Wafa et al.

BMC Psychiatry (2019) 19:163

https://doi.org/10.1186/s12888-019-2154-z

STUDY PROTOCOL Open Access

Identification of biopSychoSocial factors

predictive of post-traUmatic stress disorder
in patients admitted to the Emergency
department after a trauma (ISSUE): protocol
for a multicenter prospective study
Mohammad-Hashim Wafa1* , Marie Viprey1,2, Laurent Magaud1,2, Julie Haesebaert1,2, Edouard Leaune3,5,
Emmanuel Poulet3,4, Clemence Bied4 and Anne-Marie Schott1,2

Abstract
Background: Traumatic exposure is a frequent issue in patients visiting emergency departments (EDs). Some
patients will subsequently develop post-traumatic stress disorder (PTSD) while other will not. The problem is under-
diagnosed in EDs and no standardized management is provided to prevent PTSD. Most studies focused on a
particular group of trauma whereas we need a global approach to further develop interventions for detecting and
treating patients at high risk. We aim to assess the prevalence of traumatic exposure and situation at high risk of
further PTSD and identify pre and peri-traumatic biopsychosocial factors predisposing individuals to PTSD in the
general context of EDs.
Methods: This comprehensive multicenter study will have two steps. The first step will be a cross-sectional study
on moderate and high risk of PTSD prevalence among EDs visitors with a recent history of trauma. All patients
aged 18–70 years, presenting with a recent history of trauma (< 1 month) in one of the six EDs in the Auvergne-
Rhône-Alpes region (≈1/10° of the French population) will be included over a 1-month period and approximately
1500 subjects are expected in this cross-sectional step. The risk of PTSD will be assessed using the Impact of Event
Scale Revised (IES-R). Self-administered questionnaires will be used to measure acute stress (IES–R), and a number of
potential bio-psycho-social risk factors. Demographic and physical health-related data will be collected from medical
file. Second step will be a prospective cohort study within a sub-sample of 400 patients enrolled in step 1, randomly
selected with stratification on sex, age, ED, and IES–R score. At 3 months, PTSD will be defined by a ≥ 33 score at PTSD
Check List for DSM–5 (PCL–5) through a telephone interview. We will evaluate definite PTSD biopsychosocial predictive
factors using a multivariate logistic regression model and describe evolution of PTSD at 3 months.
Discussion: This is the first study to assess PTSD predictors prospectively with a biopsychosocial approach within a
cohort representative of EDs visitors. The results will inform the development of dedicated interventions to decrease
the risk of subsequent PTSD.
Trial registration: ClinicalTrials.gov: NCT03615014; ISSUE protocol 2nd version was approved on 07/08/2018.
Keywords: Post-traumatic stress, Biopsychosocial, Emergency, Trauma, Addiction, Anxiety, Depression, Dissociation

* Correspondence: [email protected]
1
HESPER EA 7425, Univ Lyon, Université Claude Bernard Lyon 1, Lyon, France
Full list of author information is available at the end of the article

© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Wafa et al. BMC Psychiatry (2019) 19:163 Page 2 of 10

