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Introduction: Social adaptation is a multifaceted process that encompasses cognitive, social, and affective factors. Previous research often focused on isolated variables, overlooking their interactions, especially in challenging environments. Our study addresses this by investigating how cognitive (working memory, verbal intelligence, self-regulation), social (affective empathy, family networks, loneliness), and psychological (locus of control, self-esteem, perceived stress) factors interact to influence social adaptation. Methods: We analyzed data from 254 adults (55% female) aged 18 to 46 in economically vulnerable households in Santiago, Chile. We used Latent profile analysis (LPA) and machine learning to uncover distinct patters of socioadaptive features and identify the most discriminating features. Results: LPA showed two distinct psychosocial adaptation profiles: one characterized by effective psychosocial adaptation and another by poor psychosocial adaptation. The adaptive profile featured individuals with strong emotional, cognitive, and behavioral self-regulation, an internal locus of control, high self-esteem, lower stress levels, reduced affective empathy, robust family support, and decreased loneliness. Conversely, the poorly adapted profile exhibited the opposite traits. Machine learning pinpointed six key differentiating factors in various adaptation pathways within the same vulnerable context: high self-esteem, cognitive and behavioral self-regulation, low stress levels, higher education, and increased social support. Discussion: This research carries significant policy implications, highlighting the need to reinforce protective factors and psychological resources, such as self-esteem, self-regulation, and education, to foster effective adaptation in adversity. Additionally, we identified critical risk factors impacting social adaptation in vulnerable populations, advancing our understanding of this intricate phenomenon.
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BACKGROUND: Standard treatment for patients with newly diagnosed glioblastoma includes surgery, radiotherapy (RT) and temozolomide (TMZ) chemotherapy (TMZ/RTâTMZ). The proteasome has long been considered a promising therapeutic target because of its role as a central biological hub in tumor cells. Marizomib is a novel pan-proteasome inhibitor that crosses the blood brain barrier. METHODS: EORTC 1709/CCTG CE.8 was a multicenter, randomized, controlled, open label phase 3 superiority trial. Key eligibility criteria included newly diagnosed glioblastoma, age > 18 years and Karnofsky performance status > 70. Patients were randomized in a 1:1 ratio. The primary objective was to compare overall survival (OS) in patients receiving marizomib in addition to TMZ/RTâTMZ with patients receiving only standard treatment in the whole population, and in the subgroup of patients with MGMT promoter-unmethylated tumors. RESULTS: The trial was opened at 82 institutions in Europe, Canada and the US. A total of 749 patients (99.9% of planned 750) were randomized. OS was not different between the standard and the marizomib arm (median 17 vs 16.5 months; HR=1.04; p=0.64). PFS was not statistically different either (median 6.0 vs. 6.3 months; HR=0.97; p=0.67). In patients with MGMT promoter-unmethylated tumors, OS was also not different between standard therapy and marizomib (median 14.5 vs 15.1 months, HR=1.13; p=0.27). More CTCAE grade 3/4 treatment-emergent adverse events were observed in the marizomib arm than in the standard arm. CONCLUSIONS: Adding marizomib to standard temozolomide-based radiochemotherapy resulted in more toxicity, but did not improve OS or PFS in patients with newly diagnosed glioblastoma.
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BACKGROUND: Glioblastoma (GBM) is a highly malignant brain tumor that affects men more often than women. In addition, the former shows a poorer survival prognosis. To date, the reason for this sex-specific aggressiveness remains unclear. Therefore, the aim of this study is to investigate tumor processes that explain these sex differences. METHODS: This was a retrospective study of GBM patients which was stratified according to sex. A cohort with 73 tumors was analyzed with immunohistochemistry, RNA-seq and RT-qPCR to characterize differences in vascular and immunological profiles. Transcriptomic profiling, gene set enrichment analysis, and pathway enrichment analysis were used for discovering molecular pathways predominant in each group. We further investigated the therapeutic effect of bevacizumab (vascular endothelial growth factor A (VEGFA) blocking antibody) in a retrospective GBM cohort (36 tumors) based on sex differences. RESULTS: We found that under hypoxic tumor conditions, 2 distinct tumor immuno-angiogenic ecosystems develop linked to sex differences and ESR1 expression is generated. One of these subgroups, which includes male patients with low ESR1 expression, is characterized by vascular fragility associated with the appearance of regions of necrosis and high inflammation (called necroinflamed tumors). This male-specific tumor subtype shows high inflammation related to myeloid-derived suppressor cells infiltration. Using this stratification, we identified a possible group of patients who could respond to bevacizumab (BVZ) and revealed a genetic signature that may find clinical applications as a predictor of those who may benefit most from this treatment. CONCLUSIONS: This study provides a stratification based on the sexual differences in GBM, which associates the poor prognosis with the presence of immunosuppressive myeloid cells in the necrotic areas. This new stratification could change the current prognosis of GBM and identifies those who respond to BVZ treatment.
