RESUMO
Patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) following allogeneic hematopoietic stem cell transplantation (alloHSCT) have a poor prognosis, and alternative therapies are needed for this patient population. Blinatumomab, a bispecific T cell engager immunotherapy, was evaluated in an open-label, single-arm, phase II study of adults with R/R Philadelphia chromosome-negative B cell precursor ALL and resulted in a rate of complete remission (CR) or CR with partial hematologic recovery of peripheral blood counts (CRh) of 43% within 2 treatment cycles. We conducted an exploratory analysis to determine the efficacy and safety of blinatumomab in 64 patients who had relapsed following alloHSCT before enrollment in the phase II study. Forty-five percent of the patients (29 of 64) achieved a CR/CRh within the first 2 cycles of treatment, 22 of whom had a minimal residual disease (MRD) response (including 19 with a complete MRD response). After 1 year and 3 years of follow-up, the median relapse-free survival was 7.4 months for patients who achieved CR/CRh in the first 2 cycles, and the median overall survival was 8.5 months; overall survival rate (Kaplan-Meier estimate) was 36% at 1 year and 18% at 3 years. Grade 3 and 4 adverse events were reported in 20 patients (31%) and 28 patients (44%), respectively, with grade 3 and 4 neurologic events in 8 and 2 patients, respectively, and grade 3 cytokine release syndrome in 2 patients. Eight patients had fatal adverse events, including 5 due to infections. Seven patients had grade ≤ 3 graft-versus-host disease during the study, none of which resulted in the discontinuation of blinatumomab or hospitalization. Our data suggest that blinatumomab is an effective salvage therapy in this patient population.
Assuntos
Anticorpos Biespecíficos/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Adulto , Idoso , Aloenxertos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras B/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Recidiva , Indução de Remissão , Taxa de SobrevidaRESUMO
Neurologic events (NEs) have been reported during treatment with blinatumomab, a bispecific T cell engager (BiTE®) construct. We evaluated the occurrence, severity, and management of NEs; the relationship between NEs and blinatumomab dose; and the potential clinical risk factors in an open-label, single-arm, phase 2 study (N = 189). Patients had Philadelphia chromosome-negative, relapsed/refractory acute lymphoblastic leukemia (ALL) and ≥ 10% bone marrow blasts. The relationship between blinatumomab exposure and NE incidence and severity was assessed. Clinical risk factors for NEs were assessed in a post hoc multivariate analysis. Overall, 98 patients (52%) experienced NEs: most frequently, dizziness, tremor, confusional state, and encephalopathy. NEs occurred predominantly during cycle 1 (median onset, 9 days) and were usually grades 1 or 2. Grade ≥ 3 NEs (13-17% incidence), serious NEs (16-19% incidence), and recurring NEs were managed with infusion interruptions or dexamethasone treatment. The incidence of NEs increased with increasing blinatumomab exposure at a given dose, but exposure appeared unrelated to NE severity. NEs were more frequent in patients ≥ 65 years than < 65 years (72 vs 49%). In a multivariate analysis, race other than white (hazard ratio [HR], 2.11; P = 0.009), > 2 prior salvage therapies (HR, 2.48; P = 0.006), and prior NEs (HR, 1.65; P = 0.020) were risk factors for time to first on-study NE. Although the mechanism underlying NEs associated with blinatumomab treatment in patients with relapsed/refractory ALL remains unclear, NEs tended to occur early during treatment and were often resolved by interrupting treatment and with dexamethasone. Additional research is warranted to investigate the risk factors for NEs.
