Inappropriate antimicrobial use favours the spread of resistance, and multidrug-resistant microorganisms (MDR) are currently of major concern. Antimicrobial stewardship programmes (ASPs) are ...essential for improving antibiotic use in hospitals. However, their impact on entire healthcare systems has not been thoroughly assessed. Our objective was to provide the results of an institutionally supported ASP involving 31 public hospitals in Andalusia, Spain.
We designed an ecologic time-series study from 1 January 2014 to 31 December 2017. Quarterly, data on indicators were collected prospectively, and feedback reports were provided. PIRASOA is an ongoing clinically based quality-improvement programme whose key intervention is the educational interview, regular peer-to-peer interventions between advisors and prescribers to reinforce the appropriate use of antibiotics. Seventy-two indicators were monitored to measure prescribing quality (inappropriate treatments), antimicrobial consumption (defined daily doses per 1000 occupied bed-days), incidence density of MDR per 1000 occupied bed-days and crude mortality rate associated with bloodstream infections. We used Joinpoint regression software to analyse the trends.
The quality of antimicrobial prescribing improved markedly, and the inappropriate treatment rate was significantly lower, with quarterly percentage change (QPC) = −3.0%, p < 0.001. Total antimicrobial consumption decreased (QPC = −0.9%, p < 0.001), specifically carbapenems, amoxicillin/clavulanic acid, quinolones and antifungal agents, whereas antipseudomonal cephalosporin use increased. While the incidence of MDR showed a sustained decreasing trend (QPC = −1.8%; p 0.002), the mortality of patients with bloodstream infections remained stable (QPC = −0.2%, p 0.605).
To date, the PIRASOA programme has succeeded in optimizing the use of antimicrobial agents and has had a positive ecologic result on bacterial resistance at level of an entire healthcare system.
Mycobacterium chimaera is involved in a worldwide alert due to contaminated heater–cooler units. A real-time polymerase chain reaction (RT-PCR)-based procedure was implemented to survey undetected ...cases of M. chimaera infection. PCR was negative in the 59 prosthetic heart valves from patients with PCR-16SrRNA-negative infective endocarditis. PCR identified M. chimaera in one of 15 clinically significant retrospective Mycobacterium avium–Mycobacterium intracellulare complex isolates, which corresponded to a patient who had undergone heart valve replacement in a different institution. Whole-genome sequencing demonstrated that he was the first case in Spain with involvement of the strain responsible for the global outbreak. These results highlight the relevance of retrospective tracking for undetected M. chimaera infections.
Background and purpose
Although the causes of multiple sclerosis (MS) remain partially unknown, environmental and genetic factors are thought to play a role in its aetiopathogenesis. Hypovitaminosis ...D, Epstein–Barr virus (EBV) and human herpesvirus 6 (HHV‐6) infections have been described as possible MS triggers. Our aim was to analyse the possible link between 25‐hydroxyvitamin D 25(OH)D and viruses in patients with MS.
Methods
We included 482 patients with MS in a 2‐year study. Serum samples were collected to analyse 25(OH)D levels and, according to sample availability, antibody titres against EBV and HHV‐6 by enzyme‐linked immunosorbent assay. DNA was extracted from blood in order to analyse EBV and HHV‐6 viral load by quantitative real‐time polymerase chain reaction and to genotype MS‐related single nucleotide polymorphisms (rs3135388, rs2248359 and rs12368653) when possible.
Results
The 25(OH)D levels were significantly higher in the first semester of the year than in the second. Carriers of the risk allele rs2248359‐C showed lower 25(OH)D levels than non‐carriers. For EBV, viral load was significantly higher when 25(OH)D levels were low, demonstrating an inverse correlation between 25(OH)D levels and EBV load.
Conclusions
The 25(OH)D levels could be involved in the regulation of EBV replication/reactivation in patients with MS.
