RESUMO
Cancer-associated cachexia, a multifactorial syndrome involving loss of muscle mass and anorexia, affects the survival of cancer patients. Anamorelin was the first drug approved in Japan for the treatment of cachexia. However, cases in which anamorelin is discontinued within 3 weeks are often observed in clinical practice. This study aimed to explore the factors associated with continued anamorelin dosing. We retrospectively reviewed records of patients with lung, gastric, pancreatic, and colorectal cancer who started anamorelin at Fukuoka University Hospital from April 2021 to November 2022. Patients were divided into two groups based on the duration of anamorelin administration: 15 patients were classified into the <3 weeks group and 22 were classified into the ≥3 weeks group. The primary objective was to explore the potential factors associated with the continuation of anamorelin, and the secondary objectives were to compare survival and nutritional indices. In the univariate analysis, there were significant differences between the two groups in terms of cancer type (p=0.007) and serum albumin level (p=0.026). In the multivariate analysis, gastric cancer and albumin 2.7 g/dL or less were associated with the continuation of anamorelin. Survival was significantly shorter in the <3 weeks group (p=0.019). This study suggests that the continuation of anamorelin may be influenced by specific tumor types and serum albumin levels. Furthermore, the duration of anamorelin administration may affect patient survival.
Assuntos
Caquexia , Neoplasias , Humanos , Caquexia/etiologia , Caquexia/tratamento farmacológico , Estudos Retrospectivos , Masculino , Feminino , Idoso , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Pessoa de Meia-Idade , Oligopeptídeos/administração & dosagem , Fatores de Tempo , Idoso de 80 Anos ou mais , Albumina Sérica/análise , Hidrazinas/administração & dosagem , Esquema de MedicaçãoRESUMO
OBJECTIVE: Serum alanine aminotransferase (ALT), which is an indicator of liver dysfunction, may increase during treatment in patients in the acute phase of stroke. However, the cause of the ALT elevation is unclear, as multiple medications are often being used. We investigated the relationship between medications used in acute ischemic stroke, including cerebral infarction and transient ischemic attack, and ALT elevation. METHODS: The subjects were 230 patients who had been diagnosed with cerebral infarction or TIA and treated at the Stroke Care Unit of Fukuoka University Hospital. We investigated ALT abnormalities that occurred from the start of the treatment over the subsequent 14 days. We also followed patients for an additional seven days to confirm the peak ALT levels. A binomial logistic regression analysis was performed to evaluate the association between medications used during the period and ALT elevation. RESULTS: The incidence of ALT abnormality was 23.9% (55/230). ALT elevation was mostly mild and peaked within 21 days of treatment initiation in 93.2% of the patients, excluding indeterminate patients. A binary logistic regression analysis showed that unfractionated heparin (odds ratio [OR] 2.759, 95% confidence interval [CI] 1.328-5.729, p = 0.007) was extracted as a cause of ALT elevation. In a receiver operating characteristic (ROC) analysis for the administration period of unfractionated heparin, the cut-off value (area under the ROC curve) for ALT elevation was 6 days (0.575). Significant factors contributing to ALT elevation caused by unfractionated heparin included an unfractionated heparin administration period of ≥ 6 days (OR 2.951, 95% CI 1.244-7.000, p = 0.014) and edaravone combination (OR 2.594, 95% CI 1.159-5.808, p = 0.021). CONCLUSION: In the acute phase of stroke, we believe that unfractionated heparin discontinuation is not necessary when hepatotoxicity of unfractionated heparin is suspected. However, physicians should be aware of the risk of liver toxicity when unfractionated heparin is administered for more than six days or when edaravone is used in combination.
Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Heparina , Enoxaparina , AVC Isquêmico/tratamento farmacológico , Edaravone , Acidente Vascular Cerebral/epidemiologia , Infarto Cerebral/tratamento farmacológico , Fígado , Resultado do Tratamento , Anticoagulantes/uso terapêuticoRESUMO
Patients undergoing chemotherapy for cancer frequently experience fatigue, which can significantly lower their quality of life and interfere with treatment. However, the risk factors for the occurrence of chemotherapy-induced fatigue (CIF) are unclear. In this study, we investigated the occurrence of CIF in 415 patients newly treated with chemotherapy at Fukuoka University Hospital between December 2020 and July 2022, and analyzed the factors that influence the occurrence of fatigue. The observation period was defined as the two-week period starting from the day after the induction of chemotherapy, and we collected data retrospectively from medical records. Fatigue was assessed based on Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 by pharmacists who interviewed patients. The prevalence of fatigue was 56.4% (234/415). Nausea and vomiting, anorexia, hypoalbuminemia, and a high blood urea nitrogen/creatinine (BUN/Cr) ratio were extracted as risk factors for CIF. The prevalence of fatigue in 95 patients with nausea and vomiting was 83.2% (79/95), of whom 74.7% (59/79) had concomitant anorexia. Patients with nausea and vomiting had a high prevalence of both fatigue and anorexia, indicating that control for nausea and vomiting is crucial for the prevention of CIF. The serum albumin level reflects the nutritional status of patients approximately three weeks before chemotherapy, and BUN/Cr ≥20 indicates dehydration. Patients with a poor nutritional status or dehydration should be closely monitored for fatigue before and during treatment. These findings offer new prospects for healthcare providers to avoid or reduce CIF and improve patients' quality of life by early control of CIF risk factors.
