RESUMEN
Total sialic acid content (TSA) in biotherapeutic proteins is often a critical quality attribute as it impacts the drug efficacy. Traditional wet chemical assays to quantify TSA in biotherapeutic proteins during cell culture typically takes several hours or longer due to the complexity of the assay which involves isolation of sialic acid from the protein of interest, followed by sample preparation and chromatographic based separation for analysis. Here, we developed a machine learning model-based technology to rapidly predict TSA during cell culture by using typically measured process parameters. The technology features a user interface, where the users only have to upload cell culture process parameters as input variables and TSA values are instantly displayed on a dashboard platform based on the model predictions. In this study, multiple machine learning algorithms were assessed on our dataset, with the Random Forest model being identified as the most promising model. Feature importance analysis from the Random Forest model revealed that attributes like viable cell density (VCD), glutamate, ammonium, phosphate, and basal medium type are critical for predictions. Notably, while the model demonstrated strong predictability by Day 14 of observation, challenges remain in forecasting TSA values at the edges of the calibration range. This research not only emphasizes the transformative power of machine learning and soft sensors in bioprocessing but also introduces a rapid and efficient tool for sialic acid prediction, signaling significant advancements in bioprocessing. Future endeavors may focus on data augmentation to further enhance model precision and exploration of process control capabilities.
RESUMEN
Background: Stroke is a leading cause of long-term disability among stroke survivors. Despite the availability of numerous stroke rehabilitative therapies, such as mirror therapy, bilateral arm training, and robot-assisted therapy, the recovery of motor function after stroke remains incomplete. Bilateral arm function is a key component in stroke patients to perform activities of daily living and to reflect their functional autonomy. Objective: This clinimetric study investigated and compared the construct validity and responsiveness of 2 bimanual activity outcome measures, the Chedoke Arm and Hand Activity Inventory (CAHAI) and the ABILHAND Questionnaire, in individuals receiving stroke rehabilitation. Methods: The present study is a secondary analysis following the framework of the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN). Individuals with chronic stroke (N = 113) were recruited from outpatient rehabilitation settings. Participants received 18 to 20 sessions of robot-assisted therapy, mirror therapy, combined therapy, or conventional rehabilitation for 4 to 6 weeks. The CAHAI, ABILHAND Questionnaire, and a comparison instrument, the Motor Activity Log (MAL), were administered twice at a 4- to 6-week interval to all participants. ABILHAND scores, in logits, were converted from raw ordinal scores into a linear measure. Results: There was medium to large correlation of the CAHAI and the MAL (ρ = 0.60-0.62, p < 0.01) as well as the ABILHAND Questionnaire and the MAL (ρ = 0.44-0.51, p < 0.01). Change scores from the initial measurement to the post-intervention measurement demonstrated small to medium correlation of the CAHAI and the MAL (ρ = 0.27-0.31, p < 0.01) and medium to large correlation of the ABILHAND Questionnaire and the MAL (ρ = 0.37-0.41, p < 0.01). Overall, 7 of 8 hypotheses were supported. The hypothesis testing regarding the construct validity and responsiveness of the CAHAI and ABILHAND Questionnaire was confirmed. Conclusion: The CAHAI and ABILHAND Questionnaire are both responsive and suitable to detect changes in bilateral arm functional daily activities in individuals with chronic stroke. Patient-reported outcome measures are recommended to use along with therapist-rated outcome measures for upper limb capacity evaluation in stroke rehabilitation. Further study with a prospective study design to capture specific clinical features of participants and the use of body-worn sensors, such as the arm accelerometer, is suggested.
