This study evaluated the cost-effectiveness and cost-utility of a therapist-guided, internet-delivered early intervention for trauma. Exposure to traumatic events is common and can lead to substantial psychological distress, functional impairment, and societal costs. Early psychological interventions have the potential to mitigate these effects. We developed Condensed Internet-delivered Prolonged Exposure (CIPE), a digital intervention delivered within two months of trauma exposure. In a randomized controlled trial (N = 102), CIPE was more effective than a waiting-list control in reducing post-traumatic stress symptoms at post-intervention (3 weeks) and at a prespecified 7-week follow-up while the waiting-list control remained intact (prior to crossover). In this study, we evaluated CIPE from a societal cost perspective, aggregating direct medical costs (healthcare contacts, medication) and indirect costs (sick leave, reduced productivity, domestic loss) with equal weight in total cost calculations using a self-report questionnaire. Cost-effectiveness was assessed using responder status (≥10-point symptom reduction) and subthreshold symptom status on the PTSD Checklist for DSM-5. Cost-utility was assessed using quality-adjusted life years (QALYs) from the EQ-5D. Incremental cost-effectiveness ratios (ICERs) were estimated using bootstrapped regression analyses and visualized in cost-effectiveness planes and acceptability curves. CIPE showed a 95 % probability of being cost-effective at a willingness-to-pay threshold of €939–1181 per additional responder or subthreshold case. The corresponding cost per QALY gained was €2929–3636. Effects were sustained at 12-month follow-up. These findings suggest that therapist-guided digital exposure therapy delivered soon after trauma can reduce symptoms at a relatively low cost to society. Future research should examine CIPE's long-term economic impact and potential for broader implementation.

Background. Exposure to trauma is common and can have a profoundly negative impact on mental health. Interventions based on trauma-focused cognitive behavioural therapy have shown promising results to facilitate recovery. The current trial evaluated whether a novel, scalable and digital early version of the intervention, Condensed Internet-Delivered Prolonged Exposure (CIPE), is effective in reducing post-traumatic stress symptoms.

Method. A single-site randomised controlled trial with self-referred adults (N = 102) exposed to trauma within the last 2 months. The participants were randomised to 3 weeks of CIPE or a waiting list (WL) for 7 weeks. Assessments were conducted at baseline, week 1–3 (primary endpoint), week 4–7 (secondary endpoint) and at 6-month follow-up. The primary outcome measure was PTSD Checklist for DSM-5 (PCL-5).

Results. The main analysis according to the intention-to-treat principle indicated statistically significant reductions in symptoms of post-traumatic stress in the CIPE group as compared to the WL group. The between-group effect size was moderate at week 3 (bootstrapped d = 0.70; 95% CI 0.33–1.06) and large at week 7 (bootstrapped d = 0.83; 95% CI 0.46–1.19). Results in the intervention group were maintained at the 6-month follow-up. No severe adverse events were found.

Conclusions. CIPE is a scalable intervention that may confer early benefits on post-traumatic stress symptoms in survivors of trauma. The next step is to compare this intervention to an active control group and also investigate its effects when implemented in regular care.

Exposure to trauma is common and may have detrimental psychological consequences. Brief exposure therapy provided early after trauma has shown encouraging results in promoting recovery. To scale up treatment availability, we developed a 3-week internet-delivered intervention comprised of four modules based on prolonged exposure (condensed internet-delivered prolonged exposure; CIPE) with therapist support. In this pilot study, we assessed the feasibility, acceptability, and preliminary efficacy of CIPE delivered within 2 months after the index event. Thirty-three participants were randomised to CIPE or a waiting list (WL). The frequency, vividness and distress of intrusive recollections or flashback memories of the traumatic event were assessed using an intrusive memory smartphone app. Symptoms of post-traumatic stress were assessed by the PTSD Symptom Checklist for DSM-5 (PCL-5). The most common index traumas in the sample were rape, interpersonal violence and life-threatening accidents. A majority of participants (82%) randomised to CIPE completed all modules, and the number of logins per participant to the Internet platform was high during the three-week intervention (M = 19.6, SD = 11.8). At post-treatment, the CIPE participants had a more favourable reduction than the WL group on the vividness and distress ratings, as well as on the PCL-5 sum score (bootstrapped d = 0.85; 95% CI [0.25-1.45]). Treatment effects were sustained at 6-months follow up and no severe adverse events associated with the intervention were found. CIPE seems to be a feasible and possibly efficacious early intervention after trauma. Large-scale trials are needed to assess its efficacy and long-term benefits.

