Understanding treatment goals and their application in clinical trial design for patients with Alzheimer disease and caregivers.

Background: As research continues towards improved treatments for Alzheimer disease (AD), there is growing interest in the views and needs from patients and caregivers on AD treatments. Methods: In this study, we surveyed patients with AD and caregivers to determine the treatment goals that are most important to them. Patients with AD and caregivers were independently recruited in Europe and North America to complete a web-based survey. Eligible participants were ≥18 years old and diagnosed with mild cognitive impairment or mild-to-moderate AD (patient-reported group) or persons involved in the care of patients with AD (caregiver-reported group). A total of 322 patients and 614 caregivers completed the survey. Results: The demographic characteristics of patients in the patient-reported and the caregiver-reported groups were similar. Disease severity of patients was greater in the caregiver-reported group compared with the patient-reported group (72.1% versus 46.9% moderate AD). The most important goal of AD treatment in both groups was maintenance of quality of life (QoL) (patient-reported group 31.1% and caregiver-reported group 38.8%; p=0.01). This was consistent across disease stages or symptom severity except for patients with mild cognitive impairment in the caregiver-reported group where slowing the progression of memory loss was the most important treatment goal. Conclusions: Patient QoL was consistently the most relevant treatment goal for patients with AD and caregivers. In AD clinical trials, patient-relevant outcomes, for example, QoL, should be given high priority to reflect the needs and demands of patients with AD and their caregivers.A preliminary report of this work was presented at the 14th Clinical Trials on Alzheimer's Disease meeting (November 9-12, 2021).

Application of a Novel Endpoint Staging Framework: Proof of Concept in the AMBAR Study.

Background: A theoretical endpoint staging framework was previously developed and published, aligning outcomes (i.e., memory) to the stage of Alzheimer's disease (AD) in which a given outcome is most relevant (i.e., has the greatest risk of degradation). The framework guides the selection of endpoints measuring outcomes relevant within a target AD population. Here, a proof of concept is presented via post-hoc analyses of the Alzheimer Management by Albumin Replacement (AMBAR) Phase 2b clinical trial in patients with AD (NCT01561053, 2012). Objective: To evaluate whether aligning endpoints measuring cognition, function, and quality of life to hypothesized 'target' stages of AD yields magnitudes of treatment efficacy greater than those reported in the AMBAR full analysis set (FAS). Methods: Three endpoints were tested: ADAS-Cog 12, ADCS-ADL, and QoL-AD. The magnitude of treatment efficacy was hypothesized to be maximized in the target stages of mild, mild-to-moderate, and very mild AD, respectively, compared to the full analysis set (FAS) and non-target stages. Results: For ADAS-Cog 12, the magnitude of treatment efficacy was largest in the non-target stage (-4.0, p = 0.0760) compared to target stage and FAS. For ADCS-ADL and QoL-AD, the magnitude of treatment efficacy was largest in the target stage (14.2, p = 0.0003; 2.4, p < 0.0001, respectively) compared to non-target stage and FAS. Conclusions: Findings indicated that evaluating endpoints in the most relevant AD stage can increase the magnitude of the observed treatment efficacy. Evidence provides preliminary proof of concept for the endpoint staging framework.

Toward the optimized assessment of clinical outcomes in studies of novel treatments for Alzheimer's disease.

INTRODUCTION: Alzheimer's disease (AD) is characterized by a progressive decline in cognition and daily function, leading to a greater need for caregiver support. Clinical disease is segmented into a preclinical stage, mild cognitive impairment, and mild, moderate, and severe stages of Alzheimer's dementia. Although AD trials enroll participants at various stages of illness, treatment efficacy is often assessed using endpoints based on measures of outcomes that are held fixed across disease stages. We hypothesize that matching the primary outcomes measured in the endpoint hierarchy to the stage of disease targeted by the trial will increase the likelihood of detecting true treatment benefits. AREAS COVERED: We discuss current approaches to assessing clinical outcomes in AD trials, followed by a consideration of how effect detection can be improved by linking the stage of AD to the endpoints that most likely reflect stage-specific disease progression. EXPERT OPINION: Failing to account for stage-specific relevance and sensitivity of clinical outcomes may be one factor that contributes to trial failures in AD. Given the history of failure, experts have begun to scrutinize the relevance and sensitivity of outcomes as a potentially modifiable barrier to successful trials. To this end, we present a framework for refining trial endpoint selection and evaluation.

