Purpose
To investigate the chondrogenic-regenerative properties of a novel autologous-made matrix composed of hyaline cartilage chips combined with a growth factors-based clot for full-thickness ...defects in sheep.
Methods
A full-thickness, 8-mm diameter cartilage defect was created in the weight-bearing area of the medial femoral condyle in 6 sheep. Treatment consisted of surgical implantation of an autologous-based matrix of hyaline cartilage chips combined with a clot of plasma poor in platelets and intraarticular injection of plasma rich in growth factors. Outcome measures at 1, 3 and 6 months included macroscopic International Cartilage Repair Society (ICRS) score, histological and immunohistochemical analysis for collagen expression, and transmission electron microscopy study.
Results
The 6-month macroscopic evaluation showed nearly normal (11.1 ± 0.7) cartilage repair assessment. The ICRS score was significantly higher at 6 months compared to 3 months (5.5 ± 1.3;
p
< 0.0001) and 1 (1.1 ± 0.4;
p
< 0.0001) month. At 6 months, hyaline cartilage tissue filling the defect was observed with adequate integration of the regenerated cartilage at the surrounding healthy cartilage margin. At 6 months, mature chondrons and cartilage matrix contained collagen fibers with masked fibrillary structure, and the expression of collagen in the newly formed cartilage was similar in intensity and distribution pattern compared to the healthy adjacent cartilage.
Conclusions
This novel treatment enhanced chondrogenesis and regenerated hyaline cartilage at 6 months with nearly normal macroscopic ICRS assessment. Histological analysis showed equivalent structure to mature cartilage tissue in the defect and a collagen expression pattern in the newly formed cartilage similar to that found in adjacent healthy articular cartilage. The present technique may have clinical application for chondral injuries in humans because this procedure is cheap (no need for allograft, or expensive instrumentation/biomaterials/techniques), easy and fast-performing through a small arthrotomy, and safe (no rejection possibility because the patients’ own tissue, cells, and plasma are used).
Aims
Benzodiazepines have been used as safe anxiolytic drugs for decades and some authors have suggested they could be an alternative for morphine for treating acute cardiogenic pulmonary oedema ...(ACPE). We compared the efficacy and safety of midazolam and morphine in patients with ACPE.
Methods and results
A randomized, multicentre, open‐label, blinded endpoint clinical trial was performed in seven Spanish emergency departments (EDs). Patients >18 years old clinically diagnosed with ACPE and with dyspnoea and anxiety were randomized (1:1) at ED arrival to receive either intravenous midazolam or morphine. Efficacy was assessed by in‐hospital all‐cause mortality (primary endpoint). Safety was assessed through serious adverse event (SAE) reporting, and the composite endpoint included 30‐day mortality and SAE. Analyses were made on an intention‐to‐treat basis. The trial was stopped early after a planned interim analysis by the safety monitoring committee. At that time, 111 patients had been randomized: 55 to midazolam and 56 to morphine. There were no significant differences in the primary endpoint (in‐hospital mortality for midazolam vs. morphine 12.7% vs. 17.9%; risk ratioRR 0.71, 95% confidence interval CI 0.29–1.74; p = 0.60). SAE were less common with midazolam versus morphine (18.2% vs. 42.9%; RR 0.42, 95% CI 0.22–0.80; p = 0.007), as were the composite endpoint (23.6% vs. 44.6%; RR 0.53, 95% CI 0.30–0.92; p = 0.03).
Conclusion
Although the number of patients was too small to draw final conclusions and there were no significant differences in mortality between midazolam and morphine, a significantly higher rate of SAEs was found in the morphine group.
There were no significant differences in mortality between morphine and midazolam but the rate of serious adverse events was significantly higher in the morphine group, although the number of patients was too small to draw final conclusions.
The Gartner Hype Cycle for Emerging Technologies highlights “augmented human technologies” as one of their emerging trends, while the Future Today Institute alludes to the potential of extended ...reality (digitally manipulated environments encompassing virtual and augmented reality) for the development of new applications with great informative value. Based on this, the current study brings together in-depth interviews with experts who analyze the possibilities of augmented reality (AR) in journalism, including its weaknesses and some proposals for new journalistic scenarios. The study concludes that, according to experts, the use of AR in daily systems and applications is key to establishing this technology. In addition, experts stress the need to carry out sociological and ethical studies of its impact, as well as experimental research on the use of augmented senses in humans, including both visual and haptic augmentation and hearing.
