RESUMO
Medications that target programmed cell death protein-1 (PD-1) have proven effective. However, blockade of PD-1/Programmed death-ligand 1(PD-L1) causes immune-related adverse events (irAEs). Characteristics of this irAE include many symptom, low in frequency, and difficulty in prevention. The key to a successful ICI-related treatment lies in the management of irAEs resulting from immune checkpoint inhibitor (ICI) treatment. Although it is difficult to predict irAE, we tried to extract features of irAE expression from analysis of real-world database. This study used data extracted from the Japan Adverse Drug Event Report (JADER) database to assess risk factors associated with serious side effects of irAE, type 1 diabetes (T1DM). The analysis targets were nivolumab, atezolizumab, durvalumab, and pembrolizumab, and the study period was from July 2014 to June 2019. Analysis of Japanese population data confirmed that being women and having melanoma were risk factors for developing ICI-related T1DM. Analysis using this database in combination with information on ICI-related T1DM provides information and guidelines that will help in the safer treatment of ICI in the future.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bases de Dados Factuais , Diabetes Mellitus Tipo 1/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias/tratamento farmacológico , Idade de Início , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Diabetes Mellitus Tipo 1/induzido quimicamente , Diabetes Mellitus Tipo 1/patologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Seguimentos , Saúde Global , Humanos , Masculino , Neoplasias/patologia , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
<p><b>BACKGROUND</b>Although various studies have been conducted on the effects of radiation therapy for prostate cancer, rectal toxicity after radiation therapy for prostate cancer, which is an important late adverse event associated with radiation therapy, has not been sufficiently examined. This study aimed to assess the associations of late rectal disorder (LRD) with dosimetric, anatomic, and clinical factors in patients with prostate cancer who underwent three-dimensional conformal radiation therapy (3D-CRT).</p><p><b>METHODS</b>We retrospectively analyzed 104 patients undergoing 3D-CRT between January 2009 and October 2011. Thirty patients were administered anticoagulation/antiplatelet (AC/AP) agents. The standard dose was 74 Gy. Uni- and multi-variate analyses were performed to identify factors predictive of LRD after 3D-CRT.</p><p><b>RESULTS</b>The median follow-up period was 66 (range: 14-87) months. LRD occurred in 10.6% (11/104) of patients. The median time from RT to LRD was 15 months (range: 7-41 months). Sixty-four percent of those with LRD (7/11 patients) had been given AC/AP agents. Fifty-five (6/11) patients had severe internal iliac artery calcification. By univariate analysis, significant predictors of LRD were internal iliac artery calcification, administration of AC/AP agents, and age. Being very elderly was the significant predictor identified by multivariate analysis (P = 0.0276). For patients receiving AC/AP agents and those with severe internal iliac artery calcification, the LRD incidences were 23.3% (7/30 patients) and 23.1% (6/26 patients), respectively, and being 75 years of age or older was a significant predictor in these subsets.</p><p><b>CONCLUSIONS</b>Our results suggest advanced age, administration of AC/AP agents, and severe internal iliac artery calcification to be risk factors for LRD in patients undergoing standard RT. Therefore, it is necessary to administer radiation with particular caution in the very elderly, especially those receiving AC/AP agents and/or with severe internal iliac artery calcification.</p>
RESUMO
<b>Objective</b>: To nurture pharmacists capable of contributing to the prevention of adverse reactions to psychotropic agents, the Sapporo Hospital Pharmacist Association has been holding a seminar for psychiatric pharmacy specialist. A questionnaire survey was conducted to clarify the usefulness of this seminar and its future direction, and evaluate the necessity of providing information on psychotropic drugs.<br><b>Methods</b>: An anonymous 21-item questionnaire was distributed to participants in the 2008 Sapporo Hospital Pharmacist Association seminar for psychiatric pharmacy specialist.<br><b>Results</b>: The mean recovery rate was 76.3%, and the respondents had a broad background in terms of age, gender, etc. The seminar was identified as being beneficial, and the participants’ awareness of the accreditation of Board Certified Pharmacist in Psychiatric Pharmacy showed regional characteristics.<br><b>Conclusion</b>: Based on the survey results, guidelines on conducting the seminar in the future were successfully developed. From now on, it is important to create an environment to nurture psychiatric pharmacy specialist in the Sapporo area. Additional efforts should be made so that the provision of information on psychotropic drugs in the seminar can contribute to the prevention of adverse reactions to them.
RESUMO
Twenty endurance-trained athletes (five male speed-skaters, eleven male and four female cross-country skiers, 16-18 years) ran on a treadmill by a protocol of incremental graded increase in workload until exhaustion during an endurance training period in off-season summer. Immediately after exercise, all developed peripheral leukocytosis (1.9 times; p<0.01) due mainly to lymphocytosis (2.6 times; p<0.01) with a predominant effect on large granular lymphocyte (natural killer cell) count (5.9 times ; p<0.01) . Monocyte count was also enhanced 2.3 times (p<0.01) . These increases were transitory and returned to the pre-exercise levels 1 h later. Peripheral neutrophilia was also observed by 43% (p<0.01) immediately after exercise and remained elevated by 25% (p<0.01) 1 h after exercise, but a shift to the left did not take place. The capacity of isolated neutrophils to produce reactive oxygen species was assessed by luminol-dependent chemiluminescence which detects mainly myeloperoxidase (MPO) -mediated formation of such hyperreactive oxidants as HOCl. The maximum intensity of chemiluminescence (peak height) upon stimulation with opsonized zymosan was significantly enhanced following exercise (p<0.05) . Similar results were obtained when phorbol myristate acetate was employed as nonphagocytic soluble stimulus (p<0.01), suggesting that the capacity of neutrophils to degranulate MPO rather than phagocytosis was enhanced following exercise. In addition, the enhancements of chemiluminescence were positively correlated with the increase in segmented neutrophil count. These data indicate that maximal exercise not only mobilized mature neutrophils from the marginated pool into the circulation, but also augmented their capacity to generate reactive oxygen species of higher reactivity.