What is Clostridioides difficile (C. diff) infection?

  • Infectious gut bacteria causing diarrhoea: affecting >15,000 people
  • Often occurs in people who have recently taken antibiotics
  • Painful symptoms, prolonged hospital stays, and isolation
  • Can be fatal and recurrence is common

Investigating risk factors for C diff infection

  • UKHSA surveillance data suggests incidence and mortality has been increasing since around 2020
  • PPI panel member: “Answers are needed: we know that prevalence has gone up but it’s not clear why.”
  • Anonymised electronic health records data can provide valuable information: Infections in Oxfordshire Research Database (IORD)
  • Toxin-positive cases since 2012: 1750 cases, 210 recurrences, 832 deaths

Methods: SplineHazardRegression

  • “SplineHazardRegression” R package (Espuny Pujol & Rosenberg)
  • Hazard functions show patterns of “events” in the data and can provide valuable information
  • Flexible modelling with B-splines: non-linearity

Data structure

Example survival data for 100 randomly selected patients

Kaplan-Meier survival curve

Survival curve by surveillance classification

Context: those with a negative test

Survival curve by surveillance classification, dotted line for those with a negative test

CDI onset

Example survival data for 100 randomly selected patients

Hazard regression with B-splines

SplineHazardRegression, degree=3, bootstrap=100

What about recurrence?

SplineHazardRegression, degree=3, bootstrap=100

Importance of competing risks!

SplineHazardRegression, degree=3, bootstrap=100

Competing risks continued

Competing risks

Take-aways

  • CDI hazards vary with surveillance classifications
  • Recurrence more common in community-onset cases?
  • Splines may help us better reflect non-linearity in data
  • Knots could be a guide in analysis?
  • Challenges when outcomes are rare
  • Competing risk methods are crucial: but interesting to look at outcomes separately
  • Potential packages: “rms”, “cmprsk”, “mgcv”, “flexsurv” - any other ideas?