RESUMEN
INTRODUCTION: Prostate cancer (PCa) is the most common non-cutaneous tumor among American men. Androgen receptor signaling inhibitors such as abiraterone and enzalutamide have been approved for similar disease states among patients with advanced PCa. Existing data suggest using steroids is associated with an increased risk of infection. Because abiraterone is usually prescribed with prednisone, we sought to compare the risk of septicemia in patients using abiraterone vs. enzalutamide. MATERIALS AND METHODS: We utilized the SEER-Medicare-linked data and used negative binomial regression models to compare the changes in the rates of septicemia-related hospitalizations six months pre- and post-abiraterone and enzalutamide initiation. RESULTS: We found that the incidence of septicemia-related hospitalizations increased 2.77 fold within six months of initiating abiraterone (incidence rate ratio [IRR]: 2.77, 95% confidence interval [CI]: 2.17-3.53) 1.97 fold within six months of starting enzalutamide (IRR: 1.97, 95% CI: 1.43-2.72). However, the difference in the changes did not reach statistical significance (interaction IRR: 0.71, 95% CI: 0.48-1.06). DISCUSSION: The findings suggest that both abiraterone and enzalutamide are associated with an increased risk of septicemia-related hospitalizations. However, the difference in the increase of septicemia risk following the two treatments did not reach statistical significance. Further studies are warranted to understand the mechanisms at play.
Asunto(s)
Androstenos , Benzamidas , Nitrilos , Feniltiohidantoína , Sepsis , Humanos , Masculino , Feniltiohidantoína/uso terapéutico , Feniltiohidantoína/análogos & derivados , Feniltiohidantoína/efectos adversos , Nitrilos/uso terapéutico , Benzamidas/uso terapéutico , Sepsis/epidemiología , Sepsis/inducido químicamente , Anciano , Androstenos/uso terapéutico , Androstenos/efectos adversos , Anciano de 80 o más Años , Estados Unidos/epidemiología , Hospitalización/estadística & datos numéricos , Programa de VERF , Neoplasias de la Próstata/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Antineoplásicos/efectos adversos , Incidencia , MedicareRESUMEN
INTRODUCTION: Evidence is limited on whether fibroblast growth factor receptor gene alterations (FGFRalt) impact clinical outcomes in patients with locally advanced or metastatic urothelial cancer (mUC). This study evaluated progression-free survival (PFS) in patients with mUC based on FGFRalt status in the first-line setting (1L). PATIENTS AND METHODS: Data on mUC patients were retrieved via convenience sampling of oncologists/urologists surveyed between August and September 2020 who treated at least 1 FGFRalt patient between July 2017 and June 2019. The questionnaire included information on patient demographics, FGFR status, treatment, and clinical and radiographic measures of progression. Primary endpoint was time from metastatic diagnosis to disease progression from initial treatment for FGFRalt and FGFRwt (wild-type) mUC. Cox proportional hazards models quantified adjusted risk of FGFR status relating to PFS. RESULTS: A total of 414 patients were analyzed. Mean age was 64.5 years, 73.9% were male, and 52.7% had an FGFRalt. Among FGFRalt, 47.2% received chemotherapy, 27.5% immune checkpoint inhibition (ICI), 11.5% chemotherapy+ICI, and 13.8% other treatments in 1L. FGFR status did not influence PFS from time of mUC diagnosis or among 224 stratified patients receiving either chemotherapy or chemotherapy+ICI. However, among 97 patients with an FGFRalt receiving 1L ICI therapy only, adjusted risk of progression was twice that of FGFRwt (HR: 2.12; 95% CI: 1.13-4.00). CONCLUSION: Although FGFRalt did not predict outcomes in the overall cohort, for patients treated with 1L ICI, FGFRalt had significantly higher rates of progression than FGFRwt patients. Further validation is needed to determine whether FGFRalt has a decreased benefit from ICI therapy.