Background specific features of the index trauma (perception of

Post-traumatic stress disorder (PTSD), one of the most death threat, head trauma, intentional aggression), and
serious sequelae of a traumatic exposure, is a chronic post-traumatic psychosocial factors such as peri-
disorder with a high level of anxiety and neurovegetative traumatic dissociation, acute stress disorder and low so-
symptoms that interrupt normal psychosocial function- cial support [1–3, 5, 15, 21–40]. However, these studies
ing of the person [1–4]. There are four main categories have methodological limitations. For instance, they suffer
of diagnostic symptoms, namely, symptoms of re- from selection bias as they usually focus only on a par-
experiencing the trauma, avoidance and numbing symp- ticular population [32, 41–44] or on a single trauma type
toms, negative alterations in mood and cognition, and such as road traffic accident [32, 43–46]. Most used
hyper-arousal symptoms. [4–9]. The mean duration of case-control or retrospective designs that suffer from in-
PTSD is 5.3 years (range: 0.2–28.1) [10]. Patients with formation/recall bias [41, 42, 44, 46–49], and were con-
PTSD are more likely to develop other psychiatric disor- ducted on small samples and/or had high loss-to-follow-
ders such as depression, anxiety disorders, substance use up rates for prospective studies reducing the
disorders, and/or attempt suicide [11, 12]. The likelihood generalization of the results [20, 26, 28, 43, 45, 46, 50–
of developing somatic pathologies such as cardio-vascular 54]. Furthermore, studies usually focused on either bio-
disorders is also very high [13, 14]. Therefore, such pa- logical, psychological, or social factors; none considered
tients, in addition to the disorder itself, suffer from its a comprehensive biopsychosocial approach to study the
physical, occupational, and social sequelae. Such conse- predictive factors [19, 20, 25, 32, 48, 50, 52, 54, 55]. It is
quences result in a significant economic impact [5]. also of note that, to the best of our knowledge, there is
Worldwide approximately 60.7% of all men and 51.2% no published prospective epidemiological study that has
of all women encounter at least one traumatic event in evaluated the prevalence of acute stress in survivors of
their lifetime. However, not all of them will develop diverse trauma visiting an ED.
PTSD; it is estimated that after a trauma, 8% of men and We therefore aim to address all these limitations in a
20% of women will subsequently develop PTSD [15]. prospective multicenter study that will recruit a large
Prevalence of the condition is highly variable (4–86%), number of patients in the ED who were exposed to vari-
but is higher among those who experienced the stressors ous types of trauma. We will measure prevalence of
directly, such as victims of intimate partner violence acute stress and level of PTSD risk through an initial
(IPV), sexual victimization, servicemen, refugees, and cross-sectional study. We will then adopt a holistic view-
asylum seekers [5]. In the French population, the life- point to determine the predictive factors such as specific
time exposure to a traumatic event is estimated to be features of the trauma as well as demographic, bio-
72.7% and lifetime prevalence of PTSD to 3.9% [10], logical, psychological and social risk factors through a
which is lower than that found in the United States cohort study.
(7.8%), but higher than rates in Spain (2.2%) or Italy
(2.4%) [10].
Objectives
Among the patients consulting EDs after a recent
Primary objectives
trauma, 18 to 42% suffer from acute stress disorder
The primary objective of the cross-sectional study is to
(ASD) [16–18], which is highly predictive of subsequent
estimate the prevalence of patients with high or moder-
occurrence of PTSD [16, 19, 20]. However, ASD is often
ate risk of developing PTSD in all consecutive cases ad-
underdiagnosed in ED, mainly due to the assessment fo-
mitted to the EDs after recent trauma (< 1 month).
cused on urgent physical problems, complaints of the
The primary objective of the prospective cohort study
patient (pain, insomnia), and overlooking the traumatic
is to determine predictors of PTSD occurrence at 3
context [1, 21].
months in a randomly selected sub-sample of patients
PTSD predictive factors are worthwhile for identify-
included in the cross-sectional study and identified as
ing populations at high risk, which in turn could lead
“at moderate or high risk” for developing PTSD at ad-
to early diagnosis and management of these cases,
mission to the ED.
and therefore could help reduce the occurrence of
the disorder. Screening for such factors, however, is
not incorporated into any structured assessment pro- Secondary objectives
cedure in EDs. The secondary objectives are to measure acute stress,
Previous research has identified the following predict- anxiety disorder, and dissociative experiences in patients
ive factors for PTSD: pre-traumatic factors (e.g. female at inclusion. At 3 months, the incidence of PTSD, its
sex, extreme age, low Intelligence quotient (IQ), child- complications and comorbidities will be estimated, as
hood or prior traumatic exposure, pre-existing mental well as the impact of trauma on occupational and psy-
health problem, substance abuse, anxious personality), chosocial functioning of the study subjects.
Wafa et al. BMC Psychiatry (2019) 19:163 Page 3 of 10