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Bevacizumab , Neoplasias Encefálicas , Glioblastoma , Necrosis , Humanos , Bevacizumab/uso terapéutico , Glioblastoma/tratamiento farmacológico , Glioblastoma/patología , Glioblastoma/metabolismo , Masculino , Femenino , Estudios Retrospectivos , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/metabolismo , Pronóstico , Persona de Mediana Edad , Antineoplásicos Inmunológicos/uso terapéutico , Inflamación/patología , Inflamación/tratamiento farmacológico , Anciano , Adulto , Inhibidores de la Angiogénesis/uso terapéutico , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Estudios de Seguimiento , Caracteres Sexuales , Tasa de SupervivenciaRESUMEN
BACKGROUND: Vertebral body tethering and other non-fusion techniques for the treatment of pediatric idiopathic scoliosis are increasing in popularity. There is limited physician consensus on this topic as the result of a paucity of published data regarding which patients most benefit from non-fusion strategies. Thus, much of the decision-making is left to patients and parents, who must select a treatment based on their goals and values and the information available from health-care providers, the internet, and social media. We sought to understand patient and family preferences regarding the attributes of fusion versus non-fusion surgery that drive these choices. METHODS: Patients and families were recruited from 7 pediatric spine centers and were asked to complete a survey-based choice experiment that had been jointly developed with the U.S. Food and Drug Administration (FDA) to evaluate patient preferences. Choices between experimentally designed alternatives were analyzed to estimate the relative importance of outcomes and requirements associated with the choice options (attributes). The attributes included appearance, confidence in the planned correction, spinal motion, device failure, reoperation, and recovery period. The inclusion criteria were (1) an age of 10 to 21 years and (2) a diagnosis of adolescent idiopathic scoliosis in patients who were considering, or who had already undergone, treatment with fusion or non-fusion surgery. Preference weights were estimated from the expected changes in choice given changes in the attributes. RESULTS: A total of 344 respondents (124 patients, 92 parents, and 128 parent/patient dyads) completed the survey. One hundred and seventy-three patients were enrolled prior to surgery, and 171 were enrolled after surgery. Appearance and motion were found to be the most important drivers of choice. For the entire cohort, fusion was preferred over non-fusion. For patients who were considering surgery, the most important attributes were preservation of spinal motion and appearance. CONCLUSIONS: Patients and families seeking treatment for idiopathic scoliosis value appearance and preservation of spinal motion and, to a lesser extent, reoperation rates when considering fusion versus non-fusion surgery.
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Escoliosis , Fusión Vertebral , Adolescente , Humanos , Niño , Adulto Joven , Adulto , Escoliosis/cirugía , Columna Vertebral , Padres , Prioridad del Paciente , Consenso , Fusión Vertebral/métodos , Resultado del TratamientoRESUMEN
OBJECTIVE: In this study, we aimed to develop education to assist BRCA mutation carriers in making informed decisions about HRT in the context of risk-reducing surgery, while simultaneously clarifying their treatment-specific values and reducing decisional conflict. METHODS: We enrolled premenopausal BRCA mutation carriers ages 19-49 without prior cancer or risk-reducing salpingo-oophorectomy to structured interviews in which they reviewed education about the risks and benefits of HRT. Materials included literature-derived data demonstrating associations between HRT and commonly considered health outcomes (breast cancer, vasomotor symptoms, sexual functioning, cardiovascular disease, osteoporosis, and blood clots). Participants completed the 16-item Decisional Conflict Scale (DCS) before and after education, communicated their preferences by rating and ranking the six outcomes, and provided feedback to inform iterative revisions of the educational content. RESULTS: 25 participants completed interviews. DCS scores decreased significantly from 54.6 to 22.8 following education (p < 0.001); sub-scores for uncertainty (71.7 to 37.3), informed (71.7 to 15.3), values clarity (53.7 to 17.0), effective decision (44.2 to 25.5), and support (35.0 to 17.7) also decreased significantly. Participants ranked cardiovascular disease as the most important outcome to consider, followed by breast cancer, osteoporosis, blood clots, decline in sexual function, and hot flashes. Participants with prior mastectomy (N = 10) ranked breast cancer as the most important outcome 25% of the time, compared to 80% in participants without mastectomy (N = 15). CONCLUSION: Following education, BRCA mutation carriers had significantly less decisional conflict regarding the choice to use HRT. This pilot study was successful in generating a prototype educational aid for further testing.