Assuntos
Antieméticos , Antineoplásicos , Neoplasias , Humanos , Anorexia/induzido quimicamente , Anorexia/epidemiologia , Qualidade de Vida , Desidratação/induzido quimicamente , Desidratação/complicações , Desidratação/tratamento farmacológico , Estudos Retrospectivos , Vômito/induzido quimicamente , Vômito/epidemiologia , Vômito/tratamento farmacológico , Náusea/induzido quimicamente , Náusea/epidemiologia , Náusea/tratamento farmacológico , Neoplasias/tratamento farmacológico , Neoplasias/complicações , Fadiga/etiologia , Fadiga/induzido quimicamente , Análise Fatorial , Antineoplásicos/efeitos adversos , Antieméticos/efeitos adversosRESUMO
To identify causative substances for allergies to drugs or foods, the lymphocyte transformation test (LTT) is currently widely used as in vitro test, but its accuracy is not satisfactory. We have developed a novel method designated high-sensitivity allergy test (HiSAT) for determining allergy expression by measuring cell kinetics, using the chemotactic cells from non-allergic volunteers against a gradient field of cytokines released from immune cells when allergy develops. HiSAT requires a very small sample of 5 µL or less, and is applicable to three types of tests, depending on the situation in clinical practice: (i) diagnosis of the allergic expression, (ii) identification of the causative drug, and, in principle, (iii) pre-inspection.
RESUMO
Drug-induced allergy (DIA), an unexpectedly triggered side effect of drugs used for therapeutic purposes, is a serious clinical issue that needs to be resolved because it interrupts the treatment of the primary disease. Since conventional allergy testing is insufficient to accurately predict the occurrence of DIA or to determine the drugs causing it, the development of diagnostic and predictive tools for allergic reactions is important. We demonstrated a novel method, termed high-sensitive allergy test (HiSAT), for the rapid diagnosis of allergy (within 1 hr; with true-positive diagnosis rates of 89% and 9% for patients with and without allergy-like symptoms, respectively). HiSAT analyzes the cell kinetics as an index against chemotactic factors in a patient's serum, as different from the diagnosis using conventional methods. Once allergy has occurred, HiSAT can be used to determine the causative medicine using culture supernatants incubated with the subject's lymphocytes and the test allergen. This test is more efficient (60%) than the lymphocyte transformation test (20%). Furthermore, in HiSAT, cell mobility significantly increases in a dose-dependent manner against supernatant incubated with lymphocytes from a subject with pollinosis collected at a time when the subject is without allergic symptoms and the antigen. The result demonstraed that HiSAT might be a promising method to rapidly diagnose DIA or to determine with high accuracy the antigen causing allergy.
Assuntos
Alérgenos/isolamento & purificação , Fatores Quimiotáticos/metabolismo , Hipersensibilidade a Drogas/diagnóstico , Linfócitos/imunologia , Rinite Alérgica Sazonal/imunologia , Alérgenos/imunologia , Estudos de Casos e Controles , Movimento Celular , Relação Dose-Resposta a Droga , Hipersensibilidade a Drogas/imunologia , Diagnóstico Precoce , Citometria de Fluxo , Humanos , Células Jurkat , Sensibilidade e Especificidade , Fatores de TempoRESUMO
OBJECTIVE: Ways of introducing a rotigotine patch to Parkinson disease (PD) patients include initial induction for dopamine agonist (DA)-free patients and overnight switch (OS), cross-titration (CT), and add-on (AO) for patients already taking oral DAs. We investigated whether or not the introductions method affects the continuation rate of rotigotine patch. METHODS: The subjects were 188 PD patients who started using a rotigotine patch at the Department of Neurology, Fukuoka University Hospital. The rate of successful continuation of rotigotine patch for one year after initiation and the reasons for discontinuation were investigated; for the patients who discontinued due to poor efficacy, the DA dose before and after the start of rotigotine patch treatment was determined. RESULTS: The 1-year continuation rates were 38.5 % (20/52) in the OS group, 61.5 % (8/13) in the CT group, 35.3 % (6/17) in the AO group, and 50.9 % (54/106) in the de novo group. The most common reason for discontinuation in all groups was skin reactions. Compared with the de novo group, only the OS group had a significantly higher discontinuation rate due to poor efficacy (3.8 % vs. 21.2 %, Pâ¯<⯠0.001). However, in the OS group, the continuation rate in the subjects with an increased total DA dose, after rotigotine was introduced, was significantly higher than that in the subjects with a decreased total DA dose (p = 0.031). CONCLUSION: The use of a rotigotine patch with an equivalent dose should be considered when switching from oral DAs, and appropriate care should be administered for any skin reactions. The present findings suggested that not the introduction method but the use of an equivalent dose between DA formulations might affect the continuation rate of rotigotine patch.
