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OBJECTIVES: Patients with malignant wounds suffer from physical and psychological symptom burden. Despite psychological support being required, the impact of malignant wounds on patients' psychological distress is poorly investigated. We evaluated psychological distress associated with malignant wounds for patients at their end of life. METHODS: This study used the secondary analysis of the results of a large prospective cohort study, which investigated the dying process among patients with advanced cancer in 23 palliative care units in Japan. The primary outcome of this study was the prevalence of moderate to severe psychological symptom burden, evaluated by the Integrated Palliative Care Outcome Scale (IPOS)-feeling at peace scores of 2-4. In addition, the factors affecting psychological symptoms were investigated. The quality of death was also evaluated upon death using the Good Death Scale score. RESULTS: Out of the total 1896 patients, 156 had malignant wounds (8.2%). Malignant wounds were more common in female and young people. The breast, head, and neck were the most prevalent primary sites. More patients with malignant wounds had IPOS-feeling at peace scores of 2-4 than patients without malignant wounds (41.0% vs. 31.3%, p = 0.024). Furthermore, psychological distress was associated with moderate to severe IPOS-pain and the frequency of dressing changes. The presence of malignant wounds did not affect the quality of death. SIGNIFICANCE OF RESULTS: This study showed increased psychological distress due to malignant wounds. Patients with malignant wounds require psychological support in addition to the treatment of physical symptoms for maintaining their quality of life.
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Qualidade de Vida , Carga de Sintomas , Humanos , Feminino , Adolescente , Estudos Prospectivos , Cuidados Paliativos , DorRESUMO
OBJECTIVE: the role of benzodiazepines in relieving dyspnea in patients with cancer has not yet been established. This systematic review and meta-analysis aimed to determine the efficacy and safety of benzodiazepines alone or in combination with opioids for dyspnea in patients with cancer. METHODS: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and Ichushi-Web were searched for articles published from database inception to 23 September 2019. Studies of benzodiazepines alone or in combination with opioids for dyspnea were included. The primary outcome measure was the relief of dyspnea. The secondary outcome measures were anxiety, somnolence and severe adverse events. RESULTS: of 505 publications initially identified, two trials and one trial were included in the meta-analysis of midazolam alone and in combination with morphine, respectively. With regard to the relief of dyspnea, midazolam alone showed no significant difference compared with morphine alone, with a relative risk of 0.95 (95% confidence interval: 0.47-1.89). Meanwhile, midazolam plus morphine was significantly more effective than morphine alone, with a relative risk of 1.33 (95% confidence interval: 1.02-1.75). For anxiety relief, a meta-analysis could not be performed because of insufficient data. The incidence of somnolence and severe adverse events was not significantly different between the experimental and control groups for either midazolam alone or in combination with morphine. CONCLUSIONS: benzodiazepines alone do not significantly improve dyspnea compared with opioids alone, but a combination of benzodiazepines and opioids may be more effective. Evidence from randomized controlled trials focusing on patients with cancer has not been generated in recent years. Further appropriately designed randomized controlled trials are required.
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Benzodiazepinas , Neoplasias , Humanos , Benzodiazepinas/uso terapêutico , Midazolam/efeitos adversos , Sonolência , Dispneia/tratamento farmacológico , Dispneia/etiologia , Neoplasias/complicações , Morfina/efeitos adversos , Analgésicos Opioides/efeitos adversosRESUMO
Dyspnea is a prevalent symptom that significantly reduces quality of life of cancer patients. Palliative treatment is necessary when the symptoms do not respond to treatment for their cause. Opioids are widely used as pharmacological therapy, but evidence for individual agents is inconsistent. The purpose of this study was to evaluate the efficacy and safety of opioids for dyspnea in cancer patients. We searched the CENTRAL, MEDLINE, EMBASE, and ICHUSHI for studies using opioids for dyspnea in adult cancer patients reported by September 2019. Screening of the retrieved literature and assessment of risk of bias and outcomes were performed by two independent authors. A meta-analysis was performed on the primary endpoint, relief of dyspnea, and secondary endpoints including quality of life, somnolence as a side effect, and serious adverse events. Twelve randomized controlled trials were evaluated regarding relief of dyspnea. Somnolence and serious adverse events were evaluated in seven and four randomized controlled trials, respectively, but no randomized controlled trials were evaluable for quality of life. Overall, opioids were more effective than placebo for dyspnea (standardized mean difference - 0.43, 95% confidence interval [CI] - 0.75 to - 0.12). Although significant difference was found between systemic morphine and placebo in the drug-specific analysis, no significant difference could be detected in the other analyses. Systemic administration of opioids is more effective than placebo in relieving dyspnea in cancer patients. Robust evidence on the efficacy and safety of opioids on dyspnea in cancer patients is lacking, and further studies are needed.
