Enzyme replacement therapy for the treatment of Hunter disease: A systematic review with narrative synthesis and meta-analysis

Background: In the last 10 years enzyme replacement therapy (ERT) has become an alternative for the treatment of patients with Hunter disease (HD). Nevertheless, the information regarding efficacy and safety is scarce and mainly based on the pivotal trials. This scarcity is especially evident for adults and severe forms of HD. Methods: A systematic review of publications in the electronic databases PUBMED, EMBASE and Cochrane Central was undertaken. Clinical trials and observational studies were included. The data about efficacy and security were retrieved and analysed with Review Manager version 5.3. Results: 677 records were found, 559 remaining after the removal of duplicates. By title and abstract review, 427 were excluded. Full reading of the rest was made (122 publications) and 42 were finally included. It was not possible to perform meta-analysis of all the endpoints due to high heterogeneity in the reporting and measuring of variables in each publication. Eight clinical trials were included, 6 with high risk of bias. The quality of the other studies was low in 12%, average in 68% and good in 21%. Main findings were: a reduction in the elimination of glycosaminoglycans (GAG) in urine in all the studies (26/26), decrease in liver and spleen size (18/18), increase of 52.59 m (95% CI, 36, 42-68.76, p < .001) in the 6-min walk test (TM6M), increase in forced vital capacity (FVC) of 9.59% (95% CI 4.77-14.51, p < .001), reduction of the left ventricular mass index of 3.57% (95% CI 1.2-5.93) and reduction in mortality (OR) of 0.44 (0.27-0.71). Discussion: The data suggests a clear and consistent effect of ERT in HD reducing the accumulation of GAGs in the body, demonstrated by the reduction of its urinary excretion, as well as by the reduction of its deposits (spleen, liver and heart). Likewise, there is an improvement in physical and respiratory function. In addition, a reduction in mortality has been observed. Lack of studies, small size of the samples, and methodological deficiencies are the main limitations to establish definite conclusions. Conclusions: The data suggests that ERT is effective and safe in the treatment of HD. There is a need to evaluate patient-centred outcomes and the impact on quality of life

Inappropriate antibiotic use in the COVID-19 era: Factors associated with inappropriate prescribing and secondary complications. Analysis of the registry SEMI-COVID

Background: Most patients with COVID-19 receive antibiotics despite the fact that bacterial co-infections are rare. This can lead to increased complications, including antibacterial resistance. We aim to analyze risk factors for inappropriate antibiotic prescription in these patients and describe possible complications arising from their use. Methods: The SEMI-COVID-19 Registry is a multicenter, retrospective patient cohort. Patients with antibiotic were divided into two groups according to appropriate or inappropriate prescription, depending on whether the patient fulfill any criteria for its use. Comparison was made by means of multilevel logistic regression analysis. Possible complications of antibiotic use were also identified. Results: Out of 13,932 patients, 3047 (21.6%) were prescribed no antibiotics, 6116 (43.9%) were appropriately prescribed antibiotics, and 4769 (34.2%) were inappropriately prescribed antibiotics. The following were independent factors of inappropriate prescription: February-March 2020 admission (OR 1.54, 95%CI 1.18-2.00), age (OR 0.98, 95%CI 0.97-0.99), absence of comorbidity (OR 1.43, 95%CI 1.05-1.94), dry cough (OR 2.51, 95%CI 1.94-3.26), fever (OR 1.33, 95%CI 1.13-1.56), dyspnea (OR 1.31, 95%CI 1.04-1.69), flu-like symptoms (OR 2.70, 95%CI 1.75-4.17), and elevated C-reactive protein levels (OR 1.01 for each mg/L increase, 95% CI 1.00-1.01). Adverse drug reactions were more frequent in patients who received ANTIBIOTIC (4.9% vs 2.7%, p < .001). Conclusion: The inappropriate use of antibiotics was very frequent in COVID-19 patients and entailed an increased risk of adverse reactions. It is crucial to define criteria for their use in these patients. Knowledge of the factors associated with inappropriate prescribing can be helpful