The BROADEN study: The design of an observational study to assess the absolute burden of HPV-related head and neck cancers.

BACKGROUND: Persistent human papillomavirus (HPV) infection is an important risk factor for a subset of head and neck cancers (HNCs). However, estimates of the HPV-attributable fraction of oropharyngeal cancers vary greatly, and the proportion is increasing. Growing evidence indicates smaller proportions of oral cavity and laryngeal cancers are also HPV-attributable, but this requires further investigation. The primary objective of the BROADEN study is to estimate the fraction of HNCs attributable to HPV in selected European and Asian countries by anatomic site. Secondary objectives are to determine HPV genotypes involved and to describe primary tumor and patient characteristics by HPV status. METHODS: BROADEN is a non-interventional, cross-sectional study of patients with HNC in China, France, Germany, Italy, Japan, Portugal, and Spain. The HPV-attributable HNC fraction will be determined within pre-defined time-periods (2008-2009, 2013-2014 [China only], 2018-2019). Approximately 9000 patients from an estimated 90 hospitals with reference HNC diagnostic units and local reference pathology laboratories will participate. Sample size estimates were generated by grouped anatomic site (oropharynx, oral cavity, nasopharynx, hypopharynx, and larynx) and country. HPV testing (HPV-DNA and p16 immunohistochemistry [IHC]) will be performed at a central laboratory on formalin-fixed paraffin-embedded tissue samples. All HPV-DNA-positive samples and HPV-DNA-negative/p16 IHC-positive samples, plus 10% of remaining HPV DNA-negative (control) samples will be tested for HPV mRNA. DISCUSSION: BROADEN is a large global epidemiologic study to estimate current and recent past HPV burden in oropharyngeal and non-oropharyngeal HNCs. BROADEN is expected to provide robust estimates of HPV attributability by anatomic site in participating countries.

Complicated carbapenem-resistant infections: a treatment pathway analysis in Italian sites.

INTRODUCTION: Efforts to curb a growing prevalence of carbapenem resistance are prominent worldwide and especially in countries where high levels of carbapenem resistance are reported, such as Italy. Complicated infections, including complicated urinary tract infections (cUTI), complicated intra-abdominal infections (cIAI), and hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP), are often caused by carbapenem-resistant Gram-negative (CRGN) bacteria and as such, these infection sites and their causative bacteria are important areas of focus for healthcare practitioners seeking to follow good antimicrobial stewardship practices. The aim of this study was to assess the clinical management and associated clinical and economic outcomes of patients with cUTI, cIAI, and HABP/VABP resulting from CRGN bacteria in Italy. METHODS: We first conducted a hospital survey focusing on Gram-negative infections and their antibacterial susceptibility profile in four participating Italian hospitals. The second part of the study involved a non-interventional, retrospective single cohort chart review of 100 patients with cUTI, cIAI, or HABP/VABP caused by CRGN bacteria, in which patient characteristics, index hospitalization characteristics, infection characteristics, patient outcomes, treatment pathways, and healthcare resource use were assessed. RESULTS: The hospital survey demonstrated carbapenem resistance in approximately 17% of complicated infections, mostly associated with Acinetobacter baumannii. The non-interventional, retrospective cohort component showed that complicated CRGN infections were hospital- or healthcare-acquired in 99.0% of cases and were most often caused by Klebsiella pneumoniae (66.0%). Despite the carbapenem-resistant nature of the included infections, carbapenems were used in 19.0% of patients as empirical therapy, in 43.0% as late empirical (i.e. immediately before receipt of susceptibility test results), and in 64.0% as targeted therapy (post-susceptibility test result receipt). Colistin was used in 61.0% of patients after susceptibility results were available. High clinical and economic burden was evident, with the average length of hospital stay being greater than 50 days, clinical cure achievement in only 43.0% of patients, and an overall mortality rate of 65.0% by the end of the follow-up period. CONCLUSION: Our results reflect the considerable burden associated with complicated CRGN infections in Italy and the limitations in current treatment strategies. Our study pinpoints potential areas for improvement. For example, regular and detailed local surveillance and state of the art microbial diagnostic capabilities might aid and hasten clinical decision-making and facilitate improved antimicrobial stewardship when treating complex CRGN infections. New therapeutic options which more appropriately address CRGN infections may assist in improving outcomes which are important to both patients and healthcare providers.

