Safety and efficacy of triple therapy with peginterferon, ribavirin and boceprevir within an early access programme in Spanish patients with hepatitis C genotype 1 with severe fibrosis: SVRw12 analysis.

BACKGROUND & AIMS: The addition of protease inhibitors (PIs) changed the hepatitis C virus (HCV) treatment standards and improved sustained viral response (SVR) rates in patients with genotype 1 HCV infection. METHODS: Prospective, multicentre, national registry that includes naïve and treatment-experienced patients with HCV genotype 1 infection, who had bridging fibrosis or cirrhosis and were treated with triple therapy (peginterferon alfa-2a or alfa-2b, ribavirin and boceprevir) as compassionate use, and in accordance with the Summary of Product Characteristics. RESULTS: Most of the patients (68.2%) were male, with a mean age of 53 years, 75% (n = 128) had HCV 1b genotype and baseline viral load of 6.2 log. According to prior treatment, 20% of patients were treatment-naïve and 80% had received prior treatment. Approximately 36.5% of patients (n = 62) reported at least one serious adverse events (SAEs) (total SAEs = 103). The most common SAEs were neutropenia (57.6%), anaemia (47.6%) and grade 3 thrombopenia (25.9%). Patients with albumin <3.5 g/dl and bilirubin >2 mg/dl had an increased relative risk (greater than one-fold) for SAEs, including infections and hepatic decompensation. In the intent-to-treat analysis (n = 170), the overall percentage of patients with SVRw12 was 46.5%. In patients with 1 log decrease at week 4 (lead-in phase), the overall SVRw12 rate was 67.0%. In the patients initiating triple therapy with boceprevir (n = 139), the global response rate was 56.4%. In a multivariate analysis, an increased probability of achieving SVR was associated with response to prior treatment (relapsers), >1 log decrease in viral load in the lead-in phase and baseline albumin >3.5 g/dl. CONCLUSIONS: Triple therapy in patients with severe fibrosis/cirrhosis is associated with a higher rate of SAE and a lower rate in comparison with patients with mild disease. However, for patients with intact liver function, it could be considered as a treatment option, when other alternatives would not be available.

A Randomized Study of Peginterferon Lambda-1a Compared to Peginterferon Alfa-2a in Combination with Ribavirin and Telaprevir in Patients with Genotype-1 Chronic Hepatitis C.

BACKGROUND: A randomized, double-blind, multinational, phase 3 study was conducted comparing the efficacy and safety of peginterferon lambda-1a (Lambda)/ribavirin (RBV)/telaprevir (TVR) vs. peginterferon alfa-2a (Alfa)/RBV/TVR in patients with chronic hepatitis C virus (HCV) genotype-1 (GT-1) infection. METHODS: Patients (treatment-naïve or relapsers on prior Alfa/RBV treatment) were randomly assigned in a 2:1 ratio to receive Lambda/RBV/TVR or Alfa/RBV/TVR. Total duration of treatment was either 24 or 48 weeks (response-guided treatment), with TVR administered for the first 12 weeks. The primary endpoint was the proportion of patients who achieved a sustained virologic response at post treatment week 12 (SVR12), which was tested for noninferiority of Lambda/RBV/TVR. RESULTS: A total of 838 patients were enrolled, and 617 were treated; 411 and 206 patients received Lambda/RBV/TVR and Alfa/RBV/TVR, respectively. The majority of patients were treatment-naïve, with HCV GT-1b and a high baseline viral load (≥800,000 IU/mL). Less than 10% of patients had cirrhosis (Lambda, 7.5%; Alfa, 6.8%). Lambda/RBV/TVR did not meet the criterion for noninferiority (lower bound of the treatment difference interval was -12.3%); the SVR12 in all patients (modified intent-to-treat) was 76.2% in the Lambda arm and 82.0% in the Alfa arm. Overall, the frequency of adverse events in each arm was comparable (Lambda, 91.7%; Alfa, 97.1%). As expected based on the safety profile of the 2 interferons, there were more hepatobiliary events observed in the Lambda arm and more hematologic events in the Alfa arm. CONCLUSIONS: In this comparison of Lambda/RBV/TVR and Alfa/RBV/TVR in patients who were treatment-naïve or had relapsed on prior Alfa/RBV treatment, Lambda failed to demonstrate noninferiority based on SVR12 results. Treatment with Lambda/RBV/TVR was associated with a higher incidence of relapse. More patients discontinued Lambda/RBV/TVR treatment during the first 4 weeks of study treatment, mainly due to hepatobiliary-related events, and more Lambda patients were lost to follow-up.

On the relationships of postcanine tooth size with dietary quality and brain volume in primates: implications for hominin evolution.