Resumen
El Gartner hype cycle for emerging technologies destaca las “tecnologías humanas aumentadas” como una de las tendencias emergentes; mientras que el Future Today Institute alude al potencial de la realidad extendida (entornos manipulados digitalmente que abarca la realidad virtual y aumentada) para el desarrollo de nuevas aplicaciones de gran valor informativo. Partiendo de ello, el estudio reúne entrevistas en profundidad a expertos que analizan las posibilidades de la realidad aumentada (RA) en el periodismo y sus debilidades, y propone nuevos escenarios a nivel periodístico. Según los expertos, el uso de RA en sistemas y aplicaciones de uso diario es el punto clave para asentar esta tecnología. Además, inciden en la necesidad de realizar estudios sociológicos y éticos de su impacto, así como investigaciones experimentales sobre el uso de sentidos aumentados en humanos, tanto el aumento visual como la háptica y la audición.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Short stay unit (SSU) is an alternative to conventional hospitalization in patients with acute heart failure (AHF), but the prognosis is not known compared to direct discharge from the emergency ...department (ED). To determine whether direct discharge from the ED of patients diagnosed with AHF is associated with early adverse outcomes versus hospitalization in SSU. Endpoints, defined as 30-day all-cause mortality or post-discharge adverse events, were evaluated in patients diagnosed with AHF in 17 Spanish EDs with an SSU, and compared by ED discharge vs. SSU hospitalization. Endpoint risk was adjusted for baseline and AHF episode characteristics and in patients matched by propensity score (PS) for SSU hospitalization. Overall, 2358 patients were discharged home and 2003 were hospitalized in SSUs. Discharged patients were younger, more frequently men, with fewer comorbidities, had better baseline status, less infection, rapid atrial fibrillation and hypertensive emergency as the AHF trigger, and had a lower severity of AHF episode. While their 30-day mortality rate was lower than in patients hospitalized in SSU (4.4% vs. 8.1%,
p
< 0.001), 30-day post-discharge adverse events were similar (27.2% vs. 28.4%,
p
= 0.599). After adjustment, there were no differences in the 30-day risk of mortality of discharged patients (adjusted HR 0.846, 95% CI 0.637–1.107) or adverse events (1.035, 0.914–1.173). In 337 pairs of PS-matched patients, there were no differences in mortality or risk of adverse event between patients directly discharged or admitted to an SSU (0.753, 0.409–1.397; and 0.858, 0.645–1.142; respectively). Direct ED discharge of patients diagnosed with AHF provides similar outcomes compared to patients with similar characteristics and hospitalized in a SSU.
Abstract
Objectives
To undertake a Spanish nationwide survey on Pseudomonas aeruginosa molecular epidemiology and antimicrobial resistance.
Methods
Up to 30 consecutive healthcare-associated P. ...aeruginosa isolates collected in 2017 from each of 51 hospitals were studied. MICs of 13 antipseudomonal agents were determined by broth microdilution. Horizontally acquired β-lactamases were detected by phenotypic methods and PCR. Clonal epidemiology was evaluated through PFGE and MLST; at least one XDR isolate from each clone and hospital (n = 185) was sequenced.
Results
The most active antipseudomonals against the 1445 isolates studied were colistin and ceftolozane/tazobactam (both 94.6% susceptible, MIC50/90 = 1/2 mg/L) followed by ceftazidime/avibactam (94.2% susceptible, MIC50/90 = 2/8 mg/L). Up to 252 (17.3%) of the isolates were XDR. Carbapenemases/ESBLs were detected in 3.1% of the isolates, including VIM, IMP, GES, PER and OXA enzymes. The most frequent clone among the XDR isolates was ST175 (40.9%), followed by CC235 (10.7%), ST308 (5.2%) and CC111 (4.0%). Carbapenemase production varied geographically and involved diverse clones, including 16.5% of ST175 XDR isolates. Additionally, 56% of the sequenced XDR isolates showed horizontally acquired aminoglycoside-modifying enzymes, which correlated with tobramycin resistance. Two XDR isolates produced QnrVC1, but fluoroquinolone resistance was mostly caused by QRDR mutations. Beyond frequent mutations (>60%) in OprD and AmpC regulators, four isolates showed AmpC mutations associated with resistance to ceftolozane/tazobactam and ceftazidime/avibactam.
