Quality of life of patients with metastatic pancreatic adenocarcinoma initiating first-line chemotherapy in routine practice.

BACKGROUND: Despite advances in surgery, radiotherapy, and chemotherapy, pancreatic adenocarcinoma often progresses rapidly and causes death. The physical decline of these patients is expected to impact their quality of life (QoL). Therefore, in addition to objective measures of effectiveness, the evaluation of health-related QoL should be considered a matter of major concern when assessing therapy outcomes. METHODS: Observational, prospective, multicenter study including patients with metastatic pancreatic adenocarcinoma who started first-line chemotherapy in 12 Spanish centers. Treatment and clinical characteristics were recorded at baseline. Patients' health-related quality of life, ECOG, and Karnofsky index were measured at baseline, at Days 15 and 30, and every four weeks up to 6 months of chemotherapy. Health-related quality of life was measured using the EORTC-QLQ-C30 and EQ-5D questionnaires. Other endpoints included overall survival and progression-free survival. RESULTS: The study sample included 116 patients (median age of 65 years). Mean (SD) scores for the QLQ-C30 global health status scale showed a significant increasing trend throughout the treatment (p = 0.005). Patients with either a Karnofsky index of 70-80 or ECOG 2 showed greater improvement in the QLQ-C30 global health status score than the corresponding groups with better performance status (p ≤ 0.010). Pain, appetite, sleep disturbance, nausea, and constipation significantly improved throughout the treatment (p < 0.005). Patients with QLQ-C30 global health status scores ≥50 at baseline had significantly greater overall survival and progression-free survival (p = 0.005 and p = 0.021, respectively). No significant associations were observed regarding the EQ-5D score. CONCLUSIONS: Most metastatic pancreatic adenocarcinoma patients receiving first-line chemotherapy showed an increase in health-related quality of life scores throughout the treatment. Patients with lower performance status and health-related quality of life at baseline tended to greater improvement. The EORTC QLQ-C30 scale allowed us to measure the health-related quality of life of metastatic pancreatic adenocarcinoma patients receiving first-line chemotherapy.

Prognostic factors for survival with nab-paclitaxel plus gemcitabine in metastatic pancreatic cancer in real-life practice: the ANICE-PaC study.

BACKGROUND: Treatment with nab-paclitaxel plus gemcitabine increases survival in patients with metastatic pancreatic cancer. However, the assessment of treatment efficacy and safety in non-selected patients in a real-life setting may provide useful information to support decision-making processes in routine practice. METHODS: Retrospective, multicenter study including patients with metastatic pancreatic cancer, who started first-line treatment with nab-paclitaxel plus gemcitabine between December 2013 and June 2015 according to routine clinical practice. In addition to describing the treatment pattern, overall survival (OS) and progression-free survival (PFS) were assessed for the total sample and the exploratory subgroups based on the treatment and patients' clinical characteristics. RESULTS: All 210 eligible patients had a median age of 65.0 years (range 37-81). Metastatic pancreatic adenocarcinoma was recurrent in 46 (21.9%) patients and de novo in 164 (78.1%); 38 (18%) patients had a biliary stent. At baseline, 33 (18.1%) patients had an ECOG performance status ≥2. Patients received a median of four cycles of treatment (range 1-21), with a median duration of 3.5 months; 137 (65.2%) patients had a dose reduction of nab-paclitaxel and/or gemcitabine during treatment, and 33 (17.2%) discontinued treatment due to toxicity. Relative dose intensity (RDI) for nab-paclitaxel, gemcitabine, and the combined treatment was 66.7%. Median OS was 7.2 months (95% CI 6.0-8.5), and median PFS was 5.0 months (95% CI 4.3-5.9); 50 patients achieved either a partial or complete response (ORR 24.6%). OS was influenced by baseline ECOG PS, NLR and CA 19.9, but not by age ≥ 70 years and/or the presence of hepatobiliary stent or RDI < 85%. All included variables, computed as dichotomous, showed a significant contribution to the Cox regression model to build a nomogram for predicting survival in these patients: baseline ECOG 0-1 vs. 2-3 (p = 0.030), baseline NLR > 3 vs. ≤ 3 (p = 0.043), and baseline CA 19.9 > 37 U/mL vs. ≤37 U/mL (p = 0.004). CONCLUSIONS: Nab-Paclitaxel plus gemcitabine remain effective in a real-life setting, despite the high burden of dose reductions and poorer performance of these patients. A nomogram to predict survival using baseline ECOG performance status, NLR and CA 19.9 is proposed.

