthly out-of-pocket costs and treatment adherence. We evaluated the effects of 1) hospital 340B participation, 2) a regional measure vulnerability, the social vulnerability index (SVI), and 3) the interaction between hospital 340B participation and SVI on outcomes. RESULTS: There were 2237 and 1100 men who received care at 340B and non-340B hospitals. There was no difference in specialty drug use between 340B and non-340B hospitals, whereas specialty drug use decreased with increased SVI (odds ratio, 0.95, p = .038). However, the interaction between hospital 340B participation and SVI on specialty drug use was not significant. Neither 340B participation, SVI, or their interaction were associated with out-of-pocket costs. Although hospital 340B participation and SVI were not associated with treatment adherence, their interaction was significant (p = .020). This demonstrated that 340B was associated with better adherence among socially vulnerable men. CONCLUSIONS: The 340B program was not associated with specialty drug use in men with advanced prostate cancer. However, among those who were started on therapy, 340B was associated with increased treatment adherence in more socially vulnerable men.
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Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/economía , Anciano , Estudios Retrospectivos , Estados Unidos , Administración Oral , Anciano de 80 o más Años , Medicare , Gastos en Salud/estadística & datos numéricos , Antineoplásicos/uso terapéutico , Antineoplásicos/economíaRESUMEN
BACKGROUND: Urologists practicing in single-specialty groups with ownership in radiation vaults are more likely to treat men with prostate cancer. The effect of divestment of vault ownership on treatment patterns is unclear. METHODS: A 20% sample of national Medicare claims was used to perform a retrospective cohort study of men with prostate cancer diagnosed between 2010 and 2019. Urology practices were categorized by radiation vault ownership as nonowners, continuous owners, and divested owners. The primary outcome was use of local treatment, and the secondary outcome was use of intensity-modulated radiation therapy (IMRT). A difference-in-differences framework was used to measure the effect of divestment on outcomes compared to continuous owners. Subgroup analyses assessed outcomes by noncancer mortality risk (high [>50%] vs. low [≤50%]). RESULTS: Among 72 urology practices that owned radiation vaults, six divested during the study. Divestment led to a decrease in treatment compared with those managed at continuously owning practices (difference-in-differences estimate, -13%; p = .03). The use of IMRT decreased, but this was not statistically significant (difference-in-differences estimate, -10%; p = .13). In men with a high noncancer mortality risk, treatment (difference-in-differences estimate, -28%; p < .001) and use of IMRT (difference-in-differences estimate, -27%; p < .001) decreased after divestment. CONCLUSIONS: Urology group divestment from radiation vault ownership led to a decrease in prostate cancer treatment. This decrease was most pronounced in men who had a high noncancer mortality risk. This has important implications for health care reform by suggesting that payment programs that encourage constraints on utilization, when appropriate, may be effective in reducing overtreatment.
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Neoplasias de la Próstata , Urólogos , Masculino , Humanos , Anciano , Estados Unidos , Estudios Retrospectivos , Propiedad , Medicare , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/diagnósticoRESUMEN
INTRODUCTION: Rural populations routinely rank poorly on common health indicators. While it is understood that rural residents face barriers to health care, the exact nature of these barriers remains unclear. To further define these barriers, a qualitative study of primary care physicians practicing in rural communities was performed. METHODS: Semistructured interviews were conducted with primary care physicians practicing in rural areas within western Pennsylvania, the third largest rural population within the USA, using purposively sampling. Data were then transcribed, coded, and analyzed by thematic analysis. RESULTS: Three key themes emerged from the analysis addressing barriers to rural health care: (1) cost and insurance, (2) geographic dispersion, and (3) provider shortage and burnout. Providers mentioned strategies that they either employed or thought would be beneficial for their rural communities: (1) subsidize services, (2) establish mobile and satellite clinics (particularly for specialty care), (3) increase utilization of telehealth, (4) improve infrastructure for ancillary patient support (ie social work services), and (5) increase utilization of advanced practice providers. CONCLUSION: There are numerous barriers to providing rural communities with quality health care. Barriers that are encountered are multidimensional. Patients are unable to obtain the care they need because of cost-related barriers. More providers need to be recruited to rural areas to combat the shortage and burnout. Advanced care-delivery methods such as telehealth, satellite clinics, or advanced practice providers can help bridge the gaps caused by geographic dispersion. Policy efforts should target all these aspects in order to appropriately address rural healthcare needs.
