Search

Introduction: Rheumatoid arthritis (RA) is the most common chronic inflammatory rheumatic disease, its management and morbidity impose a great burden to healthcare systems. Development and rollout of biological disease modifying anti-rheumatic drugs has contributed to improvements for patients, however, high costs have prevented them to be widely used. This is being addressed with biosimilars, with equal benefit-risk profile and reduced costs. The objective is to analyze the cost-effectiveness of subcutaneous biosimilar tocilizumab (bsTCZ) for patients with moderate-severe RA in Spain from a healthcare system perspective., Methods: A Markov model was developed with a lifetime horizon including 5 health states: remission of the disease; low, moderate, or high activity; and death. A PICO-S-T search retrieved efficacy of treatments in meta-analysis and network meta-analysis, and was further complemented with published clinical trials. Pharmacological costs were obtained from the BotPlus database, and medical resources costs from regional tariffs. Deterministic and probabilistic sensitivity analysis were performed to validate the robustness of results. Incremental cost-effectiveness ratio (ICER) for cost/percentage of remission and cost/quality-adjusted life year (QALY) gain were calculated., Results: Lifetime cost of bsTCZ was 183 741€ (lowest) versus comparative costs ranging from 184 317€ for infliximab to 201 972€ (highest) for certolizumab. QALYs were 13.74 for upadacitinib and 13.73 for sarilumab and tocilizumab with values between 13.53 and 13.72 for the comparators. ICERs as €/remission and €/QALY showed that bsTCZ was either dominant in most of the comparisons or the most cost-effective alternative. The sensitivity analysis showed that bsTCZ long term cost, and transition from low to moderate disease activity health status were the most influential factors. Moreover, bsTCZ was either dominant or cost-effective in all the comparisons., Conclusions: bsTCZ demonstrated to be a cost-effective and cost-saving alternative for the treatment of patients with RA in Spain when compared to all the available therapeutic alternatives., Competing Interests: Declaration of competing interest FPR has earned advisory fees from protalix, horizon, arthrosis, and LG Pharma; speaker fees from Menarini, and Bioepis; and research grants from Asociación de Reumatólogos de Cruces. CCD has earned fees from: Abbvie, Almirall, Amgen, Biogen, Bristol Myers Squibb, Fresenius Kabi, Janssen-Cilag, Kern Pharma, Merck Sharp Done, Pfizer, Roche, UCB Pharma. JASA has earned fees from Fresenius Kabi and IQVIA. MC and CC are employees of Axentiva, a consulting firm that works for several pharmaceutical and medical devices companies. MAG and JIPF are employees of Fresenius Kabi Spain. MCM has earned fees from Abbvie, Fresenius Kabi, Janssen-Cilag, Kern Pharma, Leo-Pharma, Pfizer, and Roche., (Copyright © 2024. Publicado por Elsevier España, S.L.U.)

Objectives : Mitral regurgitation (MR) is the second most common valve disease in Europe, and differences between men and women have been described in relation to aetiology or management, which might impact the decision for intervention and patients' clinical and economic outcomes. Thus, the objective was to analyse the burden of MR in Spain by aetiology and sex, and the management of all patients suffering from MR being admitted to hospital between 2016-2021. Methods : An analysis was carried out with the Ministry of Health's database, including all patients in public and subsidised hospitals and defining two groups, general MR and those patients undergoing Transcatheter Edge-to-Edge repair (TEER), using a descriptive analysis of patients' characteristics, use of resources, and outcomes; standardised rates were calculated and observed outcomes were described. Results : Hospital admissions increased from 2016 ( n = 32,806) to 2021 (total n = 61,036). In general, the women were older and presented more complications. The majority of patients suffered from degenerative MR (DMR) ( n = 183,005, 59.55%), and 61.56% were women, contrary to functional MR (FMR) ( n = 124,278), which consisted of 62.15% males. In total, 1,689 TEERs were performed, 23.33% of them in urgent admissions, and mostly in men (65.66%). All groups showed higher rates of intervention for males. Regarding costs, women presented lower mean costs in the general MR groups but those undergoing TEER presented, in all cases, costs higher than men. Conclusions : MR entails a significant burden for patients and the Spanish healthcare system, increasing over the period of study. Differences in aetiologies by sex have been found in patients' characteristics as well as outcomes. Further studies are needed to optimise patients' management and their outcomes in relation to sex and aetiology.

