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1.
Arthritis Care Res (Hoboken) ; 74(1): 126-130, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-32860731

RESUMO

OBJECTIVE: Systemic lupus erythematosus (SLE) has one of the highest 30-day hospital readmission rates among chronic diseases in the US. This quality improvement initiative developed and assessed the feasibility of a multidisciplinary postdischarge intervention to reduce 30-day readmission rates among SLE patients. METHODS: A retrospective study was performed using electronic health records of patients with SLE admitted to a university hospital prior to (nonintervention group) and after initiation of the study intervention (intervention group). The study population included patients with a diagnosis of SLE who were admitted to the hospital for any reason during an 8-month time period. The intervention involved sending a templated message at the time of discharge to the rheumatology clinic nurses, which prompted the nurses to call the patient to coordinate future visits and provide education. The primary outcome was the 30-day hospital readmission rate. Data were analyzed using a multivariate mixed binomial regression model. RESULTS: There were 59 hospitalizations in the nonintervention group and 73 hospitalizations in the intervention group during the 8-month study period. The 30-day readmission rate was 29% in the nonintervention group and 19% in the intervention group. The difference in readmission rates between the 2 groups was not statistically significant based on the multivariate model. CONCLUSION: Our study demonstrates the feasibility of implementing a multidisciplinary postdischarge intervention to reduce readmission rates for patients with SLE in a large academic medical center. Further investigation is warranted to determine if this approach reduces the unacceptably high hospital readmission rates among SLE patients.


Assuntos
Assistência ao Convalescente/métodos , Lúpus Eritematoso Sistêmico , Readmissão do Paciente , Melhoria de Qualidade , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
2.
Circ Cardiovasc Qual Outcomes ; 14(3): e006570, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33653116

RESUMO

BACKGROUND: Among Medicare value-based payment programs for acute myocardial infarction (AMI), the Hospital Readmissions Reduction Program uses International Classification of Diseases, Tenth Revision (ICD-10) codes to identify the program denominator, while the Bundled Payments for Care Improvement Advanced program uses diagnosis-related groups (DRGs). The extent to which these programs target similar patients, whether they target the intended population (type 1 myocardial infarction), and whether outcomes are comparable between cohorts is not known. METHODS: In a retrospective study of 2176 patients hospitalized in an integrated health system, a cohort of patients assigned a principal ICD-10 diagnosis of AMI and a cohort of patients assigned an AMI DRG were compared according to patient-level agreement and outcomes such as mortality and readmission. RESULTS: One thousand nine hundred thirty-five patients were included in the ICD-10 cohort compared with 662 patients in the DRG cohort. Only 421 patients were included in both AMI cohorts (19.3% agreement). DRG cohort patients were older (70 versus 65 years, P<0.001), more often female (48% versus 30%, P<0.001), and had higher rates of heart failure (52% versus 33%, P<0.001) and kidney disease (42% versus 25%, P<0.001). Comparing outcomes, the DRG cohort had significantly higher unadjusted rates of 30-day mortality (6.6% versus 2.5%, P<0.001), 1-year mortality (21% versus 8%, P<0.001), and 90-day readmission (26% versus 19%, P=0.006) than the ICD-10 cohort. Two observations help explain these differences: 61% of ICD-10 cohort patients were assigned procedural DRGs for revascularization instead of an AMI DRG, and type 1 myocardial infarction patients made up a smaller proportion of the DRG cohort (34%) than the ICD-10 cohort (78%). CONCLUSIONS: The method used to identify denominators for value-based payment programs has important implications for the patient characteristics and outcomes of the populations. As national and local quality initiatives mature, an emphasis on ICD-10 codes to define AMI cohorts would better represent type 1 myocardial infarction patients.


Assuntos
Prestação Integrada de Cuidados de Saúde , Infarto do Miocárdio , Idoso , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Grupos Diagnósticos Relacionados , Feminino , Humanos , Classificação Internacional de Doenças , Masculino , Medicare , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/terapia , Readmissão do Paciente , Indicadores de Qualidade em Assistência à Saúde , Estudos Retrospectivos , Estados Unidos/epidemiologia
3.
Clin Cancer Res ; 27(3): 819-830, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33109736

