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1.
N Engl J Med ; 384(12): 1101-1112, 2021 03 25.
Artículo en Inglés | MEDLINE | ID: mdl-33761207

RESUMEN

BACKGROUND: The oral Janus kinase 1 (JAK1) inhibitor abrocitinib, which reduces interleukin-4 and interleukin-13 signaling, is being investigated for the treatment of atopic dermatitis. Data from trials comparing JAK1 inhibitors with monoclonal antibodies, such as dupilumab, that block interleukin-4 receptors are limited. METHODS: In a phase 3, double-blind trial, we randomly assigned patients with atopic dermatitis that was unresponsive to topical agents or that warranted systemic therapy (in a 2:2:2:1 ratio) to receive 200 mg or 100 mg of abrocitinib orally once daily, 300 mg of dupilumab subcutaneously every other week (after a loading dose of 600 mg), or placebo; all the patients received topical therapy. The primary end points were an Investigator's Global Assessment (IGA) response (defined as a score of 0 [clear] or 1 [almost clear] on the IGA [scores range from 0 to 4], with an improvement of ≥2 points from baseline) and an Eczema Area and Severity Index-75 (EASI-75) response (defined as ≥75% improvement from baseline in the score on the EASI [scores range from 0 to 72]) at week 12. The key secondary end points were itch response (defined as an improvement of ≥4 points in the score on the Peak Pruritus Numerical Rating Scale [scores range from 0 to 10]) at week 2 and IGA and EASI-75 responses at week 16. RESULTS: A total of 838 patients underwent randomization; 226 patients were assigned to the 200-mg abrocitinib group, 238 to the 100-mg abrocitinib group, 243 to the dupilumab group, and 131 to the placebo group. An IGA response at week 12 was observed in 48.4% of patients in the 200-mg abrocitinib group, 36.6% in the 100-mg abrocitinib group, 36.5% in the dupilumab group, and 14.0% in the placebo group (P<0.001 for both abrocitinib doses vs. placebo); an EASI-75 response at week 12 was observed in 70.3%, 58.7%, 58.1%, and 27.1%, respectively (P<0.001 for both abrocitinib doses vs. placebo). The 200-mg dose, but not the 100-mg dose, of abrocitinib was superior to dupilumab with respect to itch response at week 2. Neither abrocitinib dose differed significantly from dupilumab with respect to most other key secondary end-point comparisons at week 16. Nausea occurred in 11.1% of the patients in the 200-mg abrocitinib group and 4.2% of those in the 100-mg abrocitinib group, and acne occurred in 6.6% and 2.9%, respectively. CONCLUSIONS: In this trial, abrocitinib at a dose of either 200 mg or 100 mg once daily resulted in significantly greater reductions in signs and symptoms of moderate-to-severe atopic dermatitis than placebo at weeks 12 and 16. The 200-mg dose, but not the 100-mg dose, of abrocitinib was superior to dupilumab with respect to itch response at week 2. Neither abrocitinib dose differed significantly from dupilumab with respect to most other key secondary end-point comparisons at week 16. (Funded by Pfizer; JADE COMPARE ClinicalTrials.gov number, NCT03720470.).


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Dermatitis Atópica/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/administración & dosificación , Pirimidinas/administración & dosificación , Sulfonamidas/administración & dosificación , Administración Oral , Adulto , Anticuerpos Monoclonales Humanizados/efectos adversos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Inmunoglobulina A/sangre , Inyecciones Subcutáneas , Subunidad alfa del Receptor de Interleucina-4/antagonistas & inhibidores , Janus Quinasa 1/antagonistas & inhibidores , Masculino , Placebos/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos , Prurito/tratamiento farmacológico , Pirimidinas/efectos adversos , Índice de Severidad de la Enfermedad , Sulfonamidas/efectos adversos
2.
Allergol Int ; 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38735810

