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Travel behaviour of patients with haemophilia
Travel Medicine and Infectious Disease (2013) 11, 159e165
Available online at www.sciencedirect.com
journal homepage: www.elsevierhealth.com/journals/tmid
Travel behaviour of patients with haemophilia Juergen Ringwald a,*, Pamela Rudolph a, Melanie Biner a, Cornelia Fießler b, Andreas Mayr b, Martin Lohmann c, Julian Strobel a, Reinhold Eckstein a, Karin Kurnik d a
Department of Transfusion Medicine and Haemostaseology, University Hospital of Erlangen, Erlangen, Germany b Department of Medical Informatics, Biometry and Epidemiology, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany c Leuphana University, Department of Business Psychology, Lu¨neburg, and North European Institute for Tourism Research, Kiel, Germany d Pediatric Haemophilia Center, Dr. von Hauner’s Children’s Hospital, University of Munich, Munich, Germany Received 10 October 2012; received in revised form 6 March 2013; accepted 13 March 2013 Available online 19 April 2013
KEYWORDS Long-haul travel; Frequent travel; Self-application; Travel habits; Bleedings
Summary Background: We aimed to identify socio-demographic, or illness-specific variables, influencing travel behaviour of haemophilic patients. Methods: A standardised questionnaire was sent to more than 2000 members of two German Haemophilia associations. Multivariable logistic regression with the outcomes frequent (at least two journeys per year) and long-haul travel (outside of Europe) was applied separately on adult patients and patients younger than 18 years. Results: Among 345 adults, high education level, living in a partnership or travelling alone was significantly associated with frequent travel with odds ratios (ORs)/95%-confidence intervals (95%-CI) of 3.10/1.72-5.80, 1.99/1.10-3.62 and 1.73/1.01-3.62, respectively. High education level and self-application of clotting factors were significant variables for long-haul travel (OR/95%-CI: 2.45/1.43-4.26 and 3.25/1.33-8.52, respectively). Among 144 non-adults, a younger age or performing permanent prophylactic treatment was significantly associated with a lower likelihood for long-haul travel (OR/95%-CI: 0.51/0.22-0.95 and 0.10/0.01-0.65, respectively). Longer awareness of the disease increased the likelihood for long-haul travel (OR/95%CI: 1.06/1.01-1.14). Conclusions: High education level and self-application of clotting factors influence travel intensity of adult patients most strikingly. Parents of very young patients on permanent
* Corresponding author. Transfusionsmedizinische und Ha ¨mostaseologische Abteilung, Universita ¨tsklinikum Erlangen, Krankenhausstr. 12, D-91054 Erlangen, Germany. Tel.: þ49 9131 85 36972; fax: þ49 9131 85 36973. E-mail address: [email protected] (J. Ringwald). 1477-8939/$ - see front matter ª 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tmaid.2013.03.008
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J. Ringwald et al. prophylactic treatment might need special education to facilitate holiday travel for these families. ª 2013 Elsevier Ltd. All rights reserved.
Introduction Up to the 1940s, life of patients with haemophilia was, at best, miserable.1 Mean life expectancy of patients with severe or moderate/mild haemophilia was 16.5 and 27 years, respectively. Due to the lack of therapeutic options, these patients became disabled before the age of 20. Travelling was unimaginable for haemophilic patients during this period of time. With the availability of cryoprecipitate and factor concentrates during the 1960s, the treatment of patients with haemophilia changed dramatically. Patients became able to perform their treatment at home and to start substitution therapy early in life to prevent joint bleeding and physical disability.2 During this first golden era in the 1970s, the start of comprehensive care for haemophilic patients further improved the quality of life and increased life expectancy above 60 years.3,4 The major drawback in the treatment of haemophilic patients appeared during the early 1980s when more than 50% of haemophilic patients in the developed world had become infected with human immunodeficiency virus (HIV). With the availability of safe plasma products and improved treatment options for haemophilic patients who developed antibodies (so called “inhibitors”) against the missing clotting factor during substitution therapy, a new golden era of haemophilia treatment started in the 1990s. Nowadays, children and adolescence with severe haemophilia are usually on permanent prophylactic treatment receiving twice or three times per week a body weight adjusted dosage of the missing clotting factor. In adulthood, ondemand treatment with the application of factor concentrates when bleeding occurs can be sufficient. This new treatment options preventing physical disability and increasing the mobility of haemophilic patients enabled these patients to become full members of our mobile society with an increased desire to travel the world similar to healthy individuals. Up-to-date, there has been no data available which socio-demographic or illness-specific variables might influence travel behaviour of haemophilic patients. Such information would be very useful in facilitating travel for haemophilic patients. We therefore collected this information among German patients with haemophilia A or B.
(continued ) Terminology
Definition
Haemophilia B
X-chromosomal-recessive inherited deficiency of clotting factor IX Allo-Antibodies against the missing clotting factor (induced by substitution) Residual clotting factor activity < 1%
Inhibitors
Severe Haemophilia Moderate Residual clotting factor activity 1e5% haemophilia Mild haemophiliaResidual clotting factor activity 6e40% Cryoprecipitate Frozen blood product prepared from plasma containing fibrinogen, factor VIII, von-Willebrand-factor and factor XIII Permanent Application of clotting factors prophylactic concentrates two to three times treatment per week to prevent bleeding on a regular base On demand Application of clotting factors in treatment case of bleeding episodes
Methods
Terminology
Definition
The study was performed in cooperation with the German Haemophilia Society (GHS) and the community of interest of patients with haemophilia (CIH). A standardized questionnaire with 36 questions was sent to all members of the organizations: 1560 and 450 members of the GHS and the CIH, respectively. The questionnaire was answered by the affected patient or his parents. Collected data included socio-demographic data (age, education, current profession, and marital status), type and severity of haemophilia, presence of an inhibitor, type of therapy (permanent prophylactic or on-demand treatment), person applying the factor concentrates, and frequency and type of haemorrhages in the domestic environment. Furthermore, we asked for frequency of holiday trips, duration and destinations of journeys, at which age the patient had started to travel, and whether the patient travels alone or only with an accompanying person. The study was approved by the Institutional Ethics Committee of the University Erlangen-Nuremberg. The patients were informed about the aims of the study in an accompanying letter and had to give their written informed consent.
Haemophilia A
X-chromosomal-recessive inherited deficiency of clotting factor VIII
Statistical analysis
Box. Definition of terminology in haemophilia used in this article
(continued on next page)
Results are given as mean standard deviation if not stated otherwise. Data analysis followed a two-step approach.