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Servicios de Salud Rural , Telemedicina , Humanos , Salud Rural , Investigación Cualitativa , Atención a la Salud , Población Rural , Accesibilidad a los Servicios de SaludRESUMEN
BACKGROUND: Surgeons play a pivotal role in combating the opioid crisis that currently grips the United States. Changing surgeon behavior is difficult, and the degree to which behavioral science can steer surgeons toward decreased opioid prescribing is unclear. METHODS: This was a single-institution, single-arm, pre- and postintervention study examining the prescribing of opioids by urologists for adult patients undergoing prostatectomy or nephrectomy. The primary outcome was the quantity of opioids prescribed in oral morphine equivalents (OMEs) after hospital discharge. The primary exposure was a multipronged behavioral intervention designed to decrease opioid prescribing. The intervention had 3 components: 1) formal education, 2) individual audit feedback, and 3) peer comparison performance feedback. There were 3 phases to the study: a pre-intervention phase, an intervention phase, and a washout phase. RESULTS: Three hundred eighty-two patients underwent prostatectomy, and 306 patients underwent nephrectomy. The median OMEs decreased from 195 to 19 in the prostatectomy patients and from 200 to 0 in the nephrectomy patients (P < .05 for both). The median OMEs prescribed did not increase during the washout phase. Prostatectomy patients discharged with opioids had higher levels of anxiety than patients discharged without opioids (P < .05). Otherwise, prostatectomy and nephrectomy patients discharged with and without opioids did not differ in their perception of postoperative pain management, activity levels, psychiatric symptoms, or somatic symptoms (P > .05 for all). CONCLUSIONS: Implementing a multipronged behavioral intervention significantly reduced opioid prescribing for patients undergoing prostatectomy or nephrectomy without compromising patient-reported outcomes.
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Analgésicos Opioides/administración & dosificación , Prescripciones de Medicamentos/estadística & datos numéricos , Morfina/administración & dosificación , Nefrectomía , Manejo del Dolor/métodos , Dolor Postoperatorio/tratamiento farmacológico , Prostatectomía , Administración Oral , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Manejo del Dolor/psicología , Medición de Resultados Informados por el Paciente , Cirujanos/psicología , Resultado del Tratamiento , Estados Unidos , Urólogos/psicologíaRESUMEN
PURPOSE: Clinical trials serve as a critical source of information to guide evidence-based practices in urology. Conversely, trials that are abandoned consume significant resources and results are underreported in the literature. MATERIALS AND METHODS: ClinicalTrials.gov was queried for urology trials from 2006 to 2016. Trials were screened by 2 screeners for applicability to urology and disputes were resolved by a third independent reviewer. Overall 1,340 trials met final inclusion criteria (722 successful trials, 618 failed trials). Univariable analysis used Fisher's exact, chi-squared and Wilcoxon rank sum tests. Trial characteristics, including AUA (American Urological Association) section, phase, subspecialty, intervention type, source of funding and randomization were examined for association with failure using multivariable logistic regression. RESULTS: Trial failure is associated with oncology subspecialty (adjusted odds ratio 2.25, 95% CI 1.60-3.18), infertility/andrology subspecialty (AOR 4.99, CI 1.60-17.61), device trials (AOR 1.64, CI 1.00-2.70) and combination funding by industry/government/grants (AOR 3.13, CI 2.21-4.48). Clinical trials in AUA sections were less likely to fail than international and multisectional trials. Among trials that failed, poor accrual was the primary reason for trial failure, comprising 41% of all failures. Other reasons for failure include inadequate budget (9%), sponsor cancellation (7%), poor interim results (7%) and toxicity (3%). CONCLUSIONS: Despite their significance, many urological trials fail prematurely due to poor accrual. Complex features inherent to oncology, andrology/infertility, devices and multisectional trials pose significant barriers to success.