RESUMEN

BACKGROUND: We investigated the efficacy and safety of dupilumab in Japanese patients aged ≥6 months to <18 years old with moderate-to-severe atopic dermatitis not adequately controlled with existing therapies. METHODS: In this randomized, double-blind, phase 3 study, patients received dupilumab (n = 30) or placebo (n = 32) with concomitant topical corticosteroids for 16 weeks, then all patients received dupilumab from 16 to 52 weeks. The primary endpoint was the proportion of patients with ≥75% improvement in Eczema Area and Severity Index (EASI) score from baseline (EASI-75) to Week 16. Key secondary endpoints included changes in EASI score, proportion of patients with investigator global assessment (IGA) scores of 0/1, and changes in worst daily itch numerical rating scale (NRS) scores (evaluated in patients aged ≥6 to <12 years [n = 35]). RESULTS: At Week 16, more patients achieved EASI-75 with dupilumab than placebo (43.3% vs 18.8%; P = 0.0304), and the least squares mean (LSM) difference in percent change in EASI scores at Week 16 of dupilumab vs placebo was -39.4% (P = 0.0003). However, no significant difference in the proportion of patients achieving IGA scores of 0/1 at Week 16 with dupilumab versus placebo were seen (10.0% vs 9.4%; P = 0.8476). The percent change in worst daily itch NRS scores at Week 16 was higher with dupilumab (LSM difference: -33.3%; nominal P = 0.0117). Dupilumab was well tolerated; no new safety signals were identified. CONCLUSIONS: Dupilumab showed consistent efficacy and was well tolerated in Japanese patients aged ≥6 months to <18 years with moderate-to-severe atopic dermatitis previously insufficiently controlled with existing therapies.

3.
Arerugi ; 73(2): 171-179, 2024.
Artículo en Japonés | MEDLINE | ID: mdl-38522931

RESUMEN

BACKGROUND: Itch is the most troublesome symptom of atopic dermatitis, and it is important to assess it appropriately for optimal treatment. We discussed issues regarding itch and the most appropriate methods of assessment at the Atopic Itch Consensus Meeting (AICOM), attended by physicians and researchers with expertise in itch treatment and research. METHODS: The AICOM participants prepared a draft consensus statement that addressed the most appropriate itch assessment methods for age groups <2 years, 2-6 years, 7-14 years, and ≥15 years. Consensus was defined as agreement by ≥80% of the participants. RESULTS: Votes were cast by 20 participants (8 dermatologists, 7 pediatricians, and 5 researchers), and a consensus on the best current methods of itch assessment was reached with 95% agreement. For infants and preschool children, because subjective evaluation is difficult, a checklist for itch assessment was developed for caregivers. CONCLUSION: For itch assessment, we recommend subjective evaluation by the patient using a rating scale. For infants and preschoolers, evaluation should be done by the caregiver using a checklist, combined with objective evaluation (of skin lesions, for example) by a physician. We anticipate that more objective itch assessment indices will be established in the future.


Asunto(s)
Dermatitis Atópica , Prurito , Lactante , Preescolar , Humanos , Índice de Severidad de la Enfermedad , Prurito/diagnóstico , Prurito/etiología , Dermatitis Atópica/complicaciones , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/terapia
4.
Cancer Sci ; 114(3): 750-763, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36411518

RESUMEN

In lung cancer, tumor-associated macrophages (TAMs), especially M2-like TAMs, represent the main tumor progression components in the tumor microenvironment (TME). Therefore, M2-like TAMs may serve as a therapeutic target. The purpose of this study was to investigate the effect of M2-like TAM depletion in the TME on tumor growth and chemotherapy response in lung cancer. The levels of secreted monocyte chemoattractant protein (MCP-1) and prostaglandin E2 (PGE2) in the supernatants of lung cancer cell lines A549 and LLC were evaluated via ELISA. Cell migration assays were performed to assess the recruitment ability of macrophage cell lines THP-1 and J774-1 cells. Differentiation of macrophages was assessed via flow cytometry. Immunohistochemical staining was performed to visualize M2-like TAMs in transplanted lung cancer in mouse. We used the COX-2 inhibitor nimesulide to inhibit the secretion of MCP-1 and PGE2, which promotes macrophage migration and M2-like differentiation. Nimesulide treatment decreased the secretion of MCP-1 and PGE2 from lung cancer cells. Nimesulide treatment suppressed the migration of macrophages by blocking MCP-1. Lung cancer supernatant induced the differentiation of macrophages toward the M2-like phenotype, and nimesulide treatment inhibited M2-like differentiation by blocking MCP-1 and PGE2. In the lung cancer mouse model, treatment with nimesulide depleted M2-like TAMs in the TME and enhanced the tumor inhibitory effect of cisplatin. Our results indicated that blocking the secretion of MCP-1 and PGE2 from tumor cells depleted M2-like TAMs in the TME and the combination therapy with cisplatin considerably suppressed tumor growth in the LLC mouse model.