Post-Hospital Syndrome and Hyponatremia

Introduction: Post-hospital syndrome (PHS) is defined as a period of vulnerability during the first 30 days after a patient is discharged from hospital, in which multiple factors come into play. Hyponatremia is the most frequent hydroelectrolytic disorder in hospitalized patients and may be related to the appearance of PHS. Objective: The objective is to estimate the prevalence of PHS that is assessed as the rate of readmissions in the first 30 days after discharge, in patients with hyponatremia. Material and Methods: It is a descriptive observational study of patients with hyponatremia who were discharged from 1 September 2010 to 2 February 2020 at the Internal Medicine Service of the Hospital University of San Juan (Alicante, Spain). Results: Of the 25 included patients, 5 (20%) were readmitted within a month of discharge, after a mean of 11.4 days (standard deviation [SD] 5.1). The overall mortality of the study was 20% (n = 5), with one case of death in the first 30 days post-hospitalization (4%). In 12 patients (48%) the origin of the hyponatremia was undetermined. The most frequently recorded etiology for the condition was pharmacological (n = 7, 28%), and there was pronounced variability in its clinical and laboratory study. The most widely used corrective measure was drug withdrawal, in 16 patients (64%). Water intake restriction was the most common treatment after discharge (5 patients, 20%), followed by urea (2 patients, 8%), while tolvaptan was not used. Conclusion: Hyponatremia may be the cause of PHS, which could increase the rate of early readmission. Hyponatremia is an underdiagnosed and undertreated entity, so it is necessary to apply an appropriate system to optimize its management and, in future studies, to assess its impact on PHS

La ampliación de la Unión Europea de 2004-2007: Pasado, Presente y Futuro

Desde la suscripción de los primeros tratados que dieron origen a la Comunidad Europea, constituida por seis países, hasta la actualidad en que la Unión Europea está conformada por veintisiete países se han producido seis procesos distintos de ampliación, siete si se cuenta la reunificación alemana: - En 1958 los seis estados fundadores de Comunidad Europea del Carbón y del Acero (Bélgica, República Federal Alemana, Francia, Italia, Luxemburgo y los Países Bajos), constituyeron la Comunidad Económica Europea y la Comunidad Europea de la Energía Atómica. - En 1973 se incorporaron el Reino Unido, Irlanda y Dinamarca (incluida Groenlandia y excluidas las Islas Feroe). - En 1981 se incorporó Grecia. En 1985 se retiró Groenlandia como consecuencia del referéndum de 1982. - En 1986 se incorporaron España y Portugal. - En 1990 se produjo la reunificación de la República Federal Alemana y la República Democrática Alemana (RDA) en una nueva RFA unificada, constituye una ampliación de la Unión sin que aumente el número de estados miembros. Comienza a usarse formalmente, en el año 1993, el término Unión Europea. - En 1995 se incorporaron Austria, Finlandia y Suecia. - En 2004 se incorporaron República Checa, Chipre (sólo la parte greco-chipriota), Eslovaquia, Eslovenia, Estonia, Hungría, Letonia, Lituania, Malta y Polonia. - En 2007 se incorporaron Rumanía y Bulgaria

La ampliación de la Unión Europea de 2004-2007: Pasado, Presente y Futuro

Desde la suscripción de los primeros tratados que dieron origen a la Comunidad Europea, constituida por seis países, hasta la actualidad en que la Unión Europea está conformada por veintisiete países se han producido seis procesos distintos de ampliación, siete si se cuenta la reunificación alemana: -;En 1958 los seis estados fundadores de Comunidad Europea del Carbón y del Acero (Bélgica, República Federal Alemana, Francia, Italia, Luxemburgo y los Países Bajos), constituyeron la Comunidad Económica Europea y la Comunidad Europea de la Energía Atómica. -;En 1973 se incorporaron el Reino Unido, Irlanda y Dinamarca (incluida Groenlandia y excluidas las Islas Feroe). -;En 1981 se incorporó Grecia. En 1985 se retiró Groenlandia como consecuencia del referéndum de 1982. -;En 1986 se incorporaron España y Portugal. -;En 1990 se produjo la reunificación de la República Federal Alemana y la República Democrática Alemana (RDA) en una nueva RFA unificada, constituye una ampliación de la Unión sin que aumente el número de estados miembros. Comienza a usarse formalmente, en el año 1993, el término Unión Europea. -;En 1995 se incorporaron Austria, Finlandia y Suecia. -;En 2004 se incorporaron República Checa, Chipre (sólo la parte greco-chipriota), Eslovaquia, Eslovenia, Estonia, Hungría, Letonia, Lituania, Malta y Polonia. -;En 2007 se incorporaron Rumanía y Bulgaria

