Epidemiological studies of risk
factors for injuries in an adult
population
Birgit Modén
Faculty of Medicine
Malmö 2012
Abstract
Injuries are often associated with long-term suffering and lowered functioning, and personal
injuries impose a huge burden on medical care and health services in addition to the costs
associated with impaired functional ability. Each year in Sweden, falling accidents are
experienced by a third of those aged 60 or over and half of those aged 80 or over, while injuries
from traffic accidents still account for many of the serious accidents in youths and younger adults.
From a public health perspective an increased knowledge about risk factors for injuries is
important to decisions influencing the focus of public health prevention strategies. In this thesis,
risk factors for various types of injuries were investigated during 2006 and 2007, that is, its
associations with sociodemographic variables, previous disease and psychotropic drug use in both
men and women. Three of the studies in this thesis were longitudinal in that sense that the levels
of the independent variables were measured before the onset of the injury and one study was a
case-control study. The studies were register-based and comprised the whole adult population of
the county of Scania, Sweden, with various restrictions in age. The results presented in this thesis
showed that about one third of the middle-aged population and nearly half of the elderly
population had used psychotropic drugs during a period of 1.5 years. Considering their high
prevalence, side effects related to the use of psychotropic drugs may be a relevant risk factor for
injuries that could be prevented by an increased rational medication use. Psychotropic drug use
was also associated with increased odds of injuries from falling and transportation accidents in
nearly all age groups in both men and women, even after adjustment for potential confounders.
Studying the elderly general population and falling accidents, it was shown that such an effect was
the largest immediately after initiating therapy. Psychotropic drug use was also related to
increased odds of assault-related injuries and intentional self-injuries during the observation
period, with a clear dose-response relationship with diagnosed intentional self-injury. The results
further showed that sociodemographic factors generally had weaker associations with
unintentional injuries such as falling accidents and transportation accidents, compared to
intentional injuries such as assault-related injuries and intentional self-injury. A number of chronic
diseases and conditions have in earlier studies been shown to be associated with a higher risk of
injuries. In the studies presented in this thesis, psychiatric disease and neurological disease were
associated with increased odds of unintentional as well as intentional injuries during the
observation period. There were also associations between diseases related to drug- or alcohol
abuse and intentional injuries. Such disease-related injuries might be reduced by early
identification with correct treatment as well as restrictions with regard to driving. In conclusion,
the results presented in this thesis expand the knowledge base on risk factors for injuries in adults.
One strength of the results presented is that the data covers the total general population in Scania,
which minimises the risk of selection bias. Considering the high prevalence and the often
devastating consequences, the field of injury and its risk factors is an important topic for research.
An increased awareness of such risk factors might be of help to reduce the number of injuries by
affecting the planning of local, regional and national public health intervention programs and
strategies.
ISBN 978-91-87189-18-0
ISSN 1652-8220
© Birgit Modén
Social Medicine and Health Policy
Faculty of Medicine, Lund University, 2012
Printed by Media-Tryck, Lund
To my dear life companion Frida
and my parents Nore and Asta
“Do not take life too seriously.
You will never get out of it alive”
Elbert Hubbard
Contents
List of Papers .................................................................................................. 11
Abbreviations .................................................................................................. 12
Introduction..................................................................................................... 13
Injuries
a) Epidemiology of unintentional injuries
Definition ……………… ....................................................................... 14
Time trends .......................................................................................... 15
Geographical differences ..................................................................... 16
Factors related to risk .......................................................................... 17
Sociodemographic factors ............................................................... 17
Alcohol and drug abuse ................................................................... 17
Medication ....................................................................................... 18
Psychological characteristics ........................................................... 18
Chronic disease ............................................................................... 19
Environmental factors ...................................................................... 19
b) Epidemiology of intentional injuries
Definition ……………… ....................................................................... 20
Time trends .......................................................................................... 20
Geographical differences ..................................................................... 21
Factors related to risk .......................................................................... 21
Sociodemographic factors ............................................................... 21
Alcohol and drug abuse ................................................................... 22
Medication ....................................................................................... 23
Psychological characteristics ........................................................... 23
Chronic disease ............................................................................... 24
Environmental factors ...................................................................... 24
Causal model ...................................................................................................25
Aims
General aim ................................................................................................27
Specific aims...............................................................................................27
Material and methods
LOMAS .......................................................................................................28
Scania .........................................................................................................29
Studied factors
Sociodemographic factors ....................................................................30
Previous disease ..................................................................................30
Psychotropic drug use ..........................................................................31
Outcomes .............................................................................................32
Statistics
Paper I ........................................................................................................33
Paper II .......................................................................................................33
Paper III ......................................................................................................34
Paper IV ......................................................................................................34
Results and conclusions
Paper I ........................................................................................................35
Paper II .......................................................................................................38
Paper III ......................................................................................................40
Paper IV ......................................................................................................42
General discussion
Findings
Psychotropic drug use and accidents ...................................................45
Risk factors for injuries from assault.....................................................46
Risk factors for intentional self-injury ....................................................46
Methodological issues
Study design .........................................................................................48
Propensity score ...................................................................................48
Validity of measures of outcome variables ...........................................49
Validity of psychotropic drug use ..........................................................50
Representativity ....................................................................................50
Confounding .........................................................................................51
Implications for future research and prevention ...................................51
Conclusions .................................................................................................... 54
Populärvetenskaplig sammanfattning .......................................................... 55
Acknowledgements ........................................................................................ 57
References ...................................................................................................... 58
Appendix
Paper I........................................................................................................ 81
Paper II....................................................................................................... 87
Paper III...................................................................................................... 95
Paper IV ................................................................................................... 111
Birgit Modén
_______________________________________________________________________
Birgit Modén
_______________________________________________________________________
List of papers
This thesis is based on the following publications which will be referred to by their
Roman numerals:
I.
Modén B, Ohlsson H, Merlo J, Rosvall M. Psychotropic drugs and accidents
in Scania, Sweden. Eur J Public Health 2011 Sep 6 [Epub ahead of print].
II.
Modén B, Merlo J, Ohlsson H, Rosvall M. Psychotropic drugs and falling
accidents among the elderly: a nested case control study in the whole population of
Scania, Sweden. J Epidemiol Community Health 2010;64(5):440-6.
III. Modén B, Ohlsson H, Merlo J, Rosvall M. Risk factors for assault-related
injuries: A total population-based study. Submitted.
IV. Modén B, Ohlsson H, Merlo J, Rosvall M. Risk factors for intentional selfinjury: A total population-based study. Submitted.
Paper I is reproduced by permission of Oxford University Press, and Paper II by
permission from the BMJ Publishing Group Ltd.
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Abbreviations
ATC
Anatomical Therapeutic Chemical Classification
CI
Confidence interval
DDD
Defined daily dose
EU
European Union
EFTA
European Free Trade Association
ICD
International Classification of Diseases
IDB
Injury Database
IoT
Register of Income and Taxation
LISA
Longitudinal Integration Database for Health
Insurance and Labour Market Studies
LOMAS
Longitudinal Multilevel Analysis in Scania
MSB
Myndigheten för samhällsskydd och beredskap
OR
Odds ratio
WHO
World Health Organization
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Introduction
In Sweden, about 135 000 individuals per year are hospitalised due to an injury.
Around 13% of people discharged from hospital during 2008 had been there due to
an injury [1]. Furthermore, injuries comprise the third most common cause of death
after cardiovascular diseases and cancer [2]. Injuries are often associated with longterm suffering and lowered functioning, and personal injuries impose a huge burden
on medical care and health services in addition to the costs associated with impaired
functional ability [1]. The total number of injuries occurring in Sweden is hard to
estimate, due to incomplete registration of less severe cases which do not require
admission to hospital or specialised care [1]. When injuries are categorized on the
basis of their seriousness, ranging from injuries treated in primary care, through
injuries needing hospital care, to lethal injuries, unsurprisingly show that the first
group is by far the largest. Of all individuals hospitalised during 2010 with an
external cause of morbidity, falling accidents accounted for 46%, transportation
accidents for 7%, intentional self-inflicted injuries for 5%, and violence-related
injuries for 2% [3].
“An injury may be described as the result of a sudden event causing trauma to a
person” [1]. Injury is a broad term; it includes the consequences of a number of
phenomena, where the causes of the actual injury may vary considerably and for
which different types of interventions are possible. For example, the cause of a
traffic injury differs from the cause of a violence-related injury even though they
might both result in a hip fracture [1]. According to the commonly-cited “Injury
Fact Book” by Baker et al., an injury is defined as “a bodily lesion at the organic
level, resulting from acute exposure to energy (mechanical, thermal, electrical,
chemical or radiant) in amounts that exceed the threshold of physiological
tolerance. In some cases (e.g. drowning, strangulation, freezing), the injury results
from an insufficiency of a vital element” [4]. One frequently-used primary
classification of injuries is based on whether they are intentional or unintentional.
Furthermore, unintentional injuries are often categorised according to the direct
cause of the accident, such as falling accidents, transportation accidents, drownings,
poisonings, or burns.
Injuries make a considerable contribution to the disease burden in all countries in all
regions of the world [5]. In comparison with other EU member countries, Sweden
has relatively fewer deaths and hospitalisations from traffic or workplace injuries,
but relatively more deaths or hospitalisations due to injuries in the home or leisure
environment [6].
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A number of chronic diseases have been associated with a higher risk of injuries, as
have several classes of medical treatments and drugs, particularly psychotropic
drugs such as tranquillizers and antidepressants, alcohol, and narcotics [7-18].
Furthermore, the risk of injury varies with sociodemographic factors such as sex,
age, ethnicity, geographical area, and socioeconomic position [1, 2, 6]. In Sweden,
men have higher death rates from injuries than women in all age groups.
Furthermore, even though injuries are the leading cause of death among children
and young adults, the absolute number of deaths due to injuries increases with age
[1]. People aged 65 years or more constitute less than one fifth of the population,
but account for two thirds of fatal accidents and half of all serious accidents
requiring hospital care [1, 19, 20]. Psychological characteristics and psychosocial
factors such as impulsivity, self-confidence, stress, and social support are also
associated with the risk of injuries [2, 21, 22]. Most of the evidence for all the
abovementioned associations comes from studies based on clinical samples from
emergency departments [23-25], case studies, studies in specific settings such as
nursing homes and long-term care [26-36], cross-sectional studies on patient
populations [21, 37-39], and there are generally few epidemiological studies on risk
factors for injuries in an adult general [40] population. This thesis aims at
longitudinal identification of risk factors for injuries using the whole population (18
years and over) of the county of Scania, Sweden as the study population. The thesis
focuses on individual factors (e.g., age, sex, lifestyle habits, health, medication) and
group-related factors (e.g., family, socioeconomic position, culture/ethnicity).
However, there are also environmental factors, vector-related factors and
psychosocial factors of importance to the occurrence of injuries, not studied in this
thesis. All these factors are described in the next section, which introduces the area
of injuries by describing some basic concepts and findings such as definitions, time
trends, geographical differences, and factors related to risk. Injuries are classified
based on their intentionality into unintentional and intentional injuries.
Injuries
a) Epidemiology of unintentional injuries
Definition
Unintentional injuries are related to events in which there was no intent for an
injury to occur (accidents). They are usually subdivided by their casual mechanism
(i.e. how they occurred). The most commonly used subcategories are road traffic
injuries, falls, burns and scalds, drownings, poisonings, and stabbings/cuts [41].