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Ensayos Clínicos Controlados Aleatorios como Asunto , Predicción , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto/normasRESUMEN
PURPOSE: Compared to urban populations, rural populations rank poorly on numerous health indicators, including cancer outcomes. We examined the relationship of rural residence with stage and treatment among patients with prostate cancer, the second most common malignancy in men. MATERIALS AND METHODS: Using the Pennsylvania Cancer Registry we identified all men diagnosed with prostate cancer between 2009 and 2015. Patients were classified as residing in a rural area, a large town or an urban area using the Rural-Urban Commuting Area classification. Our primary outcomes included indicators of prostate cancer treatment and treatment types but we also examined disease stage and mortality. We used the chi-square tests to assess differences between groups and estimated multivariable logistic regression models to assess the association between rural residence and treatment. RESULTS: We identified 51,024 men diagnosed with localized or metastatic prostate cancer between 2009 and 2015. The overall incidence of prostate cancer decreased during the study period from 416 to 304/100,000 men while the incidence of metastatic disease increased from 336 to 538/100,000. Rural residents were less likely to undergo treatment than urban residents even when stratified by low, intermediate and high risk disease (aOR 0.77, 95% CI 0.64-0.91; aOR 0.71, 95% CI 0.58-0.89; and aOR 0.68, 95% CI 0.53-0.89, respectively). Rural status did not affect the receipt of radiation therapy compared to other treatment types. CONCLUSIONS: Prostate cancer treatment differs between urban and rural residents. Rural residents are less likely to receive treatment even when stratified by disease risk.
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Neoplasias de la Próstata/terapia , Población Rural , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pennsylvania/epidemiología , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Sistema de RegistrosRESUMEN
OBJECTIVE: To examine factors associated with PET scan use in the pre-operative evaluation of patients diagnosed with bladder cancer. METHODS: Using SEER-Medicare data, we identified bladder cancer patients who underwent radical cystectomy from 2006 to 2011 (n = 4,138). The primary outcome was PET scan use within 6 months before surgery. To examine predictors of PET scan use, we fit a mixed logit model with health service area as a random effect to account for patients nested within health service areas. We also calculated the adjusted probability of use over time and examined variation among the highest volume surgeons. RESULTS: Among the 4,138 patients, 406 (10%) received a pre-operative PET scan. The adjusted probability of a patient undergoing a PET scan increased from 0.04 in 2004 to 0.10 in 2011 (p < .001). Among the 78 highest volume surgeons, there was significant variation in PET scan use (p < .001). Patients with non-urothelial histology, measurement of alkaline phosphatase levels, and receipt of neoadjuvant chemotherapy were more likely to receive PET scan (all p < .05). CONCLUSION: Use of PET prior to radical cystectomy doubled over a 5-year period, suggesting its increased use in patients with muscle-invasive bladder cancer, particularly those with high-risk disease. Whether its use is warranted and improves patient outcomes is not clear and requires further studies.
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Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Transicionales/diagnóstico por imagen , Cistectomía , Medicare , Tomografía de Emisión de Positrones/tendencias , Neoplasias de la Vejiga Urinaria/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Fosfatasa Alcalina/sangre , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/cirugía , Femenino , Humanos , Modelos Logísticos , Masculino , Músculo Liso/patología , Terapia Neoadyuvante , Invasividad Neoplásica , Cuidados Preoperatorios/tendencias , Programa de VERF , Estados Unidos , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/cirugía , Derivación UrinariaRESUMEN
Numerous studies have sought to examine the relationship between hypogonadal symptoms and total serum testosterone levels in men in order to identify a threshold at which symptoms occur and at which treatment is beneficial. However, the search for a discrete threshold may be futile given emerging evidence. Recent studies suggest that testosterone threshold varies by symptoms and among individuals. In addition, thresholds may vary between young and old men. Therefore, initiation of treatment should rely more on symptoms and less on a discrete numerical threshold.