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Analgésicos Opioides , Neoplasias , Adulto , Humanos , Analgésicos Opioides/efeitos adversos , Sonolência , Qualidade de Vida , Dispneia/etiologia , Dispneia/induzido quimicamente , Neoplasias/complicações , Neoplasias/tratamento farmacológicoRESUMO
PURPOSE: For appropriate advance care planning, functional prognostication is necessary. However, there are no studies of functional prognostication in patients with cancer. The aim of this study was to develop a functional prognostic scoring system for patients with advanced cancer. METHODS: In this multicenter prospective observational study, 1896 patients were enrolled. First, Cox regression analysis and the combination of forward and backward variable selection were used to identify the best subset of predictors. Second, the prognostic score value was defined from each regression coefficient of a significant prognostic factor. The Functional Palliative Prognostic Index (FPPI) was calculated by summing the prognostic scores. RESULTS: Patients were classified into three groups by the FPPI. For walking, the 14-day functional survival probability was > 72.8% for group A (score 0), 28.4-72.8% for group B (score 1), and < 28.4% for group C (score 2-3). For eating, the 14-day functional survival probability was > 71.8% for group A (score 0-3), 29.6-71.8% for group B (score 3.5-5.5), and < 29.6% for group C (score 6-9). For communicating, the 14-day functional survival probability was > 76.6% for group A (score 0-6.5), 22.6-76.6% for group B (score 7-10), and < 22.6% for group C (score 10.5-16). Regarding each item, group B functionally survived significantly longer than group C, and group A functionally survived significantly longer than either of the others. CONCLUSION: We firstly developed a functional prognostic scoring system for patients with advanced cancer. This FPPI system promises to be helpful in advance care planning.
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Indicadores Básicos de Saúde , Neoplasias/diagnóstico , Cuidados Paliativos , Adolescente , Adulto , Planejamento Antecipado de Cuidados , Idoso , Idoso de 80 Anos ou mais , Tomada de Decisões , Progressão da Doença , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Neoplasias/patologia , Cuidados Paliativos/métodos , Cuidados Paliativos/normas , Prognóstico , Estudos Prospectivos , Projetos de Pesquisa , Análise de Sobrevida , Adulto JovemRESUMO
PURPOSE: Although corticosteroids can relieve dyspnea in advanced cancer patients, factors predicting the response remain unknown. We aimed to explore potential factors predicting the response to corticosteroids for dyspnea in advanced cancer patients. METHODS: In this preliminary multicenter prospective observational study, we included patients who had metastatic or locally advanced cancer, were receiving specialized palliative care services, and had a dyspnea intensity of ≥3 on a 0-10 Numerical Rating Scale (NRS) (worst during the last 24 h). The primary endpoint was NRS of dyspnea on day 3 after the administration of corticosteroids. Univariate/multivariate analyses were conducted to identify factors predicting ≥1-point reduction in NRS. RESULTS: Of 74 patients who received corticosteroids, 50 (68%) showed ≥1-point reduction in dyspnea NRS. Factors that significantly predicted the response were an age of 70 years or older (82 vs. 53%, p = 0.008), absence of liver metastases (77 vs. 46%, p = 0.001), Palliative Prognostic Index (PPI) ≤ 6 (90 vs. 61%, p = 0.041), presence of pleuritis carcinomatosa with a small collection of pleural effusions (84 vs. 55%, p = 0.011), presence of audible wheezes (94 vs. 60%, p = 0.014), and baseline dyspnea NRS ≥7 (76% vs. 52%, p = 0.041). In a multivariate analysis, factors predicting response included PPI <6 (odds ratio (OR), 36.2; p = 0.021), baseline dyspnea NRS (worst) ≥7 (OR, 6.6; p = 0.036), and absence of liver metastases (OR, 0.19; p = 0.029) or ascites/liver enlargement (OR, 0.13; p = 0.050). CONCLUSIONS: The patient characteristics, etiologies of dyspnea, and clinical manifestations may predict responses to corticosteroids for dyspnea. Larger prospective studies are promising to confirm our findings.