Background: The use of remotely delivered early intervention after trauma may prevent and/or reduce symptoms of post-traumatic stress. Our research group evaluated a novel three-week therapist-guided internet-delivered intervention based on prolonged exposure (Condensed Internet-Delivered Prolonged Exposure; CIPE) in a pilot trial. The results indicated that the intervention was feasible, acceptable and reduced symptoms of post-traumatic stress at post-intervention compared to a waiting-list condition. Exposure to traumatic memories can be emotionally demanding and there is a need for detailed investigation of participants' experiences in receiving this type of intervention remotely.

Objective: Investigate participants' experiences of receiving CIPE early after trauma.

Method: In this study, qualitative thematic analysis was used and semi-structured interviews with 11 participants six months after intervention completion were conducted. All interviews were audio-recorded and transcribed verbatim.

Results: One overarching theme labelled as 'demanding and effective' was identified. Participants expressed that treatment effects could only be achieved by putting in a lot of effort and by being emotionally close to the trauma memory during exposure exercises. Participants reported CIPE to be a highly credible- and educative intervention that motivated them to fully engage in exposure exercises. The most distressing parts of the intervention was perceived as tolerable and important to do to heal psychologically after trauma. For many participants, the possibility to engage in the intervention whenever and where it suited them was helpful, although some participants described it as challenging to find a balance between their own responsibility and when to expect therapist support. The internet-based format was perceived as a safe forum for self-disclosure that helped some participants overcome avoidance due to shame during imaginal exposure.

Conclusion: CIPE was considered demanding, yet effective by the interviewed participants. The most distressing parts of the intervention was perceived to be the most important and were tolerable and feasible to provide online.

Antecedentes: El uso de una intervención temprana administrada a distancia después de un trauma puede prevenir y/o reducir los síntomas de estrés postraumático. Nuestro grupo de investigación evaluó una nueva intervención de tres semanas entregada por internet y guiada por un terapeuta, basada en exposición prolongada (Exposición prolongada condensada por Internet; CIPE por sus siglas en inglés) en un ensayo piloto. Los resultados indicaron que la intervención fue factible, aceptable y redujo los síntomas de estrés postraumático en la postintervención en comparación con una condición de lista de espera. La exposición a recuerdos traumáticos puede ser emocionalmente exigente y es necesario realizar una investigación detallada de las experiencias de los participantes al recibir este tipo de intervención de forma remota.

Objetivo: Investigar las experiencias de los participantes al recibir CIPE en forma temprana después del trauma.

Método: En este estudio se utilizó un análisis temático cualitativo y se realizaron entrevistas semiestructuradas con 11 participantes seis meses después de finalizada la intervención. Todas las entrevistas fueron grabadas en audio y transcritas textualmente.

Resultados: Se identificó un tema general etiquetado como ‘exigente y eficaz’. Los partici-pantes expresaron que los efectos del tratamiento solo se pueden lograr haciendo un gran esfuerzo y estando cerca emocionalmente del recuerdo del trauma durante los ejercicios de exposición. Los participantes informaron que CIPE era una intervención educativa y de gran credibilidad que los motivó a participar plenamente en los ejercicios de exposición. Las partes más angustiantes de la intervención se percibieron como tolerables e importantes para sanar psicológicamente después del trauma. Para muchos participantes, la posibilidad de participar en la intervención cuando y donde les convenía fue útil, aunque algunos participantes describieron como desafiante el encontrar un equilibrio entre su propia responsabilidad y cuándo esperar el apoyo del terapeuta. El formato basado en Internet se percibió como un foro seguro para la autorrevelación que ayudó a algunos participantes a superar la evitación debida a la vergüenza durante la exposición imaginaria.

