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BACKGROUND: Based on previous results obtained with non-pegylated liposomal-encapsulated doxorubicin (TLC-D99) together with paclitaxel and trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer (BC), a similar regimen was evaluated in the neoadjuvant setting in a prospectively selected series of consecutive patients with clinical stage II-III BC. Primary and secondary objectives included the rate of pathologic complete response (pCR), safety, and predictive factors of pCR. METHODS: Patients received six cycles of TLC-D99 (50 mg/m(2) every 3 weeks), paclitaxel (80 mg/m(2) weekly) and trastuzumab (4 mg/kg initial dose and 2 mg/kg weekly). All patients underwent surgery after treatment. pCR was defined as the absence of invasive cancer cells in the breast and the axilla. RESULTS: Sixty-two patients with a median age of 46.6 years were analyzed. Stage IIIA was diagnosed in 43.5% of patients and 14.5% had inflammatory BC. Conservative surgery was performed in 46.8% of the patients and pCR was achieved in 63% (95% CI 50.5-75.5). Patients with estrogen receptor (ER)-negative tumors presented a significantly higher pCR rate than patients with ER-positive tumors (74.4 vs 43.5%; P = 0.028). Forty-five patients (72.6%) completed study treatment and 80.6% received at least five treatment cycles. No patients developed congestive heart failure and 14.5% of patients showed a ≥ 10 % decrease in the left ventricular ejection fraction. CONCLUSION: The triple combination therapy assessed is effective and safe, offering a high pCR rate in patients with HER2-positive BC.
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Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Adenocarcinoma/metabolismo , Adulto , Anciano , Neoplasias de la Mama/metabolismo , Doxorrubicina/administración & dosificación , Doxorrubicina/análogos & derivados , Femenino , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante , Paclitaxel/administración & dosificación , Polietilenglicoles/administración & dosificación , Receptor ErbB-2/metabolismo , Inducción de Remisión , Trastuzumab/administración & dosificación , Resultado del Tratamiento , Adulto JovenRESUMEN
Drug safety issues pose serious health threats to the population and constitute a major cause of mortality worldwide. Due to the prominent implications to both public health and the pharmaceutical industry, it is of great importance to unravel the molecular mechanisms by which an adverse drug reaction can be potentially elicited. These mechanisms can be investigated by placing the pharmaco-epidemiologically detected adverse drug reaction in an information-rich context and by exploiting all currently available biomedical knowledge to substantiate it. We present a computational framework for the biological annotation of potential adverse drug reactions. First, the proposed framework investigates previous evidences on the drug-event association in the context of biomedical literature (signal filtering). Then, it seeks to provide a biological explanation (signal substantiation) by exploring mechanistic connections that might explain why a drug produces a specific adverse reaction. The mechanistic connections include the activity of the drug, related compounds and drug metabolites on protein targets, the association of protein targets to clinical events, and the annotation of proteins (both protein targets and proteins associated with clinical events) to biological pathways. Hence, the workflows for signal filtering and substantiation integrate modules for literature and database mining, in silico drug-target profiling, and analyses based on gene-disease networks and biological pathways. Application examples of these workflows carried out on selected cases of drug safety signals are discussed. The methodology and workflows presented offer a novel approach to explore the molecular mechanisms underlying adverse drug reactions.