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Corticosteroides/uso terapêutico , Dispneia/tratamento farmacológico , Neoplasias/fisiopatologia , Idoso , Dispneia/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Cuidados Paliativos , Valor Preditivo dos Testes , Prognóstico , Estudos ProspectivosRESUMO
PURPOSE: Although corticosteroids are widely used to relieve anorexia, information regarding the factors predicting responses to corticosteroids remains limited. The purpose of the study is to identify potential factors predicting responses to corticosteroids for anorexia in advanced cancer patients. METHODS: Inclusion criteria for this multicenter prospective observational study were patients who had metastatic or locally advanced cancer and had an anorexia intensity score of 4 or more on a 0-10 Numerical Rating Scale (NRS). Univariate and multivariate analyses were conducted to identify the factors predicting ≥2-point reduction in NRS on day 3. RESULTS: Among 180 patients who received corticosteroids, 99 (55 %; 95 % confidence interval [CI], 47-62 %) had a response with ≥2-point reduction. Factors that significantly predicted responses were Palliative Performance Scale (PPS) > 40 and absence of drowsiness. In addition, factors that tended to be associated with ≥2-point reduction in NRS included PS 0-3, absence of diabetes mellitus, absence of peripheral edema, presence of lung metastasis, absence of peritoneal metastasis, baseline anorexia NRS of >6, presence of pain, and presence of constipation. A multivariate analysis showed that the independent factors predicting responses were PPS of >40 (odds ratio = 2.7 [95 % CI = 1.4-5.2]), absence of drowsiness (2.6 [1.3-5.0]), and baseline NRS of >6 (2.4 [1.1-4.8]). CONCLUSIONS: Treatment responses to corticosteroids for anorexia may be predicted by PPS, drowsiness, and baseline symptom intensity. Larger prospective studies are needed to confirm these results.
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Corticosteroides/uso terapêutico , Anorexia/tratamento farmacológico , Neoplasias/complicações , Cuidados Paliativos/métodos , Corticosteroides/administração & dosagem , Corticosteroides/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Dyspnea is one of the most common and distressing symptoms in patients with cancer and noncancer advanced diseases. The Japanese Society for Palliative Medicine revised previous guidelines for the management of respiratory symptoms in patients with cancer and newly developed clinical guidelines for managing dyspnea in patients with advanced disease, based on the result of systematic reviews for each clinical question and consensus among experts. We describe the recommendations of the guidelines as well as provide insights into the reasoning behind the recommendations and their development process. There has been a paucity of evidence regarding the interventions for dyspnea in patients with advanced disease. Thus, more clinical research that includes not only randomized controlled trials but also real-world observational studies is warranted.