Conclusión: CIPE fue considerada exigente, pero eficaz por los participantes entrevistados. Las partes más angustiantes de la intervención fueron percibidas como las más importantes y fueron tolerables y factibles de proporcionar en línea.

背景: 在创伤后使用远程早期干预可以预防和/或减轻创伤后应激症状。我们的研究组在预 试验中, 评估了一种为期三周的基于延长暴露, 有治疗师指导的新颖网络干预措施 (密集型 网络延长暴露 CIPE) 。结果表明, 干预是可行的, 可接受的并且相较于等候名单条件, 在干 预后减轻了创伤后应激症状。暴露于创伤性记忆可能在情感上是高需求的, 需要对参与者 远程接受此类干预的体验进行详细考查。

目的: 考查参与者在创伤后早期接受CIPE的体验。

方法: 在本研究中, 使用定性主题分析, 在干预完成六个月后对11名参与者进行了半结构化 访谈。所有采访均进行录音并逐字记录。

结果: 确定了一个标记为‘高需求和有效’的总体主题。参与者表示, 只有通过付出大量努力 并在暴露练习中在情感上贴近创伤记忆, 才能达到治疗效果。参与者报告说, CIPE是一种 高度可靠且具有教育意义的干预措施, 可以促使他们充分参与暴露练习。在创伤后为了治 愈心理, 干预中最痛苦的部分被认为是可以忍受且很重要的。对于许多参与者, 能够在适 合他们的时间和地点参加干预的可能性是有帮助的, 尽管一些参与者认为在其责任与何时 期望治疗师支持之间寻求平衡是一个挑战。基于网络的方式被认为是一个自我披露的安 全论坛, 可以帮助一些参与者克服在假想曝光时因羞耻感产生的回避。

结论: 受访者认为CIPE是高需求但有效的。干预中最痛苦的部分被认为是最重要的, 可以容 忍并且可以在线提供。

The main purpose of the current trial was to test if a brief trauma-focused cognitive-behaviour therapy protocol (prolonged exposure; PE) provided within 72 h after a traumatic event could be effective in decreasing the incidence of post-traumatic stress disorder (PTSD), thus replicating and extending the findings from an earlier trial. After a pilot study (N = 10), which indicated feasible and deliverable study procedures and interventions, we launched an RCT with a target sample size of 352 participants randomised to either three sessions of PE or non-directive support. Due to an unforeseen major reorganisation at the hospital, the RCT was discontinued after 32 included participants. In this paper, we highlight obstacles and lessons learned from our feasibility work that are relevant for preventive psychological interventions for PTSD in emergency settings. One important finding was the high degree of attrition, and only 75% and 34%, respectively, came back for the 2-month and 6-month assessments. There were also difficulties in reaching eligible patients immediately after the event. Based on our experiences, we envisage that alternative models of implementation might overcome these obstacles, for example, with remote delivery of both assessments and interventions via the internet or smartphones combined with multiple recruitment procedures. Lessons learned from this terminated RCT are discussed in depth.

Background: In recent decades, millions of refugees and migrants have fled wars and sought asylum in Europe. The aim of this study was to quantify the risk of mortality and major diseases among migrants during the 1991-2001 Balkan wars to Sweden in comparison to other European migrants to Sweden during the same period.

Methods and findings: We conducted a register-based cohort study of 104,770 migrants to Sweden from the former Yugoslavia during the Balkan wars and 147,430 migrants to Sweden from 24 other European countries during the same period (1991-2001). Inpatient and specialized outpatient diagnoses of cardiovascular disease (CVD), cancer, and psychiatric disorders were obtained from the Swedish National Patient Register and the Swedish Cancer Register, and mortality data from the Swedish Cause of Death Register. Adjusting for individual-level data on sociodemographic characteristics and emigration country smoking prevalence, we used Cox regressions to contrast risks of health outcomes for migrants of the Balkan wars and other European migrants. During an average of 12.26 years of follow-up, being a migrant of the Balkan wars was associated with an elevated risk of being diagnosed with CVD (HR 1.39, 95% CI 1.34-1.43, p < 0.001) and dying from CVD (HR 1.45, 95% CI 1.29-1.62, p < 0.001), as well as being diagnosed with cancer (HR 1.16, 95% CI 1.08-1.24, p < 0.001) and dying from cancer (HR 1.27, 95% CI 1.15-1.41, p < 0.001), compared to other European migrants. Being a migrant of the Balkan wars was also associated with a greater overall risk of being diagnosed with a psychiatric disorder (HR 1.19, 95% CI 1.14-1.23, p < 0.001), particularly post-traumatic stress disorder (HR 9.33, 95% CI 7.96-10.94, p < 0.001), while being associated with a reduced risk of suicide (HR 0.68, 95% CI 0.48-0.96, p = 0.030) and suicide attempt (HR 0.57, 95% CI 0.51-0.65, p < 0.001). Later time period of migration and not having any first-degree relatives in Sweden at the time of immigration were associated with greater increases in risk of CVD and psychiatric disorders. Limitations of the study included lack of individual-level information on health status and behaviors of migrants at the time of immigration.