Introduction and Aim: Dalbavancin is an antibiotic with activity against gram-positive bacteria that allows early discharge of patients requiring intravenous therapy. Outpatient treatment helps offset hospitalisation costs associated with standard intravenous treatment. Our objective was to assess the cost of disease management, including treatment with dalbavancin, in a Spanish hospital for 1 year, and the hypothetical costs associated with treatment with other therapeutic alternatives to dalbavancin., Methods: A single-centre, observational, retrospective post-hoc analysis was conducted based on electronic medical records analysing all patients who received dalbavancin treatment throughout 1 year; cost analysis was performed for the whole process. In addition, three scenarios designed on the basis of real clinical practice by clinical experts were hypothesised: (i) individual therapeutic alternative to dalbavancin, (ii) all patients treated with daptomycin, and (iii) all days of dalbavancin as outpatient treatment transformed into hospital stay. Costs were obtained from the hospital., Results: Thirty-four patients were treated with dalbavancin; their mean age was 57.9 years, and 70.6% were men. The main reasons for dalbavancin use were outpatient management (61.7%, n  = 21) and ensuring treatment adherence (26.5%, n  = 9). The main indications were: osteoarticular infection (32.4%) and infective endocarditis (29.4%). One-half (50%) of the infections were due to Staphylococcus aureus (23.5% were methicillin resistant). All patients achieved clinical resolution, and no costs associated with dalbavancin-associated adverse events or re-admissions were reported. The mean total cost of treatment was 22,738€ per patient, with the greatest expenditures in interventions (8,413€) and hospital stay (6,885€). The mean cost of dalbavancin treatment was 3,936€; without dalbavancin, this cost could have been increased to 3,324-11,038€ depending on the scenario, mainly due to hospital stays., Main Limitation: Limited sample size obtained from a single centre., Conclusion: The economic impact of the management of these infections is high. The cost of dalbavancin is offset by the decreased length of stay.

Background: The objective of the FeminFER project was to assess the value of ferric carboxymaltose following a multicriteria decision analysis in obstetrics and gynaecology in Spain., Methods: Ferric carboxymaltose (FCM) and ferrous sulphate were evaluated using the EVIDEM framework. Ten stakeholders participated to collect different perspectives. The framework was adapted considering evidence retrieved with a PICO-S search strategy and grey literature. Criteria/subcriteria were weighted by level of relevance and an evidence-based decision-making exercise was developed in each criterion; weights and scores were combined to obtain the value of intervention relative to each criterion/subcriterion, that were further combined into the Modulated Relative Benefit-Risk Balance (MRBRB)., Results: The most important criterion favouring FCM was Compared Efficacy/Effectiveness (0.183 ± 0.07), followed by Patient Preferences (0.059 ± 0.10). Only Direct medical costs criterion favoured FS (-0.003 ± 0.03). MRBRB favoured FCM; 0.45 ± 0.19; in a scale from -1 to + 1., Conclusions: In conclusion, considering the several criteria involved in the decision-making process, participants agreed with the use of FCM according to its MRBRB., (© 2022. The Author(s).)