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Sistemas de Administración de Bases de Datos , Bases de Datos Factuales , Documentación/métodos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/clasificación , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Almacenamiento y Recuperación de la Información/métodos , Sistema de Registros , Simulación por Computador , Humanos , Modelos BiológicosRESUMEN
PURPOSE: Pharmacovigilance methods have advanced greatly during the last decades, making post-market drug assessment an essential drug evaluation component. These methods mainly rely on the use of spontaneous reporting systems and health information databases to collect expertise from huge amounts of real-world reports. The EU-ADR Web Platform was built to further facilitate accessing, monitoring and exploring these data, enabling an in-depth analysis of adverse drug reactions risks. METHODS: The EU-ADR Web Platform exploits the wealth of data collected within a large-scale European initiative, the EU-ADR project. Millions of electronic health records, provided by national health agencies, are mined for specific drug events, which are correlated with literature, protein and pathway data, resulting in a rich drug-event dataset. Next, advanced distributed computing methods are tailored to coordinate the execution of data-mining and statistical analysis tasks. This permits obtaining a ranked drug-event list, removing spurious entries and highlighting relationships with high risk potential. RESULTS: The EU-ADR Web Platform is an open workspace for the integrated analysis of pharmacovigilance datasets. Using this software, researchers can access a variety of tools provided by distinct partners in a single centralized environment. Besides performing standalone drug-event assessments, they can also control the pipeline for an improved batch analysis of custom datasets. Drug-event pairs can be substantiated and statistically analysed within the platform's innovative working environment. CONCLUSIONS: A pioneering workspace that helps in explaining the biological path of adverse drug reactions was developed within the EU-ADR project consortium. This tool, targeted at the pharmacovigilance community, is available online at https://bioinformatics.ua.pt/euadr/.
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Sistemas de Registro de Reacción Adversa a Medicamentos/organización & administración , Internet , Farmacovigilancia , Sistemas de Registro de Reacción Adversa a Medicamentos/estadística & datos numéricos , Minería de Datos/métodos , Bases de Datos Factuales/estadística & datos numéricos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Europa (Continente) , Humanos , Programas InformáticosRESUMEN
We describe a new procedure, sonographically guided intralesional triamcinolone injection, for the treatment of mammillary fistulas. Six patients with mammillary fistulas were enrolled in this prospective study. Clinical improvement was rapid after the first triamcinolone injection. The initial response to treatment was assessed as complete in 4 cases, and the remaining 2 cases resolved successfully with additional injections. On the basis of the excellent results obtained in this study, it is thought that intralesional triamcinolone injection may be a good alternative to surgery.
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Absceso/diagnóstico por imagen , Absceso/tratamiento farmacológico , Enfermedades de la Mama/diagnóstico por imagen , Enfermedades de la Mama/tratamiento farmacológico , Fístula/diagnóstico por imagen , Fístula/tratamiento farmacológico , Triamcinolona/administración & dosificación , Ultrasonografía Intervencional/métodos , Adulto , Antiinflamatorios/administración & dosificación , Femenino , Humanos , Inyecciones Intralesiones , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
BACKGROUND: The global prevalence of postpartum depression is about 20%. This disease has serious consequences for women, their infants, and their families. The aim of this randomized clinical trial was to analyze the effectiveness and safety of a moderate-intensity aerobic water exercise program on postpartum depression, sleep problems, and quality of life in women at one month after delivery. METHODS: This was a multi-center, parallel, randomized, evaluator blinded, controlled trial in a primary care setting. Pregnant women (14-20 weeks gestational age) who had low risk of complications and were from five primary care centers in the area covered by the obstetrics unit of Son Llatzer Hospital (Mallorca, Spain) were invited to participate. A total of 320 pregnant women were randomly assigned to two groups, an intervention group (moderate aquatic aerobic exercise) and a control group (usual prenatal care). One month after birth, sleep quality (MOS sleep), quality of life (EQ-5D), and presence of anxiety or depression (EPDS) were recorded. FINDINGS: Women in the intervention group were less likely to report anxiety or depression on the EQ5D (11.5% vs. 22.7%; p < 0.05) and had a lower mean EPDS score (6.1 ± 1.9 vs. 6.8 ± 2.4, p < 0.010). The two groups had no significant differences in other outcomes, maternal adverse events, and indicators of the newborn status. CONCLUSION: Moderate-intensity aquatic exercise during pregnancy decreased postpartum anxiety and depressive symptoms in mothers and was safe for mothers and their newborns.
