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BACKGROUND: Diabetes mellitus (DM) is a known risk factor for active TB. A key activity in the Philippines is to integrate TB services with other disease programmes, with a target of DM screening in 90% of TB cases. However, costs of providing DM outpatient services for TB patients are not well known. METHODS: We estimated the costs of providing integrated DM outpatient services within TB services from the health system perspective. Resources for outpatient DM services were valued using the bottom-up approach for capital goods, staff time and consumables. Resource quantities were obtained by interviewing 60 healthcare professionals in 11 health facilities in the Philippines. RESULTS: The mean cost per service ranged from USD0.53 for DM risk assessment to USD23.72 for oral glucose tolerance test. The cost per case detected for different algorithms varied from USD17.43 to USD80.81. The monthly cost per patient was estimated at USD8.95 to USD12.36. CONCLUSION: Our study provides the first estimates of costs for providing integrated DM outpatient services and TB care in a low- and middle-income country. The costs of DM detection in TB patients suggests that it may be useful to further investigate the cost-effectiveness and affordability of service delivery.
CONTEXTE: Le diabète (DM) est un facteur de risque bien établi pour la TB active. Aux Philippines, l'une des principales initiatives est d'intégrer les services de lutte contre la TB dans d'autres programmes de santé, dans le but de dépister le DM chez 90% des patients atteints de TB. Cependant, les coûts des services ambulatoires de traitement du DM pour les patients atteints de TB ne sont pas clairement définis. MÉTHODES: Nous avons évalué les coûts des services ambulatoires intégrés pour le traitement du DM dans le cadre des services de lutte contre la TB, du point de vue du système de santé. Les ressources pour les services ambulatoires de DM ont été évaluées en utilisant l'approche ascendante pour les biens d'équipement, le temps du personnel et les consommables. Les quantités de ressources ont été recueillies en interrogeant 60 professionnels de la santé dans 11 établissements de santé aux Philippines. CONCLUSION: Notre étude présente les premières estimations des coûts des services ambulatoires intégrés pour le traitement du DM et de soins de la TB dans un pays à revenu faible ou intermédiaire. Il est suggéré d'approfondir l'étude du rapport coût-efficacité et de l'accessibilité des services de détection de la DM chez les patients atteints de TB, compte tenu des coûts impliqués.
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BACKGROUND: This study was to meet a practical need to design a simple tool to identify TB patients who may potentially be facing catastrophic costs while seeking TB care in the public sector. Such a tool may help prevent and address catastrophic costs among individual patients. METHODS: We used data from the national TB patient cost survey in the Philippines. We randomly allocated TB patients to either the derivation or validation sample. Using adjusted odds ratios (ORs) and ß coefficients of logistic regression, we developed four scoring systems to identify TB patients who may be facing catastrophic costs from the derivation sample. We validated each scoring system in the validation sample. RESULTS: We identified a total of 12 factors as predictive indicators associated with catastrophic costs. Using all 12 factors, the ß coefficients-based scoring system (area under the curve [AUC] 0.783, 95% CI 0.754-0.812) had a high validity. Even with seven selected factors with OR > 2.0, the validity remained in the acceptable range (ß coefficients-based: AUC 0.767, 95% CI 0.737-0.798). CONCLUSION: The ß coefficients-based scoring systems in this analysis can be used to identify those at high risk of facing catastrophic costs due to TB in the Philippines. Operational feasibility needs to be investigated further to implement this in routine TB surveillance.
CONTEXTE: Cette étude visait à répondre à un besoin pratique de concevoir un outil simple pour identifier les patients atteints de TB qui pourraient potentiellement être confrontés à des coûts catastrophiques lorsqu'ils recherchent des soins de TB dans le secteur public. Un tel outil pourrait aider à prévenir et à traiter les coûts catastrophiques chez les patients individuels. MÉTHODES: Nous avons utilisé des données de l'enquête nationale sur les coûts des patients atteints de TB aux Philippines. Nous avons réparti aléatoirement les patients atteints de TB dans l'échantillon de dérivation ou de validation. À l'aide des odds ratio (OR) ajustés et des coefficients ß de la régression logistique, nous avons développé quatre systèmes de notation pour identifier les patients atteints de TB qui pourraient être confrontés à des coûts catastrophiques à partir de l'échantillon de dérivation. Nous avons validé chaque système de notation dans l'échantillon de validation. RÉSULTATS: Nous avons identifié un total de 12 facteurs en tant qu'indicateurs prédictifs associés à des coûts catastrophiques. En utilisant les 12 facteurs, le système de notation basé sur les coefficients ß (aire sous la courbe [AUC] 0,783 ; IC 95% 0,7540,812) avait une validité élevée. Même avec sept facteurs sélectionnés avec OR > 2,0, la validité est restée dans la plage acceptable (basée sur les coefficients ß : AUC 0,767 ; IC 95% 0,7370,798). CONCLUSION: Les systèmes de notation basés sur les coefficients ß dans cette analyse peuvent être utilisés pour identifier les personnes à haut risque de faire face à des coûts catastrophiques liés à la TB aux Philippines. La faisabilité opérationnelle doit être étudiée plus avant pour mettre en Åuvre cela dans la surveillance de routine de la TB.