Real-world treatment patterns, healthcare resource use and clinical outcomes of patients receiving second line therapy for advanced or metastatic gastric cancer.

BACKGROUND: Second-line (2 L) chemotherapies for advanced or metastatic gastric cancer have shown improved survival but there is no commonly accepted standard of care. This study examines real-world patient characteristics, treatment patterns, healthcare resource use (HCRU) and clinical outcomes in this setting. METHODS: Retrospective chart reviews were performed at participating institutions from Australia, Canada, Italy and UK for adult patients receiving 2 L treatment for advanced/metastatic disease from January 2013 to July 2015. Data were collected for 12 months or until death. RESULTS: Two hundred eighty patients were included, mean age was 60.9 years and 68.9% were male. Half (51.8%) received monotherapy in 2 L, of whom 69.0% received taxanes. Irinotecan monotherapy was common in Australia (30.0% of monotherapy patients) and Canada (43.8%), but infrequent in Italy and UK. Doublet chemotherapy was used in 36.4% of 2 L patients, most commonly fluoropyrimidine + irinotecan. Use of targeted therapies (trastuzumab, ramucirumab) was infrequent except in Italy. Estimated median real-world progression-free survival (rwPFS) and real-world overall survival (rwOS) from the time of 2 L treatment initiation was 3.09 (95% CI: 2.76-3.68) and 6.54 (5.29-7.76) months, respectively, and estimated 12-month rwPFS and rwOS rate was 8 and 26%, respectively. Only a minority (26.8%) of patients were hospitalized during the follow-up period, with the lowest hospitalization in Italy (16.7%). Laboratory and imaging tests were performed for 93.2 and 70.4%, respectively. CONCLUSIONS: About half of patients received monotherapy as 2 L chemotherapy for advanced/metastatic gastric cancer and a third received doublets. Real-world clinical outcomes for 2 L treatment are poor and HCRU is considerable.

[Anthropometric characteristics and functional fitness of Chilean community-dwelling older adults]. / Características antropométricas y condición física funcional de adultos mayores chilenos insertos en la comunidad.

INTRODUCTION: Anthropometry and functional fitness (FF) are fundamental aspects for functional independence conservation of older adults (OA). However, little has been investigated in chilean OA. OBJECTIVE: To analyze anthropometric and FF characteristics of non-disabled OA. METHODS: One hundred and sixteen subjects participated in the study. It was determined the prevalence of weight categories (Body Mass Index [BMI]) and cardiometabolic risk (CMR) (Waist Circumference [WC], Waist-Hip Ratio [WHR] and Waist-to-Height ratio [WHtR]). Additionally, "under the norm" physical performance and performance standards (Senior Fitness Test Battery [SFT]). Anthropometric and FF differences were analyzed according sex and age categories. RESULTS: A total of 63.8% and 73.5% of men and women respectively were overweight. The highest prevalence of CMR was obtained through WHtR and the tests with the highest prevalence of low performance were 2-minute step Test and Back scratch Test. The performance standard was reached in 29.7% and 17.3%, in men and women respectively. Men presented greater height, WHR, strength and aerobic capacity. Women had greater hip circumference, BMI, WHtR and flexibility. These results tends to be maintained in the analyzes according age categories. CONCLUSIONS: The studied sample presented a high prevalence of overweight, CMR and low physical performance especially in women. Due its low cost and complexity, it is proposed that integral evaluation of anthropometric and FF parameters should be implemented in primary care programs aimed to preserving functionality of OA.