[Factors associated with quality of life related to health in persons with Diabetes Mellitus of the University Social Work of Cordoba]. / Factores asociados con la calidad de vida relacionada con la salud en personas con Diabetes Mellitus de la Obra Social Universitaria de Córdoba

The objective of the study was to describe clinical, sociodemographic and habits characteristics in adults with diabetes mellitus and to study their association with health-related quality of life. A sample of 311 patients from the Diabetes Program of a university social work in the province of Córdoba was selected. Data were analyzed for the proportions and physical and mental components of the SF-36® questionnaire. 57.4% reached a level of tertiary or university education. High blood pressure was the most prevalent cardiovascular risk factor (86.8%), followed by dyslipidemia (50.6%) and obesity (46.5%). 24.8% had macrovascular complications and 29% had microvascular complications. In the physical material (FC) of quality of life the women had a 4.2 times greater opportunity to report a lower value in relation to the men. Between the ages of 50 and 70, the number of people in the CF group was three times higher, and those older than 70 years were 4 times worse than the younger ones. Macro and microvascular complications and those reporting less than 2 healthy lifestyles were twice as likely to score below the overall CF average. The association between complications and poorer quality of life is one more reason to achieve a good metabolic control, to optimize the management of risk factors, avoiding or delaying the appearance of complications.

El objetivo del estudio fue describir características clínicas, sociodemográficas y hábitos en adultos con diabetes mellitus y estudiar su asociación con la calidad de vida relacionada con la salud. Se seleccionó una muestra de 311 pacientes del Programa de Diabetes de una obra social universitaria, de la provincia de Córdoba. Se analizaron los datos a como proporciones y los componentes físico y mental del cuestionario SF-36® . El 57,4% alcanzó un nivel de instrucción terciario o universitario. La hipertensión arterial fue el factor de riesgo cardiovascular más prevalente (86,8%), seguida por dislipemia (50,6%) y obesidad (46,5%). El 24,8% tenía complicación macrovascular y el 29% microvascular. En el componente físico (CF) de calidad de vida las mujeres tuvieron una chance 4,2 veces mayor de reportar un valor inferior en relación a los varones. Entre los 50 y los 70 años se triplicó y los mayores de 70 años tuvieron 4 veces peor una puntuación en el CF respecto a los más jóvenes. Las complicaciones macro y microvasculares y los que reportaron menos de 2 hábitos de vida saludables tuvieron el doble de chances de puntuar por debajo del promedio general en el CF. La asociación entre complicaciones y peor calidad de vida es un motivo más para alcanzar un buen control metabólico, optimizar el manejo de factores de riesgo, evitando o retrasando la aparición de complicaciones.

[Characteristics of diabetes mellitus patients under a chronic disease program]. / Características de una población de personas con diabetes mellitus en un programa de enfermedades crónicas.

UNLABELLED: Diabetes Mellitus (DM) is a chronic noncommunicable disease with a prevalence of 9.8% in Argentina. A Chronic Disease Program was developed for monitoring of patients with DM at the Ambulatory Center of DASPU, in National University of Cordoba Argentina. OBJECTIVE: To describe clinical characteristics of DM patients under a chronic disease program and to identify metabolic control variables associated with the presence of complications. MATERIAL AND METHODS: Observational, cross-sectional, descriptive study of DM Patients who attended at ambulatory center of DASPU since 2010. Categorical variables were described as proportions and number as mean ± SD. The comparison of means was performed using student test. RESULTS: 1017 patients were analyzed with mean age of 61 ± 14 years, with 54.6% of male, 8.5% had type 1 DM, and 90.9% had DM type 2: O.7% had gestational DM. Cardiovascular risk factor were: hypertension in 78%, dyslipidemia in 35. 25.5% of patients had micro vascular complications and 18.6% had macro vascular complications. Coronary heart disease was the most frequent complication in 14.5% of the patients. . 69% had values of glycated hemoglobin (HbA1C) ≤ 7, 4%; the average total cholesterol was 185 mg / dl and LDL cholesterol 111 mg / dl. The average HbA1C was higher in patients with micro vascular complications, HbA1c 7.47% vs. 7.18% (p = 0.009). In patients with macrovascular complications there was no significant inverse trend, HbA1c 7.21% vs 7.26% with and without complications (p = 0.65). The average total cholesterol was lower in the group with macro vascular complications 173 mg / dl and 189 mg / dl (p = 0.001). Similar result was observed in LDL-C: 101 vs 113 mg / dl (p = 0.001) in patients with and without complications, respectively. CONCLUSION: Clinical characteristics of the patients under the program were similar to other studies reported in the literature, but the values of HbA1c and total cholesterol have better results, achieving optimal values in a large percentage of the population, with lower levels in patients with macrovascular complications.