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Time trends
Age and sex standardized mortality per 100 000 population
In Sweden, the mid-1970s to the mid-1990s saw a decline in mortality from
unintentional injuries. However, from the end of the 1990s this positive trend began
to change. The mortality level from unintentional injuries increased by 15%,
between 1999 and 2003, though there has been a decrease in later years (Figure 1).
A strong increase of mortality in the year 2004 was due to the tsunami disaster in
Thailand where a lot of Swedes on vacation died.
90
80
70
60
Total
50
Men
40
Women
30
20
10
0
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
Figure 1. Age-standardised mortality rates due to unintentional injuries (per 100 000
population) in Sweden during 2000-2010. Source: Causes of Death 2010, National Board
of Health and Welfare, Sweden.
Falling accidents are the most common type of unintentional injury leading to
hospitalisation, accounting for 70% of those hospitalised after an accidental injury
[19]. Each year in Sweden, falling accidents are experienced by a third of those
aged 60 or over and half of those aged 80 or over [2]. National data show that the
death rate due to falling accidents has increased by 60% between 2000 and 2010,
from 11.8 to 19 per 100 000 persons [3]. Some of this increase might be an effect of
an older population and a more mobile older generation, leading to an increased
proportion of injuries as causes of death relative to other causes.
The mortality rate from transportation accidents has markedly declined in Sweden
over the last twenty years and in the last ten years has halved from 14.2 to 6.3
deaths per 100 000 persons [42]. However, traffic accidents still accounts for many
of the serious and fatal accidents in youths and younger adults [43]. This positive
trend in traffic-related accidents and injuries reflects the presence of legislation on
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alcohol-impaired driving, on the quality of motor vehicles, seat belt use, bicycle
helmet use among young people, and safety improvements on roads [44-48].
Occupational injuries have also long been in decline, with the greatest reduction in
the areas of vehicle manufacturing and care for old people [1]. Around 50
employees per year currently die from occupational injuries, most of them in the
construction industry [19].
Geographical differences
Worldwide, approximately 5 million people died from injuries at the beginning of
this century, giving a mortality rate of 83.7 per 100 000 population [5], and
accounting for 9% of the world’s deaths. Twice as many men die as a result of an
injury as women. Road traffic injuries are the main cause of injury-related mortality
worldwide. Compared to other EU member states, Sweden has low mortality and
morbidity rates from transportation and occupational accidents [19, 49]. However,
setting aside child injury fatality rates, which are among the lowest in the world [49,
50], Sweden’s record on accidents in the home and leisure sector is worse than
average [49] . There are also regional differences within Sweden, with the highest
levels of accidental injuries in the north of Sweden and the lowest in the south [51].
Furthermore, mortality from motor vehicle accidents is higher in rural areas than in
urban areas [51, 52]. Area of residence have also shown to be related to the risk of
injuries [53, 54]. For example, in a study by Laflamme et al. it was shown that
contextual socioeconomic attributes were associated with increased odds of injuries
for motor-vehicle riders among younger adults [55].
Factors related to risk
Sociodemographic factors
There are clear differences in the risk of unintentional injuries when considered in
terms of sociodemographic factors such as sex, age, geographical area, ethnicity,
and socioeconomic position [1, 55-59]. For example, falling accidents are more
common in women than in men, while men are more frequently injured in the traffic
environment and have a doubled mortality risk from motor vehicle accidents
compared to women. Traffic accidents cause a large proportion of serious and fatal
injuries among young people [43]. Fractures due to falling accidents are the most
common type of injury among the elderly, and 85% of fatal fall injuries occur
among those aged 65 or over [2]. Social and economic status also affects the risk of
being involved in an accident. Unemployed persons, those living alone [59, 60], and
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those with a low education level are at higher risk of an accident compared to other
groups in society [61], while children of single parents are at a higher risk of an
accident than other children [55, 62]. Furthermore, traffic injuries are more common
among children from lower social positions and among children living in deprived
socioeconomic areas [63]. Hip fracture after a falling accident is also more frequent
among elderly people living in low-income communities than among those living in
middle-income and high-income areas [64]. Male blue-collar workers have one and
a half times higher risk of death from accidental injuries than white-collar workers,
and men with a low educational level have the highest risk of dying in a car crash
[43]. A similar pattern of association is seen for children of blue-collar workers
compared to children of white collar workers [1].
Alcohol and drug abuse
Numerous studies have shown an association between high alcohol consumption
and the incidence of traffic injuries [7]. National data have shown that over 10% of
fatal traffic accidents involved drivers with a blood alcohol concentration exceeding
0.2‰ [66]. Alcohol is also a factor in accidents other than traffic accidents: it has
been estimated that 28% of all deaths in unintentional accidents in Sweden are
alcohol-related [67]. More than 70% of men and almost 60% of women who died in
fires, in Sweden 2005, were under influence of alcohol, and alcohol is present in the
same scope for drownings [68]. Furthermore, studies have shown that excessive use
of alcohol is a risk factor for falls among older adults due to its effect on awareness
and balance [69-71], while other studies have shown no association between
moderate alcohol use and falling accidents [72, 73].
The use of illicit drugs is another important risk factor in traffic accidents [74, 75].
For example, studies have shown that the severity of a car crash is higher when
combining alcohol with illicit or medical drugs [76]. A high level of illegal drug use
has been found among those who die from fires or drowning accidents, especially
among young people [19]. Furthermore, the use of illicit drugs among young adult
males is related to an increased risk of workplace accidents [77] as well as
workplace fatalities and occupational traffic accidents [78].
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Medication
Psychotropic drugs are mainly used for psychiatric conditions such as psychosis,
depression, sleeping problems, anxiety, and worrying [79, 80]. Like all
pharmacological treatments, psychotropic drugs are associated with side-effects
[81]. The side-effects in this case include dizziness, sedation, and tiredness with
negative effects on cognition, alertness, and psychomotor function [82-84], which
in turn increase the risk of injuries [7, 9, 10, 14, 59, 85]. Several studies have shown
that psychotropic drugs have a negative effect on driving capability [84, 86-97], and
that side effects of these drugs can cause falling accidents in the elderly [8, 11, 13,
14, 26, 27, 98, 100-105]. Furthermore, antihistamines and diabetes medication
(injected and oral medication) are associated with a higher risk of occupational
injuries [106], while the use of antihypertensive medication has been associated
with an increased risk of falling accidents [107]. Taking five or more prescribed
medications has been shown to be a significant risk factor in many falling accidents
[108, 109]. Experimental studies have shown that first-generation antihistamines
(e.g. triprolidine, clemastine) have adverse effects on driving capability [110, 111].
Moreover, the use of nonsteroidal antinflammatory drugs (i.e. anti-inflammatories,
analgesics, antipyretics) and antihypertensive drugs (ACE inhibitors) among the
elderly is associated with an increased risk of being involved in a traffic accident
[112]. One older drug for treatment of epilepsy, carbamazepine, has also been
related to an impaired adaptation to speed limits and therefore an increased risk of
traffic accidents [113].
Psychological characteristics
Fear, worry, and stress have been shown to be associated with an increased risk of a
falling accident [114-116]. Elderly people who experience a falling accident often
develop a fear of falling which may lead to social isolation, depression, and an
increased risk of a new falling accident [59, 117]. Many road accidents are the
result of driving violations. Such violations are dependent on past behaviour,
norms, and denial of negative consequences of the action [118, 119].
Previous injury has been shown to be a risk factor for a new injury, which might
indicate that there is something at the individual level, such as psychological
characteristics, that affects the risk. The risk of a new injury is highest soon after the
initial injury, but studies have shown that the higher risk persists for at least five
years [120]. This increased risk might also be due to other factors such as alcohol
and drug use, or prevalent disease and treatments.
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Chronic disease
A number of chronic diseases and conditions have been shown to be associated with
a higher risk of accidents. Diseases such as stroke, Parkinson’s disease, dementia,
previous hip fracture, dizziness, and reduced sight are associated with an increased
risk of a future falling accident [59, 121-123]. Muscle weakness, often seen among
old people, might by impaired balance and an altered gait with short steps increase
the risk for falling accidents [59, 124]. Furthermore, low body weight is also one
risk factor for falling accidents among old people, in the same way as muscle
weakness. Patients with depressive disorders are more likely to take risks with little
regard to the consequences of their actions, and are more likely to be involved in
some kind of accident [83]. Persons with disabilities also are at a greater risk of
being involved in accidents. Not to be able to read, hear or to see properly or being
wheelchair bound, means that one cannot assimilate important information and
warnings about e.g. fire and also to quickly get to safety [19, 125]. Diabetes
mellitus, neurological diseases such as Parkinson’s disease, multiple sclerosis or
other neurodegenerative diseases, dementia, and cognitive disorders might affect
driving capability and are associated with an increased risk of traffic accidents
[126-128]. Furthermore, psychiatric illnesses such as psychosis and affective
syndromes might also affect driving, leading to an increased risk of traffic
accidents. Conditions such as reduced sight, dizziness, and impaired cognition
might additionally be associated with such increased risk. Studies have shown that
almost 50% of the drivers, riders, or pedestrians involved in a crash suffer from at
least one medical condition, and that in approximately 13% of cases, the medical
condition of the car driver was the direct causal factor [129].
Environmental factors
In addition to the risk factors for accidents that have already been mentioned, there
are also several other noteworthy potential risk factors, such as environmental and
vector-related factors. In Sweden there is no environment where so many people are
injured or die as a result of accidents as in or near the home [130]. The risk is the
highest among children and the elderly. For example, children might fall down
stairs, from furniture and tables, cut themselves, become poisoned by drugs and
chemicals, or are burned by hot liquids and objects. Adults are often injured in “doit-yourself-accidents” and in gardening. Older people are primarily injured in falling
accidents [19]. Two-thirds of all pedestrian hospital days are caused by falling
accidents outdoors and with no vehicle involved [131]. The most common injury
reason among these pedestrians are slippery roads and uneven pavements [131133], but also problems with accessibility due to parked bicycles, advertising signs,
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streetlights, and distance between the benches and rest areas [132]. Studies have
shown that factors such as slippery surfaces, poor lightning, level differences,
trailing wires, and uneven thresholds are all important risk factors for falling
accidents in the home environment [19, 134]. Contributory factors to traffic
accidents include speed, road construction, grip, lighting conditions [133], and the
condition of the vehicle.
b) Epidemiology of intentional injuries
Definition
Intentional injuries are often subdivided according to the parties involved in the
event; the three main categories are intentional self-injury (e.g. suicide, attempted
suicide, self-abuse) [135], interpersonal violence (fatal or non-fatal injuries
inflicted by one person against another, e.g. homicide, violence between intimate
partners, sexual violence, child abuse and neglect, abuse of the elderly), and
collective violence (e.g. due to war or civil insurrection, acts of terrorism, gangs).