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We present the first search for the pair production of dark particles X via K_{L}^{0}âXX with X decaying into two photons using the data collected by the KOTO experiment. No signal was observed in the mass range of 40-110 MeV/c^{2} and 210-240 MeV/c^{2}. This sets upper limits on the branching fractions as B(K_{L}^{0}âXX)<(1-4)×10^{-7} and B(K_{L}^{0}âXX)<(1-2)×10^{-6} at the 90% confidence level for the two mass regions, respectively.
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A visible light tomographic imaging system has been developed for the collisional merging experiment of field-reversed configurations (FRCs) on the FRC Amplification via Translation-Collisional Merging device at Nihon University. Two FRCs formed by field-reversed theta-pinch translate at super-Alfvénic velocity and collide with each other. The translation and collision processes are completed in 20-30 µs, and a single FRC is reformed in â¼70 µs. To study these translation and collisional merging processes, the tomographic system, including fast response tomographic cameras and a reconstruction method assuming a Rigid-Rotor (RR) model, is developed. The developed tomographic cameras simply consist of 16 channels of multi-anode photomultipliers, a band-pass filter, a slit, and a cylindrical lens, which expands the viewing angle. Because the viewing angle is limited by the size of the viewports of the metal chamber, the iterative method assuming the RR model has been applied to reconstruct tomographic images from a small number of projections. The developed tomographic imaging system can estimate the behavior of FRCs. Four cameras are installed in the two cross sections near the collision point. The radial shift of each translated FRC can be calculated by this system. Details of the developed tomographic camera system and RR reconstruction method are reported.
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The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of localised colon cancer was published in 2020. It was decided by both the ESMO and the Japanese Society of Medical Oncology (JSMO) to convene a special virtual guidelines meeting in March 2021 to adapt the ESMO 2020 guidelines to take into account the ethnic differences associated with the treatment of localised colon cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with localised colon cancer representing the oncological societies of Japan (JSMO), China (CSCO), India (ISMPO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug availability and reimbursement situations in the different Asian countries.
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Neoplasias del Colon , Oncología Médica , Asia/epidemiología , Neoplasias del Colon/diagnóstico , Neoplasias del Colon/terapia , Estudios de Seguimiento , Humanos , República de CoreaRESUMEN
BACKGROUND: Recent advances in adjuvant chemotherapy for early colon cancer have widened physicians' recommendations on the regimen and duration (3 or 6 months) of the treatment. We conducted this prospective study to evaluate whether the 12-gene recurrence score (12-RS) assay affected physicians' recommendations on adjuvant treatment selection. PATIENTS AND METHODS: Patients with stage IIIA/IIIB or stage II colon cancer were enrolled. After the patients discussed adjuvant treatment with their treating physicians, the physicians filled in the questionnaire before assay indicating the treatment recommendation. When the 12-RS assay results were available, the physicians again filled in the questionnaire after assay. The primary endpoint was the rate of change in treatment recommendations from before to after the assay, with a threshold rate of change being 20%. Patients with stage IIIA/B to II were enrolled in a ratio of 2 : 1. RESULTS: Overall, the treatment recommendations changed in 40% of cases after obtaining 12-RS assay results. Recommendations were changed in 45% (80/178; 95% confidence interval, 37% to 53%; P < 0.001) and 30% (29/97; 95% confidence interval, 21% to 40%; P < 0.001) of patients with stage IIIA/B and II colon cancer, respectively. Patients with stage IIIA/B cancer had significantly more change than those with stage II cancer (P = 0.0148). From before to after the 12-RS assay, the percentage of patients whose physicians reported being confident in their treatment recommendations significantly increased from 54% to 81% in stage IIIA/B (P < 0.001) and from 65% to 83% in stage II (P < 0.001). CONCLUSION: Our study confirmed the usefulness of the 12-RS assay in aiding the physician-patient decision-making process for tailoring adjuvant chemotherapy for stage IIIA/B colon cancer.
