The burden of injury in Central, Eastern, and Western European sub-region: a systematic analysis from the Global Burden of Disease 2019 Study

Background Injury remains a major concern to public health in the European region. Previous iterations of the Global Burden of Disease (GBD) study showed wide variation in injury death and disability adjusted life year (DALY) rates across Europe, indicating injury inequality gaps between sub-regions and countries. The objectives of this study were to: 1) compare GBD 2019 estimates on injury mortality and DALYs across European sub-regions and countries by cause-of-injury category and sex; 2) examine changes in injury DALY rates over a 20 year-period by cause-of-injury category, sub-region and country; and 3) assess inequalities in injury mortality and DALY rates across the countries. Methods We performed a secondary database descriptive study using the GBD 2019 results on injuries in 44 European countries from 2000 to 2019. Inequality in DALY rates between these countries was assessed by calculating the DALY rate ratio between the highest-ranking country and lowest-ranking country in each year. Results In 2019, in Eastern Europe 80 [95% uncertainty interval (UI): 71 to 89] people per 100,000 died from injuries; twice as high compared to Central Europe (38 injury deaths per 100,000; 95% UI 34 to 42) and three times as high compared to Western Europe (27 injury deaths per 100,000; 95%UI 25 to 28). The injury DALY rates showed less pronounced differences between Eastern (5129 DALYs per 100,000; 95% UI: 4547 to 5864), Central (2940 DALYs per 100,000; 95% UI: 2452 to 3546) and Western Europe (1782 DALYs per 100,000; 95% UI: 1523 to 2115). Injury DALY rate was lowest in Italy (1489 DALYs per 100,000) and highest in Ukraine (5553 DALYs per 100,000). The difference in injury DALY rates by country was larger for males compared to females. The DALY rate ratio was highest in 2005, with DALY rate in the lowest-ranking country (Russian Federation) 6.0 times higher compared to the highest-ranking country (Malta). After 2005, the DALY rate ratio between the lowest- and the highest-ranking country gradually decreased to 3.7 in 2019. Conclusions Injury mortality and DALY rates were highest in Eastern Europe and lowest in Western Europe, although differences in injury DALY rates declined rapidly, particularly in the past decade. The injury DALY rate ratio of highest- and lowest-ranking country declined from 2005 onwards, indicating declining inequalities in injuries between European countries.

Background An injury is defined as any intentional or unintentional bodily harm that results from tissue damage due to acute exposure to energy (mechanical, thermal, electrical, chemical, radiation), or cellular death, or loss of homeostasis [1]. Injuries are recognized as a major concern in public health worldwide. Results of the Global Burden of Disease (GBD) study showed that globally in 2019, 8% of all deaths were due to injury [2]. In the European region, the share of injury deaths was 5% [3]; however, major differences across European countries are observed, ranging from a low of 3% in Bulgaria to a high of 8% in Russia.
Apart from a major cause of death, injury is also often cited as an important cause of disability. Cohort studies among trauma patients showed that the majority of trauma patients had lower health-related quality of life scores one year after sustaining the injury, compared to their pre-injury health status or the general population [4,5]. Only a share of patients with long-term consequences of injury will recover, whereas most will experience permanent disabilities [6][7][8]. These findings highlight the importance of including both fatal and non-fatal consequences of injury, when describing the population health impact of injury.
A widely used population health metric that incorporates the years of life lost due to premature mortality (YLL) and years lived with disability (YLD) is the disability adjusted life year (DALY) [9]. This composite measure allows comparison of the population health impact of diseases and injuries with varying incidence and case fatality rates. By calculating age-standardized DALY rates, the DALYs are adjusted for differences in age structure and size of the populations. Hence, population health impact of different causes of disease and injury can be compared across countries and over time.
Comparisons of the population health impact of different causes of injury are crucial for the identification of major causes of injury and injury DALY trends over time, which may serve as input for priority-setting with regards to national injury prevention measures and their effects and health service planning [10]. Moreover, comparison of injury DALY rates may help to identify the existence of health inequality gaps between countries. Health inequality gaps are unfair differences in health status between sub-groups of a population that are avoidable [11]. Injuries are highly preventable [12], but prevention of injury requires material, economic or social means to protect oneself or others in the community. However, injuries are not equally distributed within societies and subsequently may result in health inequalities that can be measured by differences in injury incidence and mortality rates across populations [13,14]. A recently published systematic review on inequalities in injuries in the European region identified two cross-country studies that investigated inequalities over time [14]. Both studies were limited to children aged 1 to 14 years and used mortality rate ratios to investigate inequalities in injuries, instead of an integrative measure that includes both fatal and nonfatal outcomes, such as the DALY [15,16]. Insight into health inequalities in injuries across countries and within populations, using the DALY metric is currently lacking in Europe.
Therefore, the objectives of this study were to: 1) compare the GBD 2019 estimates on injury mortality and DALYs across 44 countries of the GBD European region (i.e., Central, Eastern, and Western Europe) by causeof-injury category and sex; 2) examine changes in injury DALY over a 20 year-period by cause-of-injury category, sub-region and country; and 3) assess inequalities in injury mortality and DALY rates across Central, Eastern, and Western European countries.