RESUMO

PURPOSE: The prognosis of patients with multiple myeloma who are resistant to proteasome inhibitors, immunomodulatory drugs (IMiD), and daratumumab is extremely poor. Even B-cell maturation antigen-specific chimeric antigen receptor T-cell therapies provide only a temporary benefit before patients succumb to their disease. In this article, we interrogate the unique sensitivity of multiple myeloma cells to the alternative strategy of blocking protein translation with omacetaxine. EXPERIMENTAL DESIGN: We determined protein translation levels (n = 17) and sensitivity to omacetaxine (n = 51) of primary multiple myeloma patient samples. Synergy was evaluated between omacetaxine and IMiDs in vitro, ex vivo, and in vivo. Underlying mechanism was investigated via proteomic analysis. RESULTS: Almost universally, primary patient multiple myeloma cells exhibit >2.5-fold increased rates of protein translation compared with normal marrow cells. Ex vivo treatment with omacetaxine resulted in >50% reduction in viable multiple myeloma cells. In this cohort, high levels of translation serve as a biomarker for patient multiple myeloma cell sensitivity to omacetaxine. Unexpectedly, omacetaxine demonstrated synergy with IMiDs in multiple myeloma cell lines in vitro. In addition, in an IMiD-resistant relapsed patient sample, omacetaxine/IMiD combination treatment resensitized the multiple myeloma cells to the IMiD. Proteomic analysis found that the omacetaxine/IMiD combination treatment produced a double-hit on the IRF4/c-MYC pathway, which is critical to multiple myeloma survival. CONCLUSIONS: Overall, protein translation inhibitors represent a potential new drug class for myeloma treatment and provide a rationale for conducting clinical trials with omacetaxine alone and in combination with IMiDs for patients with relapsed/refractory multiple myeloma.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Mepesuccinato de Omacetaxina/farmacologia , Mieloma Múltiplo/tratamento farmacológico , Biossíntese de Proteínas/efeitos dos fármacos , Inibidores da Síntese de Proteínas/farmacologia , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea/patologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Sinergismo Farmacológico , Mepesuccinato de Omacetaxina/uso terapêutico , Humanos , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/uso terapêutico , Fatores Reguladores de Interferon/antagonistas & inibidores , Fatores Reguladores de Interferon/metabolismo , Camundongos , Mieloma Múltiplo/patologia , Cultura Primária de Células , Inibidores da Síntese de Proteínas/uso terapêutico , Proteínas Proto-Oncogênicas c-myc/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-myc/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Blood Adv ; 4(10): 2227-2235, 2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32442301

RESUMO

We compared outcomes among adult matched related donor (MRD) patients undergoing peripheral blood stem cell transplantation and adult patients undergoing double unit cord blood transplantation (CBT) at our center between 2010 and 2017. A total of 190 CBT patients were compared with 123 MRD patients. Median follow-up was 896 days (range, 169-3350) among surviving CBT patients and 1262 days (range, 249-3327) among surviving MRD patients. Comparing all CBT with all MRD patients, overall survival (OS) was comparable (P = .61) and graft-versus-host disease (GVHD) relapse-free survival (GRFS) was significantly improved among CBT patients (P = .0056), primarily because of decreased moderate to severe chronic GVHD following CBT (P < .0001; hazard ratio [HR], 3.99; 95% confidence interval [CI], 2.26-7.04). Among patients undergoing our most commonly used MRD and umbilical cord blood (CB) myeloablative regimens, OS was comparable (P = .136) and GRFS was significantly improved among CBT patients (P = .006). Cumulative incidence of relapse trended toward decreased in the CBT group (P = .075; HR, 1.85; CI 0.94-3.67), whereas transplant-related mortality (TRM) was comparable (P = .55; HR, 0.75; CI, 0.29-1.95). Among patients undergoing our most commonly used nonmyeloablative regimens, OS and GRFS were comparable (P = .158 and P = .697). Cumulative incidence of both relapse and TRM were comparable (P = .32; HR, 1.35; CI, 0.75-2.5 for relapse and P = .14; HR, 0.482; CI, 0.18-1.23 for TRM). Our outcomes support the efficacy of CBT and suggest that among patients able to tolerate more intensive conditioning regimens at high risk for relapse, CB may be the preferred donor source.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Adulto , Sangue Fetal , Doença Enxerto-Hospedeiro/etiologia , Humanos , Condicionamento Pré-Transplante
5.
Blood Adv ; 4(8): 1628-1639, 2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32311014