Asunto(s)
Receptores de Factores de Crecimiento de Fibroblastos , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Pronóstico , Receptores de Factores de Crecimiento de Fibroblastos/genética , Carcinoma de Células Transicionales/genética , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/secundario , Carcinoma de Células Transicionales/mortalidad , Carcinoma de Células Transicionales/patología , Supervivencia sin Progresión , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/mortalidad , Mutación , Estudios Retrospectivos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Progresión de la EnfermedadRESUMEN
This study examined the relative and absolute reliability of the Taiwanese version of the MoCA (MoCA-T) in people with stroke. The study recruited 114 individuals who were at least 3 months after the onset of a first-ever unilateral stroke. The MoCA-T was administered twice, at a 6-week interval, to all participants. The relative reliability was assessed using the intraclass correlation coefficient (ICC), and the absolute reliability was assessed using standard error of measurement (SEM), the smallest real difference (SRD), the SRD percentage, and the Bland-Altman method. The ICC analysis showed the MoCA-T was highly reliable (ICCâ =â 0.85). The absolute reliability was between an acceptable and excellent level, where the SEM and the SRD at the 95% confidence interval were 1.38 and 3.83, respectively. The Bland-Altman analyses showed no systematic bias between repeated measurements. The range of the 95% limits of agreement was narrow, indicating a high level of stability over time. These findings suggest that the MoCA-T has high agreement between repeated measurements without systematic bias. The threshold to detect real change stands between an acceptable and excellent level. The MoCA-T is a reliable tool for cognitive screening in stroke rehabilitation.
Asunto(s)
Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Humanos , Reproducibilidad de los Resultados , Pruebas de Estado Mental y Demencia , Examen NeurológicoRESUMEN
BACKGROUND: Identification of emerging molecular biomarkers on circulating tumor cells (CTCs) represents an attractive feature of liquid biopsy that facilitates precision and tailored medicine in the management of metastatic castration-resistant prostate cancer (mCRPC). Prostein is an androgen-regulated transmembrane protein with high prostate specificity. Prostein-positive circulating tumor cell (CTC) was recently suggested to have diagnostic potential; however, no study has been conducted to evaluate its prognostic value in mCRPC. METHODS: CTCs from mCRPC patients were enumerated using the CellSearch System. Prostein-positive CTCs were identified by immunostaining results. The relationships between prostein expression on CTCs and PSA response rate, PSA progression-free survival (PSA-PFS), radiographic progression-free survival (PFS), and overall survival (OS) were tested by Fisher's exact test or evaluated using Kaplan-Meier and multivariate Cox analyses. RESULTS: Prostein-positive CTCs were identified in 31 of 87 baseline samples from mCRPC patients and 16 of 51 samples collected at the first follow-up visit. PSA response rates were significantly lower in baseline prostein-positive patients (0%, 0/31) than in prostein-negative patients (19.6%, 11/56) (p = 0.007). The 31 prostein-positive patients had significantly shorter PSA-PFS (p < 0.001), radiographic PFS (p < 0.001), and OS (p = 0.018), compared to the 56 prostein-negative patients at baseline. The association with PSA-PFS maintained its significance (p = 0.028) in multivariate analyses. Analyzing prostein expression at the first follow-up as well as the conversion of prostein expression from baseline to follow-up samples not only confirmed the association with PSA-PFS, but also demonstrated prognostic significance with OS. CONCLUSION: Our study provides the first evidence to support the potential of prostein expression on CTCs to serve as a novel prognostic marker in mCRPC patients. Future large-scale prospective studies are needed to validate our findings.
RESUMEN
The purpose of this study is to understand psychosocial impacts on cancer survivors using the patient-reported outcomes measurement information system (PROMIS) Psychosocial Illness Impact banks. Cancer survivors (n = 509; age: 59.5 ± 1.4; 51.5% men) completed the PROMIS positive and negative illness impact items consisting of four sub-domains: self-concept (SC), social impact (SI), stress response (SR), and spirituality (Sp). Illness impact was defined as changed scores from items measuring "current" experiences to recalled experiences prior to cancer diagnosis. Descriptive statistics, effect sizes (ES), and coefficient of variation (CV) were calculated at item and sub-domain levels. Analysis of variance was used to identify potentially influential factors on the impacts. Our study found survivors reported stronger positive than negative impacts (overall ES mean: 0.30 vs. 0.23) in general; and more moderate (ES ⧠0.30) positive than negative impacts at the item level, 54.3% (25 of 46) and 40% (16 of 40) for positive and negative items, respectively. Participants reported more positive impacts on SI and Sp but more negative impacts on SR. The CV results showed more individual differences appeared on positive SC items. Younger survivors reported stronger positive and negative impacts. Women reported higher positive impacts. Survivors with higher education levels tended to have higher positive SI impacts, while those with a lower family income reported higher negative SI and negative SR impacts. We conclude positive and negative psychosocial impacts coexisted-the strength of impacts varied across sub-domains. Age, gender, education, and family income influenced the psychosocial impacts reported by survivors. These findings provide a foundation to develop interventions to strengthen positive and minimize negative impacts and improve cancer survivors' overall well-being.