La Diabetes Mellitus (DM) es una enfermedad crónica no transmisible con una prevalencia en Argentina del 9,8%. El seguimiento de pacientes con DM se realiza en un Programa de Enfermedades Crónicas desarrollado en la obra social universitaria DASPU, de la Universidad Nacional de Córdoba Argentina. Objetivo: describir características clínicas de personas con DM de un programa de seguimiento. Identificar variables de control metabólico asociadas a la presencia de complicaciones. Material y método. Estudio observacional, transversal, descriptivo. Se incluyeron datos de pacientes con DM bajo programa del año 2010. Las variables categóricas se describen como proporciones y las numéricas como media ±DE. La comparación de medias se realizó mediante test de Student. Resultados: total 1017 casos, edad media 61 ±14 años, 54,6% masculinos, DM tipo 1: 8,5%, DM tipo 2: 90,9%, DM gestacional: 0,7%. Factores de riesgo cardiovascular: hipertensión arterial en 78%, dislipemia en 35%. Complicaciones microvasculares: 25,5%, macrovasculares: 18,6%. La enfermedad coronaria fue la complicación más frecuente: 14,5%. El 69% presentó valores de hemoglobina glicosilada (HbA1C) ≤7,4%; el promedio de colesterol total fue 185 mg/dl y de colesterol LDL 111 mg/dl. El promedio de HbA1C fue más elevado en pacientes con complicaciones microvasculares que sin complicaciones: 7,47% vs 7,18% (p=0,009). En pacientes con complicaciones macrovasculares hubo una tendencia inversa, no significativa (7,21% vs 7,26%; p=0,65). El promedio de colesterol total fue menor en el grupo con complicaciones macrovasculares (173 mg/dl vs 189 mg/dl; p=0,001). Igual comportamiento se observó en relación al C-LDL (101 vs 113 mg/dl; p=0,001). Conclusión: Las características clínicas evaluadas coinciden en su distribución y complicaciones con estudios epidemiológicos reportados en la bibliografía, los valores de HbA1C y colesterol total alcanzan valores óptimos en un gran porcentaje de nuestra población, con menores niveles en los pacientes con complicaciones macrovasculares.

Hypothyroidism during neonatal and perinatal period induced by thyroidectomy of the mother causes depressive-like behavior in prepubertal rats.

The objective of this study was to see if neonatal and perinatal hypothyroidism caused anxiety and depressive-like behaviors. Twenty female Wistar rats were randomly divided into two groups: 1) thyroidectomy caused hypothyroidism, in which the thyroid gland had been removed and the parathyroid reimplanted; and 2) false thyroidectomy. The thyroidectomy was made on rats anesthetized with ketamine-xylazine. The rats were mated and one day after giving birth, eight pups were assigned to each group randomly and they were distributed into two groups: a hypothyroid group containing male pups of a hypothyroid mother with a hypothyroid wet nurse; and a euthyroid group of male pups of a euthyroid mother with a euthyroid wet nurse. We analyzed the behavioral test at a prepubertal age. The neonatal and perinatal hypothyroidism caused by the mother's thyroidectomy caused a decrease in body weight and length. We found that the neonatal and perinatal hypothyroidism enhanced the total exploratory activity without affecting social contact and the time spent in the open and closed arms in an elevated plus-maze. The hypothyroidism caused immobility without altering the lower climbing duration in the swimming test. This study shows a novel model to cause neonatal and perinatal hypothyroidism without using pharmacological drugs. We demonstrated that hypothyroid animals had a reduction in body weight and length, a retardation of neurodevelopment, and they had depressive-like behavior.

Methimazole-induced hypothyroidism causes alteration of the REDOX environment, oxidative stress, and hepatic damage; events not caused by hypothyroidism itself.