RESUMO

The oncogenic drivers and progression factors in multiple myeloma (MM) are heterogeneous and difficult to target therapeutically. Many different MM drugs have emerged, however, that attack various phenotypic aspects of malignant plasma cells. These drugs are administered in numerous, seemingly interchangeable combinations. Although the availability of many treatment options is useful, no clinical test capable of optimizing and sequencing the treatment regimens for an individual patient is currently available. To overcome this problem, we developed a functional ex vivo approach to measure patients' inherent and acquired drug resistance. This method, which we termed myeloma drug sensitivity testing (My-DST), uses unselected bone marrow mononuclear cells with a panel of drugs in clinical use, followed by flow cytometry to measure myeloma-specific cytotoxicity. We found that using whole bone marrow cultures helped preserve primary MM cell viability. My-DST was used to profile 55 primary samples at diagnosis or at relapse. Sensitivity or resistance to each drug was determined from the change in MM viability relative to untreated control samples. My-DST identified progressive loss of sensitivity to immunomodulatory drugs, proteasome inhibitors, and daratumumab through the disease course, mirroring the clinical development of resistance. Prospectively, patients' ex vivo drug sensitivity to the drugs subsequently received was sensitive and specific for clinical response. In addition, treatment with <2 drugs identified as sensitive by My-DST led to inferior depth and duration of clinical response. In summary, ex vivo drug sensitivity is prognostically impactful and, with further validation, may facilitate more personalized and effective therapeutic regimens.


Assuntos
Mieloma Múltiplo , Anticorpos Monoclonais , Humanos , Mieloma Múltiplo/tratamento farmacológico , Recidiva Local de Neoplasia , Inibidores de Proteassoma
6.
Cancer Discov ; 10(4): 536-551, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31974170

RESUMO

Venetoclax-based therapy can induce responses in approximately 70% of older previously untreated patients with acute myeloid leukemia (AML). However, up-front resistance as well as relapse following initial response demonstrates the need for a deeper understanding of resistance mechanisms. In the present study, we report that responses to venetoclax +azacitidine in patients with AML correlate closely with developmental stage, where phenotypically primitive AML is sensitive, but monocytic AML is more resistant. Mechanistically, resistant monocytic AML has a distinct transcriptomic profile, loses expression of venetoclax target BCL2, and relies on MCL1 to mediate oxidative phosphorylation and survival. This differential sensitivity drives a selective process in patients which favors the outgrowth of monocytic subpopulations at relapse. Based on these findings, we conclude that resistance to venetoclax + azacitidine can arise due to biological properties intrinsic to monocytic differentiation. We propose that optimal AML therapies should be designed so as to independently target AML subclones that may arise at differing stages of pathogenesis. SIGNIFICANCE: Identifying characteristics of patients who respond poorly to venetoclax-based therapy and devising alternative therapeutic strategies for such patients are important topics in AML. We show that venetoclax resistance can arise due to intrinsic molecular/metabolic properties of monocytic AML cells and that such properties can potentially be targeted with alternative strategies.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Leucemia Mieloide Aguda/tratamento farmacológico , Sulfonamidas/uso terapêutico , Idoso , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Humanos , Sulfonamidas/farmacologia
7.
Dermatol Surg ; 46(9): 1195-1201, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-31834070

RESUMO

BACKGROUND: Although gender disparities for those entering medicine have equalized, the number of women advancing in academia has remained low. Studies have demonstrated that women's representation at academic medical conferences has also remained low across multiple fields. Given that conference presentations and national reputation serve as metrics for academic promotion, women's representation at dermatology conferences may provide insight into women's academic productivity. OBJECTIVE: To examine the gender composition of presenters and speaking time at the 2 main national dermatologic surgery conferences. METHODS: Speaker's gender, presentation time, and topics were collected for 2009 to 2017 for the American College of Mohs Surgery (ACMS) and the American Society for Dermatologic Surgery (ASDS) Annual Meetings. RESULTS: Women had significantly fewer speaking opportunities and speaking minutes at both conferences. This disparity was most pronounced in reconstruction topics and least pronounced in cosmetics topics. The majority of top speakers, repeat speakers, and keynote speakers were men for both conferences. Oral abstracts showed no gender disparity at either conference. CONCLUSION: Women spoke less than men at both the ASDS and ACMS annual meetings over multiple years studied. Recently, this disparity in speaking opportunities has decreased. Further studies are needed to evaluate the speaking opportunities for women at other types of dermatology conferences.