Time trends
In Sweden today, there are about twice as many deaths from violence-related
injuries compared to the levels in the 1950s. This increase was primarily seen in the
1960s and 1970s, while the death rate from violence has been fairly constant during
the past thirty years [136]. The current rate is about 90 deaths annually [137]. It is
hard to estimate the prevalence of violence-related injuries, but self-reported data
from surveys show that about one in ten people in Sweden has been exposed to
violence during the last year [2]. During 2005-2007, about 2000 boys and men and
600 girls and women were hospitalised each year due to violence-related injuries
[2]. Regarding intentional self-injuries, several survey-based studies from Western
countries have shown that a history of non-fatal self-injury is reported by 2-4% of
the adult population [138-140], and 6-17% of adolescents and young adults [135,
141-143]. Suicide rates in Sweden have decreased since the beginning of the 1990s
in all age groups except those aged 15-24 years, where the rates have instead
increased. Suicide is the leading cause of death in Sweden among men aged 25-44
years and among women aged 20-39 years [144]. Hospitalisations due to suicidal
attempts or other types of intentional self-injury have also increased markedly in
Sweden during the past fifteen years among younger women, but also among young
men. During 2007, about 350 per 100 000 women and 160 per 100 000 men aged
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15-24 years were hospitalised due to suicide attempts or other types of intentional
self-injury [2].
Geographical differences
Worldwide, more than half a million people each year lose their lives due to
interpersonal violence [145], and violence-related injuries are one of the leading
causes of death among people aged 15-44 years [145]. Intimate partner violence and
abuse of children and elderly people are common problems in every country, but
other types of interpersonal violence vary between different parts of the world; for
example Africa and Latin America show exceptionally high levels of youth violence
compared to other regions [145]. The violence is generally rather evenly distributed
within countries and there is no sign of a higher level of fatal interpersonal violence
in the metropolitan areas than in the rest of the country [145]. Regarding intentional
self-injuries, approximately one million people worldwide commit suicide each year
and about 10 to 20 million people perform a suicide attempt [146]. The highest
suicide rates are found in Europe, while numerically most suicides occur in Asia.
China and India account for about 30% of all suicides in the world, and China has
numerically 30% more suicides than all suicides taken together in Europe [146].
Within Europe there are differences in rates of self-injury, with low rates in
southern Europe and high rates in northern Europe [147]. There are also large
regional differences within Sweden, with some counties (Västerbotten,
Västmanland, Sörmland, Östergötland, and Västra Götaland) showing rates nearly
twice as high among women aged 20-44 years as the counties with the lowest rates
(Jämtland, Västernorrland, Uppsala, Örebro, Halland , and Kalmar ). Among men
in the same age the highest rates were found in the counties Gästrikland, Dalarna,
Södermanland, Östergötland, and Gotland. In Scania the self-injury rates are in the
second quartile of the scale [144].
Factors related to risk
Sociodemographic factors
Hospitalisation due to assault-related injuries is more common among boys and men
than among girls and women, and the highest death rates are also found among men
[2]. On the whole, the risk of violence-related injury is highest among young people
and declines with age [2, 148]. Regarding intimate partner violence, death rates are
four to five times higher among women than among men [149]. Young single men
and women are more often victims of violence than non-single persons [144], and
young single women with children have also been found to have a high risk of a
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violence-related injury [148]. The rates of violence-related injuries are higher
among second-generation immigrants and among those born outside Europe.
Furthermore, some occupations have higher risks of violence-related injuries; these
include police officers, security guards, nurses, social workers, and bus drivers
[148]. Economic stress and lack of social support are also known risk factors for
assault-injuries [2]. National studies show that female gender, being adopted,
having one parent and obtaining social welfare are strong predictors of violencerelated injuries [150-152].
We mainly discuss determinants for non-fatal intentional self- injury since that was
one of the focus in this thesis. Intentional self-injury is more common among
females than among males, and also more common among young people than
among older people [135, 142, 143, 153-155]. Being single or divorced is
associated with self-injury [140, 156], as is being unemployed [157], obtaining
social welfare [153], and having economic problems in the family [143].
Alcohol and drug abuse
Approximately 50% of all violent crime has been related to alcohol [158]. It is not
only the alcohol and drug consumption of the perpetrator that has been investigated;
there are also several studies that show strong associations between alcohol
consumption, illicit drug use and being injured after an assault [24, 145]. Intentional
self-injury often co-occurs with some kind of substance abuse [21, 139, 159].
Traumatic experiences from childhood are considered to lead to disability in
emotional reactions, which can manifest itself in the form of alcohol or drug abuse
[160]. Many studies show that self-injury is associated with high-risk alcohol use
[21, 135, 141, 142, 161], and the same applies to drug abuse [141, 162, 163]. Even
smoking habits among youngsters have shown to be a risk factor for intentional
self-injury [135, 141, 142]. A Swedish study among girls with a history of alcohol
and drug abuse found that almost half of them had self-injured without the intention
of death [164]. The study also showed that alcohol was the most common, and
marijuana was the second most common drug used. Ethnicity has been discussed as
a risk factor for self-injury, and studies have shown that repeated self-injurious
behaviour is more common among white groups than among other ethnic groups
[165]. Self-injury rates have also been shown to be higher among indigenous people
[166].
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Medication
Most of the studies that have been done on medication and assault-related injuries
concern the perpetrator and not the victim of the assault. Psychotropic medication
has been discussed as a potential factor for assault-related injury, and studies have
shown a doubled risk for such injuries when using hypnotics/anxiolytics or
antidepressants [167].
Regarding self-injurious behavior, there are arguments that medication with
psychoactive drugs without management programs has a limited effect on reducing
such behavior [168], and it has even been suggested that some psychotropic drugs
might even increase the risk of a self-injuring act [161, 162]. There is even a debate
going on today regarding the possibility of an increased risk of self-injury, suicidal
thoughts and suicide attempts among young people using antidepressant medication
[21].
Psychological characteristics
A lot of risk factors for assault-related injury have been identified including school
dropout, contact with the justice system, involvement in fights and carrying
weapons [169, 170]. Furthermore, those who have been victims in community,
school or street violence are at increased risk for future injury [171, 172]. Several
studies have shown that persons with a history of self-injury are more impulsive in
their behaviour than the average [21, 143, 154, 173-180], and those with repeated
self-injuries are even more impulsive [173]. Furthermore, worries about sexual
orientation, eating disorders, feelings of powerlessness, social insecurity,
difficulties with emotional regulation, relation problems or traumatic experiences
from childhood such as neglect, assault or bullying [135, 181-190] are all associated
with an increased risk of intentional self-injury [141, 160, 184, 185]. A recent
systematic review including 90 studies showed that the median proportion of
repeated non-fatal self-injury was 1% at one year, and 23% in studies lasting longer
than four years [191]. Depression has been found to be associated with assaultrelated injury [192, 193] and it has been suggested that assessment of depressive
symptom among young people after an assault-injury might help to prevent future
risk behaviour and predict the risk of violent re-injury [194].
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Chronic disease
Individuals with psychosis have been found to have an increased risk of being
exposed to violence [195, 196]. Studies among battered women have also shown
that the risk for assault-injuries increases if the women have any psychiatric disease
is socially marginalized and/or living in poverty [195, 197]. This might be due to
behavioural signs related to psychiatric diseases such as limited perception of
reality, impaired capacity assessment, problems with social contacts and boundaries
[198].
Intentional self-injury is strongly associated with mental disorders such as
depression and anxiety [1, 21, 135, 139, 142, 162, 199], but this behavior often also
co-occurs with various other psychiatric diseases such as eating disorders, substance
abuse and personality disorders [1, 21, 139, 140, 154, 155, 199]. Higher rates of
self-injurious has been found among both adolescents and adult psychiatric patients
[39, 138, 200, 201]. Some researchers claim that repeated self-injury is basically an
impulse control disorder and should be diagnosed as an own syndrome in the
psychiatric diagnostic manual [154, 174-179]. Studies have also shown that adult
patients with self-injury behavior fulfilled the criteria for posttraumatic stress
disorder due to abuse and neglect in childhood [138], and borderline personality
disorders among adults is strongly associated with self-injury among adults [187,
202, 203].
Environmental factors
A lot of studies have shown that men and women are exposed to violence in
different places and in different situations [148, 204, 205]. Men often experience
violence in various public places such as streets, restaurants, and entertainment
venues [2, 144]. Women are often exposed to violence in their own or someone
else’s home [144], and in Sweden 60% of all victims of violence and threats in the
domestic environment are women [2]. Regarding the violence that occurs in
workplaces, some occupations have higher risks of violence-related injuries; these
occupations include police officers, security guards, nurses, social workers, and bus
drivers [148].
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Causal model
Research on risk factors for injuries in adults has mainly involved retrospective or
cross-sectional studies on patient populations [21, 37-39], or cross-sectional
epidemiological studies [140, 99, 220], while there are several population-based
prospective studies on risk factors for injuries in adolescence, mainly focusing on
sociodemographic factors in relation to intentional self-injuries and assault-related
injuries [55, 206]. Many of the studies on young people with self-injurious
behaviour are conducted as survey studies with focus on the importance of
psychosocial stressors, mental health, history of abuse, perinatal circumstances, and
social circumstances [165, 207]. However, few studies investigate predictors of
injuries over time in non-clinical samples in an adult population, and some of the
studies made lack information on risk factors that might act as confounding or
intermediate factors. For example, most epidemiological datasets with detailed data
on psychotropic drug use and diagnosed injuries do not have detailed
sociodemographic data or data on co-morbidity or drug abuse. In order to learn
more about the onset of an injury, it is important to investigate the role of various
factors in the same population. Most injuries are multicausal and encompass
biological, social, psychological, and environmental risk factors. Figure 2 shows a
simplified hypothetical model of factors that might affect the risk of having an
injury regardless of the damage caused. The onset of an injury is affected by
individual factors (e.g., age, sex, genetic disposition, lifestyle habits, health,
medication, psychological factors), group-related factors (e.g., social
support/network, family, socioeconomic position, culture/ethnicity), and
environmental factors (e.g., housing, physical environment, employment/working
environment). These factors are also interconnected; for example, socioeconomic
position is thought to be related to material conditions (e.g., housing, physical
environment) as well as the social environment (e.g., family and social support),
which in turn might affect lifestyle factors and psychosocial stressors to further
affect the onset of an injury. This thesis focuses on the importance of individual
factors (e.g., age, sex, lifestyle habits, health), and group-related factors (e.g.,
family, socioeconomic position, culture/ethnicity).
25
Birgit Modén
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Income
Medical care
and treatment
Gender
Psychological
characteristics
Genetics
Social support/
Environment
Education
Employment
Workplace
Physical
environment
Lifestyle
factors
Ethnicity and
culture
Health status
Age
Figure 2. A simplified hypothetical model of factors that might affect the risk of having an
injury.
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Aims
General aim
The general aim of this thesis was to examine potential risk factors for injuries in an
adult general population.
Specific aims
1. To investigate the associations between medication with psychotropic
drugs and injuries from two types of accidents (falling accidents and
transportation accidents) in the whole population aged 18 years and older
in the county of Scania, Sweden. (Paper I)
2. To investigate the association between medication with psychotropic
drugs and falling accidents in the whole population aged 65 years and
older in the county of Scania, Sweden. (Paper II)
3. To identify risk factors for assault-related injuries in the whole
population aged 18 to 64 years in the county of Scania, Sweden. (Paper
III)
4. To identify risk factors for non-fatal intentional self-injury in the whole
population aged 18 years and older in the county of Scania, Sweden.
(Paper IV)
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Material and methods
LOMAS
The studies included in this thesis uses data from the LOMAS database
(Longitudinal Multilevel Analysis in Scania). LOMAS is included in a research
project at the unit for Social Epidemiology (Principal investigator Prof. Juan Merlo)
which has been approved by the Regional Ethical Committee in South Sweden.
