Cost-effectiveness and resource use analysis of patients with asthma before and after treatment with mepolizumab in a real-life setting.

OBJECTIVE: To define the cost-effectiveness and health resource use of mepolizumab in a cohort of patients with severe eosinophilic asthma in real-life conditions in Spain. METHODS: This was an observational, retrospective, single-center study. Patients included were diagnosed with severe eosinophilic asthma and treated with mepolizumab 100 mg subcutaneous (SC) 4-weekly for 12 months. Outcomes evaluated: incremental cost-effectiveness ratio (ICER), number of exacerbations, disease control with the Asthma Control Test (ACT), Asthma Quality of Life Questionnaire (AQLQ), and direct and indirect cost per patient. RESULTS: 12 months after mepolizumab initiation, a significant decrease in exacerbations was shown, from a mean (standard deviation [SD]) of 3.1 (2.6) to 0.7 (1.5), an increase from 4.9 (0.4) to 6.1 (0.5) in AQLQ, and from 14.9 (5.7) to 21.5 (3.9) in ACT scores. The number of cortico-dependent patients significantly decreased from 53.3% to 13.3% during this period. There was a significant decrease of 94% in the cost of hospitalization, from a mean (SD) of €4063.9 (5423.9) pretreatment to €238.6 (1306.9) post-treatment (p = 0.0003). Total costs decreased significantly from a median of €2,423.1 (1,512.8; 9,320.9) pretreatment to €1,177.5 (965.0; 1,737.8) post-treatment if mepolizumab was excluded. ICER per exacerbation avoided was €3606.9, per 3-point ACT score increase €3934.8, and per 0.5-point AQLQ score increase €3606.9. CONCLUSIONS: Mepolizumab improves control of asthma and quality of life in patients with severe diseases in a cost-effectiveness range. The number of exacerbations decreased, and there was a clear reduction in primary care visits and hospitalizations. Further economic analyses of biological therapies for asthma are required.

Sensitisation to peach allergen Pru p 7 is associated with severe clinical symptoms in a Spanish population.

BACKGROUND: Pru p 7 has been reported as a major allergen in peach allergy, associated with severe clinical symptoms and related to IgE sensitisation to cypress pollen. The main objective of this study was to prospectively evaluate the frequency of sensitisation to Pru p 7 and its clinical relevance amongst pediatric patients with peach allergy in Madrid (Spain). METHODS: Patients with a history of IgE-mediated symptoms (oral allergy syndrome, urticaria/angioedema, rhinoconjunctivitis/asthma, gastrointestinal symptoms, or anaphylaxis) occurring within 2 h after peach intake or contact were prospectively recruited from February 2020 to September 2021. Skin tests, sIgE by ImmunoCAP® (Pru p 1, Pru p 3, Pru p 4, Pru p 7, and Cupressus arizonica) and oral food challenge (OFC) were performed. The study was approved by the local Ethics Committee (PI-4513). RESULTS: Ninety-two patients were included (53.3% male); median age, 10 (IQR 6.0-14.75) years. Seventy-four (80.4%) patients had a reaction after ingestion of fresh peach (25.0% from peel, 23.9% from pulp, and 44.6% from both). Fifteen (16.3%) patients were sensitised to Pru p 7. Upper airway symptoms, anaphylaxis, and grade 2 reactions were statistically more frequent in patients sensitised to Pru p 7. Seven (7.9%) patients presented with exercise as a cofactor, four of whom were sensitised to Pru p 7 (p = .001). Patients sensitised to Pru p 7 were significantly more likely to have a positive OFC result than patients who were not (p = .008). Four patients who reacted to peach at OFC were sensitised to Pru p 7. Specific IgE against Cupressus arizonica pollen was positive in 25 (62.5%) patients. CONCLUSIONS: Pru p 7 sensitisation was observed in 16.3% of our population and was related to severe reactions, upper airway symptoms, anaphylaxis, and the presence of an eliciting cofactor.

Chronic critical illness in polytrauma. Results of the Spanish trauma in ICU registry.