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OBJECTIVE: The physical and psychological benefits of exercise during pregnancy are well established. However, the impact of exercise on pain during labour and the use of epidural analgesia has been less explored. The main aim of this study was to analyse the effectiveness and safety of moderate aerobic water exercise by pregnant women on the subsequent use of epidural analgesia during labour, induction of labour, mode of delivery, and pain perception. DESIGN: A multi-centre, parallel, randomised, evaluator blinded, controlled trial in a primary care setting. SETTING: Primary care centres in a health district of a tertiary obstetric metropolitan hospital in Mallorca, Spain. PARTICIPANTS: Pregnant women (14 to 20 weeks' gestation) who had low risk of complications. METHODS: Three hundred and twenty pregnant women were randomly assigned to two groups: women who practiced moderate aquatic aerobic exercise with usual antenatal care, and those who received usual prenatal care alone. The gynaecologist, anaesthesiologist and midwife who assisted the women during labour were blinded to group allocations. Principal outcome: use of epidural analgesia during labour. Other outcomes: use of epidural analgesia before 6 cm cervical dilation, labour pain, type of delivery, time of active labour, episiotomy or perineal tear, and induction of labour. RESULTS: The exercise program did not affect the use of epidural analgesia (OR = 0.79, 95% CI = 0.44 to 1.40), vaginal delivery (OR = 1.35, 95% CI = 0.73 to 2.41), or caesarean section (OR = 0.94, 95% CI = 0.47 to 1.89). However, women in the exercise group reported less pain during labour (mean difference: -0.6, 95% CI = -1.11 to -0.09). The two groups (moderate aquatic aerobic exercise versus usual antenatal care) showed no significant differences in maternal or newborn adverse events. CONCLUSION: Aquatic aerobic exercise during pregnancy had no effect on the use of epidural analgesia during labour, whereas pain perception was lower after aquatic exercise compared to usual care in pregnancy. The intervention was safe for pregnant women and their newborns.
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Analgesia Epidural , Analgesia Obstétrica , Dolor de Parto , Trabajo de Parto , Cesárea , Ejercicio Físico , Femenino , Humanos , Recién Nacido , Dolor de Parto/terapia , Embarazo , AguaRESUMEN
The relationship between cognitive decline and androgen deprivation therapy (ADT) under luteinizing hormone-releasing hormone (LHRH) analogues is unclear, and there is a scarcity of longitudinal studies considering the interaction between cognition, depressive symptoms and sleep quality in men with prostate cancer (PCa) treated with ADT. This study aimed to determine if there were differences in the scores obtained in cognitive assessment, depressive symptoms, and sleep quality after one year of ADT and determine the interrelations between sleep, mood, and cognitive status. A prospective longitudinal observational study was designed, in which a cohort of men (mean age was 70.8 years) newly treated with androgen-deprivation therapy was assessed in the first six months of treatment and 12 months later. Analysis of cognitive function by the Mini-Mental State Examination (MMSE) scores indicated a significant (p < 0.05) increase after one year of treatment and by the Brief Scale for Cognitive Evaluation (BCog) scores indicated no changes in the scores before and after one year of treatment. Analysis of depressive symptoms with the Geriatric Depression Scale and sleep quality with the Athens Insomnia Scale (AIS) scores showed significant (p < 0.05) changes after one year of treatment with ADT, with men describing more depressive symptoms and more sleep disturbances. No statistically significant differences were found in the cognitive performance between men with impaired sleep or depression results and those without them. Our study showed no clinical evidence of the relationship between ADT under luteinizing hormone-releasing hormone (LHRH) analogues and cognitive deterioration in 1-year follow-up, but there are impairments in the sleep quality in men with PCa undergoing ADT and an increase in depressive symptoms which has important implications for clinicians as they would impair quality of life and adherence to treatment.