LOMAS consists of information on all individuals living in Scania, Sweden,
between 1968 and 2008, and was assembled with the permission and assistance of
Statistics Sweden, the Centre for Epidemiology at the Swedish National Board of
Health and Welfare, and Region Skåne. The personal identification number
assigned to each person in Sweden was substituted with an encrypted number by the
Swedish authorities, allowing linkage between different data sources.
One register included in the LOMAS database is the Swedish Medication Register,
which is administered by the Centre for Epidemiology at the Swedish National
Board of Health and Welfare and contains information on sales of prescribed
medication. This register includes information on the defined daily dose (DDD), the
anatomical therapeutic chemical classification (ATC) code and the date of
dispensation.
This thesis also uses information from several other registers included in the
LOMAS database: the register on the total population (RTB), the register of income
and taxation (IoT), and the longitudinal integration database for health insurance
and labour market studies (LISA). Information on age, gender, marital status, and
country of birth was retrieved from RTB; information on disposable income at the
family level was retrieved from IoT; and information on educational level was
retrieved from LISA. Information on hospital stays and outpatient specialised care
visits was collected from the Swedish Patient Register at the National Board of
Health and Welfare [208], and the Region Healthcare database at Region Skåne.
Table 1, on the next page, shows the study population, measures of exposure and
outcome in each paper
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Table 1. Study population, measures of exposure and outcome in each paper
Study
Study population
Measures of exposure
Outcome measure
I
936,449 men and
women aged ≥18 years
during 2007
Psychotropic drug use
Falling accidents
Transportation accidents
II
203,607 men and
women aged ≥65 years
during 2006
Psychotropic drug use
Falling accidents
III
728,490 men and
women aged 18 to 64
years during 2007
Psychotropic drug use
Marital status
Country of origin
Income
Education level
Age and sex
Previous disease/injury
Injuries from
assault
IV
906,051 men and
women aged ≥18 years
during 2007
Psychotropic drug use
Marital status
Country of origin
Income
Age and sex
Previous disease/injury
Intentional
self-injury
Scania
Scania is the southernmost part of Sweden and the third largest county in terms of
population size. It has about 1.2 million inhabitants corresponding to 13% of all
inhabitants in Sweden. Approximately 88% of Scanians live in urban areas. Scania
is situated close to Denmark and its capital Copenhagen, but is also close to
Germany and Poland. The proximity to the continent has both advantages and
disadvantages for Scania. Benefits include increased tourism receipts in Scania,
increased migration and an exchange of labour. The disadvantages include an
increase of smuggling of alcohol, drugs and illegal weapons into Scania and
Sweden [209]. The three largest cities in Scania are Malmö, Helsingborg, and Lund,
all of which are situated in the western part of the county. About 18% of the
inhabitants in Scania were born abroad, representing a total of 193 countries; most
immigrants come from Europe, the Nordic countries, and Middle Eastern countries
[210]. Scania has a favourable age structure compared to the rest of the country,
with a relatively young population. The educational level in Scania is high, and the
county ranks third in the country in terms of the percentage of inhabitants with
tertiary education. Employment rates vary widely throughout the county, with the
lowest employment rates in the south-west and the highest in south-east [210].
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Studied factors
Sociodemographic factors
The sociodemographic characteristics assessed were age, sex, income, educational
level, marital status, and country of origin. Income was defined as disposable family
income at the end of 2004, adjusted for family size and divided into tertiles. Marital
status was dichotomised into single (single, divorced, or widowed) vs. not single
(married, registered partnership, or cohabiting and having common children).
Unfortunately there is no register-based information available on those cohabiting
without common children i.e., these subjects are therefore classified as being single.
Educational level was divided into three categories: high educational level (≥ 12
years), middle educational level (10-11 years), and low educational level (≤ 9 years)
(Paper III). Country of origin was categorised using three different categorisations.
Paper I used the categories “born in Sweden” and “born abroad”, while Papers III
and IV used “born in Sweden”, “born in the Nordic countries”, “born in Europe”,
and “born outside Europe”. Finally, Paper II used four different groups based on the
financial status of the country of birth; these were taken from the World Bank
Classification of Country Economies, which is based on the gross national income
(GNI) per capita: high-income economies, upper-middle-income economies, lowermiddle-income economies, and low-income economies [211].
Previous disease
Previous disease (during 2004- 2006) was categorised in different diagnosis groups
using the 10th revision of the International Statistical Classification of Diseases and
Related Health Problems (ICD-10) [41]. Table 2 shows the diagnosis groups used in
the various papers. Information on previous disease was collected from the Swedish
Patient Register with national coverage.
30
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Table 2. Diagnosis groups used in the various papers
ICD10-code
Diseases of the nervous system
Diseases of the genitourinary system
Ischaemic heart diseases
Hypertensive diseases
Other forms of heart disease
Cerebrovascular diseases
Diseases of the respiratory system
Diseases of the digestive system
Diabetes mellitus
Neoplasms
Arthrosis
Hip fracture
Schizophrenia and other mental disorders
Mood (affective) disorders
Inflammatory diseases of the musculoskeletal system
Transportation accident
Falling accident
Injury from assault
Intentional self-injury
Diseases related to alcohol abuse
Diseases related to drug abuse
G00-G99
N00-N99
I20-I25
I10-I15
I30-I52
I60-I69
J00-J99
K00-K93
E10-E14
C00-D48
M15-M19
S720- S722
F00-F09, F20-F29
F30-F39
L405, M00-M03, M05-M11, M12, M315, M32- M34, M35.3
V01-V99
W00-W19
X85-Y09
X60_X84
F10, G31.2, G62.1, I42.6, K29.2, K70, T51+X45, T51+X65
F12, F14, F15, F16, F18, F19
Paper
I - IV
II
I, II
II
II
I, II
II
II
I, II, III
I, II
II
II
II, III, IV
I - IV
II
I
I, II
III, IV
IV
III, IV
III, IV
Psychotropic drug use
Information on exposure to psychotropic medication was collected from the
Swedish Medication Register [212]. This register contains information on defined
daily doses (DDD) and the anatomical therapeutic chemical classification (ATC)
code. We investigated four main groups of drugs: opioids (ATC code: NO2A),
anxiolytics (ATC code: NO5B), hypnotics and sedatives (ATC code: NO5C) and
antidepressants (ATC code: NO6A). Anxiolytics and hypnotics/sedatives were
combined into one group.
In papers I and IV, psychotropic drug use (DDD) was divided into tertiles. In those
aged 18-34 years the tertiles were 1-20 DDD, 21-250 DDD, and >250 DDD; in
those aged 35-64 years they were 1-40 DDD, 41-367 DDD, and >367 DDD; and in
those aged 65 years or more they were 1-90 DDD, 91-453 DDD, and >453 DDD. In
paper II, exposure to psychotropic drugs was classified into four different groups
based on time of exposure: exposed 0-7 days before the fall (P1), exposed 8-85 days
before the fall (P2), exposed 0-85 days before the fall (P1&P2), and not exposed
during the 85 days before the fall. In each of these categories, exposure was defined
as both having collected the drug from the pharmacy and having DDD covering the
relevant period only (so, for example, those included in group P1 were not exposed
during days 8-85, those included in group P2 were not exposed during days 0-7, and
those included in the non-exposed group either did not collect the drug or did not
have DDD covering this period). In paper III, DDD was divided into tertiles for the
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Birgit Modén
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total age group (18-64 years): 1-33 in the first tertile, 34 -332 in the second tertile,
and ≥332 in the third tertile.
Outcomes
We used ICD-10 [41] diagnosis codes to identify accidents and injuries in the
Region Healthcare database at Region Skåne: falling accidents (ICD code: W00W019) in Papers I and II, transportation accidents (ICD code: V01-V99) in Paper I,
assault-related injury (ICD code: X85-Y09) in Paper III, and intentional self-injury
(ICD code: X60-X84) in Paper IV. If more than one accident/injury in each
category occurred during the year studied, only the first occasion was used in the
analyses. The Region Healthcare database at Region Skåne provides the national
Swedish Patient Register with information on diagnoses codes for Scania.
32
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Statistics
Paper I
Logistic regression analyses were used to estimate odds ratios (ORs) for use of
psychotropic drugs in relation to falling accidents and transportation accidents,
respectively. The results were consistently stratified by sex and by three age groups:
18-34 years, 35-64 years, and ≥65 years. Cases were defined as injuries from the
relevant type of accident during 2007. If more than one accident occurred, only the
first occasion was selected in each category. The models were adjusted for marital
status, country of origin, income, previous disease, and previous accidents.
Statistical analyses were performed with PASW Statistics 18.
Paper II
In order to estimate the association between exposure to psychotropic drugs and
falling accidents, a nested case-control study with detailed information on temporal
exposure to psychotropic medication was performed with propensity score matching
(propensity score based on previous disease) to reduce the risk of confounding.
Case-control pairs were used in a conditional logistical regression analysis. The
cases were defined as injuries from falling accidents during 2006. Cases
(individuals registered with a falling accident) and controls were matched on age,
sex, date of the falling accident, living area and propensity score (based on previous
disease). The controls were selected with replacement from the population of all
individuals without a fall. Matching controls were found for 88% of the cases (n =
10 482). The tolerance for matching was set to 1%. We adjusted the models for
marital status, country of origin, income, and previous falls. Statistical analyses
were performed with PASW Statistics 19.
Calculation of propensity score
Using a logistic regression on the whole cohort representing the base population of
the nested case control-study, we obtained the probability (i.e., propensity of using
psychotropic drugs as a function of the variables on previous disease). We
performed a stepwise logistic regression on the whole Scanian population aged 65
or over, and modelled the probability of being a user of psychiatric drugs as a
function of previous diseases (over two years). Predictors with a p-value of less
than 0.10 were retained in the model. The use of psychotropic drugs (ATC codes:
NO2A, NO5A, NO5B, NO5C, and NO6A) was measured during the period of 25 31 December 2005 by looking at the last dispensation at the pharmacy and the
number of DDDs; for example, if patient X collected 15 DDDs of a psychotropic
33
Birgit Modén
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drug on 20 December, then this patient was considered as a user of psychotropic
drugs during the relevant period. For each individual, a propensity score for using a
psychiatric drug was calculated for each day during 2006 based on two years’ worth
of information on previous diseases.
Paper III
Logistic regression analyses were used to estimate ORs for sociodemographic
factors, previous disease, previous assault-related injury, substance abuse, and use
of psychotropic drugs in relation to injuries from assault. The results were stratified
by sex. Cases were defined as injuries from assault during 2007. The logistic
regression models were mutually adjusted. We also performed age- and sexadjusted logistic regression analyses to investigate factors associated with repeated
assault-related injuries, defined as having had an assault injury during 2004-2006
and a new injury from assault during 2007. Statistical analyses were performed with
PASW Statistics 19.
Paper IV
Logistic regression analyses were used to estimate ORs for diagnosed intentional
self-injury during 2007 in relation to sociodemographic factors, previous disease,
previous assault-related injury, substance abuse, and use of psychotropic drugs,
among subjects with no diagnosed intentional self-injury in the three-year period
before the baseline. The logistic regression models were mutually adjusted and the
results presented both for all ages taken together and stratified by age groups as well
as stratified by sex. We also performed mutually adjusted logistic regression
analyses to investigate factors associated with repeated episodes of intentional selfinjury, defined as having had a diagnosed intentional self-injury during 2004-2006
and a new episode of self-injury during 2007. Statistical analyses were performed
with PASW Statistics 19.