Asunto(s)
Cisplatino , Neoplasias Pulmonares , Animales , Ratones , Cisplatino/uso terapéutico , Macrófagos Asociados a Tumores/metabolismo , Dinoprostona/uso terapéutico , Neoplasias Pulmonares/patología , Microambiente Tumoral/genética , Línea Celular Tumoral
5.
Cancer Immunol Immunother ; 72(11): 3755-3764, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37646826

RESUMEN

Programmed cell death-ligand 1 (PD-L1) on tumor cells can be degraded to soluble form (sPD-L1) and enter circulation, however, the clinical significances of sPD-L1 in peripheral blood remains to be elucidated in non-small-cell lung cancer (NSCLC). We monitored plasma sPD-L1 levels during perioperative periods and evaluated PD-L1-positive cells in tumor tissues in patients with operable NSCLC. Then the correlation between preoperative plasma sPD-L1 levels and relapse-free survival (RFS) was analyzed retrospectively. In patients who underwent radical surgery (n = 61), plasma sPD-L1 levels (median; 63.5 pg/mL) significantly increased 1 month after surgery (72.2 pg/mL, P < 0.001). The combined score of PD-L1-positive cells including tumor cells and tumor-associated macrophages (TAMs) was significantly associated with preoperative plasma sPD-L1 levels. In patients with high levels of preoperative plasma sPD-L1, the probability of 5-year RFS was significantly poor for patients with low PD-L1 expression intensity of tumor cells (tcPD-L1) compared with those with high tcPD-L1 (33.3% vs. 87.5%, respectively, P = 0.016; 95% CI, 0.013-0.964). In former group, PD-L1-positive TAMs were markedly infiltrating compared with those from latter group (246.4 vs. 76.6 counts/mm2, respectively, P = 0.003). In NSCLC, plasma sPD-L1 can reflect the accumulation of PD-L1-posotive TAMs, not just PD-L1-positive tumor cells. In patients with high levels of preoperative plasma sPD-L1, the prognoses after surgery depends on which PD-L1-positive cells, tumor cells or TAMs, are the primary source of the sPD-L1. Thus, measuring both plasma sPD-L1 levels and PD-L1 expression status of tumor cells and TAMs is of benefit for assessment of postoperative prognosis in operable NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Antígeno B7-H1 , Biomarcadores de Tumor , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Recurrencia Local de Neoplasia/patología , Pronóstico , Estudios Retrospectivos , Macrófagos Asociados a Tumores/patología
6.
Arerugi ; 72(10): 1240-1247, 2023.
Artículo en Japonés | MEDLINE | ID: mdl-38092400

RESUMEN

BACKGROUND: The Recap of atopic eczema (RECAP), a new core outcome of the atopic dermatitis trial, was translated into Japanese and linguistically validated. METHODS: Translation into Japanese was accomplished according to the ISPOR (International Society for Pharmacoeconomics and Outcome Research) guidelines and the basic guidelines for scale translation. The translation process included two forward translations, reconciliation with native English speakers, third-party back translation, cognitive debriefing, review and harmonization by the original authors. Twenty-seven atopic dermatitis and pediatric specialists from 21 centers in Japan participated in the translation process. Cognitive debriefing was conducted through face-to-face interviews using a think-aloud method with the interview guide including questions about comprehensibility, relevance, comprehensiveness, recall period and suggested improvements, based on the COSMIN methodology. RESULTS: No linguistic or cultural problems were encountered in the translation into Japanese. Cognitive debriefings were conducted with 10 adult patients and 10 parents of pediatric patients. Some minor modifications were made following discussion and approval by the research team and the original authors. The Japanese version of RECAP was considered to be understandable, comprehensive and relevant for adult patients and families of pediatric patients. CONCLUSION: The Japanese version of the RECAP, which has been validated as linguistically equivalent to the original version, is now available. Further evaluation of the measurement properties is needed in the future.


