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1.
Blood ; 139(2): 287-299, 2022 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-34534280

RESUMO

Chronic graft-versus-host disease (cGVHD) is the most common cause for non-relapse mortality postallogeneic hematopoietic stem cell transplant (HSCT). However, there are no well-defined biomarkers for cGVHD or late acute GVHD (aGVHD). This study is a longitudinal evaluation of metabolomic patterns of cGVHD and late aGVHD in pediatric HSCT recipients. A quantitative analysis of plasma metabolites was performed on 222 evaluable pediatric subjects from the ABLE/PBMTC1202 study. We performed a risk-assignment analysis at day + 100 (D100) on subjects who later developed either cGVHD or late aGVHD after day 114 to non-cGVHD controls. A second analysis at diagnosis used fixed and mixed multiple regression to compare cGVHD at onset to time-matched non-cGVHD controls. A metabolomic biomarker was considered biologically relevant only if it met all 3 selection criteria: (1) P ≤ .05; (2) effect ratio of ≥1.3 or ≤0.75; and (3) receiver operator characteristic AUC ≥0.60. We found a consistent elevation in plasma α-ketoglutaric acid before (D100) and at the onset of cGVHD, not impacted by cGVHD severity, pubertal status, or previous aGVHD. In addition, late aGVHD had a unique metabolomic pattern at D100 compared with cGVHD. Additional metabolomic correlation patterns were seen with the clinical presentation of pulmonary, de novo, and progressive cGVHD. α-ketoglutaric acid emerged as the single most significant metabolite associated with cGVHD, both in the D100 risk-assignment and later diagnostic onset analysis. These distinctive metabolic patterns may lead to improved subclassification of cGVHD. Future validation of these exploratory results is needed. This trial was registered at www.clinicaltrials.gov as #NCT02067832.


Assuntos
Doença Enxerto-Hospedeiro/metabolismo , Ácidos Cetoglutáricos/metabolismo , Adolescente , Biomarcadores/sangue , Biomarcadores/metabolismo , Criança , Pré-Escolar , Doença Crônica , Feminino , Doença Enxerto-Hospedeiro/sangue , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Lactente , Ácidos Cetoglutáricos/sangue , Masculino , Metaboloma , Medição de Risco
2.
J Psychosoc Oncol ; : 1-15, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38778556

RESUMO

OBJECTIVES: Patients undergoing autologous hematopoietic stem cell transplant (HCT) are at risk for death and remain understudied relative to those undergoing allogeneic HCT. Cognitive functioning may be a useful indicator of mortality risk. We examined cognition among patients who underwent autologous HCT and its relationship to mortality. METHODS: Participants (N = 51; 11 patients deceased) completed tasks of processing speed, working memory, executive-mediated learning, and visual recall using the computerized CogState battery prior to HCT, 30 days post-autologous HCT, and 100 days post-autologous HCT. RESULTS: Slower processing speed (HR = 3.00) and more errors on an executive-mediated visual learning task (HR = 2.78) prior to HCT were associated with an increased risk of death following HCT. Our sample size limited longitudinal analyses of whether cognitive change predicted survival, however descriptive cognitive data of the deceased versus living patient's performances over time suggested different patterns of performance across groups. CONCLUSIONS: Pre-HCT cognition may have utility as an indicator of mortality risk following autologous HCT. More research is needed to examine whether cognitive changes after HCT could also predict mortality.

3.
EMBO J ; 38(11)2019 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-31053596

RESUMO

Extracellular RNAs (exRNAs) in biofluids have attracted great interest as potential biomarkers. Although extracellular microRNAs in blood plasma are extensively characterized, extracellular messenger RNA (mRNA) and long non-coding RNA (lncRNA) studies are limited. We report that plasma contains fragmented mRNAs and lncRNAs that are missed by standard small RNA-seq protocols due to lack of 5' phosphate or presence of 3' phosphate. These fragments were revealed using a modified protocol ("phospho-RNA-seq") incorporating RNA treatment with T4-polynucleotide kinase, which we compared with standard small RNA-seq for sequencing synthetic RNAs with varied 5' and 3' ends, as well as human plasma exRNA Analyzing phospho-RNA-seq data using a custom, high-stringency bioinformatic pipeline, we identified mRNA/lncRNA transcriptome fingerprints in plasma, including tissue-specific gene sets. In a longitudinal study of hematopoietic stem cell transplant patients, bone marrow- and liver-enriched exRNA genes were tracked with bone marrow recovery and liver injury, respectively, providing proof-of-concept validation as a biomarker approach. By enabling access to an unexplored realm of mRNA and lncRNA fragments, phospho-RNA-seq opens up new possibilities for plasma transcriptomic biomarker development.