Travel and haemophilia First, the complete sample of study participants was analyzed using descriptive statistics. In a second step, the data set was divided in two subgroups: Adults who participated in the study on their own (group 1), and participants younger than 18 years for whom at least one parent had answered the questionnaire (group 2). Data were analyzed separately for possible predictors for travel behaviour in these two groups. We defined two travel related outcomes: (1) Frequent travellers are participants who indicated that they regularly travel more than once a year. (2) Long-haul travellers are participants who indicated that they have travelled to destinations outside Europe at least once in their lifetime. To assess the combined effect of different personal and illness-related characteristics on travel behaviour, we applied multivariable logistic regression analysis with the above described outcomes as the dependent variable. Statistical significance was assessed by Likelihood Ratio Tests. Odds ratios (ORs) and corresponding 95%-confidence intervals (95%-CIs) were based on the effect estimates of the resulting models and were hence adjusted for all other variables, including age of the patient, severity of illness, self-application and permanent prophylactic treatment (tables one and two). The multivariable analysis was performed to identify independent predictors for frequent or long-haul travel without running the risk that these effects are biased due to confounding. Statistical analyses were conducted using the statistical computing environment R 2.14.2.5
Results We received 552 questionnaires resulting in a response rate of 27.5%. Written informed consent of 28 patients was missing. Two questionnaires were sent back unanswered. Overall, 522 questionnaires remained for analysis. Among those, the questionnaire was answered by the patient himself, or by at least one parent, in 70.7% and 29.3%, respectively. Patient age was 33.8 21.1 years (range 1e86) with approximately one third (32.4%) younger than 18 years.
Type and treatment of haemophilia of all patients 443 patients (84.9%) suffered from haemophilia A and 79 patients (15.1%) had haemophilia B. Severe haemophilia with factor VIII activity (F.VIII:C) below < 1% was present in 69.7% of all patients whereas 16.9% had moderate (F.VIII:C 1e5%) and 12.8% had mild (F.VIII:C 6e40%) haemophilia. Three patients did not indicate the severity of their haemophilia. 65 patients (12.5%) reported having had an inhibitor at least once in the past. Among 13 patients (2.5%), the inhibitor was still present. Four of these patients had been on immune tolerance therapy. The patients reported being treated with permanent prophylactic or on-demand treatment in 63.2% and 36.0%, respectively. 360 patients (69.0%) indicated to apply the factor concentrate by themselves. Parents, or other individuals (e.g. medical profession, wife, sister, girl-friend,
161 grandmother), were involved in 27.2% and 23.4%, respectively. The application of factor concentrate exclusively by medical professions was reported by 92 patients (17.6%).
Bleeding episodes in the domestic environment and during travel The number of bleeding episodes per year in the domestic environment was 10.3 16.7 (range 0e204). 24 patients (4.6%) reported no bleeding, 64 patients (12.3%) did not indicate the number of bleedings per year. Among patients indicating the type of bleeding (n Z 471), joint bleeding was predominant with 75.5% followed by muscle bleeding and skin haematoma with 45.2% and 44.4%, respectively. Visceral bleeding was indicated by 4.5% and other types of bleeding such as mucosal bleeding, or haematuria, was identified by 10.8%. Most bleedings were provoked by injury (71.5%). Spontaneous bleeding was reported by 57.3%. Other reasons such as surgery, stress, sport, and infection were indicated by 13.0%. Bleeding episodes during travel were reported by 227 patients (43.5%). Similar to bleeding in the domestic environment, joint bleeding was predominant with 66.1% followed by muscle bleeding, skin haematoma or visceral bleeding with 36.1%, 26.4% or 4.0%, respectively. Other bleedings such as mucosal bleeding or haematuria were reported by 18.5%.
Frequent and long-haul travellers Among all haemophilic patients, 511 (97.9%) had travelled at least once after having been diagnosed as haemophilic, 315 (60.3%) were frequent and 192 (36.8%) long-haul travellers whereas 138 (26.4%) were both.
Subgroup analysis of patients The two subgroups consisted of 345 adults who answered the questionnaire by themselves (group 1) and 144 patients aged 0e17 years for whom at least one parent had answered the questionnaire (group 2). 24 patients aged 17 years and younger who answered the questionnaire by themselves and nine adults for whom the questionnaire was answered by the parents were excluded from further analysis. Among adult haemophilic patients aged 45.3 16.1 years (Fig. 1), 340 (98.6%) went on a journey at least once after having been diagnosed as haemophilic, 216 (62.6%) were frequent and 159 (46.1%) long-haul travellers. Adult patients with a university degree travelled significantly more often than those with a lower education level (OR 3.10; 95%-CI 1.72e5.80). Those living in a partnership travelled significantly more often than those without a partner (OR 1.99, 95%-CI 1.10e3.62). Adults who used to travel alone showed a higher travel frequency compared to those travelling accompanied by others (OR 1.73, 95%-CI 1.01e3.02). Adult patients with a university degree travelled significantly more often to destinations far away than those with lower education levels (OR 2.45, 95%-CI 1.43e4.26). This was also found for adult patients performing self-
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number of participants
20
group 2
group 1
15
10
5
0 0
20
40
60
80
age [years]
Figure 1 Empirical distribution of the age of participants in the two different subgroups. Each column refers to the absolute number for patients with the corresponding age (group 1: 18 years and older; group 2: younger than 18 years).
application compared to those not applying the factor concentrates by themselves (OR 3.25, 95%-CI 1.33e8.52). All other tested variables did not have any relation to the travel behaviour of adult patients (Table 1). Only six adult patients reported the presence of an inhibitor, among those two were frequent and long-haul travellers. Due to the low number of patients with inhibitors, this variable was not included in the multivariable logistic regression analysis. One hundred thirty-nine (96.5%) parents of haemophilic patients aged 9.6 4.2 years (group 2, Fig. 1) reported that they travelled at least once with their children after becoming aware of the haemophilia of their child. We found 81 (56.3%) frequent and 24 (16.7%) long-haul travellers in this subgroup. Except for age and the duration of the awareness of the disease, no significant effect of any of the tested parameters with regard to travel behaviour was found among patients in group 2 (Table 2). Younger patients in this subgroup experience less long-haul travel (OR 0.51, 95%-CI 0.22e0.95). Long-term experience with the disease was associated with a significantly increased likelihood to visit countries outside of Europe (OR 1.06, 95%-CI 1.01e1.14). Three patients aged 17 and below reported the presence of an inhibitor with one travelling more than once per year.
Discussion To our knowledge, we performed the first survey studying travel behaviour of patients with haemophilia A or B. Most importantly, the vast majority of responding patients (approximately 98%) have travelled at least once since being diagnosed as haemophilic. Moreover, approximately 60% travel at more than once per year (“frequent travellers”) and 37% have been travelling outside Europe (“longhaul travellers”).