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Terapia de Reemplazo de Hormonas/métodos , Hipogonadismo/tratamiento farmacológico , Testosterona/deficiencia , Testosterona/uso terapéutico , Humanos , MasculinoRESUMEN
ER stress leads to upregulation of multiple folding and quality control components, known as the unfolded protein response (UPR). Glucose Regulated Protein 78 (GRP78) (also known as binding immunoglobulin protein, BiP, and HSPA5) and GRP94 are often upregulated coordinately as part of this homeostatic response. Given that endoplasmic reticulum (ER) chaperones have distinct sets of clients, we asked how cells respond to ablation of individual chaperones. The cellular responses to silencing BiP, GRP94, HSP47, PDIA6 and OS-9, were distinct. When BiP was silenced, a widespread UPR was observed, but when GRP94 was either inhibited or depleted by RNA interference (RNAi), the expression of only some genes was induced, notably those encoding BiP and protein disulfide isomerase A6 (PDIA6). Silencing of HSP47 or OS-9 did not lead to any compensatory induction of other genes. The selective response to GRP94 depletion was distinct from a typical ER stress response, both because other UPR target genes were not affected and because the canonical UPR signaling branches were not activated. The response to silencing of GRP94 did not preclude further UPR induction when chemical stress was imposed. Importantly, re-expression of wild-type GRP94 in the silenced cells prevented the upregulation of BiP and PDIA6, whereas re-expression of an ATPase-deficient GRP94 mutant did not, indicating that cells monitor the activity state of GRP94. These findings suggest that cells are able to distinguish among folding resources and generate distinct responses.
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Proteínas de Choque Térmico , Glicoproteínas de Membrana , Pliegue de Proteína , Respuesta de Proteína Desplegada/genética , Animales , Chaperón BiP del Retículo Endoplásmico , Estrés del Retículo Endoplásmico/genética , Silenciador del Gen , Células HeLa , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Humanos , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Ratones , Células 3T3 NIH , Proteína Disulfuro Isomerasas/genética , Proteína Disulfuro Isomerasas/metabolismo , Transducción de SeñalRESUMEN
PURPOSE: Community factors and structural barriers may contribute to disparities and underrepresentation in cancer clinical trials. We evaluate the influence of community-level social determinants of health, as measured by the Centers for Disease Control and Prevention Social Vulnerability Index (SVI), on disparities in cancer clinical trial discussion and participation. METHODS: We performed a cross-sectional analysis of the 2021 Health Information National Trends Survey-SEER, a representative survey of cancer survivors sampled from three SEER registries. The primary outcomes included patient-reported clinical trial discussion and participation. The primary exposure was county-level SVI, linked to each survey respondent by ZIP code of residence and categorized into quintiles. Survey-weighted bivariate comparisons and multivariable logistic regression were performed to evaluate the association between SVI and clinical trial discussion and participation, adjusting for age, sex, race and ethnicity, education, income, and cancer stage. RESULTS: We identified 1,220 respondents residing in 153 counties with a median SVI of 0.41 (IQR, 0.27-0.62), representing a population of over 400,000 cancer survivors on weighted analysis. Of the cohort, 15.1% reported clinical trial discussion and 7.7% reported clinical trial participation. Patients who are most socially vulnerable (fifth quintile of SVI) had significantly lower odds of clinical trial discussion (odds ratio [OR], 0.36 [95% CI, 0.15 to 0.87]; P = .02) and clinical trial participation (OR, 0.15 [95% CI, 0.03 to 0.75]; P = .02) compared with patients who are least socially vulnerable (first quintile of SVI). CONCLUSION: These findings suggest interventions to identify socially vulnerable communities for expansion of clinical trial opportunities and infrastructure may be an impactful strategy toward improving diversity and representation in cancer clinical trials.
