Evidence before this studyWe searched PubMed with the search terms "randomized OR randomised" AND " Implications of all the available evidenceThe pathogens isolated in this study are consistent with those commonly observed in patients with NP, including VAP. NP is among the most serious bacterial infections, and -lactams are frequently the cornerstone of antimicrobial therapy in this setting. These results add to the evidence base demonstrating the efficacy and safety of ceftazidime-avibactam in treating infections caused by Gram-negative pathogens, including those considered non-susceptible to ceftazidime. These findings collectively support a role for ceftazidime-avibactam as a potential alternative to carbapenems in patients with serious infections caused by Gramnegative pathogens, including NP/VAP.

Ceftazidime/avibactam comprises the broad-spectrum cephalosporin ceftazidime and the non-β-lactam β-lactamase inhibitor avibactam. This phase 3, randomised, double-blind study (NCT01726023) assessed the efficacy and safety of ceftazidime/avibactam plus metronidazole compared with meropenem in patients with complicated intra-abdominal infection (cIAI) in Asian countries. Subjects aged 18-90 years and hospitalised with cIAI requiring surgical intervention were randomised 1:1 to receive every 8 h either: ceftazidime/avibactam (2000/500 mg, 2-h infusion) followed by metronidazole (500 mg, 60-min infusion); or meropenem (1000 mg, 30-min infusion). Non-inferiority of ceftazidime/avibactam plus metronidazole to meropenem was concluded if the lower limit of the 95% confidence interval (CI) for the between-group difference in clinical cure rate was greater than -12.5% at the test-of-cure (TOC) visit (28-35 days after randomisation) in the clinically evaluable (CE) population. Safety was also evaluated. Of 441 subjects randomised, 432 received at least one dose of study medication (ceftazidime/avibactam plus metronidazole, n = 215; meropenem, n = 217). In the CE population at the TOC visit, non-inferiority of ceftazidime/avibactam plus metronidazole to meropenem was demonstrated, with clinical cure reported for 93.8% (166/177) and 94.0% (173/184) of subjects, respectively (between-group difference, -0.2, 95% CI -5.53 to 4.97). The clinical cure rate with ceftazidime/avibactam plus metronidazole was comparable in subjects with ceftazidime-non-susceptible and ceftazidime-susceptible isolates (95.7% vs. 92.1%, respectively). Adverse events were similar between the study groups. Ceftazidime/avibactam plus metronidazole was non-inferior to meropenem in the treatment of cIAIs in Asian populations and was effective against ceftazidime-non-susceptible pathogens. No new safety concerns were identified.

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Ceftazidime/avibactam demonstrated similar clinical efficacy to predominantly carbapenem comparators against MDR Enterobacteriaceae and P. aeruginosa, and may be a suitable alternative to carbapenem-based therapies for cIAI, cUTI and NP/VAP caused by MDR Gram-negative pathogens.

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Dominantly inherited channelopathies of the skeletal muscle voltage-gated sodium channel NaV1.4 include hypokalaemic and hyperkalaemic periodic paralysis (hypoPP and hyperPP) and myotonia. HyperPP and myotonia are caused by NaV1.4 channel overactivity and overlap clinically. Instead, hypoPP is caused by gating pore currents through the voltage sensing domains (VSDs) of NaV1.4 and seldom co-exists clinically with myotonia. Recessive loss-of-function NaV1.4 mutations have been described in congenital myopathy and myasthenic syndromes. We report two families with the NaV1.4 mutation p.R1451L, located in VSD-IV. Heterozygous carriers in both families manifest with myotonia and/or hyperPP. In contrast, a homozygous case presents with both hypoPP and myotonia, but unlike carriers of recessive NaV1.4 mutations does not manifest symptoms of myopathy or myasthenia. Functional analysis revealed reduced current density and enhanced closed state inactivation of the mutant channel, but no evidence for gating pore currents. The rate of recovery from inactivation was hastened, explaining the myotonia in p.R1451L carriers and the absence of myasthenic presentations in the homozygous proband. Our data suggest that recessive loss-of-function NaV1.4 variants can present with hypoPP without congenital myopathy or myasthenia and that myotonia can present even in carriers of homozygous NaV1.4 loss-of-function mutations.

Cross-cultural diff erences in cognition are often related to one single cultural dimension. Whether this suffi ces even for simple tasks is examined in the context of causal attribution. Culture-specifi c attribution biases are well-established for the social domain, but under dispute for the physical domain. In order to identify and assess possible impacts on assigning physical causation, we conducted a cross-cultural experiment with participants from Germany, China and Tonga (n = 377). Participants were required to identify which of two entities is the ultimate cause for a physical interaction that was varied with regard to linguistic cues and content. Our data reveal overall cultural diff erences in attribution tendencies analogous to those in the social domain, but also an impact of linguistic cues and of the task-specifi c content.

Background A high prevalence of postoperative complications is closely associated with a worse short- and long-term outcome. This current study aimed to investigate potential risk factors including albumin-to-fibrinogen ratio (AFR) for severe postoperative complications (SPCs) in surgical gastric cancer (GC) patients. Methods Elderly patients (≥65 years) with primary GC who underwent elective radical laparoscopic gastrectomy under general anesthesia were included. According to the Clavien–Dindo classification system, the severity of complications was assessed from Grade I to V and SPCs were defined as C-D Grade ≥ IIIa. The clinicopathological features, operative-associated characteristics, postoperative recovery and laboratory tests were compared between patients with or without SPCs. Receiver operating characteristic (ROC) curve analysis using Youden’s Index was established for determining the predictive value and cut-off threshold of AFR for SPCs. Binary univariate and multivariate logistic regression models were used to assess factors influencing SPCs. Results A total of 365 elderly GC patients were finally included in the analysis, of which 52 (52/365, 14.2%) patients had developed SPCs within postoperative 30 days. Preoperative AFR level predicted SPCs in surgical GC patients with an AUC of 0.841, a sensitivity of 76.36% and a specificity of 80.77%, respectively (P < 0.001). The multivariate analysis revealed that a lower AFR level (OR: 1.94, 95% CI: 1.09–3.36, P = 0.017) and an older age (OR: 1.81, 95% CI: 1.06–3.04, P = 0.023) were two independent predictive factors for SPCs in surgical GC patients. Conclusions Preoperative AFR level is a useful predictor for SPCs in elderly GC subjects after radical laparoscopic gastrectomy.