Our data shows that illness-specific and sociodemographic variables influence travel behaviour of haemophilic patients. Adult haemophilic patients with a high level of education were more likely to perform frequent and long-haul travel. Furthermore, living in partnership but also travelling alone was significantly associated with higher travel intensity. Among haemophilia-specific variables, self-application of clotting factors was the most important variable for a higher likelihood to go on long-haul travel. However, self-application was no significant variable for frequent travel. Other tested variables including the severity of haemophilia when compared between severe (<1% residual activity) and moderate/mild (1% residual activity) did not have any influence on travel behaviour of adult haemophilic patients (Table 1). Among patients aged 17 years and below, not being on permanent prophylactic treatment was associated with a higher likelihood for long-haul travel. Interestingly, the ability to administer the clotting factors by the patient or by a member of the patient’s family, did not have a significant influence on travel behaviour as this was the case for adult patients. However, this was probably due to the rather low number of patients in group 2. In contrast to the findings for adults, higher age and longer experience with the disease were significantly associated with the likelihood for long-haul travel among patients younger than 18 years. The frequency of travel, however, was not influenced by these two parameters. As data about the travel behaviour of patients with haemophilia have not been available up to now, our results can not be compared with data of other studies. Furthermore, as a control group was not part of our study we cannot directly compare our data with those of individuals not suffering from haemophilia or other chronic diseases. Such a control group would require a representative and age-matched sample of the German population. However, this was neither feasible nor within the scope of our study. Nonetheless, data from the representative annual analysis of the holiday travel behaviour of the population in Germany indicate at least, that travel patterns of patients with haemophilia might not differ to a large extent from those of the general population.6 The travel propensity of the population in Germany (individuals aged 14 years and older travelling for more than four days at least once per year), has been between 72% and 78% during the last two decades. Approximately 25% of them undertake two or more journeys annually.7 Our finding that 60% of our patients travel at least twice per year might indicate that patients with haemophilia may travel not less often than the general population at least. A share of 36.8% within our haemophilic patients had been visiting countries outside Europe at least once. So far, we are not aware of such life-time data among the German population. Approximately 17% of the German population, however, travels to destinations outside of Europe in a given year.6 Our observation that a higher education level is independently associated with more intensive travel is not specific for patients with haemophilia. Lohmann et al. reported similar findings for the general population in Germany.7 There may be several reasons for this finding. First, a higher education level is associated with an increased
Travel and haemophilia Table 1 Odds ratios (ORs) with 95% confidence intervals (95%-CIs) for different variables among adult patients with haemophilia A or B (group 1) with regard to frequent or long-haul travel. Tested variables
Frequent travel
Working University graduates Living with a partner Travelling alone Haemophilia B Severe Haemophilia Former joint, muscle, organ bleeding Permanent prophylactic treatment Self-application
Yes n Z 216
No n Z 129
n
%
n
%
128 89 151 134 29 145 182 111 172
59.3 41.2 69.9 62 13.4 67.1 84.3 51.4 79.6
71 22 67 62 16 89 106 67 104
55 17.1 51.9 48.1 12.4 69.0 82.2 51.9 80.6
Mean SD Current age [years] Age at diagnosis [years] Awareness of disease [months] Haemorrhages [per year]
46.3 5 489.2 11.4
Long-haul travel
16.3 9.2 166.5 16.4
Mean SD 43.7 5 469.9 11.2
15.6 9.9 153.2 13.6
Or (95%-CI)
p-Value
0.94 3.10 1.99 1.73 1.80 0.78 1.41 1.47 0.71
0.821 <0.001* 0.024* 0.048* 0.164 0.537 0.431 0.252 0.461
(0.53e1.66) (1.72e5.80) (1.10e3.62) (1.01e3.02) (0.79e4.38) (0.35e1.71) (0.60e3.32) (0.76e2.85) (0.28e1.74)
Yes n Z 159 n
%
n
%
98 67 103 98 22 109 138 83 135
61.6 42.1 64.8 61.6 13.8 68.6 86.8 52.2 84.9
101 44 115 98 23 125 150 95 141
54.3 23.7 61.8 52.7 12.4 67.2 80.6 51.1 75.8
OR (95%-CI)
p-Value
Mean SD
1.11 0.90 0.99 1.01
0.087 0.096 0.110 0.260
44.1 4.2 473.7 10.6
(0.99e1.37) (0.73e1.01) (0.98e1.00) (0.99e1.03)
No n Z 186
15.4 8.0 161.3 13.0
Mean SD 46.3 5.7 489.1 11.9
16.6 10.5 162.1 17.3
Or (95%-CI)
p-Value
1.04 2.45 1.27 0.97 1.48 0.66 1.90 0.84 3.25
0.421 0.001* 0.419 0.906 0.322 0.280 0.132 0.571 0.009*
(0.59e1.81) (1.43e4.26) (0.71e2.27) (0.57e1.64) (0.69e3.25) (0.31e1.39) (0.83e4.52) (0.45e1.55) (1.33e8.52)
OR (95%-CI)
p-Value
1.05 0.95 1.00 0.99
0.268 0.201 0.109 0.409
(0.97e1.22) (0.81e1.02) (0.98e1.01) (0.97e1.01)
*Significant; SD Z standard deviation. ORs and corresponding 95%-CIs are based on multivariable logistic regression models and adjusted to all other variables of this table. For categorical variables, the omitted categories are the reference groups (e.g. Haemophilia A).
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Table 2 Odds ratios (ORs) with 95% confidence intervals (95%-CIs) for different variables among patients with haemophilia A or B aged 17 years and below (group 2) with regard to frequent or long-haul travel. Tested variables
Haemophilia B Severe Haemophilia Former joint, muscle, organ bleeding Permanent prophylactic treatment Self-application
Frequent travel
Long-haul travel
Yes n Z 81
No n Z 63
n
%
n
%
12 58 52
14.8 71.6 64.2
11 48 43
17.5 76.2 68.3
0.64 (0.22e1.82) 0.56 (0.19e1.55) 0.64 (0.26e1.50)
71
87.7
55
87.3
1.03 (0.25e4.28)
34
42.0
24
38.1
Mean SD
Mean SD
OR (95%-CI)
1.92 (0.66e5.75) OR (95%-CI)
p-Value
Yes n Z 24
No n Z 120
n
%
n
0.395 0.271 0.305
4 18 16
16.7 75.0 66.7
19 88 79
0.963
19
79.2
0.231
12
50.0
p-Value Mean SD
Current age 9.5 4.1 9.7 4.4 0.88 (0.62e1.26) 0.484 [years] Awareness of 109.6 47.7 105.6 51.7 1.01 (0.98e1.04) 0.590 disease [months] Haemorrhages 6.0 8.0 11.0 28.5 0.98 (0.93e1.00) 0.092 [per year]
10.2 3.7
OR (95%-CI)
p-Value
15.8 73.3 65.8
0.76 (0.15e2.93) 2.36 (0.51e18.72) 0.95 (0.31e3.07)
0.708 0.296 0.934
107
89.2
0.10 (0.01e0.65)
0.016*
43
38.3
2.07 (0.46e10.40)
0.349
%
Mean SD 9.5 4.3
OR (95%-CI)
p-Value
0.51 (0.22e0.95) 0.031*
117.3 43.2 106.0 50.5 1.06 (1.01e1.14) 0.032*
7.1 7.7
8.2 20.6 1.00 (094e1.03)
0.929
*Significant; SD Z standard deviation. ORs and corresponding 95%-CIs are based on multivariable logistic regression models and adjusted to all other variables of this table. For categorical variables, the omitted categories are the reference groups (e.g. Haemophilia A).
