Long-term safety and efficacy of etanercept in the treatment of ankylosing spondylitis

[EN] To date, anti-tumor necrosis factor alfa (anti-TNF-α) therapy is the only alternative to nonsteroidal anti-inflammatory drugs for the treatment of ankylosing spondylitis. Etanercept is a soluble TNF receptor, with a mode of action and pharmacokinetics different to those of antibodies and distinctive efficacy and safety. Etanercept has demonstrated efficacy in the treatment of ankylosing spondylitis, with or without radiographic sacroiliitis, and other manifestations of the disease, including peripheral arthritis, enthesitis, and psoriasis. Etanercept is not efficacious in inflammatory bowel disease, and its efficacy in the treatment of uveitis appears to be lower than that of other anti-TNF drugs. Studies of etanercept confirmed regression of bone edema on magnetic resonance imaging of the spine and sacroiliac joint, but failed to reduce radiographic progression, as do the other anti-TNF drugs. It seems that a proportion of patients remain in disease remission when the etanercept dose is reduced or administration intervals are extended. Etanercept is generally well tolerated with an acceptable safety profile in the treatment of ankylosing spondylitis. The most common adverse effect of etanercept treatment is injection site reactions, which are generally self-limiting. Reactivation of tuberculosis, reactivation of hepatitis B virus infection, congestive heart failure, demyelinating neurologic disorders, hematologic disorders like aplastic anemia and pancytopenia, vasculitis, immunogenicity, and exacerbation or induction of psoriasis are class effects of all the anti-TNF drugs, and have been seen in patients with ankylosing spondylitis. However, etanercept is less likely to induce reactivation of tuberculosis than the other anti-TNF drugs and it has been suggested that etanercept might be less immunogenic, especially in ankylosing spondylitis. Acute uveitis, Crohn’s disease, and sarcoidosis are other adverse events that have been rarely associated with etanercept therapy in patients with ankylosing spondylitis.Senabre-Gallego, JM.; Santos-Ramírez, C.; Santos-Soler, G.; Salas-Heredia, E.; Sánchez Barrioluengo, M.; Barber, X.; Rosas, J. (2013). Long-term safety and efficacy of etanercept in the treatment of ankylosing spondylitis. Patient Preference and Adherence. 7:961-972. doi:10.2147/PPA.S33109S961972

NIL10: A New IL10-Receptor Binding Nanoparticle That Induces Cardiac Protection in Mice and Pigs Subjected to Acute Myocardial Infarction through STAT3/NF-kB Activation.

Background: Early response after acute myocardial infarction (AMI) prevents extensive cardiac necrosis, in which inflammation resolution, including expression of anti-inflammatory interleukin-10 (IL-10), may play a key role. (2) Methods: We synthesized NIL10, a micelle-based nanoparticle, to target IL-10 receptor in mice and pigs subjected to AMI. (3) Results: Administration of NIL10 induced cardiac protection of wild-type and IL-10 knockout mice and pigs subjected to AMI. Cardiac protection was not induced in IL-10-receptor null mice, as shown by a significant recovery of cardiac function, in which inflammatory foci and fibrosis were strongly reduced, together with the finding that resolving M2-like macrophage populations were increased after day 3 of reperfusion. In addition, anti-inflammatory cytokines, including IL-4, IL-7, IL-10, IL-13, IL-16, and IL-27 were also elevated. Mechanistically, NIL10 induced activation of the IL-10 receptor/STAT-3 signaling pathway, and STAT3-dependent inhibition of nuclear translocation of pro-inflammatory NF-kB transcription factor. (4) Conclusions: Taken together, we propose using NIL10 as a novel therapeutic tool against AMI-induced cardiac damagepost-print4711 K

Effect of Different Nucleating Agents on the Crystallization of Ziegler-Natta Isotactic Polypropylene