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BACKGROUND: Supplemental oxygen is widely used for dyspnea relief; however, its efficacy is yet to be verified. This study aimed to determine the efficacy of supplemental oxygen for dyspnea relief in patients with advanced progressive illness. METHODS: In this systematic review, several databases, including MEDLINE and EMBASE, were searched to identify eligible randomized controlled trials (RCTs) on the topic published up to September 23, 2019. The search criteria included RCTs investigating patients with advanced progressive illness (advanced cancer, chronic obstructive pulmonary disease, and chronic heart failure). The study protocol was registered with PROSPERO (No. CRD42020161838). Separate analyses were pre-planned regarding the presence or absence of resting hypoxemia. RESULTS: RCTs investigating supplemental oxygen for dyspnea relief in participants with and without resting hypoxemia (39 and five, respectively) were included in the study. Heterogeneity of supplemental oxygen for dyspnea in RCTs, including participants without resting hypoxemia was evident; hence, post-hoc analyses in four subgroups (supplemental oxygen during exercise or daily activities, short-burst oxygen, continuous supplemental oxygen, and supplemental oxygen during rehabilitation intervention) were conducted. In the meta-analysis, supplemental oxygen during exercise was found to improve dyspnea in patients without resting hypoxemia compared with that in the control (standardized mean difference = -0.57, 95% confidence interval = -0.77 to -0.38). However, supplemental oxygen for the other subgroups failed to improve patients' dyspnea. CONCLUSION: The results of this systematic review do not support supplemental oxygen therapy for dyspnea relief in patients with advanced progressive illness, except during exercise.
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Oxigenoterapia , Doença Pulmonar Obstrutiva Crônica , Humanos , Oxigenoterapia/métodos , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/terapia , Oxigênio , Dispneia/etiologia , Dispneia/terapia , Hipóxia/etiologia , Hipóxia/terapiaRESUMO
BACKGROUND: This study aimed to investigate the effectiveness of anticholinergics (AC) for death rattle in dying patients with cancer. METHODS: This is a prospective cohort study enrolled Terminally ill adult (20 years or older) patients with cancer who developed substantial death rattle (Back score ≥2) from 23 palliative care units in Japan. AC treatment for death rattle was prescribed according to primary physician's decision. The primary outcome was the proportion of patients whose death rattle improved, which was defined as a Back score of ≤1. We compared the proportion of improved cases in patients treated with (AC group) and without (non-AC group) AC, controlling potential confounders by employing propensity score weighting. RESULTS: Of the 1896 patients enrolled, we included 196 who developed a substantial death rattle. Of these, 81 received AC. 56.8% in the AC group and 35.4% in the non-AC group had an improved death rattle at 8 hours after baseline. In the weighted analysis, AC group showed significant improvements in death rattle, with an adjusted OR of 4.47 (95% CI 2.04 to 9.78; p=0.0024). All sensitivity analyses achieved essentially the same results. In the subgroup analysis, ACs were strongly associated with death rattle improvement in men, patients with lung cancer, and type 1 death rattle (adjusted OR 5.81, 8.38 and 9.32, respectively). CONCLUSIONS: In this propensity score-weighted analysis, ACs were associated with death rattle improvement in terminally ill patients with cancer who developed substantial death rattle. TRIAL REGISTRATION NUMBER: UMIN-CTR (UMIN00002545).
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Neoplasias Pulmonares , Assistência Terminal , Masculino , Adulto , Humanos , Assistência Terminal/métodos , Estudos Prospectivos , Sons Respiratórios , Antagonistas Colinérgicos/uso terapêuticoRESUMO
Background: Pain is one of the most common symptoms in cancer patients. The Japanese Society for Palliative Medicine (JSPM) first published its clinical guidelines for the management of cancer pain in 2010. Since then, more research on cancer pain management has been reported, and new drugs have become available in Japan. Thus, the JSPM has now revised the clinical guidelines using a validated methodology. Methods: This guideline was developed through a systematic review, discussion, and the Delphi method, following a formal guideline development process. Results: Thirty-five recommendations were created: 19 for the pharmacological management of cancer pain, 6 for the management of opioid-induced adverse effects, and 10 for pharmacological treatment procedures. Due to the lack of evidence that directly addressed our clinical questions, most of the recommendations had to be based on consensus among committee members and other guidelines. Discussion: It is critical to continue to build high-quality evidence in cancer pain management, and revise these guidelines accordingly.