Assuntos
Congressos como Assunto/estatística & dados numéricos , Sexismo/estatística & dados numéricos , Sociedades Médicas/estatística & dados numéricos , Cirurgia Plástica/estatística & dados numéricos , Feminino , Humanos , Masculino , Fatores Sexuais , Fala , Estados Unidos
8.
Clin Lymphoma Myeloma Leuk ; 20(1): 39-46, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31761712

RESUMO

BACKGROUND: Follicular lymphoma (FL) grading, low-grade 1-2 (LG) versus grade 3A (3A), informs management. However, accurate grading is challenging owing to disease heterogeneity and inter-reader variability. The [18F]-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) parameter maximum standardized uptake value (SUVmax) has utility in differentiating LG from 3A FL, but the utility of novel parameters total lesion glycolysis (TLG) and total metabolic tumor volume (TMTV) is unknown. PATIENTS AND METHODS: Retrospective review of diagnostic pre-treatment PET-CTs of patients aged > 18 years with FL grades 1-3A from 2009-2017 was performed. PET-CT parameters SUVmax, TLG, and TMTV values were generated using manual (MW) and semi-automated workflows (SW). Poisson regression and receiver operating characteristic curves were used to compare PET-CT parameters between LG and 3A. RESULTS: A total of 49 patients with FL were identified: 38 LG and 11 3A. PET-CT parameters were significantly higher in 3A as compared with LG in both workflows. The cutoff values, sensitivities, and specificities were as follows: SUVmax: 10.4, 64%, and 74% in MW and 11.9, 73%, and 76% in SW; TLG: 543, 82%, and 74% in MW and 371, 73%, and 74% in SW; and TMTV: 141, 73%, and 76% in MW and 93, 64%, and 76% in SW. SUVmax had identical cutoff, sensitivity, and specificity across all 3 SWs, whereas TLG and TMTV had considerable variance across all 3 SWs. CONCLUSIONS: TLG and TMTV are comparable to SUVmax in differentiating LG versus 3A FL. Cutoffs, sensitivities, and specificities varied in MW versus SW. Novel PET-CT parameters serve as reproducible adjuncts but not replacements for biopsy in differentiating grades of FL.


Assuntos
Linfoma Folicular/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Idoso , Diferenciação Celular , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Retrospectivos
9.
Perm J ; 232019.
Artigo em Inglês | MEDLINE | ID: mdl-31702983

RESUMO

CONTEXT: Geriatric hip fractures are increasingly common and confer substantial morbidity and mortality. Fragmentation in geriatric hip fracture care remains a barrier to improved outcomes. OBJECTIVE: To evaluate the impact of a comprehensive geriatric hip fracture program on long-term mortality. DESIGN: We conducted a retrospective cohort study of patients aged 65 years and older admitted to our academic medical center between January 1, 2012, and March 31, 2016 with an acute fragility hip fracture. Mortality data were obtained for in-state residents from the state public health department. MAIN OUTCOME MEASURES: Mortality within 1 year of index admission and overall survival based on available follow-up data. RESULTS: We identified 243 index admissions during the study period, including 135 before and 108 after program implementation in October 2014. The postintervention cohort trended toward a lower unadjusted 1-year mortality rate compared with the preintervention cohort (15.7% vs 24.4%, p = 0.111), as well as lower adjusted mortality at 1 year (relative risk = 0.73, 95% confidence interval = 0.46-1.16, p = 0.18), although the differences were not statistically significant. The postintervention cohort had significantly higher overall survival than did the preintervention cohort (hazard ratio for death = 0.43, 95% confidence interval = 0.25-0.74, p = 0.002). CONCLUSION: Fixing fragmentation in geriatric hip fracture care such as through an orthogeriatric model is essential to improving overall survival for this patient population.


Assuntos
Assistência Integral à Saúde/métodos , Serviços de Saúde para Idosos , Fraturas do Quadril/terapia , Idoso , Idoso de 80 Anos ou mais , Assistência Integral à Saúde/organização & administração , Serviços de Saúde para Idosos/organização & administração , Fraturas do Quadril/mortalidade , Humanos , Masculino , Estudos Retrospectivos , Análise de Sobrevida
10.
Leuk Res ; 81: 43-49, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31009835