Assuntos
Biomarcadores/sangue , Ácidos Nucleicos Livres/análise , MicroRNAs/sangue , RNA Longo não Codificante/análise , RNA Mensageiro/análise , RNA-Seq/métodos , Biomarcadores/análise , Análise Química do Sangue/métodos , Ácidos Nucleicos Livres/sangue , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Humanos , MicroRNAs/análise , RNA Longo não Codificante/sangue , RNA Mensageiro/sangue , Análise de Sequência de RNA/métodos
4.
Blood ; 137(12): 1591-1602, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33275650

RESUMO

Digital protein assays have great potential to advance immunodiagnostics because of their single-molecule sensitivity, high precision, and robust measurements. However, translating digital protein assays to acute clinical care has been challenging because it requires deployment of these assays with a rapid turnaround. Herein, we present a technology platform for ultrafast digital protein biomarker detection by using single-molecule counting of immune-complex formation events at an early, pre-equilibrium state. This method, which we term "pre-equilibrium digital enzyme-linked immunosorbent assay" (PEdELISA), can quantify a multiplexed panel of protein biomarkers in 10 µL of serum within an unprecedented assay incubation time of 15 to 300 seconds over a 104 dynamic range. PEdELISA allowed us to perform rapid monitoring of protein biomarkers in patients manifesting post-chimeric antigen receptor T-cell therapy cytokine release syndrome, with ∼30-minute sample-to-answer time and a sub-picograms per mL limit of detection. The rapid, sensitive, and low-input volume biomarker quantification enabled by PEdELISA is broadly applicable to timely monitoring of acute disease, potentially enabling more personalized treatment.


Assuntos
Citocinas/sangue , Doenças do Sistema Imunitário/sangue , Testes Imediatos , Biomarcadores/sangue , Proteínas Sanguíneas/análise , Ensaio de Imunoadsorção Enzimática , Desenho de Equipamento , Humanos
6.
Endoscopy ; 55(8): 701-708, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36754065

RESUMO

BACKGROUND : Deep learning models have previously been established to predict the histopathology and invasion depth of gastric lesions using endoscopic images. This study aimed to establish and validate a deep learning-based clinical decision support system (CDSS) for the automated detection and classification (diagnosis and invasion depth prediction) of gastric neoplasms in real-time endoscopy. METHODS : The same 5017 endoscopic images that were employed to establish previous models were used for the training data. The primary outcomes were: (i) the lesion detection rate for the detection model, and (ii) the lesion classification accuracy for the classification model. For performance validation of the lesion detection model, 2524 real-time procedures were tested in a randomized pilot study. Consecutive patients were allocated either to CDSS-assisted or conventional screening endoscopy. The lesion detection rate was compared between the groups. For performance validation of the lesion classification model, a prospective multicenter external test was conducted using 3976 novel images from five institutions. RESULTS : The lesion detection rate was 95.6 % (internal test). On performance validation, CDSS-assisted endoscopy showed a higher lesion detection rate than conventional screening endoscopy, although statistically not significant (2.0 % vs. 1.3 %; P = 0.21) (randomized study). The lesion classification rate was 89.7 % in the four-class classification (advanced gastric cancer, early gastric cancer, dysplasia, and non-neoplastic) and 89.2 % in the invasion depth prediction (mucosa confined or submucosa invaded; internal test). On performance validation, the CDSS reached 81.5 % accuracy in the four-class classification and 86.4 % accuracy in the binary classification (prospective multicenter external test). CONCLUSIONS : The CDSS demonstrated its potential for real-life clinical application and high performance in terms of lesion detection and classification of detected lesions in the stomach.