Asunto(s)
Supervivientes de Cáncer , Neoplasias , Masculino , Humanos , Femenino , Persona de Mediana Edad , Sobrevivientes , Correlación de Datos , EscolaridadRESUMEN
Androgen deprivation therapy is the cornerstone of prostate cancer therapy. Recent studies have revealed an association between androgen deprivation therapy and cardiovascular adverse effects such as myocardial infarction and stroke. This review summarizes the available research on the cardiovascular risk of men using androgen deprivation therapy. We also discuss racial disparities surrounding both prostate cancer and cardiovascular disease, emphasizing the importance of biological/molecular and socioeconomic factors in assessing baseline risk in patients beginning androgen ablation. Based on the literature, we provide recommendations for monitoring patients who are at high risk for a cardiovascular adverse event while being treated on androgen deprivation therapy. This review aims to present the current research on androgen deprivation therapy and cardiovascular toxicity with an emphasis on racial disparities and provides a framework for clinicians to decrease the cardiovascular morbidity in men that are being treated with hormone therapy.
RESUMEN
OBJECTIVE: To examine the effects of bilateral robotic priming combined with mirror therapy (R-mirr) vs bilateral robotic priming combined with bilateral arm training (R-bilat), relative to the control approach of bilateral robotic priming combined with movement-oriented training (R-mov) in patients with stroke. DESIGN: A single-blind, preliminary, randomized controlled trial. SETTING: Four outpatient rehabilitation settings. PARTICIPANTS: Outpatients with stroke and mild to moderate motor impairment (N=63). INTERVENTIONS: Patients received 6 weeks of clinic-based R-mirr, R-bilat, or R-mov for 90 min/d, 3 d/wk, plus a transfer package at home for 5 d/wk. MAIN OUTCOME MEASURES: Fugl-Meyer Assessment Upper Extremity subscale (FMA-UE), ABILHAND, and Stroke Impact Scale v3.0 scores before, immediately after, and 3 months after treatment as well as lateral pinch strength and accelerometry before and immediately after treatment. RESULTS: The posttest results favored R-mirr over R-bilat and R-mov on the FMA-UE score (P<.05). Follow-up analysis revealed that significant improvement in FMA-UE score was retained at the 3-month follow-up in the R-mirr over R-bilat or R-mov (P<.05). Significant improvements were not observed in the R-mirr over R-bilat and R-mov on other outcomes. CONCLUSIONS: Between-group differences were only detected for the primary outcome, FMA-UE. R-mirr was more effective at enhancing upper limb motor improvement, and the effect has the potential to be maintained at 3 months of follow-up.
Asunto(s)
Procedimientos Quirúrgicos Robotizados , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Humanos , Brazo , Terapia del Movimiento Espejo , Método Simple Ciego , Recuperación de la Función , Extremidad Superior , Resultado del TratamientoRESUMEN
BACKGROUND: Personalized genomic classifiers have transformed the management of prostate cancer (PCa) by identifying the most aggressive subsets of PCa. Nevertheless, the performance of genomic classifiers to risk classify African American men is thus far lacking in a prospective setting. METHODS: This is a prospective study of the Decipher genomic classifier for National Comprehensive Cancer Network low- and intermediate-risk PCa. Study-eligible non-African American men were matched to African American men. Diagnostic biopsy specimens were processed to estimate Decipher scores. Samples accrued in NCT02723734, a prospective study, were interrogated to determine the genomic risk of reclassification (GrR) between conventional clinical risk classifiers and the Decipher score. RESULTS: The final analysis included a clinically balanced cohort of 226 patients with complete genomic information (113 African American men and 113 non-African American men). A higher proportion of African American men with National Comprehensive Cancer Network-classified low-risk (18.2%) and favorable intermediate-risk (37.8%) PCa had a higher Decipher score than non-African American men. Self-identified African American men were twice more likely than non-African American men to experience GrR (relative risk [RR] = 2.23, 95% confidence interval [CI] = 1.02 to 4.90; P = .04). In an ancestry-determined race model, we consistently validated a higher risk of reclassification in African American men (RR = 5.26, 95% CI = 1.66 to 16.63; P = .004). Race-stratified analysis of GrR vs non-GrR tumors also revealed molecular differences in these tumor subtypes. CONCLUSIONS: Integration of genomic classifiers with clinically based risk classification can help identify the subset of African American men with localized PCa who harbor high genomic risk of early metastatic disease. It is vital to identify and appropriately risk stratify the subset of African American men with aggressive disease who may benefit from more targeted interventions.