Ziegler-Natta isotactic polypropylene (iPP) was melt mixed with four different nucleating agents (carbon nanotubes (CNT), carbon nanofibers (CNF), lithium benzoate (LiBe), and a sorbitol derivative (Millad)) in order to study their effect on the crystallization of iPP. It was found that the four different nucleating agents promote the alpha crystalline form. At 0.01 wt%, the carbon nanoparticles produced the higher crystallization temperature “Tc” (~119°C), whereas, at 0.10 wt%, LiBe and Millad produced a markedly higher Tc (~125°C). Tc of pure iPP was 111°C. With 0.1 wt% nucleating agent, at 120°C, the crystallization half-life time of PP, when using LiBe or Millad, was 15 times faster than for pure PP, whereas, when using carbon nanoparticles, it was 20–25 times faster. At 135°C, with 0.01 wt% nucleating agent, the isothermal crystallization process of iPP was completed after 25 min, as well as with Millad. With LiBe, it was completed after just 15 min and, with any of the carbon nanoparticles, it was practically over after only a couple of minutes

Benthic Fauna of Littoral and Deep-Sea Habitats of the Alboran Sea: A Hotspot of Biodiversity

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Use of evidence during the COVID-19 pandemic in Peru, contributions from the National Institute of Health

Indexado en ScopusLa pandemia por COVID-19 ha llevado a tomar decisiones rápidamente. En este contexto el INS elaboró una serie de documentos de síntesis de evidencia científica, en función a requerimientos del Ministerio de Salud. Así mismo a partir de estos informes se desarrollaron recomendaciones para la actualización de documentos normativos relacionados al manejo de la COVID-19. Este artículo describe el proceso de construcción de una metodología aplicada por el Instituto Nacional de Salud para la síntesis de evidencias científicas durante la pandemia por COVID-19, destacando los esfuerzos y estrategias para asegurar la calidad metodológica y la aplicación del enfoque GRADE en el fortalecimiento de las decisiones. Finalmente, proporciona una breve reflexión sobre las limitaciones y los desafíos del uso de evidencias para el diseño de políticas públicas nacionales en el futuro.The COVID-19 pandemics required the countries to take decisions rapidly. Consequently, the National Institute of Health (INS) developed a series of documents of scientific evidence synthesis according to the Ministry of Health’s requirements. Based on these reports, the INS developed recommendations to update normative documents related to COVID-19’s management. This article describes the construction of anew methodology applied by the INS to synthesize scientific evidence during the COVID-19 pandemic. Moreover, it emphasizes the efforts and strategies used to guarantee the methodological quality and the implementation of the GRADE approach. Finally, it provides a short reflection on the limitations and challenges of using evidence to design national public policies in the future.Revisión por pare

Use of evidence during the COVID-19 pandemic in Peru, contributions from the National Institute of Health

The COVID-19 pandemics required the countries to take decisions rapidly. Consequently, the National Institute of Health (INS) developed a series of documents of scientific evidence synthesis according to the Ministry of Health’s requirements. Based on these reports, the INS developed recommendations to update normative documents related to COVID-19’s management. This article describes the construction of a new methodology applied by the INS to synthesize scientific evidence during the COVID-19 pandemic. Moreover, it emphasizes the efforts and strategies used to guarantee the methodological quality and the implementation of the GRADE approach. Finally, it provides a short reflection on the limitations and challenges of using evidence to design national public policies in the future.Revisión por pare

Design and evaluation of a mobile-based intervention for Maya adults during the COVID-19 pandemic

Introduction: The COVID-19 pandemic has had a direct impact on mental health. International organisations have emphasised the vulnerability of indigenous people. Digital Mental Health approaches deliver online therapy as an evidence-based, effective, and accessible treatment option for common mental health problems. However, the evidence regarding these approaches is limited in indigenous populations. The objective of this study is to describe the design, development, and evaluation of the efficacy of a self-applied online intervention regarding the psychological symptoms of depression, anxiety, and fear of COVID-19 in a sample of the Maya population. Method: A prospective longitudinal quantitative study was designed, where a single group was measured before and after receiving the online intervention. This study took place from April to September 2021 and consisted of six sessions delivered via WhatsApp in Spanish and Mayan. Results: The initial assessment was implemented with 82 participants who were evaluated using the Patient Health Questionnaire, Scale for Generalised Anxiety Disorder and the Fear of COVID-19 Scale; 18 participants remained in the intervention for the post-as-sessment. Statistical differences were observed in PRE and POST measures of depression and anxiety, but not in fear of COVID-19. Conclusions: This study produced positive results for the first online mental health intervention implemented in the Latin American indigenous population. Future studies might consider developing similar interventions for other indigenous communities in Latin America.</p