Conclusions
ST175 is the most frequent XDR high-risk clone in Spanish hospitals, but this nationwide survey also indicates a complex scenario in which major differences in local epidemiology, including carbapenemase production, need to be acknowledged in order to guide antimicrobial therapy.
Resumen: En el marco de la Estrategia de Promoción de la Salud y Prevención en el Sistema Nacional de Salud, la implementación local es una de las líneas consideradas prioritarias. Dicha ...implementación propone la adhesión voluntaria de las entidades locales para trabajar en promoción de la salud y prevención mediante la realización de dos acciones: la constitución de una mesa de coordinación intersectorial y la identificación de recursos para la promoción de la salud y la prevención en el municipio. La Guía para la Implementación Local de la Estrategia fue aprobada en 2015 por el Consejo Interterritorial del Sistema Nacional de Salud. A fecha de junio de 2018, se han adherido a ella 261 entidades locales, se han identificado 7072 recursos y 9183 actividades, y se han creado 132 mesas intersectoriales. Abstract: Within the framework of the Prevention and Health Promotion Strategy of the Spanish National Health System, local implementation is considered a priority line of action. Local implementation proposes the voluntary commitment of local entities to the Strategy in order to move forward health promotion and prevention through the implementation of two actions: the creation of a coordinating inter-sectoral body and the identification of local resources for health promotion and prevention. The Guideline for the Local Implementation of the Strategy was adopted in 2015 by the Inter-territorial Council of the National Health System. By June 2018, 261 local entities had committed to the Prevention and Health Promotion Strategy, 7072 resources and 9183 activities had been identified, and 132 inter-sectoral bodies had been created. Palabras clave: Promoción de la salud, Colaboración intersectorial, Implementación de plan de salud, Keywords: Health promotion, Intersectoral collaboration, Health plan implementation
Abstract
Objectives
To evaluate the correlation of O-antigen serotypes with resistance profiles and high-risk clones in a Spanish nationwide survey.
Methods
Up to 30 consecutive healthcare-associated ...Pseudomonas aeruginosa isolates were collected during October 2017 from each of 51 hospitals (covering all Spanish regions) with a total of 1445 isolates studied. MICs of 13 antipseudomonal agents and MDR/XDR profiles had been previously determined, as well as whole-genome sequences of 185 representative XDR isolates. O-antigen serotypes (O1–O16) were determined by agglutination using serotype-specific antisera (BioRad). The Pseudomonas aeruginosa serotyper (PAst) program was used for in silico serotyping.
Results
The most frequent serotypes were O6 (17.8%), O1 (15.4%) and O11 (13.3%). In contrast, the most frequent serotype among XDR isolates (17.3%) was O4 (34.1%), distantly followed by O11 (15.9%). Within serotypes, XDR phenotypes were more frequent for O12 (60.0%) and O4 (57.3%). The most frequent clone among the XDR isolates was ST175 (40.9%), followed by CC235 (10.7%), ST308 (5.2%) and CC111 (3.6%). Up to 81.6% of XDR ST175 isolates typed O4, whereas 18.4% were non-typeable. O4 genotype was detected in all sequenced (n=55) ST175 isolates. On the other hand, CC235 and ST308 were associated with O11, whereas CC111 was linked to serotype O12.
Conclusions
O4 serotype is linked to the MDR/XDR profile of widespread ST175 (typically only susceptible to colistin, amikacin and the novel combinations ceftolozane/tazobactam and ceftazidime/avibactam) and therefore, after local validation, its detection in the microbiology laboratory might be useful for guiding semi-empirical antipseudomonal therapies and infection control measures in Spanish hospitals.
Background
The high inter-individual variability in pharmacokinetics (PK) of factor VIII (FVIII) justifies the use of PK-guided prophylaxis, especially in switching between different products. A ...proposed definition of extended half-life (EHL) FVIII requires improvements of at least 1.3 times in half-life (t1/2) and 1.25 times the area under the curve (AUC) compared to standard half-life (SHL) products (Mahlangu et al. Haemophilia. 2018;24(3):348-358). The objective of this multicenter study was to analyze the results of a PK-guided switch from SHL to EHL in patients with hemophilia A (HA).
