Formulation and development of paediatric orally disintegrating carbamazepine tablets.

Carbamazepine is a medicine used to manage epilepsy and partial or tonic-clonic seizures. This study aimed at formulating and obtaining carbamazepine orodispersible tablets for paediatric use at a 50 mg dose, with a diameter not greater than 6 mm and a tablet weight of 80 mg, through a direct compression process. The SeDeM pre-formulation/formulation method was used to define the characteristics of both carbamazepine and the selected excipients for direct compression. This study succeeded in formulating and obtaining the proposed tablets. Following the application of the SeDeM method, the tablets met the mass uniformity test and showed appropriate hardness values for orodispersible tablets. The tablets also met the United States Pharmacopeia (USP) test specifications at t = 60 min. The orodispersible tablets obtained may improve compliance with paediatric treatment with carbamazepine, ensuring the safety and effectiveness of the medicine.

Lowering bronchoaspiration rate in an acute stroke unit by means of a 2 volume/3 texture dysphagia screening test with pulsioximetry. / Reducción de la tasa de broncoaspiración con el test 2 volúmenes/3 texturas con pulsioximetría en una unidad de ictus.

INTRODUCTION: During acute stroke, 30% of all patients present dysphagia and 50% of that subgroup will experience bronchoaspiration. Our aim was to compare mortality and bronchoaspiration rates associated with the water test compared to those associated with a 2 volume/3 texture test controlled with pulse oximetry (2v/3t-P test) in our stroke unit. PATIENTS AND METHODS: Over a 5-year period, we performed a prospective analysis of all consecutive acute ischaemic stroke patients hospitalised in the Stroke Unit. Dysphagia was evaluated using the water test between 2008 and 2010 (group 0 or G0), and the 2v/3t-P test (group 1 or G1) between 2011 and 2012. We analysed demographic data, vascular risk factors, neurological deficit on the NIHSS, aetiological subtype according to TOAST criteria, clinical subtype according to the Oxfordshire classification, prevalence of dysphagia, percentage of patients with bronchoaspiration, and mortality. RESULTS: We examined 418 patients with acute stroke (G0=275, G1=143). There were significant differences between the 2 groups regarding the percentage of patients with TACI (17% in G0 vs. 29% in G1, P=.005) and median NIHSS score (4 points in G0 vs. 7 points in G1, P=.003). Since adopting the new swallowing test, we detected a non-significant increase in the percentage of dysphagia (22% in G0 vs. 25% in G1, P=.4), lower mortality (1.7% in G0 vs. 0.7% in G1, P=.3) and a significant decrease in the bronchoaspiration rate (6.2% in G0 vs. 2.1% in G1, P=.05). CONCLUSIONS: Compared to the water test used for dysphagia screening, the new 2v/3t-P test lowered bronchoaspiration rates in acute stroke patients.

[Gout, beyond the joint: How should we treat it?] / La gota, más allá de la articulación: ¿cómo debemos tratarla?

Gout is a disease caused by the chronic deposition of monosodium urate crystals. Its clinical presentation as an acute, self-limiting arthritis and the belief that it is a banal, self-inflicted disease have led to its poor management. Despite advances in the knowledge of the disease and the simplicity of its management, no more than 30% of patients are well treated. In Spain, the prevalence of gout is 2.5% and its incidence is increasing. In the following article we will review the pathogenesis of gout and hyperuricaemia, highlighting the greater weight of genetics and renal function over diet. We will look at the consequences of crystal deposition. Gout, in addition to its joint presentation and renal involvement, has been shown to be an independent cardiovascular risk factor. Hypouricemic therapy is the most important treatment, as it is the one that dissolves the crystals and cures the disease. This requires the sustained achievement of uricemia levels below 6mg/dl. We will also review preventive and flares treatment, as well as the role of patient education in terms of both lifestyle and dietary habits and adherence to pharmacological treatment.

Exploration of moisture activated dry granulation for the development of gastroretentive tablets aided by SeDeM diagram.

