Actualización en la prevención de las úlceras gastroduodenales inducidas por antiinflamatorios no esteroideos y sus complicaciones

Los antiinflamatorios no esteroideos (AINE) son ampliamente prescritos para el tratamiento de cuadros clínicos de dolor y procesos inflamatorios. No obstante, producen efectos adversos gastrointestinales que pueden ser graves y ser causa de ingreso hospitalario, sobre todo en los pacientes de edad avanzada. Estos efectos adversos son un problema de extraordinaria relevancia clínica, por su magnitud y gravedad, y, por tanto, es muy importante su prevención. La prevención de las úlceras gastrointestinales inducidas por AINE y sus complicaciones se basa en: a) el uso, siempre que sea posible, de los analgésicos sin efecto antiinflamatorio, y b) si es necesario el uso de un AINE, en la selección de los que tienen menor riesgo, en el empleo de dosis bajas, y en el uso de tratamientos profilácticos asociados en los pacientes de mayor riesgo (edad avanzada, antecedentes de úlcera péptica y complicaciones gastrointestinales y tratamiento concomitante con fármacos anticoagulantes y corticoides, entre otros)

On-road emissions of ammonia: An underappreciated source of atmospheric nitrogen deposition

We provide updated spatial distribution and inventory data for on-road NH3 emissions for the continental United States (U.S.) On-road NH3 emissions were determined from on-road CO2 emissions data and empirical NH3:CO2 vehicle emissions ratios. Emissions of NH3 from on-road sources in urbanized regions are typically 0.1– 1.3 t km−2 yr−1 while NH3 emissions in agricultural regions generally range from 0.4–5.5 t km−2 yr−1, with a few hot spots as high as 5.5–11.2 t km−2 yr−1. Counties with higher vehicle NH3 emissions than from agriculture include 40% of the U.S. population. The amount of wet inorganic N deposition as NH4+ from the National Atmospheric Deposition Program (NADP) network ranged from 37 to 83% with a mean of 58.7%. Only 4% of the NADP sites across the U.S. had \u3c45% of the N deposition as NH4+ based on data from 2014 to 2016, illustrating the near-universal elevated proportions of NH4+ in deposition across the U.S. Case studies of on-road NH3 emissions in relation to N deposition include four urban sites in Oregon and Washington where the average NH4- N:NO3-N ratio in bulk deposition was 2.3. At urban sites in the greater Los Angeles Basin, bulk deposition of NH4-N and NO3-N were equivalent, while NH4-N:NO3-N in throughfall under shrubs ranged from 0.6 to 1.7. The NH4-N:NO3-N ratio at 7–10 sites in the Lake Tahoe Basin averaged 1.4 and 1.6 in bulk deposition and throughfall, and deposition of NH4-N was strongly correlated with summertime NH3 concentrations. On-road emissions of NH3 should not be ignored as an important source of atmospheric NH3, as a major contributor to particulate air pollution, and as a driver of N deposition in urban and urban-affected regions

Educational sessions in pharmacovigilance: What do the doctors think?

Background: The aim of this study was to determine physicians"opinion regarding pharmacovigilance feedback sessions. A survey was conducted in a teaching hospital, and the physicians who attended the sessions were invited to participate by filling out a structured questionnaire. All sessions included a review of adverse drug reactions identified at the hospital and information on pharmacovigilance issues (news on warnings released by regulatory agencies or drug toxicity problems identified by recently published studies in medical journals). The survey questions were related to the interest, satisfaction, and belief in the utility of the sessions. A Likert scale (0-10 points) was used to assess physicians" opinions. Findings: A total of 159 physicians attended the sessions and 115 (72.3%) participated in the survey. The mean (SD) age was 38.9 (12.1) years, and 72 (62.6%) were men. The mean (SD) scores of interest, satisfaction with the information provided, and belief in the utility of these sessions were 7.52 (1.61), 7.58 (1.46), and 8.05 (1.38) respectively. Significant differences were observed among physicians according to medical category and speciality in terms of interest, satisfaction, and belief in the utility of those sessions. Conclusions: Educational activities for physicians, such as feedback sessions, can be integrated into the pharmacovigilance activities. Doctors who attend the sessions are interested in and satisfied with the information provided and consider the sessions to be useful. Additional studies on the development and effectiveness of educational activities in pharmacovigilance are necessary

Outcomes of off-label drug uses in hospitals: a multicentric prospective study

Purpose: The study aims to assess the clinical evidence, outcome and cost of off-label use of medicines in the hospital setting. Methods: A multicentric prospective cohort study of patients treated with off-label medicines was carried out in five tertiary hospitals from May 2011 to May 2012. Information on clinical characteristics of patients, drugs, outcomes and costs was collected. Patients were followed up to 6 months, and information was assessed by reviewing clinical records and interviewing physicians. Results: A total of 226 patients were included. The median (interquartile range (IQR)) age of patients was 46 (3362) years; 59 % were women. Patients had received a median of three previous treatments, and a lack of response (or suboptimal) was the main reason for off-label use (72.1 %). A total of 232 off-label medicines were administered for 102 different indications. The most frequent medicines were rituximab (49; 21.1 %), botulinum toxin (25; 10.7 %) and omalizumab (14; 6.0 %). In 117 (51.8 %) cases, the level of clinical evidence for their use was low. A partial clinical response was observed in 82 patients (36.3 %), complete response in 71 (31.4 %) and stabilization in 11 (4.9 %). A total of 58 (26.5 %) patients had adverse effects, which in 11 (4.9 %) were severe. The median (IQR) cost per patient was 2,943.07 (541.95,872.54). Conclusions: There was a high variability of off-label medicines and indications. Although the clinical evidence of off-label medicines was often low, clinical response was observed in many patients with previous multiple treatment failure, but at the expense of some adverse effects and a high cost. Registers of patients would be helpful for clinical decisions, although clinical trials are needed