UNLABELLED: Our objective was to compare, over a time-course, markers of oxidative stress, the REDOX environment, and the antioxidant enzymatic system in the liver of rats with methimazole- or thyroidectomy-caused hypothyroidism. METHODS: We used 60 male Wistar rats divided into four groups: 1) the euthyroid, which received only tap water, 2) false thyroidectomy, which received the surgery and postoperative treatment, 3) thyroidectomy-caused hypothyroidism, which had the thyroid gland removed and a parathyroid reimplant, and 4) methimazole-caused hypothyroidism in rats that received 60 mg/kg/d of the antithyroid drug in drinking water. Five rats of the euthyroid and methimazole-caused hypothyroidism groups were killed at the end of the first, second, third, and fourth week after treatment, and five rats of false thyroidectomy and thyroidectomy-caused hypothyroidism groups were killed at the end of the second and eighth week after the surgical procedure. Each liver was removed and stored at -70 degrees C until oxidative stress, REDOX environment, and antioxidant enzymatic system markers were tested. We also made a histological study at the end of the treatment. RESULTS: The histological study revealed that only the methimazole-caused hypothyroidism caused cell damage. This damage is associated with an increase of oxidative stress markers that were not compensated for by the antioxidant system. The catalase activity is reduced and this allows H2O2-caused damage. In conclusion methimazole causes cell damage in the liver, whereas hypothyroidism per se does not cause hepatic-cell damage.

Neonatal bilateral lidocaine administration into the ventral hippocampus caused postpubertal behavioral changes: An animal model of neurodevelopmental psychopathological disorders.

Our aim was to investigate if neonatal bilateral administration of lidocaine into the ventral hippocampus would cause behavioral changes related to schizophrenia. A neonatal ventral-hippocampal lesion (nVH lesion) was made with lidocaine in Wistar male pups. Two groups were formed, the first received lidocaine (4 mug/0.3 muL) and the second an equal volume of vehicle. At day 35 and 56, both groups were tested for social contact, immobility caused by clamping the neck and dorsal immobility, locomotor activity in an open field, and tail flick (TF) latency after a painful heat stimulus. All animals were then killed. Coronal cuts (7 mum) of the brain were obtained and each brain section was stained with cresyl violet-eosin. The animals which received the nVH lesion with lidocaine had decreased social interaction at both ages. The rats with lesions, only at day 58 postnatal, increased their distance traveled and ambulatory time, with a decrease in their nonambulatory and reset time. The rats with lesions had a longer duration of immobility caused by clamping the neck and a longer dorsal immobility at both days 34 and 57 compared to control rats. The lidocaine-treated group spent less time to deflect the tail compared to the control group at postpubertal age. The neonatal bilateral administration of lidocaine into the ventral hippocampus caused some alterations, such as chromatin condensation, nucleolus loss, and cell shrinkage, but glial proliferation was not seen. Neonatal bilateral lidocaine administration into the ventral hippocampus caused postpubertal behavioral changes.

Lidocaine affects the redox environment and the antioxidant enzymatic system causing oxidative stress in the hippocampus and amygdala of adult rats.

AIMS: Our objective was to investigate if oxidative stress is involved in the neural damage caused by lidocaine. MAIN METHODS: Male Wistar rats were used. The control group received 0.9% saline ip and the treated group received a single 60 mg/kg lidocaine dose ip. On days 1, 2, 5, and 10 after dosing, ten rats were sacrificed and their brains were quickly removed. The amygdala and hippocampus were dissected. Five samples were used to determine lipid peroxidation, reactive oxygen species (ROS), reduced glutathione (GSH), and oxidized glutathione (GSSG). Another five were used to measure antioxidant activities of glutathione peroxidase (GPX), catalase, Cu-Zn SOD (superoxide dismutase), Mn SOD, and total SOD. KEY FINDINGS: Ten days after injection of lidocaine, lipid peroxidation increases in the hippocampus because the ROS are enhanced from day 5, whereas in the amygdala lipid peroxidation and the ROS were enhanced only on the first day postinjection. Lidocaine causes an increased concentration of GSH and GSSG in the hippocampus from the first day. In the amygdala the GSH and GSSG content were increased at day 10. In the hippocampus the catalase activity was enhanced, whereas the total SOD and Cu-Zn SOD activities were decreased. In the amygdala the lidocaine enhances the activities of catalase and GPX, but no SOD isoenzymes were modified. SIGNIFICANCE: In this research we demonstrated that lidocaine affects the redox environment and promotes increases of the oxidative markers both in the hippocampus and amygdala but in a different pattern.

