Background Spread of resistant bacteria causes severe morbidity and mortality. Stringent control measures can be expensive and disrupt hospital organization. In the present study, we assessed the effectiveness and cost-effectiveness of control strategies to prevent the spread of Carbapenemase-producing Enterobacterales (CPE) in a general hospital ward (GW). Methods A dynamic, stochastic model simulated the transmission of CPE by the hands of healthcare workers (HCWs) and the environment in a hypothetical 25-bed GW. Input parameters were based on published data; we assumed the prevalence at admission of 0.1%. 12 strategies were compared to the baseline (no control) and combined different prevention and control interventions: targeted or universal screening at admission (TS or US), contact precautions (CP), isolation in a single room, dedicated nursing staff (DNS) for carriers and weekly screening of contact patients (WSC). Time horizon was one year. Outcomes were the number of CPE acquisitions, costs, and incremental cost-effectiveness ratios (ICER). A hospital perspective was adopted to estimate costs, which included laboratory costs, single room, contact precautions, staff time, i.e. infection control nurse and/or dedicated nursing staff, and lost bed-days due to prolonged hospital stay of identified carriers. The model was calibrated on actual datasets. Sensitivity analyses were performed. Results The baseline scenario resulted in 0.93 CPE acquisitions/1000 admissions and costs 32,050 €/1000 admissions. All control strategies increased costs and improved the outcome. The efficiency frontier was represented by: (1) TS with DNS at a 17,407 €/avoided CPE case, (2) TS + DNS + WSC at a 30,700 €/avoided CPE case and (3) US + DNS + WSC at 181,472 €/avoided CPE case. Other strategies were dominated. Sensitivity analyses showed that TS + CP might be cost-effective if CPE carriers are identified upon admission or if the cases have a short hospital stay. However, CP were effective only when high level of compliance with hand hygiene was obtained. Conclusions Targeted screening at admission combined with DNS for identified CPE carriers with or without weekly screening were the most cost-effective options to limit the spread of CPE. These results support current recommendations from several high-income countries.

This year marks the 150th anniversary of the discovery of the neural crest by Wilhelm His (1831-1904). Beyond this discovery, His made possible the program of comparative anatomy at the cellular level thanks to the introduction in 1866 of the first microtome to have micrometer advance. His studies of the origin, migration, and fate of neural crest cells were foundational in the field of neuroembryology and contributed to the establishment of the neuron doctrine. The article places His' work in the scientific context of 19th century embryology, concerned with reconciling the embryonic layers theory, the cell theory and the evolution theory. From a methodological point of view, the article shows that His appears in this context at the junction of two embryological traditions, the descriptive morphological approach and the new experimental approach. The anatomical and physiological exploration of the neural crest and the controversies that followed highlight the transition between these two traditions that His enabled and of which he was one of the initiators.

At the end of the nineteenth century, approaches from experimental physiology made inroads into embryological research. A new generation of embryologists felt urged to study the mechanisms of organ formation. This new program, most prominently defended by Wilhelm Roux (1850-1924), was called Entwicklungsmechanik. Named variously as "causal embryology", "physiological embryology" or "developmental mechanics", it catalyzed the movement of embryology from a descriptive science to one exploring causal mechanisms. This article examines the specific scientific and epistemological meaning of the mechanistic approaches of embryological development by focusing on Wilhelm His' (1831-1904) histogenetic work. Roux was neither the first, nor the only one to argue for an experimental exploration of causes in embryology. At the time of Roux, physiological explanations of the genesis of the anatomical forms were developing in parallel, not only in German-speaking countries, but in France, Switzerland and English-speaking countries as well. The experimental approach and the cellular descriptions of embryogenesis were already omni-present when Roux proposed his Entwicklungsmechanik. However, these approaches remained disjointed. It appears that it was Wilhelm His who first succeeded in combining the question of the causal factors determining epigenesis, which was closely connected with experimentation on, and cellular descriptions of, development, in a coherent and concrete synthesis, making him one of the true initiators of the developmental mechanics.

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