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Dor do Câncer , Neoplasias , Medicina Paliativa , Dor do Câncer/tratamento farmacológico , Humanos , Japão , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Cuidados PaliativosRESUMO
Background: Respiration with mandibular movement (RMM) is one of the important clinical signs of impending death. However, there is very limited data on its natural course. Objective and Methods: This study was conducted in 23 inpatient palliative care units in Japan. It aimed to explore the natural course of RMM. Results: Among a total of 1526 cancer patients included, 1065 patients (69.8%) had RMM. A total of 14.8% patients experienced respiratory arrest within 30 minutes from RMM onset, 14.3% within 30-60 minutes, 34.4% within 1-4 hours, 17.5% within 4-12 hours, 8.9% within 12-24 hours, and 10.4%> 24 hours. Mean oxygen saturation and percentage of patients with SpO2 ≥90% at RMM onset were found to be significantly higher in patients with longer durations from RMM onset to death (p < 0.001). Conclusion: RMM occurred in a majority (80%) of dying patients within 12 hours. A minority of the patients survived >24 hours.
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Neoplasias , Cuidados Paliativos , Humanos , Neoplasias/diagnóstico , Pacientes , Estudos Prospectivos , RespiraçãoRESUMO
OBJECTIVES: To clarify the relationship between Phase of Illness at the time of admission to palliative care units and symptoms of patients with advanced cancer. METHODS: This study was a secondary analysis of the East Asian collaborative cross-cultural Study to Elucidate the Dying process. Palliative physicians recorded data, including Phase of Illness, physical function and the Integrated Palliative care Outcome Scale. We used multinomial logistic regression to analyse ORs for factors associated with Phase of Illness. Twenty-three palliative care units in Japan participated from January 2017 to September 2018. RESULTS: In total, 1894 patients were analysed-50.9% were male, mean age was 72.4 (SD±12.3) years, and Phase of Illness at the time of admission to the palliative care unit comprised 177 (8.9%) stable, 579 (29.2%) unstable, 921 (46.4%) deteriorating and 217 (10.9%) terminal phases. Symptoms were most distressing in the terminal phase for all items, followed by deteriorating, unstable and stable (p<0.001). The stable phase had lower association with shortness of breath (OR 0.73, 95% CI 0.57 to 0.94) and felt at peace (OR 0.73, 95% CI 0.56 to 0.90) than the unstable phase. In the deteriorating phase, weakness or lack of energy (OR 1.20, 95% CI 1.02 to 1.40) were higher, while drowsiness (OR 0.82, 95% CI 0.71 to 0.97) and felt at peace (OR 0.81, 95% CI 0.71 to 0.94) were significantly lower. CONCLUSION: Our study is reflective of the situation in palliative care units in Japan. Future studies should consider the differences in patients' medical conditions and routinely investigate patients' Phase of Illness and symptoms. TRIAL REGISTRARION NUMBER: UMIN000025457.
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CONTEXT: Several prognostic models such as the Palliative Performance Scale (PPS), Palliative Prognostic Index (PPI), Palliative Prognostic Score (PaP) have been developed to complement clinician's prediction of survival (CPS). However, few studies with large scales have been conducted to show which prognostic tool had better performance than CPS in patients with weeks of survival. OBJECTIVES: We aimed to compare the prognostic performance of the PPS, PPI, PaP, and CPS in inpatients admitted to palliative care units (PCUs). METHODS: This study was part of a multi-center prospective observational study involving patients admitted to PCUs in Japan. We computed their prognostic performance using the area under the receiver operating characteristics curve (AUROC) and calibration plots for seven, 14-, 30- and 60-day survival. RESULTS: We included 1896 patients with a median overall survival of 19 days. The AUROC was 73% to 84% for 60-day and 30-day survival, 75% to 84% for 14-day survival, and 80% to 87% for seven-day survival. The calibration plot demonstrated satisfactory agreement between the observational and predictive probability for the four indices in all timeframes. Therefore, all four prognostic indices showed good performance. CPS and PaP consistently had significantly better performance than the PPS and PPI from one-week to two-month timeframes. CONCLUSION: The PPS, PPI, PaP, and CPS had relatively good performance in patients admitted to PCUs with weeks of survival. CPS and PaP had significantly better performance than the PPS and PPI. CPS may be sufficient for experienced clinicians while PPS may help to improve prognostic confidence for inexperienced clinicians.