Assuntos
Anticorpos Biespecíficos , Crise Blástica , Dexametasona/administração & dosagem , Doenças do Sistema Nervoso , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Adulto , Fatores Etários , Idoso , Anticorpos Biespecíficos/administração & dosagem , Anticorpos Biespecíficos/efeitos adversos , Crise Blástica/tratamento farmacológico , Crise Blástica/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/induzido quimicamente , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Recidiva , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
Few patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) achieve prolonged disease-free survival. Blinatumomab, a bispecific T-cell engaging antibody construct, transiently links CD3-positive T cells to CD19-positive B cells. This phase 2 study evaluated stepwise (9-28-112 µg/d with weekly dose increases; n = 23) or flat (112 µg/d; n = 2) dosing of blinatumomab by continuous infusion, with dexamethasone prophylaxis, in patients with relapsed/refractory DLBCL. Patients received a median of 3 prior lines of therapy. Median time since last regimen was 1.5 months. Seventeen patients ended treatment in cycle 1 (induction), 7 in cycle 2 (consolidation), and 1 in retreatment. Among 21 evaluable patients, the overall response rate after 1 blinatumomab cycle was 43%, including complete responses (CRs) in 19%. Three patients had late CR in follow-up without other treatment. The most common adverse events with stepwise dosing were tremor (48%), pyrexia (44%), fatigue (26%), and edema (26%). Grade 3 neurologic events with stepwise dosing were encephalopathy and aphasia (each 9%) and tremor, speech disorder, dizziness, somnolence, and disorientation (each 4%). Of 5 (22%) patients who discontinued stepwise dosing because of adverse events, 4 (17%) had neurologic events. Most neurologic events resolved. The flat-dose cohort was stopped because of grade 3 neurologic events in both patients. Blinatumomab monotherapy appears effective in patients with relapsed/refractory DLBCL, a heavily pretreated patient population with a high unmet medical need. Further studies need to define the optimal approach to achieve the target dose without early dropout. The study was registered at www.clinicaltrials.gov as #NCT01741792.
Assuntos
Anticorpos Biespecíficos/uso terapêutico , Antineoplásicos/uso terapêutico , Imunoterapia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Terapia de Alvo Molecular , Adulto , Idoso , Anticorpos Biespecíficos/administração & dosagem , Anticorpos Biespecíficos/efeitos adversos , Anticorpos Biespecíficos/imunologia , Antígenos CD19/imunologia , Antígenos de Neoplasias/imunologia , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/imunologia , Complexo CD3/imunologia , Dexametasona/uso terapêutico , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Fadiga/induzido quimicamente , Feminino , Febre/induzido quimicamente , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/induzido quimicamente , Recidiva , Indução de Remissão , Terapia de Salvação , Carga TumoralRESUMO
BACKGROUND: Older adults with relapsed/refractory B-precursor acute lymphoblastic leukemia (r/r ALL) are reported to have a poor prognosis and few therapeutic options. In the current study, the authors evaluated treatment with single-agent blinatumomab in adults aged ≥65 years with r/r ALL. METHODS: A total of 261 adults with r/r ALL who were examined across two phase 2 studies received blinatumomab in cycles of 4-week continuous infusion and 2-week treatment-free intervals. The primary endpoint in each study was complete remission (CR) or CR with partial hematologic recovery (CRh) during the first 2 cycles. Data were pooled and analyzed according to patient age at screening (aged ≥65 years vs aged <65 years). RESULTS: Of 36 older adults, 56% (95% confidence interval [95% CI], 38%-72%) achieved CR/CRh during the first 2 cycles compared with 46% (225 patients) (95% CI, 40%-53%) of younger adults. Complete minimal residual disease responses were 60% in older and 70% in younger responders. Three older responders (15%) and 61 younger responders (59%) proceeded to allogeneic hematopoietic stem cell transplantation. Kaplan-Meier curves overlapped for relapse-free and overall survival for both age groups. Older adults were found to have a similar incidence of grade ≥3 adverse events (AEs) as younger adults (86% vs 80%) but more grade ≥3 neurologic events (28% vs 13%). Cytokine release syndrome occurred in 7 older (19%) (1 case of grade 3) and 23 younger (10%) (4 cases of grade ≥3) adults. There were no treatment-related fatal AEs reported. CONCLUSIONS: Older adults with r/r ALL who were treated with single-agent blinatumomab were found to have similar hematologic response rates and incidence of grade ≥3 AEs compared with younger adults but had more neurologic events, which were reversible and primarily resolved with treatment interruption. Cancer 2016;122:2178-85. © 2016 American Cancer Society.
