RESUMEN
BACKGROUND: Staying at home during the dying process is important for many patients; and palliative care units (PCUs) can help facilitate home death. This study compared patient survival between those who were discharged to home from a palliative care unit and those who were not, and aimed to identify the factors associated with home death after the discharge. METHODS: This retrospective cohort study used a database of patients admitted to a palliative care unit at Kouseiren Takaoka Hospital in Japan. All consecutive patients admitted to the hospital's PCU between October 2016 and March 2020 were enrolled. Patient survival and factors potentially associated with survival and place of death were obtained. A total of 443 patients with cancer were analyzed, and 167 patients were discharged to home and 276 were not. RESULTS: Propensity score matching analyses revealed that median survival time was significantly longer in patients who were discharged to home than those who were not (57 vs. 27 days, P < 0.001). Multiple logistic regression analysis identified that worse Palliative Prognostic Index (odds ratio [OR] = 1.21, 95% confidence interval [CI] = 1.03-1.44, p = 0.025) and family members' desire for home death (OR = 6.30, 95% CI = 2.32-17.1, p < 0.001) were significantly associated with home death after their discharge. CONCLUSIONS: Discharge to home from palliative care units might have some positive impacts on patient survival.
Asunto(s)
Neoplasias , Cuidados Paliativos , Humanos , Alta del Paciente , Estudios de Cohortes , Estudios Retrospectivos , Hospitalización , Neoplasias/terapiaRESUMEN
PURPOSE: In order to detect cancer therapeutics-related cardiac dysfunction (CTRCD) early, we identified which drugs were to be monitored using signal detection and the package insert, and created and applied a protocol to address this. METHODS: Adverse event data recorded in the Japanese Adverse Drug Event Report (JADER) database between April 2004 and January 2018 were used. Among small molecule tyrosine kinase inhibitors that are not described in the serious side-effects section of the package insert despite signal detection, tyrosine kinase inhibitors with severe side-effects in the background of cases reported by JADER database were selected to be monitored in clinical practice. We applied our findings clinically by creating a protocol to detect CTRCD early. All cases at Tosei General Hospital where the target tyrosine kinase inhibitors were administered from when they were first released in November 2019 were included. We compared the results from before and after we began the protocol to clarify its effects. RESULTS: We found that CTRCD was not described in the serious side-effect section of the package inserts for Bosutinib, Alectinib, and Osimertinib even though CTRCD signals were detected for them. Therefore, it is possible that we may have previously overlooked CTRCD. When we applied our protocol using Osimertinib as the target drug, we were able to detect CTRCD early in 5/21 (24%) patients. CONCLUSIONS: It was clarified that the drug identification method used in this study for early detection of adverse events leads to early detection of adverse events when applied clinically.
Asunto(s)
Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Detección Precoz del Cáncer/métodos , Cardiopatías/inducido químicamente , Neoplasias/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Bibliotecas de Moléculas Pequeñas , Adulto , Sistemas de Registro de Reacción Adversa a Medicamentos , Bases de Datos Factuales , Etiquetado de Medicamentos , Monitoreo de Drogas , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Cardiopatías/diagnóstico , Humanos , Japón , Masculino , Monitoreo Fisiológico , Neoplasias/diagnóstico , Procesamiento de Señales Asistido por ComputadorRESUMEN
BACKGROUND: Many patients wish to stay at home during the terminal stage of cancer. However, there is concern that medical care provided at home may negatively affect survival. This study therefore explored whether the survival duration differed between cancer patients who received inpatient care and those who received home care. METHODS: We retrospectively investigated the place of care/death and survival duration of 190 cancer patients after their referral to a palliative care consultation team in a Japanese general hospital between 2007 and 2012. The patients were classified into a hospital care group consisting of those who received palliative care in the hospital until death, and a home care group including patients who received palliative care at home from doctors in collaboration with the palliative care consultation team. Details of the place of care, survival duration, and patient characteristics (primary site, gender, age, history of chemotherapy, and performance status) were obtained from electronic medical records, and analyzed after propensity score matching in the place of care. RESULTS: Median survival adjusted for propensity score was significantly longer in the home care group (67.0 days, n = 69) than in the hospital care group (33.0 days, n = 69; P = 0.0013). Cox's proportional hazard analysis revealed that the place of care was a significant factor for survival following adjustment for covariates including performance status. CONCLUSIONS: This study suggests that the general concern that home care shortens the survival duration of patients is not based on evidence. A cohort study including more known prognostic factors is necessary to confirm the results.