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Neoplasias del Colon , Recurrencia Local de Neoplasia , Bioensayo , Quimioterapia Adyuvante , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/genética , Humanos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Estudios ProspectivosRESUMEN
OBJECTIVES: The JO25567 randomized Phase II study demonstrated a statistically significant progression-free survival (PFS) benefit with erlotinib plus bevacizumab compared with erlotinib monotherapy in chemotherapy-naïve Japanese patients with epidermal growth factor receptor mutation-positive (EGFR+) non-small-cell lung cancer (NSCLC). Here we present updated PFS and final overall survival (OS) data after a median follow-up of 34.7 months. MATERIALS AND METHODS: Patients with stage IIIB/IV or postoperative recurrent NSCLC were randomized to receive oral erlotinib 150â¯mg once daily (nâ¯=â¯77) or erlotinib in combination with intravenous bevacizumab 15â¯mg/kg every 21 days (nâ¯=â¯75) until disease progression or unacceptable toxicity. OS was analyzed using an unstratified Cox proportional hazards model. RESULTS: Consistent with the primary analysis, addition of bevacizumab to erlotinib was associated with a significant improvement in PFS (hazard ratio [HR] 0.52; 95 % confidence interval [CI]: 0.35-0.76; log-rank two-sided P = 0.0005; median 16.4 months vs 9.8 months, respectively). In contrast, a significant improvement in OS was not seen (HR 0.81; 95 % CI, 0.53-1.23; Pâ¯=⯠0.3267; median 47.0 months vs 47.4 months, respectively). Post-study therapy was similar between the treatment arms and EGFR mutation type did not affect OS outcomes. The 5-year OS rate was numerically higher with erlotinib plus bevacizumab vs erlotinib monotherapy (41 % vs 35 %). Updated safety analyses confirmed the previously reported manageable tolerability profile, with no new safety issues. CONCLUSION: Addition of bevacizumab to first-line erlotinib did not show significant improvement in OS in Japanese patients with stage IIIB/IV or postoperative recurrent EGFR+ NSCLC. Both treatment arms showed a similar median OS benefit (as long as 4 years), irrespective of individual patient characteristics. Results from ongoing studies evaluating the combination of EGFR and VEGF signaling inhibitors are eagerly awaited. TRIAL REGISTRATION: JapicCTI-111390 and JapicCTI-142569.
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Bevacizumab , Carcinoma de Pulmón de Células no Pequeñas , Clorhidrato de Erlotinib , Neoplasias Pulmonares , Inhibidores de Proteínas Quinasas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Supervivencia sin Enfermedad , Receptores ErbB/genética , Clorhidrato de Erlotinib/uso terapéutico , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Mutación , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Inhibidores de Proteínas Quinasas/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Oxaliplatin-based adjuvant chemotherapy may be associated with debilitating peripheral sensory neuropathy (PSN) in patients with high-risk stage II colon cancer. This open-label, multicenter, randomized phase III trial was conducted as a prospective pooled analysis to investigate the non-inferiority of 3 versus 6 months of adjuvant oxaliplatin-based chemotherapy. PATIENTS AND METHODS: From 12 February 2014 to 31 January 2017, 525 Asian patients with high-risk stage II colon cancer were randomly assigned to 3- and 6-month treatment arms. The treatment consisted of either modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or capecitabine combined with oxaliplatin (CAPOX). The primary end point was disease-free survival (DFS). The secondary end points were treatment compliance and safety. RESULTS: Of the 525 randomized patients, 11 were not treated. Among the 514 participating patients (255 in the 3-month arm; 259 in the 6-month arm), 432 (84%) received CAPOX, and 184 (36%) presented with T4 as a high-risk factor for recurrence. The 3-year DFS rate was 88.2% in the 3-month arm and 87.9% in the 6-month arm [hazard ratio (HR), 1.12; 95% confidence interval (CI), 0.67-1.87]. With CAPOX, the 3-year DFS rate was 88.2% in the 3-month arm and 88.4% in the 6-month arm (HR, 1.13; 95% CI, 0.65-1.96). The discontinuation rate in the 3- and 6-month arms was 10% and 31% for mFOLFOX6 (P = 0.0193), and 15% and 35% for CAPOX (P < 0.0001), respectively. The incidence of grade ≥2 PSN was significantly lower in the 3-month arm than in the 6-month arm (16% and 43%, respectively, P < 0.0001). CONCLUSIONS: Three months of combination therapy presented significantly less grade ≥2 PSN than the respective 6-month regimen. The shortened therapy duration did not affect the 3-year DFS rate, suggesting that a 3-month course of CAPOX can be an effective treatment option. CLINICAL TRIAL INFORMATION: UMIN Clinical Trials Registry, UMIN000013036 and Japan Registry of Clinical Trials, jRCTs031180128.