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Frailty syndrome is a functional state that includes a loss of ability to react to stressors, and is associated with poor outcomes, morbidity and premature mortality. The first line treatment in many men with prostate cancer (PCa) consists of an androgen-deprivation therapy (ADT) which can promote or favor frailty syndrome and ADT may therefore favor the progression of frailty over time. Among the pathophysiological bases of frailty, the presence of chronic low-grade inflammation has been associated with its adverse outcomes, but longitudinal studies are needed to validate these biomarkers. In this study, we prospectively evaluate frailty syndrome and blood inflammatory markers (IL1-beta, IL-6, IL-8, TNF alpha, C reactive protein) and leukocytes were measured at baseline and an average of 1 year later in PCa under ADT. Frailty was defined as having three or more of the following components: low lean mass, weakness, self-reported exhaustion, low activity level, and slow walking speed; prefrailty was defined as having one or two of those components. Multinomial regression analysis showed that among the inflammatory biomarkers, those significantly and repeatedly (baseline and follow-up time points) (p < 0.05) associated with frailty syndrome were high IL-6 levels and low lymphocyte counts in blood. Other biomarkers such as IL-8, monocyte counts and C reactive protein were significantly associated with frailty syndrome (p < 0.05) in cross-sectional analyses, but they do not predict frailty progression at 1 year-follow-up. Receiver operating characteristic curve analysis showed that both lymphocyte counts and IL-6 concentration significantly (p < 0.05) (although moderately) discriminate PCa patients that progressed in the severity of frailty syndrome. IL-6 and lymphocytes count are possible biomarkers, useful for identifying frail patients and predicting the progression of frailty in PCa under ADT. Our study suggests the use of these biomarkers to guide clinical decisions on prostate cancer treatment based on a multidisciplinary approach.
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OBJECTIVE Assess the impact of COVID-19 on medical students' internships in public and private institutions in Brasil, in addition to estimating the quality of the measures taken by their respective Universities in the face of the problem and the availability of personal protective equipment (PPE). METHODS A descriptive cross-sectional quantitative analysis study carried out with 317 students undergoing medical internship from March 31, 2020, to April 12, 2020. The survey was conducted through an online questionnaire using the SurveyMonkey tool with 20 questions. Interns from the fourth to the sixth year of medical schools in the country were randomly included in the study through a survey sent by Whatsapp application. Statistical analysis was performed using the Chi-Square, considering p <0.05 as significant. RESULTS Four main topics were identified in the research: student demographic data; how classes and courses are being taught; the use and ease of access to personal protective equipment and the students' fears and perspectives for the future. CONCLUSION The study clarified that although half of the students still have some degree of content and, in their majority, they are satisfied, there is still a lot of difficulty in obtaining personal protective equipment, which prevents students from returning safely to their internships.
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Infecciones por Coronavirus , Internado y Residencia , Pandemias , Neumonía Viral , Estudiantes de Medicina , Betacoronavirus , Brasil/epidemiología , COVID-19 , Infecciones por Coronavirus/epidemiología , Estudios Transversales , Humanos , Internado y Residencia/estadística & datos numéricos , Neumonía Viral/epidemiología , Investigación/tendencias , SARS-CoV-2 , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To evaluate the role of peripheral inflammation (leukocyte differential count, the proinflammatory cytokines IL-beta, TNF-α, IL-6, IL-8, and the inflammatory markers fibrinogen and C-reactive protein [CRP]) in frailty syndrome in patients with prostate cancer (CaP) undergoing antiandrogen therapy (ADT). METHODS: A total of 46 men between 51 and 92 years of age with CaP and receiving ADT were classified as frail, prefrail or robust according to the Fried scale. A geriatric assessment was performed, based on the Minimental State Examination for cognitive function, the Barthel index for basic activities of daily living, the Yesavage scale for geriatric depression, and the Athens insomnia scale. In addition, blood samples were collected to assess peripheral inflammation biomarkers including proinflammatory cytokines, fibrinogen, CRP and leukocyte differential count, as well as other biochemical and hematological parameters. RESULTS: A significant negative correlation between the severity of frailty syndrome and lymphocyte count was observed (P < 0.01). The concentration of IL-6 (P < 0.05), CRP (P < 0.05), and fibrinogen (P < 0.01) were significantly associated with frailty syndrome, but not of TNF-α, IL-beta, or IL-8. The severity of frailty syndrome was not dependent upon the clinical disease stage at diagnosis, the time elapsed since CaP diagnosis, the presence of metastases, or prostatectomy. CONCLUSIONS: Further research into the role of leukocyte subtypes and peripheral inflammation and the associated adverse outcomes in patients with CaP under ADT is warranted in order to tailor interventions aimed at reducing symptoms of frailty syndrome, such as loss of muscle strength and low physical activity.