Assuntos
Agonistas de Dopamina/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/psicologia , Tetra-Hidronaftalenos/administração & dosagem , Tiofenos/administração & dosagem , Administração Cutânea , Administração Oral , Idoso , Agonistas de Dopamina/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico , Psicoses Induzidas por Substâncias/diagnóstico , Psicoses Induzidas por Substâncias/etiologia , Estudos Retrospectivos , Tetra-Hidronaftalenos/efeitos adversos , Tiofenos/efeitos adversosRESUMO
Since the effect of a percutaneous absorption-type dopamine agonist (DA) preparation, rotigotine patch, stably persists by once-a-day application, this dosage form is appropriate for Parkinson's disease patients showing levodopa induced wearing off phenomenon. On the other hand, skin disorders, mainly application site reaction, are characteristic problems associated with use of the patch. In this study, to clarify the influence of a topical agent used to prevent or treat rotigotine patch-induced skin disorder on continuation of the patch application, patients who started rotigotine patch application at our hospital were retrospectively surveyed. The one-year continuation rate of rotigotine patch application was 37.3% (53 of 142 cases). It was insufficient to prevent skin disorders, only by the pre-treatment of a moisturizing agent alone. Regarding the effective rate of topical agents used to treat skin disorders, that of very strong-class steroids was 89.5%, being significantly higher than those of weak steroids, moisturizing agents, and antihistamines. It was suggested that for countermeasures against rotigotine patch-induced skin disorders, treatment with very strong-class steroids for external use early after development of skin disorders is more effective than preventive treatment with topical agents regardless of the type. (Received March 30, 2017; Accepted May 16, 2017; Published September 1, 2017).
Assuntos
Agonistas de Dopamina/efeitos adversos , Dermatopatias/induzido quimicamente , Tetra-Hidronaftalenos/efeitos adversos , Tiofenos/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Agonistas de Dopamina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tetra-Hidronaftalenos/administração & dosagem , Tiofenos/administração & dosagem , Adesivo TransdérmicoRESUMO
Rivastigmine patches exhibit stable effects when attached once a day, and may reduce Alzheimer's disease (AD) patient's or caregiver's burden. On the other hand, it was reported that adverse events, such as dermal disorder, frequently appeared after the start of rivastigmine administration. We retrospectively investigated medical records in 120 patients with moderate or mild AD in whom rivastigmine administration was started in the Department of Neurology, Fukuoka University Hospital between July 2011 and June 2014 (43 males, 77 females, mean age: 76.9±8.0 years). In 72 patients (60.0%), rivastigmine administration was discontinued within 52 weeks after its start. In 45 of these, it was discontinued before reaching a dose of 18 mg/d which was proven to be effective for AD patients. A primary reason for discontinuation was the appearance or deterioration of adverse events in 64 patients. Of these, 43 complained of dermal disorder, accounting for the highest percentage. To clarify factors influencing the continuous administration of rivastigmine, multivariate analysis was performed in 114 patients meeting criteria. Combination therapy with memantine was extracted as a factor (p=0.008). The results of this study suggest that adherence to combination therapy with rivastigmine and memantine is more favorable than that to monotherapy with rivastigmine.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Memantina/administração & dosagem , Cooperação do Paciente/estatística & dados numéricos , Rivastigmina/administração & dosagem , Rivastigmina/efeitos adversos , Adesivo Transdérmico , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Transdermal patches containing rotigotine, a dopamine agonist (DA) for treatment of Parkinson disease, continuously exert stable effects when applied once daily. Therefore, they are expected to reduce the patient burdens due to complications such as wearing-off and dysphagia. However, dosing is occasionally reduced or discontinued after application because of several reasons such as skin reactions or unsatisfactory efficacy. To identify the risk factors involved in the reduced or discontinued use of rotigotine patches, a retrospective study was conducted with reference to the medical records of patients with Parkinson disease who received rotigotine patches in our hospital. 85 patients were involved in this study. Dosing of rotigotine was reduced or discontinued in 53 patients during the study period. The factors associated with charges in treatment included combination therapy with clonazepam and oral administration of another DA before the application of rotigotine. The reduction or discontinuation rate of rotigotine patches in patients who reduced the equivalent dose of DA on the introduction of rotigotine patches was 94.7%, showing a significantly higher rate compared with 61.3% in the increased dose group. To improve adherence to rotigotine patch therapy, physicians need to carefully consider concomitant drugs and total dose of DAs. (Received December 7, 2015; Accepted February 22, 2016; Published June 1, 2016).