Methods/design assigned EDs will be screened from 08:00 to 24:00/day

This multicenter study will be conducted in two stages. and 7 days/week, based on inclusion criteria. The screen-
The first stage will consist of a cross-sectional study ing will be performed by a trained interviewer (research
within all consecutive patients admitted to the partici- assistant or medical/nurse student), supervised by a
pating EDs following a recent trauma (< 1 month), to psychiatrist or emergency physician. The investigating
systematically measure their risk of PTSD. The second physician will explain the study to each eligible patient
stage will be a prospective cohort study designed to and provide him/her with a written synopsis of the ob-
analyze the relationship between PTSD occurrence and jectives and course of the research (including that they
its putative predictive factors in a sub-sample of patients can be drawn at random to receive the questionnaires by
randomly selected among those identified as “at moder- an email or postal mail and a telephone follow-up). In
ate or high risk” for developing PTSD at admission to case the patient is willing to participate, he/she will date
the ED and followed-up for 3 months. and sign the consent form and a trained interviewer will
collect baseline data. Participation in the study will nei-
Study setting ther change any healthcare required by the patients, nor
The study will take place in six large EDs of the their right to retract from the study at any time they
Auvergne-Rhône-Alpes region of France; the four EDs desire.
in Lyon (two at the Edouard Herriot hospital, one in
Lyon Sud hospital, and one in Saint Luc Saint Joseph Constitution of the cohort
hospital), one in Saint Etienne (North university hos- The prospective cohort study will be conducted on a
pital) and one in Clermont Ferrand (university hospital). sub-sample of the participants (Fig. 1). The study bio-
The region had 7.878 million inhabitants in 2015 (source statistician will arrange a cohort of 400 subjects selected
Eurostat) and covers urban and rural, economically de- through random sampling stratified by sex (male/fe-
prived and non-deprived areas. male), age (determined by interquartile range of the col-
lected data), investigating ED (1 to 6), and IES-R score
Participant eligibility (< 12, 12 to 34, > 34). Selected subjects will receive the
The target population will be adults (≤ 70 years of age) questionnaires by email or postal mail and will be inter-
visiting the EDs during the 1-month inclusion period viewed by telephone at 3 months (± 15 days) after the
who were victims of a recent traumatic event (< 1 index trauma. Mental health professionals (a psycholo-
month) and willing to participate in the study. The gist, psychiatrist, or resident in psychiatry) who have had
trauma will be defined as a direct exposure, directly wit- special training on the PCL–5 application will conduct
nessing trauma to a third party, or discovering that a the interview.
traumatic event has happened to a close family member
or a close friend. In case of actual death or death threat Data collection
to a member of the family or a friend, the event(s) must Table 1 summarizes the different stages of data
have been violent or accidental. We will also consider collection.
the recurrent or extreme occupational exposure to trau- Following preselection and written informed consent,
matic events (e.g. front-line workers collecting human patients will be identified as study subjects. At the inclu-
remains, police repeatedly exposed to explicit child sex- sion phase, he/she will receive self-administered ques-
ual abuse) [4]. Furthermore, participants must be affili- tionnaires to measure acute stress (IES–R), dissociative
ated to the French public health insurance system, and experiences (PDEQ), anxiety disorder (STAI-Y; A & B
provide written informed consent. In case of an adult forms), social support (SSQ6), alcohol and/or tobacco
under curatorship, the recruiter will seek only his/her addiction (AUDIT & Fagerström test), depressive symp-
consent, the consent of the curator being not mandatory toms and suicidality (QIDS-SR16), marital stability, fam-
in the French law. ily history of mental health problems and/or instability,
Patients who are either unable to communicate socio-economic and familial status, history of trauma ex-
fluently in French or under guardianship, and/or have posure, and past psychiatric history. Demographic and
clinical instability that makes completing the question- physical health-related data will be collected from his/
naire(s) impossible (e.g. agitation, critical condition, dis- her medical file.
torted consciousness, etc.) will not be included in the At 3 months after the index date, the cohort study par-
study. ticipants will receive self-administered questionnaires by
an email {a link with access code to an ePRO (electronic
Recruitment process patient reported outcomes) for online completion of
Figure 1 illustrates stages of the study. Initially (for a questionnaires} or by postal mail (attached with a pre-
period of 1 month) each eligible consumer of the paid return envelope). The online version of the
Wafa et al. BMC Psychiatry (2019) 19:163 Page 4 of 10

STAGE 1
PATIENT VISITING AN
EMERGENCY DEPARTMENT

PRESELECTION
(18-70 years; Speaking French; Trauma Type and
Date; Clinical Stability; No Guardianship)

ELIGIBLE PATIENT
1. Individual Information
2. INCLUSION
3. Self-administered Questionnaires (IES–R; PDEQ STAI-Y, A & B
forms; SSQ6; AUDIT; Fagerström; QIDS-SR16)
4. Self-adminisetered questionnaires for collecting data on risk factors
STAGE 2

COHORT
STRATIFIED SAMPLING
Criteria: Sex, Age, Emergency Department, IES–R Category
1. Sending questionnaires by a mail or an email
2. First contact to make an appointment for the telephone interview

TELEPHONE ENTERVIEW AT 3 MONTHS (+/– 15 DAYS)