PURPOSE: Chronic critical illness after trauma injury has not been fully evaluated, and there is little evidence in this regard. We aim to describe the prevalence and risk factors of chronic critical illness (CCI) in trauma patients admitted to the intensive care unit. MATERIAL AND METHODS: Retrospective observational multicenter study (Spanish Registry of Trauma in ICU (RETRAUCI)). Period March 2015 to December 2019. Trauma patients admitted to the ICU, who survived the first 48 h, were included. Chronic critical illness (CCI) was considered as the need for mechanical ventilation for a period greater than 14 days and/or placement of a tracheostomy. The main outcomes measures were prevalence and risk factors of CCI after trauma. RESULTS: 1290/9213 (14%) patients developed CCI. These patients were older (51.2 ± 19.4 vs 49 ± 18.9); p < .01) and predominantly male (79.9%). They presented a higher proportion of infectious complications (81.3% vs 12.7%; p < .01) and multiple organ dysfunction syndrome (MODS) (27.02% vs 5.19%; p < .01). CCI patients required longer stays in the ICU and had higher ICU and overall in-hospital mortality. Age, injury severity score, head injury, infectious complications, and development of MODS were independent predictors of CCI. CONCLUSION: CCI in trauma is a prevalent entity in our series. Early identification could facilitate specific interventions to change the trajectory of this process.

Do specific antimicrobial stewardship interventions have an impact on carbapenem resistance in Gram-negative bacilli? A multicentre quasi-experimental ecological study: time-trend analysis and characterization of carbapenemases.

BACKGROUND: Carbapenem-resistant Gram-negative bacilli (CR-GNB) are among the most threatening microorganisms worldwide and carbapenem use facilitates their spread. Antimicrobial stewardship programmes (ASPs) can help to optimize the use of antibiotics. This study evaluates the impact of a multifaceted educational ASP on carbapenem use and on the epidemiology of CR-GNB. METHODS: We conducted a quasi-experimental, time-series study in seven hospitals, from January 2014 to September 2018. The key intervention was composed of educational interviews promoting the appropriate use of carbapenems. The primary endpoints were carbapenem consumption and incidence density (ID) of CR-GNB. All non-duplicated CR-GNB clinical isolates were tested using phenotypic assays and PCR for the presence of carbapenemases. Joinpoint regression and interrupted time-series analyses were used to determine trends. RESULTS: A decrease in carbapenem consumption throughout the study period [average quarterly percentage change (AQPC) -1.5%, P < 0.001] and a -8.170 (-16.064 to -0.277) level change following the intervention were observed. The ID of CR-Acinetobacter baumannii decreased (AQPC -3.5%, P = 0.02) and the overall ID of CR-GNB remained stable (AQPC -0.4%, P = 0.52). CR-GNB, CR-Pseudomonas aeruginosa and CR-A. baumannii IDs per hospital correlated with the local consumption of carbapenems. The most prevalent carbapenem resistance mechanisms were OXA-23 for CR-A. baumannii (76.1%), OXA-48 for CR-Klebsiella pneumoniae (66%) and no carbapenemases for CR-P. aeruginosa (91.7%). The epidemiology of carbapenemases was heterogeneous throughout the study, especially for carbapenemase-producing Enterobacteriaceae. CONCLUSIONS: In conclusion, a multifaceted, educational interview-based ASP targeting carbapenem prescribing reduced carbapenem use and the ID of CR-A. baumannii.

Inflammatory markers IL-1ß and RANK-L assessment after non-vital bleaching: A 3-month follow-up.

OBJECTIVE: This study assessed IL-1ß and RANK-L levels in vivo and color stability of non-vital teeth bleached using hydrogen (35%) and carbamide (37%) peroxides 3 months after treatment. MATERIALS AND METHODS: Fifty teeth were randomly divided into two groups(n = 25):35% hydrogen peroxide (HP) or 37% carbamide peroxide (CP). Four sessions of intracoronal walking-bleach procedure were performed. IL-1ß and RANK-L levels were assessed from gingival crevicular fluid samples (from three vestibular and three palatines sites) at eight different time-points: at the beginning of the study (baseline), after four sessions of intracanal bleaching, and at 1 week, 1 month, and 3 months posttreatment. The color variations were visually detected using Vita bleach shade guide (ΔSGU). RESULTS: Significant increases of IL-1ß and RANK-L levels were detected at all time-points (all P < .05) when comparing each time-point to baseline, and a high correlation (>0.8-Spearman) between variables. According the ΔSGU values, a color change of five for HP and four for CP were detected. CONCLUSIONS: Non-vital walking bleach technique promotes an increase in IL-1ß and RANKL levels in periodontal tissues and also, it is maintained until the third-month posttreatment. CLINICAL SIGNIFICANCE: The internal whitening of teeth increases the levels of cytokines associated with inflammation and bone resorption 3 months after the whitening procedure is finished; this should warn of possible harmful effects of this whitening technique.