Assuntos
Anticorpos Biespecíficos/uso terapêutico , Antineoplásicos/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ensaios Clínicos Fase II como Assunto , Resistencia a Medicamentos Antineoplásicos , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Estudos Multicêntricos como Assunto , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidade , Recidiva , Retratamento , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: We aimed to compare panitumumab, a fully human monoclonal antibody against EGFR, plus radiotherapy with chemoradiotherapy in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck. METHODS: In this international, open-label, randomised, controlled, phase 2 trial, we recruited patients with locally advanced squamous-cell carcinoma of the head and neck from 22 sites in eight countries worldwide. Patients aged 18 years and older with stage III, IVa, or IVb, previously untreated, measurable (≥ 10 mm for at least one dimension), locally advanced squamous-cell carcinoma of the head and neck (non-nasopharygeal) and an Eastern Cooperative Oncology Group performance status of 0-1 were randomly assigned (2:3) by an independent vendor to open-label chemoradiotherapy (two cycles of cisplatin 100 mg/m(2) during radiotherapy) or to radiotherapy plus panitumumab (three cycles of panitumumab 9 mg/kg every 3 weeks administered with radiotherapy) using a stratified randomisation with a block size of five. All patients received 70-72 Gy to gross tumour and 54 Gy to areas of subclinical disease with accelerated fractionation radiotherapy. The primary endpoint was local-regional control at 2 years, analysed in all randomly assigned patients who received at least one dose of their assigned protocol-specific treatment (chemotherapy, radiation, or panitumumab). The trial is closed and this is the final analysis. This study is registered with ClinicalTrials.gov, number NCT00547157. FINDINGS: Between Nov 30, 2007, and Nov 16, 2009, 152 patients were enrolled, and 151 received treatment (61 in the chemoradiotherapy group and 90 in the radiotherapy plus panitumumab group). Local-regional control at 2 years was 61% (95% CI 47-72) in the chemoradiotherapy group and 51% (40-62) in the radiotherapy plus panitumumab group. The most frequent grade 3-4 adverse events were mucosal inflammation (25 [40%] of 62 patients in the chemoradiotherapy group vs 37 [42%] of 89 patients in the radiotherapy plus panitumumab group), dysphagia (20 [32%] vs 36 [40%]), and radiation skin injury (seven [11%] vs 21 [24%]). Serious adverse events were reported in 25 (40%) of 62 patients in the chemoradiotherapy group and in 30 (34%) of 89 patients in the radiotherapy plus panitumumab group. INTERPRETATION: Panitumumab cannot replace cisplatin in the combined treatment with radiotherapy for unresected stage III-IVb squamous-cell carcinoma of the head and neck, and the role of EGFR inhibition in locally advanced squamous-cell carcinoma of the head and neck needs to be reassessed. FUNDING: Amgen.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias de Células Escamosas/terapia , Adolescente , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Cisplatino/administração & dosagem , Fracionamento da Dose de Radiação , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Agências Internacionais , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias de Células Escamosas/mortalidade , Neoplasias de Células Escamosas/patologia , Panitumumabe , Prognóstico , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND: Panitumumab is a fully human monoclonal antibody that targets EGFR. We aimed to compare chemoradiotherapy plus panitumumab with chemoradiotherapy alone in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck. METHODS: In this international, open-label, randomised, controlled, phase 2 trial, we recruited patients with locally advanced squamous-cell carcinoma of the head and neck from 41 sites in nine countries worldwide. Patients aged 18 years and older with stage III, IVa, or IVb, previously untreated, measurable (≥ 10 mm for at least one dimension), locally advanced squamous-cell carcinoma of the head and neck (non-nasopharygeal) and an Eastern Cooperative Oncology Group performance status of 0-1 were randomly assigned (2:3) by an independent vendor to open-label chemoradiotherapy (three cycles of cisplatin 100 mg/m(2)) or panitumumab plus chemoradiotherapy (three cycles of intravenous panitumumab 9.0 mg/kg every 3 weeks plus cisplatin 75 mg/m(2)) using stratified randomisation with a block size of five. All patients received 70 Gy to gross tumour and 50 Gy to areas at risk for subclinical disease with standard fractionation. The primary endpoint was local-regional control at 2 years, analysed in all randomised patients who received at least one dose of their assigned protocol-specific treatment (chemotherapy, radiation, or panitumumab). The trial is closed and this is the final analysis. This trial is registered with ClinicalTrials.gov, number NCT00500760. FINDINGS: Between Oct 26, 2007, and March 26, 2009, 153 patients were enrolled and 150 received treatment (63 in the chemoradiotherapy group and 87 in the panitumumab plus chemoradiotherapy group). Local-regional control at 2 years was 68% (95% CI 54-78) in the chemoradiotherapy