34
Birgit Modén
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Results and conclusions
Paper I:
Psychotropic drugs and accidents in Scania, Sweden
Aim
To investigate the associations between medication with psychotropic drugs and
injuries from two types of accidents (falling accidents and transportation accidents)
in the whole population aged 18 years and older in the county of Scania, Sweden.
Results
Figure 3 shows the psychotropic drug use in Scania, 1.5 years before baseline (1st
January 2007), divided by age group and drug type: opioids (NO2A),
anxiolytics/hypnotics/sedatives (NO5B+NO5C), and antidepressants (NO6A). The
use of psychotropic drugs increased with age among both men and women. Women
used psychotropic drugs to a greater extent than men; this was true in all age groups
and for all drug types.
45
opioids
40
anxiolytics/hypnotics and sedatives
Percent (%)
35
antidepressants
30
25
20
15
10
5
0
18-34 yrs
35-64 yrs
65+
18-34 yrs
35-64 yrs
65+
Figure 3. Psychotropic drug use in Scania, 1.5 years before baseline, divided by age
group and drug type: opioids (NO2A), anxiolytics/hypnotics/sedatives (NO5B+NO5C),
and antidepressants (NO6A).
35
Birgit Modén
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Falling accidents were more common among young men than among young women,
while the pattern was reversed in the older age groups. Men dominated the
transportation accidents in all age groups. The use of psychotropic drugs was also
associated with increased odds of falling accidents in all age groups, but a doseresponse relationship was found only among those aged 65 or over (in both men and
women), even after adjustment for marital status, country of origin, income, and
previous disease/injury (Figure 4). Among men aged 65 or over, the use of
psychotropic drugs was associated with ORs for men of 1.39 (95% CI: 1.26-1.53)
for the first tertile of DDD, 1.44 (95% CI: 1.30-1.59) for the second tertile, and 1.69
(95% CI: 1.53-1.87) for the third tertile. Among women aged 65 or over the
corresponding ORs were 1.31 (95% CI: 1.22-1.40) for the first tertile, 1.35 (95%
CI: 1.26-1.44) for the second tertile, and 1.69 (95% CI: 1.58-1.80) for the third
tertile. In each age group similar patterns of associations remained even after
classification of psychotropic drugs into different sub-groups (opioids,
anxiolytics/hypnotics/sedatives, and antidepressants). The associations did not
change after exclusion of those who died or moved outside Scania during follow-up
(data not shown).
OR
MEN
3
WOMEN
OR
3
2,5
2,5
2
2
1,5
1,5
1
1
0,5
0,5
0
0
18-34 years
35-64 years
18-34 years
≥65 years
35-64 years
≥65 years
Figure 4. Adjusted ORs and 95% CIs for falling accidents in relation to the use of at least
one psychotropic drug during 1.5 years before baseline, divided by age group and DDD
tertile with those not exposed as a reference.
Having had previous falls, being born in Sweden, and having a neurological disease
were generally associated with increased odds of a falling accident in both men and
women. Those with previous falls showed more than doubled odds of a new falling
accident during follow-up, in all age groups and among both men and women.
Use of psychotropic drugs was associated with increased odds of transportation
accidents in the 18-34 and 35-64 age groups, but not among the elderly even after
adjustment for marital status, country of origin, income, and previous disease/injury.
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Birgit Modén
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The ORs for men aged 18-34 were 2.03 (95% CI: 1.62-2.54) for the first tertile of
DDD, 2.31 (95% CI: 1.81-2.94) for the second tertile, and 2.11 (95% CI: 1.58-2.83)
for the third tertile. Among women aged 18-34, the corresponding ORs were 2.00
(95% CI: 1.57-2.54) for the first tertile, 1.91 (95% CI: 1.48-2.46) for the second
tertile, and 1.70 (95% CI: 1.30-2.26) for the third tertile. There was a dose-response
relationship only among women aged 35-64 (Figure 5). Classification of
psychotropic drugs into different sub-groups (opioids, anxiolytics/hypnotics/
sedatives, and antidepressants) showed similar patterns of associations as for all
psychotropic drugs taken together. Moreover, excluding those who died or moved
outside Scania during follow-up did not change the associations (data not shown).
There were only small sociodemographic differences between those who had a
transportation accident during the observation period and those who did not, but
having had a transportation accident during the three years before the observation
period was associated with a more than five times increased odds of having a new
transportation accident in all age groups in both men and women.
OR
MEN
WOMEN
OR
3,5
3,5
3
3
2,5
2,5
2
2
1,5
1,5
1
1
0,5
0,5
0
0
18-34 years
35-64 years
≥65 years
18-34 years
35-64 years
≥65 years
Figure 5. Adjusted ORs and 95% CIs for transportation accidents in relation to the use of
at least one psychotropic drug during 1.5 years before baseline, divided by age group
and DDD tertile with those not exposed as a reference.
Conclusions
There were nearly consistent associations between psychotropic drug use and future
falling accidents and transportation accidents in all age groups, even after
adjustment for previous accidents, previous disease, and sociodemographic
variables.
37
Birgit Modén
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Paper II:
Psychotropic drugs and falling accidents among the
elderly: a nested case-control study in the whole
population of Scania, Sweden
Aim
To investigate the association between medication with psychotropic drugs and
falling accidents in the whole population aged 65 years and older in the county of
Scania, Sweden.
Result
This nested case-control study, with cases and controls matched on age, sex, date,
living area, and propensity score (based on previous disease), showed that the use of
psychotropic drugs within three months before the fall was associated with more
than doubled odds for a falling accident among both men (OR: 2.14; 95% CI:1.872.44) and women (OR: 2.21; 95% CI: 2.04-2.39) after adjustment for marital status,
country of origin, income, and previous falls during the past year. Furthermore, use
of psychotropic drugs during the week before the accident was associated with even
higher odds for a falling accident among both men (OR: 5.61; 95% CI: 2.54-12.41)
and women (OR: 3.40; 95% CI: 2.24-5.17) (Figure 6). A similar pattern of
association was seen for the individual sub-groups of psychotropic drugs (opioids,
anxiolytics/hypnotics/sedatives, and antidepressants. Use of opioids during the
week prior to the accident only (i.e. with the fall occurring within a week of
initiating therapy) was associated with more than five times higher odds of a falling
accident among both men and women.
The results further showed that elderly people who were single had higher odds of a
falling accident than those who were not single and that men and women with
previous falls had fourfold increased odds of a new falling accident.
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Birgit Modén
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OR
14
13
12
11
10
9
8
7
6
5
4
3
2
1
0
P1
P2
P3
P1
MÄN
P2
P3
KVINNOR
Figure 6. Adjusted odds ratios and 95% confidence intervals for falling accidents in
relation to the use of at least one psychotropic drug. P1= exposed at the time of the fall
and 1-7 days before the falling accident; P2=exposed 8-85 days before the falling
accident; P1+P2=exposed at the time of the fall and 1-85 days before the falling accident.
The non-exposed group was used as the reference.
Conclusions
This study showed that the use of psychotropic drugs, especially opioids and antidepressants, was associated with higher odds for a falling accident among both men
and women aged 65 years and older. This effect seemed to be largest immediately
after initiating therapy.
39
Birgit Modén
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Paper III:
Risk factors for assault-related injuries: A total
population-based study
Aim
To investigate risk factors for assault-related injuries in the whole population aged
18 to 64 years in the county of Scania, Sweden.
Results
Sociodemographic factors such as being young, being single, having a low income,
having a low educational level, and being born outside the Nordic countries were all
associated with increased odds of being injured from assault during the observation
period (year 2007), in a mutually adjusted logistic regression model (Table 3).
Depression was the only psychiatric disease showing an association with assaultrelated injuries in both men and women, while there were strong associations with
alcohol abuse, psychotropic drug use, and previous assault-related injuries.
Psychotropic drug use (opioids, anxiolytics/ hypnotics/sedatives and
antidepressants) during the 1.5 year before baseline (1st January 2007) showed a
clear dose-response relationship with assault-related injuries in women, but no such
pattern was seen in men during the observation period.
Having repeated episodes of assault-related injuries (selecting those with previously
diagnosed assault-related injury during 2004 to 2006 and looking at factors
associated with a new episode of diagnosed assault-related injury during 2007) were
related to factors such as being single, having depression, diseases of the nervous
system, psychotropic drug use, and diseases related to alcohol abuse.
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Birgit Modén
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Table 3. Mutually adjusted ORs and 95% CIs for assault-related injuries in the total
population of Scania, Sweden, aged 18-64 years, in relation to sociodemographic
factors, previous disease, and psychotropic drug use (n=728 490)
Men
Marital status
Single (yes vs no)
Age group
55-64 yrs
45-54 yrs
35-44 yrs
25-34 yrs
18-24 yrs
Country of origin
Sweden
Nordic countries
Europe
Outside Europe
Income
High
Middle
Low
Education level
High
Middle
Low
Previous disease (yes vs no) *
Previous assault-related injuries
Diseases of the nervous system
Diabetes mellitus
Psychosis
Depression
Diseases related to alcohol abuse
Diseases related to drug abuse
Psychotropic drug †
Not exposed
First tertile
Second tertile
Third tertile
Women
Mutually adj OR
95% CI
Mutually adj OR
95% CI
2.63
(2.09, 3.31)
1.88
(1.39, 2.54)
1.00
2.83
3.68
6.12
14.90
(Ref)
(1.91, 4.20)
(2.51, 5.40)
(4.19, 8.94)
(10.21, 21.74)
1.00
1.90
3.09
3.96
7.00
(Ref)
(1.20, 3.03)
(2.00, 4.79)
(2.53, 6.20)
(4.50, 10.89)
1.00
0.85
1.68
1.97
(Ref)
(0.49, 1.48)
(1.35, 2 08)
(1.61, 2.40)
1.00
1.13
1.74
1.70
(Ref)
(0.56, 2.31)
(1.26, 2.40)
(1.23, 2.36)
1.00
1.19
1.38
(Ref)
(1.00, 1.42)
(1.16, 1.64)
1.00
1.63
2.55
(Ref)
(1.15, 2.30)
(1.84, 3.53)
1.00
1.81
1.72
(Ref)
(1.51, 2.16)
(1.47, 2.01)
1.00
1.30
2.67
(Ref)
(0.95, 1.77)
(2.09, 3.40)
6.50
1.28
0.86
1.12
1.44
3.41
1.74
(5.17, 8.18)
(0.95, 1.72)
(0.51, 1.45)
(0.67, 1.89)
(1.07, 1.94)
(2.23, 5.23)
(0.95, 3.19)
10.59
1.80
0.94
1.19
1.43
6.82
2.35
(7.26, 15.45)
(1.32, 2.46)
(0.46, 1.94)
(0.61, 2.31)
(1.04, 1.97)
(4.05, 11.47)
(1.12, 4.93)
1.00
1.95
1.73
1.27
(Ref)
(1.56, 2.44)
(1.31, 2.27)
(0.91, 1.76)
1.00
1.63
1.91
2.23
(Ref)
(1.13, 2.37)
(1.35, 2.70)
(1.58, 3.13)
* Previous disease during 2004-2006
† Use of at least one psychotropic drug, that is NO2A, NO5A, NO5B, NO5C and/or NO6A during
a period of 1,5 years before baseline
Conclusions
Sociodemographic factors such as being young, being single, having a low income,
having a low educational level, and being born outside the Nordic countries were
associated with increased odds of being injured from assault in both men and
women. Depression and diseases related to alcohol and drug abuse were also
associated with assault injury. Moreover, using psychotropic drugs or having had a
previous assault-related injury during the three years before the observation period
were associated with highly increased odds of injuries from assault in both men and
women.