Asunto(s)
Prostatectomía , Neoplasias de la Próstata , Masculino , Humanos , Estudios Prospectivos , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Negro o Afroamericano/genética , Pruebas GenéticasRESUMEN
Arsenic is a crucial environmental metalloid whose high toxicity levels negatively impact human health. It poses significant health concerns to millions of people in developed and developing countries such as the USA, Canada, Bangladesh, India, China, and Mexico by enhancing sensitivity to various types of diseases, including cancers. However, how arsenic causes changes in gene expression that results in heinous conditions remains elusive. One of the proposed essential mechanisms that still has seen limited research with regard to causing disease upon arsenic exposure is the dysregulation of epigenetic components. In this review, we have extensively summarized current discoveries in arsenic-induced epigenetic modifications in carcinogenesis and angiogenesis. Importantly, we highlight the possible mechanisms underlying epigenetic reprogramming through arsenic exposure that cause changes in cell signaling and dysfunctions of different epigenetic elements.
RESUMEN
INTRODUCTION: Abiraterone acetate and enzalutamide are commonly employed in prostate cancer therapy in an interchangeable manner. These drugs are highly efficacious in androgen antagonism to improve patient outcomes, but they also carry noteworthy risk of adverse effects. Common toxicities vary amongst the two drugs and may have differential interactions with patient co-morbidities, but these patterns are unclear as co-morbidities typically serve as exclusion criteria in clinical trials. Hence, there is no existing guidance on how clinicians may tailor treatment based on patient-specific factors. Analysis of differential patient outcomes between these two drugs can inform future systematic reviews, new clinical studies, and clinical decision making. METHOD AND ANALYSIS: The framework for this methodology was informed by the Joanna Briggs Institute methodology for scoping reviews. Title and abstract screening will be performed by two independent researchers to create an initial study inventory. This will be followed by full-text screening for study inclusion. Population-based studies describing patient outcomes, common toxicities, and associations with patient co-morbidities following abiraterone or enzalutamide therapy will be included. After data is extracted, it will be summarized for presentation. ETHICS AND DISSEMINATION: The findings of this scoping review will be published in a peer-reviewed journal. The results will be used to inform future studies on patient-specific factors informing treatment choice between abiraterone and enzalutamide for castration-resistant prostate cancer. All data are from published openly accessible sources, and therefore, no ethical clearance is necessary. The protocol is also registered at https://doi.org/10.6084/m9.figshare.19149227.
Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Acetato de Abiraterona , Androstenos/efectos adversos , Benzamidas , Humanos , Masculino , Nitrilos/uso terapéutico , Feniltiohidantoína/efectos adversos , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Literatura de Revisión como Asunto , Resultado del TratamientoRESUMEN
Abiraterone acetate (AA) and enzalutamide (ENZ) are commonly used for metastatic prostate cancer. It is unclear how their outcomes and toxicities vary with patient-specific factors because clinical trials typically exclude patients with significant comorbidities. This study aims to fill this knowledge gap and facilitate informed treatment decision making. A registered protocol utilizing PRISMA scoping review methodology was utilized to identify real-world studies. Of 433 non-duplicated publications, 23 were selected by three independent reviewers. ENZ offered a faster and more frequent biochemical response (30-50% vs. 70-75%), slowed progression (HR 0.66; 95% CI 0.50-0.88), and improved overall survival versus AA. ENZ was associated with more fatigue and neurological adverse effects. Conversely, AA increased risk of cardiovascular- (HR 1.82; 95% CI 1.09-3.05) and heart failure-related (HR 2.88; 95% CI 1.09-7.63) hospitalizations. Ultimately, AA was associated with increased length of hospital stay, emergency department visits, and hospitalizations (HR 1.26; 95% CI 1.04-1.53). Accordingly, total costs were higher for AA, although pharmacy costs alone were higher for ENZ. Existing data suggest that AA and ENZ have important differences in outcomes including toxicities, response, disease progression, and survival. Additionally, adherence, healthcare utilization, and costs differ. Further investigation is warranted to inform treatment decisions which optimize patient outcomes.