Asunto(s)
Dermatitis Atópica , Adulto , Humanos , Niño , Japón , Dermatitis Atópica/terapia , Encuestas y Cuestionarios , Lingüística , Traducciones
7.
Pharmacoepidemiol Drug Saf ; 31(5): 524-533, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35224801

RESUMEN

PURPOSE: We aimed to develop a reliable identification algorithm combining diagnostic codes with several treatment factors for inpatients with acute ischemic stroke (AIS) to conduct pharmacoepidemiological studies using the administrative database MID-NET® in Japan. METHODS: We validated 11 identification algorithms based on 56 different diagnostic codes (International Classification of Diseases, Tenth Revision; ICD-10) using Diagnosis Procedure Combination (DPC) data combined with information on AIS therapeutic procedures added as "AND" condition or "OR" condition. The target population for this study was 366 randomly selected hospitalized patients with possible cases of AIS, defined as relevant ICD-10 codes and diagnostic imaging and prescription or surgical procedure, in three institutions between April 1, 2015 and March 31, 2017. We determined the positive predictive values (PPVs) of these identification algorithms based on comparisons with a gold standard consisting of chart reviews by experienced specialist physicians. Additionally, the sensitivities of them among 166 patients with the possible cases of AIS at a single institution were evaluated. RESULTS: The PPVs were 0.618 (95% confidence interval [CI]: 0.566-0.667) to 0.909 (95% CI: 0.708-0.989) and progressively increased with adding or limiting information on AIS therapeutic procedures as "AND" condition in the identification algorithms. The PPVs for identification algorithms based on diagnostic codes I63.x were >0.8. However, the sensitivities progressively decreased to a maximum of ~0.2 after adding information on AIS therapeutic procedures as "AND" condition. CONCLUSIONS: The identification algorithms based on the combination of appropriate ICD-10 diagnostic codes in DPC data and other AIS treatment factors may be useful to studies for AIS at a national level using MID-NET®.


Asunto(s)
Accidente Cerebrovascular Isquémico , Algoritmos , Bases de Datos Factuales , Humanos , Clasificación Internacional de Enfermedades , Valor Predictivo de las Pruebas
8.
Cancer Immunol Immunother ; 70(4): 1063-1074, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33113005

RESUMEN

Programmed cell death-ligand 1 (PD-L1) expression on tumor cells is induced by interferon-gamma, suggesting the induction of an anti-tumor immune response. In turn, binding of PD-L1 to programmed cell death 1 (PD-1) triggers an immune checkpoint pathway that contributes to tumor growth. Though it remains to be elucidated, the clinical significance of PD-L1 expression might vary with tumor progression in non-small-cell lung cancer (NSCLC). Immunohistochemical analysis of PD-L1 was done in tumor specimens from patients who underwent radical surgery for stage I-IIIA NSCLC (n = 228). Tumor PD-L1 expression intensity was semi-quantitatively scored and its correlation with various clinicopathological features and postoperative relapse-free survival (RFS) was assessed relative to pathological stage. In stage I, postoperative RFS was significantly prolonged in patients with a high PD-L1 score compared with a low PD-L1 score, exhibiting 5-year relapse-free probabilities of 94.1% and 75.1%, respectively (P = 0.031). A multivariate analysis revealed that a high PD-L1 score was a prognostic factor of longer postoperative RFS (hazard ratio: 0.111, P = 0.033). Conversely, in stages II and IIIA, patients with a high PD-L1 score tended to suffer from postoperative tumor recurrence. In early-stage NSCLC, high tumor PD-L1 expression status represents a biomarker to predict good prognosis after radical surgery and may reflect the induction of an antitumor immune response. However, in locally advanced stage NSCLC, tumor PD-L1 expression status may reflect the execution of an immune checkpoint pathway and predicts the incidence of postoperative tumor recurrence.


