Systematic Review and Meta-Analysis To Estimate Antibacterial Treatment Effect in Acute Bacterial Skin and Skin Structure Infection

ABSTRACT A systematic literature review and meta-analysis were conducted to estimate the antibacterial treatment effect for linezolid and ceftaroline to inform on the design of acute bacterial skin and skin structure infection (ABSSSI) noninferiority trials. The primary endpoints included an early clinical treatment response (ECTR) defined as cessation of lesion spread at 48 to 72 h postrandomization and the test-of-cure (TOC) response defined as total resolution of the infection at 7 to 14 days posttreatment. The systematic review identified no placebo-controlled trials in ABSSSI, 4 placebo-controlled trials in uncomplicated skin and soft tissue infection as a proxy for placebo in ABSSSI, 12 linezolid trials in ABSSSI, 3 ceftaroline trials in ABSSSI, and 2 trials for nonantibacterial treatment. The ECTR rates at 48 to 72 h and corresponding 95% confidence intervals (CI) were 78.7% (95% CI, 61.1 to 96.3%) for linezolid, 74.0% (95% CI, 69.7 to 78.3%) for ceftaroline, and 59.0% (95% CI, 52.8 to 65.3%) for nonantibacterial treatment. The early clinical treatment effect could not be estimated, given no available placebo or proxy for placebo data for this endpoint. Clinical, methodological, and statistical heterogeneity influenced the selection of trials for the meta-analysis of the TOC treatment effect estimation. The pooled estimates of the TOC treatment response were 31.0% (95% CI, 6.2 to 55.9%) for the proxy for placebo, 88.1% (95% CI, 81.0 to 95.1%) for linezolid, and 86.1% (95% CI, 83.7 to 88.6%) for ceftaroline. The TOC clinical treatment effect estimation was 25.1% for linezolid and 27.8% for ceftaroline. The antibacterial treatment effect estimation at TOC will inform on the design and analysis of future noninferiority ABSSSI clinical trials

Atypical Avian Influenza (H5N1)

We report the first case of avian influenza in a patient with fever and diarrhea but no respiratory symptoms. Avian influenza should be included in the differential diagnosis for patients with predominantly gastrointestinal symptoms, particularly if they have a history of exposure to poultry

Phosphatidylserine stimulates ceramide 1-phosphate (C1P) intermembrane transfer by C1P transfer proteins

Genetic models for studying localized cell suicide that halt the spread of pathogen infection and immune response activation in plants include Arabidopsis accelerated-cell-death 11 mutant (acd11). In this mutant, sphingolipid homeostasis is disrupted via depletion of ACD11, a lipid transfer protein that is specific for ceramide 1-phosphate (C1P) and phyto-C1P. The C1P binding site in ACD11 and in human ceramide-1-phosphate transfer protein (CPTP) is surrounded by cationic residues. Here, we investigated the functional regulation of ACD11 and CPTP by anionic phosphoglycerides and found that 1-palmitoyl-2-oleoyl-phosphatidic acid or 1-palmitoyl-2-oleoyl-phosphatidylglycerol (≤15 mol %) in C1P source vesicles depressed C1P intermembrane transfer. By contrast, replacement with 1-palmitoyl-2-oleoyl-phosphatidylserine stimulated C1P transfer by ACD11 and CPTP. Notably, “soluble” phosphatidylserine (dihexanoyl-phosphatidylserine) failed to stimulate C1P transfer. Also, none of the anionic phosphoglycerides affected transfer action by human glycolipid lipid transfer protein (GLTP), which is glycolipid-specific and has few cationic residues near its glycolipid binding site. These findings provide the first evidence for a potential phosphoglyceride headgroup-specific regulatory interaction site(s) existing on the surface of any GLTP-fold and delineate new differences between GLTP superfamily members that are specific for C1P versus glycolipid

What can eye-tracking tell us?

Background: Early development of neurocognitive functions in infants can be compromised by poverty, malnutrition and lack of adequate stimulation. Optimal management of neurodevelopmental problems in infants requires assessment tools that can be used early in life, and are objective and applicable across economic, cultural and educational settings. Objective and design: The present study examined the feasibility of infrared eye tracking as a novel and highly automated technique for assessing visual-orienting and sequence-learning abilities as well as attention to facial expressions in young (9-month-old) infants. Techniques piloted in a high-resource laboratory setting in Finland (N=39) were subsequently field-tested in a community health centre in rural Malawi (N=40). Results: Parents' perception of the acceptability of the method (Finland 95%, Malawi 92%) and percentages of infants completing the whole eye-tracking test (Finland 95%, Malawi 90%) were high, and percentages of valid test trials (Finland 69-85%, Malawi 68-73%) satisfactory at both sites. Test completion rates were slightly higher for eye tracking (90%) than traditional observational tests (87%) in Malawi. The predicted response pattern indicative of specific cognitive function was replicated in Malawi, but Malawian infants exhibited lower response rates and slower processing speed across tasks. Conclusions: High test completion rates and the replication of the predicted test patterns in a novel environment in Malawi support the feasibility of eye tracking as a technique for assessing infant development in low-resource setting. Further research is needed to the test-retest stability and predictive validity of the eye-tracking scores in low-income settings