RESUMEN
INTRODUCTION: Immune checkpoint inhibitors (ICIs) have changed the treatment landscape for multiple cancer types. Sex plays an important role in both the development of cancer as well as the functioning of the immune system. Though a difference in response to immune therapy is emerging between men and women it is unclear how this difference affects cancer outcomes and what the potential underlying mechanisms are for those effects. The objective of this study is to describe the influence that sex has on the outcomes experienced by cancer patients on ICI therapy and to identify and analyse any knowledge gaps in the field. METHOD AND ANALYSIS: The framework for this methodology was guided by the Joanna Briggs Institute Manual for Evidence Synthesis. The search and review will be conducted from January 2022 to June 2022. Two independent researchers will screen titles and abstracts followed by full-text screening for manuscript inclusion. Full length studies published between 2010 and December 2021 found in PubMed, Cochrane, CINAHL, and Scopus describing the influence of sex differences on cancer outcomes in patients treated with ICIs will be included. After data are extracted it will be summarised for presentation. ETHICS AND DISSEMINATION: The findings of this scoping review will be published in a peer-reviewed journal. The results will be used to inform future studies on the potential differential impacts of ICIs. All data are from published openly accessible sources and therefore no ethical clearance is necessary.
Asunto(s)
Inhibidores de Puntos de Control Inmunológico , Neoplasias , Atención a la Salud , Femenino , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Masculino , Neoplasias/tratamiento farmacológico , Revisión por Pares , Proyectos de Investigación , Literatura de Revisión como AsuntoRESUMEN
BACKGROUND: Combining robotic therapy (RT) with task-oriented therapy is an emerging strategy to facilitate motor relearning in stroke rehabilitation. This study protocol will compare novel rehabilitation regimens that use bilateral RT as a priming technique to augment two task-oriented therapies: mirror therapy (MT) and bilateral arm training (BAT) with a control intervention: RT combined with impairment-oriented training (IOT). METHODS: This single-blind, randomized, comparative efficacy study will involve 96 participants with chronic stroke. Participants will be randomized into bilateral RT+MT, bilateral RT+BAT, and bilateral RT+IOT groups and receive 18 intervention sessions (90 min/day, 3 d/week for 6 weeks). The outcomes will include the Fugl-Meyer Assessment, Stroke Impact Scale version 3.0, Medical Research Council scale, Revised Nottingham Sensory Assessment, ABILHAND Questionnaire, and accelerometer and will be assessed at baseline, after treatment, and at the 3-month follow-up. Analysis of covariance and the chi-square automatic interaction detector method will be used to examine the comparative efficacy and predictors of outcome, respectively, after bilateral RT+MT, bilateral RT+BAT, and bilateral RT+IOT. DISCUSSION: The findings are expected to contribute to the research and development of robotic devices, to update the evidence-based protocols in postacute stroke care programs, and to investigate the use of accelerometers for monitoring activity level in real-life situations, which may in turn promote home-based practice by the patients and their caregivers. Directions for further studies and empirical implications for clinical practice will be further discussed in upper-extremity rehabilitation after stroke. TRIAL REGISTRATION: This trial was registered December 12, 2018, at www. CLINICALTRIALS: gov ( NCT03773653 ).