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Neoplasias del Colon , Compuestos Organoplatinos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Capecitabina/efectos adversos , Quimioterapia Adyuvante , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Supervivencia sin Enfermedad , Fluorouracilo/efectos adversos , Humanos , Japón , Leucovorina/efectos adversos , Estadificación de Neoplasias , Compuestos Organoplatinos/efectos adversos , Oxaliplatino/efectos adversos , Estudios ProspectivosRESUMEN
OBJECTIVE: Vertigo and dizziness are frequent symptoms in patients at out-patient services. An accurate diagnosis for vertigo or dizziness is essential for symptom relief; however, it is often challenging. This study aimed to identify differences in diagnoses between primary-care physicians and specialised neurotologists. METHOD: In total, 217 patients were enrolled. To compare diagnoses, data was collected from the reference letters of primary-care physicians, medical questionnaires completed by patients and medical records. RESULTS: In total, 62.2 per cent and 29.5 per cent of the patients were referred by otorhinolaryngologists and internists, respectively. The cause of vertigo or dizziness and diagnosis was missing in 47.0 per cent of the reference letters. In addition, 67.3 per cent of the diagnoses by previous physicians differed from those reported by specialised neurotologists. CONCLUSION: To ensure patient satisfaction and high quality of life, an accurate diagnosis for vertigo or dizziness is required; therefore, methods or materials to improve the diagnostic accuracy are needed.
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BACKGROUND: The objective of this randomized phase II trial was to evaluate efficacy and safety of the therapeutic sequence of regorafenib followed by cetuximab, compared with cetuximab followed by regorafenib, as the current standard sequence for metastatic colorectal cancer patients. PATIENTS AND METHODS: Patients with KRAS exon 2 wild-type metastatic colorectal cancer after failure of fluoropyrimidine, oxaliplatin, and irinotecan were randomized to receive sequential treatment with regorafenib followed by cetuximab ± irinotecan (R-C arm), or the reverse sequence [cetuximab ± irinotecan followed by regorafenib (C-R arm)]. The primary end point was overall survival (OS). Key secondary end points included progression-free survival (PFS) with initial treatment (PFS1), PFS with second treatment (PFS2), safety, and quality of life. Exploratory end points included serial biomarker analyses, including oncogenic alterations from circulating tumor DNA or multiple serum or plasma proteins. RESULTS: One-hundred one patients were randomized and eligible for efficacy analysis. Sequential treatment was successful in 86% patients in both arms. Median OS for R-C and C-R was 17.4 and 11.6 months, respectively (P = 0.0293), with a hazard ratio (HR) of 0.61 for OS [95% confidence interval (CI) 0.39-0.96]. The HR for PFS1 (regorafenib in R-C versus cetuximab in C-R) was 0.97 (95% CI 0.61-1.54), and PFS2 (C in R-C versus R in C-R) was 0.29 (95% CI 0.17-0.50). No unexpected safety signals were observed. The quality of life scores during the entire treatment period was not significantly different between the two arms. Circulating biomarker analyses showed emerging oncogenic alterations in RAS, BRAF, EGFR, HER2, and MET, which were more commonly detected after cetuximab than after regorafenib. CONCLUSIONS: The therapeutic sequence of regorafenib followed by cetuximab suggests a longer OS than the current standard sequence.