Outcomes of off-label drug uses in hospitals : a multicentric prospective study

Altres ajuts: We would to thank the Spanish Ministry of Health, Social Affairs and Equality for their financial support given though a grant from the scholarship EC-206 in the public call for the promotion of independent clinical research (SAS/2370/2010 order of September 27)The study aims to assess the clinical evidence, outcome and cost of off-label use of medicines in the hospital setting. A multicentric prospective cohort study of patients treated with off-label medicines was carried out in five tertiary hospitals from May 2011 to May 2012. Information on clinical characteristics of patients, drugs, outcomes and costs was collected. Patients were followed up to 6 months, and information was assessed by reviewing clinical records and interviewing physicians. A total of 226 patients were included. The median (interquartile range (IQR)) age of patients was 46 (33-62) years; 59 % were women. Patients had received a median of three previous treatments, and a lack of response (or suboptimal) was the main reason for off-label use (72.1 %). A total of 232 off-label medicines were administered for 102 different indications. The most frequent medicines were rituximab (49; 21.1 %), botulinum toxin (25; 10.7 %) and omalizumab (14; 6.0 %). In 117 (51.8 %) cases, the level of clinical evidence for their use was low. A partial clinical response was observed in 82 patients (36.3 %), complete response in 71 (31.4 %) and stabilization in 11 (4.9 %). A total of 58 (26.5 %) patients had adverse effects, which in 11 (4.9 %) were severe. The median (IQR) cost per patient was €2,943.07 (541.9-5,872.54). There was a high variability of off-label medicines and indications. Although the clinical evidence of off-label medicines was often low, clinical response was observed in many patients with previous multiple treatment failure, but at the expense of some adverse effects and a high cost. Registers of patients would be helpful for clinical decisions, although clinical trials are needed. The online version of this article (doi:10.1007/s00228-014-1746-2) contains supplementary material, which is available to authorized users

Available evidence and outcome of off-label use of rituximab in clinical practice

Purpose: To analyze the therapeutic indications for off-label use of rituximab, the available evidence for its use, the outcomes, and the cost. Methods: This was a retrospective analysis of patients treated with rituximab for off-label indications from January 2007 to December 2009 in two tertiary hospitals. Information on patient characteristics, medical conditions, and therapeutic responses was collected from medical records. Available evidence for the efficacy of rituximab in each condition was reviewed, and the cost of treatment was calculated. Results: A total of 101 cases of off-label rituximab use were analyzed. The median age of the patients involved was 53 [interquartile range (IQR) 37.5-68.0] years; 55.4 % were women. The indications for prescribing rituximab were primarily hematological diseases (46 %), systemic connective tissue disorders (27 %), and kidney diseases (20 %). Available evidence supporting rituximab treatment for these indications mainly came from individual cohort studies (53.5 % of cases) and case series (25.7 %). The short-term outcome (median 3 months, IQR 2-4 months) was a complete response in 38 % of cases and partial response in 32.6 %. The highest short-term responses were observed for systemic lupus erythematosus and membranous glomerulonephritis, and the lowest was for neuromyelitis optica, idiopathic thrombocytopenic purpura, and miscellaneous indications. Some response was maintained in long-term follow-up (median 23 months IQR 12-30months) in 69.2%of patients showing a short-term response. Median cost per patient was 5,187.5 (IQR 5,187.5-7,781.3). Conclusions: In our study, off-label rituximab was mainly used for the treatment of hematological, kidney, and systemic connective tissue disorders, and the response among our patient cohort was variable depending on the specific disease. The level of evidence supporting the use of rituximab for these indications was low and the cost was very high. We conclude that more clinical trials on the off-label use of rituximab are needed, although these may be difficult to conduct in some rare diseases. Data from observational studies may provide useful information to assist prescribing in clinical practice

Information and feedback to improve occupational physicians’ reporting of occupational diseases: a randomised controlled trial