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Paper IV:
Risk factors for intentional self-injury: A total
population-based study
Aim
To identify risk factors for non-fatal intentional self-injury in the whole population
aged 18 years and more in the county of Scania, Sweden. Furthermore, groups at
risk of repeat episodes of self-injury will be identified.
Results
Sociodemographic factors such as being single, young or middle-aged, having a low
income, and being born in Nordic countries were associated with higher odds of
intentional self-injury during the observation period (year 2007) in both men and
women (Table 4). Diseases of the nervous system, psychiatric disease, substance
abuse, and previous assault-related injury were also strongly associated with
intentional self-injury during the observation period. Psychotropic drug use during
the 1.5 year before baseline (1st January 2007) showed a clear dose-response
relationship with both diagnosed intentional self-injury during follow-up and repeat
episodes of intentional self-injury. There were similar patterns of associations
between the studied factors and intentional self-injury in men and women.
However, drug abuse and being single showed statistically significant associations
with self-injury only in men, but not in women. The opposite pattern was seen for
previously diagnosed assault-injury and psychosis.
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Table 4. Mutally adjusted ORs and 95% CIs of diagnosed intentional self-injury during
2007 among those with no previously diagnosed intentional self-injury during 2004-2006
a, and among those with previously diagnosed intentional self-injury during 2004-2006 b,
respectively.
Sex
Women (yes vs no)
Marital status
Single (yes vs no)
Age group
65+ yrs
35-64 yrs
18-34 yrs
Country of origin
Sweden
Nordic countries
Europe
Outside Europe
Income
High
Middle
Low
Previous disease (yes vs no) c
Previous assault-related injury
Diseases of the nervous system
Psychosis
Depression
Diseases related to alcohol abuse
Diseases related to drug abuse
Psychotropic drug d
Not exposed
First tertile
Second tertile
Third tertile
a
b
Intentional self-injury 2007
No intentional self-injury 2004-2006
Intentional self-injury 2007
Intentional self-injury 2004-2006
Adj ORs
95% CI
Adj ORs
95% CI
1.09
(0.94, 1.26)
1.35
(0.99, 1.84)
1.27
(1.05, 1.54)
1.00
(0.65, 1.55)
1.00
2.49
6.47
(Ref)
(1.96, 3.16)
(5.04, 8.30)
1.00
3.62
4.45
(Ref)
(1.72, 7.60)
(2.09, 9.49)
1.00
1.38
0.81
0.84
(Ref)
(1.07, 1.77)
(0.60, 1.08)
(0.53, 1.33)
1.00
0.40
0.51
1.44
(Ref)
(0.19, 0.83)
(0.26, 0.98)
(0.66, 3.16)
1.00
1.34
1.66
(Ref)
(1.10, 1.64)
(1.34, 2.06)
1.00
1.53
2.19
(Ref)
(0.92, 2.52)
(1.35, 3.56)
1.81
1.56
1.60
2.78
5.13
5.57
(1.09, 2.98)
(1.27, 1.92)
(1.20, 2.12)
(2.33, 3.33)
(3.62, 7.28)
(3.66, 8.48)
1.54
1.15
1.07
1.18
1.59
1.94
(0.90, 2.62)
(0.79, 1.67)
(0.70, 1.63)
(0.87, 1.61)
(1.10, 2.27)
(1.27, 2.96)
1.00
2.41
4.11
7.45
(Ref)
(1.85, 3.15)
(3.28, 5.17)
(6.06, 9.16)
1.00
1.50
1.91
2.55
(Ref)
(0.78, 2.92)
(1.15, 3.18)
(1.63, 3.99)
a
No previous intentional self-injury; i.e., no diagnosed intentional self-injury (X60-X84) during 2004-2006
Repeated episodes of intentional self-injury; i.e., diagnosed intentional self-injury (X60-X84) during the period of 2004-2006 and 2007
c
Previous disease during 2004-2006
d
Use of at least one psychotropic drug, that is NO2A, NO5A, NO5B, NO5C and/or NO6A during a period of 1,5 years before baseline
b
Conclusions
The odds of having a diagnosis of intentional self-injury was related to being single,
young or middle age, having low income, and being born in the Nordic countries.
Diseases of the nervous system, psychiatric diseases, substance abuse and previous
assault injury were also strongly associated with future intentional self-injury. The
use of psychotropic drugs (i.e., opioids, antidepressants, anxiolytics and
hypnotics/sedatives) showed a clear dose-response relationship with diagnosed
intentional self-injury during follow-up and also with having repeat episodes of
intentional self-injury.
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General discussion
The main purpose of this thesis was to study risk factors for injuries and specifically
to investigate the role of psychotropic drug use as a risk factor for unintentional and
intentional injuries. The results of Paper I-IV support the notion that psychotropic
drug use (i.e., opioids, antidepressants, anxiolytics and hypnotics/sedatives) is
associated with increased odds of unintentional injuries such as falling and
transportation accidents as well as intentional injuries, i.e., assault-related injury and
self-injury among both men and women. The use of psychotropic drugs also showed
dose-response relationships with some injury groups, i.e., falling accidents,
diagnosed assault-related injury, and intentional self-injury, although not always
consistent across sex and age groups. Furthermore, the results of Paper I-IV showed
that sociodemographic factors such as age, sex, marital status, country of birth,
educational level and income as well as previous disease (e.g. depression,
psychosis, previous fall, diseases from the nervous system, ischemic heart disease,
cerebrovascular disease, diabetes mellitus, neoplasm, substance abuse) are related to
future injuries. The studied factors are illustrated in Figure 7 and the results and
some methodological issues are discussed in the next section.
Medical care
and treatment
Psychotropic
drug use
Income
Gender
Psychological
characteristics
Genetics
Social support/
Environment
Marital status
Education
Employment
Workplace
Physical
environment
Lifestyle
factors
Ethnicity and
culture
Health status
Previous disease
Age
Figure 7. A simplified hypothetical model of the factors studied in this thesis (marked in
grey) that was shown to affect the odds of having an injury.
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Findings
Psychotropic drug use and accidents
The results in Paper I showed that the use of psychotropic drugs was associated
with increased odds of transportation accidents among those aged 18-34 years and
35-64 years, respectively, and with falling accidents in all age groups (i.e., 18-34
years, 35-64 years and 65 years or more) in both men and women. Similarly, the
nested case-control study in an elderly population (with cases and controls matched
on age, sex, date of the falling accident, living area and propensity score (based on
previous disease)) described in Paper II showed that the use of psychotropic drugs
within three months before a falling accident was associated with more than
doubled odds for such accident among both men and women after adjustment for
marital status, country of origin, income, and previous falls during the past year.
This effect was the largest immediately after initiating therapy. Regarding
transportation accidents the found results are in line with the results from previous
studies, although they often concentrate on the use of one specific drug such as
benzodiazepines, antidepressants or lithium [76, 84, 86, 87, 89, 90, 92] and focus on
short term use. In a study by Neutel it was shown that using benzodiazepines during
a 4 week period created a four times higher odds for a transportation accident than
among non-users [84]. Similar findings were seen in a study by Gibson et al. [91].
In a Norwegian study by Engeland et al. there was a more than doubled risk of
being involved in a traffic accident during the first week after dispensation of a
psychotropic drug [88]. Such an association could be due to lack of adaptation to
the side effects of medication during the first days of treatment [111, 128, 213].
There are several recent studies indicating that psychotropic drugs have the
potential to impair driving ability and increase the risk of being involved in a
transportation accident [76, 95-97]. The results in Papers I and II showed generally
small sociodemographic differences between those who had a transportation
accident and those who had not, while other studies have shown such differences
[63, 214]. Regarding falling accidents, there are few population-based studies on
the association with psychotropic drug use, and most of these studies have hip
fracture as an outcome [12, 215-217]. However, similar findings as those presented
in Papers I and II have been seen in other population-based studies [8, 12, 98, 218].
For example, a meta-analysis by Woolcott et al. and a recent review by Bloch et al.
showed that the use of psychotropic drugs was associated with an increased risk of
falls in elderly people [14, 105]. Being born in Sweden was associated with
increased odds of having a falling accident. Similar results have been found in other
Swedish studies [219].
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Risk factors for assault-related injuries
The results in Paper III showed that injuries from assault were associated with
sociodemographic factors, previous disease/injury and the use of psychotropic
drugs, even after mutual adjustment. Both among men and among women factors
such as being young, being single, having low income, being born outside the
Nordic countries, having had a depression or diseases related to alcohol abuse were
associated with higher odds for an assault-related injury. The only mental health
problem that showed a consistent association with injuries from assault was
depression, a result also seen in other studies [205]. In a Canadian report on
“Violence and Trauma in the Lives of Women with Serious Mental Illness” by
Morrow it was argued that mental illness is a risk factor for abuse [197].
Furthermore, there are arguments in the same report that trauma symptoms
sometimes are misdiagnosed as mental illness, and that depression could be a result
of a violent event rather than opposite [194]. We have tried to reduce such an effect
by using a longitudinal approach and also excluding those with previous assaultrelated injuries in some of the analyses. A similar reasoning could be applied with
regard to the use of psychotropic drugs. Compared to the knowledge on alcohol and
drug abuse, there is little knowledge on medical drugs affecting victims of an
assault. Earlier studies have shown that battered women reported higher levels of
psychiatric symptoms and psychotropic drug use [65, 145]. However, it can be hard
to know if the assault is an effect of the use of psychotropic drugs or vice versa. The
results presented in paper III further showed associations between alcohol and drug
consumption and injuries from assault. Earlier studies have shown that it is not only
the alcohol and drug consumption of the perpetrator that matters; there are also
several studies that show strong associations between alcohol consumption, illicit
drug use and being injured after an assault [24, 145].