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OBJECTIVE: To evaluate the association between a population-level measure of social determinants of health, the Centers for Disease Control and Prevention Social Vulnerability Index (SVI), and receipt of neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy. METHODS: We queried our institutional database for patients with nonmetastatic MIBC treated with radical cystectomy between 2000 and 2022. Patients were assigned an SVI via ZIP code of residence and grouped into quintiles of SVI (ie, least vulnerable to most vulnerable). Multivariable logistic regression was performed to evaluate the association between SVI and receipt of neoadjuvant chemotherapy, adjusting for age, race, gender, and cancer stage. A sub-analysis was performed to evaluate the association between subthemes of SVI (socioeconomic status, household composition/disability, race/ethnicity/language, and housing/transportation) and receipt of neoadjuvant chemotherapy. RESULTS: Of the 978 patients identified, 490 (50.1%) received neoadjuvant chemotherapy. Patients that received neoadjuvant chemotherapy had a lower SVI, were younger, and had >cT2 stage (all, P <.05). The most vulnerable patients had lower odds of receiving neoadjuvant chemotherapy (OR 0.61, 0.39-0.95) compared to the least vulnerable patients. Analysis of subthemes of SVI demonstrated similar associations by socioeconomic status (OR 0.56, 0.36-0.86) and household composition/disability (OR 0.57, 0.33-0.99). CONCLUSION: Adverse social determinants of health, or social vulnerability, are associated with suboptimal and disparate utilization of neoadjuvant chemotherapy in patients with MIBC undergoing radical cystectomy. Strategies for identifying vulnerable populations may allow for more targeted interventions that would improve equity in bladder cancer care.
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BACKGROUND: Deciding whether to treat or conservatively manage patients with prostate cancer is challenging. Recent changes in guidelines, advances in treatment technologies, and policy can influence decision making surrounding management, particularly for those for whom the decision to treat is discretionary. Contemporary trends in management of newly diagnosed prostate cancer are unclear. METHODS: Using national Medicare data, men with newly diagnosed prostate cancer were identified between 2014 and 2019. Patients were classified by 5- and 10-year noncancer mortality risk. Multinomial logistic regression models were fit to assess adjusted trends in management over time. The primary outcome was management of prostate cancer: local treatment (inclusive of surgery, radiation, brachytherapy, or cryotherapy), hormone therapy, or observation. RESULTS: Local treatment was the most common form of management and stable across years (68%). Use of observation increased (21%-23%, P < .001) and use of hormone therapy decreased (11%-8%, P < 0.001). After stratifying by 10-year non-cancer mortality risk, observation increased among men with low (22.3%-26.1%, P < .001) and moderate (19.9%-23.5%, P < .001) mortality risk. Conversely, use of treatment increased among those with high (62.8%-68.0%, P = .004) and very high (45.5%-54.1%, P < .001) risk of noncancer mortality. These trends were similar across groups when stratified by 5-year noncancer mortality risk. CONCLUSION: Nationally, use of local treatment remains common and was stable throughout the study period. However, while local treatment declined among men with a lower risk of noncancer mortality, it increased among men with a higher risk of non-cancer mortality.