Assuntos
Sistemas de Apoio a Decisões Clínicas , Aprendizado Profundo , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia , Projetos Piloto , Estudos Prospectivos , Endoscopia/métodos , Endoscopia Gastrointestinal
7.
Proc Natl Acad Sci U S A ; 117(37): 22815-22822, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32868420

RESUMO

The sensitive and accurate quantification of protein biomarkers plays important roles in clinical diagnostics and biomedical research. Sandwich ELISA and its variants accomplish the capture and detection of a target protein via two antibodies that tightly bind at least two distinct epitopes of the same antigen and have been the gold standard for sensitive protein quantitation for decades. However, existing antibody-based assays cannot distinguish between signal arising from specific binding to the protein of interest and nonspecific binding to assay surfaces or matrix components, resulting in significant background signal even in the absence of the analyte. As a result, they generally do not achieve single-molecule sensitivity, and they require two high-affinity antibodies as well as stringent washing to maximize sensitivity and reproducibility. Here, we show that surface capture with a high-affinity antibody combined with kinetic fingerprinting using a dynamically binding, low-affinity fluorescent antibody fragment differentiates between specific and nonspecific binding at the single-molecule level, permitting the direct, digital counting of single protein molecules with femtomolar-to-attomolar limits of detection (LODs). We apply this approach to four exemplary antigens spiked into serum, demonstrating LODs 55- to 383-fold lower than commercially available ELISA. As a real-world application, we establish that endogenous interleukin-6 (IL-6) can be quantified in 2-µL serum samples from chimeric antigen receptor T cell (CAR-T cell) therapy patients without washing away excess serum or detection probes, as is required in ELISA-based approaches. This kinetic fingerprinting thus exhibits great potential for the ultrasensitive, rapid, and streamlined detection of many clinically relevant proteins.


Assuntos
Ligação Proteica/fisiologia , Imagem Individual de Molécula/métodos , Anticorpos/imunologia , Especificidade de Anticorpos/imunologia , Especificidade de Anticorpos/fisiologia , Biomarcadores/sangue , Ensaio de Imunoadsorção Enzimática/métodos , Humanos , Cinética , Limite de Detecção , Nanotecnologia , Proteínas , Reprodutibilidade dos Testes
8.
Pediatr Hematol Oncol ; 40(4): 412-421, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36125251

RESUMO

During COVID-19, public health measures including masks and social distancing decreased viral upper respiratory infections (URI). Upper respiratory infections are the most common infectious etiology for low-risk pediatric febrile neutropenia (FN). This single-center, quasi-experimental, pre-post study was designed to understand the impact of public health measures on FN admissions and outcomes in the general pediatric oncology population during the COVID (March 2020-February 2021) vs. pre-COVID era (January 2018-February 2020) and their respective respiratory seasons (November-February). Episodes were risk-stratified using a tool recommended by the Children's Oncology Group. Descriptive and bivariate statistics were used to compare admission characteristics and outcomes. Comparing respiratory seasons, the Covid-era season had 60% fewer URI diagnoses (5/12), while high-risk episodes (63.6% [28/44] vs. 44.2% [23/52]) and intensive care admissions (18.2% [8/44] vs. 3.8% [2/52]) increased. Between eras, URIs were lower in the COVID-era (10.8% [16/148] vs. 19.9% [67/336]; p = 0.01), but admission characteristics and severe outcomes were not different. The impact of public health measures was most prominent during the respiratory season. Despite decreased incidence of URIs, the overall admission characteristics and severe outcomes were minimally impacted due to the brevity of respiratory seasons, but larger studies are warranted.


Assuntos
COVID-19 , Neutropenia Febril , Neoplasias , Infecções Respiratórias , Humanos , Criança , SARS-CoV-2 , COVID-19/epidemiologia , COVID-19/complicações , Pandemias , Neoplasias/epidemiologia , Neoplasias/complicações , Infecções Respiratórias/epidemiologia , Neutropenia Febril/epidemiologia
9.
Blood ; 135(15): 1287-1298, 2020 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-32047896

