-
Lyhne posted an update 7 months, 1 week ago
The authors wish to make the following changes to this paper […].C-reactive protein (CRP) point-of-care testing (POCT) is increasingly being promoted to reduce diagnostic uncertainty and enhance antibiotic stewardship. In primary care, respiratory tract infections (RTIs) are the most common reason for inappropriate antibiotic prescribing, which is a major driver for antibiotic resistance. We systematically reviewed the available evidence on the impact of CRP-POCT on antibiotic prescribing for RTIs in primary care. Thirteen moderate to high-quality studies comprising 9844 participants met our inclusion criteria. Meta-analyses showed that CRP-POCT significantly reduced immediate antibiotic prescribing at the index consultation compared with usual care (RR 0.79, 95%CI 0.70 to 0.90, p = 0.0003, I2 = 76%) but not during 28-day (n = 7) follow-up. The immediate effect was sustained at 12 months (n = 1). In children, CRP-POCT reduced antibiotic prescribing when CRP (cut-off) guidance was provided (n = 2). Meta-analyses showed significantly higher rates of re-consultation within 30 days (n = 8, 1 significant). Clinical recovery, resolution of symptoms, and hospital admissions were not significantly different between CRP-POCT and usual care. CRP-POCT can reduce immediate antibiotic prescribing for RTIs in primary care (number needed to (NNT) for benefit = 8) at the expense of increased re-consultations (NNT for harm = 27). The increase in re-consultations and longer-term effects of CRP-POCT need further evaluation. Overall, the benefits of CRP-POCT outweigh the potential harms (NNTnet = 11).This manuscript presents quantitative findings on the actual effectiveness of terminal complement component 5 (C5) inhibitors and complement component 1 (C1) esterase inhibitors through their formal and common “off-label” (compassionate) indications. The results emanated from pairwise and network meta-analyses to present evidence until September 2019. Clinical trials (CT) and real-life non-randomized studies of the effects of interventions (NRSI) are consistent on the benefits of C5 inhibitors and of the absence of effects of C1 esterase inhibitors (n = 7484) Mathematically, eculizumab (surface under the cumulative ranking area (SUCRA) >0.6) and ravulizumab (SUCRA ≥ 0.7) were similar in terms of their protective effect on hemolysis in paroxysmal nocturnal hemoglobinuria (PNH), thrombotic microangiopathy (TMA) in atypical hemolytic uremic syndrome (aHUS), and acute kidney injury (AKI) in aHUS, in comparison to pre-/off-treatment state and/or placebo (SUCRA less then 0.01), and eculizumab was efficacious on thrombotic events in PNH (odds ratio (OR)/95% confidence interval (95% CI) in CT and real-life NRSI, 0.07/0.03 to 0.19, 0.24/0.17 to 0.33) and chronic kidney disease (CKD) occurrence/progression in PNH (0.31/0.10 to 0.97, 0.66/0.44 to 0.98). In addition, meta-analysis on clinical trials shows that eculizumab mitigates a refractory generalized myasthenia gravis (rgMG) crisis (0.29/0.13 to 0.61) and prevents new acute antibody-mediated rejection (AMR) episodes in kidney transplant recipients (0.25/0.13 to 0.49). The update of findings from this meta-analysis will be useful to promote a better use of complement inhibitors, and to achieve personalization of treatments with this class of drugs.The objectives of the present work were to evaluate the in vivo antimethanogenic effects of Cymbopogon citratus (CC), Matricaria chamomilla (MC) and Cosmos bipinnatus (CB) on beef cattle fed a high in concentrate diet (forage-to-concentrate ratio [FC] of 19.480.6), and the effects of increasing levels of CC (0%, 2%, 3%, and 4% of the daily DM intake (DMI)) on enteric CH4 emissions by beef cattle fed a ration low in concentrate (FC ratio of 49.350.7). Two experiments were conducted to address the objectives. For the first experiment, eight Charolais × Brown Swiss steers distributed in a replicated 4 × 4 Latin square experimental design were used. Four treatments were evaluated (1) control diet (CO), (2) CO + 365 g dry matter (DM)/d CB, (3) CO + 365 g DM/d MC, (4) CO + 100 g DM/d CC. Acetylcholine Chloride concentration For Experiment 2, four Charolais x Brown Swiss steers distributed in a single 4 × 4 Latin square design were used. It was concluded that 100 g DM per day CC and 365 g DM per day CB (Experiment 1) reduced CH4 yield of beef cattle. In Experiment 2, CC supplementation levels exceeding 2% of DMI reduced daily CH4 emissions but at the expense of decreasing digestibility of DM.Personalized medicine in treating pancreatic ductal adenocarcinoma (PDAC) is still in its infancy, albeit PDAC-related deaths are projected to rise over the next decade. Only recently, maintenance therapy with the PARP inhibitor olaparib showed improved progression-free survival in germline BRCA1/2-mutated PDAC patients after platinum-based induction for the first time. Transferability of such a concept to other DNA damage response (DDR) genes remains unclear. Here, we conducted a placebo-controlled, three-armed preclinical trial to evaluate the efficacy of multi-DDR interference (mDDRi) as maintenance therapy vs. continuous FOLFIRINOX treatment, implemented with orthotopically transplanted ATM-deficient PDAC cell lines. Kaplan-Meier analysis, cross-sectional imaging, histology, and in vitro analysis served as analytical readouts. Median overall survival was significantly longer in the mDDRi maintenance arm compared to the maintained FOLFIRINOX treatment. This survival benefit was mirrored in the highest DNA-damage load, accompanied by superior disease control and reduced metastatic burden. In vitro analysis suggests FOLFIRINOX-driven selection of invasive subclones, erased by subsequent mDDRi treatment. Collectively, this preclinical trial substantiates mDDRi in a maintenance setting as a novel therapeutic option and extends the concept to non-germline BRCA1/2-mutant PDAC.Pansharpening is a technique that fuses a low spatial resolution multispectral image and a high spatial resolution panchromatic one to obtain a multispectral image with the spatial resolution of the latter while preserving the spectral information of the multispectral image. In this paper we propose a variational Bayesian methodology for pansharpening. The proposed methodology uses the sensor characteristics to model the observation process and Super-Gaussian sparse image priors on the expected characteristics of the pansharpened image. The pansharpened image, as well as all model and variational parameters, are estimated within the proposed methodology. Using real and synthetic data, the quality of the pansharpened images is assessed both visually and quantitatively and compared with other pansharpening methods. Theoretical and experimental results demonstrate the effectiveness, efficiency, and flexibility of the proposed formulation.