Methods
We analyzed levels and trends of incidence, mortality, and DALY and its components: YLL and YLD of injury in the European region of the GBD 2019 study [2]. The DALY is calculated by adding YLLs and YLDs. YLLs are calculated by multiplying deaths by the remaining life expectancy at the age of death. YLDs are calculated by multiplying the number of cases with a certain health outcome with the disability weight assigned to this health outcome. One DALY is equivalent to one healthy life year lost from mortality and disability.
The GBD 2019 study provided global and regional estimates for 286 causes of death, 369 diseases and injuries, for 23 age groups, male and female sex, and for 204 countries and territories from 1990 to 2019 [2]. Detailed descriptions of the methodology and approach of the GBD study and supplemental information on methods that were used to calculate incidence, mortality, YLL, YLD and DALY estimates have been published elsewhere [1,2]. For the present study, we used the GBD 2019 interactive data visualization tool 'GBD Compare' to retrieve the estimates for injury incidence, mortality, YLLs, YLDs, and DALYs (GBD 2019 Results. Seattle, United States: Institute for Health Metrics and Evaluation (IHME), 2019; http:// vizhub. healt hdata. org/ gbd-compa re/). In our study, we used estimates for each year in the period between 2000 and 2019. We compared incidence, mortality, YLL, YLD, and DALY by sex, country, and over time.

Cause-of-injury categories
Injury incidence and mortality data, coded according to the International Classification of Diseases, Ninth Revision (ICD-9) and the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10), were categorized into mutually exclusive and collectively exhaustive GBD cause-of-injury categories [1]. The cause-of-injury categories covered by the GBD were arranged in standard hierarchical categories of four levels. Level 1 causes consist of the category "Injuries" (Group III). This level can be broken down into three Level 2 cause-of-injury classifications, namely "Unintentional injury", "Transport injury" and "Selfharm and interpersonal violence". These level 2 causes can be further broken down into seventeen Level 3 and twenty-four Level 4 cause-of-injury categories. The Level 4 cause-of-injury categories convey the most detail about the causes of injury. For example, the Level 2 cause-ofinjury category "Self-harm and interpersonal violence" is subdivided into Level 3 cause-of-injury categories "Selfharm" and "Interpersonal violence". The Level 3 cause-of injury-category "Interpersonal violence" can be broken down into four Level 4 categories "Psychical violence by firearm", "Psychical violence by sharp object", "Psychical violence by other means" and "Sexual violence". The case definitions and ICD-codes of each of the cause-of-injury categories used in the GBD 2019 study can be found elsewhere [1,2]. For the present analysis, we report the Level 3 cause-of-injury categories. Injury incidence was restricted to cases warranting some form of healthcare, including General Practitioner and Emergency Department visits, in a healthcare system, where patients have full, unrestricted access to healthcare.

Selection of countries
In GBD 2019, Europe is divided into three regions: the Central European region (13 countries), the Eastern European region (7 countries) and the Western European region (24 countries

Percent change
The percent change over the 2000-2019 period is calculated by subtracting the DALY estimates for the year 2000 from the DALY estimate for the year 2019 and dividing it by the DALY estimate of the reference starting-point (i.e., the year 2000). A positive change indicates an increase of the burden resulting from that specific cause-of-injury during the 20-year study period, whereas a negative change indicates a decrease.

Assessment of inequality in mortality and DALY rates
Inequality in mortality rate between these 44 countries was calculated using the ratio of mortality rate for the highest-ranking country according to injury mortality rates to lowest-ranking country in each year. Inequality in DALY rate between countries was calculated using the ratio of DALY rate for the highest-ranking country according to injury DALY rates to lowest-ranking country in each year.

