22 research outputs found
Survey of clustered regularly interspaced short palindromic repeats and their associated Cas proteins (CRISPR/Cas) systems in multiple sequenced strains of Klebsiella pneumoniae
Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study
Background Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8–13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05–6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50–75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life. Funding Pfizer, Amgen, Merck Sharp & Dohme, Sanofi–Aventis, Daiichi Sankyo, and Regeneron
Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease
Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.
Cost–consequence analysis of fluticasone furoate/vilanterol 92/22 mcg for the management of COPD in the Spanish NHS
Laura Amanda Vallejo-Aparicio,1 Germán Peces-Barba,2 Alicia Gil,3 Alicia Huerta Hernandez1 1Market Access, GlaxoSmithKline, Tres Cantos, Madrid, Spain; 2IIS-Fundación Jiménez Díaz. CIBERES, Madrid, Spain; 3Omakase Consulting, Barcelona, Spain Objectives: The Salford Lung Study in Chronic Obstructive Pulmonary Disease (SLS COPD) is a 12-month, open-label randomized clinical trial comparing clinical effectiveness and safety of initiating once-daily fluticasone furoate/vilanterol (FF/VI) 92/22 mcg with continuing usual care (UC) in patients with COPD followed in primary care in the UK. The objective of this analysis is to estimate the economic impact of these results when applied to Spain. Materials and methods: An Excel-based cost–consequence model with a one-year time horizon was populated with SLS COPD results, adopting the Spanish National Health System (NHS) perspective. Patients analyzed were diagnosed COPD patients ≥40 years old, currently managed with maintenance treatment and with a history of exacerbations (total number estimated from Spanish data). Mean least squares annual rates of moderate/severe exacerbations after 1 year for the intention-to-treat population from SLS COPD were included in the model (1.50 [FF/VI] and 1.64 [UC]); serious adverse events were excluded from the analysis as no differences between treatment arms were found. Medication and exacerbation management costs in euros were estimated from Spanish public sources for 2016. Model base-case analysis assumed an increased usage of FF/VI from 4% to 10% within 1 year, and a 100% proportion of days covered with study medications. Deterministic sensitivity analyses were performed for mitigating uncertainty. Results: At base case, within 50,522 COPD patients analyzed, substitution of UC with FF/VI 92/22 mcg was associated with reduced medication and exacerbation management costs, leading to potential total annual savings of €353,623. Deterministic sensitivity results ranged from €218,333 up to €1,532,366 potential cost savings associated with FF/VI, showing the robustness of base-case results. Conclusion: The decreased rate of exacerbations with FF/VI 92/22 mcg compared with UC observed in SLS COPD could be translated into potential health care savings for the Spanish NHS. These results may be useful to inform decision-making processes. Keywords: cost–consequence analysis, COPD, fluticasone furoate/vilanterol, COPD Salford Lung Stud
Cost-Effectiveness of Once-Daily Single-Inhaler COPD Triple Therapy in Spain: IMPACT Trial
Victoria Federico Paly,1 Laura Amanda Vallejo-Aparicio,2 Alan Martin,3 José Luis Izquierdo,4 Juan Antonio Riesco,5 Juan José Soler-Cataluña,6 Catarina Abreu,7 Chandroday Biswas,8 Afisi S Ismaila9,10 1ICON plc, Philadelphia, PA, USA; 2GSK, Madrid, Spain; 3GSK, Brentford, UK; 4Hospital Universitario de Guadalajara, Guadalajara, Spain; 5Hospital San Pedro de Alcántara, Cáceres, Spain; 6Hospital Arnau de Vilanova, Valencia, Spain; 7ICON Plc, New York, NY, USA; 8ICON Plc, Bengaluru, Karnataka, India; 9Value Evidence and Outcomes, GSK, Collegeville, PA, USA; 10Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, CanadaCorrespondence: Afisi S Ismaila, Value Evidence and Outcomes, GSK, 1250 South Collegeville Road, Collegeville, PA, 19426-0989, USA, Tel +1 919 315 8229, Email [email protected]: Given between-country differences in healthcare systems, treatment costs, and disease management