STAGE 3

POST TRAUMA
Self-administered questionnaires
(PCL–5; STAI-Y, A & B forms; SSQ6; AUDIT; Fagerström; QIDS-
SR16)

STUDY EXIT

Fig. 1 Inclusion stages and follow-up of subjects

questionnaires will have to be completed at least one Selected patients will receive an email or a postal mail
day prior to the telephone interview. These question- reminding them of their participation in the second
naires will help us assess trauma impact on the pa- stage of the study around 1 month prior to the theoret-
tient’s occupational and psychosocial functioning ical date of the interview.
{SSQ6 & STAI-Y (A & B forms)} and PTSD compli- Within 15 days of the interview, we will contact the
cations and comorbidities such as depression & sui- subject via telephone or email in order to set the date
cidality (QIDS-SR16), and addiction (AUDIT & and time for the interview.
Fagerström test). In case the first attempt to contact the subject is un-
Additionally, through a telephone interview, a mental successful, we plan three more attempts of telephone
health professional (psychologist, psychiatrist, or psychi- call or email. If we fail to establish any (telephone/email)
atric intern) will assess PTSD using the PCL–5 question- contact up to the intended date of the interview, the
naire and determine whether the subject received any subject will be considered as lost to follow-up.
therapeutic care in the 3-month period. The estimated Subject participation in the study will end with the
duration of this interview is 15 to 30 min. completion of this telephone interview.
Inclusion, follow-up and data collection stages are pre- Patients with an IES-R score of > 34 will be proposed
sented in Table 1. to consult a specialized healthcare professional (psych-
We will apply the following measures in order to limit iatrist or addictionologist) for the diagnosis and treat-
the number of dropouts: ment (if necessary) of PTSD or its complications
Wafa et al. BMC Psychiatry (2019) 19:163 Page 5 of 10

Table 1 Patient inclusion, follow-up, and data collection stages of the study
Steps Preselection V1 Establishment of V2
Inclusion the Cohort Telephone Follow-up
End of the Study
Preselection Criteria Verification (1) X
Information, Consent Collection and Inclusion X
Self-administered questionnaires {IES–R; PDEQ; STAI-Y X
(A & B forms); AUDIT; Fagerström; QIDS-SR16; SSQ6}
Clinical Data Collection & Self-administered questionnaire X
(risk factors) (2)
Stratified sampling (weighted) X
Mailing self-administered questionnaires to subjects to X
prepare for the telephone interview
Telephone Interview: X
PCL–5; STAI-Y (A & B forms); AUDIT; Fagerström; QIDS-SR16;
SSQ6 (+ back to work time)
Intercurrent psychological care (consultation, hospitalization, X X
psychotropic)
(1) Emergency patient with a recent history of trauma (< 1 month), aged 18 to 70 years, speaks French, and has no guardianship
(2) This self-administered questionnaire consists of PTSD risk factors