group and 61% (50-71) in the panitumumab plus chemoradiotherapy group. The most frequent grade 3-4 adverse events were dysphagia (17 [27%] of 63 patients in the chemoradiotherapy group vs 35 [40%] of 87 in the panitumumab plus chemoradiotherapy group), mucosal inflammation (15 [24%] vs 48 [55%]), and radiation skin injury (eight [13%] vs 27 [31%]). Serious adverse events were reported in 20 (32%) of 63 patients in the chemoradiotherapy group and in 37 (43%) of 87 patients in the panitumumab plus chemoradiotherapy group. INTERPRETATION: In patients with locally advanced squamous-cell carcinoma of the head and neck, the addition of panitumumab to standard fractionation radiotherapy and cisplatin did not confer any benefit, and the role of EGFR inhibition in these patients needs to be reassessed. FUNDING: Amgen.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias de Células Escamosas/terapia , Adolescente , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Cisplatino/administração & dosagem , Fracionamento da Dose de Radiação , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Agências Internacionais , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias de Células Escamosas/mortalidade , Neoplasias de Células Escamosas/patologia , Panitumumabe , Prognóstico , Taxa de Sobrevida , Adulto JovemRESUMO
Direct support professionals (DSPs) may be at increased risk of contracting COVID-19 due to the proximal nature of their work. In response to the pandemic a three-wave study was launched to understand experiences of DSPs. An on-line national survey found that 70% of DSPs were vaccinated. Vaccinated DSPs were older and had higher education levels. Among the unvaccinated, 56% reported concerns about COVID-19 vaccination safety. Unvaccinated DSPs were more likely to report that the people they supported were also unvaccinated. Encouraging DSPs to get vaccinated to protect the people they support is essential. Paid time off, arranging for vaccinations, and setting an expectation for vaccination may encourage vaccination uptake among DSPs.
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COVID-19 , Deficiência Intelectual , Humanos , Vacinas contra COVID-19 , COVID-19/prevenção & controle , Vacinação , PandemiasRESUMO
Direct support professionals (DSPs) are at increased risk of contracting COVID-19. A four-wave survey series was conducted, in part, to understand DSPs' COVID-19 vaccination experiences. Fourth wave data were used to compare those vaccinated against COVID-19 when they became eligible (early adopters) and those waiting at least three months before vaccination (in-betweeners). Findings indicated that in-betweeners were more likely to be female, younger, and people of color with lower education levels and annual incomes, with employers requiring COVID-19 vaccination to remain employed. COVID-19 vaccination motivators included protection for self, family, or people supported; an employer who mandated COVID-19 vaccination; and having had COVID-19 or knowing someone who did.
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COVID-19 , Deficiência Intelectual , Humanos , Feminino , Masculino , COVID-19/prevenção & controle , Vacinas contra COVID-19RESUMO
Choice making is an important aspect of everyone's life in terms of fully becoming an adult within a democratic society. People with intellectual and developmental disabilities (IDD) are at risk for diminished choice making due to various factors, including guardianships; dependence on supports that are not person-centered; and, in some cases, limited capacity to express one's desires effectively. Independent Monitoring for Quality (IM4Q) data for 9,195 and 9,817 for adult services users with IDD were analyzed across two types of choice. Repeated measures mixed regression examined choice over time after controlling for age, support needs, residence type, and community type. We found significant increases in everyday choice making among IDD service users in Pennsylvania, but not in support-related choice. This study is the first to our knowledge to consider change in choice making, an important indicator of rights and inclusion for persons with IDD. By comparing three waves of data from the state of Pennsylvania (2013, 2016, and 2019), we were able to detect changes in choice making over time among home and community-based service (HCBS) users with IDD.
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Serviços de Saúde Comunitária , Deficiência Intelectual , Adulto , Criança , Humanos , Deficiências do Desenvolvimento/terapia , Medicaid , HabitaçãoRESUMO
Direct support professionals (DSPs) and frontline supervisors (FLSs) have critical roles in home and community-based services for people with intellectual and developmental disabilities. Low wages and high levels of responsibility created a long-term crisis in recruitment and retention and are exacerbated by the COVID-19 pandemic. A national sample of DSPs and FLSs were compared on demographics and work-related circumstances using data from the third Direct Support Workforce COVID-19 Survey. Significant differences were found in demographics, hours worked, wages, wage augmentations, and quality of work-life. Policy recommendations to address the worsening workforce crisis are provided.