guidelines, country-specific cost-effectiveness analyses are important. This study evaluated the cost-effectiveness of once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI and UMEC/VI among patients with symptomatic chronic obstructive pulmonary disease (COPD) at risk of exacerbations from a Spanish healthcare system perspective.Patients and Methods: Baseline data and treatment effects from the IMPACT trial were populated into the validated GALAXY COPD progression model. Utilities were estimated using Spanish observational data. Direct healthcare costs (2019 €) were informed by Spanish public sources. A 3% discount rate for costs and benefits was applied. The time horizon and treatment duration were 3 years (base case). One-way sensitivity, scenario, and probabilistic sensitivity analyses were performed.Results: FF/UMEC/VI treatment resulted in fewer exacerbations over 3 years (4.130 vs 3.648) versus FF/VI, with a mean (95% confidence interval [CI]) incremental cost of € 444 (€ 149, € 713) per patient and benefit of 0.064 (0.053, 0.076) quality-adjusted life years (QALYs), resulting in an incremental cost-effectiveness ratio (ICER) of € 6887 per QALY gained. FF/UMEC/VI was a dominant treatment strategy versus UMEC/VI, resulting in fewer exacerbations (4.130 vs 3.360), with a mean (95% CI) incremental cost of –€ 450 (–€ 844, –€ 149) and benefit of 0.054 (0.043, 0.064) QALYs. FF/UMEC/VI was cost-effective versus FF/VI and UMEC/VI across all analyses.Conclusion: FF/UMEC/VI was predicted to be a cost-effective treatment option versus FF/VI or UMEC/VI in symptomatic COPD patients at risk of exacerbations in Spain, across all scenarios and sensitivity analyses.Keywords: chronic obstructive pulmonary disease, cost-effectiveness, single-inhaler triple therapy, Spain, triple inhaled therap
The dromedary in Al-Andalus. The archaeological record in the south of the Iberian Peninsula during the Islamic period (10th-14th centuries)
En este trabajo se presenta el estado de la cuestión y nuevos hallazgos sobre la constatación arqueológica de la presencia de dromedario, Camelus dromedarius L., en el sur de al-Andalus. De igual modo, se aborda el uso al que fueron destinados a partir del análisis de las noticias aportadas por las fuentes escritas, así como una primera aproximación a la significación simbólica de este animal. Por otra parte, se evidencia que la mayoría de las manipulaciones observadas en los restos óseos de dromedario analizados estaría relacionada con la fabricación de distintos utensilios de hueso. En cuanto a la distribución geográfica que alcanzaron estos animales en la península ibérica y su aumento o disminución en al-Andalus, concluimos que estuvieron presentes a lo largo del periodo islámico.This paper presents the state-of-the-art regarding the archaeological verification of the presence of dromedaries, Camelus dromedarius L. in the south of Al-Andalus, together with new findings regarding this topic. This research also ana-lyzes several written sources, which clarify the usage given to these animals and, at the same time, offers a first symbolic meaning given to them. On the other hand, we demonstrate that most of the bone manipulations found in the bone remains from dromedaries corresponds to the manufacturing of several different bone tools. As far as the geographical distribution of these animals within the iberian peninsula and their increase or decrease in al-Andalus, we conclude that they were present during the Islamic period.Junta de Andalucía AAPUN 08/2021Ministerio de Ciencia, Innovación y Universidades HAR2017-87060-
On-line science to be use for prevention and improvement of the Covid-18 effects
El proyecto se planteó con el objetivo general de actuar ante la necesidad de hacer más motivador y comprensible el estudio de alguna de las materias que se imparten hoy en nuestras facultades, poniendo de relieve la prevención y mejora que los efectos del confinamiento por el Covid-19 pudieran acentuarse de cara al futuro.The project has slightly improved some of the material used for the university students, especially for the prevention and improvement of the confinements effect due to Covid-19.Depto. de Química FísicaFac. de Ciencias QuímicasFALSEsubmitte