(alcoholism and/or substance abuse, suicidality, and de- and 2 items E (questions 15–20). The cut-off score for
pressive symptomatology). PCL-5 is ≥33 [66, 67]. This tool has a good sensitivity
for a provisional diagnosis of PTSD, and has the advan-
Outcome criteria and measure instruments tage to have a shorter completion time (about 5 to 10
Primary outcome criteria min) than the CAPS–IV [16, 19, 20].
The primary endpoint for the cross-sectional study is
the IES–R score of the subjects reflecting their risk of
developing PTSD at inclusion in the ED. An IES-R Secondary outcome criteria
score > 34 will be considered as a high-risk of subse- Anxiety disorder will be assessed using the State-Trait
quent PTSD, an IES-R score of 12–34 as a moderate Anxiety Inventory (STAI-Y; form A & B) [68, 69] at in-
risk, and an IES-R < 12 a low risk [44, 56, 57]. IES-R is clusion and at 3-month follow-up. STAI-Y is a self-
a 22-item self-administered questionnaire composed of report tool that assesses momentary as well as habitual
three subcomponents: intrusion (8 items), hyperarousal anxiety. It includes two scales of 20 items, each rated
(6 items), and avoidance (8 items). Patients evaluate for from 1 = not at all/almost never to 4 = very much so/al-
each item the experience during the last 7 days on a most always [68, 69]. The State-Anxiety subscale (STAI-
Likert scale 0 = not at all to 5 = extremely. The total Y A), assesses the intensity of subjective feelings of ten-
score (from 0 to 88) is the sum of all the evaluations. sion, worry, apprehension, and nervousness at the
IES-R has good psychometric characteristics [56–62], current moment. The Trait-Anxiety subscale (STAI-Y B),
and is recommended in France for PTSD surveillance measures frequency of anxiety vulnerability that includes
[63]. The IES-R is among the most used scales [64], it is overall degree of security, confidence, and calmness.
validated in French with a mean completion time of 5 to The presence or absence of dissociative experiences
10 min [65]. will be assessed through the validated French version of
The primary endpoint of the prospective cohort study Peritraumatic Dissociative Experiences Questionnaire
is the presence or absence of 3-month PTSD defined by (PDEQ) [64, 70] at inclusion. PDEQ is a self-
PCL-5 (PTSD Check List for DSM-5). PCL-5 is a 20- administered questionnaire designed to assess the pres-
item self-reported measure. Consistent with the Diag- ence and intensity of peritraumatic dissociative reactions
nostic and Statistical Manual of Mental Disorders, Fifth during or immediately following a potentially traumatic
Edition (DSM-5), it assesses 20 symptoms of PTSD. The event. In accord with the peritraumatic dissociative
questionnaire uses “0=not at all” to “4 = extremely” rat- symptoms, the questionnaire has 10 corresponding
ings to evaluate each symptom. A probable diagnosis of items. For each item, the subject selects the answer most
PTSD is made by considering any item with a score of adapted to his/her experience from 1 (not at all true) to
≥2 as present and then by adhering to DSM-5 instruc- 5 (extremely true). The final score is the sum of all the
tions that require at least: 1 item B (questions 1–5), 1 selected answers, varying from 10 to 50, 10 being the
item C (questions 6(− 7), 2 items D (questions 8–14), minimum signifying absence of dissociative experiences
Wafa et al. BMC Psychiatry (2019) 19:163 Page 6 of 10

and a score greater than 10 indicates that the patient has time for documenting all the questionnaires is around
dissociative experiences. 30 min.
At inclusion, we will evaluate patient’s social support
as a risk factor and at 3-month follow-up as a psycho- Sample size
social and occupational consequence of the trauma. For The total number of ED visits in the assigned six centers
this purpose, we will ask his/her return time to the over a period of 1 month is more than 20,000. We plan
workplace and use the validated French version of the to screen around 15,000 patients (75%) with an age
Social Support Questionnaire 6 (SSQ6) [71, 72]. SSQ6 is range of 18 to 70. Following a traumatic context, 10 to
a 6-item questionnaire that measures two aspects of per- 50% of survivors consult EDs [3, 15, 79, 80]. Considering
ceived social support, i.e. availability and satisfaction. the most conservative hypothesis (10% of the 15,000 vis-
Availability is defined as the individual’s estimation of iting 18–70 year old patients), we estimate that 1500 pa-
the number of people who can help him/her if required. tients could be included in the study to participate in
Satisfaction is defined as the perceived adequacy be- the cross-sectional part of the study.
tween the support received and his/her expectations and The main objective of the cohort study is to identify
needs. For each item, the respondent lists the people factors associated with the occurrence of 3-month
(max. 9) he/she can count on in the situation de- PTSD. In the literature, incidence of PTSD in various
scribed and expresses his/her degree of satisfaction populations and after different types of trauma usually
(from 1 to 6) with regard to this support. We then ranges from 30 to 60% [3, 15, 79, 80]. Considering
calculate one score for availability (score N, that var- the hypothesis of a 40% incidence of PTSD in the
ies from 0 to 54), and another for satisfaction (score “unexposed” group, the inclusion of 305 patients
S, that varies from 6 to 36). should allow, with an alpha risk of 0.05, and a power
For the assessment of alcoholism and nicotine depend- of 80%, to identify factors associated with a relative
ence at inclusion and at 3-month follow-up (as PTSD- risk of at least 1.4 [81].
related complications), we will use Alcohol Use Disorder As we anticipate 30% of the subjects may be either lost
Identification Test (AUDIT) and Fagerström test, re- to follow-up or unwilling to participate at 3 months, we
spectively [73, 74]. will randomly select a cohort of 400 patients.
The AUDIT consists of 10 questions and screens for
risky or harmful use of alcohol. It is the reference for de-
tecting alcohol misuse. Men scoring ≥7 and women Statistical methods
scoring ≥6 raise the suspicion of alcohol misuse [73, 75]. We use SAS v9.3 software (SAS institute, Cary, NC,
The Fagerström test is a quick 6-item test that quanti- USA) for data analysis, and will not impute missing data.
fies patient’s level of nicotine dependence [75]. The score A significance level of 5% will be considered for the
ranges from 0 to 10. Dependency is deemed to be null if analysis.
the score is from 0 to 2, low from 3 to 4, average from 5
to 6, strong from 7 to 8, and very strong from 9 to 10. Descriptive analysis of the emergency departments and
In order to assess depression and suicidal ideation (as patients participating in the study
risk factors at inclusion), and as PTSD-related complica- Unwillingness of the EDs and/or patients to participate
tions or comorbidities at 3 months, we will use the in the study could lead to selection bias. For a critical
Quick Inventory of Depressive Symptomatology (Self- appraisal of the study findings, we will compare the
Report) (QIDS-SR16). The QIDS-SR16 is a self- characteristics of patients included and not included in
administered questionnaire with 16 items describing the the cross-sectional study and/or in the cohort study.
9 symptom domains of DSM-IV associated with depres- Mean and standard deviation (with 95% confidence
sive feeling [76–78]. The assessment of depression sever- interval of the mean) will summarize continuous nor-
ity is based on the total score as follows: from 1 to 5, mally distributed variables. Median and interquartile
absence of depression; from 6 to 10, slight depression; range will summarize continuous non-normally distrib-
from 11 to 15, moderate depression; from 16 to 20, se- uted variables. Frequency tables will summarize discrete
vere depression; and from 21 to 27, very severe depres- variables.
sion. We will also ask for the number of suicide There will be a description of characteristics of the
attempts over the last 3 months. two populations studied: total population included in the
first cross-sectional phase and the prospective cohort
PTSD risk factors population followed-up at 3 months. Additionally, we
Table 2 summarizes the biopsychosocial factors that will describe and compare characteristics of the subjects
have the potential to increase PTSD occurrence. These who were lost to follow-up to those who completed the
factors will be assessed at inclusion in the ED. Estimated follow-up.
Wafa et al. BMC Psychiatry (2019) 19:163 Page 7 of 10

