Drug eruptions induced by telaprevir in patients with chronic hepatitis C virus genotype 1 infection: a prospective study.

INTRODUCTION: When co-administered with interferon and ribavirin, the prescription drug telaprevir significantly improves treatment response in patients with chronic hepatitis C virus (HCV) infection. Its use, however, also increases the likelihood of adverse effects that may lead to discontinuation of treatment. Cutaneous adverse effects are particularly common. OBJECTIVE: To determine the frequency and clinical characteristics of drug eruptions induced by telaprevir in patients receiving HCV treatment and to analyze the clinical course of lesions and response to treatment. MATERIAL AND METHODS: We performed a prospective observational study of all patients who started a treatment regimen that included telaprevir between May 2012 and July 2013. We recorded the demographic characteristics of the patients who developed telaprevir-induced eruptions, and analyzed the clinical characteristics of the lesions and their clinical course following the application of guideline-based treatment recommendations. RESULTS: Twenty (46%) of the 43 patients who received triple therapy with interferon, ribavirin, and telaprevir during the study period developed drug reactions attributable to telaprevir. The reaction was classified as mild or moderate (grades 1 or 2) in 90% of cases and consisted of an exanthem with erythematous-edematous scaling plaques and papules. The rash worsened, mainly by spreading, in about one-third of cases. The skin lesions led to discontinuation of treatment in 2 patients (4.6%). Sustained viral response was achieved in 34 patients (79%). CONCLUSIONS: Telaprevir-induced eruptions are common and often progress, but they rarely require patients to discontinue treatment.

The dynamics of arsenic and copper in solid and aqueous phases in reactive confluences receiving acid drainage: The role of turbidity and particle size.

The fate of suspended solids in aqueous systems enriched with copper (Cu) and arsenic (As) is still poorly understood, especially in mildly acidic streams with natural turbidity. This study integrated field, laboratory, and modeling to determine how turbidity, particle size distribution, and the partition of Cu and As interact in two model river confluences in an Andean watershed (upper Elqui, North-Central Chile). The mildly acidic Toro River (40.4 mgL-1; CuTOTAL>8 mgL-1) was diluted and neutralized at two consecutive confluences, resulting in dissolved As and Cu lower than 0.04 and 0.1 mgL-1, respectively. On-site laser scattering measurements showed that the size of suspended sediments was dominated by ultrafine (d<6 µm) and fine (6200 µm) were not observed, contrasting with other reactive Andean confluences that work as natural coagulation-flocculation reactors. Laboratory mixing experiments with filtered endmembers followed closely the trends observed in the field measurements. SEM observations and thermodynamic calculations, suggested that As-rich amorphous Fe minerals dominated the fine suspended solid inflow (d<15 µm) from the Toro River, while XRD did not reveal significant amounts of crystalline forms of Fe, As, or Cu minerals. Despite fresh precipitates that further associated dissolved As and Cu, the particles from the Toro River grew only slightly after the confluences, thus limiting particle settling potential and a significant metal-(loid)s removal. Consequently, the seasonal variation in the size and chemical nature of suspended solids in acid drainage inflows control the distinct physical and chemical fates of As and Cu after neutralization, as well as hydrodynamic or hydraulic conditions likely also constrain sediment deposition. The combined monitoring of chemical parameters and particle size distributions is a simple and cost-effective method to obtain information about the behavior of metal(loid)s and sediments.

Usefulness and correlation with clinical response of serum ustekinumab levels measured at 6 weeks versus 12 weeks.

BACKGROUND: Monitoring serum drug levels has been proposed as a useful tool for improving and personalizing the management of psoriasis. However, in the case of ustekinumab the usefulness of such monitoring was not demonstrated when drug levels were measured at week 12. OBJECTIVES: To evaluate the correlation of serum ustekinumab levels measured at weeks 6 and 12 with clinical response. METHODS: In a prospective cohort study, we enrolled patients with psoriasis treated with ustekinumab 45 mg every 12 weeks for at least 24 weeks. We measured serum ustekinumab levels at weeks 6 and 12 in each patient. Using the absolute PASI score, response to treatment was defined as optimal (≤1), excellent (≤3), appropriate (>3 and ≤5), or inappropriate (>5). RESULTS: About 54 serum samples from 27 patients were analyzed. No correlation was found between serum drug levels and absolute PASI at week 12. At week 6, an inverse linear correlation was found (p = .0001). Moreover, serum levels at week 6 were higher in patients with optimal, excellent and appropriate responses than in patients with an inappropriate response. CONCLUSIONS: Assessment of ustekinumab serum levels at week 6 could provide useful information in routine clinical practice.