Asunto(s)
Terapia del Movimiento Espejo , Robótica , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Actividades Cotidianas , Brazo , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Recuperación de la Función , Método Simple Ciego , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/terapia , Rehabilitación de Accidente Cerebrovascular/métodos , Resultado del Tratamiento , Extremidad SuperiorRESUMEN
BACKGROUND: There is substantial variability in prostate cancer (PCa) mortality rates across Caucasian American (CA), African American (AA), Asian, and Hispanic men; however, these estimates are unable to disentangle race or ethnicity from confounding factors. The current study explores survival differences in long-term PCa outcomes between self-reported AA and CA men, and examines clinicopathologic features across self-reported CA, AA, Asian, and Hispanic men. METHODS: This retrospective cohort study utilized the Center for Prostate Disease Research (CPDR) Multi-center National Database from 1990 to 2017. Subjects were consented at military treatment facilities nationwide. AA, CA, Asian, or Hispanic men who underwent radical prostatectomy (RP) for localized PCa within the first year of diagnosis were included in the analyses. Time from RP to biochemical recurrence (BCR), BCR to metastasis, and metastasis to overall death were evaluated using Kaplan-Meier unadjusted estimation curves and adjusted Cox proportional hazards regression. RESULTS: This study included 7067 men, of whom 5155 (73%) were CA, 1468 (21%) were AA, 237 (3%) were Asian, and 207 (3%) were Hispanic. AA men had a significantly decreased time from RP to BCR compared to CA men (HR = 1.25, 95% CI = 1.06-1.48, p = 0.01); however, no difference was observed between AA and CA men for a time from BCR to metastasis (HR = 0.73, 95% CI = 0.39-1.33, p = 0.302) and time from metastasis to overall death (HR = 0.67, 95% CI = 0.36-1.26, p = 0.213). CONCLUSIONS: In an equal access health care setting, AA men had a shorter survival time from RP to BCR, but comparable survival time from BCR to metastasis and metastasis to overall death.
Asunto(s)
Salud Militar , Neoplasias de la Próstata , Masculino , Humanos , Estudios Retrospectivos , Recurrencia Local de Neoplasia/patología , Neoplasias de la Próstata/patología , Prostatectomía , Antígeno Prostático Específico , Estudios de CohortesRESUMEN
BACKGROUND: Previous research exploring the role of race on prostate cancer (PCa) outcomes has demonstrated greater rates of disease progression and poorer overall survival for African American (AA) compared to Caucasian American (CA) men. The current study examines self-reported race as a predictor of long-term PCa outcomes in patients with low and favorable-intermediate risk disease treated with external beam radiation therapy (EBRT). METHODS: This retrospective cohort study examined patients who were consented to enrollment in the Center for Prostate Disease Research Multicenter National Database between January 01, 1990 and December 31, 2017. Men self-reporting as AA or CA who underwent EBRT for newly diagnosed National Comprehensive Cancer Network-defined low or favorable-intermediate risk PCa were included. Dependent study outcomes included: biochemical recurrence-free survival, (ii) distant metastasis-free survival, and (iii) overall survival. Each outcome was modeled as a time-to-event endpoint using race-stratified Kaplan-Meier estimation curves and multivariable Cox proportional hazards analysis. RESULTS: Of 840 men included in this study, 268 (32%) were AA and 572 (68%) were CA. The frequency of biochemical recurrence, distant metastasis, and deaths from any cause was 151 (18.7%), 29 (3.5%), and 333 (39.6%), respectively. AA men had a significantly younger median age at time of EBRT and slightly higher biopsy Gleason scores. Multivariable Cox proportional hazards analyses demonstrated no racial differences in any of the study endpoints. CONCLUSIONS: These findings reveal no racial disparity in PCa outcomes for AA compared to CA men, in a long-standing, longitudinal cohort of patients with comparable access to cancer care.