RESUMEN
Candida glabrata was continuously isolated in cultured urine samples from a subject with thrombotic thrombocytopenic purpura. Yeast-like fungal phagocytosis found in gram staining led to agents being tested for antifungal susceptibility, revealing hyposensitivity to micafungin (MCFG) of MIC < 2 mg/mL. MCFG administered for 10 days failed to cure C. glabrata infection. To clarify why hyposensitivity occurred, we analyzed the FKS gene sequence using the PCR, finding a deficit of 3 bases coding phenylalanine at FKS2 gene amino acid 659. MCFG hyposensitivity may thus occur in long-term candin-class anti-fungal agent treatment. Candin-class agents have potent anti-fungal activity with fewer adverse effects and are widely used clinically. Hyposensitivity due to resistant C. glabrata species showed thus be considered in fungal infection treatment.
Asunto(s)
Antifúngicos/farmacología , Candida glabrata/efectos de los fármacos , Candida glabrata/genética , Farmacorresistencia Fúngica , Equinocandinas/farmacología , Genes Fúngicos/genética , Lipopéptidos/farmacología , Mutación , Anciano , Femenino , Proteínas Fúngicas/genética , Glucosiltransferasas/genética , Humanos , Proteínas de la Membrana/genética , MicafunginaRESUMEN
We investigated the susceptibility of Candida species from clinical aseptic samples, including blood, at some hospitals in Saitama prefecture. Candida spp. detected from aseptic samples in the 6 institutes in Saitama prefecture from November 2007 to July 2011 were studied. The number of isolates was 85, which are 43 (50.6%) of Candida albicans, 24 (28.2%) of Candida parapsilosis, 5 (5.9%) of Candida glabrata, 5 (5.9%) of Candida tropicalis, 4 (4.7%) of Candida guilliermondii, 2 (2.4%) of Candida fermentati, 1 (1.2%) of Candida famata and Candida lusitaniae, respectively. All isolates were susceptible to amphotericin B. However, resistant isolates against micafungin were 3 in 5 of C. glabrata. We analyzed susceptibility of Candida spp. in Saitama prefecture in the article, and our study might be useful for the fungal therapy in the region.
Asunto(s)
Antifúngicos/farmacología , Candida/efectos de los fármacos , Candidiasis/microbiología , Farmacorresistencia Fúngica , Candida/citología , Candida/aislamiento & purificación , Humanos , Japón , Pruebas de Sensibilidad MicrobianaRESUMEN
In May, 2009, a man in his 30s presented to the department of outpatient palliative care of this hospital. His chief complaints were of severe nausea and abdominal fullness associated with cancerous peritonitis following surgery for gastric cancer. Abdominal fullness was reduced after the initiation of a continued subcutaneous administration of octreotide acetate, but combination therapy with metoclopramide and domperidone did not relieve nausea. The administration of olanzapine orally disintegrating tables (OLZ-ODT) at a dose of 10 mg twice daily was associated with the tendency to reduce nausea. As the symptoms were relieved, palliative care at his home was initiated. The patient's self-discontinuation of OLZ-ODT because the nausea was relieved resulted in its aggravation, but it was relieved again when the administration was resumed. Subsequently, home care was possible for approximately two and half a months without aggravation. Maintaining nausea control well leads to higher-quality care. OLZ-ODT appears to not only be effective for relieving nausea associated with cancerous peritonitis, but is also important for disseminating palliative care at home.