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Raciocínio Clínico , Modelos Estatísticos , Cuidados Paliativos , Humanos , Prognóstico , Estudos Prospectivos , Reprodutibilidade dos Testes , Análise de SobrevidaRESUMO
PURPOSE: A sudden unexpected death has significant negative impacts on patients, family caregivers, and medical staff in hospice/palliative care. This study aimed to clarify the incidence and associated factors of sudden unexpected death according to four definitions in advanced cancer patients. METHODS: We performed a prospective cohort study in 23 inpatient hospices/palliative care units in Japan. Advanced cancer patients aged ≥18 years who were admitted to inpatient hospices/palliative care units were included. The incidence and associated factors of sudden unexpected death were evaluated in all enrolled patients according to four definitions: (a) rapid decline death, defined as a sudden death preceded by functional decline over 1-2 days; (b) surprise death, defined if the primary responsible palliative care physician answered "yes" to the question, "Were you surprised by the timing of the death?"; (c) unexpected death, defined as a death that occurred earlier than the physicians had anticipated; and (d) performance status (PS)-defined sudden death, defined as a death that occurred within 1 week of functional status assessment with an Australia-modified Karnofsky PS ≥50. RESULTS: Among 1896 patients, the incidence of rapid decline death was the highest (30-day cumulative incidence: 16.8%, 95% CI: 14.8-19.0%), followed by surprise death (9.6%, 8.1-11.4%), unexpected death (9.0%, 7.5-10.8%), and PS-defined sudden death (6.4%, 5.2-8.0%). Male sex, liver metastasis, dyspnea, malignant skin lesion, and fluid retention were significantly associated with the occurrence of sudden unexpected death. CONCLUSION: Sudden unexpected death is not uncommon even in inpatient hospices/palliative care units, with range of 6.4-16.8% according to the different definitions.
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Morte Súbita/epidemiologia , Neoplasias/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Deterioração Clínica , Intervalos de Confiança , Morte Súbita/etiologia , Feminino , Enfermagem de Cuidados Paliativos na Terminalidade da Vida/estatística & dados numéricos , Humanos , Incidência , Japão/epidemiologia , Avaliação de Estado de Karnofsky , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND & AIMS: The benefits of artificial nutrition and hydration in patients with advanced cancer remain unknown. Therefore, we conducted a prospective study to evaluate effects of enteral nutrition (EN) and parenteral nutrition and hydration (PNH) on survival in palliative care units. METHODS: This study involved a secondary analysis of a multicenter cohort study. Data of primary nutritional administration routes during the first week after admission (oral intake, enteral tube feeding, parenteral nutrition, parenteral hydration, poor oral intake) were obtained. Data of averaged calorie sufficiency rate/total calorie intake [high (75% ≤ or 750 kcal/day ≤), moderate (50-75% or 500-750 kcal/day), low (25-50% or 250-500 kcal/day), very low (<25% or <250 kcal/day)] were also obtained. After investigating the implementation of artificial nutrition and hydration, participants were divided into three groups according to the nutritional administration route and calorie sufficiency rate/total calorie intake: EN, PNH, and control. We conducted time-to-event analyses using the Kaplan-Meier method, log-rank test, and univariate and multivariate Cox regression analyses. RESULTS: Patients were divided into the EN group (n = 730), PNH group (n = 190), and control group (n = 533). Differences in survival rates among the three groups were significant (Log-rank P < 0.001). Median survival times were 43.0 (95% CI 40-46), 33.0 (95% CI 29-37), and 15.0 (95% CI 14-16) days, respectively (P < 0.001). In the multivariate-adjusted model, a significantly lower risk of mortality was observed in Cox's proportional hazard model in the EN group and PNH groups (HR 0.43 [95% CI 0.37-0.49], P < 0.001; and HR 0.52 [95% CI 0.44-0.62], P < 0.001, respectively) than in the control group. CONCLUSIONS: This study indicated the clinical benefits of EN and PNH for patients with advanced cancer. Nevertheless, managing symptoms to improve oral intake is essential before initiation of PNH, because EN was superior to PNH.