Methods
Multicenter comparative, cross-sectional, prospective study in HA severe/moderate patients in prophylaxis analyzing PK differences after switch from SHL to EHL (efmoroctocog alfa rFVIII-Fc and rurioctocog alfa pegol PEG-rFVIII). WAPPS-Hemo® was used to analyze PK parameters with 2-3 samples: t1/2; AUC, peak level (PL); trough level at 24, 48 and 72 h (TL24, TL48, TL72); and time to reach FVIII levels of 1, 2, 5% (T1%, T2%, T5%). We have also compared the ratio of t1/2 and AUC, the number of weekly doses and the dose/kg/week before and after the switch. Wilcoxon and Kruskal-Wallis tests (SPSS®) were used to compare the PK parameters. Results are expressed with the median and interquartile range (IQR) or range, and mean and standard deviation (SD).
Results
Eighty-one patients from 8 Spanish hospitals were analyzed (61 rFVIII-Fc; 20 PEG-rFVIII), 78 had severe HA and 3 moderate HA. Mean age was 30 years (range=3-64) and no differences in weight were observed between both periods 70 (range=12-116) vs 70 (13.7-116) kg; p=0,141.
Dose/kg/week and weekly infusion frequency were reduced after the switch to EHL, and significant improvements were observed in all PK parameters after the change from SHL to EHL (Table 1). These results were similar in adult and pediatric patients switching to rFVIII-Fc. The median ratios of t1/2 and AUC were 1.3 (IQR:1.2-1.6) and 1.5 (IQR:1.3-2.3) in the entire cohort. These results were reproduced in the subset of patients with ≥12 years treated with rFVIII-Fc and PEG-rFVIII (ratio t1/2: 1.4 IQR:1.3-1.6; ratio AUC: 1.6 IQR:1.3-2.3), and were slightly in the cohort of 15 patients <12 years treated with rFVIII-Fc (ratio t1/2: 1.3 IQR:0.9-1.3; ratio AUC: 1.3 IQR:1.1-1.9), the only EHL approved in Europe for children.
After the switch to EHL, weekly dose frequency (median 23.3%, IQR:0-33.3%) and dose/kg/week (median 16%, IQR:5.3-30%) were reduced. In a small subset of 17 patients the dose/kg/week increased a median of 31.4%, and this subset was younger than the patients with dose/kg/week reduction or no changes (median age 18 IQR:8-22 vs. 33 IQR:16.5-42.5). No differences were observed in any of the PK parameters and median ratios of t1/2 and AUC in patients aged ≥12 years treated with rFVIII-Fc vs. PEG-rFVIII (46 rFVIII-Fc; 20 PEG-rFVIII; Table 2).
Conclusions
EHL FVIII have shown significant PK improvements in clinical real practice, allowing to reduce weekly infusion number and dose/kg/week, especially in adult patients. Outside the clinical trial setting, we have observed an increase in t1/2 and AUC ratios accordingly to EHL definition. Comparisons regarding clinical outcomes (bleeding rate after switch) will be performed after a follow-up of 1 year with EHL for the full cohort. WAPPS-Hemo PK-guided switch easily facilitates individualization of prophylaxis with a potential reduction in the cost of treatment and patient perceived outcomes.
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Megias:Baxalta US INC.: Research Funding; Grifols: Research Funding. Bonanad Boix:Baxalta US INC.: Research Funding. Berrueco:NovoNordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SOBI: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CSL-Bering: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Mingot-Castellano:Sobi: Consultancy; Bayer: Consultancy; Amgen: Consultancy; Roche: Consultancy; Novartis: Consultancy; Novonordisk: Consultancy; Takeda: Consultancy; CSL Behring: Consultancy. Cid:Shire, a Takeda company: Honoraria; Novo Nordisk: Honoraria. Sanz:AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Boehringer-Ingelheim: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Helsinn Healthcare: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen - Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Onconova: Membership on an entity's Board of Directors or advisory committees, Research Funding; Hoffman - La Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.