Moisture activated dry granulation (MADG) is an attractive granulation process. However, only a few works have explored modified drug release achieved by MADG, and to the best of the authors knowledge, none of them have explored gastroretention. The aim of this study was to explore the applicability of MADG process for developing gastroretentive placebo tablets, aided by SeDeM diagram. Floating and swelling capacities have been identified as critical quality attributes (CQAs). After a formulation screening step, the type and concentration of floating matrix formers and of binders were identified as the most relevant critical material attributes (CMAs) to investigate in ten formulations. A multiple linear regression analysis (MLRA) was applied against the factors that were varied to find the design space. An optimized product based on principal component analysis (PCA) results and MLRA was prepared and characterized. The granulate was also assessed by SeDeM. In conclusion, granulates lead to floating tablets with short floating lag time (<2min), long floating duration (>4h), and showing good swelling characteristics. The results obtained so far are promising enough to consider MADG as an advantageous granulation method to obtain gastroretentive tablets or even other controlled delivery systems requiring a relatively high content of absorbent materials in their composition.

Clot Burden Score and Collateral Status and Their Impact on Functional Outcome in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Collateral status and thrombus length have been independently associated with functional outcome in patients with acute ischemic stroke. It has been suggested that thrombus length would influence functional outcome via interaction with the collateral circulation. We investigated the individual and combined effects of thrombus length assessed by the clot burden score and collateral status assessed by a FLAIR vascular hyperintensity-ASPECTS rating system on functional outcome (mRS). MATERIALS AND METHODS: Patients with anterior circulation acute ischemic stroke due to large-vessel occlusion from the ASTER and THRACE trials treated with endovascular thrombectomy were pooled. The clot burden score and FLAIR vascular hyperintensity score were determined on MR imaging obtained before endovascular thrombectomy. Favorable outcome was defined as an mRS score of 0-2 at 90 days. Association of the clot burden score and the FLAIR vascular hyperintensity score with favorable outcome (individual effect and interaction) was examined using logistic regression models. RESULTS: Of the 326 patients treated by endovascular thrombectomy with both the clot burden score and FLAIR vascular hyperintensity assessment, favorable outcome was observed in 165 (51%). The rate of favorable outcome increased with clot burden score (smaller clots) and FLAIR vascular hyperintensity (better collaterals) values. The association between clot burden score and functional outcome was significantly modified by the FLAIR vascular hyperintensity score, and this association was stronger in patients with good collaterals, with an adjusted OR = 6.15 (95% CI, 1.03-36.81). CONCLUSIONS: The association between the clot burden score and functional outcome varied for different collateral scores. The FLAIR vascular hyperintensity score might be a valuable prognostic factor, especially when contrast-based vascular imaging is not available.

[Renal failure stages as predictors of mortality following acute coronary syndrome]. / El grado de insuficiencia renal como predictor de mortalidad tras un síndrome coronario agudo.

INTRODUCTION: renal glomerular filtration rate on hospital admission in patients presented with an acute coronary syndrome as a predictor for mortality. PATIENTS AND METHODS: The study analysed 290 patients admitted on hospital with an acute coronary syndrome during one year (2003). Renal function was estimated using the renal glomerular filtration rate by the MDRD formula. Patients were stratified in three groups: patients with a GFR > or = 60 ml/min/1,73 m2; n = 186, patients with GFR < 60 or > 30; n = 93 and patients with GFR < 30; n = 11. RESULTS: 66.6% of patients were males and 66.5% were older than 65 years old. 54.5% suffered from hypertension and 39% were diabetics. All patients with GFR < 30 ml/min had an acute coronary syndrome without elevation of ST segment. They were the oldest with a major proportion of previous cardiovascular events as cerebrovascular disease, peripheral vascular disease or myocardial infarction. Diagnostic procedures and treatments were less administered in patients with GFR < 30 ml/min. Although in the univariate analysis demonstrated that hospital mortality was related to GFR < 30 ml/min, sex, ageing, Killip > 1, ventricular function and cTnT elevation, only GFR < 30 ml/min, ageing, heart failure and ventricular dysfunction persisted significant in the multivariate analysis. Hospital mortality was 27.3% in patients with GFR < 30 ml/min, 7.5% in patients with GFR between 30-60 ml/min and 3.8% in patients with a GFR > or = 60 ml/min. Mortality after two years follow up was 27.3% in patients with GFR < 30 ml/min, 20.4% in patients with GFR between 30-60 ml/min and 10.2% in patients with a GFR > or = 60 ml/min. Mortality (hospital mortality and after two years of follow up) was increased in patients with GFR< 30 ml/min, ageing, heart failure and diabetes after adjusted for other prognostic factors. CONCLUSIONS: A reduced glomerular filtration rate is an independent risk factor for mortality in patients with an acute coronary syndrome. Estimation of the renal glomerular filtration rate might be used as prognostic value in these patients.