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Caquexia/mortalidade , Nutrição Enteral/mortalidade , Neoplasias/mortalidade , Nutrição Parenteral/mortalidade , Idoso , Idoso de 80 Anos ou mais , Caquexia/etiologia , Caquexia/terapia , Ingestão de Energia , Nutrição Enteral/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Estado Nutricional , Cuidados Paliativos/estatística & dados numéricos , Nutrição Parenteral/métodos , Modelos de Riscos Proporcionais , Estudos Prospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: To investigate the efficacy of two types of palliative sedation: proportional and deep sedation, defined by sedation protocols. METHODS: From a multicenter prospective observational study, we analyzed the data of those patients who received the continuous infusion of midazolam according to the sedation protocol. The primary endpoint was goal achievement at 4 hours: in proportional sedation, symptom relief (Integrated Palliative care Outcome Scale: IPOS ≤ 1) and absence of agitation (modified Richmond Agitation-Sedation Scale: RASS ≤ 0); in deep sedation, the achievement of deep sedation (RASS ≤ -4). Secondary endpoints included deep sedation as a result of proportional sedation, communication capacity (Communication Capacity Scale item 4 ≤ 2), IPOS and RASS scores, and adverse events. RESULTS: A total of 81 patients from 14 palliative care units were analyzed: proportional sedation (n = 64) and deep sedation (n = 17). At 4 hours, the goal was achieved in 77% (n = 49; 95% confidence interval: 66-87) with proportional sedation; and 88% (n = 15; 71-100) with deep sedation. Deep sedation was necessary in 45% of those who received proportional sedation. Communication capacity was maintained in 34% with proportional sedation and 10% with deep sedation. IPOS decreased from 3.5 to 0.9 with proportional sedation, and 3.5 to 0.4 with deep sedation; RASS decreased from +0.3 to -2.6, and +0.4 to -4.2, respectively. Fatal events related to the treatment occurred in 2% (n = 1) with proportional and none with deep sedation. CONCLUSION: Proportional sedation achieved satisfactory symptom relief while maintaining some patients' consciousness, and deep sedation achieved good symptom relief while the majority of patients lost consciousness.
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Sedação Profunda , Humanos , Hipnóticos e Sedativos/uso terapêutico , Unidades de Terapia Intensiva , Midazolam/uso terapêutico , Estudos Multicêntricos como Assunto , Estudos Observacionais como Assunto , Cuidados Paliativos/métodos , Estudos Prospectivos , Respiração ArtificialRESUMO
Lung cancer patients ≥75 years represent nearly 40% of all lung cancer patients and continue to increase. If elderly patients have a good performance status and adequate organ function, they can be treated the same as non-elderly patients. However, few comparative studies limited to elderly patients (≥75 years) have been conducted. We review the evidence on using immune check inhibitors for the treatment of elderly patients (≥75 years old) with advanced non-small cell lung cancer. Prospective randomized or non-randomized, retrospective, registrational, insurance-based, and community-based studies have shown that elderly (≥75 years) and non-elderly patients are similarly treated with immune check inhibitors effectively and safely. However, such analyses have not shown that immune check inhibitors are significantly more effective than chemotherapy alone. In addition, patient selection might be critically performed to administer immune check inhibitors in the elderly because they are more likely to have a poor performance status with comorbidities, which lead to little benefit, even in non-elderly patients. There is a need for more evidence showing the benefit of immune check inhibitors in non-small cell lung cancer patients ≥75 years.
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OBJECTIVE: Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is overexpressed in a subset of malignant cells. However, it remains unknown whether ROR1 is targetable in malignant mesothelioma (MM). Therefore, in this study, we investigated the effects of ROR1 inhibition in mesothelioma cells. MATERIALS AND METHODS: Growth inhibition, colony formation, apoptosis, and mRNA/protein levels using siRNA-transfected MM cells were evaluated. Cluster analysis using Gene Expression Omnibus repository of transcriptomic information was also performed. RESULTS: Our results indicated that in three (H2052, H2452, and MESO-1) among four MM cell lines, ROR1 inhibition had anti-proliferative and apoptotic effects and suppressed the activation of AKT and STAT3. Although growth inhibition by siROR1 was minimal in another mesothelioma cell line (H28), colony formation was significantly suppressed. Microarray, quantitative polymerase chain reaction, and Western blot analyses showed that there were differences in the suppression of mRNA and proteins between H2452 and H28 cells transfected with siROR1 compared with those transfected with control siRNA. Cluster analysis further showed that MM tumors had relatively high ROR1 expression, although the cluster in them was different from that in MM cell lines. Thymidylate synthase, a target of pemetrexed, was downregulated in H2452 cells transfected with siROR1. Accordingly, a combination of pemetrexed with siROR1 was found to be effective in the three MM cell lines we studied. CONCLUSION: Our findings may provide novel therapeutic insight into the treatment of advanced MM.