Table 2 PTSD risk factors evaluated in the study, evaluation instruments and timing
Factor Category Predictive Factors Measure Timeline
Trauma Type and timing of the trauma Pre-screening questionnaire 1st visit
Characteristics
After trauma: Hospitalization (±); Intensive care (±) Consumer file 1st visit
Demographics Sex Consumer file 1st visit
Age Consumer file 1st visit
Socio-economic status Self-administered questionnaire 1st visit
Educational level Self-administered questionnaire 1st visit
Marital status Self-administered questionnaire 1st visit
Biological Heart rate Consumer file 1st visit
Blood pressure Consumer file 1st visit
Blood alcohol level Consumer file 1st visit
Psychological Trauma history Self-administered questionnaire 1st visit
Chronic anxiety STAI-Y (A & B forms) [68, 69] 1st & Final
visits
Past and current psychiatric pathology Self-administered questionnaire 1st visit
Current psychotropic treatment at inclusion and during the 3- Self-administered questionnaire 1st & Final
month period visits
Psychological care during the 3 months Self-administered questionnaire Final visit
Dissociative Experiences Self-administered questionnaire: PDEQ [70] 1st visit
Social Alcohol misuse Self-report: AUDIT [73, 75] 1st & Final
visits
Smoking addiction Self-administered questionnaire: Fagerström 1st & Final
test [74] visits
Family history of psychopathy or instability Self-administered questionnaire 1st visit
Marital stability Self-administered questionnaire 1st visit
Social support Self-administered questionnaire: SSQ6 1st & Final
[71, 72] visits
Others Somatic pathology Patient file 1st visit
Emergency care time Patient file 1st visit