Uncertainty
The GBD estimates have varying degrees of uncertainty in the input data, the data adjustments, and the statistical models used to estimate values for all geographical locations over time [1,2]. Standard GBD methodology is that for each outcome variable (incidence, mortality, YLL, YLD, and DALY), uncertainty from each source is propagated at the level of 1000 draws; that is, all estimates were calculated 1000 times, each time drawing from the posterior distributions. In the Results section, we present the median value of the 1000 draws of the sampled incidence, mortality, YLL, YLD, and DALY values. We also present the 95% uncertainty interval (UI), which corresponds to the 2.5th and 97.5th percentiles of the corresponding distribution. Table 1 shows the incidence and mortality rates by all causes of injury and by European sub-region. The age-standardized incidence rates per 100,000 varied between Central, Eastern, and Western Europe. In 2019 in Central Europe, we observed 22,527 (95% UI: 20,338 to 24,899) new cases per 100,000, while incidence rates of all causes of injury in Eastern and Western Europe were 18,983 (95% UI: 17,295 to 20,784) and 12,313 (95%UI 11,049 to 13,739) per 100,000, respectively. Between 2000 and 2019, the change in incidence rates for all injuries has been decreased only by -3.3% (Central Europe) and -3.5% (Western Europe), and by -18.9% in Eastern Europe. Over the same period, falls and exposure to mechanical forces tend to be the highest incident causes of injury across all the European regions.

Age-standardized injury mortality rates by European sub-region, 2019
In 2019, in all European countries taken together, the incidence of all-cause injury was 109.7 million and 458,669 people died from injuries. The injury mortality rate per 100,000 individuals varied between European sub-regions. In Eastern Europe, 80 (95% UI: 71.4 to 89.2) individuals per 100,000 died from injuries; twice as high compared to Central Europe (injury deaths 37.8 per 100,000; 95% UI: 33.5 to 42.3) and almost three times as high compared to Western Europe (26.7 injury deaths per 100,000; 95% UI: 25.2 to 27.6). In Eastern Europe selfharm, road injuries and interpersonal violence contributed the most to the injury mortality rate (see Table 1). In Central and Western Europe, the causes of injury that contributed the most to the injury mortality rate were self-harm, road injuries, and falls. The highest variation in mortality rates by cause-of-injury death between European sub-regions was observed for poisonings (21 times higher in Eastern Europe compared to Western Europe), interpersonal violence (16 times higher in Eastern Europe compared to Western Europe) and environmental cold and heat exposure (13 times higher in Eastern Europe compared to Western Europe). Highest variation in injury DALY rates between the European sub-regions was observed for environmental heat and cold exposure (12 times higher in Eastern    Europe compared to Western Europe) and interpersonal violence, poisoning and drowning (all 9 times higher in Eastern Europe compared to Western Europe).  Figure 2 shows the DALY rates per 100,000 by causeof-injury category, by sex, and by country for 2019. Across all the European region countries, injury rates were higher in males than females. For males, DALY rates per 100,000 varied from a high of 9024 (95% UI: 7680 to 10,582) in Ukraine to a low of 1952 (95% UI: 1689 to 2290) in the Netherlands, whereas in females DALY rates varied from a high of 2587 (95% UI: 2173 to 3097) in the Russian Federation to a low of 866 (95% UI: 713 to 1054) in Italy. In females, the DALY rates are driven by falls, with highest falls DALY rates in Belgium (751 DALYs per 100,000; 95% UI: 558 to 998), Finland (747 DALYs per 100,000; 95% UI: 542 to 1008), and Slovenia (731 DALYs per 100,000; 95% UI: 538 to 978). However, in Ukraine and the Russian Federation, highest DALY rates in females were observed for road injury rather than falls. In males, falls, self-harm and road injuries were the most prominent causes of injury in the countries with lowest injury DALY rates. The DALY rate due to exposure to mechanical forces were far higher in Romania, Slovakia, Bulgaria, and Albania compared to other European countries. Moreover, in countries with the highest injury DALY rates in males (Republic of Moldova, Latvia, Lithuania, Belarus, the Russian Federation and Ukraine) the DALY rates due to self-harm stand out.