Assuntos
COVID-19 , Deficiência Intelectual , Criança , Humanos , Pandemias , Pessoal de Saúde , Deficiências do Desenvolvimento , Deficiência Intelectual/epidemiologia , Recursos HumanosRESUMO
The purpose of this study is to lay a foundation for illustrating the importance of longitudinal data collection by sharing the results of the Independent Monitoring for Quality (IM4Q) program in Pennsylvania designed to collect data over time on the quality of services for adults with intellectual and developmental disabilities. In this article, we report on the history and characteristics of the IM4Q program, describe the key variables of interest, and highlight the trends in the key variables over 3 years of data collection (2013, 2016, and 2019). The descriptive results indicate mixed trends for the three areas of focus: comparable rates of people employed in community-based settings, less support-related choice, and better everyday choice-making outcomes.
Assuntos
Deficiência Intelectual , Adulto , Criança , Humanos , Deficiências do Desenvolvimento/terapiaRESUMO
Rationale & Objective: There is conflicting evidence regarding the type of ß-blockers to use in dialysis patients. This systematic review seeks to determine whether highly dialyzable ß-blockers are associated with higher rates of cardiovascular events and mortality in hemodialysis patients than poorly dialyzable ß-blockers. Study Design: A systematic review of the existing literature was conducted. A meta-analysis was performed using data from the selected studies. Setting & Study Populations: Participants were from the United States, Canada, and Taiwan. The mean ages of participants ranged from 55.9-75.7 years. Selection Criteria for Studies: We searched the Ovid MEDLINE database from 1990 to September 2020. Studies without adult hemodialysis participants and without comparisons of at least 2 ß-blockers of different dialyzability were excluded. Data Extraction: Baseline and adjusted outcome data were extracted from each study. Analytical Approach: Random-effects models were used to calculate pooled risk ratios using fully adjusted models from individual studies. Results: Four cohort studies were included. Pooling fully adjusted models, highly dialyzable ß-blockers did not influence mortality (HR, 0.94; 95% CI, 0.81-1.08; I2 = 0.84) compared with poorly dialyzable ß-blockers but were associated with a reduction in cardiovascular events (HR, 0.88; 95% CI, 0.83-0.93). There was significant heterogeneity between studies (I2 = 0.35). Only 1 study reported on adverse events. Intradialytic hypotension was more common in those on carvedilol (a poorly dialyzable ß-blocker) compared with those on metoprolol (a highly dialyzable ß-blocker; adjusted incidence rate ratio, 1.10; 95% CI, 1.09-1.11). Limitations: No randomized controlled trials were identified. Each study used different analytic methods and different definitions for outcomes. Classifications of ß-blockers varied. Only 1 study reported on adverse events. Conclusions: Pooled data suggest highly dialyzable ß-blockers are associated with similar mortality events and fewer cardiovascular events compared with poorly dialyzable ß-blockers.
RESUMO
Direct support professionals (DSPs) and frontline supervisors (FLSs) play an invaluable role in delivering home and community-based services to people with intellectual and developmental disabilities (IDD). DSPs provide support with employment, community living, developing social connections, health and well-being, and many other areas. FLSs' primary responsibility is to provide direction and guidance to DSPs in their work; however, they also frequently provide direct support to people with IDD. This workforce has been in crisis with high turnover and vacancy which threaten the inclusion of individuals with disabilities in their communities. The COVID-19 pandemic exacerbated an already fraught situation.
RESUMO
The phase 2 portion of this open-label phase 2/3 study assessed the efficacy and safety of blinatumomab as second salvage for aggressive relapsed or refractory (r/r) aggressive B-cell non-Hodgkin lymphoma (B-NHL) following platinum-based first salvage chemotherapy. Forty-one patients with aggressive disease (32% relapsed; 68% refractory) enrolled and received stepwise blinatumomab (9-28-112 µg/day) in a 70-day cycle 1 and an optional 28-day cycle 2; 19 (46%) completed cycle 1 and 3 (7%) completed cycle 2. The overall response rate after 12 weeks was 37%, including 9 (22%) complete metabolic responses. Eight (20%) patients (all responders) subsequently received stem cell transplants. Grade ≥3 adverse events were reported in 29 (71%) patients. Grade 3 cytokine release syndrome occurred in one patient. Grade 3 neurologic events occurred in 10 (24%) patients; all resolved. Blinatumomab monotherapy appears effective as second salvage therapy in patients with r/r aggressive B-NHL. Trial registration: NCT02910063.