Conclusions: Our findings indicate that migrants of the Balkan wars faced considerably elevated risks of major diseases and mortality in their first decade in Sweden compared to other European migrants. War migrants without family members in Sweden or with more recent immigration may be particularly vulnerable to adverse health outcomes. Results underscore that persons displaced by war are a vulnerable group in need of long-term health surveillance for psychiatric disorders and somatic disease.

Background: This study aimed to examine the psychometric properties of the Swedish PG-13 in a bereaved trauma exposed sample. A second aim was to examine the latent structure of prolonged grief using the PG-13.

Methods: The participants were adults (n = 123) taking part in an ongoing longitudinal study regarding the effects of potentially traumatic events. Participants had experienced a potentially traumatic event in the past 5 years and had reported a death of a significant other either as their primary traumatic event or in addition to another traumatic event. Assessment included self-report of prolonged grief, posttraumatic stress, and general psychological distress. Clinical interviews were used to assess depression, posttraumatic stress disorder, and disability level. The psychometric properties of the Swedish PG-13 were examined through reliability tests and assessment of associations with symptoms of posttraumatic stress, depression, general psychological distress, and disability level. Principal component analysis (PCA) and confirmatory factor analyses (CFA) were used to assess the latent structure.

Results: The internal consistency (Cronbach's alpha = 0.86) and test-retest (r = 0.86) reliability were good. PCA suggested a three-factor model as descriptive of the latent structure of the instrument. Therefore, the CFA used this model, as well as two models suggested in the literature. The three-factor model had the best fit to data. Support of concurrent validity of PG-13 was shown by moderate positive associations with measures of posttraumatic stress, depression, and general psychological distress.

Conclusions: The Swedish PG-13 demonstrated good psychometric properties, and its use in research and practice to assess prolonged grief was supported. The factor analyses provided stronger support for models with two or three factors, as compared with a unidimensional model of prolonged grief, with the three-factor model having the best fit.

OBJECTIVE To assess the association between stress related disorders and subsequent risk of cardiovascular disease.

DESIGN Population based, sibling controlled cohort study. SETTING Population of Sweden.

PARTICIPANTS 136 637 patients in the Swedish National Patient Register with stress related disorders, including post-traumatic stress disorder (PTSD), acute stress reaction, adjustment disorder, and other stress reactions, from 1987 to 2013; 171 314 unaffected full siblings of these patients; and 1 366 370 matched unexposed people from the general population.

MAIN OUTCOME MEASURES Primary diagnosis of incident cardiovascular disease-any or specific subtypes (ischaemic heart disease, cerebrovascular disease, emboli/thrombosis, hypertensive diseases, heart failure, arrhythmia/conduction disorder, and fatal cardiovascular disease)-and 16 individual diagnoses of cardiovascular disease. Hazard ratios for cardiovascular disease were derived from Cox models, after controlling for multiple confounders.