Assuntos
Agonistas de Dopamina/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Tetra-Hidronaftalenos/uso terapêutico , Tiofenos/uso terapêutico , Administração Cutânea , Adulto , Idoso , Idoso de 80 Anos ou mais , Agonistas de Dopamina/administração & dosagem , Agonistas de Dopamina/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Tetra-Hidronaftalenos/administração & dosagem , Tetra-Hidronaftalenos/efeitos adversos , Tiofenos/administração & dosagem , Tiofenos/efeitos adversosRESUMO
Disruption of beta-amyloid (Aß) transport across the blood-brain barrier is thought to cause Aß accumulation in the brain, thus leading to the development of Alzheimer's disease (AD). As AD patients show increased serum tumor necrosis factor-α (TNFα) levels, we examined the effect of TNFα on the function and expression of Aß transport-related proteins including cellular prion protein (PrP(C)) in the mouse brain microvascular endothelial cell line MBEC4. TNFα decreased PrP(C) levels and intracellular radiolabeled Aß. Similarly, anti-prion protein antibody also decreased radiolabeled Aß. These results suggest that TNFα lowers PrP(C) levels, which in turn, reduces Aß in the brain endothelium.
Assuntos
Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Príons/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Linhagem Celular , CamundongosRESUMO
Recently, 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors were reported to induce neurite outgrowth in vitro. However, the mechanism underlying this effect remains unclear. Cellular prion protein (PrP(C)) is a ubiquitous glycoprotein present on the surfaces of various cells, including neurons, and is suggested to be involved in neurite outgrowth. Therefore, the present study aimed to determine whether PrP(C) mediates neurite outgrowth induced by HMG-CoA reductase inhibitors. Atorvastatin, a strong HMG-CoA reductase inhibitor, induced neurite outgrowth and increased PrP(C) levels in Neuro2a cells in a time- and dose-dependent manner. PrP(C) mRNA expression was also increased by atorvastatin. Farnesol, a non-sterol mevalonate derivative, attenuated the atorvastatin-induced neurite outgrowth and increase in PrP(C). Neuro2a cells overexpressing PrP(C) showed a remarkable enhancement of atorvastatin-induced neurite outgrowth compared with mock cells transfected with empty pCI-neo vector. These findings suggest that PrP(C) contributes, at least in part, to atorvastatin-induced neurite outgrowth. This phenomenon may be included among the mechanisms underlying decreased risk of Alzheimer's disease in patients treated with HMG-CoA reductase inhibitors.
Assuntos
Ácidos Heptanoicos/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Neuritos/metabolismo , Príons/metabolismo , Pirróis/farmacologia , Animais , Atorvastatina , Linhagem Celular Tumoral , Camundongos , Neuritos/efeitos dos fármacos , Neuroblastoma , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The conversion of cellular prion protein (PrP(C)) to its protease-resistant isoform is involved in the pathogenesis of prion disease. Although PrP(C) is a ubiquitous glycoprotein that is present in various cell types, the physiological role of PrP(C) remains obscure. The present study aimed to determine whether PrP(C) mediates migration of brain microvascular endothelial cells. Small interfering RNAs (siRNAs) targeting PrP(C) were transfected into a mouse brain microvascular endothelial cell line (bEND.3 cells). siPrP1, selected among three siRNAs, reduced mRNA and protein levels of PrP(C) in bEND.3 cells. Cellular migration was evaluated with a scratch-wound assay. siPrP1 suppressed migration without significantly affecting cellular proliferation. This study provides the first evidence that PrP(C) may be necessary for brain microvascular endothelial cells to migrate into damaged regions in the brain. This function of PrP(C) in the brain endothelium may be a mechanism by which the neurovascular unit recovers from an injury such as an ischemic insult.