Predictive Power of the "Trigger Tool" for the detection of adverse events in general surgery: a multicenter observational validation study

Background In spite of the global implementation of standardized surgical safety checklists and evidence-based practices, general surgery remains associated with a high residual risk of preventable perioperative complications and adverse events. This study was designed to validate the hypothesis that a new “Trigger Tool” represents a sensitive predictor of adverse events in general surgery. Methods An observational multicenter validation study was performed among 31 hospitals in Spain. The previously described “Trigger Tool” based on 40 specific triggers was applied to validate the predictive power of predicting adverse events in the perioperative care of surgical patients. A prediction model was used by means of a binary logistic regression analysis. Results The prevalence of adverse events among a total of 1,132 surgical cases included in this study was 31.53%. The “Trigger Tool” had a sensitivity and specificity of 86.27% and 79.55% respectively for predicting these adverse events. A total of 12 selected triggers of overall 40 triggers were identified for optimizing the predictive power of the “Trigger Tool”. Conclusions The “Trigger Tool” has a high predictive capacity for predicting adverse events in surgical procedures. We recommend a revision of the original 40 triggers to 12 selected triggers to optimize the predictive power of this tool, which will have to be validated in future studies

Effectiveness of Fosfomycin for the Treatment of Multidrug-Resistant Escherichia coli Bacteremic Urinary Tract Infections

IMPORTANCE The consumption of broad-spectrum drugs has increased as a consequence of the spread of multidrug-resistant (MDR) Escherichia coli. Finding alternatives for these infections is critical, for which some neglected drugs may be an option. OBJECTIVE To determine whether fosfomycin is noninferior to ceftriaxone or meropenem in the targeted treatment of bacteremic urinary tract infections (bUTIs) due to MDR E coli. DESIGN, SETTING, AND PARTICIPANTS This multicenter, randomized, pragmatic, open clinical trial was conducted at 22 Spanish hospitals from June 2014 to December 2018. Eligible participants were adult patients with bacteremic urinary tract infections due to MDR E coli; 161 of 1578 screened patients were randomized and followed up for 60 days. Data were analyzed in May 2021. INTERVENTIONS Patients were randomized 1 to 1 to receive intravenous fosfomycin disodium at 4 g every 6 hours (70 participants) or a comparator (ceftriaxone or meropenem if resistant; 73 participants) with the option to switch to oral fosfomycin trometamol for the fosfomycin group or an active oral drug or pa renteral ertapenem for the comparator group after 4 days. MAIN OUTCOMES AND MEASURES The primary outcome was clinical and microbiological cure (CMC) 5 to 7 days after finalization of treatment; a noninferiority margin of 7% was considered. RESULTS Among 143 patients in the modified intention-to-treat population (median [IQR] age, 72 [62-81] years; 73 [51.0%] women), 48 of 70 patients (68.6%) treated with fosfomycin and 57 of 73 patients (78.1%) treated with comparators reached CMC (risk difference, -9.4 percentage points; 1-sided 95% CI, -21.5 to infinity percentage points; P = .10). While clinical or microbiological failure occurred among 10 patients (14.3%) treated with fosfomycin and 14 patients (19.7%) treated with comparators (risk difference, -5.4 percentage points; 1-sided 95% CI. -infinity to 4.9; percentage points; P = .19), an increased rate of adverse event-related discontinuations occurred with fosfomycin vs comparators (6 discontinuations [8.5%] vs 0 discontinuations; P = .006). In an exploratory analysis among a subset of 38 patients who underwent rectal colonization studies, patients treated with fosfomycin acquired a new ceftriaxone-resistant or meropenem-resistant gram-negative bacteria at a decreased rate compared with patients treated with comparators (0 of 21 patients vs 4 of 17 patients [23.5%]; 1-sided P = .01). CONCLUSIONS AND RELEVANCE This study found that fosfomycin did not demonstrate noninferiority to comparators as targeted treatment of bUTI from MDR E coli; this was due to an increased rate of adverse event-related discontinuations. This finding suggests that fosfomycin may be considered for selected patients with these infections