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Braquiterapia , Neoplasias de la Próstata , Masculino , Humanos , Anciano , Estados Unidos/epidemiología , Medicare , Neoplasias de la Próstata/cirugía , Modelos Logísticos , HormonasRESUMEN
INTRODUCTION: We performed a study to evaluate the association between urologist performance in the Merit-Based Incentive Payment System (MIPS), and quality and spending for prostate cancer care. METHODS: Medicare beneficiaries with prostate cancer diagnosed between 2017 and 2019 were assigned to their primary urologist. Associated MIPS scores were identified and categorized based on thresholds for payment adjustment as low (worst), moderate, and high (best). Multivariable mixed effects models were used to measure the association between MIPS performance and adherence to quality measures and price standardized spending for prostate cancer. RESULTS: Adherence to quality measures did not vary across MIPS performance groups for pretreatment counselling by both a urologist and radiation oncologist (low-76%, [95% CI 73%-80%], moderate-77% [95% CI 74%-79%], and high-75% [95% CI 74%-76%]) and avoiding treatment in men with a high risk of noncancer mortality within 10 years of diagnosis (low-40% [95% CI 35%-45%], moderate-39% [95% CI 36%-43%], high-38% [95% CI 36%-39%]). Men on active surveillance managed by high performers more likely received a confirmatory test (44% [95% CI 43%-46%]) compared to those managed by moderate (38% [95% CI 33%-42%]) performers, but not low performers (36% [95% CI 29%-44%]). There was no difference in adjusted spending across MIPS performance groups. CONCLUSIONS: Better performance in MIPS is associated with a higher rate of confirmatory testing in men initiating active surveillance for prostate cancer. However, performance was not associated with other dimensions of quality nor spending.
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Medicare , Neoplasias de la Próstata , Masculino , Humanos , Anciano , Estados Unidos , Urólogos , Motivación , Neoplasias de la Próstata/diagnóstico , PróstataRESUMEN
OBJECTIVE: To examine the effect of urologist participation in value-based payment models on the initial management of men with newly diagnosed prostate cancer. METHODS: Medicare beneficiaries with prostate cancer diagnosed between 2017 and 2019, with 1 year of follow-up, were assigned to their primary urologist, each of whom was then aligned to a value-based payment model (the merit-based incentive payment system [MIPS], accountable care organization [ACO] without financial risk, and ACO with risk). Multivariable mixed-effects logistic regression was used to measure the association between payment model participation and treatment of prostate cancer. Additional models estimated the effects of payment model participation on use of treatment in men with very high risk (i.e., >75%) of non-cancer mortality within 10 years of diagnosis (i.e., a group of men for whom treatment is generally not recommended) and price-standardized prostate cancer spending in the 12 months after diagnosis. RESULTS: Treatment did not vary by payment model, both overall (MIPS-67% [95% CI 66%-68%], ACOs without risk-66% [95% CI 66%-68%], ACOs with risk-66% [95% CI 64%-68%]). Similarly, treatment did not vary among men with very high risk of non-cancer mortality by payment model (MIPS-52% [95% CI 50%-55%], ACOs without risk-52% [95% CI 50%-55%], ACOs with risk-51% [95% CI 45%-56%]). Adjusted spending was similar across payment models (MIPS-$16,501 [95% CI $16,222-$16,780], ACOs without risk-$16,140 [95% CI $15,852-$16,429], ACOs with risk-$16,117 [95% CI $15,585-$16,649]). CONCLUSIONS: How urologists participate in value-based payment models is not associated with treatment, potential overtreatment, and prostate cancer spending in men with newly diagnosed disease.