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Neoplasias de la Mama , Enfermedades Cardiovasculares , Osteoporosis , Neoplasias Ováricas , Trombosis , Femenino , Humanos , Neoplasias de la Mama/genética , Neoplasias de la Mama/cirugía , Proyectos Piloto , Mastectomía , Terapia de Reemplazo de Hormonas , Neoplasias Ováricas/genética , Neoplasias Ováricas/prevención & control , Neoplasias Ováricas/cirugía , Trombosis/cirugía , Atención Dirigida al Paciente , Mutación , OvariectomíaRESUMEN
Objective of this study is to quantify benefit-risk tradeoffs pertaining to potential gene therapies among adults and parents/caregivers of children with sickle cell disease (SCD). A discrete-choice experiment survey was developed in which respondents selected their preferred treatment alternatives in a series of experimentally controlled pairs of hypothetical gene therapies and a "no gene therapy" option. Gene therapy alternatives were defined based on the chance of eliminating SCD symptoms, expected increases in life expectancy they could offer, treatment-related risk of death, and potential increases in lifetime cancer risk. Respondents made selections based on their current disease severity and in the context of expectations of worsened disease. Three clinical sites and 1 patient organization recruited 174 adult patients and 109 parents of children with SCD to complete the survey. Adult and parent respondents were generally willing to choose gene therapies, but the adults required higher expected levels of efficacy (ie, higher chance of eliminating symptoms) than parents to choose gene therapies that conferred mortality risks of ≥10%. When adults and parents of children with less severe symptoms were asked to consider scenarios of higher levels of disease severity, the increased risk tolerance, and the lowest acceptable level of efficacy for gene therapies with mortality risks dropped by >50%. Baseline SCD symptoms are a major driver of gene therapy acceptability. Adults and parents of patients with milder symptoms may prefer other treatment options; however, an expectation of symptoms deterioration triggers strong reassessment of the acceptable benefit-risk balance of this novel technology.
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Anemia de Células Falciformes , Adulto , Niño , Humanos , Anemia de Células Falciformes/genética , Anemia de Células Falciformes/terapia , Medición de Riesgo , Padres , Encuestas y Cuestionarios , Terapia Genética/efectos adversosRESUMEN
BACKGROUND: In the United States, more than 50% of kidneys in the lowest 15% quality range (those with Kidney Donor Profile Index >85) are discarded. Studies suggest that using more of these kidneys could benefit patients waiting for a transplant. This study assesses the trade-offs physicians make when selecting recipients for lower-quality kidneys. METHODS: A discrete choice experiment (DCE) was administered to surgeons and nephrologists in the United States who are involved in kidney acceptance decisions. The DCE presented kidneys that varied in terms of Kidney Donor Profile Index, expected cold ischemia time, donor age, pump parameters, serum creatinine levels, glomerulosclerosis, donor diabetes status, and whether donation was made after circulatory death. Candidate characteristics included recipients' age, diabetes history, time on dialysis, ejection fraction, HLA mismatch, calculated panel reactive antibody, and Karnofsky performance score. Regression analysis was used to estimate acceptability weights associated with kidney and recipient characteristics. RESULTS: A total of 108 physicians completed the DCE. The likelihood of acceptance was significantly lower with deterioration of kidney quality, expected cold ischemia time at transplantation, and missing biopsy and pump information. Acceptance was prioritized for patients who were higher on the waiting list, younger recipients, those who have spent less time on dialysis, and those without a history of diabetes. Performance status (Karnofsky score) and calculated panel reactive antibody also had a statistically significant but smaller association. Finally, ejection fraction had a marginally significant association, and HLA match had no significant association with the acceptance of marginal kidneys. A group of respondents were found to be primarily concerned about cold ischemia time. CONCLUSIONS: In this DCE, physicians considered the recipient characteristics that inform expected post-transplant survival score when they decided whether to accept a marginal kidney for a given recipient.