ability to speak foreign languages facilitating international travel. Furthermore, individuals with a higher education level might be more interested in the history and culture of other countries. Likewise, long-distance travel is expensive therefore the typically higher income of individuals with higher education levels might further facilitate travelling. The positive effect of higher income on travel activity was shown by Lohmann et al.7 However, the education level seems to be an independent predictor for travel activity as poor college students travelled more often than rich graduates of secondary school.7 The increased travel activity of individuals living together with a partner is also not specific for patients with haemophilia. According to recent data on German holiday travel behaviour, the travel propensity of individuals living in a partnership was higher across different age groups.6 Conformity with general travel patterns was found as well with respect to the increased travel activities of patients travelling alone. Within the population in Germany those who made at least one holiday trip without travel companions had a higher frequency of travel and a greater share of long-haul trips in 2011. Beside prevention of bleeding episodes, the introduction of self-application of clotting factors in the late 1960s and early 1970s.2,8e10 enabled patients with haemophilia to travel more independently from their physician or treatment centre with increased safety while travelling. Our finding that self-application was the most significant variable to increase the likelihood to travel outside Europe is reflecting this fact. To our knowledge this is the first time that this effect has been shown. The frequency of travel, however, was
not influenced by the ability to apply the clotting factors by themselves. Patient’s awareness of the availability of good treatment options in haemophilia care centres in most European countries might explain this finding. Parents of patients younger than 18 years were less likely to travel outside of Europe if their children were on permanent prophylactic treatment. However, our results might be biased as the vast majority of the patients in group 2 (87.5%) were on permanent prophylactic treatment. The number of patients aged 17 years and below performing self-application of clotting factors was higher among frequent and long-haul travellers but this did not reach statistical significance which might be due to the rather low number of patients. Younger age as well as brief experience with the disease were associated with a lower likelihood for parents with haemophilic children to go on long-haul travel. Whereas the latter finding may be specific for haemophilia, data on travel behaviour for the general population in Germany show that the travel intensity of families with children aged five years and below is lower than that of families with older children.6 Considering that a longer-term experience by the parents with treating and managing haemophilia’s impact on their child’s in daily life, it is not surprising that the frequency of long-haul travel is dependent on the period of time that the disease is known. A potential limitation of our study is the response rate (27.5%) together with a possible self-selection of respondents. We cannot exclude that the questionnaire may have been answered only by patients, or parents, being
Travel and haemophilia interested in travelling. Therefore, we do not know whether the patients not returning the questionnaire travel or not. The rather high values for travel participation (compared to key data for the German population6,7) may indicate such a self-selection bias in our sample. Furthermore, we do not know whether the cohort of responding patients is representative for all haemophilic patients in Germany with regard to the severity of haemophilia. The two large patient associations with whom this study was performed do not ask their members for the severity of their haemophilia. According to the annual multicentric survey about morbidity and mortality of patients with haemophilia in Germany,11 approximately 58.7% of patients with haemophilia A or B have a residual factor activity 2%. As 69.7% of our patients reported having severe haemophilia with residual factor activity <1%, our results might be biased by this increased rate of patients with severe haemophilia. However, severe haemophilia was at least no significant variable for frequent or long-haul travel in our study. Another limitation was that the answers of the patients, or their parents, could not be validated by a physician to avoid misunderstandings. Further limitations of our study include the low number of patients in group 2 and the lack of a direct representative control group. The separate analysis for adults and patients younger than 18 years allowed us to consider their different life situation. Furthermore, we wanted to get a clear picture of the influence of the socio-demographic background on travel patterns of adult patients.
Conclusions Our data allows for the first time insights into the travel behaviour of haemophilic patients. The respondents report a rather high level of travel activity. Socio-demographic variables associated with more intensive travel are similar to those known to drive travel in the general population. High education level and self-application of clotting factors influence travel intensity of adult patients most strikingly. Parents of very young patients on permanent prophylactic treatment might need special education facilitating travel.
Funding The study was supported by a grant of CSL Behring GmbH, Marburg, Germany.
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Conflict of interest The authors state that they have no conflicts of interest to declare.
Acknowledgements The authors thank the staff and all members of the German Haemophilia Society (especially Dr. Anna Griesheimer and Mr. Werner Kalnins) and the Community of Interest of patients with Haemophilia (especially Mr. Guenter Schelle and Dr. Thomas Becker) for their valuable support in performing this study. Furthermore, we thank FUR (Forschungsgemeinschaft Urlaub und Reisen e.V., Kiel, Germany) for providing representative data of their yearly survey “Reiseanalyse” on the travel behaviour of the population in Germany.
References 1. Evatt BL. The tragic history of AIDS in the hemophilia population, 1982e1984. J Thromb Haemost 2006;4:2295e301. 2. Mannucci PM. Back to the future: a recent history of haemophilia treatment. Haemophilia 2008;14(Suppl. 3):10e8. 3. Mejia-Carvajal C, Czapek EE, Valentino LA. Life expectancy in hemophilia outcome. J Thromb Haemost 2006;4:507e9. 4. Plug I, Van der Bom JG, Peters M, Mauser-Bunschoten EP, De Goede-Bolder A, Heijnen L, et al. Mortality and causes of death in patients with hemophilia, 1992e2001: a prospective cohort study. J Thromb Haemost 2006;4:510e6. 5. R Development Core Team. R: a language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing, ISBN 3-900051-07-0; 2012. http://www. R-project.org/; 2012. 6. FUR Forschungsgemeinschaft Urlaub und Reisen e.V. Reiseanalyse 2012, Kiel, Germany (unpublished data). 7. Lohmann M, Aderhold P. Urlaubsreisetrends 2020-Die RA Trendstudie. Kiel, Germany (Forschungsgemeinschaft Urlaub und Reisen). 8. Seitz R. The history of haemophilia treatment. Pharm Unserer Zeit 2006;35:14e8. 9. Aledort LM. Hemophilia. Yesterday, today, and tomorrow. Mt Sinai J Med 1996;63:225e35. 10. Besmens I, Brackmann HH, Oldenburg J. Comprehensive care center bonn from 1980 to 2009. Changes in the epidemiology and regional composition of the haemophilia population. Ha¨mostaseologie 2011;31(Suppl. 1):S4e10. 11. Schramm W, Rieger A. Morbidity and mortality of patients with haemophilia in Germany e update 2010/2011. Ha¨mostaseologie 2012;32(Suppl. 1):S5e11.