RESUMO

BACKGROUND: Patients with relapsed and refractory (R/R) acute myeloid leukemia (AML) have limited treatment options. Genomically-defined personalized therapies are only applicable for a minority of patients. Therapies without identifiable targets can be effective but patient selection is challenging. The sequential combination of azacitidine with high-dose lenalidomide has shown activity; we aimed to determine the efficacy of this genomically-agnostic regimen in patients with R/R AML, with the intention of applying sophisticated methods to predict responders. METHODS: Thirty-seven R/R AML/myelodysplastic syndrome patients were enrolled in a phase 2 study of azacitidine with lenalidomide. The primary endpoint was complete remission (CR) and CR with incomplete blood count recovery (CRi) rate. A computational biological modeling (CBM) approach was applied retrospectively to predict outcomes based on the understood mechanisms of azacitidine and lenalidomide in the setting of each patients' disease. FINDINGS: Four of 37 patients (11%) had a CR/CRi; the study failed to meet the alternative hypothesis. Significant toxicity was observed in some cases, with three treatment-related deaths and a 30-day mortality rate of 14%. However, the CBM method predicted responses in 83% of evaluable patients, with a positive and negative predictive value of 80% and 89%, respectively. INTERPRETATION: Sequential azacitidine and high-dose lenalidomide is effective in a minority of R/R AML patients; it may be possible to predict responders at the time of diagnosis using a CBM approach. More efforts to predict responses in non-targeted therapies should be made, to spare toxicity in patients unlikely to respond and maximize treatments for those with limited options.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biologia Computacional/métodos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Leucemia Mieloide Aguda/tratamento farmacológico , Síndromes Mielodisplásicas/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Terapia de Salvação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Azacitidina/administração & dosagem , Feminino , Seguimentos , Humanos , Lenalidomida/administração & dosagem , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/patologia , Recidiva Local de Neoplasia/patologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
12.
High Alt Med Biol ; 19(4): 367-372, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30281336

RESUMO

BACKGROUND: High-altitude (HA) pregnancies have been associated with decreased glucose levels and increased insulin sensitivity versus sea level. Our objective was to determine if the prevalence of gestational diabetes mellitus (GDM) and the impact of demographic characteristics on GDM diagnosis differed at moderate altitude (MA) versus HA. METHODS: Using a retrospective cohort design, we compared women living at HA (>8250 ft) and MA (4000-7000 ft) during pregnancy. Exclusion criteria were as follows: multiple gestation, preexisting diabetes, unavailable GDM results, or relocation from a different altitude during pregnancy. GDM diagnosis was determined using Carpenter and Coustan criteria. Data were compared by t-test (continuous variables) or chi-squared tests (categorical variables). Univariate, multivariate, and stepwise regression models were used to assess the impact of various factors on GDM prevalence. RESULTS: There was no difference in GDM prevalence between altitudes in these populations; the relationship between altitude and GDM was nonsignificant in all regression analyses. At MA, maternal age, Hispanic ethnicity, body mass index (BMI), and gestational age (GA) at testing increased GDM incidence in univariate analyses. At HA, maternal age, Hispanic ethnicity, and multiparity increased GDM incidence in univariate analyses. CONCLUSION: While GDM prevalence did not differ between MA and HA, the impact of maternal demographic characteristics on GDM risk varied by altitude group. Higher BMI and greater GA at testing increased the incidence of GDM at MA, but not at HA. Multiparity had an effect at HA, but not MA. These differences may represent subtle differences in glucose metabolism at HA.


Assuntos
Altitude , Diabetes Gestacional/epidemiologia , Adulto , Distribuição de Qui-Quadrado , Diabetes Gestacional/etiologia , Feminino , Hispânico ou Latino/estatística & dados numéricos , Humanos , Incidência , Idade Materna , Análise Multivariada , Paridade , Gravidez , Prevalência , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco
13.
J Infect Dis ; 218(suppl_2): S81-S87, 2018 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-30247596

RESUMO

Background: Live attenuated (ZV) and recombinant adjuvanted (HZ/su) zoster vaccines differ with respect to efficacy, effect of age, and persistence of protection. We compared cell-mediated immunity (CMI responses to ZV and HZ/su. Methods: This was a randomized, double-blind, placebo-controlled trial stratified by age (50-59 and 70-85 years) and by HZ vaccination status (received ZV ≥5 years before entry or not). Varicella zoster virus (VZV)- and glycoprotein E (gE)-specific CMI were analyzed by interleukin 2 (IL-2) and interferon gamma (IFN-γ) FluoroSpot and flow cytometry at study days 0, 30, 90, and 365. Results: Responses to ZV peaked on day 30 and to HZ/su (administered in 2 doses separated by 60 days) peaked on day 90. Age and vaccination status did not affect peak responses, but higher baseline CMI correlated with higher peak responses. HZ/su generated significantly higher VZV-specific IL-2+ and gE-specific IL-2+, IFN-γ+, and IL-2+/IFN-γ+ peak and 1-year baseline-adjusted responses compared with ZV. VZV-specific IFN-γ+ and IL-2+/IFN-γ+ did not differ between vaccines. HZ/su generated higher memory and effector-memory CD4+ peak responses and ZV generated higher effector CD4+ responses . Conclusions: The higher IL-2 and other memory responses generated by HZ/su compared with ZV may contribute to its superior efficacy. Clinical Trials Registration: NCT02114333.