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Diabetes Mellitus , Trasplante de Riñón , Médicos , Obtención de Tejidos y Órganos , Humanos , Estados Unidos , Riñón , Donantes de Tejidos , Supervivencia de InjertoRESUMEN
Background: Mental disorders affect about one in seven children and adolescents worldwide. Investment in effective child and adolescent mental health prevention, promotion and care is essential. To date, however, the evidence from this field is yet to be comprehensively collected and mapped. Objectives: The objective of this evidence and gap map (EGM) is to provide an overview of the existing evidence on the effectiveness of interventions aimed at promoting mental health and reducing or preventing mental health conditions among children and adolescents in lower-middle-income countries (LMICs). Search Methods: We searched for studies from a wide range of bibliographic databases, libraries and websites. All searches were conducted in December 2021 and covered the period between 2010 and 2021. Selection Criteria: We included evidence on the effectiveness of any Mental Health and Psychosocial Support (MHPSS) interventions targeting children and adolescents from 0 to 19 years of age in LMICs. The map includes systematic reviews and effectiveness studies in the form of randomised control trials and quasi-experimental studies, and mixed-methods studies with a focus on intervention effectiveness. Data Collection and Analysis: A total of 63,947 records were identified after the search. A total of 19,578 records were removed using machine learning. A total of 7545 records were screened independently and simultaneously by four reviewers based on title and abstract and 2721 full texts were assessed for eligibility. The EGM includes 697 studies and reviews that covered 78 LMICs. Main Results: School-based interventions make up 61% of intervention research on child and adolescent mental health and psychosocial support. Most interventions (59%) focusing on treating mental health conditions rather than preventing them or promoting mental health. Depression (40%, N = 282) was the most frequently researched outcome sub-domain analysed by studies and reviews, followed by anxiety disorders (32%, N = 225), well-being (21%, N = 143), and post-traumatic stress disorder (18%, N = 125). Most included studies and reviews investigated the effectiveness of mental health and psychosocial support interventions in early (75%, N = 525) and late adolescence (64%, N = 448). Conclusions: The body of evidence in this area is complex and it is expanding progressively. However, research on child and adolescent MHPSS interventions is more reactive than proactive, with most evidence focusing on addressing mental health conditions that have already arisen rather than preventing them or promoting mental health. Future research should investigate the effectiveness of digital mental health interventions for children and adolescents as well as interventions to address the mental health and psychosocial needs of children in humanitarian settings. Research on early childhood MHPSS interventions is urgently needed. MHPSS research for children and adolescents lacks diversity. Research is also needed to address geographical inequalities at the regional and national level. Important questions also remain on the quality of the available research-is child and adolescent MHPSS intervention research locally relevant, reliable, well-designed and conducted, accessible and innovative? Planning research collaborations with decision-makers and involving experts by experience in research is essential.
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Social adaptation arises from the interaction between the individual and the social environment. However, little empirical evidence exists regarding the relationship between social contact and social adaptation. We propose that loneliness and social networks are key factors explaining social adaptation. Sixty-four healthy subjects with no history of psychiatric conditions participated in this study. All participants completed self-report questionnaires about loneliness, social network, and social adaptation. On a separate day, subjects underwent a resting state fMRI recording session. A hierarchical regression model on self-report data revealed that loneliness and social network were negatively and positively associated with social adaptation. Functional connectivity (FC) analysis showed that loneliness was associated with decreased FC between the fronto-amygdalar and fronto-parietal regions. In contrast, the social network was positively associated with FC between the fronto-temporo-parietal network. Finally, an integrative path model examined the combined effects of behavioral and brain predictors of social adaptation. The model revealed that social networks mediated the effects of loneliness on social adaptation. Further, loneliness-related abnormal brain FC (previously shown to be associated with difficulties in cognitive control, emotion regulation, and sociocognitive processes) emerged as the strongest predictor of poor social adaptation. Findings offer insights into the brain indicators of social adaptation and highlight the role of social networks as a buffer against the maladaptive effects of loneliness. These findings can inform interventions aimed at minimizing loneliness and promoting social adaptation and are especially relevant due to the high prevalence of loneliness around the globe. These findings also serve the study of social adaptation since they provide potential neurocognitive factors that could influence social adaptation.
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Encéfalo , Soledad , Humanos , Soledad/psicología , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Lóbulo Parietal , Red SocialRESUMEN
INTRODUCTION: Vision standards for driving are typically based on visual acuity, despite evidence that it is a poor predictor of driving safety and performance. However, visual motion perception is potentially relevant for driving, as the vehicle and surroundings are in motion. This study explored whether tests of central and mid-peripheral motion perception better predict performance on a hazard perception test (HPT), which is related to driving performance and crash risk, than visual acuity. Additionally, we explored whether age influences these associations, as healthy ageing impairs performance on some motion sensitivity tests. METHODS: Sixty-five visually healthy drivers (35 younger, mean age: 25.5; SD 4.3 years; 30 older adults, mean age: 71.0; SD 5.4 years) underwent a computer-based HPT, plus four different motion sensitivity tests both centrally and at 15° eccentricity. Motion tests included minimum displacement to identify motion direction (Dmin ), contrast detection threshold for a drifting Gabor (motion contrast), coherence threshold for a translational global motion stimulus and direction discrimination for a biological motion stimulus in the presence of noise. RESULTS: Overall, HPT reaction times were not significantly different between age groups (p = 0.40) nor were maximum HPT reaction times (p = 0.34). HPT response time was associated with motion contrast and Dmin centrally (r = 0.30, p = 0.02 and r = 0.28, p = 0.02, respectively) and with Dmin peripherally (r = 0.34, p = 0.005); these associations were not affected by age group. There was no significant association between binocular visual acuity and HPT response times (r = 0.02, p = 0.29). CONCLUSIONS: Some measures of motion sensitivity in central and mid-peripheral vision were associated with HPT response times, whereas binocular visual acuity was not. Peripheral testing did not show an advantage over central testing for visually healthy older drivers. Our findings add to the growing body of evidence that the ability to detect small motion changes may have potential to identify unsafe road users.