Asunto(s)
Benzodiazepinas/uso terapéutico , Servicios de Atención de Salud a Domicilio , Cuidados Paliativos , Peritonitis/tratamiento farmacológico , Neoplasias Gástricas/terapia , Administración Oral , Adulto , Benzodiazepinas/administración & dosificación , Resultado Fatal , Humanos , Masculino , Olanzapina , Peritonitis/etiología , Neoplasias Gástricas/complicaciones , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: The aim of this study was to prevent drug-related medication errors in the operating room by clarifying the association between the medication error category with related drugs and contributing factors. METHODS: We used data from the Japan Council for Quality Health Care's open database on the web. We researched the medication error category, related drugs, and contributing factors. We classified each medication error category into case groups and other medication error categories into control groups. We compared the medication error factors of the 2 groups using multivariate logistic regression analysis on the medication error factors. RESULTS: The total number of analyzed cases was 541. Incorrect dose was the most common medication error category in 170 cases, followed by incorrect drug in 152 cases. Medication error factors (odds ratio, 95% confidence interval) that were found to be significantly positively associated with incorrect dose were "pressor drugs" (3.0, 1.4-6.4), "anesthesia-inducing drugs" (6.3, 1.7-23.4), "lack of knowledge" (2.0, 1.3-3.3), and "drug administration" (3.4, 1.6-7.4). The medication error factors that were found to be significantly positively associated with incorrect drug were "preparation" (5.7, 3.1-10.5) and "medication passed or picked up" (102.2, 35.7-292.8). CONCLUSIONS: Medication errors are frequently occurring during drug preparation and administration in the operating room. Medical staff should thoroughly learn about operating room-specific drugs and closely monitor every step of the drug preparation and administration process. It is also important to create a workflow and improve the environment so that it reduces the likelihood of medication errors.
Asunto(s)
Quirófanos , Preparaciones Farmacéuticas , Bases de Datos Factuales , Humanos , Japón , Errores de Medicación/prevención & controlRESUMEN
BACKGROUND: The purpose of this study was to clarify how the Regional Referral Clinical Pathway for Home-based Palliative Care (RRCP-HPC) and an outreach program by a palliative care team (PCT) lead to an improvement in the outcome. DESIGN AND METHODS: We conducted questionnaire surveys using the mailing method involving the regional medical staff involved in cancer patients introduced to the PCT of a single hospital, as well as bereaved families. The questionnaire was prepared through interviews with the medical staff and bereaved families. Subsequently, factor analysis was performed to identify factor structures and calculate the correlation coefficient with each outcome. RESULTS: For the questionnaire survey involving the medical staff, responses were collected from 119 regional medical institutions and 84 regional medical staff. The response rate per institution was 51.3%. Similarly, for the questionnaire survey involving bereaved families, the response rate was 42.4%. For the survey involving the medical staff, 6 factors, such as "improved awareness of an interdisciplinary team," were extracted. For the survey involving the bereaved families, 4 factors, such as "improvement of communications between patients and healthcare professionals," were extracted. There were significant (≥moderate) correlations between these factors and all outcomes. CONCLUSION: In this study, we clarified the process of achieving palliative care until death at home without difficulties using the outreach program and RRCP-HPC. The results suggest the importance of improving communications. The outreach program and RRCP-HPC may have contributed to palliative care at home without difficulties through an improvement in communications.