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Organizaciones Responsables por la Atención , Medicare , Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/terapia , Neoplasias de la Próstata/economía , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/mortalidad , Medicare/economía , Estados Unidos , Anciano , Organizaciones Responsables por la Atención/economía , Anciano de 80 o más Años , Urólogos/economía , Reembolso de Incentivo/economía , Gastos en SaludRESUMEN
B cells are subjected to selection at multiple checkpoints during their development. The selection of Ab H chains is difficult to study because of the large diversity of the CDR3. To study the selection of individual Ab H chain V region genes (V(H)), we performed CDR3 spectratyping of â¼ 75-300 rearrangements per individual V(H) in C57BL6/J mice. We measured the fraction of rearrangements that were in-frame in B cell DNA. We demonstrate that individual V(H)s have different fractions of in-frame rearrangements (IF fractions) ranging from 10 to 90% and that these IF fractions are reproducible in different mice. For most V(H)s, the IF fraction in pro-B cells approximated 33% and then shifted to the nearly final (mature) B cell value by the cycling pre-B cell stage. The frequency of high in-frame (IF) V(H) usage increased in cycling pre-B cells compared with that in pro-B cells, whereas this did not occur for low IF V(H)s. The IF fraction did not shift as much in BCR-expressing B cells and was minimally affected by L chain usage for most V(H). High IF clan II/III V(H)s share more positively charged CDR2 sequences, whereas high IF clan I J558 CDR2 sequences are diverse. These data indicate that individual V(H)s are subjected to differential selection, that V(H) IF fraction is mainly established through pre-BCR-mediated selection, that it may operate differently in clan I versus II/III V(H)s, and that it has a lasting influence on the Ab repertoire.
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Regiones Determinantes de Complementariedad/metabolismo , ADN/metabolismo , Células Precursoras de Linfocitos B/metabolismo , Hipermutación Somática de Inmunoglobulina/fisiología , Animales , Regiones Determinantes de Complementariedad/genética , Regiones Determinantes de Complementariedad/inmunología , ADN/genética , ADN/inmunología , Regulación de la Expresión Génica/fisiología , Ratones , Células Precursoras de Linfocitos B/citología , Células Precursoras de Linfocitos B/inmunología , Proteínas Proto-Oncogénicas c-bcr/biosíntesis , Proteínas Proto-Oncogénicas c-bcr/genética , Proteínas Proto-Oncogénicas c-bcr/inmunologíaRESUMEN
The management of prostate cancer has significantly evolved over the last few decades with the emergence of new diagnostic and treatment technologies, which are typically more expensive than the previous alternatives. However, decision-making regarding which diagnostics and treatment to pursue is often influenced by perceived benefits, adverse effects, and physician recommendations, without considering the financial liability borne by patients. New technologies may exacerbate financial toxicity by replacing less costly alternatives, promoting unrealistic expectations, and expanding treatment to those who would have previously gone untreated. More judicious use of technologies with an understanding of the contexts in which they are most beneficial may help prevent avoidable financial toxicity to patients.
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Estrés Financiero , Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/terapia , Neoplasias de la Próstata/prevención & controlRESUMEN
INTRODUCTION: Most urologists are required to participate in Merit-based Incentive Payment System-an alternative payment model in which physicians must track and report quality measures. However, Merit-based Incentive Payment System measures are urology-specific, and it remains unclear what measures urologists are choosing to track and report. METHODS: We performed a cross-sectional analysis of Merit-based Incentive Payment System measures reported by urologists for the most recent performance year. Urologists were categorized by their reporting affiliation (ie, individual, group, or alternative payment model). We identified the measures most frequently reported by urologists. Among reported measures, we identified those that were specific to urological conditions and those that were "topped out" (ie, measures considered indiscriminate by Medicare because high performance is easily achieved). RESULTS: A total of 6,937 urologists reported in Merit-based Incentive Payment System during the 2020 performance year, of whom 14% reported as an individual, 56% as a group, and 30% as an alternative payment model. Among the top 10 most frequently reported measures, none were urology-specific. Eleven percent of urologists reported measures that were directly specific to urological conditions; 65% of individual urologists, 58% of those in groups, and 92% in alternative payment models reported at least 1 or more "topped out" measures. CONCLUSIONS: Most measures reported by urologists are not specific to urological conditions, and therefore performance within Merit-based Incentive Payment System may be a poor indicator of the quality of urological care provided. As Medicare transitions Merit-based Incentive Payment System to implement specific quality measures, the urological community will need to develop and submit measures that will be most impactful for urology patients.