Assuntos
Linfoma não Hodgkin , Terapia de Salvação , Adulto , Anticorpos Biespecíficos , Protocolos de Quimioterapia Combinada Antineoplásica , Linfócitos B , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Recidiva Local de NeoplasiaRESUMO
As part of a university-based quality improvement project, we aimed to evaluate child psychiatrists' knowledge, skills, attitudes, and practices regarding assessment and treatment of pediatric sleep problems. We developed a nine-question survey of knowledge, skills, attitudes, and practices regarding assessing for and treating sleep complaints in pediatric patients, and administered this survey to child psychiatrists in training and in practice in the state of Missouri. Respondents reported sleep hygiene as the first-line treatment strategy, followed by the use of supplements or over-the-counter remedies. The most common barriers to evidence-based assessment and treatment of sleep problems were the lack of ability to obtain reliable history, and parental preference for medications over behavioral approaches for sleep concerns. These results suggest potential opportunities for enhancing knowledge regarding validated assessment tools and non-pharmacological treatment options for sleep problems. Additional research is needed to further assess the quality and type of sleep education provided in child psychiatry training programs.
RESUMO
For the biomanufacturing of protein biologics, establishing stable cell lines with high transgene transcription is critical for high productivity. Modern genome engineering tools can direct transgene insertion to a specified genomic locus and can potentially become a valuable tool for cell line generation. In this study, the authors survey transgene integration sites and their transcriptional activity to identify characteristics of desirable regions. A lentivirus containing destabilized Green Fluorescent Protein (dGFP) is used to infect Chinese hamster ovary cells at a low multiplicity of infection, and cells with high or low GFP fluorescence are isolated. RNA sequencing and Assay for Transposase Accessible Chromatin using sequencing data shows integration sites with high GFP expression are in larger regions of high transcriptional activity and accessibility, but not necessarily within highly transcribed genes. This method is used to obtain high Immunoglobulin G (IgG) expressing cell lines with a single copy of the transgene integrated into transcriptionally active and accessible genomic regions. Dual recombinase-mediated cassette exchange is then employed to swap the IgG transgene for erythropoietin or tumor necrosis factor receptor-Fc. This work thus highlights a strategy to identify desirable sites for transgene integration and to streamline the development of new product producing cell lines.
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Proteínas Recombinantes , Ativação Transcricional , Transgenes , Animais , Células CHO , Cricetulus , Proteínas de Fluorescência Verde , Lentivirus , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genéticaRESUMO
BACKGROUND: The Plastic Surgery In-Service Training Exam is a knowledge assessment tool widely used during plastic surgery training in the United States. This study analyzed literature supporting correct answer choices to determine highest yield sources, journal publication lag, and journal impact factors. METHODS: Digital syllabi of 10 consecutive Plastic Surgery In-Service Training Exam administrations (2006 to 2015) were reviewed. The most-referenced articles, journals, and textbooks were determined. Mean journal impact factor and publication lag were calculated and differences were elucidated by section. RESULTS: Two thousand questions and 5386 references were analyzed. From 2006 to 2015, the percentage of journal citations increased, whereas textbook references decreased (p < 0.001). Plastic and Reconstructive Surgery was cited with greatest frequency (38.5 percent), followed by Clinics in Plastic Surgery (5.6 percent), Journal of Hand Surgery (American volume) (5.1 percent), and Annals of Plastic Surgery (3.8 percent). There was a trend toward less publication lag over the study period (p = 0.05), with a mean publication lag of 9.1 ± 9.0 years for all journal articles. Mean journal impact factor was 2.3 ± 4.3 and lowest for the hand and lower extremity section (1.7 ± 2.8; p < 0.001). The highest yield textbooks were elucidated by section. CONCLUSION: Plastic surgery faculty and residents may use these data to facilitate knowledge acquisition during residency.