Assuntos
Vacina contra Herpes Zoster/imunologia , Herpes Zoster/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Citocinas/genética , Citocinas/metabolismo , Método Duplo-Cego , Feminino , Humanos , Interferon gama/metabolismo , Interleucina-2/metabolismo , Masculino , Pessoa de Meia-Idade , Linfócitos T/classificação , Linfócitos T/fisiologia
14.
J Clin Invest ; 128(10): 4429-4440, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30024861

RESUMO

The adjuvanted varicella-zoster virus (VZV) glycoprotein E (gE) subunit herpes zoster vaccine (HZ/su) confers higher protection against HZ than the live attenuated zoster vaccine (ZV). To understand the immunologic basis for the different efficacies of the vaccines, we compared immune responses to the vaccines in adults 50 to 85 years old. gE-specific T cells were very low/undetectable before vaccination when analyzed by FluoroSpot and flow cytometry. Both ZV and HZ/su increased gE-specific responses, but at peak memory response (PMR) after vaccination (30 days after ZV or after the second dose of HZ/su), gE-specific CD4+ and CD8+ T cell responses were 10-fold or more higher in HZ/su compared with ZV recipients. Comparing the vaccines, T cell memory responses, including gE-IL-2+ and VZV-IL-2+ spot-forming cells (SFCs), were higher in HZ/su recipients and cytotoxic and effector responses were lower. At 1 year after vaccination, all gE-Th1 and VZV-IL-2+ SFCs remained higher in HZ/su compared with ZV recipients. Mediation analyses showed that IL-2+ PMR were necessary for the persistence of Th1 responses to either vaccine and VZV-IL-2+ PMR explained 73% of the total effect of HZ/su on persistence. This emphasizes the biological importance of the memory responses, which were clearly superior in HZ/su compared with ZV participants.


Assuntos
Vacina contra Herpes Zoster/administração & dosagem , Herpes Zoster/imunologia , Herpes Zoster/prevenção & controle , Herpesvirus Humano 3/imunologia , Memória Imunológica , Células Th1/imunologia , Vacinação , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/imunologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Feminino , Herpes Zoster/patologia , Vacina contra Herpes Zoster/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Células Th1/patologia , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/imunologia
15.
Biol Blood Marrow Transplant ; 24(8): 1671-1677, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29684565

RESUMO

The "Minnesota" reduced-intensity conditioning (RIC) cord blood transplantation (CBT) regimen (standard RIC) of fludarabine (Flu) (200 mg/m2), cyclophosphamide (Cy) (50 mg/kg), and 200- or 300-cGy total body irradiation (TBI) is the most published RIC CBT regimen. Though well tolerated, high relapse rates remain a concern with this regimen. Intensification of conditioning may reduce relapse without increasing transplant-related mortality (TRM). We performed a retrospective cohort comparison of outcomes in adult patients who underwent first double-unit CBT with standard RIC as compared with the intensified regimen of Flu 150 mg/m2, Cy 50 mg/kg, thiotepa 10 mg/kg, and 400-cGy TBI (intensified RIC). Of the 99 patients studied, 47 received intensified RIC. Acute myelogenous leukemia was the major indication for transplant. The median age at transplant was 67 years (range, 24 to 74 years) and 54 years (range, 25 to 67 years) in standard RIC and intensified RIC, respectively. Median hematopoietic stem cell transplantation comorbidity index was 3 (range, 0 to 5) and 1 (range, 0 to 6) in the standard RIC and intensified RIC groups, respectively. Median follow-up among survivors was 22 months (range, 3.7 to 79 months) following standard RIC and 15 months (range, 2.8 to 36 months) following intensified RIC. The cumulative incidence (CI) of relapse was significantly lower following intensified RIC compared with standard RIC (P = .0013); this finding maintained significance in multivariate analysis (P = .045). TRM was comparable between the 2 groups (P = .99). Overall survival (OS) was significantly improved following intensified RIC as compared with standard RIC (P = .03). Median OS was 17 months following standard RIC versus not reached followed intensified RIC. The CI of grade II to IV acute graft-versus-host disease (GVHD) was significantly higher in the intensified RIC cohort than the standard RIC-cohort (P = .007), while CI of grade III to IV acute GVHD, any chronic GVHD, and moderate-to-severe chronic GVHD was comparable in each cohort (P = .20, P = .21, and P = .61, respectively). This retrospective analysis shows an improvement in OS and decreased relapse without increase in TRM in patients receiving intensified RIC as compared with standard RIC. Our data suggest that consideration of thiotepa-based intensified RIC may improve outcomes in fit, older patients undergoing double-unit CBT.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Tiotepa/uso terapêutico , Condicionamento Pré-Transplante/métodos , Adulto , Idoso , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/mortalidade , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Agonistas Mieloablativos/uso terapêutico , Recidiva , Estudos Retrospectivos , Análise de Sobrevida , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/mortalidade , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico , Irradiação Corporal Total , Adulto Jovem
17.
Acad Emerg Med ; 24(7): 839-845, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28391603