Primary outcome criteria analysis group. To ensure the convergence and robustness of the
To assess the baseline risk of developing PTSD based on statistical model, we will not integrate more than twelve
the IES-R score (< 12, 12 to 34, > 34) we will calculate explanatory variables into the multivariate predictive
the proportion of the subjects at high risk (IES-R score > model [82].
34) and moderate-risk (IES-R score 12 to 34) to develop
PTSD and their 95% confidence interval. Secondary outcome criteria analysis
To analyze the biopsychosocial factors associated with In the cross-sectional study subjects, we will analyze the
the occurrence of PTSD at 3 months (yes / no) we will em- proportion of patients at moderate risk (IES-R score 12
ploy a univariate model. For statistical testing, we will use to 34) and at high risk (IES-R score > 34) of PTSD at in-
the Chi-squared test for qualitative variables, Student’s test clusion and their 95% confidence interval.
for quantitative variables following a normal distribution, In the cohort study population, we will analyze the
Wilcoxon test for quantitative variables following a non- proportion of subjects with a diagnosis of PTSD at 3
normal distribution, and a Kruskal & Wallis rank test for months with its 95% confidence interval.
ordered quantitative variables of the score type. Univariate To describe results of the questionnaires, we will con-
and multivariate logistic regression modeling will facilitate sider total score of PDEQ, STAI-Y (A & B forms),
estimation of the association between the studied factors AUDIT, Fagerström, QIDS-SR16 and SSQ6 evaluated at
and the 3-month risk of PTSD by calculating the crude inclusion. To present the results of the questionnaires at
and adjusted odds ratio and their 95% confidence interval. 3 months, we will focus on total score of STAI-Y (A & B
Among 305 analyzable patients, with a 40% incidence forms), AUDIT, Fagerström, QIDS-SR16 and SSQ6 eval-
rate of PTSD, we expect 122 patients in the PTSD uated again after 3 months.
Wafa et al. BMC Psychiatry (2019) 19:163 Page 8 of 10

Among subjects with 3-month PTSD To describe with invaluable information for the identification of the
PTSD complications and comorbidities, we will consider population at risk of PTSD and to plan preventive
the proportion of patients with excessive alcohol con- screening and therapeutic procedures.
sumption (AUDIT), the proportion of patients with to-
bacco addiction and its level (low, medium or high; Challenges
Fagerström test), the severity of depressive symptoms One challenge that we may probably encounter at the
(QIDS) and the proportion of patients in each of the five cross-sectional stage is that we will not be able to recruit
categories (from no depression to very severe depres- every patient consulting the EDs. Due to their either un-
sion), and the response to item 12 of QIDS-SR16 which willingness to participate or failure to meet the inclusion
will depict proportion of subjects with suicidal ideation. criteria. To address this problem, we will elaborate their
We will use mean, standard deviation, median, and respective characteristics in contrast to the patients
interquartile range to illustrate the number of days lost included.
from work and the number of suicide attempts over the A second potential challenge will be an unexpected
last 3 months. The proportion of patients with at least rate of dropout in the cohort stage. In order to address
one of these events will also be measured. this potential issue, selected subjects will receive re-
We will present secondary endpoint results for the minder letters and/or emails 1 month prior to the tele-
total study population and the subgroups according to phone interview, and we will send them the self-
the level of risk identified at inclusion by the IES–R administered questionnaires with a pre-paid return enve-
score (moderate risk = IES-R score 12 to 34; high risk = lope. In addition, a professional will call or email them
IES-R score > 34). 15 days in advance to set the date and time of the inter-
view. In case of “no reply”, three more attempts will be
Discussion made. Finally, the multicenter nature of the study and
Strengths of the study recruitment capacity of participating EDs (significantly
Firstly, to the best of our knowledge, this will be the first higher than required) ensure feasibility of recruiting ex-
study to assess prevalence of acute stress and risk of pected number of subjects.
PTSD in diverse trauma survivors visiting the ED due to
a recent trauma. Previous studies have focused on a spe- Abbreviations
ASD: Acute Stress Disorder; AUDIT: Alcohol Use Disorder Identification Test;
cific trauma such as road traffic accidents or rape vic- CAPS-IV: Clinician Administered PTSD Scale for DSM-IV; ED: Emergency
tims, etc. Secondly, the prospective design of the study Department; ePRO: electronic Patient Reported Outcomes; IES-R: Impact of
will minimize potential information or recall bias. A Event Scale-Revised; IPV: Intimate Partner Violence; PCL-5: PTSD Check List for
DSM-5; PDEQ: Peri-traumatic Dissociative Experiences Questionnaire;
number of similar studies have used case-control or PTSD: Post-Traumatic Stress Disorder; QIDS-SR16: 16-item Quick Inventory of
retrospective designs, and assessed the subjects after Depressive Symptomatology (Self-Report); SSQ6: 6-item Social Support
months and in some cases after years, which increases Questionnaire; STAI-Y (A + B): State-Trait Anxiety Inventory-Y (form A & B)
the probability of recall bias. Thirdly, the large sample
Acknowledgements
size of this study will ensure the generalizability of the First of all the authors highly appreciate proofreading of the manuscript by
findings. Small sample size is a very common problem in Philip Robinson. The authors are particularly grateful to the authorities of the
studies on PTSD; some studies have been conducted on assigned six EDs. We would like to extend our appreciation to all clinical
evaluators who are willing to assist in the inclusion and recruitment process.
a very low sample size while others studies suffer from Finally, we are thanking the ED patients who will participate.
huge dropout rates that subsequently. Fourthly, we use a
holistic biopsychosocial approach to evaluate PTSD pre- Authors’ contributions
dictive factors, while studies investigating PTSD predic- All authors, namely MHW, MV, LM, JH, EL, EP, CB and AMS, contributed in the
conception and design of the study and the manuscript, and all reviewed
tors usually explore a single domain (biological, and approved the final version of the manuscript.
psychological, social, or demographic). Fifthly, the find-
ings will determine PTSD risk in trauma survivors who Funding
The ISSUE study is supported by grants of the French Ministry of Health and
have an IES-R score between 12 and 34 on, for whom APICIL foundation. The funders are not involved in the design of the study
there is no literature on PTSD vulnerability. Sixthly, the and collection, analysis, and interpretation of data and writing the
use of PCL-5, a standardized scale for diagnosing PTSD manuscript.
at 3 months, is one of the strengths of this study. Specif-
Availability of data and materials
ically trained staff (psychologist, psychiatrist, or intern in Not applicable.
psychiatry) will complete the scale during a telephone
interview with the consumer. Seventhly, the results will Ethics approval and consent to participate
represent a wide geographical area and its innate diver- The protocol version 2 was approved by Les Comités de Protection des
Personnes (CPP) Nord-Ouest IV on August 7, 2018 (Reference Number: 2018-
sity through the multicenter nature of the study. Finally, A00883–52). Written informed consent will be obtained from each patient
the results will provide carers and healthcare providers willing to participate.
Wafa et al. BMC Psychiatry (2019) 19:163 Page 9 of 10