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Antagonistas de Andrógenos/efectos adversos , Fragilidad/inmunología , Mediadores de Inflamación/sangre , Neoplasias de la Próstata/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Estudios Transversales , Fragilidad/sangre , Fragilidad/inducido químicamente , Fragilidad/diagnóstico , Evaluación Geriátrica , Humanos , Mediadores de Inflamación/inmunología , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/complicaciones , Neoplasias de la Próstata/inmunología , Índice de Severidad de la EnfermedadRESUMEN
PURPOSE: To evaluate the likelihood of preserving the breast in women who show close or positive margins after conservative surgery for early breast carcinoma. METHODS AND MATERIALS: Since 1996, 125 women with less than 5 mm or positive margins and positive separate cavity margin sampling were entered in a prospective trial with high-dose radiotherapy. A standard dose of 50 Gy to the whole breast was followed by a high-dose-rate brachytherapy application delivering 3 fractions of 4.4 Gy in 24 hours. The median follow-up was 84 months. RESULTS: There were only seven local recurrences, with an actuarial local control rate of 95.8% at 5 years and 91.1% at 9 years. Actuarial overall and cause-specific survival rates were 92.6% and 95% at 5 years and 86.7% and 90.4% at 9 years, respectively. Late fibrosis was the most common complication, in 30% of patients, with good or excellent cosmetic results in 77%. The final result was that 95.2% of breasts were preserved. CONCLUSIONS: Close or positive-margin breast cancer can be well managed with a high-dose boost in a wide tumor bed by means of high-dose-rate brachytherapy. This technique can avoid mastectomy or poor cosmetic resection, with minimal risk of local or general failure.
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Braquiterapia/métodos , Neoplasias de la Mama/radioterapia , Mama , Carcinoma Ductal de Mama/radioterapia , Mastectomía Segmentaria , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/cirugía , Carcinoma Ductal de Mama/cirugía , Terapia Combinada/métodos , Femenino , Humanos , Persona de Mediana Edad , Neoplasia Residual , Estudios Prospectivos , Tasa de SupervivenciaRESUMEN
SUMMARY OBJECTIVE Assess the impact of COVID-19 on medical students' internships in public and private institutions in Brasil, in addition to estimating the quality of the measures taken by their respective Universities in the face of the problem and the availability of personal protective equipment (PPE). METHODS A descriptive cross-sectional quantitative analysis study carried out with 317 students undergoing medical internship from March 31, 2020, to April 12, 2020. The survey was conducted through an online questionnaire using the SurveyMonkey tool with 20 questions. Interns from the fourth to the sixth year of medical schools in the country were randomly included in the study through a survey sent by Whatsapp application. Statistical analysis was performed using the Chi-Square, considering p <0.05 as significant. RESULTS Four main topics were identified in the research: student demographic data; how classes and courses are being taught; the use and ease of access to personal protective equipment and the students' fears and perspectives for the future. CONCLUSION The study clarified that although half of the students still have some degree of content and, in their majority, they are satisfied, there is still a lot of difficulty in obtaining personal protective equipment, which prevents students from returning safely to their internships.