RESUMO

OBJECTIVE: The objective was to evaluate the impact of evidence-based clinical decision support tools integrated directly into provider workflow in the electronic health record on utilization of computed tomography (CT) brain, C-spine, and pulmonary embolism (PE). METHODS: Validated, well-accepted scoring tools for head injury, C-spine injury, and PE were embedded into the electronic health record in a manner minimally disruptive to provider workflow. This was a longitudinal, before/after study in five emergency departments (EDs) in a healthcare system with a common electronic health record. Attending ED physicians practicing during the entire study period were included. The main outcome measure was proportion of CTs ordered by provider (total number of CT scans of a given type divided by total patients seen by that provider) in aggregate in the pre- and post intervention period. RESULTS: There were 235,858 total patient visits analyzed in this study with an absolute decrease of 6,106 CT scan ordering for the three studies. Across all sites, there was greater than 6% decrease in utilization of CT brain and CT C-spine (-10%, 95% CI = -13% to -7%, p < 0.001; and -6%, 95% CI =-11% to -1%, p = 0.03, respectively). The use of CT PE also decreased but was not significant (-2%, 95% CI = -9% to +5%, p = 0.42). For all CT types, high utilizers in the pre-intervention period decreased usage over 14% in the post-intervention period with CT brain (-18%, 95% CI = -22% to -15%, p < 0.001), CT C-spine (-14%, 95% CI = -20% to -8%, p = 0.001), and CT PE (-23%, 95% CI = -31% to -14%, p < 0.001). For all three studies, the average utilizers did not change their usage practices. For CT brain, the low utilizers also did not increase usage but for CT C-spine and CT PE usage was increased (+29%, 95% CI = 10% to 52%, p = 0.003; and +46%, 95% CI = 26% to 70%, p < 0.001, respectively). CONCLUSION: Embedded clinical decision support is associated with decreased overall utilization of high-cost imaging, especially among higher utilizers. It also affected low utilizers, increasing their usage consistent with improved adherence to guidelines, but this effect did not offset the overall decreased utilization for CT brain or CT C-spine. Thus, integrating clinical decision support into the provider workflow promotes usage of validated tools across providers, which can standardize the delivery of care and improve compliance with evidence-based guidelines.


Assuntos
Sistemas de Apoio a Decisões Clínicas/organização & administração , Serviço Hospitalar de Emergência/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Embolia Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Estudos Controlados Antes e Depois , Registros Eletrônicos de Saúde , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Risco
18.
Prehosp Disaster Med ; 31(5): 509-15, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27491645