Correlation between trough serum levels of adalimumab and absolute PASI score in a series of patients with psoriasis.

BACKGROUND: The possibility of monitoring serum drug levels has opened the door to optimising biologic therapy. To consolidate this advance, it is imperative to demonstrate an adequate correlation between serum drug levels and clinical course. OBJECTIVES: To investigate whether a correlation exists between adalimumab levels and clinical response measured as absolute PASI. METHODS: In a prospective cohort study, we enrolled 51 patients with psoriasis treated with adalimumab for at least 16 s. Patients received approved doses of adalimumab, but after 52 s the dosing interval could be modified according to clinical criteria. Excellent response was defined as PASI ≤3, appropriate response as PASI >3 and ≤5 and inappropriate response as PASI> 5. Correlations were calculated using Spearman's correlation test. RESULTS: A total of 92 serum samples from 51 patients were analysed. Significant differences were found in serum trough levels between patients achieving an excellent response (6.46 µg/mL), versus an appropriate (2.5 µg/mL) and an inappropriate response (2 µg/mL). The therapeutic range for adalimumab serum levels was from 3.30 to 7.30 µg/mL. CONCLUSIONS: We found an adequate correlation between drug serum levels and PASI scores. Monitoring of absolute PASI and serum levels can provide a personalised and cost-effective evaluation.

[Serological survey of human leptospirosis in a high risk population in Chile]. / Encuesta serológica de leptospirosis humana en ocupaciones de alto riesgo en Chile.

Two hundred and sixty five subjects with high risk works for leptospirosis were submitted to microscopic agglutination test for leptospira. 122 worked at animal farms, 71 in rice growing fields and 72 in slaughter houses. 30 control subjects were also tested. A total of 66 samples (22%) were positive, most of them with low titers. Percentage of positive reactions were higher for persons working in rice fields, followed by those working in slaughter houses and animal farms. The 21-40 year age group was most affected in all working sites. Serovars found most commonly were ichterohemorrhagic in rice field workers, hardjo and ballum in slaughter houses and pomona and hardjo in animal farms.

Physicochemical properties of a beta-lactamase from Streptomyces UCSM-104.

A purified beta-lactamase from Streptomyces UCSM-104 shows the presence of three subforms when stained for protein and/or for activity after polyacrylamide gel electrophoresis or after electrofocusing. The pI values of the three subforms were 5.45, 5.30 and 5.10, respectively. The respective electrophoretic mobilities were 4.6 X 10(-5), 5.2 X 10(-5) and 5.9 X 10(-5)m2/sV. Relative molecular mass of 14,900 was determined. The amino acid composition was established. Cysteine was not detected. A fairly high proline content (8.3%) differentiates this enzyme from other beta-lactamases. Lysine was the only N-terminal amino acid detected after dansylation. The possible origin of the subforms is discussed.

Bocio endemico: encuesta de prevalencia en escolares de la comuna de Alhue - 1983. / Endemic goiter: prevalence study among school children in Alhue

Se presentan los resultados de un estudio de prevalencia de bocio en una area endemica (Alhue). Se examinaron 556 escolares basicos de ambos sexos (72.7% de la poblacion escolar); encontrandose una prevalencia de 36.2% (201 casos). La cifra mas alta se observo en Hacienda Alhue: 44.9% (22 casos) y la mas baja: 23.5% (4 casos) en Polulo. Entre las mujeres se observo una prevalencia de 39.9% (110 casos) y una de 32.5% (91 casos) entre los hombres (diferencia no significativa). Los grados mas frecuentes de bocio fueron Ia (99 casos) 7.8% y Ib (94 casos); 16.9%. El sexo femenino presento frecuencias mayores aunque no significativas de bocio de todos los tipos. Basados en estudios anteriores se concluye que la situacion regional no ha mejorado en tres decadas. Se formulan recomendaciones para el estudio y control del problema