Suspected adverse reaction to compounded preparations prescribed for weight loss: two cases of cerebral venous thrombosis

We report two cases of cerebral venous thrombosis associated with the use of compounded preparations containing several active substances prescribed for weight loss. In both cases there is suspicion of additive/synergic interaction with oral contraceptives. The adverse drug reactions were considered serious, being life-threatening and causing hospitalisation for days.

Assembly of the Heparin Removal Device for patients with suspected adverse reaction to protamine sulphate

Protamine sulphate is routinely used after cardiopulmonary bypass (CPB) to restore the patient’s baseline coagulatory state. However, adverse reactions are encountered, and alternative means to neutralize heparin are, therefore, necessary. The Heparin Removal Device (HRD) constitutes an extracorporeal circuit that allows ex vivo deheparinization by mean of a polycationic ligand that binds heparin molecules. This paper presents the setup of the HRD circuit. It is illustrated by the report of a 68-year-old man with a known severe crustacean allergy. The patient (78 kg, 170 cm) was admitted for elective coronary artery bypass graft surgery. It was decided that the HRD would be used as a precaution in order to avoid the risks of using protamine sulphate. The CPB time and aortic crossclamp time were 70 and 40 min, respectively. At the end of CPB, the device was inserted and processing started. Activated coagulation time values were monitored over a 130 min period and diminished from 480 to 300 s after 45 min, 220 s after 90 min, and settled at 150 s. Haemostasis was acceptable and processing stopped. The operation was terminated and the patient transferred to the intensive care unit. Clinical evolution was excellent, with minimal postoperative bleeding. The HRD presents an alternative to protamine sulphate when this drug is contraindicated for a certain patient population who might have a suspected, known or emergency adverse reaction.

Probabilistic expert systems and graphical modelling: a case study in drug safety

Probabilistic expert systems are intended to provide reasoned guidance in complex environments characterized by extensive uncertainty . An explicit 'causal' model is constructed for the process being observed, in which an acyclic directed graph is used to express conditional independence assumptions about variables, and probability assessments specify a full joint probability distribution. The resulting graphical structure can cope with a range of issues that arise in realistic modelling. Here we consider a particular example of assessing the chance that a suspected adverse reaction is due to a particular drug under suspicion. The background biological knowledge provides an appropriate model and probability assessments are obtained from expert microbiologists. The model allows a variety of interpretations for ‘causality’. Details of the graphical and computational algorithms used to perform efficient calculations of conditional probabilities on complex graphical structures are provided and illustrated with the example. Further developments should allow updating of the risk parameters in the light of a series of case reports, and may form the basis for a flexible expert system for causality assessment and post-marketing surveillance.