Asunto(s)
Adenocarcinoma del Pulmón/patología , Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/patología , Neoplasias Pulmonares/patología , Recurrencia Local de Neoplasia/patología , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/cirugía , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias , Tasa de Supervivencia
9.
Acta Derm Venereol ; 101(11): adv00585, 2021 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-34618162

RESUMEN

Optimal management of atopic dermatitis requires a comprehensive assessment of response to treatment in order to inform therapeutic decisions. In a real-world setting, successful response to atopic dermatitis treatment is measured by sustained improvements in signs, symptoms, and quality of life. Post-hoc analyses of a 1-year, randomized, double-blinded, placebo- controlled trial (NCT02260986) of dupilumab with concomitant topical corticosteroids in 421 adults with moderate-to-severe atopic dermatitis (of whom 315/106 received placebo/dupilumab (of whom 315 received placebo and 106 received dupilumab) was performed to assess the proportion of responders to dupilumab through a multidimensional composite endpoint. At 6-months, 80.2% of dupilumab-treated vs 40.0% placebo patients (p < 0.0001) achieved improvement in signs (Eczema Area and Severity Index ≤ 7), symptoms (worst itch score ≤ 4), or quality of life (Dermatology Life Quality Index ≤5), representative of minimal/clear atopic dermatitis. All 3 endpoints, indicative of no/minimal atopic dermatitis, were achieved by 44.3% of dupilumab-treated vs 10.2% placebo patients (p < 0.0001) and sustained through 1 year. Dupilumab treatment provided sustained clinically meaningful improvement in signs, symptoms, and quality of life in adults with moderate-to-severe atopic dermatitis.


Asunto(s)
Dermatitis Atópica , Eccema , Adulto , Anticuerpos Monoclonales Humanizados , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/tratamiento farmacológico , Método Doble Ciego , Humanos , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
10.
Kyobu Geka ; 73(2): 117-119, 2020 Feb.
Artículo en Japonés | MEDLINE | ID: mdl-32393718

RESUMEN

A 53-year-old man underwent surgical repair and drainage of a spontaneous esophageal rupture through a left anterolateral intercostal thoracotomy. Thereafter, wound infection persisted for 3 years with formation of cutaneous fistulae and granulation tissue. Chest computed tomography revealed osteolysis, swollen ribs and costal cartilage, and cutaneous fistulous tracts. Bone scintigraphy with 99mTechnetium revealed abnormal accumulation in the ribs and costal cartilage, indicating costochondritis and osteomyelitis of ribs with cutaneous fistulae. Surgical resection of the skin including the cutaneous fistulae, infected ribs and costal cartilage were performed successfully.


Asunto(s)
Cartílago Costal , Osteomielitis , Humanos , Masculino , Persona de Mediana Edad , Osteomielitis/cirugía , Costillas , Toracotomía , Tomografía Computarizada por Rayos X
11.
Arerugi ; 69(10): 979-988, 2020.
Artículo en Japonés | MEDLINE | ID: mdl-33310981

RESUMEN

BACKGROUND: Dupilumab, an anti-IL (Interleukin) -4 receptorα mAb, inhibits IL-4/IL-13 signaling and is indicated for the treatment of inadequately controlled AD, asthma and CRSwNP because IL-4/IL-13 signaling is a key driver of type2/Th2 immune diseases (atopic/allergic diseases). As well as the above diseases, a therapeutic effect of dupilumab on PAR can be expected. We investigated the effect of dupilumab on PAR in severe AD patients with comorbid PAR. METHODS: Prospective observational study. 21 severe AD patients with PAR who started dupilumab were enrolled and we devided them into 2 groups: more than moderate group and less than moderate group. We investigated subjective symptoms, QOL scores, face scale, findings of nasal cavity and laboratory findings before start of therapy and 12 months later. RESULTS: In more than moderate group, significant improvements were observed in subjective symptoms (except a part), QOL scores (except a part), face scale and findings of nasal cavity. On the other hand, in less than moderate group, no improvement was observed in all items. Subjective symptom assessments were estimated lowlier than objective finding assessments. CONCLUSION: Dupilumab has a therapeutic effect on severe PAR in severe AD patients.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Dermatitis Atópica , Dermatitis Atópica/tratamiento farmacológico , Humanos , Estudios Prospectivos , Calidad de Vida
12.
N Engl J Med ; 375(24): 2335-2348, 2016 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-27690741

