A causal proportional hazards estimator under homogeneous or heterogeneous selection in an IV setting.

In this paper we present a framework to do estimation in a structural Cox model when there may be unobserved confounding. The model is phrased in terms of a selection bias function and a baseline model that describes how covariates affect the survival time in a scenario without exposure. In this way model congeniality is ensured. The method uses an instrumental variable. Interestingly, the formulated model turns out to have similarities to the so-called Cox-Aalen survival model for the observed data. We exploit this to enhance estimation of the unknown parameters. This also allows us to derive large sample properties of the proposed estimator.

Asparaginase-associated pancreatitis is not predicted by hypertriglyceridemia or pancreatic enzyme levels in children with acute lymphoblastic leukemia.

BACKGROUND: l-Asparaginase is an important drug for treatment of childhood acute lymphoblastic leukemia (ALL), but is associated with serious toxicities, including pancreatitis and hypertriglyceridemia (HTG). Asparaginase-associated pancreatitis (AAP) is a common reason for stopping asparaginase treatment. The aim of this study was to explore if HTG or early elevations in pancreatic enzymes were associated with the subsequent development of AAP. METHOD: Children (1.0-17.9 years) diagnosed with ALL, treated with asparaginase for 30 weeks, according to the NOPHO ALL2008 protocol at the University Hospital Rigshospitalet, Copenhagen, Denmark, were eligible. Pancreatic enzymes, triglycerides, and cholesterol were measured regularly. RESULTS: Thirty-one patients were included. Seven patients were diagnosed with AAP. HTG was most evident when PEG-asparaginase and dexamethasone were administered concomitantly. Overall, there was no significant difference in triglyceride levels in patients who experienced AAP and patients who did not. An increase in triglyceride levels during concomitant dexamethasone therapy in delayed intensification was significantly associated with an increase in pancreas-specific amylase levels two weeks later (P = 0.005). CONCLUSIONS: AAP does not seem to be associated with HTG. Continuous monitoring of pancreas enzymes does not predict AAP.