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Conducción de Automóvil , Percepción de Movimiento , Humanos , Anciano , Adulto , Percepción de Movimiento/fisiología , Agudeza Visual , Percepción Visual/fisiología , Visión Ocular , Tiempo de Reacción/fisiologíaRESUMEN
BACKGROUND: Isocitrate dehydrogenase (IDH)-mutant grade 2 gliomas are malignant brain tumors that cause considerable disability and premature death. Vorasidenib, an oral brain-penetrant inhibitor of mutant IDH1 and IDH2 enzymes, showed preliminary activity in IDH-mutant gliomas. METHODS: In a double-blind, phase 3 trial, we randomly assigned patients with residual or recurrent grade 2 IDH-mutant glioma who had undergone no previous treatment other than surgery to receive either oral vorasidenib (40 mg once daily) or matched placebo in 28-day cycles. The primary end point was imaging-based progression-free survival according to blinded assessment by an independent review committee. The key secondary end point was the time to the next anticancer intervention. Crossover to vorasidenib from placebo was permitted on confirmation of imaging-based disease progression. Safety was also assessed. RESULTS: A total of 331 patients were assigned to receive vorasidenib (168 patients) or placebo (163 patients). At a median follow-up of 14.2 months, 226 patients (68.3%) were continuing to receive vorasidenib or placebo. Progression-free survival was significantly improved in the vorasidenib group as compared with the placebo group (median progression-free survival, 27.7 months vs. 11.1 months; hazard ratio for disease progression or death, 0.39; 95% confidence interval [CI], 0.27 to 0.56; P<0.001). The time to the next intervention was significantly improved in the vorasidenib group as compared with the placebo group (hazard ratio, 0.26; 95% CI, 0.15 to 0.43; P<0.001). Adverse events of grade 3 or higher occurred in 22.8% of the patients who received vorasidenib and in 13.5% of those who received placebo. An increased alanine aminotransferase level of grade 3 or higher occurred in 9.6% of the patients who received vorasidenib and in no patients who received placebo. CONCLUSIONS: In patients with grade 2 IDH-mutant glioma, vorasidenib significantly improved progression-free survival and delayed the time to the next intervention. (Funded by Servier; INDIGO ClinicalTrials.gov number, NCT04164901.).
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Antineoplásicos , Glioma , Recurrencia Local de Neoplasia , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Progresión de la Enfermedad , Método Doble Ciego , Glioma/tratamiento farmacológico , Glioma/genética , Isocitrato Deshidrogenasa/genética , Recurrencia Local de Neoplasia/tratamiento farmacológico , Piridinas/efectos adversos , Antineoplásicos/uso terapéutico , Inhibidores Enzimáticos/uso terapéuticoRESUMEN
Introduction: Early detection of depression is a cost-effective way to prevent adverse outcomes on brain physiology, cognition, and health. Here we propose that loneliness and social adaptation are key factors that can anticipate depressive symptoms. Methods: We analyzed data from two separate samples to evaluate the associations between loneliness, social adaptation, depressive symptoms, and their neural correlates. Results: For both samples, hierarchical regression models on self-reported data showed that loneliness and social adaptation have negative and positive effects on depressive symptoms. Moreover, social adaptation reduces the impact of loneliness on depressive symptoms. Structural connectivity analysis showed that depressive symptoms, loneliness, and social adaptation share a common neural substrate. Furthermore, functional connectivity analysis demonstrated that only social adaptation was associated with connectivity in parietal areas. Discussion: Altogether, our results suggest that loneliness is a strong risk factor for depressive symptoms while social adaptation acts as a buffer against the ill effects of loneliness. At the neuroanatomical level, loneliness and depression may affect the integrity of white matter structures known to be associated to emotion dysregulation and cognitive impairment. On the other hand, socio-adaptive processes may protect against the harmful effects of loneliness and depression. Structural and functional correlates of social adaptation could indicate a protective role through long and short-term effects, respectively. These findings may aid approaches to preserve brain health via social participation and adaptive social behavior.