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Travel behaviour of patients with haemophilia Juergen Ringwald a,*, Pamela Rudolph a, Melanie Biner a, Cornelia Fießler b, Andreas Mayr b, Martin Lohmann c, Julian Strobel a, Reinhold Eckstein a, Karin Kurnik d a
Department of Transfusion Medicine and Haemostaseology, University Hospital of Erlangen, Erlangen, Germany b Department of Medical Informatics, Biometry and Epidemiology, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany c Leuphana University, Department of Business Psychology, Lu¨neburg, and North European Institute for Tourism Research, Kiel, Germany d Pediatric Haemophilia Center, Dr. von Hauner’s Children’s Hospital, University of Munich, Munich, Germany Received 10 October 2012; received in revised form 6 March 2013; accepted 13 March 2013 Available online 19 April 2013
KEYWORDS Long-haul travel; Frequent travel; Self-application; Travel habits; Bleedings
Summary Background: We aimed to identify socio-demographic, or illness-specific variables, influencing travel behaviour of haemophilic patients. Methods: A standardised questionnaire was sent to more than 2000 members of two German Haemophilia associations. Multivariable logistic regression with the outcomes frequent (at least two journeys per year) and long-haul travel (outside of Europe) was applied separately on adult patients and patients younger than 18 years. Results: Among 345 adults, high education level, living in a partnership or travelling alone was significantly associated with frequent travel with odds ratios (ORs)/95%-confidence intervals (95%-CI) of 3.10/1.72-5.80, 1.99/1.10-3.62 and 1.73/1.01-3.62, respectively. High education level and self-application of clotting factors were significant variables for long-haul travel (OR/95%-CI: 2.45/1.43-4.26 and 3.25/1.33-8.52, respectively). Among 144 non-adults, a younger age or performing permanent prophylactic treatment was significantly associated with a lower likelihood for long-haul travel (OR/95%-CI: 0.51/0.22-0.95 and 0.10/0.01-0.65, respectively). Longer awareness of the disease increased the likelihood for long-haul travel (OR/95%CI: 1.06/1.01-1.14). Conclusions: High education level and self-application of clotting factors influence travel intensity of adult patients most strikingly. Parents of very young patients on permanent
* Corresponding author. Transfusionsmedizinische und Ha ¨mostaseologische Abteilung, Universita ¨tsklinikum Erlangen, Krankenhausstr. 12, D-91054 Erlangen, Germany. Tel.: þ49 9131 85 36972; fax: þ49 9131 85 36973. E-mail address: [email protected] (J. Ringwald). 1477-8939/$ - see front matter ª 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tmaid.2013.03.008
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J. Ringwald et al. prophylactic treatment might need special education to facilitate holiday travel for these families. ª 2013 Elsevier Ltd. All rights reserved.
Introduction Up to the 1940s, life of patients with haemophilia was, at best, miserable.1 Mean life expectancy of patients with severe or moderate/mild haemophilia was 16.5 and 27 years, respectively. Due to the lack of therapeutic options, these patients became disabled before the age of 20. Travelling was unimaginable for haemophilic patients during this period of time. With the availability of cryoprecipitate and factor concentrates during the 1960s, the treatment of patients with haemophilia changed dramatically. Patients became able to perform their treatment at home and to start substitution therapy early in life to prevent joint bleeding and physical disability.2 During this first golden era in the 1970s, the start of comprehensive care for haemophilic patients further improved the quality of life and increased life expectancy above 60 years.3,4 The major drawback in the treatment of haemophilic patients appeared during the early 1980s when more than 50% of haemophilic patients in the developed world had become infected with human immunodeficiency virus (HIV). With the availability of safe plasma products and improved treatment options for haemophilic patients who developed antibodies (so called “inhibitors”) against the missing clotting factor during substitution therapy, a new golden era of haemophilia treatment started in the 1990s. Nowadays, children and adolescence with severe haemophilia are usually on permanent prophylactic treatment receiving twice or three times per week a body weight adjusted dosage of the missing clotting factor. In adulthood, ondemand treatment with the application of factor concentrates when bleeding occurs can be sufficient. This new treatment options preventing physical disability and increasing the mobility of haemophilic patients enabled these patients to become full members of our mobile society with an increased desire to travel the world similar to healthy individuals. Up-to-date, there has been no data available which socio-demographic or illness-specific variables might influence travel behaviour of haemophilic patients. Such information would be very useful in facilitating travel for haemophilic patients. We therefore collected this information among German patients with haemophilia A or B.
(continued ) Terminology
Definition
Haemophilia B
X-chromosomal-recessive inherited deficiency of clotting factor IX Allo-Antibodies against the missing clotting factor (induced by substitution) Residual clotting factor activity < 1%
Inhibitors
Severe Haemophilia Moderate Residual clotting factor activity 1e5% haemophilia Mild haemophiliaResidual clotting factor activity 6e40% Cryoprecipitate Frozen blood product prepared from plasma containing fibrinogen, factor VIII, von-Willebrand-factor and factor XIII Permanent Application of clotting factors prophylactic concentrates two to three times treatment per week to prevent bleeding on a regular base On demand Application of clotting factors in treatment case of bleeding episodes
Methods
Terminology
Definition
The study was performed in cooperation with the German Haemophilia Society (GHS) and the community of interest of patients with haemophilia (CIH). A standardized questionnaire with 36 questions was sent to all members of the organizations: 1560 and 450 members of the GHS and the CIH, respectively. The questionnaire was answered by the affected patient or his parents. Collected data included socio-demographic data (age, education, current profession, and marital status), type and severity of haemophilia, presence of an inhibitor, type of therapy (permanent prophylactic or on-demand treatment), person applying the factor concentrates, and frequency and type of haemorrhages in the domestic environment. Furthermore, we asked for frequency of holiday trips, duration and destinations of journeys, at which age the patient had started to travel, and whether the patient travels alone or only with an accompanying person. The study was approved by the Institutional Ethics Committee of the University Erlangen-Nuremberg. The patients were informed about the aims of the study in an accompanying letter and had to give their written informed consent.
Haemophilia A
X-chromosomal-recessive inherited deficiency of clotting factor VIII
Statistical analysis
Box. Definition of terminology in haemophilia used in this article
(continued on next page)
Results are given as mean standard deviation if not stated otherwise. Data analysis followed a two-step approach.