Abstract
Biologic and targeted synthetic disease-modifying antirheumatic drugs (ts/bDMARDs) play a pivotal role in the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ...ankylosing spondylitis (AS). Persistence of therapy provides an index of a drug’s overall effectiveness. The objective of the study was to identify factors associated with discontinuation of ts/bDMARDs in a real-world dataset. The study population comprised patients diagnosed with RA, PsA, and AS included in the BIOBADASER registry for whom follow-up data were available until November 2019. Patient features and treatment data were included in the analysis. The Kaplan–Meier method was used to study survival of the different drugs according to the reason for discontinuation. Factors associated with discontinuation were studied using Cox regression models and bivariate and multivariate analyses. P values of less than 0.05 were regarded as statistically significant. The study population comprised 4,752 patients who received a total of 8,377 drugs, of which 4,411 (52.65%) were discontinued. The Kaplan–Meier curves showed that survival for first-line treatment was greater in all 3 groups (p < 0.001). Patients with RA had a greater risk of discontinuation if they were younger (HR, 0.99; 95% CI 0.99–1.00), if they were receiving anti-TNFα agents (HR, 0.61; 95% CI 0.54–0.70), and if they had more comorbid conditions (HR, 1.09; 95% CI 1.00–1.17). Patients with PsA had a higher risk if they were women (HR, 1.36; 95% CI 1.15–1.62) and if they were receiving other ts/bDMARDs (HR, 1.29; 95% CI 1.05–1.59). In patients with AS, risk increased with age (HR, 1.01; 95% CI 1.00–1.02), as did the number of comorbid conditions (HR, 1.27; 95% CI 1.12–1.45). The factors that most affected discontinuation of ts/bDMARDs were line of treatment, age, type of drug, sex, comorbidity and the year of initiation of treatment. The association with these factors differed with each disease, except for first-line treatment, which was associated with a lower risk of discontinuation in all 3 diseases.
Seventeen Middle Pleistocene crania from the Sima de los Huesos site (Atapuerca, Spain) are analyzed, including seven new specimens. This sample makes it possible to thoroughly characterize a Middle ...Pleistocene hominin paleodeme and to address hypotheses about the origin and evolution of the Neandertals. Using a variety of techniques, the hominin-bearing layer could be reassigned to a period around 430,000 years ago. The sample shows a consistent morphological pattern with derived Neandertal features present in the face and anterior vault, many of which are related to the masticatory apparatus. This suggests that facial modification was the first step in the evolution of the Neandertal lineage, pointing to a mosaic pattern of evolution, with different anatomical and functional modules evolving at different rates.
Background
Allergic reactions to β‐lactams are among the most frequent causes of drug allergy and constitute an important clinical problem. Drug covalent binding to endogenous proteins (haptenation) ...is thought to be required for activation of the immune system. Nevertheless, neither the nature nor the role of the drug protein targets involved in this process is fully understood. Here, we aim to identify novel intracellular targets for haptenation by amoxicillin (AX) and their cellular fate.
Methods
We have treated B lymphocytes with either AX or a biotinylated analog (AX‐B). The identification of protein targets for haptenation by AX has been approached by mass spectrometry and immunoaffinity techniques. In addition, intercellular communication mediated by the delivery of vesicles loaded with AX‐B‐protein adducts has been explored by microscopy techniques.
Results
We have observed a complex pattern of AX‐haptenated proteins. Several novel targets for haptenation by AX in B lymphocytes have been identified. AX‐haptenated proteins were detected in cell lysates and extracellularly, either as soluble proteins or in lymphocyte‐derived extracellular vesicles. Interestingly, exosomes from AX‐B‐treated cells showed a positive biotin signal in electron microscopy. Moreover, they were internalized by endothelial cells, thus supporting their involvement in intercellular transfer of haptenated proteins.
Conclusions
These results represent the first identification of AX‐mediated haptenation of intracellular proteins. Moreover, they show that exosomes can constitute a novel vehicle for haptenated proteins, and raise the hypothesis that they could provide antigens for activation of the immune system during the allergic response.
Patients with end‐stage renal disease have longer survival after kidney transplantation than they would by remaining on dialysis; however, outcome with kidneys from donors aged ≥75 years and the ...survival of recipients of these organs compared with their dialysis counterparts with the same probability of obtaining an organ is unknown. In a longitudinal mortality study, 2040 patients on dialysis were placed on a waiting list, and 389 of them received a first transplant from a deceased donor aged ≥75 years. The adjusted risk of death and survival were calculated by non–proportional hazards analysis with being transplanted as a time‐dependent effect. Projected years of life since placement on the waiting list was almost twofold higher for transplanted patients. Nonproportional adjusted risk of death after transplantation was 0.44 (95% confidence interval CI 0.61–0.32; p < 0.001) in comparison with those that remained on dialysis. Stratifying by age, adjusted hazard ratios for death were 0.17 (95% CI 0.47–0.06; p = 0.001) for those aged <65 years, 0.56 (95% CI 0.92–0.34; p = 0.022) for those aged 65–69 years and 0.82 (95% CI 1.28–0.52; p = 0.389) for those aged ≥70 years. Although kidney transplantation from elderly deceased donors is associated with reduced graft survival, transplanted patients have lower mortality than those remaining on dialysis.