Características antropométricas y condición física funcional de adultos mayores chilenos insertos en la comunidad / Anthropometric characteristics and functional fitness of Chilean community-dwelling older adults

Introducción: la antropometría y condición física funcional (CFF) son aspectos fundamentales para la conservación de la independencia funcional del adulto mayor (AM). Sin embargo, poco se ha investigado en AM chilenos. Objetivo: analizar características antropométricas y CFF de AM autovalentes. Métodos: participaron 116 sujetos del estudio. Se determinó la prevalencia de categorías de peso (índice de masa corporal [IMC]) y riesgo cardiometabólico (RCM) (perímetro de la cintura [PCIN], índice cintura-cadera [ICC] e índice cintura-talla [ICT]). Además, rendimiento físico «bajo la norma» y estándares de rendimiento (Batería Senior Fitness Test [SFT]). Se analizaron las diferencias antropométricas y de CFF en función del sexo y categorías etarias. Resultados: un 63,8% y 73,5% de hombres y mujeres respectivamente presentó exceso de peso. La mayor prevalencia de RCM se obtuvo mediante ICT y las pruebas con mayor prevalencia de bajo rendimiento fueron «Paso 2 minutos» (P2M) y «Juntar las manos detrás de la espalda» (JME). El estándar de rendimiento se alcanzó en un 29,7% y 17,3%, en hombres y mujeres respectivamente. Hombres presentaron mayor talla, ICC, fuerza y capacidad aeróbica. Mujeres presentaron mayor perímetro de cadera, IMC, ICT y flexibilidad. Estos resultados tienden a conservarse en los análisis de acuerdo a categorías etarias. Conclusiones: la muestra presentó una alta prevalencia de exceso de peso, RCM y bajo rendimiento físico, especialmente en mujeres. Debido a su bajo costo y complejidad, se plantea que la evaluación integral de parámetros antropométricos y de CFF debiese implementarse en programas de atención primaria orientados a la conservación de la funcionalidad del AM (AU)

Introduction: Anthropometry and functional fitness (FF) are fundamental aspects for functional independence conservation of older adults (OA). However, little has been investigated in chilean OA. Objective: To analyze anthropometric and FF characteristics of non-disabled OA. Methods: One hundred and sixteen subjects participated in the study. It was determined the prevalence of weight categories (Body Mass Index [BMI]) and cardiometabolic risk (CMR) (Waist Circumference [WC], Waist-Hip Ratio [WHR] and Waist-to-Height ratio [WHtR]). Additionally, «under the norm» physical performance and performance standards (Senior Fitness Test Battery [SFT]). Anthropometric and FF differences were analyzed according sex and age categories. Results: A total of 63.8% and 73.5% of men and women respectively were overweight. The highest prevalence of CMR was obtained through WHtR and the tests with the highest prevalence of low performance were 2-minute step Test and Back scratch Test. The performance standard was reached in 29.7% and 17.3%, in men and women respectively. Men presented greater height, WHR, strength and aerobic capacity. Women had greater hip circumference, BMI, WHtR and flexibility. These results tends to be maintained in the analyzes according age categories. Conclusions: The studied sample presented a high prevalence of overweight, CMR and low physical performance especially in women. Due its low cost and complexity, it is proposed that integral evaluation of anthropometric and FF parameters should be implemented in primary care programs aimed to preserving functionality of OA (AU)

Systematic Review of Tumor Necrosis Factor Antagonists in Extraintestinal Manifestations in Inflammatory Bowel Disease.

BACKGROUND & AIMS: This systematic review investigated the efficacy and the effectiveness of biologic drugs in extraintestinal manifestations (EIMs) in inflammatory bowel disease (IBD). METHODS: Literature search was conducted in PubMed, Embase, and Cochrane until October 2015. Main inclusion criteria were adults with IBD, use of a biologic drug, evolution of EIMs, interventional study, or non-interventional study. RESULTS: Nine interventional studies (2 randomized controlled trials [N = 797], 7 open label trials [N = 1143], and 13 non-interventional studies [N = 914]) were included. Tumor necrosis factor (TNF) antagonists achieved complete response for pyoderma gangrenosum in 21%-25% of patients in interventional studies and in 92%-100% patients in non-interventional studies, with similar results for other cutaneous manifestations such as erythema nodosum or stomatitis. Adalimumab significantly reduced the prevalence of anemia vs placebo after 56 weeks in 1 randomized controlled trial. In 2 non-interventional studies, anti-TNF therapy improved anemia in the short-term (67%) and in the long-term (34%). Complete response after anti-TNF treatment was reported in interventional studies, including arthralgia (reduction in prevalence from 47.1% to 26.8% in the mid-term in 1 open label trial) and arthritis (reduction in prevalence from 8.7% to 2.1% and from 58% to 12.5% in 2 open label trials). Anti-TNFs were beneficial for a majority of patients with ocular manifestations. Infliximab was associated with improved outcomes in bone formation and bone mineral density. CONCLUSIONS: Anti-TNFs appear to be effective alternatives for certain EIMs associated with IBD including musculoskeletal, cutaneous, and ocular manifestations, and some beneficial effect may be obtained in metabolic bone disease and on hematologic or vascular EIMs.