Executive summary of the guidelines for the use of interferon-γ release assays in the diagnosis of tuberculosis infection.

Interferon-gamma release assays are widely used for the diagnosis of tuberculosis infection in Spain. However, there is no consensus on their application in specific clinical scenarios. To develop a guideline for their use, a panel of experts comprising specialists in infectious diseases, respiratory diseases, microbiology, pediatrics and preventive medicine, together with a methodologist, conducted a systematic literature search, summarized the findings, rated the quality of the evidence, and formulated recommendations following the GRADE (Grading of Recommendations of Assessment Development and Evaluations) methodology. This document provides evidence-based guidance on the use of interferon-gamma release assays for the diagnosis of tuberculosis infection in patients at the risk of tuberculosis or suspected of having active disease. The guidelines will be applicable to specialist and primary care, and public health.

Early Detection and Diagnostic Approach Through Automated Hematological Analysis for Plasma Cell Leukemia.

Plasma cell leukemia (PCL) is a clinically aggressive variant of multiple myeloma, characterized by a high burden of circulating plasma cells, necessitating swift and accurate diagnosis due to its poor prognosis. The conventional diagnostic criteria, including the recent recommendation by the International Myeloma Working Group (IMWG) of > 5% circulating plasma cells as positive, have evolved over time. In this context, we present a detailed case report that underscores the pivotal role of the ADVIA 2120 automated hematology counter in detecting plasma cells through cytogram analysis, along with the significance of routine peripheral blood smear analysis and the utility of a large unstained cells (LUCs) threshold of > 4.5% as an indicator for PCL. The case involves a 64-year-old patient with relapsed multiple myeloma and stable paraprotein levels who experienced sudden renal impairment. In this case report, we highlight how ADVIA analysis and cytochemistry assisted in the diagnosis, and further explore ADVIA's utility in this challenging leukemia.

Changes in leisure time physical activity during pregnancy compared to the prior year.

To quantify changes in leisure time physical activity (LTPA) type, frequency, duration and intensity during the first half of pregnancy as compared with the year prior to pregnancy. A cross sectional study was conducted at the Maternal University Hospital in Granada, Spain. A total of 1,175 healthy pregnant women attending a scheduled visit during the 20-22nd gestational week were enrolled in the study. Information about socio-demographic, obstetric and life-style variables during the previous year and the first half of pregnancy were collected. LTPA was quantified by assigning metabolic equivalents to each activity according to frequency, intensity and duration. The prevalence of women who met the optimal physical activity recommendations before and during pregnancy was calculated, and the McNemar-Bowker symmetry test was used to assess changes in type, frequency, intensity and duration of activities between the two periods. Some sort of LTPA was performed before and during pregnancy by 68.6% of the pregnant women. Respectively, just 27.5% and 19.4% of women fulfilled LTPA recommendations prior to pregnancy and during pregnancy; 12.6% of the women meeting recommendations prior to pregnancy later did not meet those recommendations during gestation, and 4.5% showed the reverse trend. A light increase in walking as a LTPA, and a decrease in the rest of the LTPA type activities, were seen during pregnancy. Some 13.4% of women changed from moderate--the year before- to light LTPA- during pregnancy. Pregnancy involved a decrease in LTPA, not only regarding frequency, but also duration and intensity.

Association between maternal obesity, essential fatty acids and biomarkers of fetal liver function.

