An open-source drug discovery platform enables ultra-large virtual screens.

On average, an approved drug currently costs US$2-3 billion and takes more than 10 years to develop1. In part, this is due to expensive and time-consuming wet-laboratory experiments, poor initial hit compounds and the high attrition rates in the (pre-)clinical phases. Structure-based virtual screening has the potential to mitigate these problems. With structure-based virtual screening, the quality of the hits improves with the number of compounds screened2. However, despite the fact that large databases of compounds exist, the ability to carry out large-scale structure-based virtual screening on computer clusters in an accessible, efficient and flexible manner has remained difficult. Here we describe VirtualFlow, a highly automated and versatile open-source platform with perfect scaling behaviour that is able to prepare and efficiently screen ultra-large libraries of compounds. VirtualFlow is able to use a variety of the most powerful docking programs. Using VirtualFlow, we prepared one of the largest and freely available ready-to-dock ligand libraries, with more than 1.4 billion commercially available molecules. To demonstrate the power of VirtualFlow, we screened more than 1 billion compounds and identified a set of structurally diverse molecules that bind to KEAP1 with submicromolar affinity. One of the lead inhibitors (iKeap1) engages KEAP1 with nanomolar affinity (dissociation constant (Kd) = 114 nM) and disrupts the interaction between KEAP1 and the transcription factor NRF2. This illustrates the potential of VirtualFlow to access vast regions of the chemical space and identify molecules that bind with high affinity to target proteins.

Routine Monitoring of Sodium and Phosphorus Removal in Peritoneal Dialysis (PD) Patients Treated with Continuous Ambulatory PD (CAPD), Automated PD (APD) or Combined CAPD+APD.

BACKGROUND: Adequate removal of sodium (Na) and phosphorus (P) is of paramount importance for patients with dialysis-dependent kidney disease can easily quantified in peritoneal dialysis (PD) patients. Some studies suggest that automated PD (APD) results in lower Na and P removal. METHODS: In this study we retrospectively analysed our data on Na and P removal in PD patients after implementation of a routine monitoring in 2011. Patients were stratified in those treated with continuous ambulatory PD (CAPD, n=24), automated PD (APD, n=23) and APD with one bag change (CAPD+APD, n=10). Until 2015 we collected time-varying data on Na and P removal from each patient (median 5 [interquartile range 4-8] values). RESULTS: Peritoneal Na and P removal (mmol per 24h ± standard deviation) was 102 ± 48 and 8 ± 2 in the CAPD, 90 ± 46 and 9 ± 3 in the APD and 126 ± 39 and 13 ± 2 in the CAPD+APD group (ANOVA P=0.141 and <0.001). Taking renal excretion into account total Na and P removal (mmol per 24h) was 221 ± 65 and 16 ± 5 in the CAPD, 189 ± 58 and 17 ± 6 in the APD and 183 ± 38 and 16 ± 6 in the CAPD+APD group (P=0.107 and 0.764). Over time, peritoneal removal of Na but not that of P increased in all groups. In patients with modifications of PD treatment, Na but not P removal was significantly increased over-time. CONCLUSIONS: Overall Na and P removal were similar with different PD modalities. Individualized adjustments of PD prescription including icodextrin use or higher glucose concentration can improve Na removal while P removal is mainly determined by the dialysate volume.

Implantación de una historia clínica informatizada: encuesta sobre el grado de utilización y satisfacción en un hospital terciario / Implantation of a computerised clinical history: survey on the degree of utilisation and satisfaction in a tertiary hospital

Fundamento. Evaluar en un hospital terciario, el grado de utilización de una historia clínica informatizada (HCI), las opiniones de los profesionales sobre sus ventajas e inconvenientes y su nivel de satisfacción con la misma. Material y métodos. Encuesta enviada por correo a todos los médicos del Hospital Virgen del Camino en Pamplona. Resultados. De los 445 médicos del centro, contestaron la encuesta 174 (39 por ciento). De éstos, el 79 por ciento consideran que la HCI es mejor que la historia clínica tradicional, el 61 por ciento la utilizan para consultar e introducir datos de manera habitual y el 55 por ciento están muy de acuerdo con que la HCI ofrece ventajas para el paciente. Los principales problemas detectados son la posible pérdida de confidencialidad, y la falta de tiempo, de dotación informática y de mayor formación, para el manejo del programa. El 90 por ciento de los encuestados opina que se debe continuar con su implantación y sólo el 6 por ciento dice estar poco satisfecho con la aplicación. Conclusión. Existe una extendida utilización de la HCI entre los médicos del Hospital Virgen del Camino y su opinión sobre el programa puede considerarse globalmente favorable. Se deben desarrollar medidas para subsanar los problemas detectados mediante este estudio (AU)

¿Historia clínica electrónica? Una realidad

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