[Duration of the Reimbursement Process in Spain for Innovative Drugs Approved by the European Medicines Agency during the Period 2008-2013]. / Duración del proceso de financiación en España de los fármacos innovadores aprobados por la Agencia Europea del Medicamento: 2008-2013.

BACKGROUND: In Spain, the decision of Price and Reimbursement (P&R) of a new drug must be taken between 180-270 days. The objective of this study was to assess the reimbursement timing in Spain for innovative drugs approved by the European Medicines Agency (EMA) between January 2008 and December 2013 and to explore the potential impact of drug's price on this time. METHODS: Drugs approved were extracted from EMA's website, authorization dates in Spain from the Spanish Agency (AEMPS) and, P&R dates and prices from Nomenclátor and BotPlus. Depending on days from approval to reimbursement, drugs were quick (<180), on time (180-270) and delayed (>270). Depending on posology: chronic or acute. Depending on dispensing conditions: retail or hospital drugs. It was calculated: median, maximum, minimum, first, and third quartiles of time until reimbursement. RESULTS: 431 drugs were approved by EMA; 285 were innovative, from them 147 were approved by the AEMPS and reimbursed: 103 chronic and 44 acute. Median price/day was €2.44 for chronic and €21 for acute. From 2008-2011, 80% of drugs were reimbursed, in 2012 21% and in 2013 17%. Time from approval to reimbursement move from 230 days in 2009 to 431 days in 2013. From the 139 drugs with reimbursement date 33 were quick, 44 on time and 62 delayed. CONCLUSIONS: The median time from approval by the EMA of innovative drugs since the reimbursement in Spain in 2013 is double that of 2008. The main driver of delays in the process of P&R seems to be the budget impact of the drug instead of its unit price.

Duración del proceso de financiación en España de los fármacos innovadores aprobados por la Agencia Europea del Medicamento. 2008-2013 / Duration of the reimbursement process in Spain for innovative drugs approved by the European Medicines Agency during the period 2008-2013

Fundamentos: En España la decisión de precio y financiación (PyF) de un nuevo medicamento debe tomarse entre 180 y 270 días. El objetivo de este estudio fue valorar el tiempo hasta la financiación en España de los medicamentos innovadores aprobados por la Agencia Europea de Medicamentos (EMA) entre enero 2008 y diciembre 2013 y explorar el impacto potencial del precio del fármaco sobre este tiempo. Métodos: Los medicamentos aprobados se obtuvieron de la web de la EMA, las fechas de autorización de la Agencia Española del Medicamento (AEMPS) y las fechas del PyF y los precios del Nomenclátor y BotPlus. Según los días desde la aprobación hasta la financiación se clasificó a los medicamentos en rápidos (<180), en plazo (180-270) y con demora (>270). Según la duración del tratamiento en crónicos o agudos. Y según las condiciones de dispensación: de farmacia u hospital. Del tiempo transcurrido hasta la financiación, se calculó la mediana, el máximo, el mínimo así como el primer y tercer cuartiles. Resultados: Durante el período de estudio fueron aprobados por la EMA 431 medicamentos, de los cuales 285 eran innovadores. De estos 147 fueron aprobados por la AEMPS y financiados: 103 para tratamientos crónicos y 44 para agudos. La mediana del precio/día fue de 2,44€ para crónicos y 21€ para agudos. De 2008-2011 fueron financiados el 80% , en 2012 el 21% y en 2013 el 17%. El tiempo hasta la financiación pasó de 230 días en 2009 a 431 en 2013. Los 139 medicamentos con fecha de financiación fueron: 33 rápidos, 44 en plazo y 62 con demora. Conclusiones: La mediana del tiempo desde la aprobación por la EMA de los medicamentos innovadores hasta su financiación en España en 2013 es el doble que en 2008. El motor principal de los retrasos en el proceso de PyF parece ser el impacto presupuestario del fármaco más que su precio unitario (AU)