Maternal obesity and the imbalance in linoleic acid (C18:2 n-6, LA) and alpha-linolenic acid (C18:3 n-3, ALA) levels are related with hepatic disturbances in the offspring. However, whether these alterations are present during fetal life is not well understood. Obese and normal weight pregnant women were recruited to determine fatty acids (FAs) consumption, FAs profile (in maternal erythrocytes, placenta and neonatal very low-density lipoproteins VLDL) and biomarkers of fetal liver function, such as gamma-glutamyl transferase (GGT), alpha-fetoprotein (AFP) and albumin, in umbilical cord blood. Stearic acid (C18:0, ST) was lower, and total n-3 FAs tended to be lower in umbilical cord VLDLs of obese women compared to controls. Independently of maternal obesity, GGT levels in umbilical cord blood was positively correlated with the LA content and negatively correlated with the ALA content in maternal erythrocytes. We conclude that maternal obesity and its imbalance of LA and ALA are associated with changes in biomarkers of fetal liver function.

[Use of an empirical antiretroviral treatment depends on the primary resistance rate of the human immunodeficiency virus]. / La práctica de un tratamiento antirretroviral empírico es dependiente del porcentaje de resistencias primarias del virus de la inmunodeficiencia humana.

OBJECTIVE: The objective of this study was the analysis of the prevalence and type of primary resistance to antiretroviral drugs in patients diagnosed with HIV infection, and to determine the most appropriate empirical treatment to obtain a virological and immunological response. PATIENTS AND METHODS: An observational analysis of patients with a de novo diagnosis of HIV infection during the period 2008-2010. Clinical, immunological and virological characteristics, including genotype analysis of resistance to antiretrovirals, were considered as independent variables. The dependent variable was an undetectable HIV viral load after six months of treatment. Data are provided as median (interquartile range) and absolute number (percentage). RESULTS: Seventy-three patients with a de novo diagnosis of HIV infection were included [53 males (73%); 36 (30-46) years-old; prior use of intravenous drugs: 5 patients (7%); hepatitis C virus co-infection: 13 individuals (18%)]. Ten patients (14%) showed symptoms attributable to acute HIV infection. A CD4+ T cell count lower than 350 mm(3) was detected in a 37% (n=27) of all patients. The initiation of antiretroviral therapy followed the GESIDA recommendations (no therapy: 20 patients; tenofovir+emtricitabine+efavirenz: 28 patients; abacavir+lamivudine+efavirenz: 1 patient; tenofovir+emtricitabine+protease inhibitors: 5 patients; abacavir+lamivudine+protease inhibitors: 1 patient; 18 patients were lost in the follow-up). After starting antiretroviral therapy, the resistance analyses detected the existence of primary resistance to antiretrovirals in 12.7% (confidence interval 95%: 3-22) of the patients, distributed as follows: isolated resistance to, nucleosides was detected in 2% (M184V), to nevirapine/efavirenz in 9% (K103N), and combined resistance to nucleosides and non-nucleosides in 2%; there were no cases of resistance to protease inhibitors. Consequently, antiretroviral therapy was changed in 5 (14%) out of 35 patients, attaining an undetectable HIV viral load at 6 months in all of them. The primary resistance to antiretrovirals was not related with epidemiological, virological (including infection by non B subtype) or immunological variables. CONCLUSIONS: In the present study, a change in the epidemiological pattern of de novo diagnosis of HIV infection in our area has been observed. The existence of resistance mutations in more than 5% of the new cases is noteworthy. This finding must be considered in order to establish the rules of empirical treatment in our area.

Effects of inhalation aromatherapy as a complementary therapy in pediatric patients in the clinical practice: A systematic review.

BACKGROUND: Inhalation aromatherapy is a complementary therapy in different clinical settings, but there is little evidence about its effectiveness in childcare. OBJECTIVE: To assess the effectiveness of inhalational aromatherapy in the care of hospitalized pediatric patients. METHODS: Systematic review of clinical trials and quasi-experimental studies, based on PRISMA recommendations, searching Medline, Web of Science, Scopus, SciELO, LILACS, CINAHL, Science Direct, EBSCO, and updated databases. The Down and Black 2020, RoB 2020 CLARITY, and ROBINS-I 2020 scales were used through the Distiller SR software to verify the studies' internal validity and risk of bias. RESULTS: From 446 articles identified, 9 fulfilled the inclusion criteria. Seven were randomized controlled trials (RCTs), one pilot RCT, and one non-randomized quasi-experimental trial. Different outcomes were analyzed, with pain being the most frequently measured variable. None of the 6 studies that evaluated pain showed significant effects with inhalation aromatherapy. Additionally, non-significant effects were found regarding nausea, vomiting, and behavioral/emotional variables. CONCLUSIONS: The findings are still inconclusive, and more evidence is required from future studies with high methodological quality, blinding, and adequate sample sizes.

