RESUMO
PURPOSE: Palliative care is recommended for patients with cancer with a life expectancy of <12 months. Machine learning (ML) techniques can help in predicting survival outcomes among patients with cancer and may help distinguish who benefits the most from palliative care support. We aim to explore the importance of several objective and subjective self-reported variables. Subjective variables were collected through electronic psycho-oncologic and palliative care self-assessment screenings. We used these variables to predict 1-year mortality. MATERIALS AND METHODS: Between April 1, 2020, and March 31, 2021, a total of 265 patients with advanced cancer completed a patient-reported outcome tool. We documented objective and subjective variables collected from electronic health records, self-reported subjective variables, and all clinical variables combined. We used logistic regression (LR), 20-fold cross-validation, decision trees, and random forests to predict 1-year mortality. We analyzed the receiver operating characteristic (ROC) curve-AUC, the precision-recall curve-AUC (PR-AUC)-and the feature importance of the ML models. RESULTS: The performance of clinical nonpatient variables in predictions (LR reaches 0.81 [ROC-AUC] and 0.72 [F1 score]) are much more predictive than that of subjective patient-reported variables (LR reaches 0.55 [ROC-AUC] and 0.52 [F1 score]). CONCLUSION: The results show that objective variables used in this study are much more predictive than subjective patient-reported variables, which measure subjective burden. These findings indicate that subjective burden cannot be reliably used to predict survival. Further research is needed to clarify the role of self-reported patient burden and mortality prediction using ML.
Assuntos
Aprendizado de Máquina , Neoplasias , Humanos , Neoplasias/mortalidade , Neoplasias/psicologia , Neoplasias/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Curva ROC , Cuidados Paliativos/métodos , Medidas de Resultados Relatados pelo Paciente , Prognóstico , Registros Eletrônicos de Saúde , Adulto , Idoso de 80 Anos ou maisRESUMO
PURPOSE: The Minimal Documentation System (MIDOS2) is recommended as a systematic screening tool for assessing symptom burden and patient needs in advanced cancer patients. Given the absence of an optimal weighting of individual symptoms and a corresponding cut-off value, this study aims to determine a threshold based on inpatient's subjective need for palliative support. Additionally, we investigate the correlation between symptom burden and subjective need for palliative support collected through a patient-reported outcome measure (PROM) with survival duration of less or more than one year. METHODS: Inpatients diagnosed with advanced solid cancer completed an electronic PROM, which included the MIDOS2 questionnaire among other tools. Differences in symptom burden were analysed between patients expressing subjective need for palliative support and those with survival of less or more than one year using ANOVA, Mann-Whitney-U Test, logistic regression, Pearson and Spearman correlation tests. Cut-off analyses were performed using a ROC curve. Youden-Index, sensitivity, and specificity measures were used as well. RESULTS: Between April 2020 and March 2021, 265 inpatients were included in the study. Using a ROC curve, the MIDOS2 analysis resulted in an Area under the curve (AUC) of 0.732, a corresponding cut-off value of eight points, a sensitivity of 76.36% and a specificity of 62.98% in assessing the subjective need for palliative support. The MIDOS2, with double weighting of the significant symptoms, showed a cut-off value of 14 points, achieving a sensitivity of 78.18% and a specificity of 72.38%. A total of 55 patients (20.8%) expressed a need for support from the palliative care team. This need was independent of the oncological tumour entity and increased among patients with a survival of less than one year. These patients reported significantly poorer physical (p < 0.001) or mental (p < 0.001) condition. Additionally, they reported higher intensities of pain (p = 0.002), depressive symptoms (p < 0.001), weakness (p < 0.001), anxiety (p < 0.001), and tiredness (p < 0.001). CONCLUSION: Using the established MIDOS2 cut-off value with an adjusted double weighting in our study, a large proportion of inpatients may be accurately referred to SPC based on their subjective need for palliative support. Additionally, subjective reports of poor general, mental, and physical condition, as well as pain, depressive symptoms, weakness, anxiety, and tiredness, increase the subjective need for palliative support, particularly in patients with a survival prognosis of less than one year.