RESUMO

Human graft-versus-host disease (GVHD) biology beyond 3 months after hematopoietic stem cell transplantation (HSCT) is complex. The Applied Biomarker in Late Effects of Childhood Cancer study (ABLE/PBMTC1202, NCT02067832) evaluated the immune profiles in chronic GVHD (cGVHD) and late acute GVHD (L-aGVHD). Peripheral blood immune cell and plasma markers were analyzed at day 100 post-HSCT and correlated with GVHD diagnosed according to the National Institutes of Health consensus criteria (NIH-CC) for cGVHD. Of 302 children enrolled, 241 were evaluable as L-aGVHD, cGVHD, active L-aGVHD or cGVHD, and no cGVHD/L-aGVHD. Significant marker differences, adjusted for major clinical factors, were defined as meeting all 3 criteria: receiver-operating characteristic area under the curve ≥0.60, P ≤ .05, and effect ratio ≥1.3 or ≤0.75. Patients with only distinctive features but determined as cGVHD by the adjudication committee (non-NIH-CC) had immune profiles similar to NIH-CC. Both cGVHD and L-aGVHD had decreased transitional B cells and increased cytolytic natural killer (NK) cells. cGVHD had additional abnormalities, with increased activated T cells, naive helper T (Th) and cytotoxic T cells, loss of CD56bright regulatory NK cells, and increased ST2 and soluble CD13. Active L-aGVHD before day 114 had additional abnormalities in naive Th, naive regulatory T (Treg) cell populations, and cytokines, and active cGVHD had an increase in PD-1- and a decrease in PD-1+ memory Treg cells. Unsupervised analysis appeared to show a progression of immune abnormalities from no cGVHD/L-aGVHD to L-aGVHD, with the most complex pattern in cGVHD. Comprehensive immune profiling will allow us to better understand how to minimize L-aGVHD and cGVHD. Further confirmation in adult and pediatric cohorts is needed.


Assuntos
Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Aguda , Antígenos CD/análise , Antígenos CD/imunologia , Linfócitos B/imunologia , Linfócitos B/patologia , Biomarcadores/sangue , Criança , Doença Crônica , Citocinas/sangue , Citocinas/imunologia , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/patologia , Humanos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/patologia , Linfócitos T/imunologia , Linfócitos T/patologia
10.
Haematologica ; 107(1): 178-186, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33375775

RESUMO

Mutations in the gene CBL were first identified in adults with various myeloid malignancies. Some patients with juvenile myelomonocytic leukemia (JMML) were also noted to harbor mutations in CBL, but were found to have generally less aggressive disease courses compared to other forms of Ras pathway-mutant JMML. Importantly, and in contrast to most reports in adults, the majority of CBL mutations in JMML patients are germline with acquired uniparental disomy occurring in affected marrow cells. Here, we systematically studied a large cohort of 33 JMML patients with CBL mutations and found this disease to be highly diverse in presentation and overall outcome. Moreover, we discovered somatically-acquired CBL mutations in 15% of pediatric patients who presented with more aggressive disease. Neither clinical features nor methylation profiling were able to distinguish somatic CBL patients from germline CBL patients, highlighting the need for germline testing. Overall, we demonstrate that disease courses are quite heterogeneous even among germline CBL patients. Prospective clinical trials are warranted to find ideal treatment strategies for this diverse cohort of patients.


Assuntos
Leucemia Mielomonocítica Juvenil , Adulto , Criança , Humanos , Leucemia Mielomonocítica Juvenil/genética , Mutação , Estudos Prospectivos , Proteínas Proto-Oncogênicas c-cbl/genética
11.
Pediatr Blood Cancer ; 69(9): e29835, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35735223

RESUMO

We present a case series of three febrile episodes in neutropenic pediatric cancer patients who wore a Food and Drug Administration approved high-frequency temperature monitoring (HFTM) wearable device (WD) at home. The WD detected fever events when temperature monitoring by thermometer did not detect fever or was not feasible to perform. Two of the episodes were associated with bloodstream infections and the WD detected fevers 5 and 12 h prior to fevers detected by thermometer, triggering earlier medical evaluation and more prompt administration of antibiotics. These observations provide a basis for future investigation of home-based HFTM to improve infection-related outcomes in pediatric oncology.


Assuntos
Bacteriemia , Neutropenia Febril , Neoplasias , Dispositivos Eletrônicos Vestíveis , Antibacterianos/uso terapêutico , Bacteriemia/complicações , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Criança , Neutropenia Febril/complicações , Neutropenia Febril/diagnóstico , Neutropenia Febril/tratamento farmacológico , Febre/diagnóstico , Febre/tratamento farmacológico , Febre/etiologia , Humanos , Neoplasias/tratamento farmacológico , Temperatura
12.
Handb Exp Pharmacol ; 272: 209-243, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34628553