Study Objective: Our goal is to review the outcomes of acute hypertensive/hypotensive episodes from articles published in the past 10 years that assessed the short- and long-term impact of acute hypertensive/hypotensive episodes in the perioperative setting., Methods: We conducted a systematic peer review based upon PROSPERO and Cochrane Handbook protocols. The following study characteristics were collected: study type, author, year, population, sample size, their definition of acute hypertension, hypotension or other measures, and outcomes (probabilities, odds ratio, hazard ratio, and relative risk) and the p-values; and they were classified according to the type of surgery (cardiac and non-cardiac)., Results: A total of 3,680 articles were identified, and 66 articles fulfilled the criteria for data extraction. For the perioperative setting, the number of articles varies by outcome: 20 mortality, 16 renal outcomes, 6 stroke, 7 delirium and 34 other outcomes. Hypotension was reported to be associated with mortality (OR 1.02-20.826) as well as changes from the patient's baseline blood pressure (BP) (OR 1.02-1.36); hypotension also had a role in the development of acute kidney injury (AKI) (OR 1.03-14.11). Postsurgical delirium was found in relation with BP lability (OR 1.018-1.038) and intra- and postsurgical hypotension (OR 1.05-1.22), and hypertension (OR 1.44-2.34). Increased OR (37.67) of intracranial hemorrhage was associated to postsurgical systolic BP >130 mmHg. There was a wide range of additional diverse outcomes related to hypo-, hypertension and BP lability., Conclusions: The perioperative management of BP influences short- and long-term effects of surgical procedures in cardiac and non-cardiac interventions; these findings support the burden of BP fluctuations in this setting., Competing Interests: Dr. Lizano-Díez reports being employee at Ferrer during the conduct of the study. Axentiva Solutions SL, employer of MC, ABG, and SP received consulting fees from Ferrer.

Introduction. Gram-negative bacteria are a common source of infection both in hospitals and in the community, and antimicrobial resistance is frequent among them, making antibiotic therapy difficult, especially when these isolates carry carbapenem resistance determinants. Hypothesis/Gap Statement . A simple method to detect all the commonly found carbapenemases in Germany was not available. Aim. The aim of this study was to develop a multiplex PCR for the rapid and reliable identification of the most prevalent carbapenemase-encoding genes in Gram-negative bacteria in Germany. Methodology. Data from the German Gram-negative reference laboratory revealed the most prevalent carbapenemase groups in Germany were (in order of prevalence): bla VIM , bla OXA-48 , bla OXA-23 , bla KPC , bla NDM , bla OXA-40 , bla OXA-58 , bla IMP , bla GIM , bla GES , IS Aba1-bla OXA-51 , bla IMI , bla FIM and bla DIM . We developed and tested two multiplex PCRs against 83 carbapenem-resistant Gram-negative clinical isolates. Primers were designed for each carbapenemase group within conserved regions of the encoding genes obtained from publicly available databases. Multiplex-1 included the carbapenemase groups bla VIM , bla OXA-48 , bla OXA-23 , bla KPC , bla NDM and bla OXA-40 , while multiplex-2 included bla OXA-58 , bla IMP , bla GIM , bla GES , IS Aba1-bla OXA-51 and bla IMI . Results. In the initial evaluation, all but one of the carbapenemases encoded by 75 carbapenemase-positive isolates were detected using the two multiplex PCRs, while no false-positive results were obtained from the remaining eight isolates. After evaluation, we tested 546 carbapenem-resistant isolates using the multiplex PCRs, and all carbapenemases were detected. Conclusion. A rapid and reliable method was developed for detection and differentiation of 12 of the most prevalent carbapenemase groups found in Germany. This method allows for the rapid testing of clinical isolates prior to species identification and does not require prior phenotypical characterization, constituting a rapid and valuable tool in the management of infections in hospitals.

Using a combination of short- and long-read DNA sequencing, we have investigated the location of antibiotic resistance genes and characterized mobile genetic elements (MGEs) in three clinical multi-drug resistant Acinetobacter baumannii . The isolates, collected in Bolivia, clustered separately with three different international clonal lineages. We found a diverse array of transposons, plasmids and resistance islands related to different insertion sequence (IS) elements, which were located in both the chromosome and in plasmids, which conferred resistance to multiple antimicrobials, including carbapenems. Carbapenem resistance might be caused by a Tn2008 carrying the bla OXA-23 gene. Some plasmids were shared between the isolates. Larger plasmids were less conserved than smaller ones and they shared some homologous regions, while others were more diverse, suggesting that these big plasmids are more plastic than the smaller ones. The genetic basis of antimicrobial resistance in Bolivia has not been deeply studied until now, and the mobilome of these A. baumannii isolates, combined with their multi-drug resistant phenotype, mirror the transfer and prevalence of MGEs contributing to the spread of antibiotic resistance worldwide and require special attention. These findings could be useful to understand the antimicrobial resistance genetics of A. baumannii in Bolivia and the difficulty in tackling these infections., (Copyright © 2020 Cerezales, Xanthopoulou, Wille, Krut, Seifert, Gallego and Higgins.)