The Impact of COVID-19 Outbreak on Camping Tourism in Spain: A Spatial Approach to Tourist Destinations.

The COVID-19 health crisis has wreaked devastation on the world economy, especially on the tourism sector. The camping sector has been little studied despite its high economic impact and participation rate. Moreover, the observable effects of phenomena such as the COVID-19 pandemic have received little research attention. Consequently, the objective of this paper is therefore to analyse the effects of the pandemic on camping tourism by characterising the factors that determine it. The study is carried out by providing a geographical perspective of the sector by tourist areas, whereby two types of tourist destinations are considered: campsites located in coastal areas, and campsites located in natural areas. This is the main contribution of the work, as the proposed geographical analysis studies smaller territorial units than those usually used in tourism research. For the study, Multivariate Analysis techniques are applied, specifically Factor Analysis and Cluster Analysis. The results show that there is a balance between supply and demand in the sector, with a significant economic impact, especially on employment and the performance of the sector. The impact of the COVID-19 pandemic has led to nature tourism gaining greater popularity, and shows an evolution in travellers' preferences for tourist destinations in favour of campsites located in natural areas over those located in coastal destinations. The geographical location of the tourist destination, therefore, plays a key role in the characterisation of Spanish campsites. This has practical implications for both camping companies and institutions, as the fact that some areas are more attractive than others is a decisive factor in deciding on the location of new campsites.

[Candidemias: multicentre analysis in 16 hospitals in Andalusia (Spain)]. / Candidemias: análisis multicéntrico en 16 hospitales andaluces.

INTRODUCTION: Candidemia is a nosocomial infection with high associated mortality. There have been changes in microbiology, epidemiology and treatment over the last few years, which has led us to analyse our own situation. MATERIAL AND METHODS: Prospective, multicentre and observational study. All episodes of candidemia in adult patients seen in 17 Andalusian hospitals from 1 October 2005 to 30 September 2006 were included. RESULTS: Were detected 220 cases, the incidence was 0.58 cases/1,000 hospital discharges. Candida albicans was the most frecuent species (53% of cases). The majority of isolates (89%) was susceptibility to fluconazole. Sepsis was the most frequent clinical manifestation (65.7%). The treatment was inadequate in 38.7% of cases. Overall mortality was 40%. On univarite analysis death was found to be significantly associated with: aged > 60 years, unknown candidemia focus, Pitt score ≥ 2, APACHE II, shock at onset, persistents positive second blood cultures, non-removal of the central venous catheter and Candida species different of C. parasilopsis, among others. In the multivariate analysis death was found to be significantly associated with: aged > 60 years, Pitt score ≥ 2, Candida species different of C.parasilopsis and inadequate treatment. CONCLUSIONS: The candidemia clinical epidemiology in our region is similar to other areas and receiving inadequate treatment is the only modifiable risk factor associated with higher odds of mortality. Therefore, this modifiable factor needs to be improved to reduce the mortality.

[Girl with hypersensitivity pneumonitis. A case report]. / Niña con neumonitis por hipersensibilidad. Reporte de un caso.

BACKGROUND: Hypersensitivity pneumonitis entails several inflammatory lung diseases that preferentially affect the alveolar and perialveolar tissue. It is a very rare disease in children, with a complicated diagnosis due to the fact that antigen exposure usually goes unnoticed. CASE REPORT: A 12-year-old girl with dry cough, dyspnea, wheezing, and tachypnea, with partial improvement after treatment with inhaled bronchodilators and corticoids. The spirometry showed a restrictive pattern and reduced lung diffusion capacity; in the CT scan, centrilobular ground-glass opacities were observed, and a lymphocyte count of CD4/CD8 of 2.46 (lymphocytosis) was obtained from the bronchoalveolar lavage. IgG positivity to bird feathers was obtained. CONCLUSIONS: The treatment of hypersensitivity pneumonitis is based on avoiding exposure to the causative agent, which is determined by the prognosis; for which taking an extensive medical history is of paramount importance. Corticosteroids can be prescribed based on the clinical response, the pulmonary function, and the radiological improvement.