RESUMO

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for high-risk hematologic disorders. There are multiple immune-mediated complications following allo-HSCT that are prevented and/or treated by immunosuppressive agents. Principal among these immune-mediated complications is acute graft-versus-host disease (aGVHD), which occurs when the new donor immune system targets host tissue antigens. The immunobiology of aGVHD is complex and involves all aspects of the immune system. Due to the risk of aGVHD, immunosuppressive aGVHD prophylaxis is required for nearly all allogeneic HSCT recipients. Despite prophylaxis, aGVHD remains a major cause of nonrelapse mortality. Here, we discuss the clinical features of aGVHD, the immunobiology of aGVHD, the immunosuppressive therapies used to prevent and treat aGVHD, how to mitigate the side effects of these immunosuppressive therapies, and what additional immune-mediated post-allo-HSCT complications are also treated with immunosuppression.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Terapia de Imunossupressão
13.
Am J Otolaryngol ; 43(6): 103524, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35672189

RESUMO

BACKGROUND: Balloon eustachian tuboplasty (BET) is a minimally invasive surgical treatment that is effective and safe for obstructive eustachian tube dysfunction. However, BET complications include excessive widening of the eustachian tube, causing a patulous eustachian tube (PET). Herein, we report a case of PET following BET in a patient who underwent radiation therapy and reviewed the literature on considerations for reducing complications after BET. CASE PRESENTATION: A 63-year-old woman complained of bilateral ear fullness after concurrent chemoradiation therapy for nasopharyngeal lymphoma. BET was performed on the left side because the left-sided serous otitis media persisted. A left-sided PET was performed two weeks after the BET, along with eustachian tube silicone plug insertion on the left side. The patient became asymptomatic immediately after the surgery, with no recurrence reported after a 12-month follow-up period. CONCLUSIONS: To our knowledge, there has been no report of PET following BET in a post-radiation patient, and it was successfully treated via ET silicone plug insertion.


Assuntos
Otopatias , Tuba Auditiva , Otite Média com Derrame , Otite Média , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Otite Média/patologia , Otite Média com Derrame/cirurgia , Otopatias/etiologia , Otopatias/cirurgia , Otopatias/patologia , Silicones
14.
Am J Otolaryngol ; 43(3): 103455, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35398740

RESUMO

PURPOSE: Sudden sensorineural hearing loss (SSNHL) is an otologic emergency. Despite multiple efforts to clarify the factors affecting the prognosis of severe-to-profound SSNHL, various studies showed inconsistent results and lack of clinical significance. Therefore, we examined the clinical features and outcomes of severe-to-profound SSNHL. MATERIALS AND METHODS: We included patients who experienced SSNHL between 2018 and 2021 and were diagnosed according to the American Academy of Otolaryngology-Head and Neck Surgery criteria; hearing loss over 70 dB on initial pure tone audiometry (PTA) was used to define severe-to-profound SSNHL. We retrospectively examine the demographic, laboratory, radiologic, and audiometric data of SSNHL patients. We also evaluated the final hearing gain of these patients by assessing their PTA findings and word-recognition scores. RESULTS: Of the 178 patients, 94 (52.81%) and 84 (47.19%) showed profound (>90 dB) and severe (>70 to 90 dB) hearing loss, respectively. The presence of vertigo and hypertension differed significantly between the severe and profound groups (p < 0.001 and p = 0.012, respectively), as did the initial serum creatinine level (p = 0.043). Recovery in PTA showed a reliable correlation with the interval between onset and treatment in the severe group and periventricular white-matter findings in the profound group (p < 0.001 and p = 0.011, respectively). The presence of hypertension was related to recovery of low tone (p = 0.023 for 250 Hz; p = 0.034 for 500 Hz), while glycated hemoglobin level was related to recovery of high tone in the severe group (p = 0.049 for 4000 Hz; p = 0.047 for 8000 Hz). CONCLUSIONS: Severe-to-profound SSNHL showed poor prognosis for hearing gain. The interval from onset to treatment was a significant prognostic factor for severe SSNHL, while the presence of vertigo, estimated glomerular filtration rate, and periventricular white-matter findings were significant prognostic factors for profound SSNHL.