Asunto(s)
Neoplasias , Cuidados Paliativos , Vías Clínicas , Humanos , Cuerpo Médico , Cuidados Paliativos/métodos , Derivación y Consulta , Encuestas y CuestionariosRESUMEN
BACKGROUND: There is limited research regarding the use of glaucoma medicines during pregnancy. Prostaglandins contract uterine smooth muscle; however, it is not clear whether prostaglandin eye drops are associated with pregnancy loss in pregnant women. OBJECTIVES: We conducted a pharmacovigilance study using spontaneous report databases from Japan and the USA to evaluate the association between pregnancy loss and the use of prostaglandin eye drops during pregnancy. METHODS: The Japanese Adverse Drug Event Report database and the Food and Drug Administration Adverse Event Reporting System were used for analysis. Disproportionality analyses and a review of individual case safety reports were conducted. RESULTS: As for prostaglandin eye drops in pregnancy-related reports, there were eight reports involving latanoprost in the Japanese Adverse Drug Event Report database and no reports of pregnant women using other prostaglandin eye drops. In the Food and Drug Administration Adverse Event Reporting System, there were 25 reports involving latanoprost, 23 involving bimatoprost, 13 involving travoprost, and three involving tafluprost. The drug safety signal was detected during latanoprost usage and pregnancy loss. In the Japanese Adverse Drug Event Report database, there were five reports of pregnancy loss related to latanoprost, with a reporting odds ratio of 12.84 (95% confidence interval 3.06-53.86), and in the Food and Drug Administration Adverse Event Reporting System, pregnancy loss was reported in 12 cases of latanoprost usage with a reporting odds ratio of 4.35 (95% confidence interval 1.98-9.54). Uterine contractions were observed as concomitant adverse events in one case. CONCLUSIONS: Although a disproportionality analysis cannot determine causality, we need to keep an eye on the signal detected in this study. This signal should be validated using a causal design study.
RESUMEN
Candida glabrata was continuously isolated in cultured urine samples from a subject with thrombotic thrombocytopenic purpura. Yeast-like fungal phagocytosis found in gram staining led to agents being tested for antifungal susceptibility, revealing hyposensitivity to micafungin (MCFG) of MIC <2 mg/mL. MCFG administered for 10 days failed to cure C. glabrata infection. To clarify why hyposensitivity occurred, we analyzed the FKS gene sequence using the PCR, finding a deficit of 3 bases coding phenylalanine at FKS2 gene amino acid 659. MCFG hyposensitivity may thus occur in long-term candin-class anti-fungal agent treatment. Candin-class agents have potent anti-fungal activity with fewer adverse effects and are widely used clinically. Hyposensitivity due to resistant C. glabrata species showed thus be considered in fungal infection treatment.
Asunto(s)
Antifúngicos/farmacología , Candida glabrata/genética , Equinocandinas/farmacología , Proteínas Fúngicas/genética , Lipopéptidos/farmacología , Mutación , Anciano , Candida glabrata/efectos de los fármacos , Farmacorresistencia Fúngica/genética , Femenino , Humanos , MicafunginaRESUMEN
INTRODUCTION: Small molecule tyrosine kinase inhibitors (TKIs) inhibit not only the target kinase but also various kinases as off-target inhibitors not mentioned in the package insert. However, there are no reports that comprehensively examine the relationship between adverse events and kinase affinity. OBJECTIVE: In this study, we combined basic data and clinical data to visualize the relationship between kinase affinity and adverse events, which will be useful for the management of adverse events in clinical practice. METHODS: We targeted TKIs that have been used domestically and for which the dissociation constant was obtained as reported by Davis et al. Adverse event data recorded in the Japanese Adverse Drug Event Report (JADER) database provided by the Pharmaceuticals and Medical Devices Agency between April 2004 and January 2018 were used. We calculated the reporting rates of the Standardized MedDRA Queries (SMQ) for the adverse events of interest and visualized the correlation coefficients with kinase affinity. We used the adverse events associated with VEGFR2 and EGFR to assess their validity. RESULTS: We found a correlation among known kinase-related adverse events, suggesting that the methodology may be used as a signal detection method to generate hypotheses for clinical and basic research. CONCLUSION: Our comprehensive analysis of the kinase affinity of TKIs in this study, which was based on basic TKI kinase affinity data and the clinical data of the reporting rates, suggested that our comprehensive analysis method is useful for generating hypotheses about possible causal relationships between pharmacological effects and adverse events.
RESUMEN
We experienced a case in which zoledronate was effective for alleviating gastrointestinal symptoms arising from urinary bladder cancer-associated hypercalcemia, and long-term palliative home care was feasible by continuation of the administration. A female in her eighties was found to have bladder cancer. After transurethral resection of the bladder tumor, part of it was left unresected. Since dizziness, appetite loss, and general fatigue became severer, blood tests were carried out and hypercalcemia was observed. Then, zoledronate was administered and clinical symptoms quickly improved. After discussion with her and her family, palliative home care was selected. Home care was possible for about six months by continuation of zoledronate administration. In conclusion, it was suggested that careful continuous administration of zoledronate was also useful for symptom control in the palliative home care, and that it would potentially be a key drug for promotion of palliative home care.