Risk factors for intentional self-injuries
The results in Paper IV showed associations between sociodemographic factors
such as being single, being born in the Nordic countries, having low income and
being young or middle aged and diagnosed intentional self-injury during the
observation period. Our study generally showed stronger associations between
sociodemographic factors and intentional self-injury than other population-based
studies in the field [138, 140, 159, 227]. This might be due to an inclusion of more
severe non-fatal intentional self-injuries since we included only hospitalized and
outpatient specialized care visits. The results in Paper IV further showed that
diagnosed intentional self-injury was related to presence of neurologic disease (e.g.,
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Birgit Modén
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degenerative disorders, Mb Parkinson, epilepsy), psychiatric disease (i.e.,
depression and psychosis) and substance abuse. Earlier studies have shown that
self-injury often co-occur with various neurologic and psychiatric diseases such as
degenerative disorders, eating disorders, depression, substance abuse, and several
personality disorders [21, 159]. It has also been proposed that similar psychological
processes may underlie the behaviours of self-injury and substance abuse since both
involve causing physiological harm to the body [140]. Our study further showed
that using psychotropic drugs (i.e., opioids, antidepressants, anxiolytics and
hypnotics/sedatives) during a 1.5 year-period before baseline was associated with
diagnosed intentional self-injury during the observation time. The results showed a
clear dose-response relationship among self-injurers so that a higher use of
psychotropic drugs was associated with higher odds of intentional self-injury during
follow-up and also higher odds of having repeated episodes of intentional selfinjuries. Earlier studies have shown that psychotropic medication might have
limited effects on this kind of behaviour and that some psychotropic drugs even
might increase the risk of suicide and self-harm [161, 162, 168]. Psychotropic drug
use, alcohol and illicit drug consumption might increase the risk of intentional selfinjury through an effect on impulse and emotion control and through negative
effects on cognition and alertness, effects that has been demonstrated in previous
studies [21, 161]. In the present study we found that drug abuse only showed
statistically significant associations with self-injury among men, while the opposite
pattern was found regarding psychosis and previously diagnosed assault-injury. This
finding is supported by previous studies [1, 181, 228] that have demonstrated
increased odds for intentional self-injury after traumatic experiences such as assault
and bullying. As mentioned before the result also showed that those diagnosed with
self-injury in the three-year period before baseline had greatly increased odds of
having a new self-injury during follow-up. Such repeated self-injury episodes was
more than twice as common among subjects born in Sweden than among those born
outside the country. A study by WHO/EURO [147] also showed huge differences in
rates of self-injury, with the highest rates in northern Europe.
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Methodological issues
Study design
Paper I, III and IV were longitudinal in that sense that the levels of the independent
variables were measured before the onset of the injury allowing the observation of
the temporal order of events. Longitudinal studies are often used to uncover
predictors of certain diseases with the advantage that the temporal sequencing
between an independent variable and the outcome measure is more evident than in a
cross-sectional study [229]. For example, in Paper I exposure to psychotropic drugs
was assessed during an 18-months period before baseline (1st January 2007), while
the outcome variables (falling and transportation accidents, respectively) were
measured during 2007. Paper II was a nested case-control study (i.e., the subjects
were sampled from an epidemiological cohort where the cases were identified and a
number of matched controls were selected among those without a falling accident
during the observation period. Case-control studies are used to identify factors that
may contribute to a medical condition by comparing subjects who have that
condition/disease (the 'cases') with patients who do not have the condition/disease
but are otherwise similar (the 'controls') [230]. In Paper II, all cases (individuals
registered with a falling accident) were matched with individuals without a fall, but
with the same age, gender, date, municipality and propensity of psychotropic drug
use for the day of the fall based on the health status. Advantages with nested casecontrol studies are that they do not require a long follow-up period and they are
cost-efficient.
Propensity score
A propensity score is the probability of a person being assigned to a particular
condition in a study given a set of known covariates. Propensity scores are used to
reduce bias by equating groups based on these covariates and can be used as a
complement to multivariable regression models [231, 232]. For example, in Paper II
we performed a stepwise logistic regression on the whole cohort representing the
base population of the nested case control study and obtained the probability (i.e.,
propensity of using psychotropic drugs) as a function of numerous variables on
previous disease.
Propensity scores can be included as a covariate in multivariable logistic regression
models. It can also be used in stratified analyses using propensity score as a
stratifying variable or for matching subjects [232]. Propensity score was one of the
variables used for matching cases and controls in Paper II. For 88% of cases (n=10
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Birgit Modén
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482), matching controls were found. By matching on the propensity score the aim
was to reduce the potential confounding effect based on differences in previous
disease. In the ideal situation, the propensity of using psychoactive drugs should be
the same for cases as for controls. However, since users of psychoactive drugs are
more likely to suffer from diseases that increase the risk of falling accidents, the
association between psychoactive drugs and falling accidents is confounded by the
prevalence of such diseases. By matching for the propensity score, we reduced this
confounding effect. The use of such propensity score matching reduced the number
of covariates included in the analyses [231]. The advantages with propensity score
matching includes reduced biased and better comparability between cases and
controls. Ordinary model adjustments with regression analysis can be extremely
unreliable when the treatment groups are far apart on covariates. Some of the
drawbacks with propensity score matching is the fact that weak confounders (e.g.,
factors with moderate associations with treatment and weak associations with the
outcome) might have similar coefficients in the calculation of the propensity score
as stronger confounders [231], and the fact that propensity score matching generally
requires a large number of controls to select from to reduce the number of subjects
that are unable to be matched [231, 232].
Validity of measures of outcome variables
In Sweden, the external cause of the accident should always be reported in
connection with the diagnosis of an injury or accident. A report from the National
Board of Health and Welfare on the quality and content of the Swedish Patient
Register from 2008 showed good coverage in Scania (99 %) [3]. However, we do
not have any specific information on the validity of the diagnoses of external causes
of an accident. For example, it might be that some unintentional self-injuries are
incorrectly diagnosed as intentional self-injury and there might also be other errors.
The Swedish report mentioned above further showed that about 15 % of the
diagnoses involving hospital care are later found to be incorrect, irrespective of
speciality. Thus, there might be some misclassification of the outcome variable.
Furthermore, the information on outcome measures of injuries in the four papers in
this thesis was based on hospital stays and outpatient specialised care visits. While,
as mentioned above, there is a high coverage in the registration among persons
admitted to hospitals in Scania [233], the registration of persons visiting outpatient
specialised care might have a lower degree of coverage. Unfortunately, we lack
specific information on such coverage for Scania. Another limitation with the
studies included in this thesis is that fatal cases not reaching hospital were not
included in the outcome variables. Furthermore, the classification of transportation
accidents used in Paper I include passengers in motor vehicles and not only drivers
49
Birgit Modén
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and it also includes accidents among other road users such as pedestrians in
collision with a motor vehicle and bicyclists. These aspects might most likely lead
to a dilution of the true associations. Last, not all injuries require medical care and
such injuries are not included in our data. Such injuries are by far the most common
types of injuries [1].
Validity of psychotropic drug use
Information on individual medication use was collected from the Swedish
Medication Register at the National Board of Health and Welfare [212]. This
database includes information on the defined daily dose (DDD), the anatomical
therapeutic chemical classification (ATC) code and the date of dispensation with
good coverage [234]. However, we only had proxy information about the
consumption of psychotropic drugs, that is, we only had information that the person
had collected the drug at the pharmacy. Furthermore, we assess use of psychotropic
drugs one and a half year before baseline with possibilities of change in exposure
over time before the accident/intentional injury. However, there is no reason to
believe that this potential misclassification would differ between those having had
an accident/intentional injury and those who did not, thus leading to attenuation of
the true associations between use of psychotropic drugs and injuries from
accidents/intentional injuries towards the null.
Representativity
An important strength of our study is that the data covers the total general
population in Scania, which minimizes the risk for selection bias. We have registerbased data from registers with generally good coverage (e.g., the Swedish
Medication Register, the Swedish Patient Register, the Region Skåne Healthcare
database, LISA, the IoT-register, and the register on the whole population (RTB))
for the use of psychotropic drugs, sociodemographic factors, previous disease as
well as on injuries from different types of accidents/intentional injuries which
reduce the risk of misclassification bias and with few missing data. However, we
only include hospital stays and outpatient specialised care visits in our outcome data
and therefore the results can be generalized to such more severe injuries from
accidents or intentional injuries, while theoretically there might be other potential
risk factors when focusing on milder injuries.
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Birgit Modén
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Confounding
In addition to the effect of a studied exposure on the risk of developing a specific
disease/injury, there might be other factors associated with the exposure that affects
the risk/odds of developing the disease/injury. These factors can result in a
distortion in the estimated effect of exposure if their prevalence differ between
those exposed and unexposed [229]. Such distorting variables are called
confounding factors. A confounding factor must not be affected by the exposure
under study, i.e., it cannot be an intermediate step between exposure and disease
[229]. The definition of a factor as a confounding factor is often grounded on
theoretical assumptions based on the results of previous studies and theoretical
reasoning. It is important to control for confounding to isolate the effect of
exposure. The decision to regard variables as confounders in the present studies was
based on evidence from studies of factors that might affect the specific outcomes
used and factors associated with the exposure. We also considered confounding by
indication, i.e., it is most likely that the use of psychotropic drugs is related to
presence of mental health problems (e.g., diseases of the nervous system, affective
disorders and cerebrovascular diseases) in themselves being risk factors for injuries
[235]. We have tried to reduce such an effect by adjusting for presence of some
mental health problems, however, there might still be others that we have not
accounted for. There may also be other potential confounders not included in our
analyses, such as other medications, factors in the physical environment,
psychosocial stressors or various lifestyle habits.
Implications for future research and prevention
The main explanation for the declining mortality due to injuries in Sweden over the
last decades encompass the application of national and local strategies for safety
promotion as well as legislation, e.g. safety planning in smaller areas of living,
bicycle-helmet use, improvements in traffic infrastructure and the adoption of
information systems with regard to work-related injuries and injuries from
transportation accidents [226, 236, 237]. However, injuries still comprise an
important part of the visits in primary health care and of those admitted to hospitals
[2]. Each year in Sweden, falling accidents are experienced by a third of those aged
60 or over and half of those aged 80 or over, while injuries from traffic accidents
still account for many of the serious accidents in youths and younger adults [2, 40].
Injuries are often associated with long-term suffering as well as lowered
functioning and injuries impose a huge burden on medical care and health services.
From a public health perspective an increased knowledge about risk factors for
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Birgit Modén
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injuries is important to decisions influencing the focus of public health prevention
strategies. Considering their high prevalence, side effects related to the use of
psychotropic drugs may be a relevant risk factor for injuries that could be prevented
by an increased rational medication use. Psychotropic drugs affect the central
nervous system, and can cause a variety of changes in behaviour or perception.
Experimental studies have among other things shown that the use of psychotropic
drugs may impair the ability to drive a motor vehicle [86]. However, few studies
have assessed the independent association between the use of psychotropic drugs
and injuries from falling accidents [8, 12, 14, 98, 100, 218] or transportation
accidents [86-91, 112, 221-225] in a general adult population. The results in paper I
showed that about one third of the population aged 35-64 years and nearly half of
those aged 65 years or over had used psychotropic drugs during a period of 1.5
years. The results in papers I and II further showed that psychotropic drug use was
associated with increased odds of injuries from falling and transportation accidents
in nearly all age groups in both men and women even after adjustment for potential
confounders. In Paper II studying the elderly general population, it was shown that
such an effect was the largest immediately after initiating therapy. In a chapter by
Wall et al. in a recently published book in Traffic Medicine, it was suggested that
patients starting therapy with psychotropic drugs such as antidepressants, sedatives,
and hypnotics should avoid driving after starting therapy until it is known that
unwanted effects do not occur [128]. Furthermore, the results in Papers III and IV
showed associations between psychotropic drug use and assault-related injuries and
intentional self-injuries. Such an effect might be mediated through influences on
impulse control and behaviour through mitigating various psychiatric conditions,
but also through negative side effects on cognition and alertness. In future studies it
would be desirable to also include other medications and investigate potential
interactive effects between treatment groups.
Sociodemographic factors generally showed weaker associations with unintentional
injuries such as falling accidents and transportation accidents, compared to
intentional injuries such as assault-related injuries and intentional self-injury.
However, young age was associated with increased odds/incidence of transportation
accidents, assault-related injuries and intentional self-injury. Furthermore, male
gender was associated with increased odds/incidence of transportation accidents and
assault-related injury, while female gender was associated with increased
odds/incidence of falling accidents among the elderly and intentional self-injury.