[Peritoneal implants in patients affected by chronic renal failure in hemodialysis programme]. / Implantes peritoneales en pacientes con insuficiencia renal crónica en programa de hemodiálisis.

The presence of peritoneal implants detected by computered axial tomography (CT) is usually related to mesothelial primary neoformative processes or, more frequently to peritoneal metastasis or peritoneal carcinomatosis. Although the higher prevalence of neoplastic processes in the chronic renal failure population, the association of peritoneal implants and constitutional syndrome is not always correlated to peritoneal carcinomatosis. We present the case of two patients with chronic renal failure in hemodialysis programme, with abdominal insidious clinical, constitutional syndrome and similar peritoneal implants seen by CAT: the histologic analysis of peritoneal implants gave the definitive diagnostic of secondary amyloidosis and peritoneal tuberculosis respectively.

Tuberculosis meningoencefálica y espinal tras parto / Postpartum meningoencephalitis and spinal tuberculosis

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Triiodothyronine (T3)-induced down-regulation of the nuclear T3 receptor in mouse preadipocyte cell lines.

As previously reported, preadipocytes cloned from the epididymal fat of lean or genetically obese mice (HGFu and ob 17, respectively) contain the nuclear T3 receptor. The number of receptor sites was similar in confluent cells of both lines and approximately doubled during adipocyte differentiation. T3 added to the culture medium increased triacylglycerol synthesis. T3 also increased fatty acid synthase specific activity, relative synthesis rate, and relative mRNA content (1.5- to 2.5-fold). Optimal responses were obtained at 1.5 nM. This study shows that under the same culture conditions in both cell lines, 1.5 nM T3 decreased the receptor concentration with no significant change in the affinity for T3. The receptor depletion was time dependent, rapid, stable in the presence of T3, and reversible in less than 24 h after its withdrawal. Receptor depletion was also dependent on T3 concentration and close to maximum at 1.5 nM T3 [45.1 +/- 2.7% (+/- SE) of the data values without T3; n = 14]. A linear relationship was observed between receptor occupancy by T3 and receptor loss. T4 and triiodothyroacetic acid also decreased the T3 receptor content, as expected from their own affinity for the receptor. These last two observations suggest that the receptor reduction is related to its occupancy by T3. The reported results, also observed in several other cell types, indicate that down-regulation of the nuclear T3 receptor by thyroid hormones is probably a generalized event in T3 target cells at least in vitro. Interpretation of its significance in preadipocyte cell lines requires further studies of rapid nuclear events following T3 receptor occupancy.

Comparison of aceclofenac with piroxicam in the treatment of osteoarthritis.