Background: In Spain, the decision of Price and Reimbursement (P&R) of a new drug must be taken between 180-270 days. The objective of this study was to assess the reimbursement timing in Spain for innovative drugs approved by the European Medicines Agency (EMA) between January 2008 and December 2013 and to explore the potential impact of drug’s price on this time. Methods: Drugs approved were extracted from EMA’s website, authorization dates in Spain from the Spanish Agency (AEMPS) and, P&R dates and prices from Nomenclátor and BotPlus. Depending on days from approval to reimbursement, drugs were quick (<180), on time (180-270) and delayed (>270). Depending on posology: chronic or acute. Depending on dispensing conditions: retail or hospital drugs. It was calculated: median, maximum, minimum, first, and third quartiles of time until reimbursement. Results: 431 drugs were approved by EMA; 285 were innovative, from them 147 were approved by the AEMPS and reimbursed: 103 chronic and 44 acute. Median price/day was €2.44 for chronic and €21 for acute. From 2008-2011, 80% of drugs were reimbursed, in 2012 21% and in 2013 17%. Time from approval to reimbursement move from 230 days in 2009 to 431 days in 2013. From the 139 drugs with reimbursement date 33 were quick, 44 on time and 62 delayed. Conclusions: The median time from approval by the EMA of innovative drugs since the reimbursement in Spain in 2013 is double that of 2008. The main driver of delays in the process of P&R seems to be the budget impact of the drug instead of its unit price (AU)

Estudio comparado de la intensidad de entrenamiento sobre la máxima tasa de oxidación de grasas / Effect of training intensity on the fat oxidation rate

Introducción: El ejercicio físico es un importante modulador de la máxima tasa de oxidación de grasas (MFO). Sin embargo, en la relación MFO-ejercicio, las zonas de transición metabólica en la prescripción del ejercicio no son consideradas. Objetivo: Conocer el efecto del entrenamiento en diferentes zonas de transición metabólica sobre la cinética de la MFO y su localización (Fatmax) en jóvenes varones activos. Método: 97 varones fueron distribuidos en 4 grupos homogéneos, 3 experimentales y un grupo control (GC). Cada grupo experimental participó en 8 semanas de entrenamiento administrado de forma continua a intensidad de umbral aeróbico o VT1 (CCVT1), interválica en umbral anaeróbico o VT2 (ITVT2), y en potencia aeróbica máxima o VO2max (ITVO2max). Antes y después del tratamiento los sujetos fueron testados en sendas pruebas con control de gases espirados para determinar el VO2max, VT1 y VT2, y la MFO (calorimetría indirecta) y Fatmax. Resultados: Los resultados muestran un incremento (entre 16,49 y 18,51%; p<0,01) en la MFO en los grupos experimentales. La Fatmax se redujo de media del 60,72±10,52 al 52,35±7,61 %VO2max (p<0,01) por efecto del entrenamiento. El grupo control no experimentó cambios de interés. El análisis intergrupo no presentó diferencias entre los grupos experimentales en ambas variables, sin embargo la comparación contra el GC, reflejó un mayor descenso de la Fatmax en CCVT1 (p<0,05). No se registraron cambios en el rendimiento, salvo un descenso del VO2max en el GC (p<0,05). Conclusión: 8 semanas de entrenamiento de diferente intensidad incrementan la MFO y reducen la Fatmax (AU)