Brain volume and cheek-tooth size have traditionally been considered as two traits that show opposite evolutionary trends during the evolution of Homo. As a result, differences in encephalization and molarization among hominins tend to be interpreted in paleobiological grounds, because both traits were presumably linked to the dietary quality of extinct species. Here we show that there is an essential difference between the genus Homo and the living primate species, because postcanine tooth size and brain volume are related to negative allometry in primates and show an inverse relationship in Homo. However, when size effects are removed, the negative relationship between encephalization and molarization holds only for platyrrhines and the genus Homo. In addition, there is no general trend for the relationship between postcanine tooth size and dietary quality among the living primates. If size and phylogeny effects are both removed, this relationship vanishes in many taxonomic groups. As a result, the suggestion that the presence of well-developed postcanine teeth in extinct hominins should be indicative of a poor-quality diet cannot be generalized to all extant and extinct primates.

Tooth size and metabolic requirements in primates: the 'equivalence between exponents' under discussion / Tamaño de la dentición y requerimientos metabólicos en primates: la 'equivalencia entre exponentes' bajo discusión

The functional significance of teeth size, specifically postcanine tooth size has contributed a vast amount of scientific literature. Nevertheless, these studies have been based on 'equivalence between exponents'. That is, when the tooth size scales to the 0.75 power of body size exponent is interpreted as reflecting differences in metabolic requirements. On the contrary, if the obtained exponent is close to isometry, such slope is interpreted as that variation in teeth size is an incidental consequence of body size variation. In this paper, we show the results of a study in which the relationship between postcanine tooth occlusal area (PCOA) and basal metabolic rate (BMR) has been evaluated in 28 primate species. On one hand, the results obtained indicate that there is a high correlation between the BMR and the size of the PCOA, even when phylogenetic control tests are used, and that isometry cannot be discarded in both cases. However, if the effects of body mass are removed, a null slope cannot be discarded. On the other hand, when body mass (BM) is taken as the independent variable and PCOA as the dependent one, the slope obtained evidences a negative allometry, and this holds also when phylogenetic control is used. Given these contradictory results, we suggest that the rule of 'equivalence between exponents' is not a good approach for obtaining inferences on the function of postcanine teeth...

El significado funcional del tamaño de los dientes, y más concretamente del tamaño de la dentición poscanina, ha contribuido al desarrollo de una vasta literatura científica. No obstante, casi todos estos trabajos se han centrado en la 'equivalencia entre exponentes'. Así, cuando el tamaño de los dientes escala siguiendo una pendiente de 0,75 respecto al tamaño corporal se interpreta que las diferencias en tamaño reflejan los cambios en los requerimientos metabólicos. Si, por el contrario, el exponente obtenido es cercano a la isometría, la inferencia que se establece es que el cambio en el tamaño de la dentición es una consecuencia incidental del cambio en el tamaño corporal. En este artículo mostramos los resultados de un estudio en el que se han evaluado las relaciones entre el área de la dentición poscanina (PCOA) y la tasa metabólica basal (BMR) en 28 especies de primates. Los resultados obtenidos indican, en primer lugar, que existe una fuerte correlación entre BMR y PCOA, incluso cuando el efecto de la filogenia es controlado. Sin embargo, cuando se evita el efecto del tamaño no se puede descartar que la pendiente sea igual a cero. En segundo lugar, cuando se realiza una regresión usando el tamaño corporal (BM) como variable independiente y PCOA como dependiente, la pendiente obtenida es alométricamente negativa, lo que se mantiene cuando se controla para la filogenia. Dado que los resultados son contradictorios, sugerimos que la regla de la 'equivalencia entre exponentes' no es una buena aproximación para obtener inferencias sobre la función de la dentición poscanina...

Fibromatosis gingival: diagnóstico y tratamiento: reporte de un caso / Gingival fibromatosis: diagnosis and treatment: case report

La fibromatosis gingival es una deformidad desarrollada de baja prevalencia. Las características clínicas de la FG incluyen tejidos gingivales hiperplásicos de consistencia firme y nodular, presentándose en forma generalizada o localizada. Las características histológicas de la FG incluyen principalmente tejido conectivo con un denso infiltrado rico en fibras de colágeno y un epitelio denso con papilas epiteliales largas. Se presenta un reporte de caso de un paciente masculino de 12 años referido para su tratamiento al servicio de Periodoncia e Implantes dentales de la Clínica Estomatológica Central de la Universidad Peruana Cayetano Heredia.

Gingival fibromatosis is a developed deformity with low prevalence. The clinical features of FG include hyperplastic gingival tissues usually firm and nodular, occurring in a generalized or localized form. The histologic features of FG mainly include connective tissue with a dense infiltrate rich in collagen fibers and dense epithelium with epithelial papillae long. This is a case report of a male patient of 12 years referred for treatment to a Periodontics and Implants Service of the Central Dental Clinic of the Cayetano Heredia Peruvian University.