A multicentre, double-blind, randomised, parallel group study was undertaken to investigate the efficacy and safety of aceclofenac (123 patients, 100 mg twice daily) in comparison to piroxicam (117 patients, 20 mg once daily and placebo once daily) in patients with osteoarthritis of the knee. The treatment period of two months was preceded by a washout period of one week duration. On completion of the study, patients in both aceclofenac and piroxicam-treated groups exhibited significant improvement in pain intensity and functional capacity of the affected knee, as represented by the Osteoarthritis Severity Index (OSI) (p < 0.0001 and p < 0.001 respectively). This was further substantiated following the patient's assessment of pain intensity using the Visual Analogue Scale (VAS), in which significant improvements were demonstrated at all time points for each treatment group (p < 0.001). Although both treatment groups showed a significant improvement in all investigator's clinical assessments (functional exploration of the knee, knee flexion and extension (EXT)), there were no significant differences between the groups. There was, however, a more rapid improvement in knee flexion in the aceclofenac group after 15 days of treatment. Both aceclofenac and piroxicam were well tolerated by patients, the most commonly reported adverse events being gastrointestinal, although their incidence was low. Only 24 patients on aceclofenac, as opposed to 33 on piroxicam complained of dyspepsia, epigastralgia and pyrosis. While 7 patients in each group were withdrawn because of adverse events, only one patient with piroxicam was withdrawn because of severe upper gastrointestinal bleeding. Twice as many reports of fecal blood loss were made in the piroxicam group in comparison to the aceclofenac group. In summary, this study confirms the therapeutic efficacy of aceclofenac and suggests that it is a well-tolerated alternative NSAID to piroxicam in the treatment of osteoarthritis.

[Superior vena cava thrombosis in a patient on hemodialysis]. / Trombosis de la vena cava superior en un paciente en hemodiálisis.

We present a patient with end-stage renal disease on maintenace hemodialysis through a permanent catheter (Permcath) on the right subclavian vein. One month after the catheter placement the patient exhibited a superior vena cava syndrome due to a pericatheter thrombosis. The patient was initially managed with anticoagulation with early clinical improvement. Nevertheless, the reappearance of the symptoms forced the removal of the catheter and percutaneous angioplasty of the superior vena cava. After those measures and anticoagulation with coumarin the patient remains stable with complete clinical resolution and angiographical improvement.

[Non-convulsive status epilepticus secondary to adjusted cefepime doses in patients with chronic renal failure]. / Estatus epiléptico no convulsivo secundario a cefepima a dosis ajustadas en enfermos con insuficiencia renal crónica.

Fever is one of the most frequent causes of hospital admission in patients with end-stage renal disease. Lack of an identified source of infection and/or lack of clinical response to the first empirical antibiotic treatment favour the use of broader spectrum antibiotics. The availability of fourth-generation cephalosporins (e.g. cefepime) and the increasing incidence of bacterial resistances to classical antibiotics has increased their use in the clinical practice. We present two cases of non-convulsive status epilepticus in patients with advanced chronic renal failure who received cefepime at doses corrected for the degree of renal function according to the manufacturer's instrument as. The clinical symptoms included shouthough, processes, disorientation, loss of attention, and the later appearance of myoclonus. In both cases the electroencephalogram (EEG) was compatible with non-convulsive epileptic status. After cefepime withdrawal there was a clinical remission of symptoms and normalization of the EEG. It is concluded that cefepime treatment can induce a non-convulsive epileptic status in patients with advanced chronic renal failure. Pharmacokinetic studies are urgently needed to clearly define the appropriate dose of cefepime in patients with advanced chronic renal failure.

[Anti-glomerular basement membrane antibody mediated disease: revision of 32 cases and follow-up at one year of the diagnosis]. / Enfermedad por Ac anti-MBG: revisión de 32 casos y seguimiento al año del diagnóstico.

Anti-basement membrane antibody mediated disease is an unfrequent entity but with a high mortality and morbidity. We present a revision of 32 patients diagnosed of anti-basement membrane antibody mediated disease between 1983 and 1997, and their evolution at one year of the diagnosis. The clinical pattern of presentation was as a Goodpasture's syndrome (glomerulonephritis and lung haemorrhage) in 15 patients and glomerulonephritis without lung involvement in 17. We reviewed retrospectively the features at the clinical presentation, the different treatments, and the delay of the starting of it since the beginning of the symptoms, in order to evaluate a prognosis dats of the disease. After the retrospective study we deduce that anti-basement membrane antibody mediated disease has a high mortality although the different regimes of treatment applied (25%), and the need of renal replacement therapy at one year of diagnosis is also high (70.8%). The renal survival at one year of the diagnosis is low and the response to therapy depends on the serum creatinine value at the diagnosis. The contribution of immunocompetent leucocytes to renal hypercellularity suggests that both humoral and cell-mediated immunity play a role in this disease.

