Sinem Ezgi Gulmez

Liver transplant associated with paracetamol overdose: Results from the seven-country SALT study

AIMS Acute drug overdose, especially with paracetamol, may cause acute liver failure leading to registration for transplantation (ALFT). Population statistics and between-country differences for ALFT related to overdose have been poorly described. The aim of the present study was to evaluate overdose ALFT in the multi-country Study of Acute Liver Transplantation (SALT). METHODS All adult overdose-related ALFT, with or without suicidal intent, in France, Greece, Ireland, Italy, the Netherlands, Portugal and the UK between 2005 and 2007 were identified from liver transplant registries and hospital records. These were compared with whole-country and per capita use of paracetamol. RESULTS Six hundred cases of ALFT were identified in 52 of 57 eligible transplant centres, of which 114 involved overdose (72 intentional, 10 non-intentional, 32 uncertain). Overdose represented 20% of all-cause ALFT: Ireland 52%, UK 28%, France 18%, the Netherlands 8%, and Italy 1%. Overdose ALFT were mostly females (61%), mean age 33.6 ± 10.9 years. A total of 111 (97%) of the overdoses involved paracetamol. Event rates ranged from one ALFT for 20.7 tons of paracetamol in Ireland, to one for 1074 tons in Italy and one case in 60 million inhabitants over 3 years in Italy to one case in 286 000 inhabitants per year in Ireland. Per-country event rates for non-overdose ALFT exposed to paracetamol were between 2.5 and 4.0 per million treatment-years sold. CONCLUSIONS Paracetamol overdose was found to represent one-sixth of all-cause ALFT. There was a 50-fold difference in Europe in the rates of paracetamol overdose ALFT, and a 200-fold difference per million inhabitants.

Choice of the denominator in case population studies: event rates for registration for liver transplantation after exposure to NSAIDs in the SALT study in France

The effect of denominator options on event rates was tested on the French part of the Study of Acute Liver Transplant (SALT).

Administrative complexities for a European observational study despite directives harmonising requirements

For pharmacoepidemiological studies in Europe, accessing data should require only authorisation by the relevant data protections committees, as expected from the 1995 Data Protection Directive (95/46/EC). Our experience from a multinational observational study across seven European countries shows that this is certainly not the case.

Relative risks from case-population data.

© 2013 Lippincott Williams & Wilkins www.epidem.com | 935 The case-population ratio is perpendicular to the RR: rather than the ratio of case rates among exposed and unexposed, it is the ratio of exposure rates among cases and population. In the usual two-by-two table (Table), where a is the number of exposed cases, b the number of exposed noncases, c the number of unexposed cases, and d the number of unexposed noncases, RR is (a/a+b)/ (c/c+d), OR is a/c/b/d (or ad/bc), and case-population ratio is (a/a+c)/((a+b)/ (a+b+c+d)). The analysis population may come from a representative population sample with a known sampling rate or from representative samples with unknown sampling rates (eg, the UK Clinical Practice Research Datalink). In that case, case-population ratio could be expressed as (a/(a+c))/((e/e+f)), where e and f are the exposed and unexposed in the sample, which may or not include the cases. If cases are rare, case-population ratio can be simplified to ad/bc/ ((1−Pexp)/(1−Cexp)), where Pexp is the population exposure to the drug of interest (b/b+d), and Cexp is the case exposure to the drug of interest (a/a+c). The smaller the population and case exposures, the better case-population ratio (CPR) approximates the OR. The OR estimates the RR when the event is rare, so the lower the exposure in cases and in the general population, and the rarer the event, the better the CPR approximates the real RR of the association of exposure and event. We built a table of CPR for various RR and population exposures (eTable, http://links.lww.com/EDE/A718). When population exposure is below 1%, the difference between case-population ratio and actual OR or RR is less than 1%. Above 1%, CPR underestimates RR above 1 and overestimates RR below 1. We tested this in a case-population study of liver transplantation in Europe for which drug utilization was the exposure of interest.3–5 In this study with exhaustive case identification, and full description of the country’s drug utilization over the same period and in the same population of patients, we computed the actual Relative Risks from Case-Population Data Kathrin Wolf Regina Hampel Susanne Breitner Alexandra Schneider Stephanie von Klot Josef Cyrys Helmholtz Zentrum München German Research Center for Environmental Health Institute of Epidemiology II Neuherberg, Germany

Risk of hospital admission for liver injury in users of NSAIDs and nonoverdose paracetamol: Preliminary results from the EPIHAM study

The SALT study found similar per‐user risks of acute liver failure (ALF) leading to transplantation (ALFT) between NSAIDs and a threefold higher risk in nonoverdose paracetamol (NOP) users. The objective of EPIHAM was to identify the risks of hospital admission for acute liver injury (ALI) associated with NSAIDs and NOP.