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Software

VSCode extension for NMTRAN (NONMEM)

A Visual Studio Code extension written in TypeScript, adding support for the NMTRAN language used in NONMEM control streams.

Programmatic Language Features

  • Diagnostics
  • Code completion proposals
  • Hover info

Declarative Language Features

  • Comment toggling using the VS Code command Toggle Line Comment
  • Folding (by control records)
  • Bracket matching
  • Bracket autoclosing
  • Bracket autosurrounding
Syntax Highlighting

By tokenization according to TextMate 1.5.1 naming conventions

Snippet Completion

Selection of available snippets
  • Subroutine selection
    • ADVAN and TRANS
  • Modify $DATA on-the-fly (Credit: Simon Buatois)
  • RUV (normal or log-scale)
    • RUV_add
    • RUV_prop
    • RUV_addprop
  • Creating an Xpose-friendly $TABLE scaffold (just type $TABLE).
  • MIXTURE-models (just type $MIX)
    • 2-way mixture model
    • 3-way mixture model
  • Including IIV on a parameter that is bound between 0 and 1 (type logit_iiv).
  • Baseline modeling (B1, B2, B3, B4) Dansirikul et al., 2008
  • BQL modeling (M3) Beal, 2001

Science

Population pharmacokinetics of colistin and the relation to survival in critically ill patients infected with colistin susceptible and carbapenem-resistant bacteria

Kristoffersson AN*, Rognås V*, Brill MJE*, et al. (*shared first authorship)

Clin Microbiol Infect (2020)

https://doi.org/10.1016/j.cmi.2020.03.016

Objectives

The aim was to analyse the population pharmacokinetics of colistin and to explore the relationship between colistin exposure and time to death.

Methods

Patients included in the AIDA randomized controlled trial were treated with colistin for severe infections caused by carbapenem-resistant Gram-negative bacteria. All subjects received a 9 million units (MU) loading dose, followed by a 4.5 MU twice daily maintenance dose, with dose reduction if creatinine clearance (CrCL) <50 mL/min. Individual colistin exposures were estimated from the developed population pharmacokinetic model and an optimized two-sample per patient sampling design. Time to death was evaluated in a parametric survival analysis.

Results

Out of 406 randomized patients, 349 contributed pharmacokinetic data. The median (90% range) colistin plasma concentration was 0.44 (0.14–1.59) mg/L at 15 minutes after the end of first infusion. In samples drawn 10 h after a maintenance dose, concentrations were >2 mg/L in 94% (195/208) and 44% (38/87) of patients with CrCL ≤120 mL/min, and > 120 ml/min, respectively. Colistin methanesulfonate sodium (CMS) and colistin clearances were strongly dependent on CrCL. High colistin exposure to MIC ratio was associated with increased hazard of death in the multivariate analysis (adjusted hazard ratio (95% CI): 1.07 (1.03–1.12)). Other significant predictors included SOFA score at baseline (HR 1.24 (1.19–1.30) per score increase), age and Acinetobacter or Pseudomonas as index pathogen.

Discussion

The population pharmacokinetic model predicted that >90% of the patients had colistin concentrations >2 mg/L at steady state, but only 66% at 4 h after start of treatment. High colistin exposure was associated with poor kidney function, and was not related to a prolonged survival.

Turn-over model characterizing effect of colistin on serum-creatinine in critically ill patients

Rognås V et al.

https://www.page-meeting.org/default.asp?abstract=9869

Bounded integer approach to model time-varying SOFA scores from patients with carbapenem resistant infections

Rognås V et al.

https://www.page-meeting.org/default.asp?abstract=9052

An integrated semi-mechanistic model to predict the outcome of drug-target effects on the erythropoietic system

Rognås V et al.

https://www.page-meeting.org/?abstract=10044