RESUMEN

BACKGROUND: Dupilumab, a human monoclonal antibody against interleukin-4 receptor alpha, inhibits signaling of interleukin-4 and interleukin-13, type 2 cytokines that may be important drivers of atopic or allergic diseases such as atopic dermatitis. METHODS: In two randomized, placebo-controlled, phase 3 trials of identical design (SOLO 1 and SOLO 2), we enrolled adults with moderate-to-severe atopic dermatitis whose disease was inadequately controlled by topical treatment. Patients were randomly assigned in a 1:1:1 ratio to receive, for 16 weeks, subcutaneous dupilumab (300 mg) or placebo weekly or the same dose of dupilumab every other week alternating with placebo. The primary outcome was the proportion of patients who had both a score of 0 or 1 (clear or almost clear) on the Investigator's Global Assessment and a reduction of 2 points or more in that score from baseline at week 16. RESULTS: We enrolled 671 patients in SOLO 1 and 708 in SOLO 2. In SOLO 1, the primary outcome occurred in 85 patients (38%) who received dupilumab every other week and in 83 (37%) who received dupilumab weekly, as compared with 23 (10%) who received placebo (P<0.001 for both comparisons with placebo). The results were similar in SOLO 2, with the primary outcome occurring in 84 patients (36%) who received dupilumab every other week and in 87 (36%) who received dupilumab weekly, as compared with 20 (8%) who received placebo (P<0.001 for both comparisons). In addition, in the two trials, an improvement from baseline to week 16 of at least 75% on the Eczema Area and Severity Index was reported in significantly more patients who received each regimen of dupilumab than in patients who received placebo (P<0.001 for all comparisons). Dupilumab was also associated with improvement in other clinical end points, including reduction in pruritus and symptoms of anxiety or depression and improvement in quality of life. Injection-site reactions and conjunctivitis were more frequent in the dupilumab groups than in the placebo groups. CONCLUSIONS: In two phase 3 trials of identical design involving patients with atopic dermatitis, dupilumab improved the signs and symptoms of atopic dermatitis, including pruritus, symptoms of anxiety and depression, and quality of life, as compared with placebo. Trials of longer duration are needed to assess the long-term effectiveness and safety of dupilumab. (Funded by Sanofi and Regeneron Pharmaceuticals; SOLO 1 ClinicalTrials.gov number, NCT02277743 ; SOLO 2 ClinicalTrials.gov number, NCT02277769 .).


Asunto(s)
Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Dermatitis Atópica/tratamiento farmacológico , Adulto , Antiinflamatorios/efectos adversos , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Dermatitis Atópica/complicaciones , Método Doble Ciego , Femenino , Humanos , Inyecciones Subcutáneas/efectos adversos , Interleucina-13/antagonistas & inhibidores , Interleucina-4/antagonistas & inhibidores , Masculino , Persona de Mediana Edad , Nasofaringitis/inducido químicamente , Prurito/tratamiento farmacológico , Prurito/etiología , Calidad de Vida
13.
Pharmacoepidemiol Drug Saf ; 28(7): 976-984, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31197887