RESUMO OBJETIVO Avaliar o impacto da Covid-19 durante o internato dos alunos de medicina em escolas públicas e particulares no Brasil, além de estimar a qualidade das medidas tomadas pelas respectivas universidades diante do agravo e da disponibilização de equipamento de proteção individual. MÉTODO Um estudo de análise quantitativa transversal, com caráter descritivo, foi realizado com 317 alunos cursando o internato médico durante o período de 31 de março de 2020 a 12 de abril de 2020. A pesquisa foi realizada por meio de um questionário on-line com 20 perguntas pela ferramenta SurveyMonkey. Os internos do 4o ao 6o ano das faculdades de medicina do País foram incluídos no estudo de forma randômica ao receberem a pesquisa pelo aplicativo WhatsApp. A análise estatística foi realizada por meio do Qui-quadrado, considerando p<0,05 como significante. RESULTADOS Quatro temas principais foram identificados na pesquisa: dados demográficos dos alunos; como as aulas e estágios do curso estão sendo ministrados; a utilização e facilidade de aquisição do equipamento de proteção individual e medos e perspectivas futuras dos estudantes. CONCLUSÕES O estudo mostrou que apesar de metade dos alunos continuarem tendo algum grau de conteúdo e, na maioria, estarem satisfeitos, ainda há muita dificuldade em se obter equipamento de proteção individual, o que impede que os alunos retornem com segurança aos seus campos de estágio, além de causar medo de contaminação e de continuar atendendo os pacientes.
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Humanos , Neumonía Viral/epidemiología , Estudiantes de Medicina , Infecciones por Coronavirus/epidemiología , Pandemias , Internado y Residencia/estadística & datos numéricos , Investigación/tendencias , Brasil/epidemiología , Estudios Transversales , Encuestas y Cuestionarios , Infecciones por Coronavirus , BetacoronavirusRESUMEN
We present 39 patients with lip carcinoma treated with HDR, (needles) with 5-5.5 Gy per 8-10 fractions b.i.d. (total dose 40.5-45 Gy). Three-year cause-specific survival and local control are 91 and 88% (95% T1-2, 74% T4, p<0.05). Acute and chronic reactions are like LDR cases. We think that HDR results are equivalent to LDR.
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Braquiterapia , Carcinoma de Células Escamosas/radioterapia , Neoplasias de los Labios/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Braquiterapia/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Traumatismos por Radiación , Dosificación RadioterapéuticaRESUMEN
PURPOSE: To compare the use of high-dose-rate (HDR) brachytherapy (BT) in patients with lip carcinoma with a former series previously treated with low-dose-rate (LDR) BT. METHODS AND MATERIALS: Ninety-nine patients treated with LDR-BT were compared with 104 patients treated with HDR-BT. Distribution by stage was 53.5% T1, 15.1% T2, 3.1% T3, and 28.3% T4 for LDR and 52.9% T1, 32.7% T2, 0% T3, and 14.4% T4 for HDR. Some cases with positive or close margins received BT after surgery (34.3% with LDR vs. 16.3% with HDR). Parallel metallic needles were used in 100% of HDR cases and in 76% of LDR cases. Most HDR patients were treated with HDR-BT to a dose of 4.5-5 Gy per fraction prescribed to a 90% isodose, in nine fractions delivered twice daily for 5 days. RESULTS: Median followup was 63 months for LDR-BT and 51 months for HDR-BT. Overall local control for LDR- vs. HDR-BT was 94.9% vs. 95.2%; and 100% vs. 100%, 86.6% vs. 94.1%, and 89.3% vs. 80%, for T1, T2, and T4 stage tumors, respectively. Disease-free survival for LDR vs. HDR was 95.9% vs. 94.2%. Soft tissue necrosis, bone necrosis, and fair-bad cosmesis for LDR vs. HDR was 15.1% vs. 0%, 1% vs. 0%, and 11.1% vs. 0%, respectively. CONCLUSIONS: Treatment with HDR-BT using rigid needles is a simple technique that provides good long-term results with minimal complications. LDR- and HDR-BT are regarded as equally effective in local control and disease-free survival, but fewer complications arise when using HDR-BT.