Asunto(s)
Neoplasias de la Próstata , Masculino , Humanos , Estudios Retrospectivos , Neoplasias de la Próstata/patología , Clasificación del Tumor , Negro o Afroamericano , Población BlancaRESUMEN
BACKGROUND: Prostate cancer is an important cause of death worldwide. The number of years of life lost (YLL) due to prostate cancer is a metric of the toll of prostate cancer and using projections of demographic changes, can be used to measure future burden. METHODS: Prostate cancer mortality data by country and world region was retrieved from the Global Cancer Observatory and the World Health Organization mortality data set, and life expectancy was from the United Nations Department of Economic and Social Affairs. We estimated YLL as the difference between age at death in people with prostate cancer and remaining life expectancy for people of the same age in the general population. We also estimated the age-standardized YLL rates per 100,000 males over 50 and the average annual percentage change in YLL rates over the period 2000-2019 and the number of YLL for the year 2040 by applying population projections to the 2020 YLL rates. RESULTS: In 2020, 3.5 million person-years of life were lost due to prostate cancer in males over 50, and 40% of YLL were in those aged over 75. Age-standardized rates varied greatly between and within regions. Over the last two decades, rates of YLL have increased in many Asian and African countries while they have decreased in northern American and European countries. Globally, YLL are anticipated to double by 2040 to reach 7.5 million, with the greatest increases in Africa, Asia, and Latin America and the Caribbean. CONCLUSION: There are wide variations in the burden of prostate cancer globally as measured by YLL. The burden of prostate cancer is projected to increase over time and appears to be highest in Sub-Saharan Africa, Eastern Europe, and Latin America and the Caribbean. It will be critical to plan and implement programs to reduce the burden of prostate cancer globally.
Asunto(s)
Esperanza de Vida , Neoplasias de la Próstata , Anciano , Región del Caribe/epidemiología , Humanos , Masculino , Neoplasias de la Próstata/epidemiologíaRESUMEN
The brief version of the World Health Organization's Quality of Life Questionnaire, called WHOQOL-BREF, is an internationally applicable measurement for quality of life (QOL) and is widely used in medical and psychological research. Consistent factor structure across countries is essential for the WHOQOL-BREF. However, poor construct validity was found in Lin and Yao's systematic review study. Few studies have investigated this issue. To fill this gap, this study is the first to examine the factor structure of the WHOQOL-BREF using a meta-analysis approach through exploratory factor analysis (EFA) and social network analysis (SNA). Sixteen studies published from 1998 to April 2021 were selected from two well-known academic databases: PsycINFO and MEDLINE. The findings from EFA revealed that four- and five-factor models are acceptable. Because of the weak factor structure of the five-factor model, leading to difficulty in explaining the measurement outcome, the four-factor model was chosen. All 24 items, except Item 8, were loaded on the theoretically designed factors. The theory-based four-factor model proposed by the WHOQOL group was validated. Our results not only provide additional insight into the factor structure of the WHOQOL-BREF but also facilitate its international applicability and comparability. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
Asunto(s)
Calidad de Vida , Análisis de Redes Sociales , Análisis Factorial , Humanos , Psicometría/métodos , Calidad de Vida/psicología , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Organización Mundial de la SaludRESUMEN
Immune checkpoint inhibitors (ICIs) harness the immune system and are the therapy of choice for multiple cancers. Although immunosuppressive agents such as steroids are also used in many cancers, it is unknown how their timing affects treatment outcomes. Thus, we investigated the relationship between the timing of steroid exposure preceding ICI administration and subsequent treatment outcomes in melanoma. This population-based study utilized the SEER-Medicare-linked database to identify patients diagnosed with melanoma between 1991 and 2015 and receiving ICIs between 2010 and 2016, examining last steroid exposure in the 12 months preceding ICI. The main outcome was all-cause mortality (ACM) after ICIs. Modifications of the Cox proportional hazards model were used to calculate time-dependent hazards. Of 1671 patients with melanoma receiving ICIs, 907 received steroids. Compared with no steroids, last steroid exposures ≤1 month and 1-3 months prior to ICIs were associated with a 126% and 51% higher ACM within 3 months post ICI initiation, respectively (hazard ratio (HR): 2.26, 95% CI: 1.65-3.08; and HR: 1.51, 95% CI: 1.01-2.27). Steroid exposure within 3 months of initiating ICIs was associated with increased mortality up to 6 months after ICI. Further investigation is warranted to elucidate mechanisms affecting outcomes due to steroids.