Severe sepsis and septic shock can alter the pharmacokinetics of broad-spectrum ␤-lactams (meropenem, ceftazidime/cefepime, and piperacillin-tazobactam), resulting in inappropriate serum concentrations. Obesity may further modify the pharmacokinetics of these agents. We reviewed our data on critically ill obese patients (body mass index of >30 kg/m 2 ) treated with a broadspectrum ␤-lactam in whom therapeutic drug monitoring was performed and compared the data to those obtained in critically nonobese patients (body mass index of <25 kg/m 2 ) to assess whether there were differences in reaching optimal drug concentrations for the treatment of nosocomial infections. Sixty-eight serum levels were obtained from 49 obese patients. There was considerable variability in ␤-lactam serum concentrations (coefficient of variation of 50% to 92% for the three drugs). Standard drug regimens of ␤-lactams resulted in insufficient serum concentrations in 32% of the patients and overdosed concentrations in 25%. Continuous renal replacement therapy was identified by multivariable analysis as a risk factor for overdosage and a protective factor for insufficient ␤-lactam serum concentrations. The serum drug levels from the obese cohort were well matched for age, gender, renal function, and sequential organ failure assessment (SOFA) score to 68 serum levels measured in 59 nonobese patients. The only difference observed between the two cohorts was in the subgroup of patients treated with meropenem and who were not receiving continuous renal replacement therapy: serum concentrations were lower in the obese cohort. No differences were observed in pharmacokinetic variables between the two groups. Routine therapeutic drug monitoring of ␤-lactams should be continued in obese critically ill patients.

Estimates of population structure and gene flow allow exploring the historical and contemporary processes that determine a species’ biogeographic pattern. In mangroves, large-scale genetic studies to estimate gene flow have been conducted predominantly in the Indo-Pacific and Atlantic region. Here we examine the genetic diversity and connectivity of Rhizophora mucronata across a > 3,000 km coastal stretch in the Western Indian Ocean (WIO) including WIO islands. Based on 359 trees from 13 populations and using 17 polymorphic microsatellite loci we detected genetic breaks between populations of the (1) East African coastline, (2) Mozambique Channel Area (3) granitic Seychelles, and (4) Aldabra and northern Madagascar. Genetic structure, diversity levels, and patterns of inferred connectivity, aligned with the directionality of major ocean currents, driven by bifurcation of the South Equatorial Current, northward into the East African Coastal Current and southward into the Mozambique Channel Area. A secondary genetic break between nearby populations in the Delagoa Bight coincided with high inbreeding levels and fixed loci. Results illustrate how oceanographic processes can connect and separate mangrove populations regardless of geographic distance.

In this clinically relevant model of sepsis, tetrahydrobiopterin supplementation attenuated the impairment in sublingual microvascular perfusion and permeability, which was accompanied by better preserved gas exchange, renal flow and urine output, and prolonged survival.

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BackgroundCancer chemotherapy drugs are classified as high-risk molecules. Safety of the cancer chemotherapy process is often achieved with the implementation of a health information technology to each step or to the entire process. However, computerisation could lead to the emergence of new unintended medication errors. The aim of the study was to evaluate the impact of new software designed for the management of anticancer chemotherapies.MethodThe cartography of the process and the failure modes, effects and criticality analysis were performed by a multidisciplinary team. Criticality indexes were calculated considering or not the implementation of the commercial software (CytoWeb). Quality and satisfactory indicators were measured before the implementation and during the use of the software.ResultsOur results demonstrated the complexity of the cancer chemotherapy process in the hospital. Risk analysis highlighted the positive impact of CytoWeb on the process safety but pointed out some steps that were not positively influenced by the software. Although a decrease of 38.6% of error rate was observed with the electronic system, new unintended medication errors emerged. These errors were due to inadequate use of the software (encoding of the wrong drug, the wrong dose, the wrong patient parameters or lab results and lack of prescriber adherence). Our satisfaction survey showed that the hospital pharmacists and doctors were less satisfied by the software than the nurses, mostly in terms of task achievement and time saving. Survey’s results highlighted some weaknesses in the user training and in the collaboration between the medical staff.ConclusionsOur work showed the emergence of unintended medication errors linked to computerisation that were due to an inadequate use of the software. Other issues were highlighted such as the lack of collaboration between the medical staff, the lack of prescriber implication and weaknesses in the user training or in the information related to CytoWeb.