Travel and haemophilia First, the complete sample of study participants was analyzed using descriptive statistics. In a second step, the data set was divided in two subgroups: Adults who participated in the study on their own (group 1), and participants younger than 18 years for whom at least one parent had answered the questionnaire (group 2). Data were analyzed separately for possible predictors for travel behaviour in these two groups. We defined two travel related outcomes: (1) Frequent travellers are participants who indicated that they regularly travel more than once a year. (2) Long-haul travellers are participants who indicated that they have travelled to destinations outside Europe at least once in their lifetime. To assess the combined effect of different personal and illness-related characteristics on travel behaviour, we applied multivariable logistic regression analysis with the above described outcomes as the dependent variable. Statistical significance was assessed by Likelihood Ratio Tests. Odds ratios (ORs) and corresponding 95%-confidence intervals (95%-CIs) were based on the effect estimates of the resulting models and were hence adjusted for all other variables, including age of the patient, severity of illness, self-application and permanent prophylactic treatment (tables one and two). The multivariable analysis was performed to identify independent predictors for frequent or long-haul travel without running the risk that these effects are biased due to confounding. Statistical analyses were conducted using the statistical computing environment R 2.14.2.5
Results We received 552 questionnaires resulting in a response rate of 27.5%. Written informed consent of 28 patients was missing. Two questionnaires were sent back unanswered. Overall, 522 questionnaires remained for analysis. Among those, the questionnaire was answered by the patient himself, or by at least one parent, in 70.7% and 29.3%, respectively. Patient age was 33.8 21.1 years (range 1e86) with approximately one third (32.4%) younger than 18 years.
Type and treatment of haemophilia of all patients 443 patients (84.9%) suffered from haemophilia A and 79 patients (15.1%) had haemophilia B. Severe haemophilia with factor VIII activity (F.VIII:C) below < 1% was present in 69.7% of all patients whereas 16.9% had moderate (F.VIII:C 1e5%) and 12.8% had mild (F.VIII:C 6e40%) haemophilia. Three patients did not indicate the severity of their haemophilia. 65 patients (12.5%) reported having had an inhibitor at least once in the past. Among 13 patients (2.5%), the inhibitor was still present. Four of these patients had been on immune tolerance therapy. The patients reported being treated with permanent prophylactic or on-demand treatment in 63.2% and 36.0%, respectively. 360 patients (69.0%) indicated to apply the factor concentrate by themselves. Parents, or other individuals (e.g. medical profession, wife, sister, girl-friend,
161 grandmother), were involved in 27.2% and 23.4%, respectively. The application of factor concentrate exclusively by medical professions was reported by 92 patients (17.6%).
Bleeding episodes in the domestic environment and during travel The number of bleeding episodes per year in the domestic environment was 10.3 16.7 (range 0e204). 24 patients (4.6%) reported no bleeding, 64 patients (12.3%) did not indicate the number of bleedings per year. Among patients indicating the type of bleeding (n Z 471), joint bleeding was predominant with 75.5% followed by muscle bleeding and skin haematoma with 45.2% and 44.4%, respectively. Visceral bleeding was indicated by 4.5% and other types of bleeding such as mucosal bleeding, or haematuria, was identified by 10.8%. Most bleedings were provoked by injury (71.5%). Spontaneous bleeding was reported by 57.3%. Other reasons such as surgery, stress, sport, and infection were indicated by 13.0%. Bleeding episodes during travel were reported by 227 patients (43.5%). Similar to bleeding in the domestic environment, joint bleeding was predominant with 66.1% followed by muscle bleeding, skin haematoma or visceral bleeding with 36.1%, 26.4% or 4.0%, respectively. Other bleedings such as mucosal bleeding or haematuria were reported by 18.5%.
Frequent and long-haul travellers Among all haemophilic patients, 511 (97.9%) had travelled at least once after having been diagnosed as haemophilic, 315 (60.3%) were frequent and 192 (36.8%) long-haul travellers whereas 138 (26.4%) were both.
Subgroup analysis of patients The two subgroups consisted of 345 adults who answered the questionnaire by themselves (group 1) and 144 patients aged 0e17 years for whom at least one parent had answered the questionnaire (group 2). 24 patients aged 17 years and younger who answered the questionnaire by themselves and nine adults for whom the questionnaire was answered by the parents were excluded from further analysis. Among adult haemophilic patients aged 45.3 16.1 years (Fig. 1), 340 (98.6%) went on a journey at least once after having been diagnosed as haemophilic, 216 (62.6%) were frequent and 159 (46.1%) long-haul travellers. Adult patients with a university degree travelled significantly more often than those with a lower education level (OR 3.10; 95%-CI 1.72e5.80). Those living in a partnership travelled significantly more often than those without a partner (OR 1.99, 95%-CI 1.10e3.62). Adults who used to travel alone showed a higher travel frequency compared to those travelling accompanied by others (OR 1.73, 95%-CI 1.01e3.02). Adult patients with a university degree travelled significantly more often to destinations far away than those with lower education levels (OR 2.45, 95%-CI 1.43e4.26). This was also found for adult patients performing self-
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number of participants
20
group 2
group 1
15
10
5
0 0
20
40
60
80
age [years]
Figure 1 Empirical distribution of the age of participants in the two different subgroups. Each column refers to the absolute number for patients with the corresponding age (group 1: 18 years and older; group 2: younger than 18 years).
application compared to those not applying the factor concentrates by themselves (OR 3.25, 95%-CI 1.33e8.52). All other tested variables did not have any relation to the travel behaviour of adult patients (Table 1). Only six adult patients reported the presence of an inhibitor, among those two were frequent and long-haul travellers. Due to the low number of patients with inhibitors, this variable was not included in the multivariable logistic regression analysis. One hundred thirty-nine (96.5%) parents of haemophilic patients aged 9.6 4.2 years (group 2, Fig. 1) reported that they travelled at least once with their children after becoming aware of the haemophilia of their child. We found 81 (56.3%) frequent and 24 (16.7%) long-haul travellers in this subgroup. Except for age and the duration of the awareness of the disease, no significant effect of any of the tested parameters with regard to travel behaviour was found among patients in group 2 (Table 2). Younger patients in this subgroup experience less long-haul travel (OR 0.51, 95%-CI 0.22e0.95). Long-term experience with the disease was associated with a significantly increased likelihood to visit countries outside of Europe (OR 1.06, 95%-CI 1.01e1.14). Three patients aged 17 and below reported the presence of an inhibitor with one travelling more than once per year.
Discussion To our knowledge, we performed the first survey studying travel behaviour of patients with haemophilia A or B. Most importantly, the vast majority of responding patients (approximately 98%) have travelled at least once since being diagnosed as haemophilic. Moreover, approximately 60% travel at more than once per year (“frequent travellers”) and 37% have been travelling outside Europe (“longhaul travellers”).