The latter association did not reach statistical significance in an adjusted
multivariable model. Similar results with regard to age and gender have been seen
in earlier studies [1, 2, 43, 55-59, 148-149, 150-152]. Those being single and having
low income had increased odds of assault-related injuries and intentional selfinjury. Originating from outside the Nordic countries were associated with
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Birgit Modén
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increased odds of being injured from assault in both men and women, while those
born in the Nordic countries had higher odds of intentional self-injury. The higher
odds of an assault-related injury among those born outside the Nordic countries,
being single or having low income might reflect differences in cultural or religious
norms as well as differences in the social environment and risk-taking behavior,
while the latter association might reflect differences in cultural or religious norms
as well as differences in the social environment ant risk-taking behaviour. In a
recent review restricted to the association between sociodemographic factors and
attempted suicide it was urged that there is a need for more studies in different
settings to better understand the mechanisms behind such factors and self-injurious
behavior [227]. Although it is difficult to intervene on sociodemographic factors per
se, it is important to recognise risk groups for future injuries. Such identification
might have bearings on the planning of public health intervention programs and
local and national strategies for safety promotion.
A number of chronic diseases and conditions have been shown to be associated with
a higher risk of injuries. For example, diseases such as stroke, Parkinson’s disease,
dementia, previous hip fracture, dizziness, and reduced sight have been shown to be
associated with an increased risk of a future falling accident [121-123]. The results
of the studies presented in this thesis showed associations between previous disease
and both unintentional and intentional injuries. For example, psychiatric disease
such as depression was associated with increased odds of future falling accidents,
assault-related injury and intentional self-injury, while those with diseases of the
nervous system (e.g. degenerative disorders, Mb. Parkinson, multiple sclerosis,
epilepsy) had increased odds of falling accidents, transportation accidents, assaultrelated injuries and intentional self-injury. There were also associations between
diseases related to drug- or alcohol abuse and intentional injuries. Regarding
transportation accidents, earlier studies have shown that almost 50% of the drivers,
riders, or pedestrians involved in a crashes suffer from at least one medical
condition, and that in approximately 13% of cases, the medical condition of the car
driver was the direct causal factor [129]. Early identification with correct treatment
of these disorders as well as restrictions with regard to driving might help to reduce
such disease-related injuries.
In summary, the results presented in this thesis expand the knowledge base on risk
factors for injuries in adults, that is, its associations with sociodemographic
variables, previous disease and psychotropic drug use in men and women. One
strength of the results presented is that the data covers the total general population
in Scania, which minimises the risk of selection bias. Considering the high
prevalence and the often devastating consequences, the field of injury and its risk
factors is an important topic for research. An increased awareness of such risk
53
Birgit Modén
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factors might be of help to reduce the number of injuries by affecting the planning
of local, regional and national public health intervention programs and strategies.
54
Birgit Modén
________________________________________________________________________
Conclusions
•
Psychotropic drug use (i.e., opioids, antidepressants, anxiolytics and
hypnotics/sedatives) was associated with increased odds of future falling
and/or transportation accidents, even after adjustment for previous accidents,
previous disease, and sociodemographic variables.
•
The use of psychotropic drugs, especially opioids and antidepressants, was
associated with higher odds of a falling accident among both men and women
aged 65 years and older. This effect seemed to be largest immediately after
initiating therapy.
•
Sociodemographic factors such as young age, being single, having low
income, low educational level and being born outside the Nordic countries,
were associated with increased odds of being injured from assault. Other risk
factors for assault-related injuries include having had depression or diseases
related to alcohol and drug abuse, the use of psychotropic drugs or having had
a previous assault-related injury.
•
Sociodemographic factors such as being single, young or middle age, having
low income, and being born in the Nordic countries were associated with
increased odds of non-fatal intentional self-injury. Diseases of the nervous
system, psychiatric diseases, substance abuse and previous assault-related
injury were also strongly associated with intentional self-injury. Furthermore,
the use of psychotropic drugs showed a clear dose-response relationship with
the odds of having a future diagnosed intentional self-injury.
55
Birgit Modén
________________________________________________________________________
Populärvetenskaplig sammanfattning
Dödligheten i skador i Sverige har under de senaste årtiondena minskat, en
minskning som idag dock har planat ut. Antalet dödade i transportolyckor och i
arbetsplatsolyckor i Sverige har minskat under de senaste 40 åren vilket kan ses som
ett resultat av ett effektivt säkerhetsarbete. När det gäller fallolyckor så har däremot
andelen som dör av sina skador ökat markant under de senaste åren. Förutom
dödlighet så behöver varje år cirka 135 000 människor i Sverige sjukhusvård till
följd av skador. Exakt hur många som totalt skadas i Sverige varje år är dock svårt
att uppskatta då någon heltäckande nationell skaderegistrering inte existerar. Nästan
hälften av alla skador som kräver inläggning på sjukhus utgörs av fallskador (46%),
skador i trafiken står för ca 7%, avsiktliga självtillfogade skador för 5% samt skador
till följd av våldshandlingar för 2%. Utöver mänskligt lidande renderar skador
dessutom stora kostnader för samhället varje år. Orsakerna till att människor skadas
varierar mellan olika typer av skador, och därför kategoriseras skadorna efter
uppkomstmekanism: oavsiktliga skador (där inget uppsåt till skadan finns ex.
olycksfall) och avsiktliga skador (där ett uppsåt finns ex. avsiktlig självtillfogad
skada och avsiktlig våldsskada). Det finns många faktorer som i tidigare studier
visats påverka risken att råka ut för skador som t.ex. förekomst av kroniska
sjukdomar, läkemedelsanvändning, och yttre faktorer i omgivningen, men också
sociodemografiska faktorer såsom ålder, kön, etnicitet, utbildning och ekonomi. Det
är dock få studier av dessa riskfaktorer som är genomförda på en hel vuxen
befolkning. Syftet med avhandlingen var att undersöka sambandet mellan
sociodemografiska faktorer, tidigare sjukdomar/skador, användning av
psykofarmaka och uppkomsten av skador. Det empiriska underlaget utgjordes av
data ur databasen LOMAS (Longitudinal Multilevel Analysis in Scania) vilken
innehåller uppgifter från olika register innefattande sjukvårdskonsumtion,
medicinering och sociodemografiska faktorer.
Syftet med den första studien (Paper I) var att undersöka sambandet mellan och
användning av psykofarmaka (t.ex. smärtstillande, antidepressiva mediciner, sömnoch lugnande mediciner) och transportolyckor respektive fallolyckor i Skånes
befolkning (18 år och äldre). Resultaten visade att en tredjedel av de medelålders
och nästan hälften av de äldre hade använt psykofarmaka under en 18-månaders
period. Resultaten visade vidare ett ökat odds för att råka ut för fallolyckor bland
psykofarmakaanvändare i alla åldersgrupper. Användning av psykofarmaka ökade
även oddset för en trafikolycka i de flesta åldersgrupper. Dessutom visade studien
att de som varit med om en trafikolycka tidigare betydligt oftare råkade ut för en ny
trafikolycka.
56
Birgit Modén
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Syftet med den andra studien (Paper II) var att undersöka sambandet mellan
användning av psykofarmaka (t.ex. smärtstillande, antidepressiva mediciner, sömnoch lugnande mediciner) och fallolyckor bland personer i Skåne som var 65 år och
äldre. Studien visade ett tydligt samband mellan användningen av psykofarmaka
under en tremånadersperiod och uppkomsten av en fallolycka. Högst odds återfanns
under den första veckan av medicineringen, som då var mer än fyrdubblat.
Dessutom visade studien att personer som levde ensamma alternativt hade fallit
tidigare hade ett ökat odds för en fallolycka.
Syftet med den tredje studien (Paper III) var att identifiera riskfaktorer för en
våldsskada. Studien visade att ung ålder, låg inkomst, låg utbildningsnivå, att vara
ensamstående och att vara född utanför Norden var faktorer som ökade oddset för
att utsättas för en våldsskada. Våldsskador var vidare vanligare bland män än bland
kvinnor. Dessutom var personer med diagnostiserad depression och
alkoholmissbruk mer utsatta än andra. Även användning av psykofarmaka ökade
oddset för en våldsskada, liksom att ha varit utsatt för en våldsskada tidigare.
Syftet med den fjärde studien (Paper IV) var att identifiera riskfaktorer för en
avsiktlig självtillfogad skada. Faktorer som i studien visade sig öka oddset för
denna typ av skada var att vara ung eller medelålders, ha låg inkomst och att vara
född i Norden. Att ha neurologiska eller psykiatriska sjukdomar, alkohol- eller
drogmissbruk eller att tidigare avsiktligt skadat sig själv var faktorer som kraftigt
ökade oddset för en självtillfogad skada. Användningen av psykofarmaka visade på
ett dos-respons samband med uppkomsten av en avsiktlig självtillfogad skada.
Slutsatsen man kan dra av denna avhandling är att individens socioekonomiska
ställning, förekomst av sjukdom och medicinering med psykofarmaka, utgör
riskfaktorer för uppkomsten av skador. Med tanke på mängden skador som sker och
de konsekvenser som dessa får, är skador och dess riskfaktorer ett viktigt
forskningsområde. En ökad medvetenhet, både hos den enskilde individen och i
samhället i övrigt, om dessa riskfaktorer förbättrar vidare möjligheten till effektiva
preventiva insatser för att reducera antalet skador.
57
Birgit Modén
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Acknowledgements
I wish to express my deepest gratitude to everyone involved in my education, work
and completion of this thesis. In particular I would like to thank:
My principal supervisor Maria Rosvall for your constant support and tireless
enthusiasm that always pushed me and the work of this thesis forward. You have
always been there for me when I needed help and your interest in the subject, your
incredible knowledge and creativity as a researcher have made me so thankful for
getting the chance to be your doctoral student.
My co-supervisor Professor Juan Merlo for so generously sharing “your database”
LOMAS, for your support, great ideas and constructive criticism.
My co-supervisor statistician Henrik Ohlsson for your support, constructive
criticism, for helping me with statistic questions and for helping me with the
statistics in the second paper.
Professor Martin Lindström for generously giving me the financial means to parttime work with this thesis, and for being supportive and encouraging.
My colleagues Mathias, Anita, Maria and Kristina at CRC for your support and for
always being available for discussion whatever the topic is.
My colleagues at Unit for Public Health in Region Skåne and my boss Elisabeth
Bengtsson for giving me time off in order to have time to finish my thesis.
My dear friends and previous colleagues Ulla-Britt Hedenby, Ewy Rundkvist,
Mahnaz Moghaddassi and Fiffi Tegenroth for being encouragers to me in this thesis
and for helping me with the final. I highly appreciated working and sharing time
with you all!
My precious sister Gudrun. Thanks for being a great loving and caring sister! Also
thanks to you and your life companion Anders for supporting and encouraging me
in the work with this thesis.
My wonderful parents Nore and Asta, thanks for being the great parents that you
are! Thanks for giving me the opportunity to study and encouraging me to do so
even though you yourself only had the opportunity to go to elementary school.
Finally, I want to thank my dear life companion Frida for always being there for me.
Thanks for your love, support and patience throughout the work of this thesis. You
are the meaning of my life!
58
Birgit Modén
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