Assuntos
Neoplasias , Cuidados Paliativos , Humanos , Cuidados Paliativos/métodos , Feminino , Masculino , Neoplasias/psicologia , Neoplasias/terapia , Neoplasias/diagnóstico , Pessoa de Meia-Idade , Idoso , Inquéritos e Questionários , Pacientes Internados , Medidas de Resultados Relatados pelo Paciente , Idoso de 80 Anos ou mais , Adulto , Documentação/métodos , Carga de SintomasRESUMO
For advanced cancer inpatients, the established standard for gathering information about symptom burden involves a daily assessment by nursing staff using validated assessments. In contrast, a systematic assessment of patient-reported outcome measures (PROMs) is required, but it is not yet systematically implemented. We hypothesized that current practice results in underrating the severity of patients' symptom burden. To explore this hypothesis, we have established systematic electronic PROMs (ePROMs) using validated instruments at a major German Comprehensive Cancer Center. In this retrospective, non-interventional study, lasting from September 2021 to February 2022, we analyzed collected data from 230 inpatients. Symptom burden obtained by nursing staff was compared to the data acquired by ePROMs. Differences were detected by performing descriptive analyses, Chi-Square tests, Fisher's exact, Phi-correlation, Wilcoxon tests, and Cohen's r. Our analyses pointed out that pain and anxiety especially were significantly underrated by nursing staff. Nursing staff ranked these symptoms as non-existent, whereas patients stated at least mild symptom burden (pain: meanNRS/epaAC = 0 (no); meanePROM = 1 (mild); p < 0.05; r = 0.46; anxiety: meanepaAC = 0 (no); meanePROM = 1 (mild); p < 0.05; r = 0.48). In conclusion, supplementing routine symptom assessment used daily by nursing staff with the systematic, e-health-enabled acquisition of PROMs may improve the quality of supportive and palliative care.
RESUMO
The cytidine deaminase APOBEC3G has been identified as an antiviral host factor that combats HIV-1. The protein was found to be present in HIV-1 target cells such as macrophages and dendritic cells. The antiviral state of these cells has been partially attributed to a GâA hypermutation of the HIV genome caused by APOBEC3G during reverse transcription. However, the viral infectivity factor (Vif) counteracts this antiviral mechanism by inducing the inactivation of APOBEC3G. In this study, we tested the effect of APOBEC3G expression on the HIV-1 infection of cells derived from purified CD34+ cells that have been transduced with lentiviral vectors containing APOBEC3G and/or shRNAs directed against APOBEC3G and then have been differentiated before infection with HIV-1. In cell lines, the infection was strongly inhibited after upregulation of APOBEC3G. The infection could then be rescued after transducing these cells with shRNAs targeting APOBEC3G. In cells derived from purified CD34+ cells a strong inhibition of the HIV-1 infection was observed in both a Vif defective HIV-1 virus and the corresponding wild-type HIV-1 virus with Vif. Our data implies that when APOBEC3G is expressed high enough, it can escape the inhibition from Vif, thereby exerting its antiviral activity.
Assuntos
Antígenos CD34/análise , Citidina Desaminase/genética , HIV-1/genética , Células-Tronco Hematopoéticas/citologia , Macrófagos/virologia , Desaminase APOBEC-3G , Western Blotting , Linhagem Celular , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Regulação da Expressão Gênica , Inativação Gênica , Genes vif , Vetores Genéticos , HIV-1/crescimento & desenvolvimento , Humanos , Lentivirus/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente PequenoRESUMO
In order to identify cellular genes which interfere with HIV-1 replication in monocyte-derived macrophages (MAC), cells were stimulated with interferon (IFN) or lipopolysaccharide (LPS) leading to a pronounced inhibition of HIV-1 infection in these cells, and the resulting gene expression was analyzed. Using the microarray technology we identified a gene named Stimulated Trans-Acting Factor of 50 kDa (Staf50), which is known to repress the activity of the HIV-1 LTR. Analysis of the Staf50 expression by real-time PCR showed an overexpression in IFNalpha (up to 20-fold) and LPS (up to 10-fold)-stimulated MAC as well as in infected cells (up to 3-fold). For stable overexpression, 293 T cells and primary macrophages were transduced with Staf50-IRES-GFP bicistronic pseudotype viruses. After transduction, 293 T CD4/CCR5 and MAC were infected with HIV-1, and virus replication was monitored by p24 ELISA. Overexpression of Staf50 inhibited the HIV-1 infection between 50% and 90% in 293 T CD4/CCR5 as well as in MAC. Our findings suggest that host genetic effects in combination with viral properties determine the susceptibility of an appropriate target cell for HIV-1 infection as well as the replication potential of the virus in the cell resulting in an overall productive infection.