Changes in DALY rates, 2000 -2019
Between 2000 and 2019 injury DALY rates in Eastern, Central and Western Europe have declined by 45%, 29%,  Table 2 and Fig. 3). In Eastern Europe the DALY rates of all cause-of-injury categories declined, with largest declines for conflict and terrorism (-90%), exposure to forces of nature (-90%), and drowning (-62%). In Central Europe the DALY rates of all cause-of-injury categories declined expect for exposure to forces of nature (+ 39%). The largest decreases in Central European injury DALY rates were observed for conflict and terrorism (-76%), drowning (-52%), and poisonings (-49%). In Western Europe largest declines were observed for exposure to forces of nature (-84%), road injuries (-56%), and conflict and terrorism (-54%), whereas increases were observed for police conflict and executions (+ 0.1%), falls (+ 1%), and exposure to environmental heat and cold (+ 46%). Figure 4 shows the ratio of the DALY rate per 100,000 for highest-ranked to lowest-ranked country in each year from 2000 to 2019. For all European countries, the DALY rate ratio was highest in 2005, with the DALY rate in the lowest-ranking country (Russian Federation) 6.0 times higher compared to the highest-ranking country (Malta). After 2005, the DALY rate ratio between the lowest-and highest-ranking country gradually decreased to 3.7 in 2019. When comparing the injury DALY rates of the lowest-and highest-ranking countries within sub-region over time, we observed that the DALY rate ratio between the lowest-and highest-ranking country in Central Europe, Eastern Europe and Western Europe fluctuated between 1.5 and 1.3, 2.1 and 1.8 and 2.1 and 1.7, respectively. The DALY rate ratio varied widely by major cause-ofinjury and over time. Largest differences in injury DALY rates across countries were observed for interpersonal violence, ranging from 30.

Main findings
In this systematic analysis, we found that over the period from 2000 to 2019, there was an overall reduction in the age-standardized incidence rates due to all injury categories across the European sub-regions. However, slower reductions in injury incidence rates were observed in Central and Western Europe.
Furthermore, we found that mortality and DALY rates of injury varied widely by European sub-region, country, sex and cause-of-injury category. Overall, the injury mortality rate in 2019 in Eastern Europe was twice as high compared to Central Europe and almost three times as high compared to Western Europe. The injury DALY rates showed less pronounced differences between Eastern, Central and Western Europe, although also a distinct East to West gradient was observed. Comparison of injury DALY rates by country showed a fourfold difference between the lowest-and highest-ranking country; however, the difference in injury DALY rates by country was larger for males compared to females. The difference in injury DALY rates between highest-and lowestranking country declined from 2005 onwards, indicating declining inequalities in injuries between European countries.

Comparison to other studies -change over time
From 2000 to 2019 we observed large declines in injury DALY across all European sub-regions; however, largest declines were observed for Eastern Europe. This is comparable to findings from the study by Sethi et al. on injury inequalities in Europe [17]. Particularly in the period 2005 to 2013 the difference in declined injury DALY rates between the Eastern, Central and Western Europe is striking, with rapid progress in Eastern Europe, intermediate progress in Central Europe and slow progress in Western Europe. Several factors may have contributed to the slow progress in Western Europe, including ageing of the population and the fact that Western Europe had much lower DALY rates at the beginning of the period, thus their margin for improvement is much more reduced. However, there are striking differences in allcause injury DALY rates and injury DALY rates by causeof-injury categories (e.g., falls and road injuries) across Western European countries. Therefore, it may be worthwhile to assess which injury-specific prevention measures have been taken in Western European countries that showed continuous low or decreasing incidence, mortality, and DALY rates despite ageing of the population. This may lead to the identification of opportunities to reduce the injury DALY rates in Western Europe even further and that may be transferrable to other European countries.
Furthermore, previous studies reported that the financial crisis that hit Europe in 2008 resulted in higher mortality rates, including higher suicide rates [18,19]. However, for none of the three European sub-regions we observed increasing injury mortality and DALY rates between 2008 and 2011. This finding is broadly in line with earlier results from a systematic analysis on suicide mortality trends among global, national, and regional geographies [20]. The different policy responses and particular characteristics of the societal organizations may help to explain the apparent resilience of the populations to the potentially fatal health effect of an economic downturn.
Despite the large decline in DALY rates resulting from conflict and terrorism, we observed that over this 20-year study period the burden of terrorism remained at its peak in Croatia, Serbia, and Bosnia and Herzegovina. An explanation for this may be that the Bosnian War of the early 1990s had a profound impact on health and disabilities, and that many Balkan inhabitants may therefore still be experiencing the long-term consequences of injury, almost 30-years later [21].
In addition, from 2000 to 2019, Eastern Europe had the highest injury mortality rates attributable to cold or hot temperatures. This may be in part explained by the fact that in Eastern Europe the 2003 and 2010 heat-waves led to an increased number of deaths [22,23]. Moreover, a study evaluating the global, regional, and national mortality burden associated with non-optimal ambient temperatures showed that between 2000 and 2019, Eastern Europe had the highest heat-related excess mortality and that this rate was two to five times higher compared to other European regions in the same period [24]. Climate change is expected to affect populations' health by increasing the mortality burden [25]; national prevention plans are therefore needed to reduce the heat-and/or cold-related impact on the injured.