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Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adenocarcinoma/secundario , Anciano , Cetuximab/administración & dosificación , Neoplasias Colorrectales/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Compuestos de Fenilurea/administración & dosificación , Pronóstico , Piridinas/administración & dosificación , Tasa de SupervivenciaRESUMEN
Background: The standard of care for first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) is combination treatment with platinum, 5-FU and cetuximab (PFE). However, this regimen requires hospitalization to ensure proper hydration and continuous infusion of 5-FU, and causes severe nausea and anorexia. We evaluated the efficacy and safety of paclitaxel, carboplatin and cetuximab (PCE) as first-line treatment in patients with R/M SCCHN. Patients and methods: Eligibility criteria included recurrent and/or metastatic, histologically proven SCC of the oropharynx, oral cavity, hypopharynx or larynx; PS 0-1; adequate organ function; no suitable local therapy for R/M SCCHN; and no prior systemic chemotherapy for R/M SCCHN. Chemotherapy consisted of paclitaxel 100 mg/m2 on days 1, 8; carboplatin area under the blood concentration-time curve 2.5 on days 1, 8, repeated every 3 weeks for up to 6 cycles; and cetuximab at an initial dose of 400 mg/m2, followed by 250 mg/m2 weekly until disease progression or unacceptable toxicities. Primary end point was overall response rate. Secondary end points were safety, treatment completion rate, progression-free survival, overall survival, and clinical benefit rate. Planned sample size was 45 patients. Results: Forty-seven subjects were accrued from July 2013 to October 2014. Of 45 evaluable, 40 were male; median age was 63 years; Eastern Cooperative Oncology Group Performance Status was 0/1 in 23/22 cases; site was the hypopharynx/oropharynx/oral cavity/larynx in 17/11/10/7 cases; and 36/9 cases were smokers/nonsmokers, respectively. Overall response rate, the primary end point, was 40%. Median overall survival was 14.7 months and progression-free survival was 5.2 months. Grade 3/4 adverse events included neutropenia (68%), skin reaction (15%), fatigue (9%) and febrile neutropenia (9%). A potentially treatment-related death occurred in one patient with intestinal pneumonia. Conclusions: The PCE regimen shows promising activity with acceptable toxicity in the outpatient clinic. Further studies are needed to compare PCE with PFE in this population. Registered clinical trial number: UMIN000010507.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/administración & dosificación , Cetuximab/administración & dosificación , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Metástasis de la Neoplasia , Paclitaxel/administración & dosificación , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Femenino , Neoplasias de Cabeza y Cuello/patología , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Carcinoma de Células Escamosas de Cabeza y Cuello/patologíaRESUMEN
BACKGROUND AND PURPOSE: Dual-energy CT can distinguish iodine-enhanced tumors from nonossified cartilage and has been investigated for evaluating cartilage invasion in patients with laryngeal and hypopharyngeal squamous cell carcinomas. In this study, we compared the diagnostic accuracy of MR imaging and of a combination of weighted-average and iodine overlay dual-energy CT images in detecting cartilage invasion by laryngeal and hypopharyngeal squamous cell carcinomas, in particular thyroid cartilage invasion. MATERIALS AND METHODS: Fifty-five consecutive patients who underwent 3T MR imaging and 128-slice dual-energy CT for preoperative initial staging of laryngeal or hypopharyngeal squamous cell carcinomas were included. Two blinded observers evaluated laryngeal cartilage invasion on MR imaging and dual-energy CT using a combination of weighted-average and iodine-overlay images. Pathologic findings of surgically resected specimens were used as the reference standard for evaluating sensitivity, specificity, and the areas under the receiver operating characteristic curve of both modalities for cartilage invasion by each type of cartilage and for all cartilages together. Sensitivity and specificity were compared using the McNemar test and generalized linear mixed models. RESULTS: Dual-energy CT showed higher specificity than MR imaging for diagnosing all cartilage together (84% for MR imaging versus 98% for dual-energy CT, P < .004) and for thyroid cartilage (64% versus 100%, P < .001), with a similar average area under the curve (0.94 versus 0.95, P = .70). The sensitivity did not differ significantly for all cartilages together (97% versus 81%, P = .16) and for thyroid cartilage (100% versus 89%, P = .50), though there was a trend toward increased sensitivity with MR imaging. CONCLUSIONS: Dual-energy CT showed higher specificity and acceptable sensitivity in diagnosing laryngeal cartilage invasion compared with MR imaging.