RESUMO

BACKGROUND: Bystander cardiopulmonary resuscitation (CPR) improves survival after prehospital cardiac arrest. While community CPR training programs have been implemented across the US, little is known about their acceptability in non-US Latino populations. OBJECTIVES: The purpose of this study was to identify barriers to enrolling in CPR training classes and performing CPR in San José, Costa Rica. METHODS: After consulting 10 San José residents, a survey was created, pilot-tested, and distributed to a convenience sample of community members in public gathering places in San José. Questions included demographics, CPR knowledge and beliefs, prior CPR training, having a family member with heart disease, and prior witnessing of a cardiac arrest. Questions also addressed barriers to enrolling in CPR classes (cost/competing priorities). The analysis focused on two main outcomes: likelihood of registering for a CPR class and willingness to perform CPR on an adult stranger. Odds ratios and 95% CIs were calculated to test for associations between patient characteristics and these outcomes. RESULTS: Among 371 participants, most were male (60%) and <40 years old (77%); 31% had a college degree. Many had family members with heart disease (36%), had witnessed a cardiac arrest (18%), were trained in CPR (36%), and knew the correct CPR steps (70%). Overall, 55% (95% CI, 50-60%) indicated they would "likely" enroll in a CPR class; 74% (95% CI, 70-78%) would perform CPR on an adult stranger. Cardiopulmonary resuscitation class enrollment was associated with prior CPR training (OR: 2.6; 95% CI, 1.6-4.3) and a prior witnessed cardiac arrest (OR: 2.0; 95% CI, 1.1-3.5). Willingness to perform CPR on a stranger was associated with a prior witnessed cardiac arrest (OR: 2.5; 95% CI, 1.2-5.4) and higher education (OR: 1.9; 95% CI, 1.1-3.2). Believing that CPR does not work was associated with a higher likelihood of not attending a CPR class (OR: 2.4; 95% CI, 1.7-7.9). Fear of performing mouth-mouth, believing CPR is against God's will, and fear of legal risk were associated with a likelihood of not attending a CPR class and not performing CPR on a stranger (range of ORs: 2.4-3.9). CONCLUSION: Most San José residents are willing to take CPR classes and perform CPR on a stranger. To implement a community CPR program, barriers must be considered, including misgivings about CPR efficacy and legal risk. Hands-only CPR programs may alleviate hesitancy to perform mouth-to-mouth. Schmid KM , Mould-Millman NK , Hammes A , Kroehl M , Quiros García R , Umaña McDermott M , Lowenstein SR . Barriers and facilitators to community CPR education in San José, Costa Rica. Prehosp Disaster Med. 2016;31(5):509-515.


Assuntos
Reanimação Cardiopulmonar/educação , Educação em Saúde , Parada Cardíaca Extra-Hospitalar/terapia , Adulto , Pesquisa Participativa Baseada na Comunidade , Costa Rica , Serviços Médicos de Emergência , Feminino , Educação em Saúde/estatística & dados numéricos , Humanos , Masculino , Razão de Chances , Inquéritos e Questionários
19.
J Card Fail ; 22(11): 908-912, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27150493

RESUMO

BACKGROUND: People with end-stage heart failure may have to decide about destination-therapy left ventricular assist device (DT-LVAD). Individuals facing difficult decisions often rely on heuristics, such as anchoring, which predictably bias decision outcomes. We aimed to investigate whether showing a larger historical Heartmate XVE creates an anchoring effect, making the smaller Heartmate II (HMII) appear more favorable. METHODS: With the use of Amazon Mechanical Turk, participants watched videos asking them to imagine themselves dying of end-stage heart failure, then were presented the option of LVAD as potentially life-prolonging therapy. Participants were randomized to a control group who were only shown the HMII device, and the intervention group who saw the XVE device before the HMII. Participants then completed surveys. RESULTS: A total of 487 participants completed the survey (control = 252; intervention = 235); 79% were <40 years of age, 84% were white, and 55% were male. The intervention group was not more likely to accept the LVAD therapy (68% vs 61%; P = .37). However, participants in the intervention group were more likely (51% vs 17%; P < .01) to agree or strongly agree with the statement that the HMII was "smaller than expected." Participants in the intervention group were also more likely to rate the size of the device as "important" or "very important" in their decision (61% vs 46%; P < .01). CONCLUSIONS: Although the XVE anchor did not affect likelihood of accepting the LVAD, it did affect device perception. This article highlights an important point with clinical implications: factors such as anchoring have the potential to inappropriately influence perceptions and decisions and should be carefully considered in research and practice.


Assuntos
Tomada de Decisões , Insuficiência Cardíaca/cirurgia , Coração Auxiliar/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Educação de Pacientes como Assunto/métodos , Adulto , Fatores Etários , Idoso , Feminino , Insuficiência Cardíaca/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Participação do Paciente/estatística & dados numéricos , Desenho de Prótese , Valores de Referência , Fatores de Risco , Fatores Sexuais , Estados Unidos , Gravação em Vídeo , Adulto Jovem
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