Assuntos
Perda Auditiva Neurossensorial , Perda Auditiva Súbita , Hipertensão , Audiometria de Tons Puros , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/tratamento farmacológico , Perda Auditiva Neurossensorial/etiologia , Perda Auditiva Súbita/diagnóstico , Perda Auditiva Súbita/tratamento farmacológico , Perda Auditiva Súbita/etiologia , Humanos , Prognóstico , Estudos Retrospectivos , Vertigem
15.
Am J Otolaryngol ; 43(1): 103222, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34536916

RESUMO

BACKGROUND: Vibrant SoundBridge® (VSB), a semi-implantable middle ear device, is one of the treatment options for patients with mild-to-severe sensorineural hearing loss or mixed hearing loss. Herein, we report delayed device failure after VSB surgery in two patients. CASE PRESENTATION: In both cases, a revision surgery was performed for the removal of the device; dissociation of the floating mass transducer (FMT) and coupler was noticed in one patient, and dissociation of the FMT-coupler complex from the short process of the incus in the other. In Case 1, the vibration-like sounds disappeared after the surgery. In Case 2, wearing bilateral hearing aids improved hearing after removal surgery, but complaints regarding speech discrimination persisted. Both cases show the importance of not loosening the connectivity between the FMT, coupler, and short process of the incus during VSB surgery. CONCLUSIONS: To our knowledge, there has been no report of dissociation from the short process of the incus or the dissociation between an FMT and the coupler.


Assuntos
Perda Auditiva Condutiva-Neurossensorial Mista/cirurgia , Perda Auditiva Neurossensorial/cirurgia , Prótese Ossicular/efeitos adversos , Falha de Prótese , Transdutores/efeitos adversos , Idoso , Remoção de Dispositivo , Feminino , Humanos , Bigorna/cirurgia , Masculino , Ilustração Médica , Pessoa de Meia-Idade , Desenho de Prótese
16.
Cancer Causes Control ; 32(4): 379-389, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33566250

RESUMO

BACKGROUND: Oncology settings increasingly use patient experience data to evaluate clinical performance. Given that older patients with hematologic malignancies are a high-risk population, this study examined factors associated with patient-reported health care experiences during the first year of their cancer diagnosis. METHODS: Cross-sectional study using the 2000-2015 SEER-CAHPS® data to examine patient experiences of Medicare enrollees with a primary diagnosis of leukemia or lymphoma. The primary outcomes were three CAHPS assessments: overall care, personal doctor, and health plan overall. We estimated case-mix adjusted and fully adjusted associations between factors (i.e., clinical and sociodemographic) and the CAHPS outcomes using bivariate statistical tests and multiple linear regression. RESULTS: The final sample included 1,151 patients, with 431 diagnosed with leukemia and 720 diagnosed with lymphoma (median time from diagnosis to survey 6 months). Patients who completed the survey further apart from the diagnosis date reported significantly higher adjusted ratings of care overall (ß .39, p = .008) than those closer to diagnosis. American Indian/Alaska Native, Asian, and Pacific Islander patients had lower adjusted ratings of care overall (ß - .73, p = .003) than Non-Hispanic white patients. Multimorbidity was significantly associated with higher adjusted personal doctor ratings (ß .26, p = .003). CONCLUSIONS: Unfavorable patient experiences among older adults diagnosed with hematologic malignancies warrant targeted efforts to measure and improve care quality. Future measurement of experiences of cancer care soon after diagnosis, coupled with careful sampling of high-priority populations, will inform oncology leaders and clinicians on strategies to improve care for high-risk, high-cost populations.


Assuntos
Neoplasias Hematológicas/terapia , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Estudos Transversais , Feminino , Pesquisas sobre Atenção à Saúde , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/etnologia , Humanos , Masculino , Medicare , Havaiano Nativo ou Outro Ilhéu do Pacífico , Avaliação de Resultados da Assistência ao Paciente , Satisfação do Paciente/estatística & dados numéricos , Qualidade da Assistência à Saúde/estatística & dados numéricos , Programa de SEER , Estados Unidos , População Branca
17.
Blood ; 134(3): 304-316, 2019 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-31043425