RESUMEN

PURPOSE: The purpose of this study is to evaluate the accuracy of gastrointestinal (GI) perforation ICD-10 coding in the Diagnosis Procedure Combination (DPC) database and to examine drug exposure risk factors for GI perforation. METHODS: A total of 100 patients with GI perforation ICD-10 codes were selected randomly from Kagawa University Hospital's DPC database between April 2011 and December 2016. Two experienced specialist physicians independently reviewed the medical records and classified cases as "definite A," "definite B," "probable," or "no GI perforation." The positive predictive values (PPVs) of "definite A/B" cases were calculated after stratification by sex, age, ICD-10 code, and diagnostic information in the DPC data. The number of prescribed drugs with side effects of GI perforation according to historical data was compared between "definite A/B" and "no GI perforation" cases. RESULTS: The overall PPV was 47.0% (95% confidence interval [CI], 36.9-57.2). However, the PPVs for the three categories of diagnostic information in the DPC data ("main diagnosis," "diagnosis causing admission," and "most resource-intensive diagnosis") were each more than 70% after excluding inappropriate patients. Additionally, the PPV focused on these three categories was 76.3% (95% CI, 59.8-88.6). Prescribed drugs with side effects of GI perforation were more frequently detected in "definite A/B" cases (P = .028). CONCLUSIONS: Although the overall PPV for GI perforation based on ICD-10 code was low, our results suggest that the PPV could be improved by appropriate selection of DPC diagnosis category and that use of multiple medications enhances the risk of GI perforation.


Asunto(s)
Grupos Diagnósticos Relacionados/normas , Hemorragia Gastrointestinal/epidemiología , Perforación Intestinal/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Bases de Datos Factuales , Femenino , Hemorragia Gastrointestinal/inducido químicamente , Humanos , Lactante , Recién Nacido , Perforación Intestinal/inducido químicamente , Japón/epidemiología , Masculino , Persona de Mediana Edad , Farmacoepidemiología , Valor Predictivo de las Pruebas , Medicamentos bajo Prescripción/efectos adversos , Factores de Riesgo , Adulto Joven
14.
J Clin Pharm Ther ; 44(5): 788-795, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31282013

RESUMEN

WHAT IS KNOWN AND OBJECTIVE: Since its introduction in April 2012, denosumab has been administered to approximately 7,300 patients as of August 2012, and 32 cases of serious hypocalcaemia after denosumab administration, including two deaths, have been reported in Japan. A Dear Healthcare Professional Letter of Rapid Safety Communication ('Blue letter') was released to warn about the risks of hypocalcaemia associated with denosumab. The goal of this study therefore was to measure the impact of regulatory action on denosumab-induced hypocalcaemia in Japan by using an electronic medical information database (MID). METHODS: We used two different aggregated data sets based on MIDs (data sets one and two). The patients studied were those who were newly prescribed denosumab or zoledronic acid between April 2012 and September 2014. We assessed four indicators: (a) the proportion of patients with calcium supplementation at the initial denosumab treatment, (b) the proportion of patients who underwent a serum calcium test, (c) the average number of serum calcium tests performed and (d) the prevalence of hypocalcaemia. All indices were aggregated by every 3 months. To evaluate the impact of regulatory action, we used difference in difference (DID) analysis. RESULTS AND DISCUSSION: The proportion of patients with calcium supplementation at the initial denosumab treatment increased year by year in both data sets. The average number of serum calcium tests increased year by year in data set two. There was a significant difference in the prevalence of hypocalcaemia in data set two. This suggests that the estimate of impact of the regulatory action may vary according to the database. In DID analysis, however, significant influences of the regulatory action on combination use with a calcium supplement were detected in both data sets. WHAT IS NEW AND CONCLUSION: There was a significant influence on combination use of denosumab with vitamin D and/or calcium supplement in both data sets. That there was no apparent increase in the prevalence of denosumab-induced hypocalcaemia, suggests that the regulatory action had an impact in the clinical setting studied. Such regulatory actions may play an important role in the promotion of drug safety.