Introduction. Physical exercise is a key modulator of the maximum fat oxidation rate (MFO). However, the metabolic transition zones in the MFO-exercise relationship are not generally considered for training prescription. Objective. To examine the effects of training in different metabolic transition zones on the kinetics of MFO and its localization (Fatmax) in young physically active men. Methods. 97 men were divided into 4 similar sized groups, 3 experimental groups and a control group (CG). Subjects in each experimental group undertook an 8-week running program. Training was continuous at the intensity of the aerobic threshold or VT1 (CCVT1); or performed as intervals at the intensity of the anaerobic threshold or VT2 (ITVT2); or at maximum aerobic power VO2max (ITVO2max). Before and after the training intervention, expired gases were monitored in each subject to determine VO2max, VT1, VT2, MFO (by indirect calorimetry) and Fatmax. Results. In response to training, experimental groups showed an increase in MFO (from 16,49 to 18,51%; p<0,01) and a mean reduction in Fatmax of 60,72±10,52 to 52,35±7,61 %VO2max (p<0,01). No changes of interest were observed in the control subjects. Intergroup comparisons revealed no differences in MFO and Fatmax among the experimental groups, though compared to the CG, a greater reduction in Fatmax was observed in CCVT1 (p<0,05). No changes were detected in performance except a drop in VO2max in the GC (p<0,05). Conclusion. 8 weeks of training led to an increase in MFO and reduction in Fatmax irrespective of training Intensity (AU)

Giant undifferentiated oropharyngeal sarcoma: a case report and review of the literature.

We report on a patient who presented to the Ear, Nose and Throat (ENT) clinic with swelling of the neck, dysphagia, headache, dyspnea and stridor. Imaging studies revealed an expansive heterogeneous process to the left retropharyngeal region. The mass was ovoid in shape, displaying moderate enhancement after intravenous contrast administration. Subsequently, a biopsy revealed the presence of undifferentiated sarcoma. The patient was treated with chemotherapy followed by radiation therapy, but follow-up exams at 6 months posttreatment revealed that while the tumor was stable, it persisted. Consequently, the patient was enrolled in a palliative care and pain control program and is currently being followed.

Mandibular central mucoepidermoid carcinoma: a case report and review of the literature.

We report the case of a patient whose main complaint was swelling on the right side of the mandible when he presented to the Ear, Nose and Throat (ENT) Service. Imaging studies revealed a large homogeneous, multilocular, expansive lesion in the body of the right mandibular ramus. The lesion was poorly enhanced following intravenous contrast injection. The patient was treated with hemimandibular surgical resection, fibula free flap reconstruction and adjuvant radiotherapy. Currently, the patient is disease free and free of posttreatment complications.

Orbito-ethmoidal rhabdomyosarcoma in an adult patient: a case report and review of the literature.

We report a patient who presented to the ENT service complaining of nasal obstruction, exophthalmos, edema and ipsilateral facial congestion. Imaging studies revealed an aggressive noncalcified solid mass centered in the left nasoethmoidal region and heterogeneous avid enhancement following contrast media injection. Subsequently, a biopsy confirmed the presence of solid alveolar rhabdomyosarcoma. The patient was treated with chemoradiation therapy for 7 weeks. Due to the advanced stage of the disease, the patient was enrolled in a palliative care and pain control program.

Oncocytoma of the parotid gland: a case report and review of the literature.

We report the case of a patient who presented to the ENT service with left facial swelling of 5 months duration. Imaging studies revealed a dense expansive mass confined to the inside of the left deep parotid lobule and moderate enhancement following contrast media injection. Subsequently, a biopsy confirmed the presence of an oncocytoma. The patient was treated with total parotidectomy, complete tumor resection and sparing facial nerve surgery. Today, the patient is disease free and has no complications.

[Effect of training intensity on the fat oxidation rate]. / Estudio comparado de la intensidad de entrenamiento sobre la máxima tasa de oxidación de grasas.

INTRODUCTION: Physical exercise is a key modulator of the maximum fat oxidation rate (MFO). However, the metabolic transition zones in the MFO-exercise relationship are not generally considered for training prescription. Objective. To examine the effects of training in different metabolic transition zones on the kinetics of MFO and its localization (Fatmax) in young physically active men. METHODS: 97 men were divided into 4 similar sized groups, 3 experimental groups and a control group (CG). Subjects in each experimental group undertook an 8-week running program. Training was continuous at the intensity of the aerobic threshold or VT1 (CCVT1); or performed as intervals at the intensity of the anaerobic threshold or VT2 (ITVT2); or at maximum aerobic power VO2max (ITVO2max). Before and after the training intervention, expired gases were monitored in each subject to determine VO2max, VT1, VT2, MFO (by indirect calorimetry) and Fatmax. RESULTS: In response to training, experimental groups showed an increase in MFO (from 16,49 to 18,51%; p<0,01) and a mean reduction in Fatmax of 60,72±10,52 to 52,35±7,61 %VO2max (p<0,01). No changes of interest were observed in the control subjects. Intergroup comparisons revealed no differences in MFO and Fatmax among the experimental groups, though compared to the CG, a greater reduction in Fatmax was observed in CCVT1 (p<0,05). No changes were detected in performance except a drop in VO2max in the GC (p<0,05). CONCLUSION: 8 weeks of training led to an increase in MFO and reduction in Fatmax irrespective of training intensity.