Comparison to other studies -inequalities in injury
Our findings suggest that health inequalities associated with injuries between European countries decline over time. This is in contrast to the findings of two cross-country studies that reported increasing inequalities across Europe over time [15,16]. Reasons for these differences in findings may be the different metrics that were used to measure health inequalities, namely mortality ratios versus DALY rate ratios. Second, there are differences in the populations that were studied. Göpfert et al. [15] and Sethi et al. [16] studied age mortality rates among children aged 0 to 14 years old in 53 countries included in the WHO European region, whereas our study included all ages in 42 European countries. Third, there were differences in the period that was studied. Göpfert et al. [15] and Sethi et al. [16] reported differences in injury mortality rates for the years 2000 and 2011 and 2015, respectively to measure differences in health inequalities over time, whereas in our study differences in DALY rate ratios from 2000 to 2019 were reported.
From 2003 to 2005 the observed inequalities in DALY rate ratio increased. Main reason for this was that the DALY rate in the Eastern European region increased during this period. An explanation for this finding may be the impact of dissolution of the former Soviet Union and its social and economic consequences on health and mortality in subsequent years [26]. However, others have argued that causes of the increased mortality rates in Eastern European countries are more intricate and may be the result of a combination of lifestyle habits, economic impoverishment, widening social inequality and the breakdown of political institutions [27,28]. From 2005 onwards, DALY rates in Eastern Europe have decreased more rapidly compared to Central and Western Europe. A possible contributing factor may be the anti-alcohol policies implemented in Russia in 2005-2006, although other factors, such as economic growth and national initiatives to combat the road safety, childhood injury prevention efforts and violence prevention most probably have played a role as well [29][30][31]. Therefore, governments should consider to introduce stricter preventive policies including marketing controls and/or use of taxation to reduce the injury disease burden across European countries.

Strengths and limitations
A strength of this systematic analysis is that the DALY metric was used to assess the population health impact of injuries in Europe, describe trends over time and inequalities in injuries across countries. The DALY incorporates mortality and disability, which allows for a more complete assessment of the population health impact. Previous studies that investigated injury inequalities across European countries were based on mortality rate ratios [15,16] rather than DALY rate ratios.
A second strength of this study is that the mortality rate estimates in European countries were based on complete cause-of-death registration systems [32]. However, a limitation is that nationally representative injury incidence data -essential input for the YLD calculations -were available for 19 of the 44 included countries, of which many datasets were collected 10 or more years ago. Incidence estimates for every European country and recent years were made by using statistical models that use available data on incidence, prevalence, remission, duration and extra risk of mortality due to the injury from the year and country for which incidence is estimated, as well as from previous years and other countries, but these estimates are inherently less accurate for countries without national representative incidence data [1][2][3].
A second limitation is that the cause versus nature-ofinjury matrices, required for the injury YLD calculations, were based on outpatient, inpatient, and emergency room discharge data from an even smaller number of countries, namely seventeen European countries that are spread across the three European regions (Bulgaria, Cyprus, Czechia, Denmark, Estonia, Hungary, Iceland, Italy, Latvia, North Macedonia, Malta, Netherlands, Norway, Portugal, Slovenia, Spain, and Sweden).
A third limitation of our study is that the analytical approach chosen to explore inequalities associated to injuries across countries focuses on the extremes by calculating rate ratios between countries with highest and lowest injury rates. The GBD study does not provide DALY rates for sub-groups of the population, by socio-economic status or on a small area deprivation level [2]. As a result, we were not able to investigate health inequalities within countries over time. Therefore, we did not investigate injury inequalities by age groups and sex.
Finally, another limitation of our study is that the DALY estimates were based on prevalence-based data. The epidemiological Disease Modeling -Metaregression (Dis-Mod-MR) software tool is used to stream out prevalence from incidence, and this process assumes a steady state where rates are not changing over time [1]. This steadystate assumption may lead to inaccurate estimates of prevalence of long-term disability if there are large trends in incidence rates or mortality.

Conclusions
Injuries in Europe are still a major public health problem. In 2019 across all European region countries, 109.7 million people sustained injuries that warranted some type of healthcare and 458,669 people died from injuries. However, mortality and DALY rates of injury varied widely by European region, country, sex and cause-of-injury category. Injury mortality and DALY rates were highest in Eastern Europe and lowest in Western Europe, although differences in injury DALY rates declined rapidly, particularly in the past decade. The injury DALY rate ratio of highest-and lowest-ranking country declined from 2005 onwards, indicating continuous declining inequalities in injuries between European countries.