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Neoplasias Hipofaríngeas/diagnóstico por imagen , Neoplasias Laríngeas/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Metástasis de la Neoplasia/diagnóstico por imagen , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Neoplasias Hipofaríngeas/patología , Cartílagos Laríngeos/diagnóstico por imagen , Cartílagos Laríngeos/patología , Neoplasias Laríngeas/patología , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia/patología , Curva ROC , Sensibilidad y Especificidad , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Cartílago Tiroides/diagnóstico por imagen , Cartílago Tiroides/patologíaRESUMEN
Background: Amrubicin is approved for treating non-small-cell lung cancer (NSCLC) and small-cell lung cancer. However, no direct comparisons between amrubicin and docetaxel, a standard treatment for NSCLC, have been reported. Patients and methods: We conducted a randomized phase III trial of Japanese NSCLC patients after one or two chemotherapy regimens. Patients were randomized to amrubicin (35 mg/m2 on days 1-3 every 3 weeks) or docetaxel (60 mg/m2 on day 1 every 3 weeks). Outcomes included progression-free survival, overall survival, tumor responses, and safety. Results: Between October 2010 and June 2012, 202 patients were enrolled across 32 institutions. Median progression-free survival (3.6 versus 3.0 months; P = 0.54) and overall survival (14.6 versus 13.5 months; P = 0.86) were comparable in the amrubicin and docetaxel groups, respectively. The overall response rate was 14.4% (14/97) and 19.6% (19/97) in the amrubicin and docetaxel groups, respectively (P = 0.45). The disease control rate was 55.7% in both groups. Adverse events occurred in all patients, and included grade ≥3 neutropenia occurred in 82.7% and 78.8% of patients in the amrubicin and docetaxel groups, respectively, grade ≥3 leukopenia occurred in 63.3% and 70.7%, and grade ≥3 febrile neutropenia occurred in 13.3% and 18.2% of patients in the amrubicin and docetaxel groups, respectively. Of eight cardiac-related events in the amrubicin group, three were considered related to amrubicin and resolved without treatment discontinuation. Conclusions: This was the first phase III study to compare amrubicin and docetaxel in patients with pretreated NSCLC. Amrubicin did not significantly improve the primary endpoint of PFS compared with docetaxel. Clinical trial registration: NCT01207011 (ClinicalTrials.gov).
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Antraciclinas/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Taxoides/uso terapéutico , Anciano , Antraciclinas/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Supervivencia sin Enfermedad , Docetaxel , Resistencia a Antineoplásicos , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Taxoides/efectos adversos , Resultado del TratamientoRESUMEN
We demonstrate a novel form of thermally-assisted hysteresis in the transfer curves of monolayer MoS2 FETs, characterized by the appearance of a large gate-voltage window and distinct current levels that differ by a factor of â¼102. The hysteresis emerges for temperatures in excess of 400 K and, from studies in which the gate-voltage sweep parameters are varied, appears to be related to charge injection into the SiO2 gate dielectric. The thermally-assisted memory is strongly suppressed in equivalent measurements performed on bilayer transistors, suggesting that weak screening in the monolayer system plays a vital role in generating its strongly sensitive response to the charge-injection process. By exploiting the full features of the hysteretic transfer curves, programmable memory operation is demonstrated. The essential principles demonstrated here point the way to a new class of thermally assisted memories based on atomically thin two-dimensional semiconductors.
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BACKGROUND: There has been no phase III study of comparing the efficacy of first- and second-generation 5-HT3 receptor antagonists in the triplet regimen with dexamethasone and aprepitant for preventing chemotherapy-induced nausea and vomiting after highly emetogenic chemotherapy (HEC). PATIENTS AND METHODS: Patients with a malignant solid tumor who would receive HEC containing 50 mg/m(2) or more cisplatin were randomly assigned to either palonosetron (0.75 mg) arm (Arm P) or granisetron (1 mg) arm (Arm G), on day 1, both arms with dexamethasone (12 mg on day 1 and 8 mg on days 2-4) and aprepitant (125 mg on day 1 and 80 mg on days 2-3). The primary end point was complete response (CR; no vomiting/retching and no rescue medication) at the 0-120 h period and secondary end points included complete control (CC; no vomiting/retching, no rescue medication, and no more than mild nausea) and total control (TC; no vomiting/retching, no rescue medication, and no nausea). RESULTS: Between July 2011 and June 2012, 842 patients were enrolled. Of 827 evaluable, 272 of 414 patients (65.7%) in Arm P had a CR at the 0-120 h period when compared with 244 of 413 (59.1%) in Arm G (P = 0.0539). Both arms had the same CR rate of 91.8% at the acute (0-24 h) period, while at the delayed (24-120 h) period, Arm P had a significantly higher CR rate than Arm G (67.2% versus 59.1%; P = 0.0142). In secondary end points, Arm P had significantly higher rates than Arm G at the 0-120 h period (CC rate: 63.8% versus 55.9%, P = 0.0234; TC rate: 47.6% versus 40.7%, P = 0.0369) and delayed periods (CC rate: 65.2% versus 55.9%, P = 0.0053; TC rate: 48.6% versus 41.4%, P = 0.0369). CONCLUSION: The present study did not show the superiority of palonosetron when compared with granisetron in the triplet regimen regarding the primary end point. CLINICAL TRIAL REGISTRY IDENTIFIER: UMIN000004863.