In total, 95 Acinetobacter baumannii isolates recovered from patients from two hospitals in Cochabamba, Bolivia were studied. The presence of class D and B β-lactamases was investigated using polymerase chain reaction, and antimicrobial susceptibility testing was performed by agar dilution and broth microdilution. The resistance rate to carbapenems was 53.7%. All carbapenem-resistant A. baumannii (CRAb, n=51) and four carbapenem-susceptible isolates were further analysed by whole-genome sequencing. The resulting genome assemblies were used to identify the acquired resistome, and core genome multi-locus sequence typing (cgMLST) was used to determine their molecular epidemiology. All but one of the CRAb isolates (n=50) belonged to international clone (IC) 7 and they clustered into five sequence types; on cgMLST, they were found to be separated by ≥40 alleles. All CRAb isolates carried bla OXA-23 on transposon Tn2008. Metallo-β-lactamases were not detected. These data show that dissemination of several IC7 A. baumannii clones harbouring the carbapenem resistance determinant bla OXA-23 is occurring in these two hospitals in Cochambamba., (Copyright © 2019 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Acinetobacter baumannii causes serious hospital-acquired infections and has been positioned as a priority organism by the World Health Organization. This study includes 36 A. baumannii isolates from a children hospital recovered between March 2014 and May 2015 in Cochabamba. The majority of the isolates were recovered from blood cultures (n = 10, 31.3%) and respiratory samples (n = 11, 34.4%); 53% of the patients were younger than 1 month old. Most of these isolates (n = 30, 80.6%) were extremely drug resistant and 8.3% were multidrug resistant. The circulation of 2 predominant clones including 25 isolates was determined by pulsed-field gel electrophoresis; 9 of the isolates were considered sporadic strains. The isolates grouped in the predominant clones and 5 of the unrelated sporadic strains were single-locus variant or double locus variant of clonal complex (CC110), belonging to international clone 7; the rest of the isolates were single-locus variant or double locus variant of another clonal complex. All the carbapenem-resistant isolates (88.9%) carried the blaOXA-23-like in a similar structure to Tn2008 located on the chromosome, and the aac(3)-IIa gene was present in all the aminoglycoside-resistant isolates (86.1%). Strong biofilm producers were found among these isolates, being the strongest ones those recovered from the hospital environment, catheter, blood and cerebrospinal fluid (CSF) all of them belonged to the unrelated sporadic strains. The present study demonstrated the predominance and spread of closely related extremely drug-resistant A. baumannii isolates, what confers increasing risk to children and is of major concern because of the kind of infections and the lack of therapeutic alternatives to treat them.

Acinetobacter seifertii is a recently described species that belongs to the Acinetobacter calcoaceticus-Acinetobacter baumannii complex. It has been recovered from clinical samples and is sometimes associated with antimicrobial resistance determinants. We present here the case of three A. seifertii clinical isolates which were initially identified as Acinetobacter sp. by phenotypic methods but no identification at the species level was achieved using semi-automated identification methods. The isolates were further analysed by whole genome sequencing and identified as A. seifertii. Due to the fact that A. seifertii has been isolated from serious infections such as respiratory tract and bloodstream infections, we emphasize the importance of correctly identifying isolates of the genus Acinetobacter at the species level to gain a deeper knowledge of their prevalence and clinical impact.

The susceptibility to infection, the pathogenesis and the clinical manifestations of tuberculosis (TB) depend on the immunological status of the host. Immunological status is largely determined by age and comorbidities, but is also affected by other less well known factors. In Spain, most incidental cases of TB arise from the reactivation of remotely acquired latent infections and are favored by the aging of the population and the use of aggressive immunosuppressive therapies. The diagnosis and management of TB in these circumstances is often challenging. On the one hand, the atypical presentation with extrapulmonary involvement may delay diagnosis, and on the other, the toxicity and interactions of the antituberculous drugs frequently make treatment difficult. Immigration from resource-poor, high incidence TB countries, where the social and economic conditions are often suboptimal, adds a new challenge to the control of the disease in Spain. This chapter summarizes our current knowledge of epidemiological, clinical and treatment aspects of TB in particularly susceptible populations., (Copyright © 2011 Elsevier España S.L. All rights reserved.)