Reducción de la tasa de broncoaspiración con el test 2 volúmenes/3 texturas con pulsioximetría en una unidad de ictus / Lowering bronchoaspiration rate in an acute stroke unit by means of a 2 volume/3 texture dysphagia screening test with pulsioximetry

Introducción: En la fase aguda del ictus el 30% de los pacientes presentan disfagia, y de ellos, el 50% experimentarán broncoaspiración. Nuestro objetivo fue evaluar los resultados de mortalidad y broncoaspiración del test del agua comparado con el test 2 volúmenes/3 texturas controlado con pulsioximetría (2v/3t-P) en una unidad de ictus. Pacientes y métodos: Durante 5 años se analizaron de forma prospectiva y consecutiva todos los pacientes con infarto cerebral en la Unidad de Ictus. Del año 2008 al 2010 se utilizó el test del agua (grupo 0 o G0), y del 2011 al 2012, el test 2v/3t-P (grupo 1 o G1). Se recogieron las siguientes variables: demográficas, factores de riesgo vascular, gravedad neurológica con la escala NIHSS, subtipo etiológico según criterios TOAST, subtipo clínico según la clasificación Oxfordshire, prevalencia de disfagia, broncoaspiración y exitus. Resultados: Se analizaron 418 pacientes con infarto cerebral agudo (G0 = 275, G1 = 143). Se detectaron diferencias significativas entre ambos grupos en el porcentaje de pacientes con TACI (17% en G0 vs. 29% en G1, p = 0,005) y en la mediana de NIHSS (4 puntos en G0 vs. 7 puntos en G1, p = 0,003). Con el test 2v/3t-P se detectó un aumento no significativo en el porcentaje de disfagia (22% en G0 vs. 25% en G1, p = 0,4), una menor tasa de mortalidad (1,7% en G0 vs. 0,7% en G1, p = 0,3) y una reducción significativa de broncoaspiración (6,2% en G0 vs. 2,1% en G1, p = 0,05). Conclusiones: El nuevo test 2v/3t-P, comparado con el test del agua, mejoró significativamente los resultados de broncoaspiración en los pacientes con infarto cerebral agudo

Introduction: During acute stroke, 30% of all patients present dysphagia and 50% of that subgroup will experience bronchoaspiration. Our aim was to compare mortality and bronchoaspiration rates associated with the water test compared to those associated with a 2 volume/3 texture test controlled with pulse oximetry (2v/3t-P test) in our stroke unit. Patients and methods. Over a 5-year period, we performed a prospective analysis of all consecutive acute ischaemic stroke patients hospitalised in the Stroke Unit. Dysphagia was evaluated using the water test between 2008 and 2010 (group 0 or G0), and the 2v/3t-P test (group 1 or G1) between 2011 and 2012. We analysed demographic data, vascular risk factors, neurological deficit on the NIHSS, aetiological subtype according to TOAST criteria, clinical subtype according to the Oxfordshire classification, prevalence of dysphagia, percentage of patients with bronchoaspiration, and mortality. Results: We examined 418 patients with acute stroke (G0 = 275, G1 = 143). There were significant differences between the 2 groups regarding the percentage of patients with TACI (17% in G0 vs. 29% in G1, P = .005) and median NIHSS score (4 points in G0 vs. 7 points in G1, P = .003). Since adopting the new swallowing test, we detected a non-significant increase in the percentage of dysphagia (22% in G0 vs. 25% in G1, P = .4), lower mortality (1.7% in G0 vs. 0.7% in G1, P = .3) and a significant decrease in the bronchoaspiration rate (6.2% in G0 vs. 2.1% in G1, P = .05). Conclusions: Compared to the water test used for dysphagia screening, the new 2v/3t-P test lowered bronchoaspiration rates in acute stroke patients