Antecedentes: La neumonitis por hipersensibilidad agrupa varias enfermedades inflamatorias pulmonares que afectan preferentemente el tejido alveolar y perialveolar. En niños se trata de una enfermedad muy rara, con diagnóstico complicado debido a que la exposición antigénica suele pasar desapercibida. Caso clínico: Niña de 12 años que presentaba tos seca, disnea, sibilancias y taquipnea con mejoría parcial al tratamiento con broncodilatadores y corticoides inhalados. En la espirometría presentó un patrón restrictivo y una capacidad de difusión pulmonar reducida; en la tomografía computarizada se observaron opacidades centrolobulillares en vidrio esmerilado y del lavado broncoalveolar se obtuvo un cociente de linfocitosis CD4/CD8 de 2.46. Se obtuvo IgG positiva a plumas de aves. Conclusiones: El manejo de la neumonitis por hipersensibilidad se basa en evitar la exposición al agente causante, lo que determina el pronóstico; de ahí que resulta de vital importancia realizar una historia clínica exhaustiva. Pueden indicarse corticosteroides en función de la respuesta clínica, la función pulmonar y la mejoría radiológica.

Evaluation of the Integrated Tuberculosis Research Program Sponsored by the Spanish Society of Pulmonology and Thoracic Surgery: 11 Years on. / Evaluación del Programa Integrado de Investigación en Tuberculosis promovido por la sociedad española de Neumología y Cirugía Torácica tras 11 años de funcionamiento.

OBJECTIVE: The objective of the study was to determine the trend of variables related to tuberculosis (TB) from the Integrated Tuberculosis Research Program (PII-TB) registry of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR), and to evaluate the PII-TB according to indicators related to its scientific objectives. METHOD: Cross-sectional, population-based, multicenter study of new TB cases prospectively registered in the PII-TB between 2006 and 2016. The time trend of quantitative variables was calculated using a lineal regression model, and qualitative variables using the χy test for lineal trend. RESULTS: A total of 6,892 cases with an annual median of 531 were analyzed. Overall, a significant downward trend was observed in women, immigrants, prisoners, and patients initially treated with 3 drugs. Significant upward trends were observed in patients aged 40-50 and > 50 years, first visit conducted by a specialist, hospitalization, diagnostic delay, disseminated disease and single extrapulmonary location, culture(+), sensitivity testing performed, drug resistance, directly observed treatment, prolonged treatment, and death from another cause. The scientific objectives of the PII-TB that showed a significant upward trend were publications, which reached a maximum of 8 in 2016 with a total impact factor of 49,664, numbers of projects initiated annually, presentations at conferences, and theses. CONCLUSIONS: PII-TB provides relevant information on TB and its associated factors in Spain. A large team of researchers has been created; some scientific aspects of the registry were positive, while others could have been improved.

Influence of extravascular lung water determination in fluid and vasoactive therapy.

INTRODUCTION: Preload parameters in postresuscitation phase are not sufficiently sensitive to guide fluid therapy in critically ill patients. We analyzed modifications in the fluid therapy and vasoactive drugs of critically ill patients that were produced by inclusion of extravascular lung water (EVLW) data in the treatment protocol and evaluated the short-term response. METHODS: This observational and prospective study included consecutive patients with hypotension or hypoxemia, comparing the therapeutic plan for fluid and vasoactive drug treatment between before and after knowing the EVLW value. RESULTS: We studied 42 patients. After knowing the EVLW, 52.4% (n = 22) of initial therapeutic plans were changed, modifying fluid therapy in all of these cases and vasoactive therapy in 22% of them. EVLW value was 13.91 +/- 5.62 in patients with change of therapeutic plan versus 10 +/- 4.52 in those with no change (p < 0.05). No differences were found in preload parameters as a function of change/no change. The most frequent decision change (n = 13) was to fluid reduction plus diuretic administration, and patients with this modification had significantly (p < 0.05) higher EVLW values compared with the remaining patients with a change in fluid therapy. Out of the 22 patients with a modified therapeutic decision, the therapy proved effective in 18 patients CONCLUSION: Quantification of EVLW in patients who can be considered euvolemic induces important modifications in fluid and vasoactive therapy. These changes generally resulted in a lower volume loading and a positive outcome for the patient.