Interferon-γ-based assays, collectively known as IFN-γ release assays (IGRAs), have emerged as a reliable alternative to the old tuberculin skin test (TST) for the immunodiagnosis of tuberculosis (TB) infection. The 2 commercially available tests, the enzyme-linked immunosorbent assay (ELISA), QuantiFERON-TB Gold Intube (QFT-IT), and the enzyme-linked immunospot assay (ELISPOT), T-SPOT.TB, are more accurate than TST for the diagnosis of TB, since they are highly specific and correlate better with the existence of risk factors for the infection. According to the available data, T-SPOT.TB obtains a higher number of positive results than QFT-IT, while its specificity seems to be lower. Although the sensitivity of the IFN-γ -based assays may be impaired to some extent by cellular immunosuppression and extreme ages of life, they perform better than TST in these situations. Data from longitudinal studies suggest that IFN-γ-based tests are better predictors of subsequent development of active TB than TST; however this prognostic value has not been consistently demonstrated. This review focuses on the clinical use of the IFN-γ -based tests in different risk TB groups, and notes the main limitations and areas for future development., (Copyright © 2011 Elsevier España S.L. All rights reserved.)

Mucormycosis is an infection caused by fungi in the Mucorales order, of which the most relevant family is Mucoraceae, which includes the Rhizopus, Mucor and Absidia genera. It is a severe infection which involves diabetic patients with ketoacidotic decompensation and immunosuppressed patients. We report here five cases (four with rhino-cerebral forms) attended at our hospital in the last ten years. Three patients had diabetes, one was infected with the human immunodeficiency virus, and the other was on a programme of peritoneal dialysis due to renal failure. The most relevant clinical manifestation was the presence of the necrotic lesion in three of the four patients with rhinocerebral involvement (two in the palate, one in the nasal mucosa). Two patients died as a result of the direct infection a few days after diagnosis. In summary, mucormycosis is an infection with a low prevalence but still maintaining a high mortality rate. An early diagnosis is essential and thereby a high index of clinical suspicion is required in patients with predisposing factors.

Objective: To describe the clinical spectrum of bronchopulmonary infections caused by Pseudomonas aeruginosa in patients infected with HIV., Methods: A retrospective study of cases with P. aeruginosa pneumonia and tracheo-bronchitis in patients infected with HIV, diagnosed over a 5-year period (January 1990-December 1994) in a third level university hospital., Results: Seven patients with pneumonia and 15 with tracheobronchitis were identified, with a mean age of 33 years. All patients were in an advanced stage of immunosuppression (median CD4 count 11/mm3) and 21 (95%) had AIDS. In 6 cases (86%) pneumonia was acquired in the community and no patient had severe neutropenia. Clinical presentation ranged from severe pneumonia with respiratory insufficiency and shock to subacute less severe disease. Two patients (29%) died in the first episode as a result of pneumonia. The combination of cough, purulent expectoration and fever was the usual presenting form of tracheo-bronchitis. Nine out of the 15 patients (60%) had been treated previously because of tracheo-bronchitis and/or bacterial pneumonia episodes not caused by P. aeruginosa. Twelve patients required hospital admission; ten patients (83%) because of tracheo-bronchitis symptoms. The initial response to therapy was satisfactory, but 12 (80%) relapsed, with 2.6 relapses per patient after a mean follow-up of 7.4 months., Conclusions: P. aeruginosa bronchopulmonary infections emerge in late stages of HIV disease. P. aeruginosa should be considered in the differential diagnosis of every patient with pneumonia and advanced AIDS, even in the absence of the traditionally reported risk factors. Initially, tracheo-bronchitis responds well to therapy, but its management is difficult because of the frequent relapses and the development of antibiotic resistance.