Our data shows that illness-specific and sociodemographic variables influence travel behaviour of haemophilic patients. Adult haemophilic patients with a high level of education were more likely to perform frequent and long-haul travel. Furthermore, living in partnership but also travelling alone was significantly associated with higher travel intensity. Among haemophilia-specific variables, self-application of clotting factors was the most important variable for a higher likelihood to go on long-haul travel. However, self-application was no significant variable for frequent travel. Other tested variables including the severity of haemophilia when compared between severe (<1% residual activity) and moderate/mild (1% residual activity) did not have any influence on travel behaviour of adult haemophilic patients (Table 1). Among patients aged 17 years and below, not being on permanent prophylactic treatment was associated with a higher likelihood for long-haul travel. Interestingly, the ability to administer the clotting factors by the patient or by a member of the patient’s family, did not have a significant influence on travel behaviour as this was the case for adult patients. However, this was probably due to the rather low number of patients in group 2. In contrast to the findings for adults, higher age and longer experience with the disease were significantly associated with the likelihood for long-haul travel among patients younger than 18 years. The frequency of travel, however, was not influenced by these two parameters. As data about the travel behaviour of patients with haemophilia have not been available up to now, our results can not be compared with data of other studies. Furthermore, as a control group was not part of our study we cannot directly compare our data with those of individuals not suffering from haemophilia or other chronic diseases. Such a control group would require a representative and age-matched sample of the German population. However, this was neither feasible nor within the scope of our study. Nonetheless, data from the representative annual analysis of the holiday travel behaviour of the population in Germany indicate at least, that travel patterns of patients with haemophilia might not differ to a large extent from those of the general population.6 The travel propensity of the population in Germany (individuals aged 14 years and older travelling for more than four days at least once per year), has been between 72% and 78% during the last two decades. Approximately 25% of them undertake two or more journeys annually.7 Our finding that 60% of our patients travel at least twice per year might indicate that patients with haemophilia may travel not less often than the general population at least. A share of 36.8% within our haemophilic patients had been visiting countries outside Europe at least once. So far, we are not aware of such life-time data among the German population. Approximately 17% of the German population, however, travels to destinations outside of Europe in a given year.6 Our observation that a higher education level is independently associated with more intensive travel is not specific for patients with haemophilia. Lohmann et al. reported similar findings for the general population in Germany.7 There may be several reasons for this finding. First, a higher education level is associated with an increased
Travel and haemophilia Table 1 Odds ratios (ORs) with 95% confidence intervals (95%-CIs) for different variables among adult patients with haemophilia A or B (group 1) with regard to frequent or long-haul travel. Tested variables
Frequent travel
Working University graduates Living with a partner Travelling alone Haemophilia B Severe Haemophilia Former joint, muscle, organ bleeding Permanent prophylactic treatment Self-application
Yes n Z 216
No n Z 129
n
%
n
%
128 89 151 134 29 145 182 111 172
59.3 41.2 69.9 62 13.4 67.1 84.3 51.4 79.6
71 22 67 62 16 89 106 67 104
55 17.1 51.9 48.1 12.4 69.0 82.2 51.9 80.6
Mean SD Current age [years] Age at diagnosis [years] Awareness of disease [months] Haemorrhages [per year]
46.3 5 489.2 11.4
Long-haul travel
16.3 9.2 166.5 16.4
Mean SD 43.7 5 469.9 11.2
15.6 9.9 153.2 13.6
Or (95%-CI)
p-Value
0.94 3.10 1.99 1.73 1.80 0.78 1.41 1.47 0.71
0.821 <0.001* 0.024* 0.048* 0.164 0.537 0.431 0.252 0.461
(0.53e1.66) (1.72e5.80) (1.10e3.62) (1.01e3.02) (0.79e4.38) (0.35e1.71) (0.60e3.32) (0.76e2.85) (0.28e1.74)
Yes n Z 159 n
%
n
%
98 67 103 98 22 109 138 83 135
61.6 42.1 64.8 61.6 13.8 68.6 86.8 52.2 84.9
101 44 115 98 23 125 150 95 141
54.3 23.7 61.8 52.7 12.4 67.2 80.6 51.1 75.8
OR (95%-CI)
p-Value
Mean SD
1.11 0.90 0.99 1.01
0.087 0.096 0.110 0.260
44.1 4.2 473.7 10.6
(0.99e1.37) (0.73e1.01) (0.98e1.00) (0.99e1.03)
No n Z 186
15.4 8.0 161.3 13.0
Mean SD 46.3 5.7 489.1 11.9
16.6 10.5 162.1 17.3
Or (95%-CI)
p-Value
1.04 2.45 1.27 0.97 1.48 0.66 1.90 0.84 3.25
0.421 0.001* 0.419 0.906 0.322 0.280 0.132 0.571 0.009*
(0.59e1.81) (1.43e4.26) (0.71e2.27) (0.57e1.64) (0.69e3.25) (0.31e1.39) (0.83e4.52) (0.45e1.55) (1.33e8.52)
OR (95%-CI)
p-Value
1.05 0.95 1.00 0.99
0.268 0.201 0.109 0.409
(0.97e1.22) (0.81e1.02) (0.98e1.01) (0.97e1.01)
*Significant; SD Z standard deviation. ORs and corresponding 95%-CIs are based on multivariable logistic regression models and adjusted to all other variables of this table. For categorical variables, the omitted categories are the reference groups (e.g. Haemophilia A).
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Table 2 Odds ratios (ORs) with 95% confidence intervals (95%-CIs) for different variables among patients with haemophilia A or B aged 17 years and below (group 2) with regard to frequent or long-haul travel. Tested variables
Haemophilia B Severe Haemophilia Former joint, muscle, organ bleeding Permanent prophylactic treatment Self-application
Frequent travel
Long-haul travel
Yes n Z 81
No n Z 63
n
%
n
%
12 58 52
14.8 71.6 64.2
11 48 43
17.5 76.2 68.3
0.64 (0.22e1.82) 0.56 (0.19e1.55) 0.64 (0.26e1.50)
71
87.7
55
87.3
1.03 (0.25e4.28)
34
42.0
24
38.1
Mean SD
Mean SD
OR (95%-CI)
1.92 (0.66e5.75) OR (95%-CI)
p-Value
Yes n Z 24
No n Z 120
n
%
n
0.395 0.271 0.305
4 18 16
16.7 75.0 66.7
19 88 79
0.963
19
79.2
0.231
12
50.0
p-Value Mean SD
Current age 9.5 4.1 9.7 4.4 0.88 (0.62e1.26) 0.484 [years] Awareness of 109.6 47.7 105.6 51.7 1.01 (0.98e1.04) 0.590 disease [months] Haemorrhages 6.0 8.0 11.0 28.5 0.98 (0.93e1.00) 0.092 [per year]
10.2 3.7
OR (95%-CI)
p-Value
15.8 73.3 65.8
0.76 (0.15e2.93) 2.36 (0.51e18.72) 0.95 (0.31e3.07)
0.708 0.296 0.934
107
89.2
0.10 (0.01e0.65)
0.016*
43
38.3
2.07 (0.46e10.40)
0.349
%
Mean SD 9.5 4.3
OR (95%-CI)
p-Value
0.51 (0.22e0.95) 0.031*
117.3 43.2 106.0 50.5 1.06 (1.01e1.14) 0.032*
7.1 7.7
8.2 20.6 1.00 (094e1.03)
0.929
*Significant; SD Z standard deviation. ORs and corresponding 95%-CIs are based on multivariable logistic regression models and adjusted to all other variables of this table. For categorical variables, the omitted categories are the reference groups (e.g. Haemophilia A).