Multidisciplinary Scientific Cruise to the Northern Mid-Atlantic Ridge and Azores Archipelago

This work presents the preliminary result of the multidisciplinary cruise EXPLOSEA2 surveying the northern Mid-Atlantic Ridge and Azores Archipelago from 46° 30′ N to 38° 30′ N aboard the R/V Sarmiento de Gamboa and ROV Luso over 54 days (June 11 to July 27, 2019). In this cruise report, we detail the geophysical, hydrographic, geological, oceanographic, ecological, and microbiological data acquired and a brief of main findings. The cruise addressed the exploration and comprehensive characterization of venting sites, including the water column, the sediments and rocks that host the hydrothermal activity, and the associated mineralizations, biology, and microbiology. Deep hydrothermal chimneys and massive sulfide deposits (up 3,000 m in depth) within the Moytirra hydrothermal active field were identified on slopes that had not been explored previously. Another striking finding made during the EXPLOSEA2 cruise was the field of carbonate chimneys named the “Magallanes-Elcano” field, a potentially relict ultramafic-hosted hydrothermal site sourced by abiotic methane. This field is related to a serpentinite and gabbro rock outcropping on a dome-shaped massif named the “Iberian Massif.” An outstanding finding of the EXPLOSEA2 survey was the identification of the first garden of soft corals growing after active submarine eruptions were reported in the Azores Archipelago composed by a high density of soft corals the suborder Alcyoniina at the summit and flanks of a recent volcanic cone at 160 m water depth developed during the 1957–1958 eruption of Capelinhos. Several cold-water coral habitats formed by colonial scleractinians (e.g., Lophelia pertusa and Madrepora oculata), coral gardens composed of mixed assemblages of black corals (Leiopathes sp.), and octocorals and dense aggregations of the glass sponge Pheronema carpenteri that may be classified as vulnerable marine ecosystems (VMEs) have been discovered during the EXPLOSEA2 cruise along the northern Mid-Atlantic Ridge. This work reveals the importance of multidisciplinary surveys to the knowledge of deep-sea environments

Contemporary use of cefazolin for MSSA infective endocarditis: analysis of a national prospective cohort

Objectives: This study aimed to assess the real use of cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) in the Spanish National Endocarditis Database (GAMES) and to compare it with antistaphylococcal penicillin (ASP). Methods: Prospective cohort study with retrospective analysis of a cohort of MSSA IE treated with cloxacillin and/or cefazolin. Outcomes assessed were relapse; intra-hospital, overall, and endocarditis-related mortality; and adverse events. Risk of renal toxicity with each treatment was evaluated separately. Results: We included 631 IE episodes caused by MSSA treated with cloxacillin and/or cefazolin. Antibiotic treatment was cloxacillin, cefazolin, or both in 537 (85%), 57 (9%), and 37 (6%) episodes, respectively. Patients treated with cefazolin had significantly higher rates of comorbidities (median Charlson Index 7, P <0.01) and previous renal failure (57.9%, P <0.01). Patients treated with cloxacillin presented higher rates of septic shock (25%, P = 0.033) and new-onset or worsening renal failure (47.3%, P = 0.024) with significantly higher rates of in-hospital mortality (38.5%, P = 0.017). One-year IE-related mortality and rate of relapses were similar between treatment groups. None of the treatments were identified as risk or protective factors. Conclusion: Our results suggest that cefazolin is a valuable option for the treatment of MSSA IE, without differences in 1-year mortality or relapses compared with cloxacillin, and might be considered equally effective