RESUMO

Chronic graft-versus-host disease (cGVHD) and late acute graft-versus-host disease (L-aGVHD) are understudied complications of allogeneic hematopoietic stem cell transplantation in children. The National Institutes of Health Consensus Criteria (NIH-CC) were designed to improve the diagnostic accuracy of cGVHD and to better classify graft-versus-host disease (GVHD) syndromes but have not been validated in patients <18 years of age. The objectives of this prospective multi-institution study were to determine: (1) whether the NIH-CC could be used to diagnose pediatric cGVHD and whether the criteria operationalize well in a multi-institution study; (2) the frequency of cGVHD and L-aGVHD in children using the NIH-CC; and (3) the clinical features and risk factors for cGVHD and L-aGVHD using the NIH-CC. Twenty-seven transplant centers enrolled 302 patients <18 years of age before conditioning and prospectively followed them for 1 year posttransplant for development of cGVHD. Centers justified their cGVHD diagnosis according to the NIH-CC using central review and a study adjudication committee. A total of 28.2% of reported cGVHD cases was reclassified, usually as L-aGVHD, following study committee review. Similar incidence of cGVHD and L-aGVHD was found (21% and 24.7%, respectively). The most common organs involved with diagnostic or distinctive manifestations of cGVHD in children include the mouth, skin, eyes, and lungs. Importantly, the 2014 NIH-CC for bronchiolitis obliterans syndrome perform poorly in children. Past acute GVHD and peripheral blood grafts are major risk factors for cGVHD and L-aGVHD, with recipients ≥12 years of age being at risk for cGVHD. Applying the NIH-CC in pediatrics is feasible and reliable; however, further refinement of the criteria specifically for children is needed.


Assuntos
Doença Enxerto-Hospedeiro/diagnóstico , Doença Aguda , Adolescente , Fatores Etários , Criança , Pré-Escolar , Doença Crônica , Conferências para Desenvolvimento de Consenso de NIH como Assunto , Feminino , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Guias de Prática Clínica como Assunto , Fatores de Risco , Índice de Gravidade de Doença , Avaliação de Sintomas , Fatores de Tempo , Transplante Homólogo , Estados Unidos , Fluxo de Trabalho
18.
Support Care Cancer ; 29(1): 247-254, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32346799

RESUMO

PURPOSE: Hematopoietic stem cell transplant (HSCT) recipients are at risk for cognitive decline. Cross-sectional studies show patients' complaints of cognitive decline do not correlate well with concurrently measured objective neuropsychological performance, but rather with emotional variables and health-related quality of life. This longitudinal study investigated whether patient self-report of cognitive status would be concordant with objectively measured neuropsychological performance after accounting for change from their own pre-transplant objective baseline. METHODS: Pre-HSCT and at 30 and 100 days post-HSCT, 46 patients underwent computerized neuropsychological testing (CogState) and completed surveys assessing patient-reported cognitive complaints, emotional symptoms (depression, anxiety), sleep quality, daytime sleepiness, and physical and functional well-being. Correlations were calculated between cognitive complaints and neuropsychological performance (at each time-point and across time-points), as well as all other patient-reported variables. RESULTS: Patient-reported cognitive complaints were largely independent of concurrently assessed objective neuropsychological performance. Uniquely, our longitudinal data demonstrated significant medium to large effect size associations between subjective cognitive complaints post-HSCT with objectively measured change from pre-HSCT in attention, visual learning, and working memory (p < .05-.01). Subjective cognitive complaints post-HSCT were also associated with depression, anxiety, daytime sleepiness and physical well-being (p < .05-.001). CONCLUSIONS: Patients appear better able to assess their cognitive functioning relative to their own baseline and changes across time rather than relative to community norms. Thus, patient complaints of cognitive compromise justify further in-depth neuropsychological, emotional, and functional assessment. Future research into relationships between cognitive complaints and neuropsychological performance should account for changes in performance over time.


Assuntos
Disfunção Cognitiva/psicologia , Transplante de Células-Tronco Hematopoéticas/psicologia , Testes Neuropsicológicos , Qualidade de Vida/psicologia , Autoavaliação (Psicologia) , Transplantados/psicologia , Adulto , Ansiedade/psicologia , Atenção , Cognição/fisiologia , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Masculino , Memória de Curto Prazo/fisiologia , Pessoa de Meia-Idade , Psicometria/métodos , Autorrelato , Inquéritos e Questionários
19.
Am J Otolaryngol ; 42(2): 102858, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33445040