The authors compare the outcomes of kidney transplantation from donors over 75 years old with a time‐dependent survival model with recipients on the waitlist remaining on dialysis, and they find significantly better survival in transplanted patients, especially in those under 65 years old.
The Madín Dam is a reservoir located in the municipalities of Naucalpan and Atizapán, in the metropolitan area adjacent to Mexico City. The reservoir supplies drinking water to nearby communities and ...provides an area for various recreational activities, including kayaking, sailing and carp fishing. Over time, the number of specimens of common carp has notably diminished in the reservoir, which receives direct domestic drainage from two towns as well as numerous neighborhoods along the Tlalnepantla River. Diverse studies have demonstrated that the pollutants in the water of the reservoir produce oxidative stress, genotoxicity and cytotoxicity in juvenile Cyprinus carpio, possibly explaining the reduction in the population of this species; however, it is necessary to assess whether these effects may also be occurring directly in the embryos. Hence, surface water samples were taken at five sites and pharmaceutical drugs, personal care products (especially sunscreens), organophosphate and organochlorine pesticides, and other persistent organic pollutants (e.g., polychlorinated biphenyls and polycyclic aromatic hydrocarbons) were identified. Embryos of C. carpio were exposed to the water samples to evaluate embryolethality, modifications in embryonic development, lipoperoxidation, the quantity of hydroperoxide and oxidized proteins, and antioxidant enzyme activity (superoxide dismutase, catalase and glutathione peroxidase). It was found that the polluted water of the Madín Dam gave rise to embryolethality, embryotoxicity, congenital abnormalities, and oxidative stress on the common carp embryos.
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•The water of the Madin dam contains hydrocarbons of various types.•These hydrocarbons in combination with other contaminants from the site produce embryotoxicity in the common carp.•Cyprinus carpio is at risk in the Madín reservoir.
The water of the Madín dam contains a complex mixture of pollutants, including hydrocarbons, which produce oxidative stress and embryotoxicity on Cyprinus carpio.
Summary
We reviewed systematically sugammadex vs neostigmine for reversing neuromuscular blockade. We included 17 randomised controlled trials with 1553 participants. Sugammadex reduced all signs of ...residual postoperative paralysis, relative risk (95% CI) 0.46 (0.29–0.71), p = 0.0004 and minor respiratory events, relative risk (95% CI) 0.51 (0.32–0.80), p = 0.0034. There was no difference in critical respiratory events, relative risk (95% CI) 0.13 (0.02–1.06), p = 0.06. Sugammadex reduced drug‐related side‐effects, relative risk (95% CI) 0.72 (0.54–0.95), p = 0.02. There was no difference in the rate of postoperative nausea or the rate of postoperative vomiting, relative risk (95% CI) 0.94 (0.79–1.13), p = 0.53, and 0.87 (0.65–1.17), p = 0.36 respectively.
Landscape features have been shown to strongly influence dispersal and, consequently, the genetic population structure of organisms. Studies quantifying the effect of landscape features on gene flow ...of large mammals with high dispersal capabilities are rare and have mainly been focused at large geographical scales. In this study, we assessed the influence of several natural and human-made landscape features on red deer gene flow in the Scottish Highlands by analysing 695 individuals for 21 microsatellite markers. Despite the relatively small scale of the study area (115 x 87 km), significant population structure was found using F-statistics (FST = 0.019) and the program structure, with major differentiation found between populations sampled on either side of the main geographical barrier (the Great Glen). To assess the effect of landscape features on red deer population structure, the ArcMap GIS was used to create cost-distance matrices for moving between populations, using a range of cost values for each of the landscape features under consideration. Landscape features were shown to significantly affect red deer gene flow as they explained a greater proportion of the genetic variation than the geographical distance between populations. Sea lochs were found to be the most important red deer gene flow barriers in our study area, followed by mountain slopes, roads and forests. Inland lochs and rivers were identified as landscape features that might facilitate gene flow of red deer. Additionally, we explored the effect of choosing arbitrary cell cost values to construct least cost-distance matrices and described a method for improving the selection of cell cost values for a particular landscape feature.
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