RESULTS During up to 27 years of follow-up, the crude incidence rate of any cardiovascular disease was 10.5, 8.4, and 6.9 per 1000 person years among exposed patients, their unaffected full siblings, and the matched unexposed individuals, respectively. In sibling based comparisons, the hazard ratio for any cardiovascular disease was 1.64 (95% confidence interval 1.45 to 1.84), with the highest subtype specific hazard ratio observed for heart failure (6.95, 1.88 to 25.68), during the first year after the diagnosis of any stress related disorder. Beyond one year, the hazard ratios became lower (overall 1.29, 1.24 to 1.34), ranging from 1.12 (1.04 to 1.21) for arrhythmia to 2.02 (1.45 to 2.82) for artery thrombosis/embolus. Stress related disorders were more strongly associated with early onset cardiovascular diseases (hazard ratio 1.40 (1.32 to 1.49) for attained age < 50) than later onset ones (1.24 (1.18 to 1.30) for attained age >= 50; P for difference=0.002). Except for fatal cardiovascular diseases, these associations were not modified by the presence of psychiatric comorbidity. Analyses within the population matched cohort yielded similar results (hazard ratio 1.71 (1.59 to 1.83) for any cardiovascular disease during the first year of follow-up and 1.36 (1.33 to 1.39) thereafter).

CONCLUSION Stress related disorders are robustly associated with multiple types of cardiovascular disease, independently of familial background, history of somatic/psychiatric diseases, and psychiatric comorbidity.

IMPORTANCE Psychiatric reactions to life stressors are common in the general population and may result in immune dysfunction. Whether such reactions contribute to the risk of autoimmune disease remains unclear. OBJECTIVE To determine whether there is an association between stress-related disorders and subsequent autoimmune disease. DESIGN, SETTING, AND PARTICIPANTS Population-and sibling-matched retrospective cohort study conducted in Sweden from January 1, 1981, to December 31, 2013. The cohort included 106 464 exposed patients with stress-related disorders, with 1 064 640 matched unexposed persons and 126 652 full siblings of these patients. EXPOSURES Diagnosis of stress-related disorders, ie, posttraumatic stress disorder, acute stress reaction, adjustment disorder, and other stress reactions. MAIN OUTCOMES AND MEASURES Stress-related disorder and autoimmune diseaseswere identified through the National Patient Register. The Cox model was used to estimate hazard ratios (HRs) with 95% CIs of 41 autoimmune diseases beyond 1 year after the diagnosis of stress-related disorders, controlling for multiple risk factors. RESULTS The median age at diagnosis of stress-related disorders was 41 years (interquartile range, 33-50 years) and 40% of the exposed patients were male. During a mean follow-up of 10 years, the incidence rate of autoimmune diseases was 9.1, 6.0, and 6.5 per 1000 person-years among the exposed, matched unexposed, and sibling cohorts, respectively (absolute rate difference, 3.12 [95% CI, 2.99-3.25] and 2.49 [95% CI, 2.23-2.76] per 1000 person-years compared with the population-and sibling-based reference groups, respectively). Compared with the unexposed population, patients with stress-related disorders were at increased risk of autoimmune disease (HR, 1.36 [95% CI, 1.33-1.40]). The HRs for patients with posttraumatic stress disorder were 1.46 (95% CI, 1.32-1.61) for any and 2.29 (95% CI, 1.72-3.04) for multiple (>= 3) autoimmune diseases. These associations were consistent in the sibling-based comparison. Relative risk elevations were more pronounced among younger patients (HR, 1.48 [ 95% CI, 1.42-1.55]; 1.41 [ 95% CI, 1.33-1.48]; 1.31 [ 95% CI, 1.24-1.37]; and 1.23 [95% CI, 1.17-1.30] for age at <= 33, 34-41, 42-50, and >= 51 years, respectively; P for interaction <.001). Persistent use of selective serotonin reuptake inhibitors during the first year of posttraumatic stress disorder diagnosis was associated with attenuated relative risk of autoimmune disease (HR, 3.64 [95% CI, 2.00-6.62]; 2.65 [95% CI, 1.57-4.45]; and 1.82 [95% CI, 1.09-3.02] for duration <= 179, 180-319, and >= 320 days, respectively; P for trend =.03). CONCLUSIONS AND RELEVANCE In this Swedish cohort, exposure to a stress-related disorder was significantly associated with increased risk of subsequent autoimmune disease, compared with matched unexposed individuals and with full siblings. Further studies are needed to better understand the underlying mechanisms.