Consent for publication 18. Mayou R, Bryant B, Duthie R. Psychiatric consequences of road traffic
Not applicable. accidents. Bmj. 1993;307(6905):647–51.
19. Bryant RA. Predicting posttraumatic stress disorder from acute reactions. J
Trauma Dissociation. 2005;6(2):5–15.
Competing interests 20. Holeva V, Tarrier N. Personality and peritraumatic dissociation in the
We wish to confirm that there are no known conflicts of interest associated prediction of PTSD in victims of road traffic accidents. J Psychosom Res.
with thispublication and there has been no significant financial support for 2001 Nov;51(5):687–92.
this work that could haveinfluenced its outcome. 21. Forbes D, Wolfgang B, Cooper J, Creamer M, Barton D. Post-traumatic stress
disorder--best practice GP guidelines. Aust Fam Physician. 2009 Mar;38(3):
Author details 106–11.
1
HESPER EA 7425, Univ Lyon, Université Claude Bernard Lyon 1, Lyon, France. 22. Benedek DM, Friedman MJ, Zatzick D, Ursano RJ. Guideline watch (march
2
Pôle de santé publique, Hospices Civils de Lyon, Lyon, France. 3PsyR2 Team, 2009): practice guideline for the treatment of patients with acute stress
U 1028, INSERM and UMR 5292, CNRS, Center for Neuroscience Research of disorder and posttraumatic stress disorder. Focus. 2009;7(2):204–13.
Lyon (CRNL), CH Le Vinatier, Lyon-1 University, Bron, France. 4Department of 23. Bomyea J, Risbrough V, Lang AJ. A consideration of select pre-trauma
Psychiatry Emergencies, CHU Lyon, Hôpital Edouard Herriot, Lyon, France. factors as key vulnerabilities in PTSD. Clin Psychol Rev. 2012;32(7):630–41.
5
SHU, CH Le Vinatier, Lyon 1 Université, Bron, France. 24. Te Brake H, Dückers M, De Vries M, Van Duin D, Rooze M, Spreeuwenberg C.
Early psychosocial interventions after disasters, terrorism, and other
Received: 5 March 2019 Accepted: 20 May 2019 shocking events: guideline development. Nurs Health Sci. 2009 Dec;11(4):
336–43.
25. Bryant RA, Creamer M, O’Donnell M, Silove D, McFarlane AC. The capacity of
acute stress disorder to predict posttraumatic psychiatric disorders. J
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