To assess the effectiveness of supplying occupational physicians (OPs) with targeted and stage-matched information or with feedback on reporting occupational diseases to the national registry in the Netherlands. In a randomized controlled design, 1076 OPs were divided into three groups based on previous reporting behaviour: precontemplators not considering reporting, contemplators considering reporting and actioners reporting occupational diseases. Precontemplators and contemplators were randomly assigned to receive stage-matched, stage-mismatched or general information. Actioners were randomly assigned to receive personalized or standardized feedback upon notification. Outcome measures were the number of OPs reporting and the number of reported occupational diseases in a 180-day period before and after the intervention. Precontemplators were significantly more male and self-employed compared to contemplators and actioners. There was no significant effect of stage-matched information versus stage-mismatched or general information on the percentage of reporting OPs and on the mean number of notifications in each group. Receiving any information affected reporting more in contemplators than in precontemplators. The mean number of notifications in actioners increased more after personalized feedback than after standardized feedback, but the difference was not significant. This study supports the concept that contemplators are more susceptible to receiving information but could not confirm an effect of stage-matching this information on reporting occupational diseases to the national registr

Actualización en la prevención de las úlceras gastroduodenales inducidas por antiinflamatorios no esteroideos y sus complicaciones

Los antiinflamatorios no esteroideos (AINE) son ampliamente prescritos para el tratamiento de cuadros clínicos de dolor y procesos inflamatorios. No obstante, producen efectos adversos gastrointestinales que pueden ser graves y ser causa de ingreso hospitalario, sobre todo en los pacientes de edad avanzada. Estos efectos adversos son un problema de extraordinaria relevancia clínica, por su magnitud y gravedad, y, por tanto, es muy importante su prevención. La prevención de las úlceras gastrointestinales inducidas por AINE y sus complicaciones se basa en: a) el uso, siempre que sea posible, de los analgésicos sin efecto antiinflamatorio, y b) si es necesario el uso de un AINE, en la selección de los que tienen menor riesgo, en el empleo de dosis bajas, y en el uso de tratamientos profilácticos asociados en los pacientes de mayor riesgo (edad avanzada, antecedentes de úlcera péptica y complicaciones gastrointestinales y tratamiento concomitante con fármacos anticoagulantes y corticoides, entre otros). En este artículo de actualización se revisan y discuten los artículos originales más relevantes que se han publicado durante los últimos años y en los que se ha evaluado el uso de nuevos AINE con un hipotético menor riesgo gastrointestinal y en la eficacia de diferentes estrategias terapéuticas para prevenir el riesgo de las úlceras inducidas por AINE. Se han utilizado las palabras clave Anti-inflammatory agents, Non-steroidal, NSAID, Peptic ulcer, Prevention and control y Helicobacter pylori para la identificación y selección de los artículos más relevantes, a partir de las bases de datos bibliográficas PubMed, SIETES (www.sietes. org), Cochrane Database of Systematic Reviews y Cochrane Controlled Trials Register, publicados desde el año 2000

A structural basis for the unequal sensitivity of the major cardiac and liver gap junctions to intracellular acidification: the carboxyl tail length.

The regulation of junctional conductance (Gi) of the major cardiac (connexin43; Cx43) and liver (connexin32; Cx32) gap junction proteins by intracellular hydrogen ion concentration (pH; pHi), as well as well as that of a truncation mutant of Cx43 (M257) with 125 amino acids deleted from the COOH terminus, was characterized in pairs of Xenopus laevis oocytes expressing homologous channels. Oocytes were injected with 40 nl mRNAs (2 micrograms/microliters) encoding the respective proteins; subsequently, cells were stripped, paired, and incubated for 20-24 h. Gj was measured in oocyte pairs using the dual electrode voltage-clamp technique, while pHi was recorded simultaneously in the unstimulated cell by means of a proton-selective microelectrode. Because initial experiments showed that the pH-sensitive microelectrode responded more appropriately to acetate than to CO2 acidification, oocytes expressing Cx32 and wild type and mutant Cx43 were exposed to a sodium acetate saline, which was balanced to various levels of pH using NaOH and HCl. pH was changed in a stepwise manner, and quasi-steady-state Gj -pHi relationships were constructed from data collected at each step after both Gj and pHi had reached their respective asymptotic values. A moderate but significant increase of Gj was observed in Cx43 pairs as pHi decreased from 7.2 to 6.8. In both Cx32 and M257 pairs, Gj increased significantly over a wider pH range (i.e., between 7.2 and 6.3). Further acidification reversibly reduced Gj to zero in all oocyte pairs. Pooled data for the individual connexins obtained during uncoupling were fitted by the Hill equation; apparent 50%-maximum (pK;pKa) values were 6.6 and 6.1 for Cx43 and Cx32, respectively, and Hill coefficients were 4.2 for Cx43 and 6.2 for Cx32. Like Cx32, M257 had a more acidic pKa (6.1) and steeper Hill coefficient (6.0) than wild type Cx43. The pKa and Hill coefficient of M257 were very similar to those of Cx32. These experiments provide the first direct comparison of the effects of acidification on Gj in oocyte pairs expressing Cx43 or Cx32. The results indicate that structural differences in the connexins are the basis for their unequal sensitivity to intracellular acidification in vivo. The data further suggest that a common pH gating mechanism may exist between amino acid residues 1 and 256 in both Cx32 and Cx43. However, the longer carboxyl tail of Cx43 relative to Cx32 or M257 provides additional means to facilitate acidification-induced gating; its presence shifts the pKa from 6.1 (Cx32 and M257) to 6.6 (Cx43) in the conductance of these channels