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Braquiterapia/métodos , Neoplasias de los Labios/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Braquiterapia/efectos adversos , Supervivencia sin Enfermedad , Relación Dosis-Respuesta en la Radiación , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Neoplasias de los Labios/mortalidad , Masculino , Persona de Mediana Edad , Traumatismos por Radiación/epidemiología , Dosificación Radioterapéutica , Estudios Retrospectivos , España/epidemiología , Tasa de SupervivenciaRESUMEN
Pharmacovigilance plays a key role in the healthcare domain through the assessment, monitoring and discovery of interactions amongst drugs and their effects in the human organism. However, technological advances in this field have been slowing down over the last decade due to miscellaneous legal, ethical and methodological constraints. Pharmaceutical companies started to realize that collaborative and integrative approaches boost current drug research and development processes. Hence, new strategies are required to connect researchers, datasets, biomedical knowledge and analysis algorithms, allowing them to fully exploit the true value behind state-of-the-art pharmacovigilance efforts. This manuscript introduces a new platform directed towards pharmacovigilance knowledge providers. This system, based on a service-oriented architecture, adopts a plugin-based approach to solve fundamental pharmacovigilance software challenges. With the wealth of collected clinical and pharmaceutical data, it is now possible to connect knowledge providers' analysis and exploration algorithms with real data. As a result, new strategies allow a faster identification of high-risk interactions between marketed drugs and adverse events, and enable the automated uncovering of scientific evidence behind them. With this architecture, the pharmacovigilance field has a new platform to coordinate large-scale drug evaluation efforts in a unique ecosystem, publicly available at http://bioinformatics.ua.pt/euadr/.
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Interacciones Farmacológicas , Internet , Farmacovigilancia , Programas Informáticos , Femenino , Humanos , MasculinoRESUMEN
PURPOSE: We present the results of a prospective ten-year follow-up study to prove the effectiveness of a single fraction of 192-Ir high-dose-rate (HDR) brachytherapy (BT) as a boost. PATIENTS AND METHODS: Between 1999 and 2000, 84 consecutive patients with invasive breast carcinoma, with over 4 mm free margins after conservative surgery, were treated. All cases were stages T1-2, except for one case, a stage T3, 81% pN0, 19% pN1-2. Chemotherapy was used in 47% and hormonal therapy in 87%. Whole breast external beam radiotherapy (46 Gy) was followed 1-2 weeks later by an implant with metallic needles. A 7 Gy single dose of HDR BT to the 90% isodose line was delivered on an outpatient basis. Dosimetry was performed theoretically. This technique is called FAST-boost because the whole treatment is delivered in about two hours. RESULTS: With a median follow-up of 120 months, three patients relapsed in the margin of the implant and two in a different quadrant (5/84, 6%). Actuarial local control at five and ten years was 98.5% and 95.6%. Overall survival was 92.7% and 90.2%, and disease-free survival 90.2% and 79.9%. Cosmetic results were good or excellent in 92.5%. CONCLUSIONS: A single-fraction HDR boost with rigid needles (FAST-boost) is a good, quick, simple technique when surgical margins are free.
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Braquiterapia , Neoplasias de la Mama/radioterapia , Carcinoma Ductal de Mama/radioterapia , Carcinoma Lobular/radioterapia , Carcinoma Papilar/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/mortalidad , Carcinoma Ductal de Mama/patología , Carcinoma Lobular/mortalidad , Carcinoma Lobular/patología , Carcinoma Papilar/mortalidad , Carcinoma Papilar/patología , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Dosificación Radioterapéutica , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
The degree of applicability of chemogenomic approaches to protein families depends on the accuracy and completeness of pharmacological data and the corresponding level of pharmacological similarity observed among their protein members. The recent public domain availability of pharmacological data for thousands of small molecules on 204 G protein-coupled receptors (GPCRs) provides a firm basis for an in-depth cross-pharmacology analysis of this superfamily. The number of protein targets included in the cross-pharmacology profile of the different GPCRs changes significantly upon varying the ligand similarity and binding affinity criteria. However, with the exception of muscarinic receptors, aminergic GPCRs distinguish themselves from the rest of the members in the family by their remarkably high levels of pharmacological similarity among them. Clusters of non-GPCR targets related by cross-pharmacology with particular GPCRs are identified and the implications for unwanted side-effects, as well as for repurposing opportunities, discussed.