RESUMO

PURPOSE: Idiopathic sudden sensorineural hearing loss (ISSHL) is an emergency otological disease, and its definite prognostic factors remain unclear. This study applied machine learning methods to develop a new ISSHL prognosis prediction model. MATERIALS AND METHODS: This retrospective study reviewed the medical data of 244 patients who underwent combined intratympanic and systemic steroid treatment for ISSHL at a tertiary referral center between January 2015 and October 2019. We used 35 variables to predict hearing recovery based on Siegel's criteria. In addition to performing an analysis based on the conventional logistic regression model, we developed prediction models with five machine learning methods: least absolute shrinkage and selection operator, decision tree, random forest (RF), support vector machine, and boosting. To compare the predictive ability of each model, the accuracy, precision, recall, F-score, and the area under the receiver operator characteristic curves (ROC-AUC) were calculated. RESULTS: Former otological history, ear fullness, delay between symptom onset and treatment, delay between symptom onset and intratympanic steroid injection (ITSI), and initial hearing thresholds of the affected and unaffected ears differed significantly between the recovery and non-recovery groups. While the RF method (accuracy: 72.22%, ROC-AUC: 0.7445) achieved the highest predictive power, the other methods also featured relatively good predictive power. In the RF model, the following variables were identified to be important for hearing-recovery prediction: delay between symptom onset and ITSI or the initial treatment, initial hearing levels of the affected and non-affected ears, body mass index, and a previous history of hearing loss. CONCLUSIONS: The machine learning models predictive of hearing recovery following treatment for ISSHL showed superior predictive power relative to the conventional logistic regression method, potentially allowing for better patient treatment outcomes.


Assuntos
Glucocorticoides/administração & dosagem , Perda Auditiva Neurossensorial/tratamento farmacológico , Perda Auditiva Súbita/tratamento farmacológico , Audição , Modelos Logísticos , Aprendizado de Máquina , Adulto , Feminino , Perda Auditiva Neurossensorial/fisiopatologia , Perda Auditiva Súbita/fisiopatologia , Humanos , Injeções Intralesionais , Masculino , Pessoa de Meia-Idade , Prognóstico , Recuperação de Função Fisiológica , Estudos Retrospectivos
20.
Am J Otolaryngol ; 42(1): 102788, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33171411

RESUMO

PURPOSE: The use of endoscopes in otologic procedures has been increasing worldwide. This study aimed to compare the efficacy of microscopic tympanoplasty (MT) and endoscopic tympanoplasty (ET) for tympanic membrane and middle ear surgery. MATERIALS AND METHODS: We retrospectively analyzed 81 patients who underwent MT (n = 44) and ET (n = 37) for chronic otitis media with tympanic membrane perforation performed by a single surgeon between January 2013 and September 2019. The hearing outcomes, graft success rate, complications, operation time and hospital stay, and cost-effectiveness were recorded and compared between groups. Hearing outcomes were determined by pure tone audiometry. Cost-effectiveness was determined by the operation cost and total cost. RESULTS: There was no significant difference between the MT and ET groups regarding demographic characteristics, with the exception of the male:female ratio. There was no significant difference in the pre- and postoperative air conduction, bone conduction thresholds, and air-bone gap values between the two groups, but a significant audiologic improvement was observed in both groups (p < 0.05). In terms of recurrence of tympanic membrane perforation, postoperative otorrhea, and discomfort symptoms, there was no significant difference between groups (p > 0.05). The operation time and hospital stay were shorter in the ET group than in the MT group (p < 0.05). There were no significant differences in operation cost between the two groups (p > 0.05), but the total cost was significantly lower in the ET group than the MT group (p < 0.05). CONCLUSION: ET is as safe and medically efficacious as conventional MT, shortens the operation time and hospital stay, and is cost-effective.


Assuntos
Orelha Média/cirurgia , Endoscopia/métodos , Microscopia/métodos , Otite Média/cirurgia , Cirurgiões , Perfuração da Membrana Timpânica/cirurgia , Membrana Timpânica/cirurgia , Timpanoplastia/métodos , Adulto , Doença Crônica , Análise Custo-Benefício , Endoscopia/economia , Endoscopia/instrumentação , Feminino , Audição , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Microscopia/economia , Microscopia/instrumentação , Pessoa de Meia-Idade , Duração da Cirurgia , Otite Média/economia , Otite Média/fisiopatologia , Resultado do Tratamento , Perfuração da Membrana Timpânica/economia , Perfuração da Membrana Timpânica/fisiopatologia , Timpanoplastia/economia , Timpanoplastia/instrumentação
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