Asunto(s)
Conservadores de la Densidad Ósea/uso terapéutico , Difosfonatos/uso terapéutico , Servicios de Atención de Salud a Domicilio , Hipercalcemia/tratamiento farmacológico , Imidazoles/uso terapéutico , Cuidados Paliativos , Neoplasias de la Vejiga Urinaria/terapia , Anciano de 80 o más Años , Resultado Fatal , Femenino , Humanos , Hipercalcemia/etiología , Cuidado Terminal , Neoplasias de la Vejiga Urinaria/complicaciones , Ácido ZoledrónicoRESUMEN
We investigated the possibility that having pharmacists give asthma patients informational sheets on climate and environmental changes at insurance pharmacies during patient counseling might prevent the worsening of asthma symptoms. Patients with hyperlipidemia were comparative subjects. We created informational sheets about climate and environmental changes and their influence on asthma. During patient counseling, pharmacists gave them to all asthma patients who visited insurance pharmacies over a period of 2 months, between November and December 2017. Based on previous studies, we called days which showed certain climate or environmental changes as compared to the previous day "change days". We compared the number of visiting patients on change days after preventative information was provided (between January and March 2018) with the number before information was provided (between January and March 2017). In addition, we compared those numbers with the number of patients who visited the target pharmacies between January and March 2016 in order to examine the influence of yearly climate change. The same procedure was used with hyperlipidemic patients. The number of visiting asthma patients after information was provided significantly decreased (5.1±2.1, p=0.03) compared with the number before information was provided, between January and March 2017 (6.1±2.8). The number of aforementioned visits compared to those between January and March 2016 also significantly decreased (p=0.01). Our results suggest that preventative information about climate and environmental changes provided by pharmacists during patient counseling might influence the number of asthma patient visits and prevent the exacerbation of their symptoms.
Asunto(s)
Asma/prevención & control , Clima , Consejo/métodos , Ambiente , Difusión de la Información/métodos , Seguro de Servicios Farmacéuticos , Farmacéuticos , Asma/etiología , Presión Atmosférica , Progresión de la Enfermedad , Exposición a Riesgos Ambientales/efectos adversos , Humanos , Humedad , Material Particulado , Estaciones del Año , Temperatura , Factores de TiempoRESUMEN
BACKGROUND: Patients and their families are able to obtain information about palliative care from websites easily nowadays. However, there are concerns on the accuracy of information on the Web and how up to date it is. OBJECTIVE: The objective of this study was to elucidate problematic points of medical information about palliative care obtained from websites, and to compare the quality of the information between Japanese and US websites. METHODS: We searched Google Japan and Google USA for websites relating to palliative care. We then evaluated the top 50 websites from each search using the DISCERN and LIDA instruments. RESULTS: We found that Japanese websites were given a lower evaluation of reliability than US websites. In 3 LIDA instrument subcategories-engagability (P<.001), currency (P=.001), and content production procedure (P<.001)-US websites scored significantly higher and had large effect sizes. CONCLUSIONS: Our results suggest that Japanese websites have problems with the frequency with which they are updated, their update procedures and policies, and the scrutiny process the evidence must undergo. Additionally, there was a weak association between search ranking and reliability, and simultaneously we found that reliability could not be assessed by search ranking alone.