Desarrollo e implementación de un sistema de evaluación objetiva estructurada en el curso libre de Farmacología Aplicada Ciclo 2007 / Development and implementation of an objective assesment system for the free course on applied pharmacology of the year 2007

La evaluación, como instrumento de medición del proceso de enseñanza-aprendizaje, constituye un tema complejo y de permanente debate, por lo cual los docentes deben capacitarse,debatir y construir instrumentos de evaluación válidos, confiables,aceptables y de bajo costo. Métodos: El Curso Libre de Farmacología Aplicada utiliza la Guía de la Buena Prescripción con el objetivo de contribuir adesarrollar habilidades y destrezas para el uso razonado de los medicamentos. La regularidad en la materia se obtiene con un examen grupal realizado en los últimos dos días de cursadointensivo de cinco semanas. En dicho examen se resuelven dos casos clínicos con problemas de salud (un caso simple y otro complejo) a través de los seis pasos del proceso de la terapéuticarazonada. Para su evaluación, se desarrolló un instrumentoestructurado y objetivo. En una primera instancia el grupo docente desarrolló durante un largo proceso un instrumentodenominado “tabla guía” (“(ver tabla 1) para establecer prioridades en el planteo de las patologías prevalentespreviamente abordadas en las actividades grupales programáticas (trabajos prácticos)...

Hippocampus and amygdala neurotoxicity produced by systemic lidocaine in adult rats.

There is evidence that using lidocaine-treated cellular culture produces cell damage. However, there are no studies in vivo demonstrating the potential injurious effect of lidocaine on the central nervous system. Therefore, the aim of our study was to investigate if lidocaine is involved in neuronal damage in the CA3 hippocampus and amygdala regions when using a single subconvulsive or a convulsive lidocaine dose. Two-month-old male Wistar rats (57) were used. The animals were randomly assigned to one of three groups. Group I received 0.9% saline ip (n=9), group II received a single lidocaine dose of 60 mg/kg (n=18), and group III received 90 mg/kg ip (n=12). At day 2, 7, and 10 after the dosing, three to six rats per group were sacrificed. The brains of the rats were removed and were embedded in paraffin. Coronal cuts of 7 microm were made. Each brain section was stained with cresyl-eosin. We evaluated the number of normal and abnormal neurons in the hippocampal CA3 (pyramidal) and basolateral amygdala (large and medium neurons) regions in a 10,000 microm2 section. To explore an association between lidocaine-induced seizure and neuronal damage, diazepam was used (10 mg/kg ig) as an anticonvulsant two hours before a 90 mg/kg dose of lidocaine. Lidocaine causes a morphological neuronal alteration in the CA3 hippocampal region and the basolateral amygdala and possibly an inhibition-excitation imbalance. Diazepam prevents lidocaine-induced seizures, but not neuronal damage in brain structures. Interaction of lidocaine with the membrane components produces disrupted Ca+2 homeostasis and causes neuronal damage. Moreover, it is possible that lidocaine or its metabolites could actively participate in the neuronal damage observed.

Perinatal hypothyroidism increases the susceptibility to lidocaine-kindling in adult rats.

The present study was developed to ascertain whether or not susceptibility to lidocaine-kindling persists into adulthood in perinatal hypothyroid rats. Pregnant Wistar rats were randomly divided into two groups: the first one, a control group, that drank tap water; and a second one, a hypothyroid group, were treated with 0.02% propylthiouracil in their drinking water from the 14th gestational day to the 10th postpartum day. The pups of both groups were maintained with food and tap water ad libitum until the experiment was over. The pups of each group were divided to test the susceptibility to lidocaine-kindling at 30 and 100 days old, for this, lidocaine (50 mg/kg, i.p.) was administered daily. The seizures were usually present in the form of tonic attacks of fore and hind limbs, followed by intermittent clonic movements. An animal was considered kindled when it showed clonic movements for two consecutive days. We observed that the number of stimuli necessary to produce lidocaine-kindling seizures in hypothyroid rats was significantly lower than in the control group for both ages. Also, the percentage of kindled rats aged 30 days (73% and 89%) was greater than aged of 100 days (26% and 59%) in both control and hypothyroid groups, respectively. In conclusion, the perinatal hypothyroidism increases the susceptibility to lidocaine-kindling in adult rats.