Asunto(s)
Conservadores de la Densidad Ósea/efectos adversos , Denosumab/efectos adversos , Hipocalcemia/inducido químicamente , Anciano , Calcio/sangre , Bases de Datos Factuales , Femenino , Humanos , Hipocalcemia/sangre , Japón , Masculino , Factores de Riesgo , Vitamina D/administración & dosificación , Ácido Zoledrónico/uso terapéutico
16.
Arerugi ; 68(1): 48-53, 2019.
Artículo en Japonés | MEDLINE | ID: mdl-30787243

RESUMEN

A 16-year-old male high-school student experienced generalized itchy wheal and dyspnea during physical exercise after lunch. Each food material of his lunch was examined using a prick-prick test, allergen-specific IgE test (ImmunoCAP®), and provocation test. The prick-prick test was positive for black tiger shrimp (raw and heated) and white leg shrimp (heated). Allergen-specific IgE test (ImmunoCAP®) showed absolutely negativity for all suspected foods. The food-exercise provocation test using heated black tiger shrimp with additional aspirin intake finally induced anaphylaxis.We studied the IgE-binding molecules from shrimp using a purification procedure and Western blotting, with sera from the patient and several controls. A 40-kDa protein, corresponding to FBA, was found to be the major IgE-binding allergen component in this patient. Currently, the precise history and the prick-prick test using both raw and heated shrimps are useful to diagnose shrimp-induced FDEIA. Because the allergen-specific IgE test is insufficient to diagnose the cause of the symptoms, a component allergen-specific IgE test after the identification of the causative allergenic protein, such as FBA, is required.


Asunto(s)
Anafilaxia/diagnóstico , Asma Inducida por Ejercicio/diagnóstico , Hipersensibilidad a los Alimentos/diagnóstico , Fructosa-Bifosfato Aldolasa , Adolescente , Alérgenos , Animales , Ejercicio Físico , Fructosa , Humanos , Inmunoglobulina E , Masculino , Penaeidae , Alimentos Marinos
19.
Pestic Biochem Physiol ; 108: 80-5, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24485319

RESUMEN

We examined the genomic organization of the sodium channel α-subunit gene in two strains of melon thrips, Thrips palmi, having differing sensitivity to cypermethrin. The nucleotide sequences of the strains included 18 or 16 putative exons which covered the entire coding region of the gene producing 2039 amino acid residues. Deduced amino acid sequences of both strains showed 80% homology with those of Periplaneta americana and Cimex lectularius. Comparison of deduced amino acid sequences of both strains showed no consistent amino acid difference. In addition to the previously reported resistant amino acid (Ile) at the T929I site, both strains encoded another resistant amino acids at two positions which are involved in pyrethroid resistance in other arthropods. These amino acids might also involve in the basal levels of resistance to pyrethroids of both strains.


Asunto(s)
Proteínas de Insectos/genética , Insecticidas/farmacología , Piretrinas/farmacología , Canales de Sodio/genética , Thysanoptera/efectos de los fármacos , Thysanoptera/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Genómica , Proteínas de Insectos/química , Proteínas de Insectos/metabolismo , Resistencia a los Insecticidas , Datos de Secuencia Molecular , Alineación de Secuencia , Canales de Sodio/química , Canales de Sodio/metabolismo , Thysanoptera/química , Thysanoptera/metabolismo
20.
Exp Appl Acarol ; 63(3): 313-32, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24659516

RESUMEN

A population survey of phytoseiid mites and spider mites was conducted on peach leaves and wild plants in Japanese peach orchards having different pesticide practices. The phytoseiid mite species composition on peach leaves and wild plants, as estimated using quantitative sequencing, changed during the survey period. Moreover, it varied among study sites. The phytoseiid mite species compositions were similar between peach leaves and some wild plants, such as Veronica persica, Paederia foetida, Persicaria longiseta, and Oxalis corniculata with larger quantities of phytoseiid mites, especially after mid-summer. A PCR-based method to detect the ribosomal ITS sequences of Tetranychus kanzawai and Panonychus mori from phytoseiid mites was developed. Results showed that Euseius sojaensis (specialized pollen feeder/generalist predator) uses both spider mites as prey in the field.


Asunto(s)
Ácaros/fisiología , Control de Plagas/métodos , Prunus , Tetranychidae/fisiología , Acaricidas , Animales , Secuencia de Bases , Clonación Molecular , Resistencia a Medicamentos , Ácaros/clasificación , Ácaros/genética , Datos de Secuencia Molecular , Dinámica Poblacional , Alineación de Secuencia , Tetranychidae/clasificación , Tetranychidae/genética
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