RESUMEN
OBJECT: To examine the clinical outcomes of a project to enhance the awareness of community-based palliative care (awareness-enhancing project), focusing on home death and care rates in communities. METHODS: A single-center study on community-based intervention was conducted. The awareness-enhancing project, consisting of three intervention approaches (outreach, palliative care education for community-based medical professionals, and information-sharing tool use), was executed, and changes in the home death rate in the community were examined. RESULTS: The home death rate markedly exceeded the national mean from 2010. In 2012-2013, it was as high as 19.9%, greater than the previous 5.9% (p = 0.001). Through multivariate analysis, the participation of home care physicians and visiting nurses in a palliative care education program, and patients' Palliative Prognostic Index values were identified as factors significantly influencing the home death rate. CONCLUSION: The three intervention approaches time dependently increased the home death rate as a clinical outcome in the community, although they targeted limited areas. These approaches may aid in increasing the number of individuals who die in their homes.
Asunto(s)
Concienciación , Muerte , Servicios de Atención de Salud a Domicilio/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Cuidados Paliativos , Femenino , Humanos , MasculinoRESUMEN
Background: Toileting independence is considered to be important factors for achieving a "good death" for terminally ill patients. Aim: To clarify the period from loss of the ability to access toilets independently to death in end-stage cancer patients. Design: Observational study. Setting/Participants: The medical records of all end-stage cancer patients who had died while using home care services provided by Medical Corporation Kagayaki General Home Care Clinic between September 2011 and August 2017, were retrospectively reviewed. Results: A total of 220 patients were included. The median time from total dependence in toileting to death was 6.0 (95% confidence interval: 5.0-7.0) days. When the duration was 7 days or shorter and 21 days or shorter, the cumulative death rate was 55.9% and 86.4% respectively. Conclusion: A large percentage of terminally ill cancer patients maintained the ability to access toilets independently until very close to the end of their lives, so the duration of total assistance needed was shorter. These findings may be useful to make a care plan to support achieving "good death" for patients.
Asunto(s)
Vida Independiente , Neoplasias , Enfermo Terminal , Cuartos de Baño , Actividades Cotidianas , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Auditoría Médica , Persona de Mediana Edad , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
INTRODUCTION: With recent advances in medicines, many patients with schizophrenia have become able to conceive. One common second-generation antipsychotic given to patients with schizophrenia is aripiprazole. The label information of aripiprazole in Japan states that according to one case report "there is a report of miscarriage in clinical trial". OBJECTIVE: The aim of this study was to evaluate the relationship between aripiprazole and miscarriage by conducting a disproportionality analysis of an adverse drug event report database. METHODS: We conducted a disproportionality analysis of second-generation antipsychotic exposure during pregnancy using the Japanese Adverse Drug Event Report database, which is a spontaneous reporting database in Japan. We investigated aripiprazole and other approved second-generation antipsychotics in Japan. In accordance with the previous report, we created a data set for analysis consisting of pregnancy-related reports. RESULTS: A potential signal for miscarriage was detected for aripiprazole [proportional reporting ratio: 2.39, χ 2: 13.77, reporting odds ratio (95% confidence interval): 2.76 (1.62-4.69); n = 18]. In contrast, no potential signal for miscarriage was detected for other second-generation antipsychotics. CONCLUSION: Through our analysis of the Japanese Adverse Drug Event Report database, we found a potential signal for miscarriage for aripiprazole. Safety information on the use of aripiprazole during pregnancy is very limited. Therefore, we suggest that the potential signal detected in our analysis be explored further.
Asunto(s)
Aborto Espontáneo/inducido químicamente , Aborto Espontáneo/epidemiología , Sistemas de Registro de Reacción Adversa a Medicamentos/estadística & datos numéricos , Antipsicóticos/efectos adversos , Aripiprazol/efectos adversos , Bases de Datos Factuales/estadística & datos numéricos , Femenino , Humanos , Japón/epidemiología , EmbarazoRESUMEN
BACKGROUND: Approximately 70% of the patients who receive chemotherapy suffer from fatigue, which lowers their quality of life and also has a negative influence on therapeutic efficacy. Previous studies have suggested a relationship between blood carnitine levels and fatigue. We conducted a prospective observational study to examine the relationship between carnitine pharmacokinetics and chemotherapy-induced fatigue in patients receiving cancer chemotherapy regimens that include cisplatin. PATIENTS AND METHODS: 11 patients receiving chemotherapy including cisplatin (60-80 mg/m2) were included in the study. We performed 24-h urine collections and took blood samples on day 1 (before the initiation of chemotherapy) and days 2, 3, 4, and 8 in order to measure the carnitine concentrations in the serum and urine. These were compared with measures of self-reported fatigue. The primary endpoint was the change in self-reported fatigue subscales from baseline to day 8. RESULTS: Urinary carnitine concentrations differed significantly on days 2 and 3 (p = 0.003). The Functional Assessment of Chronic Illness Therapy-Fatigue scale version 4A score on day 8 indicated significantly higher levels of fatigue as compared to day 1 (p = 0.013). CONCLUSION: This study suggests that there is an association between urinary carnitine levels and self-reported fatigue.