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Cisplatino/administración & dosificación , Granisetrón/administración & dosificación , Isoquinolinas/administración & dosificación , Neoplasias/tratamiento farmacológico , Quinuclidinas/administración & dosificación , Adulto , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Cisplatino/efectos adversos , Método Doble Ciego , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Granisetrón/efectos adversos , Humanos , Isoquinolinas/efectos adversos , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Náusea/patología , Neoplasias/patología , Palonosetrón , Quinuclidinas/efectos adversos , Antagonistas de la Serotonina/administración & dosificación , Antagonistas de la Serotonina/efectos adversos , Vómitos/inducido químicamente , Vómitos/patologíaRESUMEN
OBJECTIVES: Hepatic artery thrombosis (HAT) is a serious complication after living-donor liver transplantation (LDLT) leading to patient death in the absence of revascularization. With the recent advances in interventional radiology, interventional endovascular techniques have been used as alternative therapeutic options for HAT. This study evaluates the feasibility and clinical outcomes of endovascular treatment for HAT after LDLT. METHODS: The medical records of 120 patients who underwent adult-to-adult LDLT between February 2002 and February 2015 in our hospital were retrospectively reviewed to evaluate the frequency of HAT and outcomes of endovascular treatment. RESULTS: A total of nine patients (7.5%) developed HAT after LDLT, and the all patients underwent endovascular treatment. Overall technical success with endovascular treatment was achieved in 77.8% (7 of 9) of the patients. Intra-arterial thrombolysis was successful in one patient. Further intervention after intra-arterial thrombolysis was performed in the form of percutaneous transluminal angioplasty in six patients, and percutaneous transluminal angioplasty with stenting in two patients. Two patients with failure of revascularization by endovascular treatment were treated conservatively and developed hepatic arterial collaterals, and the both patients could avoid the graft failure. The overall survival rates did not differ significantly between the patients without HAT (n = 111) and those with HAT (n = 9) (1-, 3-, and 5-year overall survival rates of the patients without HAT vs. with HAT: 78.1%, 67.8%, and 65.3% vs. 66.7%, 66.7%, and 66.7%, respectively; P = .77). CONCLUSION: Interventional endovascular treatment of HAT in LDLT is a feasible and reliable procedure in avoiding early graft failure with acceptable long-term patient outcome.
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Angioplastia/métodos , Procedimientos Endovasculares/métodos , Arteria Hepática/cirugía , Hepatopatías/cirugía , Trasplante de Hígado , Complicaciones Posoperatorias/cirugía , Terapia Trombolítica/métodos , Trombosis/cirugía , Adulto , Anciano , Estudios de Factibilidad , Femenino , Humanos , Donadores Vivos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Stents , Resultado del Tratamiento , Adulto JovenRESUMEN
INTRODUCTION: Choline is essential for the synthesis of the major membrane phospholipid phosphatidylcholine (PC), the methyl donor betaine and the neurotransmitter acetylcholine (ACh), which is involved in several vital biological functions that play key roles in fetal development. In this study, we examined the molecular and functional characteristics of choline uptake in the human trophoblastic cell line JEG-3. METHODS: We examined [(3)H]choline uptake in the human trophoblastic cell line JEG-3. The expression of CTL1 and CTL2 was evaluated by quantitative real-time PCR, western blotting and immunocytochemistry. RESULTS: We demonstrated that JEG-3 cells take up [(3)H] choline by a saturable process that is mediated by a Na(+)-independent and pH-dependent transport system. The cells have two different [(3)H] choline transport systems, high- and low-affinity, with Km values of 28.4 ± 5.0 µM and 210.6 ± 55.1 µM, respectively. Cationic compounds and hemicholinium-3 (HC-3) inhibited choline uptake. Choline transporter-like protein 1 (CTL1) and CTL2 mRNA and protein were highly expressed in JEG-3 cells and were localized to the plasma membrane. DISCUSSION: The present results suggest that choline is mainly transported via a high-affinity choline transport system (CTL1) and a low-affinity choline transport system (CTL2) in human trophoblastic JEG-3 cells. These transporters play an important role in the growth of the fetus.