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Bromodomain and extraterminal proteins (BET) play key roles in regulation of gene expression, and may play a role in cancer-cell proliferation, survival, and oncogenic progression. CC-90010-ST-001 (NCT03220347) is an open-label phase I study of trotabresib, an oral BET inhibitor, in heavily pretreated patients with advanced solid tumors and relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Primary endpoints were the safety, tolerability, maximum tolerated dose, and RP2D of trotabresib. Secondary endpoints were clinical benefit rate (complete response [CR] + partial response [PR] + stable disease [SD] of ≥4 months' duration), objective response rate (CR + PR), duration of response or SD, progression-free survival, overall survival, and the pharmacokinetics (PK) of trotabresib. In addition, part C assessed the effects of food on the PK of trotabresib as a secondary endpoint. The dose escalation (part A) showed that trotabresib was well tolerated, had single-agent activity, and determined the recommended phase 2 dose (RP2D) and schedule for the expansion study. Here, we report long-term follow-up results from part A (N = 69) and data from patients treated with the RP2D of 45 mg/day 4 days on/24 days off or an alternate RP2D of 30 mg/day 3 days on/11 days off in the dose-expansion cohorts (parts B [N = 25] and C [N = 41]). Treatment-related adverse events (TRAEs) are reported in almost all patients. The most common severe TRAEs are hematological. Toxicities are generally manageable, allowing some patients to remain on treatment for ≥2 years, with two patients receiving ≥3 years of treatment. Trotabresib monotherapy shows antitumor activity, with an ORR of 13.0% (95% CI, 2.8-33.6) in patients with R/R DLBCL (part B) and an ORR of 0.0% (95% CI, 0.0-8.6) and a CBR of 31.7% (95% CI, 18.1-48.1) in patients with advanced solid tumors (part C). These results support further investigation of trotabresib in combination with other anticancer agents.
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Antineoplásicos , Linfoma de Células B Grandes Difuso , Linfoma no Hodgkin , Humanos , Antineoplásicos/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/patología , Linfoma no Hodgkin/tratamiento farmacológicoRESUMEN
BACKGROUND: During their clinical practice, health Sciences students get acquainted with the cultural diversity of patients and learn to deal with this reality in a model of social learning. AIM: To determine the level of Intercultural Competence in Health Sciences students based on the Confrontation, Resistance, and Cultural Openness (CRAC) model, specific for health professionals. MATERIAL AND METHODS: Semi-structured interviews were conducted with 106 Health Sciences students from three universities in Chile. Content analysis was supported by the software ATLAS.ti version 9. RESULTS: The students progressed through the CRAC model and were able to configure a new level called Cultural Understanding, in which the participants innovated care models and offered new therapeutic schemes with cultural relevance. In addition, a fifth level called Cultural Inclusion was proposed. However, a training process with a marked theoretical/scientific emphasis can overshadow the learning process resulting from reflexive practical experience, reducing its real value such as traditional/ancestral medicine. CONCLUSIONS: The students were able to update the Confrontation, Resistance, Openness, Understanding and Intercultural Inclusion Model. The features of those participants who achieve the highest levels of intercultural competences should be explored and used for the training process.
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Humanos , Estudiantes , Comunicación , Personal de Salud , Diversidad Cultural , Competencia Cultural , AprendizajeRESUMEN
BACKGROUND: Advances in multiple myeloma treatment and a proliferation of treatment options have resulted in improved survival rates and periods of symptom-free remission for many multiple myeloma patients. As a result, health-related quality of life (HRQoL) concerns related to myeloma treatments have become increasingly salient for this patient population and represent an important consideration guiding patients' treatment choices. To gain an understanding of patients' experiences with choosing myeloma therapies and explore the HRQoL concerns that are most important to them, we interviewed a diverse sample of US-based multiple myeloma patients about their treatment considerations. METHODS: We conducted a qualitative descriptive study using in-depth interviews. Participants reflected on (1) the factors that were most important to them when thinking about multiple myeloma treatment and how these have changed over time, (2) how they might weigh the importance of treatment efficacy vs. side effects, (3) trade-offs they would be willing to make regarding efficacy vs. HRQoL, and (4) treatment changes they had experienced. Interviews were audio-recorded and transcribed, and narratives were analyzed using applied thematic analysis. RESULTS: We interviewed 21 patients, heterogeneous in their disease trajectory and treatment experience. Participants were 36 to 78 years, 52% female, and 38% Black. Efficacy was named as the most important treatment consideration by almost two-thirds of participants, and over half also valued HRQoL aspects such as the ability to maintain daily functioning and enjoyment of life. Participants expressed concern about potential treatment side effects and preferred more convenient treatment options. Although participants stated largely trusting their clinicians' treatment recommendations, many said they would stop a clinician-recommended treatment if it negatively impacted their HRQoL. Participants also said that while they prioritized treatment efficacy, they would be willing to change to a less efficacious treatment if side effects became intolerable. CONCLUSIONS: Our findings link to other reports reflecting considerations that are important to multiple myeloma patients, including the importance placed on increasing life expectancy and progression-free survival, but also the tension between treatment efficacy and quality of life. Our results extend these findings to a racially diverse US-based patient population at different stages in the disease trajectory.