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Descubrimiento de Drogas/métodos , Receptores Acoplados a Proteínas G/química , Bases de Datos Factuales , Diseño de Fármacos , Genómica , Humanos , Ligandos , Farmacología , Receptores Acoplados a Proteínas G/antagonistas & inhibidores , Receptores Acoplados a Proteínas G/metabolismoRESUMEN
La papulosis bowenoide es un carcinoma espinocelular in situ de bajo grado que se observa mayormente en genitales. El agente etiológico es el virus del papiloma humano. Existen múltiples opciones terapéuticas médicas y quirúrgicas pero debería ser tratado de forma conservadora. Presentamos dos casos de papulosis bowenoide tratados exitosamente con crioterapia (AU)
Bowenoid papulosis is a low grade squamous cell in situ carcinoma. It is usually seen in genitals. Etiologic agent is the human papilloma virus. There are many treatments available but it should be treated conservatively. Two cases of bowenoid papulosis with good response to cryotherapy are reported (AU)
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Humanos , Masculino , Adulto , Papillomaviridae/patogenicidad , Neoplasias del Pene/etiología , Carcinoma in Situ/diagnóstico , Terapéutica , CrioterapiaRESUMEN
BACKGROUND: The main treatment given for initial stage facial epitheliomas is surgery, although there are alternatives. We present our results with Ir-192 high-dose rate (HDR) contact brachytherapy. METHODS AND MATERIALS: Fifty-one epitheliomas, with a mean size of 1.5 cm and a maximum thickness of 3mm, were treated with HDR contact brachytherapy by means of customized molds, with plastic tubes on bolus for flat surfaces and on wax molds for the nose. A total dose of 48-57 Gy, 3-4 Gy/fraction three times a week, was administered. RESULTS: After a median followup of 45 months, five tumors relapsed (9.8%), four of them on the tip of the nose. The 5-year actuarial local control rate was 89%, 100% for flat surfaces, and 83% for the nose. All of them were salvaged with surgery. The treatment was well tolerated, 21.6% developed severe acute toxicity, with good or very good late cosmetic results. CONCLUSION: HDR contact brachytherapy is a good alternative to treat facial epitheliomas with a maximum thickness of 3mm. Tip of the nose tumors are not well covered with this technique and a different procedure is required.
Asunto(s)
Braquiterapia/instrumentación , Braquiterapia/métodos , Neoplasias Faciales/radioterapia , Neoplasias Cutáneas/radioterapia , Anciano , Anciano de 80 o más Años , Diseño de Equipo , Análisis de Falla de Equipo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
PURPOSE: To evaluate the results of high-dose-rate (HDR)-interstitial brachytherapy (ISBT) in oral tongue carcinomas. METHODS AND MATERIALS: Between September 1999 and August 2007, 50 patients were treated for oral tongue carcinoma with HDR-ISBT. The patient's mean age was 58 years. Forty-two patients were in T1-2 stage and 8 patients were in T3 stage; 16 patients were in N+ stage and 34 patients in N0 stage. Exclusive ISBT was given to 17 patients (34%) in T1-2 N0 stage and complementary to external beam radiotherapy (EBRT) to 33 patients (66%). A perioperative technique was performed on 14 patients. The median total dose was 44 Gy when HDR was used alone (4 Gy per fraction) and 18 Gy when complementary to 50 Gy EBRT (3 Gy per fraction). RESULTS: The median followup was 44 months. Actuarial disease-free survival rates at 3 and 5 years were 81% and 74%, respectively. Local failure developed in 7 patients. Actuarial local control (LC) rates were 87% and 79% at 3 and 5 years in T1-2 stage 94.5% and 91% and T3 stage 43% and 43% (with salvage surgery). Exclusive HDR cases showed LC in 100% of the cases, and the combined group (EBRT+HDR) showed LC in 80% and 69% of the cases at 3 and 5 years (p=0.044). Soft-tissue necrosis developed in 16% and bone necrosis in 4% of the cases. CONCLUSIONS: HDR brachytherapy is an effective method for the treatment of oral tongue carcinoma in low-risk cases. Doses per fraction between 3 and 4 Gy yield LC and complication rates similar to low-dose rate. The perioperative technique promises encouraging results.