Introducción: El ejercicio físico es un importante modulador de la máxima tasa de oxidación de grasas (MFO). Sin embargo, en la relación MFO-ejercicio, las zonas de transición metabólica en la prescripción del ejercicio no son consideradas. Objetivo: Conocer el efecto del entrenamiento en diferentes zonas de transición metabólica sobre la cinética de la MFO y su localización (Fatmax) en jóvenes varones activos. Método: 97 varones fueron distribuidos en 4 grupos homogéneos, 3 experimentales y un grupo control (GC). Cada grupo experimental participó en 8 semanas de entrenamiento administrado de forma continua a intensidad de umbral aeróbico o VT1 (CCVT1), interválica en umbral anaeróbico o VT2 (ITVT2), y en potencia aeróbica máxima o VO2max (ITVO2max). Antes y después del tratamiento los sujetos fueron testados en sendas pruebas con control de gases espirados para determinar el VO2max, VT1 y VT2, y la MFO (calorimetría indirecta) y Fatmax. Resultados: Los resultados muestran un incremento (entre 16,49 y 18,51%; p.

Intraosseous hemangioma of the mandible: case report and review of the literature / Hemangioma intraóseo de la mandíbula: presentación de un caso y revisión de la literatura

We report on a two year old female patient who presented with expansion to the left side of the ramus and body of the mandibule. Imaging studies revealed a lesion with characteristics suggestive of vascular origin. Histopathological analysis determined the presence of an intraosseous Hemangioma. Embolization guided angiography of the left external carotid artery was performed followed by surveillance to monitor regression of the lesion.

Se presenta en una paciente de sexo femenino de dos años que presentó expansión del lado izquierdo de la rama y cuerpo de la mandíbula. Los estudios de imágenes revelaron una lesión con características sugerentes a un origen vascular. El análisis histopatológico determinó la presencia de un hemangioma intraóseo. Se realizó la embolización guiada por angiografía de la arteria carótida externa izquierda junto y seguimiento de control para supervisar la regresión de la lesión.

Multifocal extramedullary plasmocytoma of the sinonasal region: a case report and literature review / Plasmocitoma multifocal extramedular de la región sinonasal: reporte de un caso y revisión de la literatura

We report on a patient who presented to ENT services with right side epistaxis, frontal lobe headache, right infraorbital pain and the feeling of having a stuffy nose. CT and MRI were performed and later a biopsy confirmed the presence of sinonasal plasmocytoma. The Head and Neck oncology committee recommended radiotherapy as the choice of treatment. At the present time the patient is being followed on scheduled medical visits.

Se reporta el caso de un paciente que se presentó en el servicio de Otorrinolaringología con epistaxis, cefalea del lóbulo frontal derecho, dolor infraorbitario derecho y la sensación de tener la nariz tapada. Se realizaron TC y RNM, y luego una biopsia confirmó la presencia de un plasmocitoma nasosinusal. El comité de oncología de cabeza y cuello recomendó radioterapia como tratamiento de elección. En la actualidad, el paciente está en siguimiento y control en las visitas médicas regulares.

Skull base clear cell carcinoma, metastasis of renal primary tumor: a case report and literature review.

We report on a patient who presented with cranial nerve VI bilateral paresis, absence of pharyngeal reflex, dysarthria, right tongue deviation, and right facial paralysis. Imaging studies showed an expansive process in the cranial base with clivus and petrous apex osteolysis. A biopsy confirmed the presence of clear cell adenocarcinoma and suspicion of renal tumor metastases. Abdominal imaging studies revealed a mass in the right kidney. Consequently, radiotherapy was performed, and the patient was enrolled in a palliative care and pain control program.