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Mieloma Múltiple , Humanos , Femenino , Masculino , Mieloma Múltiple/tratamiento farmacológico , Calidad de Vida , Investigación CualitativaRESUMEN
BACKGROUND: Pilot clinical trials have shown the safety of intra-arterial bone marrow mononuclear cells (BMMNCs) in stroke. However, the efficacy of different doses of intra-arterial BMMNCs in patients with acute stroke has not been tested in a randomised clinical trial. We aimed to show safety and efficacy of two different doses of autologous intra-arterial BMMNC transplantation in patients with acute stroke. METHODS: The IBIS trial was a multicentre phase 2, randomised, controlled, investigator-initiated, assessor-blinded, clinical trial, in four stroke centres in Spain. We included patients (aged 18-80 years) with a non-lacunar, middle cerebral artery ischaemic stroke within 1-7 days from stroke onset and with a National Institutes of Health Stroke Scale score of 6-20. We randomly assigned patients (2:1:1) with a computer-generated randomisation sequence to standard of care (control group) or intra-arterial injection of autologous BMMNCs at one of two different doses (2â×â106 BMMNCs/kg or 5â×â106 BMMNCs/kg). The primary efficacy outcome was the proportion of patients with modified Rankin Scale scores of 0-2 at 180 days in the intention-to-treat population, comparing each BMMNC dose group and the pooled BMMNC group versus the control group. The primary safety endpoint was the proportion of serious adverse events. This trial was registered at ClinicalTrials.gov, NCT02178657 and is completed. FINDINGS: Between April 1, 2015, and May 20, 2021, we assessed 114 patients for eligibility. We randomly assigned 77 (68%) patients: 38 (49%) to the control group, 20 (26%) to the low-dose BMMNC group, and 19 (25%) the high-dose BMMNC group. The mean age of participants was 62·4 years (SD 12·7), 46 (60%) were men, 31 (40%) were women, all were White, and 63 (82%) received thrombectomy. The median NIHSS score before randomisation was 12 (IQR 9-15), with intra-arterial BMMNC injection done a median of 6 days (4-7) after stroke onset. The primary efficacy outcome occurred in 14 (39%) patients in the control group versus ten (50%) in the low-dose group (adjusted odds ratio 2·08 [95% CI 0·55-7·85]; p=0·28), eight (44%) in the high-dose group (1·89 [0·52-6·96]; p=0·33), and 18 (47%) in the pooled BMMNC group (2·22 [0·72-6·85]; p=0·16). We found no differences in the proportion of patients who had adverse events or dose-related events, but two patients had a groin haematoma after cell injection in the low-dose BMMNC group. INTERPRETATION: Intra-arterial BMMNCs were safe in patients with acute ischaemic stroke, but we found no significant improvement at 180 days on the mRS. Further clinical trials are warranted to investigate whether improvements might be possible at different timepoints. FUNDING: Instituto de Salud Carlos III co-funded by the European Regional Development Fund/European Social Fund, Mutua Madrileña, and the Regional Ministry of Health of Andalusia.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Masculino , Humanos , Femenino , Persona de Mediana Edad , Accidente Cerebrovascular/tratamiento farmacológico , Isquemia Encefálica/tratamiento farmacológico , España , Médula Ósea , Resultado del Tratamiento , Trasplante de CélulasRESUMEN
BACKGROUND: The bromodomain and extraterminal protein (BET) inhibitor trotabresib has demonstrated antitumor activity in patients with advanced solid tumors, including high-grade gliomas. CC-90010-GBM-001 (NCT04047303) is a phase I study investigating the pharmacokinetics, pharmacodynamics, and CNS penetration of trotabresib in patients with recurrent high-grade gliomas scheduled for salvage resection. METHODS: Patients received trotabresib 30 mg/day on days 1-4 before surgery, followed by maintenance trotabresib 45 mg/day 4 days on/24 days off after surgery. Primary endpoints were plasma pharmacokinetics and trotabresib concentrations in resected tissue. Secondary and exploratory endpoints included safety, pharmacodynamics, and antitumor activity. RESULTS: Twenty patients received preoperative trotabresib and underwent resection with no delays or cancelations of surgery; 16 patients received maintenance trotabresib after recovery from surgery. Trotabresib plasma pharmacokinetics were consistent with previous data. Mean trotabresib brain tumor tissue:plasma ratio was 0.84 (estimated unbound partition coefficient [KPUU] 0.37), and modulation of pharmacodynamic markers was observed in blood and brain tumor tissue. Trotabresib was well tolerated; the most frequent grade 3/4 treatment-related adverse event during maintenance treatment was thrombocytopenia (5/16 patients). Six-month progression-free survival was 12%. Two patients remain on treatment with stable disease at cycles 25 and 30. CONCLUSIONS: Trotabresib penetrates the blood-brain-tumor barrier in patients with recurrent high-grade glioma and demonstrates target engagement in resected tumor tissue. Plasma pharmacokinetics, blood pharmacodynamics, and safety were comparable with previous results for trotabresib in patients with advanced solid tumors. Investigation of adjuvant trotabresib + temozolomide and concomitant trotabresib + temozolomide + radiotherapy in patients with newly diagnosed glioblastoma is ongoing (NCT04324840).
Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Temozolomida/uso terapéutico , Dacarbazina/uso terapéutico , Glioma/patología , Glioblastoma/patología , Neoplasias Encefálicas/patología , Antineoplásicos Alquilantes/uso terapéuticoRESUMEN
BACKGROUND: While clinical practice guidelines underscore the need to incorporate patient preferences in clinical decision making, incorporating meaningful assessment of patient preferences in clinical encounters is challenging. Structured approaches that combine quantitative patient preferences and clinical evidence could facilitate effective patient-provider communication and more patient-centric health care decisions. Adaptive conjoint or stated-preference approaches can identify individual preference parameters, but they can require a relatively large number of choice questions or simplifying assumptions about the error with which preferences are elicited. METHOD: We propose an approach to efficiently diagnose preferences of patients for outcomes of treatment alternatives by leveraging prior information on patient preferences to generate adaptive choice questions to identify a patient's proximity to known preference phenotypes. This information can be used for measuring sensitivity and specificity, much like any other diagnostic procedure. We simulated responses with varying levels of choice errors for hypothetical patients with specific preference profiles to measure sensitivity and specificity of a 2-question preference diagnostic. RESULTS: We identified 4 classes representing distinct preference profiles for patients who participated in a previous first-time anterior shoulder dislocation (FTASD) survey. Posterior probabilities of class membership at the end of a 2-question sequence ranged from 87% to 89%. We found that specificity and sensitivity of the 2-question sequences were robust to respondent errors. The questions appeared to have better specificity than sensitivity. CONCLUSIONS: Our results suggest that this approach could help diagnose patient preferences for treatments for a condition such as FTASD with acceptable precision using as few as 2 choice questions. Such preference-diagnostic tools could be used to improve and document alignment of treatment choices and patient preferences. HIGHLIGHTS: Approaches that combine patient preferences and clinical evidence can facilitate effective patient-provider communication and more patient-centric healthcare decisions. However, diagnosing individual-level preferences is challenging, and no formal diagnostic tools exist.We propose a structured approach to efficiently diagnose patient preferences based on prior information on the distribution of patient preferences in a population.We generated a 2-question test of preferences for the outcomes associated with the treatment of first-time anterior shoulder dislocation.The diagnosis of preferences can help physicians discuss relevant aspects of the treatment options and proactively address patient concerns during the clinical encounter.
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Toma de Decisiones Conjunta , Luxación del Hombro , Humanos , Prioridad del Paciente , Encuestas y Cuestionarios , Atención a la Salud , Toma de Decisiones , Conducta de ElecciónRESUMEN
BACKGROUND: Addition of temozolomide (TMZ) to radiotherapy (RT) improves overall survival (OS) in patients with glioblastoma (GBM), but previous studies suggest that patients with tumors harboring an unmethylated MGMT promoter derive minimal benefit. The aim of this open-label, phase III CheckMate 498 study was to evaluate the efficacy of nivolumab (NIVO) + RT compared with TMZ + RT in newly diagnosed GBM with unmethylated MGMT promoter. METHODS: Patients were randomized 1:1 to standard RT (60 Gy) + NIVO (240 mg every 2 weeks for eight cycles, then 480 mg every 4 weeks) or RT + TMZ (75 mg/m2 daily during RT and 150-200 mg/m2/day 5/28 days during maintenance). The primary endpoint was OS. RESULTS: A total of 560 patients were randomized, 280 to each arm. Median OS (mOS) was 13.4 months (95% CI, 12.6 to 14.3) with NIVO + RT and 14.9 months (95% CI, 13.3 to 16.1) with TMZ + RT (hazard ratio [HR], 1.31; 95% CI, 1.09 to 1.58; P = .0037). Median progression-free survival was 6.0 months (95% CI, 5.7 to 6.2) with NIVO + RT and 6.2 months (95% CI, 5.9 to 6.7) with TMZ + RT (HR, 1.38; 95% CI, 1.15 to 1.65). Response rates were 7.8% (9/116) with NIVO + RT and 7.2% (8/111) with TMZ + RT; grade 3/4 treatment-related adverse event (TRAE) rates were 21.9% and 25.1%, and any-grade serious TRAE rates were 17.3% and 7.6%, respectively. CONCLUSIONS: The study did not meet the primary endpoint of improved OS; TMZ + RT demonstrated a longer mOS than NIVO + RT. No new safety signals were detected with NIVO in this study. The difference between the study treatment arms is consistent with the use of TMZ + RT as the standard of care for GBM.ClinicalTrials.gov NCT02617589.