ability to speak foreign languages facilitating international travel. Furthermore, individuals with a higher education level might be more interested in the history and culture of other countries. Likewise, long-distance travel is expensive therefore the typically higher income of individuals with higher education levels might further facilitate travelling. The positive effect of higher income on travel activity was shown by Lohmann et al.7 However, the education level seems to be an independent predictor for travel activity as poor college students travelled more often than rich graduates of secondary school.7 The increased travel activity of individuals living together with a partner is also not specific for patients with haemophilia. According to recent data on German holiday travel behaviour, the travel propensity of individuals living in a partnership was higher across different age groups.6 Conformity with general travel patterns was found as well with respect to the increased travel activities of patients travelling alone. Within the population in Germany those who made at least one holiday trip without travel companions had a higher frequency of travel and a greater share of long-haul trips in 2011. Beside prevention of bleeding episodes, the introduction of self-application of clotting factors in the late 1960s and early 1970s.2,8e10 enabled patients with haemophilia to travel more independently from their physician or treatment centre with increased safety while travelling. Our finding that self-application was the most significant variable to increase the likelihood to travel outside Europe is reflecting this fact. To our knowledge this is the first time that this effect has been shown. The frequency of travel, however, was
not influenced by the ability to apply the clotting factors by themselves. Patient’s awareness of the availability of good treatment options in haemophilia care centres in most European countries might explain this finding. Parents of patients younger than 18 years were less likely to travel outside of Europe if their children were on permanent prophylactic treatment. However, our results might be biased as the vast majority of the patients in group 2 (87.5%) were on permanent prophylactic treatment. The number of patients aged 17 years and below performing self-application of clotting factors was higher among frequent and long-haul travellers but this did not reach statistical significance which might be due to the rather low number of patients. Younger age as well as brief experience with the disease were associated with a lower likelihood for parents with haemophilic children to go on long-haul travel. Whereas the latter finding may be specific for haemophilia, data on travel behaviour for the general population in Germany show that the travel intensity of families with children aged five years and below is lower than that of families with older children.6 Considering that a longer-term experience by the parents with treating and managing haemophilia’s impact on their child’s in daily life, it is not surprising that the frequency of long-haul travel is dependent on the period of time that the disease is known. A potential limitation of our study is the response rate (27.5%) together with a possible self-selection of respondents. We cannot exclude that the questionnaire may have been answered only by patients, or parents, being
Travel and haemophilia interested in travelling. Therefore, we do not know whether the patients not returning the questionnaire travel or not. The rather high values for travel participation (compared to key data for the German population6,7) may indicate such a self-selection bias in our sample. Furthermore, we do not know whether the cohort of responding patients is representative for all haemophilic patients in Germany with regard to the severity of haemophilia. The two large patient associations with whom this study was performed do not ask their members for the severity of their haemophilia. According to the annual multicentric survey about morbidity and mortality of patients with haemophilia in Germany,11 approximately 58.7% of patients with haemophilia A or B have a residual factor activity 2%. As 69.7% of our patients reported having severe haemophilia with residual factor activity <1%, our results might be biased by this increased rate of patients with severe haemophilia. However, severe haemophilia was at least no significant variable for frequent or long-haul travel in our study. Another limitation was that the answers of the patients, or their parents, could not be validated by a physician to avoid misunderstandings. Further limitations of our study include the low number of patients in group 2 and the lack of a direct representative control group. The separate analysis for adults and patients younger than 18 years allowed us to consider their different life situation. Furthermore, we wanted to get a clear picture of the influence of the socio-demographic background on travel patterns of adult patients.
Conclusions Our data allows for the first time insights into the travel behaviour of haemophilic patients. The respondents report a rather high level of travel activity. Socio-demographic variables associated with more intensive travel are similar to those known to drive travel in the general population. High education level and self-application of clotting factors influence travel intensity of adult patients most strikingly. Parents of very young patients on permanent prophylactic treatment might need special education facilitating travel.
Funding The study was supported by a grant of CSL Behring GmbH, Marburg, Germany.
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Conflict of interest The authors state that they have no conflicts of interest to declare.
Acknowledgements The authors thank the staff and all members of the German Haemophilia Society (especially Dr. Anna Griesheimer and Mr. Werner Kalnins) and the Community of Interest of patients with Haemophilia (especially Mr. Guenter Schelle and Dr. Thomas Becker) for their valuable support in performing this study. Furthermore, we thank FUR (Forschungsgemeinschaft Urlaub und Reisen e.V., Kiel, Germany) for providing representative data of their yearly survey “Reiseanalyse” on the travel behaviour of the population in Germany.
References 1. Evatt BL. The tragic history of AIDS in the hemophilia population, 1982e1984. J Thromb Haemost 2006;4:2295e301. 2. Mannucci PM. Back to the future: a recent history of haemophilia treatment. Haemophilia 2008;14(Suppl. 3):10e8. 3. Mejia-Carvajal C, Czapek EE, Valentino LA. Life expectancy in hemophilia outcome. J Thromb Haemost 2006;4:507e9. 4. Plug I, Van der Bom JG, Peters M, Mauser-Bunschoten EP, De Goede-Bolder A, Heijnen L, et al. Mortality and causes of death in patients with hemophilia, 1992e2001: a prospective cohort study. J Thromb Haemost 2006;4:510e6. 5. R Development Core Team. R: a language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing, ISBN 3-900051-07-0; 2012. http://www. R-project.org/; 2012. 6. FUR Forschungsgemeinschaft Urlaub und Reisen e.V. Reiseanalyse 2012, Kiel, Germany (unpublished data). 7. Lohmann M, Aderhold P. Urlaubsreisetrends 2020-Die RA Trendstudie. Kiel, Germany (Forschungsgemeinschaft Urlaub und Reisen). 8. Seitz R. The history of haemophilia treatment. Pharm Unserer Zeit 2006;35:14e8. 9. Aledort LM. Hemophilia. Yesterday, today, and tomorrow. Mt Sinai J Med 1996;63:225e35. 10. Besmens I, Brackmann HH, Oldenburg J. Comprehensive care center bonn from 1980 to 2009. Changes in the epidemiology and regional composition of the haemophilia population. Ha¨mostaseologie 2011;31(Suppl. 1):S4e10. 11. Schramm W, Rieger A. Morbidity and mortality of patients with haemophilia in Germany e update 2010/2011. Ha¨mostaseologie 2012;32(Suppl. 1):S5e11.