Pseudomonas aeruginosa healthcare-associated infections are one of the top antimicrobial resistance threats world-wide. In order to analyze the current trends, we performed a Spanish nation-wide ...high-resolution analysis of the susceptibility profiles, the genomic epidemiology and the resistome of P. aeruginosa over a five-year time lapse.
A total of 3.180 nonduplicated P. aeruginosa clinical isolates from two Spanish nation-wide surveys performed in October 2017 and 2022 were analyzed. MICs of 13 antipseudomonals were determined by ISO-EUCAST. Multidrug resistance (MDR)/extensively drug resistance (XDR)/difficult to treat resistance (DTR)/pandrug resistance (PDR) profiles were defined following established criteria. All XDR/DTR isolates were subjected to whole genome sequencing (WGS).
A decrease in resistance to all tested antibiotics, including older and newer antimicrobials, was observed in 2022 vs 2017. Likewise, a major reduction of XDR (15.2% vs 5.9%) and DTR (4.2 vs 2.1%) profiles was evidenced, and even more patent among ICU isolates XDR (26.0% vs 6.0%) and DTR (8.9% vs 2.6%) (p < 0.001). The prevalence of Extended-spectrum β-lactamase/carbapenemase production was slightly lower in 2022 (2.1%. vs 3.1%, p = 0.064). However, there was a significant increase in the proportion of carbapenemase production among carbapenem-resistant strains (29.4% vs 18.1%, p = 0.0246). While ST175 was still the most frequent clone among XDR, a slight reduction in its prevalence was noted (35.9% vs 45.5%, p = 0.106) as opposed to ST235 which increased significantly (24.3% vs 12.3%, p = 0.0062).
While the generalized decrease in P. aeruginosa resistance, linked to a major reduction in the prevalence of XDR strains, is encouraging, the negative counterpart is the increase in the proportion of XDR strains producing carbapenemases, associated to the significant advance of the concerning world-wide disseminated hypervirulent high-risk clone ST235. Continued high-resolution surveillance, integrating phenotypic and genomic data, is necessary for understanding resistance trends and analyzing the impact of national plans on antimicrobial resistance.
MSD and the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea—NextGenerationEU.
Background & Aims We compared the ability of biennial fecal immunochemical testing (FIT) and one-time sigmoidoscopy to detect colon side-specific advanced neoplasms in a population-based, ...multicenter, nationwide, randomized controlled trial. Methods We identified asymptomatic men and women, 50–69 years old, through community health registries and randomly assigned them to groups that received a single colonoscopy examination or biennial FIT. Sigmoidoscopy yield was simulated from results obtained from the colonoscopy group, according to the criteria proposed in the UK Flexible Sigmoidoscopy Trial for colonoscopy referral. Patients who underwent FIT and were found to have ≥75 ng hemoglobin/mL were referred for colonoscopy. Data were analyzed from 5059 subjects in the colonoscopy group and 10,507 in the FIT group. The main outcome was rate of detection of any advanced neoplasm proximal to the splenic flexure. Results Advanced neoplasms were detected in 317 subjects (6.3%) in the sigmoidoscopy simulation group compared with 288 (2.7%) in the FIT group (odds ratio for sigmoidoscopy, 2.29; 95% confidence interval, 1.93–2.70; P = .0001). Sigmoidoscopy also detected advanced distal neoplasia in a higher percentage of patients than FIT (odds ratio, 2.61; 95% confidence interval, 2.20–3.10; P = .0001). The methods did not differ significantly in identifying patients with advanced proximal neoplasms (odds ratio, 1.17; 95% confidence interval, 0.78–1.76; P = .44). This was probably due to the lower performance of both strategies in detecting patients with proximal lesions (sigmoidoscopy detected these in 19.1% of patients and FIT in 14.9% of patients) vs distal ones (sigmoidoscopy detected these in 86.8% of patients and FIT in 33.5% of patients). Sigmoidoscopy, but not FIT, detected proximal lesions in lower percentages of women (especially those 50–59 years old) than men. Conclusions Sigmoidoscopy and FIT have similar limitations in detecting advanced proximal neoplasms, which depend on patients' characteristics; sigmoidoscopy underperforms for women 50–59 years old. Screening strategies should be designed on the basis of target population to increase effectiveness and cost-effectiveness. ClinicalTrials.gov number: NCT00906997
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