Asunto(s)
Antineoplásicos/síntesis química , Carnitina/farmacocinética , Cisplatino/efectos adversos , Fatiga/inducido químicamente , Neoplasias/tratamiento farmacológico , Adulto , Anciano , Antineoplásicos/uso terapéutico , Carnitina/orina , Cisplatino/uso terapéutico , Fatiga/sangre , Fatiga/orina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Tiempo , Microglobulina beta-2/orinaRESUMEN
BACKGROUND: Taxanes are known to cause onychopathy. Previous studies have reported the relationship between onychopathy and paclitaxel dosing intervals and cumulative doses. However, there are no studies of the predictive factors for docetaxel-induced nail changes. The present study used the drug accumulation rate (mg/m2/day) as a novel indicator and evaluated its usefulness for the prediction of onychopathy. METHODS: From January 2008 to December 2009, we examined patients who received docetaxel at the Toyama University Hospital and Tonami General Hospital to determine the time to onset of onychopathy, the accumulation rate, and the cumulative dose. We then divided the study subjects into two groups, and used Receiver Operating Characteristic (ROC) analysis to calculate a cut-off value. We evaluated both indicators as predictive factors for onychopathy using the log-rank test and Cox proportional hazards model. RESULTS: Ninety-five patients were included in the present study. The results of the log-rank test sub-analysis revealed that the median number of days until onychopathy onset was significantly shorter in patients with an accumulation rate greater than the cut-off (P = 0.009), and in those with a cumulative dose below the cut-off (P < 0.001). The hazard ratios for the accumulation rate and cumulative dose, evaluated using Cox proportional hazards regression analysis, were 1.44 (P = 0.036) and 0.99 (P < 0.001), respectively. CONCLUSIONS: The results of the present study indicated that the drug accumulation rate influenced the time to onset of docetaxel-induced onychopathy. TRIAL REGISTRATION: This study is not applicable for trial registration due to retrospective chart review without intervention.
RESUMEN
PURPOSE: Sodium bisulfate is known to affect the stability of octreotide. However, the critical concentration of sodium bisulfate is not known. Therefore, we assessed the critical concentration of sodium bisulfate needed to preserve the stability of octreotide using actual drugs containing sodium bisulfate. METHODS: Although morphine and metoclopramide preparations are considered to be compatible with octreotide, some of their products are known to contain sodium bisulfate. Thus, octreotide was mixed with preparations of sodium bisulfate solutions at serial concentrations and morphine and metoclopramide preparations containing sodium bisulfate, and octreotide stability was then evaluated using high performance liquid chromatography. RESULTS: Octreotide concentrations decreased significantly at a sodium bisulfate concentration of 0.1â mg/mL or higher after 10â days when octreotide was mixed with sodium bisulfate solutions at various concentrations. A significant decrease in octreotide concentrations also occurred when it was mixed with morphine and metoclopramide preparations containing sodium bisulfate and stored for 10â days; however, slight decreases were observed in the mixture with both preparations and were within the clinically acceptable range for morphine preparations. CONCLUSIONS: These results indicate that the residual rate of octreotide decreases with time in a sodium bisulfate concentration-dependent manner when octreotide was mixed with morphine or metoclopramide. However, this incompatibility may be clinically acceptable when the final sodium bisulfate concentration is lower than 0.1â mg/mL and the mixed solution is used within 7â days.