Data included coded personal identifiers, age, sex, arrival and departure dates, and nationality of the traveller (Australian citizen or non-Australian citizen). Non-Australian citizens included temporary residents, visitors, and a few people with permanent resident status. We used hospital discharge summaries for the period 1981-99 to detect all patients in Western Australia who had been admitted with a principal diagnosis of deep vein thrombosis or pulmonary embolism. These data were used to estimate age and sex specific incidences for venous thromboembolism and expected numbers of venous thromboembolic events, using state-wide incidence.
The travel records for all passenger movements to and from Australia during 1981-99 were probabilistically matched to the Western Australian hospital data for the same period.12
We thus identified patients with venous thromboembolism who had undertaken international flights, and we recorded the date of patients' first admission for venous thromboembolism and flight dates.
Travellers who had acute venous thromboembolism after leaving Australia would not be admitted to hospital in Western Australia, and so that episode would not be captured in our data. We therefore used information on passengers arriving only. The diagnosis of venous thromboembolism was unlikely to be biased by a recent flight being mentioned during consultation, as there was little awareness of flight related venous thromboembolism before 1999.
Information on travel and venous thromboembolism is incomplete while travellers are outside Western Australia. It was assumed that most non-travel time for Australian citizens resident in Western Australia would be spent in Western Australia. In contrast, many flights and hospital admissions for travellers not usually resident in Western Australia would not be visible in the data, as many international visitors leave Western Australia within days or weeks of arrival. Thus the denominator for observed number of non-Australian citizens with venous thromboembolism immediately after arrival is larger than for later after arrival. This results in proportionally more patients with venous thromboembolism being detected soon after arrival. To minimise this potential bias, our main analysis is based on Australian citizens, with summary statistics for non-Australian citizens.
Finally, venous thromboembolism in Western Australian citizens would not be captured in our data if it led to admission to hospital immediately after arrival from an overseas flight at an east coast airport and before proceeding to Perth. Such an effect would seem to be small (see ).
Frequency of venous thromboembolism in Australian citizens (n=153) by days after flight arrival for first 100 days. Day 0 was counted as 0.5 days
A few patients with venous thromboembolism could have been missed owing to failure to make a link or missing data. The matching process was, however, set to maximise specificity, and such errors would underestimate any association. Data quality may have improved between 1981 and 1999, and by the late 1990s deep vein thrombosis was more likely to be treated on an outpatient basis with anticoagulants, in accordance with new treatment protocols.13
No time related bias was found in sensitivity analyses by using different time periods.
Our principal analysis looked for evidence of any temporary increase in risk of venous thromboembolism above baseline after arrival from a flight. The method uses the conditional probability distribution of the time from the start of the observation period until the first venous thromboembolic event, given that this event occurred within the observation period. This approach is similar to a case crossover analysis.14,15
Because the incidence is low, the risk was estimated as an incidence rate ratio, which gives an approximate relative risk. The incident rate ratio during the hazard period, relative to periods beyond the immediate post flight period was modelled as a function of age, sex, and time since flight. The appendix describes the analysis in detail. This formulation gives the same estimate as the method of Marshall and Jackson, when their approach uses an individual's entire flight history to estimate the probability of a flight at any point in time.15
Hazard period and sensitivity analyses
The estimated incident rate ratio is influenced by the duration of the post flight period selected for analysis. A 30 day period of increased risk has been assumed previously, and a recent study reported a median interval of two days (range 1-14) between a trigger event and subsequent thrombosis.16
We examined the risk over intervals up to 30 days, using a model that allowed different incident rate ratios in three successive periods after travel, and we concluded that most of the excess risk was captured in the two weeks after a flight.
We analysed data subsets for 1981-89, 1981-99, 1990-5, and 1990-9. As these estimates were consistent, we present those for 1981-99, which exploits all available data.