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Apoptose , Mesotelioma Maligno/patologia , Pemetrexede/farmacologia , Neoplasias Pleurais/patologia , RNA Interferente Pequeno/genética , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/antagonistas & inibidores , Antineoplásicos/farmacologia , Proliferação de Células , Terapia Combinada , Humanos , Mesotelioma Maligno/genética , Mesotelioma Maligno/terapia , Neoplasias Pleurais/genética , Neoplasias Pleurais/terapia , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/genética , Transdução de Sinais , Células Tumorais CultivadasRESUMO
Background: Gastrointestinal symptoms, including nausea, vomiting, bowel obstruction, ascites, constipation, and anorexia, are common and often refractory in advanced cancer patients. The palliation of gastrointestinal symptoms is important in improving the quality of life of cancer patients, as well as that of their families and caregivers. Currently published clinical guidelines for the management of gastrointestinal symptoms in cancer patients do not comprehensively cover the topics or are not based on a formal process for the development of clinical guidelines. Methods: The Japanese Society for Palliative Medicine (JSPM) developed comprehensive clinical guidelines for the management of gastrointestinal symptoms in cancer patients after a formal guideline development process. Results: This article summarizes the recommendations along with their rationale and a short summary of the development process of the JSPM gastrointestinal symptom management guidelines. We established 31 recommendations, all of which are based on the best available evidence and agreement of expert taskforce members. Discussion: Future clinical studies and continuous guideline updates are required to improve gastrointestinal symptom management in cancer patients.
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Antieméticos/uso terapêutico , Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/etiologia , Gastroenteropatias/enfermagem , Neoplasias/complicações , Cuidados Paliativos/normas , Guias de Prática Clínica como Assunto , Adulto , Idoso , Idoso de 80 Anos ou mais , Anorexia/tratamento farmacológico , Anorexia/enfermagem , Constipação Intestinal/tratamento farmacológico , Constipação Intestinal/enfermagem , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Náusea/tratamento farmacológico , Náusea/enfermagem , Vômito/tratamento farmacológico , Vômito/enfermagemRESUMO
Background: Tumor fever and infection are common febrile etiologies among advanced cancer patients. To date, only few studies have been conducted to differentiate between tumor fever and infections. Objective: This study aimed to identify discriminating factors that provide rapid results and are feasible and minimally invasive for discriminating between tumor fever and infection in advanced cancer patients. Methods: This is a retrospective cohort study. Advanced cancer patients with clinically diagnosed tumor fever or infection, who received medical treatment from palliative care specialists in 10 nationwide Japanese hospitals, were consecutively identified during August 2012 and November 2014. The symptoms, physical findings, blood test results at baseline and during fever, imaging findings, and sociodemographic factors of these patients were retrospectively extracted. Results: Thirty-three patients with tumor fever and 72 patients with infection were identified. Their mean age was 68.8 years, 68 (64.8%) were men, and the median palliative performance status (PPS) was 50. Statistically significant factors predicting tumor fever by logistic regression analysis were as follows: deterioration of PPS (odds ratio, 0.078), shaking chills during fever (0.067), and change from baseline data of neutrophil/lymphocyte ratio of ≥5 (0.14). Conclusions: Shaking chills during fever, and changes from baseline of performance status and white blood cell differentiation can be useful to differentiate between tumor fever and infection among advanced cancer patients. Further confirmatory studies are needed.