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Colina/farmacología , Proteínas de Transporte de Membrana/metabolismo , Trofoblastos/metabolismo , Animales , Transporte Biológico/efectos de los fármacos , Transporte Biológico/fisiología , Células COS , Línea Celular Tumoral , Chlorocebus aethiops , Femenino , Hemicolinio 3/farmacología , Humanos , Embarazo , Trofoblastos/efectos de los fármacosRESUMEN
BACKGROUND: The best suture method to prevent incisional surgical-site infection (SSI) after clean-contaminated surgery has not been clarified. METHODS: Patients undergoing elective colorectal cancer surgery at one of 16 centres were randomized to receive either subcuticular sutures or skin stapling for skin closure. The primary endpoint was the rate of incisional SSI. Secondary endpoints of interest included time required for wound closure, incidence of wound problems, postoperative length of stay, wound aesthetics and patient satisfaction. RESULTS: A total of 1264 patients were enrolled. The cumulative incidence of incisional SSI by day 30 after surgery was similar after subcuticular sutures and stapled closure (8·7 versus 9·8 per cent respectively; P = 0·576). Comparison of cumulative incidence curves revealed that SSI occurred later in the subcuticular suture group (P = 0·019) (hazard ratio 0·66, 95 per cent c.i. 0·45 to 0·97). Wound problems (P = 0·484), wound aesthetics (P = 0·182) and postoperative duration of hospital stay (P = 0·510) did not differ between the groups; subcuticular sutures took 5 min longer than staples (P < 0·001). Patients in the subcuticular suture group were significantly more satisfied with their wound (52·4 per cent versus 42·7 per cent in the staple group; P = 0·002). CONCLUSION: Compared with skin stapling, subcuticular sutures did not reduce the risk of incisional SSI after colorectal surgery. REGISTRATION NUMBER: UMIN000004001 (http://www.umin.ac.jp/ctr).
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Neoplasias Colorrectales/cirugía , Infección de la Herida Quirúrgica/epidemiología , Técnicas de Sutura , Adulto , Anciano , Anciano de 80 o más Años , Procedimientos Quirúrgicos Electivos/métodos , Femenino , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Atención Perioperativa , Grapado Quirúrgico/métodos , Infección de la Herida Quirúrgica/etiologíaRESUMEN
REASONS FOR PERFORMING STUDY: The protection induced by an equine influenza (EI) vaccine strain depends on its antigenic relatedness to the challenge virus. Although the World Organisation for Animal Health (OIE) recommend that both Florida sublineage clade 1 (Fc1) and clade 2 (Fc2) viruses should be included in EI vaccines, Japanese EI vaccines have not, thus far, been updated to include a Fc2 virus. OBJECTIVES: To evaluate the efficacy of antibodies raised against Japanese EI vaccine strains in the neutralisation of recent Fc2 viruses. STUDY DESIGN: Antigenic analysis. METHODS: Virus neutralisation tests were performed using antisera from experimentally infected horses and from horses that had received a primary course of the currently available vaccines. RESULTS: Antiserum raised against the Japanese EI vaccine strain, A/equine/La Plata/1993, exhibited poor cross-neutralising activity against the Fc2 viruses isolated recently in Ireland and the UK, which have the substitution of alanine to valine at position 144 in antigenic site A of the haemagglutinin gene. In contrast, the antiserum exhibited good cross-neutralising activity against the Fc2 viruses without the substitution. This finding was supported in experiments with antisera collected from vaccinated horses. CONCLUSIONS: This suggests that the efficacy of the Japanese EI vaccine for some of the recent Fc2 viruses is suboptimal and that vaccines should be updated in accordance with the OIE recommendations.